Design and navigation method of a soft robot for single-port transvesical radical prostatectomy.

PURPOSE: Currently, the rigid instruments used for laparoscopic radical resection of prostate cancer not only have the risk of damage to tissues, blood vessels, and nerves, but their limited freedom will also cause surgical blind areas. Soft robots are expected to solve these issues due to inherent flexibility, compliance, and safe interaction with tissues and organs. In addition, to achieve high surgical accuracy and provide precise guidance for surgeons, the navigation method should be studied for the soft robot. METHODS: A soft robot system for single-port transvesical radical prostatectomy (STRP) is developed, and a navigation method combining fiber Bragg gratings and electromagnetic tracking is proposed for the soft robot. To validate the soft robot design and the effectiveness of the navigation method, different groups of experiments are conducted. RESULTS: The proposed navigation method can achieve accurate location and shape sensing of the soft manipulator. The experiments show that the maximum tip sensing error is 2.691 mm, which is 5.38 % of the robot length for static configurations, and that the average tip sensing error is 1.966 mm, which corresponds to 3.93 % of the robot length for dynamic scenarios. Additionally, phantom tests demonstrate that the designed soft robot can enter the prostate through navigation guidance in a master-slave control mode and cover the entire prostate space. CONCLUSIONS: The designed soft robot system, due to its soft structure, good flexibility, and accurate navigation, is expected to improve surgical safety and precision, thereby exhibiting significant potential for STRP.

Enzyme/pH Dual-Responsive Engineered Nanoparticles for Improved Tumor Immuno-Chemotherapy.

Combining immune checkpoint blockade (ICB) therapy with chemotherapy can enhance the efficacy of ICB and expand its indications. However, the limited tumor specificity of chemotherapy drugs results in severe adverse reactions. Additionally, the low tissue penetration and immune-related adverse events associated with monoclonal antibodies restrict their widespread application. To address challenges faced by traditional combination therapies, we design a dual-responsive engineered nanoparticle based on ferritin (denoted as CMFn@OXA), achieving tumor-targeted delivery and controlled release of the anti-PD-L1 peptide CLP002 and oxaliplatin (OXA). Our results demonstrate that CMFn@OXA not only exhibits tumor-specific accumulation but also responds to matrix metalloproteinase-2/9 (MMP-2/9), facilitating the controlled release of CLP002 to block PD-1/PD-L1 interaction. Simultaneously, it ensures the precise delivery of the OXA to tumor cells and its subsequent release within the acidic environment of lysosomes, thereby fostering a synergistic therapeutic effect. Compared to traditional combination therapies, CMFn@OXA demonstrates superior performance in inhibiting tumor growth, extending the survival of tumor-bearing mice, and exhibiting excellent biocompatibility. Collectively, our results highlight CMFn@OXA as a novel and promising strategy in the field of cancer immunotherapy.

Associations of multiple toxic metal exposures with metabolic dysfunction-associated fatty liver disease: NHANES 2011-2018.

Background: The occurrence of metabolic dysfunction-associated fatty liver disease (MASLD) is driven by multiple factors including obesity, hypertension, dyslipidemia, and insulin resistance. However, epidemiological research investigating the association between metal exposure and MASLD occurrence remains limited. Methods: We conducted a large cross-sectional study with 6,520 participants who were involved in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Using generalized linear regression, we examined the relationship between five heavy metals (mercury, manganese, lead, selenium, cadmium) and MASLD. Furthermore, restricted cubic spline models and weighted quantile sum (WQS) analysis were employed to characterize the exposure-response relationship between the five metals and MASLD. Results: Higher blood selenium levels were associated with an increased likelihood of MASLD among US adults. Blood lead exposure was also positively correlated with MASLD risk. However, there was no significant association observed between blood cadmium, mercury, manganese levels, and MASLD risk. Among the five metals, blood cadmium exposure accounted for the highest proportion of MASLD risk. Conclusion: Our study indicated the significant association between blood cadmium and lead exposure levels and the occurrence of MASLD in a representative sample of US adults.

FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m6A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC.

Detection of the gene mutation of epidermal growth factor receptor in lung adenocarcinoma by radiomic features from a small amount of PET data.

