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Abstract Objectives The purpose of this study is to assess the diagnostic efficacy of contrast-enhanced CT scans for small bowel bleeding. Methods This retrospective study evaluated patients diagnosed with non-neoplastic small intestinal bleeding (including duodenum) who underwent abdominal CT at our institution from December 2013 to March 2023. Patients were categorized into diverticulum and non-diverticulum groups based on the cause of bleeding. Active bleeding was defined on the CT images as extravasation of contrast material in the intestinal lumen during the arterial phase and/or progressive accumulation of contrast material during the venous phase. We have documented the original report (extracted from the medical record system and additional consultation opinions from senior radiologists), including the presence of active bleeding and its potential bleeding location. Furthermore, two radiologists reassessed the CT images, seeking consensus on the diagnosis between them. Results The study included 165 patients, predominantly male, with a median age of 30 years. Active bleeding was identified in 48.3% of patients. Notably, all identified bleeding diverticula in the diverticulum group exhibited cul-de-sac termination. Among the identified causes of bleeding, Crohn’s disease was most prevalent (46.7%, N of causes = 64). Significant differences were observed in the diagnostic methods between the diverticulum and non-diverticulum groups, with surgery predominantly applied in the diverticulum group, and endoscopy in the non-diverticulum group (n = 49 vs n = 15, p = 0.001). Contrast agent extravasation was significantly higher in the diverticulum group (n = 54 vs n = 16, p = 0.001), and Meckel’s diverticulum cases appearing tubular were significantly higher than in other diverticulum cases (n = 25 vs n = 3, p

Abstract Oral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor (A2AR) on trigeminal ganglia. Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.

In order to obtain high temperature protective coatings with low diffusivity, high entropy (HEA) as well as high entropy oxide (HEO) diffusion barriers were deposited between the NiCrAlY coating and the substrate by magnetron sputtering. These two coatings were subjected to constant temperature oxidation tests at 1050 °C. These results show that the two coatings containing diffusion barriers have better high-temperature oxidation properties compared to the NiCrAlY coating. Both HEA and HEO diffusion barriers have the desired performance in hindering the diffusion of elements between the coating and the substrate. The evolution of these two diffusion barriers and the mechanism of diffusion resistance during the oxidation process have been investigated.

Abstract Purpose Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. Methods We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2’s impacts on clear cell renal cell carcinoma (ccRCC) cells’ proliferative and invasive capacities in vitro. Results In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2’S knockdown significantly inhibited the A498 and T24 cells’ proliferation, invasion, and migration. Conclusions In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

Purpose To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget’s disease (EMPD).Materials and methods A 77-year-old male patient with non-invasive EMPD was treated with MMS followed by PDT. Preoperative fluorescence localization using 5-aminolevulinic acid (ALA) was performed to determine the surgical scope. MMS was conducted under lumbar anesthesia with intraoperative frozen-section pathology. Postoperative PDT was administered weekly for three sessions.Results The patient achieved negative surgical margins after two rounds of intraoperative pathology. Postoperative follow-up over two years showed no recurrence, and the patient did not experience significant adverse reactions.Conclusion The combination of MMS and PDT was effective in treating non-invasive EMPD, demonstrating favorable clinical outcomes and no recurrence over the two-year follow-up period.

Abstract Tumor‐initiating cells (TICs) resilience and an immunosuppressive microenvironment are aggressive oncogenic phenotypes that contribute to unsatisfactory long‐term outcomes in lung adenocarcinoma (LUAD) patients. The molecular mechanisms mediating the interaction between TICs and immune tolerance have not been elucidated. The role of Galectin‐9 in oncogenesis and immunosuppressive microenvironment is still unknown. This study explored the potential role of galectin‐9 in TIC regulation and immune modulation in LUAD. The results show that galectin‐9 supports TIC properties in LUAD. Co‐culture of patient‐derived organoids and matched peripheral blood mononuclear cells showed that tumor‐secreted galectin‐9 suppressed T cell cytotoxicity and induced regulatory T cells (Tregs). Clinically, galectin‐9 is upregulated in human LUAD. High expression of galectin‐9 predicted poor recurrence‐free survival and correlated with high levels of Treg infiltration. LGALS9, the gene encoding galectin‐9, is found to be transcriptionally regulated by the nuclear factor of activated T cells 2 (NFATc2), a previously reported TIC regulator, via in silico prediction and luciferase reporter assays. Overall, the results suggest that the NFATc2/galectin‐9 axis plays a dual role in TIC regulation and immune suppression.

