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Abstract Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

Abstract Off-line leachate collection from agricultural landscapes cannot guarantee precise evaluation of agricultural non-point source (ANPS) due to geospatial variations, time, and transportation from the field to the laboratory. Implementing an in-situ nitrogen and phosphorous monitoring system with a robust photochemical flow analysis is imperative for precision agriculture, enabling real-time intervention to minimize non-point source pollution and overcome the limitations posed by conventional analysis in laboratory. A reliable, robust and in-situ approach was proposed to monitor nitrogen and phosphorous for determining ANPS pollution. In this study, a home-made porous ceramic probe and the frequency domain reflectometer (FDR) based water content sensors were strategically placed at different soil depths to facilitate the collection of leachates. These solutions were subsequently analyzed by in-situ photochemical flow analysis monitoring system built across the field to estimate the concentrations of phosphorus and nitrogen. After applying both natural and artificial irrigation to the agricultural landscape, at least 10 mL of soil leachates was consistently collected using the porous ceramic probe within 20 min, regardless of the depth of the soil layers when the volumetric soil water contents are greater than 19%. The experimental results showed that under different weather conditions and irrigation conditions, the soil water content of 50 cm and 90 cm below the soil surface was 19.58% and 26.08%, respectively. The average concentrations of NH4 +-N, NO3 −-N, PO4 3− are 0.584 mg/L, 15.7 mg/L, 0.844 mg/L, and 0.562 mg/L, 16.828 mg/L and 0.878 mg/L at depths of 50 cm and 90 cm below the soil surface, respectively. Moreover, the comparison with conventional laboratory spectroscopic analysis confirmed R2 values of 0.9951, 0.9943, 0.9947 average concentration ranges of NH4 +-N, NO3 −-N, and PO4 3−, showcasing the accuracy and reliability of robust photochemical flow analysis in-situ monitoring system. The suggested monitoring system can be helpful in the assessment of soil nutrition for precision agriculture.

The accurate fenestration, screw implantation and assisting stabilizing‐plate placement in surgery of benign tumors in the proximal femur needs be defined easily. The aim of this study was to investigate the value of 3D printed multifunctional guides plate (3D‐MGP) based on computer aided design. Between January 2020 and June 2022, 17 patients (nine females and eight males) with benign proximal femoral tumor had lesion curettage and allograft combined with internal plate fixation using 3D‐MGP. In this study, the patients had CT scans and a technician reconstructed the 3D images of tumor and the femur, a doctor designed the location and margin of the fenestration and screws, and integrated different functions into MGP for benign proximal femoral lesions, which assisted in precise localization, fenestration and screw drilling. Musculoskeletal Tumor Society (MSTS) scoring was used to evaluate lower extremity function. Bone healing and the screws location was assessed with the radiographs. All patients underwent successful surgery with complete resection of the tumor and internal fixation with using the 3D‐MGP. The mean follow‐up was 16.4 months. The operative time was 126.47 ± 18.44 min, intraoperative bleeding was 198.23 ± 67.94 mL, intraoperative fluoroscopy was 6.47 ± 0.62, postoperative drainage was 223.82 ± 119.51 mL, and MSTS score was 27.29 ± 1.31 points. There were no unplanned fenestration and improper screw fixation. The 3D‐MGP enabled personalized and accurate location of tumor, fenestration, screw placement and assisted stabilizing‐plate placement for the treatment of benign tumor of the proximal femur. This technique has the potential to shorten operative times, decrease intraoperative bleeding, and reduce radiation exposure to patients.

AimTo investigate the effect and clinical advantage of transanal intersphincteric (ISR) under direct view in the jackknife position combined with laparoscopic total mesorectal excision (TME) for treating ultra-low rectal cancer. Additionally, the feasibility of this surgical technique was evaluated.MethodThis was a retrospective, single-center, single-arm pilot study. Ten patients with ultra-low rectal cancer underwent treatment by the same surgical team for direct view transanal ISR combined with laparoscopic TME in the Department of Anorectal Surgery, Huizhou Central People's Hospital between January 2021 and June 2021. The relevant clinical data were collected and analyzed.ResultsAll the patients underwent complete mesenteric resection without conversion to laparotomy. The circumferential and distal resection margins (CRM and DRM) were negative. The mean distance between the lower margin of the tumor and the anal margin was 2.8 ± 0.8 cm, and the mean margin of distal resection was 1.2 ± 0.2 cm. TNM pathological stages I, II, III, and IV were observed in 6, 2, 2, and 0 cases, respectively. The median follow-up period was 15 months (interquartile range, 8 months). The mean Wexner and Low Anterior Resection Syndrome scores at 12 months after ileostomy were 8.1 ± 2.1 and 22.4 ± 5.7, respectively.ConclusionTransanal ISR under direct view in the jackknife position combined with laparoscopic TME is safe and feasible for the treatment of ultralow rectal cancer.

Objective Percutaneous CT‐guided radiofrequency ablation (CT‐RFA) is a widely accepted procedure for treatment of osteoid osteomas. However, the application of CT‐RFA was restricted as a result of some drawbacks, such as radiation exposure, and inconvenience in general anesthesia. The primary aim of this study is to evaluate the safety and efficacy of intra‐operative TiRobot‐assisted percutaneous RFA of osteoid osteomas. Methods We retrospectively reviewed 21 medical files of patients who were treated with percutaneous RFA of osteoid osteomas guided by the TiRobot system in our institution between March 2021 and April 2022. The three‐dimensional images obtained by a 3D C‐arm intra‐operatively were sent to the TiRobot system. The puncture point and trajectory were designed. Then the guide pin was positioned to the lesion with the assistance of TiRobot and the biopsy sheath was inserted into the lesion through the guide pin. The tumor was biopsied for pathological examination. Then the RFA needle was inserted into the nidus through the biopsy sheath for thermal ablation. Data were extracted on the associated complications, the reduction in pain at 1 month and 1 year postoperatively assessed by the visual analogue scale (VAS). A paired t‐test was used to compare the pre‐operative and post‐operative VAS scores. Results The patients included 17 males and four females with a mean age of 19.5 ± 10.4 years (range 3–45 years). Lesions were located on the femur in nine cases, on the tibia in nine cases, on the humerus in one case, on the calcaneus in one case, and on the acetabulum in one case. TiRobot‐assisted percutaneous RFA was successfully performed on all 21 patients. There was no intra‐operative or post‐operative complications observed. Pathological diagnosis of osteoid osteoma was obtained in 11 patients, but the other 10 cases were not pathologically diagnosed. The mean follow‐up time was 18.8 months (range: 12–26 months).Post‐operative VAS scores were reduced significantly in all cases. The mean VAS score decreased from 6.5 pre‐operatively to 0.5 at 1 month post‐operatively and to 0.1 at 1 year post‐operatively. Conclusion As a reliable technique for localizing and resection of nidus, TiRobot‐assisted percutaneous RFA is a safe and effective option for the treatment of osteoid osteomas.

