3D­printed template­guided iodine­125 seed implantation to treat complete occlusion of the superior vena cava in pulmonary sarcomatoid carcinoma: A case report.

Pulmonary sarcomatoid carcinoma (PSC), which is a type of non-small-cell lung carcinoma (NSCLC), is characterized by a high degree of malignancy, poor differentiation and a high incidence of pulmonary malignancy. In addition, PSC has a stronger invasive ability than other types of NSCLC and is not sensitive to radiation or chemotherapy. Furthermore, 90% of PSC cases exhibit vascular invasion; therefore, there is a risk of multiple metastases to the lung, bone, adrenal glands and brain, and consequently a poor prognosis, in the early stage. Targeted therapy and immunotherapy currently offer a new treatment direction; however, there have not been any significant advances in localized treatment in recent years. Thus, there is an urgent need for new localized treatment strategies. The present study describes the case of a 65-year-old man with recurrence of PSC after multi-line treatment with chemotherapy, radiotherapy, gamma knife and argon-helium knife treatment. In addition, the patient developed superior vena cava syndrome, and exhibited severe compression of the superior vena cava, chest discomfort, dyspnea and severe facial edema after chemotherapy, local gamma knife therapy (35 Gy, delivered through 14 2.5-Gy doses), argon-helium knife therapy and radiation therapy (28 Gy, delivered through seven 4-Gy doses). Partial remission was achieved after local implantation of iodine-125 (I125) seed under the guidance of a 3D-printed template, with progression-free survival observed up to 8 months afterwards. In conclusion, in patients with PSC who develop superior vena cava blockage after numerous treatment regimens, salvage I125 brachytherapy with a 3D-printed template may be suitable, and may improve local control and symptoms.

MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase-signal transducer and activator of transcription pathway.

Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.

Conditional generative adversarial network-assisted system for radiation-free evaluation of scoliosis using a single smartphone photograph: a model development and validation study.

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Prognostic factors associated with acute retinal necrosis treated non-surgically.

OBJECTIVES: To analyse the prognostic factors for visual acuity in acute retinal necrosis (ARN) patients treated non-surgically. METHODS: The clinical data of ARN patients who visited our hospital from January 2010 to January 2023 were retrospectively analysed. RESULTS: Twenty-four patients (29 eyes) were included. Aqueous humour samples were collected from 20 out of 29 eyes, and PCR confirmed that 85% (17/20) of the eyes had VZV infection, 10% (2/20) had CMV infection, and 5% (1/20) had HSV infection. All patients were treated with intravenous antiviral agents. Intravitreal ganciclovir and oral corticosteroids were given according to the patients' wishes. A comparison of visual acuity at the time of first identification of inactive ARN with that at the first visit revealed that 16 (55.2%) eyes improved and 13 (44.8%) did not improve. Logistic regression analysis revealed that risk factors for failure to improve vision after treatment included retinal detachment (odds ratio [OR],33.75; 95% CI, 3.245-351.067; P = 0.003), necrotising retinitis involving the posterior pole (odds ratio [OR],8.167; 95% CI, 1.297-51.403, P = 0.025), and arteritis involving the large retinal arteries (odds ratio [OR],9.167; 95% CI, 1.493-56.297; P = 0.017). The VZV viral load in the aqueous humour at initial presentation was significantly associated with visual prognosis (r = 0.688, P = 0.013), retinal detachment (τ = 0.597, P = 0.021) and the extent of retinal necrosis (τ = 0.57, P = 0.027). The neutrophil to lymphocyte ratio (NLR) of VZV-infected patients at first presentation was significantly correlated with the prognosis of visual acuity (r = 0.616, P = 0.033) and retinal detachment (τ = 0.728, P = 0.004). CONCLUSIONS: High NLR and viral DNA copy number in the aqueous humour at the initial presentation, as well as subsequent retinal detachment, necrotising retinitis involving the posterior pole, and arteritis involving the large retinal arteries were risk factors for poor visual prognosis in VZV-infected ARN patients.

[Chemical profiling of Xiaochaihu Granules and characterization of absorbed components in rat plasma after oral administration].