OBJECTIVE: The purpose of this work was to identify the potential mutation of epidermal growth factor receptor in nonsmall cell adenocarcinoma by noninvasive method, and to explore whether the same or better effect can be achieved using a small amount of single-mode PET image data. METHOD: A total of 115 patients were recruited and the results of their 18F-FDG PET images and gene detection after resection were obtained; 117 original radiation features and 744 wavelet transform features were extracted from PET images. Several methods were used to reduce the dimension of the data, and four classifier models were established to classify it. The above process was repeated to reduce the total amount of data and the area under the receiver operating characteristic curve (AUC) value that changed with the reduction of the data and the stability of the results was recorded. RESULTS: The classifier with the best comprehensive performance under this dataset was logistic regression, whose AUC value is 0.843. And similar results can be obtained from only 30 cases of data. CONCLUSION: A similar or better result could be achieved using a small number of single-mode PET images. In addition, significant results could be obtained using only the PET images of 30 patients.

Porous polyoxotungstate/MXene hybrid films allowing for visualization of the energy storage status in high-performance electrochromic supercapacitors.

Electrochromic supercapacitors (ECSCs) have recently received growing attention for potential smart energy storage components in intelligent electronics. However, in the development of ECSCs, the design and assembly of high-performance electrode materials remain ongoing challenges. In this study, Ti3C2Tx MXene and polyoxotungstate (P2W18) were deposited on TiO2 nanowires to construct a unique three-dimensional (3D) porous hybrid film, NW@MXene/P2W18, via a convenient layer-by-layer self-assembly approach. The 3D porous structure of the nanocomposite reduced the aggregation and stacking of Ti3C2Tx MXene nanosheets during self-assembly, leading to the formation of unobstructed ion diffusion channels and interfacial charge transfer between adjacent layers, resulting in a good electrochemical performance. Compared to the tightly packed structure, the porous hybrid film demonstrated an enhanced electrochromic energy storage performance with a higher areal capacitance (i.e., 19.0 mF cm-2 at a current density of 0.6 mA cm-2), in addition to a high cycling stability (i.e., 90.7% retention rate after 2000 cycles), and an excellent color rendering efficiency. Subsequently, an asymmetric ECSC was fabricated using an NW@MXene/P2W18 film as the cathode and a TiO2 nanowire film as the anode. This ECSC exhibited a high areal capacitance of 4.0 mF cm-2 at a current density of 0.1 mA cm-2 with a wide operating window of 4.5 V, whilst also achieving high-speed color switching between olive green and dark blue during the charge/discharge processes, ultimately offering new avenues for the development of electrochromic energy storage electrode materials and the design of novel devices.

Sea-Cucumber-like Microstructure Polyoxometalate/TiO2 Nanocomposite Electrode for High-Performance Electrochromic Energy Storage Devices.

The key challenge in the practical application of electrochromic energy storage devices (EESDs) is the fabrication of high-performance electrode materials. Herein, we deposited K7[La(H2O)x(α2-P2W17O61)] (P2W17La) onto TiO2 nanowires (NW) to construct an NW-P2W17La nanocomposite using a layer-by-layer self-assembly method. In contrast to the pure P2W17La films, the nanocomposite exhibits enhanced electrochromic and electrochemical performance owing to the 3D sea-cucumber-like microstructure. An EESD using the NW-P2W17La film as the cathode exhibited outstanding electrochromic and energy storage properties, with high optical modulation (48.6% at 605 nm), high switching speeds (tcoloring = 15 s, tbleaching = 4 s), and high area capacitance (5.72 mF cm-2 at 0.15 mA cm-2). The device can reversibly switch between transparent and dark blue during the charge/discharge process, indicating that electrochromic contrast can be used as a quantitative indicator of the energy storage status.

COMMD proteins function and their regulating roles in tumors.

The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

Applications of radiomics-based analysis pipeline for predicting epidermal growth factor receptor mutation status.

BACKGROUND: This study aimed to develop a pipeline for selecting the best feature engineering-based radiomic path to predict epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). METHODS: The study enrolled 115 lung adenocarcinoma patients with EGFR mutation status from June 2016 and September 2017. We extracted radiomics features by delineating regions-of-interest around the entire tumor in 18F-FDG PET/CT images. The feature engineering-based radiomic paths were built by combining various methods of data scaling, feature selection, and many methods for predictive model-building. Next, a pipeline was developed to select the best path. RESULTS: In the paths from CT images, the highest accuracy was 0.907 (95% confidence interval [CI]: 0.849, 0.966), the highest area under curve (AUC) was 0.917 (95% CI: 0.853, 0.981), and the highest F1 score was 0.908 (95% CI: 0.842, 0.974). In the paths based on PET images, the highest accuracy was 0.913 (95% CI: 0.863, 0.963), the highest AUC was 0.960 (95% CI: 0.926, 0.995), and the highest F1 score was 0.878 (95% CI: 0.815, 0.941). Additionally, a novel evaluation metric was developed to evaluate the comprehensive level of the models. Some feature engineering-based radiomic paths obtained promising results. CONCLUSIONS: The pipeline is capable of selecting the best feature engineering-based radiomic path. Combining various feature engineering-based radiomic paths could compare their performances and identify paths built with the most appropriate methods to predict EGFR-mutant lung adenocarcinoma in 18FDG PET/CT. The pipeline proposed in this work can select the best feature engineering-based radiomic path.