Abstract Background The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. Methods In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p

Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%–17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.

Abstract Background Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+IFDCS) is a rare disease characterized by mild clinical symptoms and non-specific imaging findings. The diagnosis of the disease depends on pathological diagnosis. However, EBV+IFDCS has a very broad spectrum of histological morphology and immune phenotypes, and its histopathological features have not been fully described by pathologists. Case presentation A 59-year-old female, with no significant discomfort, was found to have a splenic mass during a routine physical examination. Microscopic examination at low magnification revealed numerous epithelioid granulomas, amidst which a substantial inflammatory response was observed. Interspersed among the dense inflammatory cells were spindle or oval-shaped cells, distributed sporadically with indistinct boundaries. Under high magnification, these spindle cells had subtle features: smooth and clear nuclear membranes, inconspicuous small nucleoli, and infrequent mitotic figures. Immunophenotypically, the spindle cells expressed CD21 and CD23, and Epstein-Barr encoding region (EBER) in situ hybridization yielded positive results. The inflammatory milieu predominantly consisted of T cells, with a minority of plasma cells expressing IgG4. The confluence of morphological and immunohistochemical findings led to the final pathological diagnosis of EBV+IFDCS in this case. Conclusions The presentation of EBV+IFDCS with pronounced granulomatous changes is rare. This morphological variant poses a high risk of misdiagnosis, frequently leading to confusion with other granulomatous diseases. Accurate diagnosis necessitates a comprehensive analysis, integrating immunohistochemistry and in situ hybridization. The case presented here is instrumental in raising awareness and understanding of EBV+IFDCS, with the goal of reducing misdiagnoses and unrecognized cases.

Objective Using a fibula autograft (FA) to reconstruct defects after en bloc resection of giant cell tumor of bone (GCTB) in the distal radius is classic but has high complication rates. We describe a novel reconstruction method employing the cooperative application of LARS® and a 3D‐printed prosthesis (L‐P) and investigate whether it improves postoperative outcomes. Methods From April 2015 to August 2022, 14 patients who underwent the cooperative L‐P reconstruction method after en bloc resection of distal radial GCTBs and 31 patients who received FA reconstruction were enrolled as two retrospective cohorts in this comparative study. The properties of the implants and critical surgical techniques were elaborated in the L‐P group. Preoperative function, intraoperative data, and postoperative clinical, functional, and radiographic outcomes of all patients were recorded and compared between the two groups. The grip strength and range of wrist motion, including extension, flexion, radial deviation, and ulnar deviation, were measured. The Mayo modified wrist and Musculoskeletal Tumor Society scores were chosen to assess wrist function and surgical functional outcomes, respectively. Kaplan–Meier curves were generated to analyze the significant differences in complication rates and implant survival between the two groups. Results In both groups, all 45 patients underwent the operation without complication with similar average osteotomy lengths and bleeding volumes, while a shorter operative duration was achieved in the L‐P group (201.43 ± 22.87 min vs. 230.16 ± 51.44 min, P = 0.015). At a mean follow‐up of 40.42 ± 18.43 months (range, 14–72 months), both reconstruction methods effectively ameliorated postoperative function. Patients who received L‐P showed higher postoperative modified Mayo wrist scores (81.43 ± 5.49 vs. 71.13 ± 16.10, P = 0.003), Musculoskeletal Tumor Society scores (27.64 ± 1.34 vs. 25.06 ± 2.95, P = 0.004), and grip strength on the normal side (68.71% ± 8.00% vs. 57.81% ± 12.31%, P = 0.005) than the FA group. Better wrist extension (63.21° ± 8.99° vs. 45.32° ± 14.53°, P

High quality and high efficiency cutting process is of great significance to the components manufacturing related to machinability of workpiece materials. As a typical difficult-to-machine material induced mainly by high toughness, NiTi alloy faces challenges such as high cutting force and difficult chip breaking during the cutting process. To solve these problems, this paper presents a novel surface dealloying assisted machining method, i.e., the preparation of nanoporous structures on the workpiece surface with dealloying treatment, to improve the machinability of NiTi alloy. Based on high speed in-situ imaging of material removal process, the presence of dealloyed layer leads to a segmented flow mode instead of homogeneous severe plastic deformation without dealloying treatment. The change in material removal mode is beneficial to decrease the cutting force and energy and improve the machined surface quality. The embrittlement effect of dealloyed layer inhibits material plastic flow and promotes periodic crack nucleation and propagation. An analytical model is developed to characterize the brittle crack propagation, which provides theoretical basis for explaining embrittlement effect of dealloyed layer. This work verifies the feasibility and effectiveness of the proposed method to modify the machinability of NiTi alloy and provides new ideas for the development of manufacturing processes.

Current challenges in collecting and analyzing subway vibration data include the absence of standardized data collection methods, limitations in data analysis techniques, and an unclear understanding of the effects of geological conditions on vibrations. This study investigated vertical vibrations of tunnel walls and the ground above tunnels under different geological conditions of soft soil and rock strata at horizontal distances of 0, 15 m, and 30 m from the tunnel center line during train passages. The collected data underwent Fourier transformation and 1/3 octave processing to extract spectral characteristics and analyze transmission losses across different frequency bands. Our findings revealed two vibration peaks in the transmission process for both soft soil and rock formation geology. Specifically, high-frequency vibrations in soft soil experienced greater attenuation when transmitted from the tunnel wall to the ground at 0 m, while low-frequency vibrations in rock formations showed greater attenuation. We also observed a vibration amplification phenomenon at 15 m under soft soil geology conditions. Although low-frequency vibrations below 12.5 Hz showed slight attenuation within a 30 m test distance under both geological conditions, vibrations above 40 Hz experienced significant attenuation. These results offer valuable insights for reducing vibrations in subway superstructures and planning subway lines under diverse geological conditions. Furthermore, this study serves not only as a basis for mitigating vibrations in metro spans and designing metro lines in various geological contexts but also establishes a scientific foundation for future research.