The chemical components of Xiaochaihu Granules and absorbed components in rats after oral administration were identified by using ultra performance liquid chromatography-quadrupole orbitrap mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS)and UPLC-triple quadrupole mass spectrometry(UPLC-MS/MS). Separation was performed on a CORTECS UPLC C~+_(18)(2.1 mm×100 mm, 1.6 µm)column with gradient elution using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. Data on the chemical components were collected in positive and negative ion modes and identified based on the retention time, precise molecular weight, fragment ion information in comparison with the reference substance, and literature report. The rat fever model was established by subcutaneous injection of dry yeast. Subsequently, the normal and model rats received oral administration of Xiaochaihu Granules. Blood samples were taken from the orbital vein at different time points after administration, and the plasma was isolated for scanning and identification of absorbed components using the multi reaction monitoring mode(MRM).A total of 112 chemical components were identified in Xiaochaihu Granules, including 63 flavonoids, 31 saponins, 6 organic acids, 4 phenylpropanoids, 3 amino acids and 5 other compounds. Additionally, 18 prototypical components were identified in rat plasma. This study lays the foundation for further study of the therapeutic material and quality control of Xiaochaihu Granules.

Construction of an extubation protocol for adult tracheal intubation patients in the intensive care unit: A Delphi study.

OBJECTIVE: The objective of this study was to develop an extubation practice protocol for adult intensive care unit (ICU) patients who underwent endotracheal intubation, providing theoretical guidance for clinical extubation procedures in the ICU. METHODS: A research team was established consisting of medical, nursing, anaesthesia, and respiratory therapy professionals; the multidisciplinary team systematically searched domestic and foreign literature, summarised the best evidence, and combined it with clinical practice experience to preliminarily develop an extubation protocol for adult ICU patients who underwent endotracheal intubation. Seventeen experts in critical care medicine, intensive care nursing, clinical anaesthesia, and respiratory therapy were invited to participate in a Delphi expert consultation to screen and modify the draft protocol. RESULTS: The response rates of the two Delphi expert enquiries were 100% and 94.1%, with expert authority coefficients of 0.94 and 0.93, respectively, and Kendall's concordance coefficients were 0.152 and 0.198, respectively, indicating statistically significant differences (p < 0.001). The final protocol included three level I indicators, 14 level II indicators, and 34 level III indicators, covering extubation evaluation, implementation, and postextubation management. CONCLUSION: The extubation protocol for adult tracheal intubation patients in the ICU constructed in this study is scientific, practical, and reliable. This study can provide theoretical guidance for extubation in ICU patients who have undergone endotracheal intubation.

5-Aminolevulinic acid photodynamic therapy is a safe and effective treatment for female patients with intractable vulvar lichen sclerosus.

BACKGROUND: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. METHODS: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). RESULTS: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were "satisfied" or "very satisfied" with the results of the treatment. CONCLUSIONS: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

Balancing functions of antifouling, nitric oxide release and vascular cell selectivity for enhanced endothelialization of assembled multilayers.

Surface endothelialization is a promising way to improve the hemocompatibility of biomaterials. However, current surface endothelialization strategies have limitations. For example, various surface functions are not well balanced, leading to undesirable results, especially when multiple functional components are introduced. In this work, a multifunctional surface was constructed by balancing the functions of antifouling, nitric oxide (NO) release and endothelial cell promotion via layer-by-layer (LBL) self-assembly. Poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methacrylate) (negatively charged) and polyethyleneimine (positively charged) were deposited on silicon substrates to construct multilayers by LBL self-assembly. Then, organic selenium, which has a NO-releasing function, and the cell-adhesive peptide Gly-Arg-Glu-Asp-Val-Tyr, which selectively promotes endothelial cells, were introduced on the assembled multilayers. Poly(oligo(ethylene glycol) methacrylate) is a hydrophilic component for antifouling properties, and poly(sodium p-styrenesulfonate) is a heparin analog that provides negative charges. By modulating the contents of poly(oligo(ethylene glycol) methacrylate) and poly(sodium p-styrenesulfonate) in the copolymers, the NO release rates catalyzed by the modified surfaces were regulated. Moreover, the behaviors of endothelial cells and smooth muscle cells on modified surfaces were well controlled. The optimized surface strongly promoted endothelial cells and inhibited smooth muscle cells to achieve endothelialization effectively.

In Vivo Study of Inoculation Approaches and Pathogenicity in African Swine Fever.