Design and path tracking control of a continuum robot for maxillary sinus surgery.

PURPOSE: Continuum robots (CRs) have been developed for maxillary sinus surgery (MSS) in recent years. However, due to the anatomically curved and narrow pathway of the maxillary sinus and the deformable characteristics of the CR, it is still a challenge to accurately approach the target in the sinus. Thus, the CR-assisted MSS demands further research, whether in robotic system design or in reliable motion control. METHODS: A continuum robotic system integrated with essential instruments and sensors for MSS is developed, and the path tracking control of the designed CR is studied. The differential kinematic model of the CR is constructed. By analyzing the potential problem of the traditional Jacobian-based control, an iterative Jacobian transpose-based closed-loop control method is proposed to improve the path tracking performance. To validate the design of the CR and the effectiveness of the proposed control scheme, different groups of experiments are performed. RESULTS: With the proposed method, the path tracking performance of the CR is improved. Compared with the open-loop Jacobian transpose-based control method, the path tracking error of the proposed method is much less. The maxillary sinus phantom tests are conducted to verify the reachability of the designed CR. Given the reference path from the nostril to the target in the maxillary sinus phantom, experiments show a mean error of 0.96 mm. CONCLUSIONS: The designed CR is slender, flexible, and able to smoothly approach the target in a tortuous and constrained environment without colliding with or damaging the surrounding tissue. The designed continuum robotic system and the proposed iterative Jacobian transpose-based closed-loop control strategy have great potential for MSS. The limitations of the proposed method are also discussed.

Biodynamic responses of adolescent idiopathic scoliosis exposed to vibration.

Patients with adolescent idiopathic scoliosis suffer severe health issues. The unclear dynamic biomechanical characteristics of scoliosis were needed to be explored to improve the prevention and treatment in clinics. Validated 3D finite element (FE) models of thoracolumbosacral spine (T1-S1) both with and without scoliosis were developed from computed tomography (CT) images. Modal and harmonic analyses were performed to investigate the biomechanical responses of the spinal models to vibration. Resonant frequencies of the scoliotic model were lower than those of the model without scoliosis. Peak amplitudes occurred at vibrational frequencies close to the modal resonant frequencies, which caused the deformed thoracic segment in scoliosis suffered the maximum amplitude. The stresses on vertebrae and intervertebral discs in the scoliotic model derived from vibrations were significantly larger than those in the non-scoliosis model, and heterogeneously concentrated on the scoliotic thoracic segment. In conclusion, the scoliotic spine in the patients with Lenke 1BN scoliosis is more prone to injuries than the non-scoliotic spine while vibrating. Scoliotic thoracic segments in patients with Lenke 1BN scoliosis were the more vulnerable and sensitive component of the T1-S1 spine to vibration than lumbar spines. This study suggested that vibration would impair the scoliotic spines, and patients with Lenke 1BN scoliosis should avoid exposure to vibration, especially the low-frequency vibration.

A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer.

Lymph node metastasis (LNM) of colorectal cancer (CRC) is an important factor for both prognosis and treatment. Given the deficiencies of conventional tests, we aim to discover novel DNA methylation markers to efficiently identify LNM status of CRC. In this study, genome-wide methylation sequencing was performed in a cohort (n=30) using fresh CRC tissue to discover differentially methylated markers. These markers were subsequently validated with fluorescence quantitative PCR in a cohort (n=221), and the optimal marker was compared to conventional diagnostic methods. Meanwhile, immunohistochemistry was used to verify the effectiveness of the antibody corresponding to this marker in a cohort (n=56). LBX2 achieved an AUC of 0.87, specificity of 87.3%, sensitivity of 75.7%, and accuracy of 81.9%, which outperformed conventional methods including imaging (CT, PET-CT) with an AUC of 0.52, CA199 with an AUC of 0.58, CEA with an AUC of 0.56. LBX2 was also superior to clinicopathological indicators including the depth of tumor invasion and lymphatic invasion with an AUC of 0.61and 0.63 respectively. Moreover, the AUC of LBX2 antibody was 0.84, which was also better than these conventional methods. In conclusion, A novel methylation marker LBX2 could be used as a simple, cost-effective, and reliable diagnostic method for LNM of CRC.