Detecting the factors affecting drivers’ safe driving and taking early warning measures can effectively reduce the probability of automobile safety accidents and improve vehicle driving safety. Considering the two factors of driver fatigue and distraction state, their influences on driver behavior are elaborated from both experimental data and an accident library analysis. Starting from three modes and six types, intelligent detection methods for driver fatigue and distraction detection from the past five years are reviewed in detail. Considering its wide range of applications, the research on machine vision detection based on facial features in the past five years is analyzed, and the methods are carefully classified and compared according to their innovation points. Further, three safety warning and response schemes are proposed in light of the development of autonomous driving and intelligent cockpit technology. Finally, the paper summarizes the current state of research in the field, presents five conclusions, and discusses future trends.

Abstract Background To reconstruct massive bone defects of the femoral diaphysis and proximal end with limited bilateral cortical bone after joint-preserving musculoskeletal tumor resections, two novel 3D-printed customized intercalary femoral prostheses were applied. Methods A series of nine patients with malignancies who received these novel 3D-printed prostheses were retrospectively studied between July 2018 and November 2021. The proximal and diaphyseal femur was divided into three regions of interest (ROIs) according to anatomic landmarks, and anatomic measurements were conducted on 50 computed tomography images showing normal femurs. Based on the individual implant-involved ROIs, osteotomy level, and anatomical and biomechanical features, two alternative 3D-printed prostheses were designed. In each patient, Hounsfield Unit (HU) value thresholding and finite element analysis were conducted to identify the bone trabecula and calcar femorale and to determine the stress distribution, respectively. We described the characteristics of each prosthesis and surgical procedure and recorded the intraoperative data. All patients underwent regular postoperative follow-up, in which the clinical, functional and radiographical outcomes were evaluated. Results With the ROI division and radiographic measurements, insufficient bilateral cortical bones for anchoring the traditional stem were verified in the normal proximal femur. Therefore, two 3D-printed intercalary endoprostheses, a Type A prosthesis with a proximal curved stem and a Type B prosthesis with a proximal anchorage-slot and corresponding locking screws, were designed. Based on HU value thresholding and finite element analysis, the 3D-printed proximal stems in all prostheses maximally preserved the trabecular bone and calcar femorale and optimized the biomechanical distribution, as did the proximal screws. With the 3D-printed osteotomy guide plates and reaming guide plates, all patients underwent the operation uneventfully with a satisfactory duration (325.00 ± 62.60 min) and bleeding volume (922.22 ± 222.36 ml). In the follow-up, Harris Hip and Musculoskeletal Tumor Society scores were ameliorated after surgery (P

Abstract Background The site information of substrates that can be cleaved by human immunodeficiency virus 1 proteases (HIV-1 PRs) is of great significance for designing effective inhibitors against HIV-1 viruses. A variety of machine learning-based algorithms have been developed to predict HIV-1 PR cleavage sites by extracting relevant features from substrate sequences. However, only relying on the sequence information is not sufficient to ensure a promising performance due to the uncertainty in the way of separating the datasets used for training and testing. Moreover, the existence of noisy data, i.e., false positive and false negative cleavage sites, could negatively influence the accuracy performance. Results In this work, an ensemble learning algorithm for predicting HIV-1 PR cleavage sites, namely EM-HIV, is proposed by training a set of weak learners, i.e., biased support vector machine classifiers, with the asymmetric bagging strategy. By doing so, the impact of data imbalance and noisy data can thus be alleviated. Besides, in order to make full use of substrate sequences, the features used by EM-HIV are collected from three different coding schemes, including amino acid identities, chemical properties and variable-length coevolutionary patterns, for the purpose of constructing more relevant feature vectors of octamers. Experiment results on three independent benchmark datasets demonstrate that EM-HIV outperforms state-of-the-art prediction algorithm in terms of several evaluation metrics. Hence, EM-HIV can be regarded as a useful tool to accurately predict HIV-1 PR cleavage sites.

Abstract Background Jingmen tick virus (JMTV) is a newly discovered tick-borne virus that can cause disease in humans. This virus has been authenticated as being extremely widespread worldwide and as posing a significant threat to public health and safety. Methods We collected 35 ticks belonging to two tick species from wild boars in Nanping, Fujian Province, China. JMTV-specific genes were amplified by qRT-PCR and nested PCR to confirm the presence of this pathogen. Results More than one third of of all ticks collected (11/35) were positive for JMTV. Viral sequences were obtained from three of the JMTV-positive ticks, including the complete genomic sequence from one tick. This was the first time that JMTV was identified in the hard-bodied tick Amblyomma testudinarium. Phylogenetic analysis revealed that JMTV from Fujian Province shared > 90% identity with other isolates derived from China, but was distinct from those reported in France and Cambodia. Conclusions JMTV is characterized by relatively low mutations and has its own local adaptive characteristics in different regions. Our findings provide molecular evidence of the presence of JMTV in an overlooked tick species from an area not unrecognized as being endemic. They also suggest that JMTV occupies a wider geographical distribution than currently believed and is a potential disease vector. Graphical abstract

Background: Current reconstruction methods of the pelvic ring after extensive resection of tumors involving the sacroiliac joint have a high incidence of failure. We aimed to study the effect of 3D-printed patient-specific implant reconstruction to show that this method is stable and has a low risk of failure.Methods: Between February 2017 and November 2021, six patients with bone tumors involving the sacroiliac joint (Enneking I + IV) who received 3D-printed patient-specific implants for pelvic reconstructive surgery were retrospectively analyzed. Two female and four male patients with a mean age of 41.83 years (range 25–65 years) were included. Two were osteosarcomas, two chondrosarcomas, one malignant fibrous histiocytoma, and one giant cell tumor of bone. For each patient, preoperative osteotomy guides were designed to ensure accurate tumor resection and individualized prostheses were designed to ensure a perfect fit of the bone defect. General, oncologic, and functional outcomes, implant status, and complications were retrospectively analyzed. The Visual Analog Scale (VAS) was used to assess pain and the Musculoskeletal Tumor Society (MSTS) score was used to assess hip function. Osseointegration was assessed by CT.Results: According to the preoperative design, complete resection of the entire tumor and reconstruction with a custom 3D-printed sacroiliac joint implant was completed without perioperative severe complications or deaths. Relatively satisfactory surgical margins were achieved. The mean operative time and intraoperative blood loss were 495 min (420–600 min) and 2533.33 mL (range, 1,200–3,500 mL), respectively. The mean follow-up was 49.83 months (range, 18–75 months). At the last follow-up, all four patients were disease-free, and the two patients who developed lung metastases were alive with tumors. All patients could walk unassisted. The mean VAS was 1.33 (range, 0–2). The mean MSTS score was 25.33 (range, 24–27). CT showed complete osseointegration of the implant to the ilium and sacrum.Conclusion: The 3D-printed custom prosthesis can effectively reconstruct pelvic stability after total sacroiliac joint resection with satisfactory clinical results.