African swine fever is an extremely infectious viral disease that can cause nearly 100% mortality in domestic pigs. In this study, we isolated an ASFV strain HB31A and characterized it using hemadsorption assay, immunofluorescence assay, and electron microscopy. We then performed animal experiments on 20-day-old pigs through intramuscular and oronasal inoculations with HB31A. Pigs in the intramuscular group exhibited more consistent clinical disease, with an incubation period of 4.33 ± 0.47 days and a 100% mortality rate within 6.67 (±0.47) days post-inoculation (dpi). In contrast, the oronasal group experienced a longer course of disease, with an incubation period of 6.00 ± 0.82 days. Two out of three pigs in the oronasal group died at 8 and 10 dpi, while the surviving pig exhibited chronic disease and persistent infection, intermittently excreting ASFV through the oral, nasal, and rectal pathways. Virus DNA was found in oral, nasal, and rectal swabs at 1-3 dpi in the intramuscular group and at 3-5 dpi in the oronasal group. In summary, HB31A is highly lethal to domestic pigs, and field-infected pigs have the potential to develop non-lethal, chronic disease and persistent infection, with intermittent viral shedding, even when infected with a highly virulent strain. These findings offer a valuable understanding of the viral dynamics and pathogenicity of ASFV and highlight the difficulties in diagnosing, preventing, and controlling African swine fever.

Establishment of an in Vitro Three-Dimensional Vascularized Micro-Tumor Model and Screening of Chemotherapeutic Drugs.

Breast cancer is the most common malignancy in women worldwide, and major challenges in its treatment include drug resistance and metastasis. Three-dimensional cell culture systems have received widespread attention in drug discovery studies but existing models have limitations, that warrant the development of a simple and repeatable three-dimensional culture model for high-throughput screening. In this study, we designed a simple, reproducible, and highly efficient microencapsulated device to co-culture MCF-7 cells and HUVECs in microcapsules to establish an in vitro vascularized micro-tumor model for chemotherapeutic drug screening. First, to construct a three-dimensional micro-tumor model, cell encapsulation devices were created using three different sizes of flat-mouthed needles. Immunohistochemistry and immunofluorescence assays were conducted to determine vascular lumen formation. Cell proliferation was detected using the Cell Counting Kit-8 assay. Finally, to observe the drug reactions between the models, anticancer drugs (doxorubicin or paclitaxel) were added 12 h after the two-dimensional cultured cells were plated or 7 days after cell growth in the core-shell microcapsules. Vascularized micro-tumors were obtained after 14 days of three-dimensional culture. The proliferation rate in the three-dimensional cultured cells was slower than that of two-dimensional cultured cells. Three-dimensional cultured cells were more resistant to anticancer drugs than two-dimensional cultured cells. This novel sample encapsulation device formed core-shell microcapsules and can be used to successfully construct 3D vascularized micro-tumors in vitro. The three-dimensional culture model may provide a platform for drug screening and is valuable for studying tumor development and angiogenesis.

Endothelium-Mimicking Materials: A "Rising Star" for Antithrombosis.

The advancement of antithrombotic materials has significantly mitigated the thrombosis issue in clinical applications involving various medical implants. Extensive research has been dedicated over the past few decades to developing blood-contacting materials with complete resistance to thrombosis. However, despite these advancements, the risk of thrombosis and other complications persists when these materials are implanted in the human body. Consequently, the modification and enhancement of antithrombotic materials remain pivotal in 21st-century hemocompatibility studies. Previous research indicates that the healthy endothelial cells (ECs) layer is uniquely compatible with blood. Inspired by bionics, scientists have initiated the development of materials that emulate the hemocompatible properties of ECs by replicating their diverse antithrombotic mechanisms. This review elucidates the antithrombotic mechanisms of ECs and examines the endothelium-mimicking materials developed through single, dual-functional and multifunctional strategies, focusing on nitric oxide release, fibrinolytic function, glycosaminoglycan modification, and surface topography modification. These materials have demonstrated outstanding antithrombotic performance. Finally, the review outlines potential future research directions in this dynamic field, aiming to advance the development of antithrombotic materials.

Research Progress on the Relationship between Parkinson's Disease and REM Sleep Behavior Disorder.

An individual's quality of life is greatly affected by Parkinson's disease (PD), a prevalent neurological degenerative condition. Rapid eye movement (REM) sleep behavior disorder (RBD) is a prominent non-motor symptom commonly associated with PD. Previous studies have shown a close relationship between PD and RBD. In addition to being a prodromal symptom of PD, RBD has a major negative impact on the prognosis of PD patients. This intrinsic connection indicates that there is a bidirectional relationship between PD and RBD. This paper provides a comprehensive review of the pathological mechanism related to PD and RBD, including the α-synuclein pathological deposition, abnormal iron metabolism, neuroinflammation, glymphatic system dysfunction and dysbiosis of the gut microbiota. Increasing evidence has shown that RBD patients have the same pathogenic mechanisms that underlie PD, but relatively little research has been done on how RBD contributes to PD progression. Therefore, a more thorough investigation is warranted to characterise how RBD affects the course of PD, in order to prepare for future therapeutic trials.