Vanadium-Substituted Dawson-Type Polyoxometalate-TiO2 Nanowire Composite Film as Advanced Cathode Material for Bifunctional Electrochromic Energy-Storage Devices.

Polyoxometalates (POMs) demonstrate potential for application in the development of integrated smart energy devices based on bifunctional electrochromic (EC) optical modulation and electrochemical energy storage. Herein, a nanocomposite thin film composed of a vanadium-substituted Dawson-type POM, i.e., K7[P2W17VO62]·18H2O, and TiO2 nanowires were constructed via the combination of hydrothermal and layer-by-layer self-assembly methods. Through scanning electron microscopy and energy-dispersive spectroscopy characterisations, it was found that the TiO2 nanowire substrate acts as a skeleton to adsorb POM nanoparticles, thereby avoiding the aggregation or stacking of POM particles. The unique three-dimensional core-shell structures of these nanocomposites with high specific surface areas increases the number of active sites during the reaction process and shortens the ion diffusion pathway, thereby improving the electrochemical activities and electrical conductivities. Compared with pure POM thin films, the composite films showed improved EC properties with a significant optical contrast (38.32% at 580 nm), a short response time (1.65 and 1.64 s for colouring and bleaching, respectively), an excellent colouration efficiency (116.5 cm2 C-1), and satisfactory energy-storage properties (volumetric capacitance = 297.1 F cm-3 at 0.2 mA cm-2). Finally, a solid-state electrochromic energy-storage (EES) device was fabricated using the composite film as the cathode. After charging, the constructed device was able to light up a single light-emitting diode for 20 s. These results highlight the promising features of POM-based EES devices and demonstrate their potential for use in a wide range of applications, such as smart windows, military camouflage, sensors, and intelligent systems.

Evaluating image quality and optimal parameters for non-linear blending dual-energy computed tomography images of hepatic portal veins by blending-property-map.

BACKGROUND: Blending technology is usually used to improve quality of dual-energy computed (DECT) images. OBJECTIVES: To evaluate the blended DECT image qualities by employing the Blending-Property-Map (BP-Map) and elucidating the optimal parameters with the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). METHODS: Sixty pairs of 80 kV and 140 kV CT images are blended non-linearly by four methods. Protocol A uses the fixed values of blending width (BW) and blending center (BC); Protocol B uses the values of BW =  (CThepatic portal vein - CThepatic parenchymal) / 2 and BC =  (CThepatic portal vein + CThepatic parenchymal) / 2; Protocol C uses a BW ranging from 10 to 100 HU at an interval of 10 HU and BC = (CThepatic portal vein + CThepatic parenchymal) / 2; Protocol D uses the BP-Map that covers all possible values of BW and BC. RESULTS: When using CT value of adipose tissue as noise, the calculated SNR and CNR of optimal blending width and blending center were 123.22±41.73 and 9.00±3.52, respectively, by the BP-Map in the protocol D. By employing the CT value of back muscle as noise, the SNR and CNR of the best-blended images were 75.90±14.52 and 6.39±2.37, respectively. The subjective score of protocol D was 4.88±0.12. CONCLUSIONS: Compared to traditional blending methods, the BP-Map technique can determine the optimal blending parameter and provide the best-blended images with the highest SNR and CNR.

Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma.

Background: THO complex members (THOCs) are essential for mRNA processing, transcription elongation, mRNA export and genome integrity, which may be associated with tumor. However, the significance of THO complex members in Hepatocellular carcinoma (HCC) has not been clarified. Methods: In this study, we investigated expression levels, clinicopathological correlation, diagnostic and prognostic value, disease associations, co-expression network, functional enrichment, genetic variation, drug sensitivity, molecular targets, and immune infiltration of THOCs in HCC using UALCAN, ICGC, HPA, Kaplan-Meier Plotter, The Open Targets Platform database, GeneMANIA, WebGestalt, GSCALite, LinkedOmics, TIMER. Meanwhile, the mRNA expression levels of THOCs in HCC were verified by qRT-PCR. Results: THOCs were significantly up-regulated at the transcription level in HCC, and overexpression of THOCs was correlated with clinicopathological features. THOCs had potential diagnostic and prognostic value for HCC. THOCs could participate in apoptosis, regulate cell cycle, and were also involved in DNA damage response. Important cancer-related signaling pathways such as EMT, RAS/MAPK pathway and RKT pathway were also related to THOCs expression. In addition, the expression level of THOC1/2/6/7 was negatively correlated with drug resistance. And miRNA, kinase, and transcription factor targets associated with THOCs have been identified. Meanwhile, THOCs were associated with immune infiltration in HCC. Conclusion: Our study revealed that THO complex members have important clinical significance for HCC and have potential clinical utility in diagnosis, treatment and prognosis.