Urban autonomous vehicles on city roads are subject to various constraints when changing lanes, and commonly used trajectory planning methods struggle to describe these conditions accurately and directly. Therefore, generating accurate and adaptable trajectories is crucial for safer and more efficient trajectory planning. This study proposes an optimal control model for local path planning that integrates dynamic vehicle constraints and boundary conditions into the optimization problem’s constraint set. Using the lane-changing scenario as a basis, this study establishes environmental and collision avoidance constraints during driving and develops a performance metric that optimizes both time and turning angle. The study employs the Gauss pseudo-spectral method to continuously discretize the state and control variables, converting the optimal control problem into a nonlinear programming problem. Using numerical solutions, variable control and state trajectories that satisfy multiple constraint conditions while optimizing the performance metric are generated. The study employs two weights in the experiment to evaluate the method’s performance, and the findings demonstrate that the proposed method guarantees safe obstacle avoidance, is stable, and is computationally efficient at various interpolation points compared to the Legendre pseudo-spectral method (LPM) and the Shooting method.

ABSTRACT Introduction: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. Methods: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. Results: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P

Objective This study aims to describe and analyze the transoral and transnasal approaches for pathologies of the ventral atlas and axis vertebrae, which are considered technically challenging regions for diagnostic biopsy. Methods A series of transnasal endoscopic approach (TNA) and transoral approach (TOA) biopsies for the pathologies of the first and second cervical vertebrae were conducted and retrospectively analyzed from July 2014 to May 2021. The depth of the biopsy trajectory was measured on computed tomography images for all nine patients (eight males and one female with an average age of 58.11 ± 11.60 years), as were the coronal, sagittal, and vertical biopsy safe ranges. The characteristics of each lesion, including radiographic features, blood supply, and destruction of anterior or posterior vertebral body edges, were evaluated to guide the biopsy. Four biopsy core techniques (BCTs), including “lesion perforating”, “aspiration”, “cutting‐and‐scraping” and “biopsy forceps utilization” were elaborated in this study. The biopsy procedures and periprocedural precautions were demonstrated. Patient demographics, clinical data, lesion characteristics, diagnostic yield, and complications were recorded for each case. Results Eight TOA biopsies for the axis vertebral body and one TNA biopsy for the atlas anterior arch were successfully performed and yielded adequate pathologies. All biopsies were organized based on the preprocedural radiographic measurements, which showed that the average length of biopsy trajectory and coronal, sagittal, and vertical safe biopsy ranges were 85.00 ± 5.88, 20.63 ± 4.75, 16.25 ± 1.49, and 24.63 ± 2.26 mm, respectively, and these corresponding data were 95, 36, 9, and 26 mm in the TNA patient. Six osteolytic lesions (66.7%), one osteoblastic lesion (11.1%), and two mixed lesions (22.2%) were observed, among which seven lesions had a rich blood supply. Biopsy forceps and core needles were utilized to obtain samples in six and three patients, respectively. All the TNA and TOA biopsies were performed with cooperative application of multiple BCTs under compound anatomic and stereotactic navigations. Intraprocedural or postprocedural complications occurred in no patients who underwent the biopsy in the follow‐up period (1–39 months). No significant differences were found between the preprocedural and postprocedural blood indexes and visual analogue scale scores. Conclusion With a sophisticated preprocedural arrangement, cooperative application of BCTs, and careful periprocedural precautions, transnasal endoscopic and transoral biopsies are two feasible, efficient, and well‐tolerated procedures that achieve satisfactory diagnostic yield, complication rate, and clinical outcome.

Abstract Solid polymer electrolytes (SPEs) are still being considered as a candidate to replace liquid electrolytes for high‐safety and flexible lithium batteries due to their superiorities including light‐weight, good flexibility, and shape versatility. However, inefficient ion transportation of linear polymer electrolytes is still the biggest challenge. To improve ion transport capacity, developing novel polymer electrolytes are supposed to be an effective strategy. Nonlinear topological structures such as hyperbranched, star‐shaped, comb‐like, and brush‐like types have highly branched features. Compared with linear polymer electrolytes, topological polymer electrolytes possess more functional groups, lower crystallization, glass transition temperature, and better solubility. Especially, a large number of functional groups are beneficial to dissociation of lithium salt for improving the ion conductivity. Furthermore, topological polymers have strong design ability to meet the requirements of comprehensive performances of SPEs. In this review, the recent development in topological polymer electrolytes is summarized and their design thought is analyzed. Outlooks are also provided for the development of future SPEs. It is expected that this review can raise a strong interest in the structural design of advanced polymer electrolyte, which can give inspirations for future research on novel SPEs and promote the development of next‐generation high‐safety flexible energy storage devices.

Background: Reconstruction after a total sacrectomy is a challenge due to the special anatomical and biomechanical factors. Conventional techniques of spinal-pelvic reconstruction do not reconstruct satisfactorily. We describe a novel three-dimensional-printed patient-specific sacral implant in spinopelvic reconstruction after total en bloc sacrectomy.Methods: We performed a retrospective cohort study including 12 patients with primary malignant sacral tumors, including 5 men and 7 women with a mean age of 58.25 years (range 20–66 years), undergoing total en bloc sacrectomy with 3D printed implant reconstruction from 2016 to 2021. There were 7 cases of chordoma, 3 cases of osteosarcoma, 1 case of chondrosarcoma and 1 case of undifferentiated pleomorphic sarcoma. We use CAD technology to determine surgical resection boundaries, design cutting guides, and individualized prostheses, and perform surgical simulations before surgery. The implant design was biomechanically evaluated by finite element analysis. Operative data, oncological and functional outcomes, complications, and implant osseointegration status of 12 consecutive patients were reviewed.Results: The implants were implanted successfully in 12 cases without death or severe complications during the perioperative period. Resection margins were wide in 11 patients and marginal in one patient. The average blood loss was 3875 mL (range, 2000–5,000 mL). The average surgical time was 520 min (range, 380–735 min). The mean follow-up was 38.5 months. Nine patients were alive with no evidence of disease, two patients died due to pulmonary metastases, and one patient survived with disease due to local recurrence. Overall survival was 83.33% at 24 months. The Mean VAS was 1.5 (range, 0–2). The mean MSTS score was 21 (range, 17–24). Wound complications occurred in 2 cases. A deep infection occurred in one patient and the implant was removed. No implant mechanical failure was identified. Satisfactory osseointegration was found in all patients, with a mean fusion time of 5 months (range 3–6 months).Conclusion: The 3D-printed custom sacral prosthesis has been effective in reconstructing spinal-pelvic stability after total en bloc sacrectomy with satisfactory clinical outcomes, excellent osseointegration, and excellent durability.