Toxic effects of ZnO NPs on immune response and tissue pathology in Mytilus galloprovincialis.

Nano-zinc oxide (ZnO NPs), as widely used nanomaterials, are inevitably released into aquatic environments, posing potential threats to aquatic organisms. Mytilus galloprovincialis is a bivalve species sensitive to changes in marine ecological environments, but there has been limited research on its toxicity response to ZnO NPs. Therefore, we selected M. galloprovincialis as the research subject and exposed them to 50 µg/L ZnO NPs for 96 h and 30 days to determine the dissolution of ZnO NPs in seawater and their distribution in M. galloprovincialis. The toxicity of ZnO NPs in M. galloprovincialis was then evaluated through gene expression, tissue pathology, and cellular immune response. The results showed that ZnO NPs could enrich Zn in various tissues of the mussel, in the order of gills > hepatopancreas > adductor muscle > mantle. Seven immune-related genes including four heat shock protein genes (HSPA12A, sHSP24.1, sHSP22, TCTP) and three apoptotic genes (Ras, p63 and Bcl-2) were altered to varying degrees. There was a downward trend in lysosomal membrane stability of M. galloprovincialis after exposure to ZnO NPs for 96 h and 30 days, while ROS and apoptosis rates increased significantly. Furthermore, the seven genes, apoptosis, LMS, and ROS were dependent on exposure time, treatment, and their interaction. Histopathological damage included disorganisation of hepatopancreas epithelial cells, gill filament swelling, and contraction of blood sinuses. These results indicated that ZnO NPs exerted toxicity in M. galloprovincialis, affecting the immune system, resulting in changes in the expression of immune-related genes and ultimately leading to histopathological changes. Our research findings could contribute to systematically understand the impact of ZnO NPs on bivalves in aquatic environments and provide a theoretical basis for marine pollution assessment.

Design and evaluation of a wedge-shaped adaptive knee orthosis for the human lower limbs.

Introduction: The incidence of knee osteoarthritis (KOA) is moderately correlated with age and body weight and increases with life span and weight gain, associated with tearing and wearing the knee joints. KOA can adjust the force through the human lower limbs, redistribute the load of the knee joint, reduce the pain, and restore mobility when the arthritis changes are mild. However, most of the existing knee orthosis cannot be adjusted adaptively according to the needs of patients. Methodology: This study establishes a biomechanical model of the knee joint to analyze the medial and lateral forces acting on the joint. The new adjustable knee orthosis is designed. It applies the principle of four-point bending to apply pressure to both sides of the knee joint, thereby adjusting the varus angle and modifying the medial and lateral forces on the knee joint. Through structural optimization, the prototype of the knee orthosis weighs only 324 g. Utilizing three-dimensional scanning technology, discrete point cloud data of the leg surface is obtained, reconstructed, and processed to create a 3D model of the human leg surface. The design ensures a close fit to the human leg surface, offering comfortable wear. A pressure sensing film system is employed to build a pressure sensing test system, where the knee orthosis is worn on a prosthesis for pressure testing to evaluate its ability to adjust knee joint forces. Results: The pressure test results demonstrate that the knee orthosis can stably provide an adjustment angle of 0-7° and sustain a maximum force of 10N on both sides of the knee joint over extended periods. A self-developed 8-channel plantar pressure sensing insole is calibrated against commercial plantar pressure sensors. Human wear tests on 15 subjects show that during the operation of the knee orthosis, it significantly adjusts plantar pressures, reducing lateral foot pressures by 22% overall, with more pronounced corrective effects observed in lighter participants. Discussion: In this study, a wedge-shaped adaptive knee orthosis was provided for KOA patients. The four-point force principle was used to balance the force between femurs and tibia and adjust the meniscus contact gap. The orthotic appliance has the advantages of simple mechanical structure, adjustable correction Angle and good wearing comfort.

Optimizing MobileNetV2 for improved accuracy in early gastric cancer detection based on dynamic pelican optimizer.