Development and validation of a two-segment continuum robot for maxillary sinus surgery.

BACKGROUND: Existing rigid instruments have difficulties in backward inspection and operation. Moreover, the pathway to the maxillary sinus is curved and narrow, resulting in complex and repetitive manual operations. There is a necessity to develop a retro-flexing robot and achieve path-following motion. METHODS: A continuum robotic system is developed for maxillary sinus surgery (MSS). And the system adopts an anatomical constraint-based optimization of the follow-the-leader strategy to generate a safe control scheme along a given path. RESULTS: The accuracy of the system is evaluated, and the task of reaching deep-seated targets is performed in a constrained anatomical space. The simulations and experiments of the path-following motion have validated the feasibility of the proposed method. Furthermore, a preliminary porcine study is performed to assess the capability of instruments. CONCLUSIONS: The developed continuum robotic system can meet the requirements of MSS.

m6A Modification-Mediated DUXAP8 Regulation of Malignant Phenotype and Chemotherapy Resistance of Hepatocellular Carcinoma Through miR-584-5p/MAPK1/ERK Pathway Axis.

Hepatocellular carcinoma (HCC) has a poor prognosis due to its high malignancy, rapid disease progression, and the presence of chemotherapy resistance. Long-stranded non-coding RNAs (lncRNAs) affect many malignant tumors, including HCC. However, their mechanism of action in HCC remains unclear. This study aimed to clarify the role of DUXAP8 in regulating the malignant phenotype and chemotherapy resistance in HCC. Using an in vivo xenograft tumor model, the regulatory functions and mechanisms of lncRNA DUXAP8 in the progression and response of HCC to chemotherapy were explored. It was found that DUXAP8 was significantly upregulated in a patient-derived xenograft tumor model based on sorafenib treatment, which is usually associated with a relatively poor prognosis in patients. In HCC, DUXAP8 maintained its upregulation in the expression by increasing the stability of m6A methylation-mediated RNA. DUXAP8 levels were positively correlated with the proliferation, migration, invasion, and chemotherapy resistance of HCC in vivo and in vitro. In the mechanistic study, it was found that DUXAP8 competitively binds to miR-584-5p through a competing endogenous RNA (ceRNA) mechanism, thus acting as a molecular sponge for miR-584-5p to regulate MAPK1 expression, which in turn activates the MAPK/ERK pathway. These findings can provide ideas for finding new prognostic indicators and therapeutic targets for patients with HCC.

Glutathionylation-dependent proteasomal degradation of wide-spectrum mutant p53 proteins by engineered zeolitic imidazolate framework-8.

Point mutations within the DNA-binding domain of the TP53 gene occur in a significant percentage of human cancer, leading to cellular accumulation of highly stabilized mutant p53 proteins (mutp53) with tumor-promoting properties. Depletion of mutp53, through inducing either autophagic or proteasomal degradation, is an attractive strategy for the therapy of p53-mutated cancer, but the currently-known degradation inducers, almost exclusively small molecules, are inadequate. Here we show that pH-responsive zeolitic imidazolate framework-8 (ZIF-8) offers a novel solution to mutp53 degradation. ZIF-8 facilitated ubiquitination-mediated and glutathionylation-dependent proteasomal degradation of all of the nine mutp53 we tested, including six hot-spot mutp53, but not the wild-type p53 protein. Sustained elevation of intracellular Zn++ level, resulted from decomposition of the internalized ZIF-8 in the acidic endosomes, decreased the intracellular reduced glutathione (GSH): oxidized glutathione (GSSG) ratio and was essential for mutp53 glutathionylation and degradation. ZIF-8 modified with an Z1-RGD peptide, exhibiting enhanced cellular internalization and improved decomposition behavior, preferentially killed mutp53-expressing cancer cells and demonstrated remarkable therapeutic efficacy in a p53 S241F ES-2 ovarian cancer model as well as in a p53 Y220C patient-derived xenograft (PDX) breast cancer model. The ability to induce wide-spectrum mutp53 degradation gives ZIF-8 a clear advantage over other degradation-inducers, and engineered nanomaterials may be promising alternatives to small molecules for the development of mutp53-targeting drugs.