Background: There are a limited but increasing number of case reports and series describing the use of 3D-printed prostheses in bone tumor surgery.Methods: We describe a new approach to performing nerve-preserving hemisacrectomy in patients with sacral giant cell tumors with reconstruction using a novel 3D-printed patient-specific modular prosthesis. The series included four female and two male patients with a mean age of 34 years (range, 28–42 years). Surgical data, imaging assessments, tumor and functional status, implant status, and complications were retrospectively analyzed in six consecutive patients.Results: In all cases, the tumor was removed by sagittal hemisacrectomy, and the prosthesis was successfully implanted. The mean follow-up time was 25 months (range, 15–32 months). All patients in this report achieved successful surgical outcomes and symptomatic relief without significant complications. Clinical and radiological follow-up showed good results in all cases. The mean MSTS score was 27.2 (range, 26–28). The average VAS was 1 (range, 0–2). No structural failures or deep infections were detected in this study at the time of follow-up. All patients had good neurological function. Two cases had superficial wound complications. Bone fusion was good with a mean fusion time of 3.5 months (range, 3–5 months).Conclusion: These cases describe the successful use of custom 3D-printed prostheses for reconstruction after sagittal nerve-sparing hemisacrectomy with excellent clinical outcomes, osseointegration, and durability.

Abstract Lithium metal batteries hold promise for energy storage applications but suffer from uncontrolled lithium dendrites. In this study, a new composite membrane based on modified natural polymer and ZIF‐67 is designed and prepared by the in situ composite method for the first time. Among them, a modified natural polymer composed of lithium alginate (LA) and polyacrylamide (PAM) can be obtained by electrospinning. Importantly, the polar functional groups of natural polymers can interact by hydrogen bonding and MOFs can construct lithium‐ion transport channels. Consequently, compared with LA‐PAM electrolyte without MOF, the electrochemical stability window of ZIF‐67‐LA‐PAM electrolyte becomes wider from 4.5 to 5.2 V, and the lithium‐ion transference number (tLi+) enhances from 0.326 to 0.627 at 30°C. It is worth noting that the symmetric cells with ZIF‐67‐LA‐PAM have superior stable cycling performance at 40 and 100 mA cm−2, and a high rate at 10C and 20C for LFP cells. Besides, the cell with NCM811 high‐voltage cathode can run stably for 400 cycles with an initial discharge capacity of 136.1 mAh g−1 at 0.5C. This work provides an effective method for designing and preparing MOF‐natural polymer composite electrolytes and exhibits an excellent application prospect in high‐energy‐density lithium metal batteries.

BackgroundThis study aims to introduce a reconstruction method of applying allografts and absorbable screws to repair large bone defects caused by the resection of giant osteochondroma.MethodsA retrospective study of a series of patients who underwent the resection of giant osteochondroma reconstructed by allografts and absorbable screws was conducted from February 2020 to September 2021. Their demographic data, location site, area of bone defect, and pertinent operative details were recorded. The reconstruction modality of allografts was elaborated on. In the follow-up, radiographic images were utilized to determine bone union, and the Musculoskeletal Tumor Society score was used to evaluate postoperative limb function.ResultsA total of seven patients were included, including three males and four females with an average age of 16.6 ± 6.5 years. Among them, three cases of tumors occurred in the humerus and four cases occurred in the femur. The average follow-up time was 11.3 ± 3.0 months. The average area of bone defect was 25.9 ± 8.3 cm2. No complications such as infection, nonunion, and allograft bone fracture were found during the follow-up period. Six months after the operation, the average Musculoskeletal Tumor Society score was 26.4 ± 1.6, with acceptable postoperative function.ConclusionsThe cooperative application of absorbable screw fixation and allografts including mixed cortical bone and cancellous bone, which yielded satisfactory functional outcomes and acceptable postoperative complications, is an effective reconstruction method for a massive bone defect after the resection of giant osteochondroma.

Lettuce (Lactuca sativa L.) is a leafy vegetable whose edible organs usually are leaf or stems, and thus high-temperature induced bolting followed by flower initiation is an undesirable trait in lettuce production. However, the molecular mechanism that controls lettuce bolting and flowering upon thermal treatments is largely unknown. Here, we identified a Lettuce auxin response factor 3 (LsARF3), the expression of which was enhanced by heat and auxin treatments. Interestingly, LsARF3 is preferentially expressed in stem apex, suggesting it might be associated with lettuce bolting. Transgenic lettuce overexpressing LsARF3 displayed early bolting and flowering, whereas knockout of LsARF3 dramatically delayed bolting and flowering in lettuce under normal or high temperature conditions. Furthermore, Exogenous application of IAA failed to rescue the late-bolting and -flowering phenotype of lsarf3 mutants. Several floral integrator genes including LsCO, LsFT, and LsLFY were co-expressed with LsARF3 in the overexpression and knockout lettuce plants. Yeast one-hybrid (Y1H) experiments suggested that LsARF3 could physically interact with the LsCO promoter, which was further confirmed by a dual luciferase assay in tobacco leaves. The results indicated that LsARF3 might directly modulate the expression of LsCO in lettuce. Therefore, these results demonstrate that LsARF3 could promote lettuce bolting in response to the high temperature by directly or indirectly activating the expression of floral genes such as LsCO, which provides new insights into lettuce bolting in the context of ARFs signaling and heat response.

Online microwave drying process monitoring has been challenging due to the incompatibility of metal components with microwaves. This paper developed a microwave drying system based on online machine vision, which realized real-time extraction and measurement of images, weight, and temperature. An image-processing algorithm was developed to capture material shrinkage characteristics in real time. Constant-temperature microwave drying experiments were conducted, and the artificial neural network (ANN) and extreme learning machine (ELM) were utilized to model and predict the moisture content of materials during the drying process based on the degree of material shrinkage. The results demonstrated that the system and algorithm operated effectively, and ELM provided superior predictive performance and learning efficiency compared to ANN.