This paper presents an innovative framework for the automated diagnosis of gastric cancer using artificial intelligence. The proposed approach utilizes a customized deep learning model called MobileNetV2, which is optimized using a Dynamic variant of the Pelican Optimization Algorithm (DPOA). By combining these advanced techniques, it is feasible to achieve highly accurate results when applied to a dataset of endoscopic gastric images. To evaluate the performance of the model based on the benchmark, its data is divided into training (80 %) and testing (20 %) sets. The MobileNetV2/DPOA model demonstrated an impressive accuracy of 97.73 %, precision of 97.88 %, specificity of 97.72 %, sensitivity of 96.35 %, Matthews Correlation Coefficient (MCC) of 96.58 %, and F1-score of 98.41 %. These results surpassed those obtained by other well-known models, such as Convolutional Neural Networks (CNN), Mask Region-Based Convolutional Neural Networks (Mask R-CNN), U-Net, Deep Stacked Sparse Autoencoder Neural Networks (SANNs), and DeepLab v3+, in terms of most quantitative metrics. Despite the promising outcomes, it is important to note that further research is needed. Specifically, larger and more diverse datasets as well as exhaustive clinical validation are necessary to validate the effectiveness of the proposed method. By implementing this innovative approach in the detection of gastric cancer, it is possible to enhance the speed and accuracy of diagnosis, leading to improved patient care and better allocation of healthcare resources.

HKDC1 promotes liver cancer stemness under hypoxia via stabilizing ß-catenin.

BACKGROUND AND AIMS: Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified HKDC1 as a top candidate associated with liver cancer metastasis. We aimed to compare its cell type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis. APPROACH AND RESULTS: We found that, compared to HK1 and HK2, the other two commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from two liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid (TCA) cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3ß to stabilize ß-catenin, leading to enhanced stemness of HCC cells. CONCLUSIONS: Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.

Progressive failure processes and mechanisms of disasters caused by interrelated failure of residual coal pillars and rock strata.

The increasing number of closed/abandoned mines being reused has become a concern for people. However, a large number of coal pillars were left behind in the closed/abandoned mines. Before effectively utilizing the underground space of mines (CO2 goaf storage, etc.), it is necessary to study the stability of the residual pillars and rock strata. However, limited laboratory experiments and numerical simulation tests have been carried out to understand the relationship between residual pillars and strata in the context of their failure process and mechanism. In this study, the progressive failure and movement of the pillars and strata during the multi-seam mining is simulated using a physical model and numerical simulation. In addition, the failure mechanism was analyzed. The results suggest that the failure process of the pillar is strongly related to the rock strata. The mining of the below seam will bring about not only the collapse of the above strata, but also penetrate the gob of the overlying seam, and then cause the roof of the overlying seam to further collapse. The damage zone acting on the pillar increases accordingly, and the pillars are also gradually damaged. When the pillar is completely destroyed, it will further cause the stable strata to fracture, collapse and become unstable, and a rock burst may be formed. It is also found that under the effect of the stress concentration of the pillar, the floor rock will be damaged to a certain depth. When the collapse height of the overlying strata overlaps with the failure depth of the floor due to the stress concentration, it is more likely to bring about the occurrence of rock burst. The mechanisms of progressive failure of the residual pillars and rock strata revealed by this study offers guidance for the control of disasters, and also provides a reference for the stability research during goaf utilization in the later stage.

3D Bioprinting of Engineered Living Materials with Extracellular Electron Transfer Capability for Water Purification.

Attention is widely drawn to the extracellular electron transfer (EET) process of electroactive bacteria (EAB) for water purification, but its efficacy is often hindered in complex environmental matrices. In this study, the engineered living materials with EET capability (e-ELMs) were for the first time created with customized geometric configurations for pollutant removal using three-dimensional (3D) bioprinting platform. By combining EAB and tailored viscoelastic matrix, a biocompatible and tunable electroactive bioink for 3D bioprinting was initially developed with tuned rheological properties, enabling meticulous manipulation of microbial spatial arrangement and density. e-ELMs with different spatial microstructures were then designed and constructed by adjusting the filament diameter and orientation during the 3D printing process. Simulations of diffusion and fluid dynamics collectively showcase internal mass transfer rates and EET efficiency of e-ELMs with different spatial microstructures, contributing to the outstanding decontamination performances. Our research propels 3D bioprinting technology into the environmental realm, enabling the creation of intricately designed e-ELMs and providing promising routes to address the emerging water pollution concerns.