Thoracic endovascular aortic repair (TEVAR) is a common treatment for Stanford type B aortic dissection (TBAD). However, re-entry tears might be found distal to the stented region which transports blood between the true and false lumens. Sealing the re-entry tears, especially for the thoracic tears, could further reduce blood perfusion to the false lumen; however, it might also bring risks by re-intervention or surgery. Wise determination of the necessity to seal the re-entry tears is needed. In this study, patient-specific models of TBAD were reconstructed, and the modified models were established by virtually excluding the thoracic re-entries. Computational hemodynamics was investigated, and the variation of the functional index and first balance position (FBP) of the luminal pressure difference, due to the sealing of the re-entries, was reported. The results showed that the direction of the net flow through the unstented thoracic re-entries varied among cases. Excluding the re-entries with the net flow toward the false lumen may induce the FBP moving distally and the relative particle residence time increasing in the false lumen. This study preliminarily demonstrated that the hemodynamic status of the re-entry tears might serve as an indicator to the necessity of sealing. By quantifying the through-tear flow exchange and shift of FBP, one can predict the hemodynamic benefit by sealing the thoracic re-entries and thus wisely determine the necessity of further interventional management.

Abstract ST2 (also known as IL1RL1) is the critical functional receptor for interleukin (IL)-33 in stimulating regulatory T cell (Treg) expansion and function in physiological and pathological conditions. We examined the correlation between ST2 cell expression and FoxP3 positive Tregs in both colorectal adenoma and cancer (CRC) microenvironment by real-time PCR, immunohistochemistry (IHC) and double immunofluorescences. The clinicopathological and prognostic significance of cellular ST2-positive cells and FoxP3-positive Tregs in patients with adenoma and CRC were evaluated. Real-time PCR results revealed increased expression levels of ST2 and FoxP3 mRNAs in both adenoma and CRC tissues as compared with control tissues. IHC analysis confirmed increased densities of ST2-positive cells in both the adenoma/CRC epithelium and stroma, which show a close positive linear association with the densities of FoxP3-positive Tregs in respective compartments. Pathological feature analysis showed that densities of ST2-positive cells in the tumor stroma were notably associated with degree of dysplastic grading in patients with adenoma, and disease stages and lymph node metastasis in patients with CRC. Kaplan-Meier survival curves suggested that CRC patients with high densities of ST2-positive cells in the stroma tend to have a shorter overall survival. We therefore concluded that increased densities of ST2-postive cells relate to Treg accumulation within the adenoma/CRC microenvironment, suggesting the IL-33/ST2 pathway as a potential contributor for immunosuppressive milieu formation that impact disease stage and prognosis in patients with CRC.

With the continuous reduction of chip feature size, the continuation of Moore's Law becomes increasingly difficult and heterogeneous integration has become one of the important orientations of electronic technology. Focusing on the issues including system integration and interconnection in submicron to 10 μm orders of magnitude, 3D heterogeneous integration formed by multiple chip connections on package substrates supported by active through-silicon vias breaks the scale barrier from micro-nano technology to system integration at the acceptable cost. 3D heterogeneous integration is gradually developing towards 3D stacking, multi-function integration and hybrid heterogeneous integration, which makes integrated products have the advantages of high integration, low power consumption, miniaturization and high reliability. This paper summarizes the development of 3D heterogeneous integration, the current researches as well as the fields and prospects of application.

As an agricultural plant, the cantaloupe contains rich nutrition and high moisture content. In this paper, the estimation problem of the moisture ratio model during a cantaloupe microwave drying process was considered. First of all, an image processing-based cantaloupe drying system was designed and the expression of the moisture ratio with regard to the shrinkage was built. Secondly, a maximum likelihood principle-based iterative evolution (MLP-IE) algorithm was put forward to estimate the moisture ratio model. After that, aiming at enhancing the model fitting ability of the MLP-IE algorithm, a maximum likelihood principle-based improved iterative evolution (MLP-I-IE) algorithm was proposed by designing the improved mutation strategy, the improved scaling factor, and the improved crossover rate. Finally, the MLP-IE algorithm and MLP-I-IE algorithm were applied for estimating the moisture ratio model of cantaloupe slices. The results showed that both the MLP-IE algorithm and MLP-I-IE algorithm were effective and that the MLP-I-IE algorithm performed better than the MLP-IE algorithm in model estimation and validation.

For food drying, moisture content and shrinkage are vital in the drying process. This paper is concerned with the moisture ratio modeling and prediction issues of the Hami melon drying process. First, an experimental system was developed; it included an adjustable-power microwave drying unit and an image-processing unit. The moisture contents and the areas of Hami melon slices at different times were sampled in real time. Then, the expression of the moisture ratio with regard to shrinkage was derived by using the Weierstrass approximation theorem. A maximum likelihood fitness function-based population evolution (MLFF-PE) algorithm was then put forward to fit the moisture ratio model and predict the moisture ratio. The results showed that the proposed MLFF-PE algorithm was effective at fitting and predicting the moisture ratio model of the drying process of Hami melon slices.

Objective: This research aims to refresh the limited understanding about the canal and vascular structures within the epiphysis and metaphysis of the tibia and femur and their oncological significance.Methods: This study was started with characterization of a novel structure using radiographs and anatomic dissections, followed by a descriptive clinical study with 55 participants to investigate the effects of tumors on this novel discovery and a retrospective cohort study with 82 participants to investigate whether the structure would be a risk factor for tumor recurrence after the curettage of giant cell tumor of bone.Results: A new anatomical knee structure, the Lijianmin-Chengkun (LC) complex, was discovered in healthy adults, and its clinical implications were examined in this study. This new-found anatomical structure is composed of an epiphyseal and metaphyseal canal which surrounds a blood vessel, foramen, and foramen-covered synovium. All LC complexes showed similar radiographical, anatomical, and histological characteristics and were located within specific tibial and femoral intercondylar regions. These LC complexes seem to facilitate tumor residue and extension and may be a risk factor for tumor recurrence after curettage of femoral and tibial giant cell tumors (P = 0.031).Conclusion: The LC complexes are related to local tumor recurrence and bidirectional tumor dissemination between intraosseous and intraarticular regions. These findings have opened up a new perspective and may provide new targets for intervention in malignant and aggressive tumors around the knee joint.

Radiant floor cooling (RFC) systems are known for their energy efficiency and comfort. However, when a conventional intermittently operating RFC system is subjected to sudden increases in heat and moisture loads, condensation, difficulties with multi-zone temperature control, inadequate cooling capacity, thermal comfort degradation, and slow thermal response may occur. A non-centralized hybrid RFC system was established with an air source heat pump, floor coils of high thermal mass, fan coils, and an outdoor air dehumidifier. The thermal comfort and cooling capacity of a given thermal zone under four modes were tested and analyzed. The results showed that the system created a satisfactory indoor environment with multi-zone control. The precooling direct-expansion (DX) outdoor air dehumidifier combined with the fan coils served the role of a conventional dispersed DOAS (dedicated outdoor air system), improved the response of the radiant system, and assisted in dehumidification. A PID-based mixing valve allows the floor surface temperature to track the dew point temperature of the zone air to improve floor cooling capacity. This hybrid system is suitable for residential homes or offices with non-centralized air conditioning systems to handle transient heat and moisture load variations.

Introduction: Reconstruction surgeries of the inguinal area pose a challenge for oncological and orthopedic surgeons, especially after radical local resection (RLR), radical inguinal lymph node dissection (RILND), or both. Although numerous surgical procedures have been reported, there is no report about a pedicle adductor longus flap method. The aim of this work is to show our experience about inguinal reconstruction with pedicled adductor longus flap and associated outcomes.Patients and Methods: A retrospective study of 16 patients with localized inguinal region interventions and reconstructed by adductor longus flap from March 2016 to July 2020. Patients' average age was 60.0 years (range = 38–79 years) and had postoperative follow-up of 10 months (ranging 2–19 months). All patients had unilateral inguinal region involvement—seven cases on the left and nine cases on the right. The patients' clinical course, operative course, and postoperative follow-up data were evaluated.Results: All 16 patients recovered well post-operatively and did not require any re-intervention. Four patients experienced negligible discomfort around the groin area. Five patients experienced a minor strength deficit in thigh adduction compared with that of preoperative strength in the same or contralateral leg. The aforementioned complications resolved during the postoperative course and had no functional impact on their activity of daily living. All adductor longus flaps survived, completely filled the inguinal dead space, and wounds healed uneventfully within 3 weeks except for three patients who suffered delayed wound healing for more than 4 weeks. Other common complications such as infection, seroma, or wound dehiscence were not encountered in this series.Conclusion: The adductor longus flap is a reliable alternative method for inguinal region reconstruction following radical local resection (RLR), radical inguinal lymph node dissection (RILND), or both.

Background: Accumulating data suggest that the tumour stroma rapidly undergoes dynamic mechanical and cellular changes by which creates a supportive milieu to promote disease progression and metastasis. Cytokines are reported to play a key role in the modulation of tumour stromal response. Methods: The activation of TH17/interleukin (IL)−17A network in association with tumour stromal proliferative and cellular response in samples from 50 patients with colorectal adenoma, 45 with colorectal cancer (CRCs) were elucidated with quantitative real-time PCR (q-PCR), immunohistochemistry and double immunofluorescence. Results: q-PCR results showed that retinoic acid-receptor-related orphan receptor-C, a critical transcriptional factor for TH17 cell differentiation, was significantly increased at the adenoma stage and slightly decreased at the CRC stage, but was still higher than that at normal controls. The level of TH17 signature cytokine IL-17A was shown in an increasing gradient throughout the adenoma-carcinoma sequence. Immunohistochemistry revealed an activated proliferative rate evaluated by Ki67 and population expansion of myofibroblasts in the adenoma/CRC stroma. Notably, densities of IL-17A-expressing cells were associated with populations of Ki67-positive cells and myofibroblasts in the adenoma/CRC stroma. Finally, CD146-positive stromal cells are an important participator for stroma remodelling, double immunofluorescence image demonstrated that IL-17 receptor C, one of the key elements for IL-17 receptor complex, was highly expressed in CD146-positive adenoma/CRC stromal cells. Conclusions: An activated TH17/IL-17A network in the tumour microenvironment is significantly associated with dynamic stromal cellular response throughout the adenoma–carcinoma sequence, which might provide a supportive environment for the initiation and progression of CRC.

Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.

Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.

Abstract Background Emerging evidence has suggested that interleukin (IL)-33 and its primary functional receptor ST2 are involved in the pathogenesis of tumorigenesis. Methods Using immunohistochemistry (IHC) and double immunofluorescence staining, we characterized the cellular and clinicopathological features of the IL-33/ST2 axis in different compartments in human esophageal squamous cell carcinoma (ESCC) surgical specimens. Results IHC data revealed an increased expression of IL-33-immunoreactivity (IR) and ST2-IR located in both ESCC cells and tumor stromal cells; which were associated with advanced clinicopathological features such as TNM stages and node involvement. However, the Kaplan–Meier analysis showed that densities of neither IL-33 positive nor ST2 positive cells in both the ESCC mass and stroma were associated with the overall survival rate in patients with ESCC. Double immunofluorescence staining for cellular feature analysis demonstrated that these IL-33 positive and ST2 positive cells in ESCCs were with a high proliferation rate, and IL-33-IR was frequently co-expressed with ST2-IR in both ESCC and stromal cells. Conclusion Significant altered cellular features of the IL-33/ST2 axis in ESCCs were associated with advanced clinicopathological variables. The data suggest that the IL-33/ST2 axis might be involved in the progression of human ESCCs.

Neutralizing tumour necrosis factor (TNF) antibodies have been widely used to treat inflammatory bowel disease (IBD) in the clinical practice. In this review, the principal biomarker analysis revealed that faecal calprotectin, C-reactive protein, serum or mucosal concentrations of anti-TNF monoclonal antibodies (mAbs) and antibodies to anti-TNF mAbs are commonly used as current biomarkers in the evaluation of anti-TNF therapeutic efficacy. However, mucosal cytokine transcripts. microRNAs, proteomics and faecal and mucosal gut microbiota profile and mucosal histological features are reported to be novel candidates of biomarkers with high clinical utility in the evaluation of anti-TNF therapeutic efficacy in patients with IBD. Therefore, a robust validation of novel promising biomarkers and comparison studies between current used and novel biomarkers are urgently required to improve their value in the evaluation of therapeutic efficacy and optimization of personalized medicine and identification of IBD candidates for anti-TNF therapy in future clinical practice.

Understanding the substrate specificity of HIV-1 protease plays an essential role in the prevention of HIV infection. A variety of computational models have thus been developed to predict substrate sites that are cleaved by HIV-1 protease, but most of them normally follow a supervised learning scheme to build classifiers by considering experimentally verified cleavable sites as positive samples and unknown sites as negative samples. However, certain noisy can be contained in the negative set, as false negative samples are possibly existed. Hence, the performance of the classifiers is not as accurate as they could be due to the biased prediction results. In this work, unknown substrate sites are regarded as unlabeled samples instead of negative ones. We propose a novel positive-unlabeled learning algorithm, namely PU-HIV, for an effective prediction of HIV-1 protease cleavage sites. Features used by PU-HIV are encoded from different perspectives of substrate sequences, including amino acid identities, coevolutionary patterns and chemical properties. By adjusting the weights of errors generated by positive and unlabeled samples, a biased support vector machine classifier can be built to complete the prediction task. In comparison with state-of-the-art prediction models, benchmarking experiments using cross-validation and independent tests demonstrated the superior performance of PU-HIV in terms of AUC, PR-AUC, and F-measure. Thus, with PU-HIV, it is possible to identify previously unknown, but physiologically existed substrate sites that are able to be cleaved by HIV-1 protease, thus providing valuable insights into designing novel HIV-1 protease inhibitors for HIV treatment.

Objective: This study aims to explore the role of MARK2 in chemotherapeutic resistance and potential mechanism within cisplatin resistance models of CD133+ MG-63 and MNNG/HOS cells. Methods: CD133− and CD133+ MG-63 and MNNG/HOS cells were differentiated and obtained by MACS(Magnetic bead sorting). Cell activity was determined by CCK-8 assay. siRNA was employed to down regulate the Microtubule Affinity Regulated Kinase 2 (MARK2) expression. Immunofluorescence detection and RT-qPCR were used to measure the expressions of MARK2 and DNA-PKcs at both protein and mRNA levels. Western blot was applied to test the levels of MARK2, γH2AX (S139), DNA-PKcs, Phospho-PI3 Kinase p85 (Tyr458), Akt, phospho-Akt (T308) antibodies, mTOR, phospho-mTOR (Ser2448). Results: Compared with CD133− MG-63 cells, CD133+ MG-63 cells showed significantly strong cisplatin resistance, with high levels of MARK2, DNA-PKcs and potent DNA damage repair ability (p

2,4-Dichlorophenoxyacetic acid (2,4-D) is a systemic conductive herbicide widely used across the world. With the large-scale and continuous use of 2,4-D, its possible harm to the environment and non-target organisms has attracted increasing attention, and the construction of a stable rapid on-site detection method is particularly important. In order to achieve on-site rapid detection of 2,4-D, we developed a gold nanoparticle immunochromatographic strip method with the visual elimination value was 50 ng/mL, and a quantitative detection limit of 11 ng/mL based on a nanobody. By combing with the color snap, the immunochromatographic strip could quantitatively analyze the amounts of 2,4-D. Meanwhile, a colorimetric card based on the true color of the test strips was developed for the qualitative analysis of 2,4-D on-site. The samples (water, fruits and vegetables) with and without 2,4-D were detected by the immunochromatographic strips, and the results showed the accuracy and reliability. Thus, this assay is a rapid and simple on-site analytical tool to detect and quantify 2,4-D levels in environmental samples, and the analytical results can be obtained in about ten minutes. In addition, the nanobody technology used in this study provides an inexhaustible supply of a relatively stable antibodies that can be archived as a nanobody, plasmid or even its sequence.

Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-adenovirus interactions studied to date have only been analyzed in vitro. In this study, we evaluated the role of α-defensin 5 (HD5) in modulating adenovirus vaccine immunogenicity using various serotype adenovirus vectors in mice. We screened a panel of human adenoviruses including Ad5 (species C), Ad26 (species D), Ad35 (species B), Ad48 (species D) and a chimeric Ad5HVR48 for HD5 sensitivity. HD5 inhibited transgene expression from Ad5 and Ad35 but augmented transgene expression from Ad26, Ad48, and Ad5HVR48. HD5 similarly suppressed antigen-specific IgG and CD8+ T cell responses elicited by Ad5 vectors in mice, but augmented IgG and CD8+ T cell responses and innate cytokine responses elicited by Ad26 vectors in mice. Moreover, HD5 suppressed the protective efficacy of Ad5 vectors but enhanced the protective efficacy of Ad26 vectors expressing SIINFEKL against a surrogate Listeria-OVA challenge in mice. These data demonstrate that HD5 differentially modulates adenovirus vaccine delivery vectors in a species-specific manner in vivo.

When using the explicit dynamic relaxation approach (DRA) to model the quasi-static rock breakage, fragmentation, and flow problems, especially the top-coal caving question, introducing numerical damping into the solution equation is inevitable for reducing the vibration frequency and impact speed of mesh nodes, which is significantly affect the fidelity of the computation results. Although the DRA has been widely adopted to simulate top-coal caving, the reasonable value and calibration method of numerical damping are still open issues. In this study, the calibration process of reasonable numerical damping for modeling top-coal caving is investigated by comparing with the experimental results, in which several geometry parameters of the drawing funnel are selected as the calibration indexes. The result shows that the most reasonable numerical damping value is 0.07 for the numerical modeling of interval top-coal caving in extra-thick coal seams. Finally, the correlation between the numerical damping and the physical top-coal drawing process is discussed. The numerical damping indirectly reflects the fragmentation in multi scale of coal mass and friction interaction between coal particles during the caving process, which reduces the vibration intensity of the top-coal caving system and dissipates the kinetic energy.

The development of colorectal cancer (CRC) is not only determined by transformed cells per se, but also by factors existing in their immune microenvironment. Accumulating scientific evidence has revealed that interleukin (IL)-33, an IL-1 family member, plays an essential role in the regulation of immune response and is relevant in CRC pathogenesis. Data from both human and experimental studies demonstrated that IL-33 inhibits host anti-tumor immunity, remodels tumor stroma and enhances angiogenesis, thereby promoting the development of CRC. These pro-tumor effects of IL-33 are mainly mediated by IL-33 receptor ST2 (also known as IL-1RL1). Based on those findings, it is currently hypothesized that the IL-33/ST2 pathway is a potential biomarker and therapeutic target for colorectal tumorigenesis. Herein, we summarize the recent discoveries in understanding the critical role of the IL-33/ST2 pathway in contributing to the pathogenesis of colorectal tumorigenesis and discuss its potential implications for the future development of effective anti-tumor strategies.

Nuclear factor-kappaB (NF-κB)/interleukin (IL-6) pathway links chronic inflammation to colitis associated cancer (CAC). In this study, we examined the dynamic temporal changes of the NF-κB/IL-6 pathway during the procession of experimental CAC mouse model. Mice were sacrificed after induction for 14, 16, 18, and 22 weeks for the examination of tumor burden, inflammation degree, and protein level of NF-κB and IL-6 in bowel tissues. The results showed that tumor burden and inflammation severity in the bowels were gradually increased over the observed time-points. The expressions of IL-6 and NF-κB proteins were gradually increased after induction of dysplastic lesions over times. These data provide new information on the dynamic temporal changes of NF-κB/IL-6 pathway in relation to CAC development that may be relevant in the design of future investigations of therapeutic interventions to effectively target CAC processes.