Multilineage-differentiating stress-enduring (Muse) cells are a type of pluripotent cell with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in the field of regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC. Methods By utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan–Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines in vitro. Results As a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population.

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.

Abstract Background Accurate assessment of the clinical staging is crucial for determining the need for radical prostatectomy (RP) in prostate cancer (PCa). However, the current methods for PCa staging may yield incorrect results. This study aimed to comprehensively analyze independent predictors of postoperative upstaging of intraprostatic cancer. Methods We conducted a retrospective analysis of data from intraprostatic cancer patients who underwent radical surgery between March 2019 and December 2022. Intraprostatic cancer was defined as a lesion confined to the prostate, excluding cases where multiparameter magnetic resonance imaging (mpMRI) showed the lesion in contact with the prostatic capsule. We assessed independent predictors of extraprostatic extension (EPE) and analyzed their association with positive surgical margin (PSM) status. In addition, based on the distance of the lesion from the capsule on mpMRI, we divided the patients into non‐transition zone and transition zone groups for further analysis. Results A total of 500 patients were included in our study. Logistic regression analysis revealed that biopsy Gleason grade group (GG) (odds ratio, OR: 1.370, 95% confidence interval, CI: 1.093–1.718) and perineural invasion (PNI) (OR: 2.746, 95% CI: 1.420–5.309) were predictive factors for postoperative EPE. Both biopsy GG and PNI were associated with lateral (GG: OR: 1.270, 95% CI: 1.074–1.501; PNI: OR: 2.733, 95% CI: 1.521–4.911) and basal (GG: OR: 1.491, 95% CI: 1.194–1.862; PNI: OR: 3.730, 95% CI: 1.929–7.214) PSM but not with apex PSM (GG: OR: 1.176, 95% CI: 0.989–1.399; PNI: OR: 1.204, 95% CI: 0.609–2.381) after RP. Finally, PNI was an independent predictor of EPE in the transition zone (OR: 11.235, 95% CI: 2.779–45.428) but not in the non‐transition zone (OR: 1.942, 95% CI: 0.920–4.098). Conclusion PNI and higher GG may indicate upstaging of tumors in patients with intraprostatic carcinoma. These two factors are associated with PSM in locations other than the apex of the prostate. Importantly, cancer in the transition zone of the prostate is more likely to spread externally through nerve invasion than cancer in the non‐transition zone.

Partially encased composite beams (PECBs) have advantages over conventional steel–concrete composite beams in load-carrying capacity, flexural stiffness and fire resistance. In order to determine whether the shearing force is sufficient to ensure the yield of the tensile reinforcement in the case of a large tensile reinforcement ratio, as well as the influence of encasing concrete strength and the addition of studs on the steel web, three PECB specimens were tested under bending. The results show that, in the case of a 5% tensile reinforcement ratio, natural bonding and friction forces ensure the yield of tensile reinforcement whether studs are added on the steel web or not. The encasing concrete strength and the addition of studs on the steel web have no obvious effect on both the elastic and plastic bending resistance of PECBs. The addition of studs on the steel web significantly slows down the stiffness deterioration of PECBs within the elastoplastic stage, while the flexural stiffness is not obviously affected by the strength of encasing concrete. The simplified plastic theory is proved to be applicable to predict the flexural capacity of PECBs with a large tensile reinforcement ratio. It is also indicated by calculation that, by increasing the tensile reinforcement ratio from 2% to 5%, the flexural capacity of PECBs has a significant increase, by about 32%.

Fractional-pixel CO2 laser therapy shows promise for treating the genitourinary syndrome of menopause (GSM). Nevertheless, it remains controversial in the field of female pelvic medicine. This is due to the inherent difficulties in obtaining noninvasive biopsies to evaluate the treatment's efficacy and safety objectively. To address this challenge, we developed a noninvasive intravaginal optical coherence tomography (OCT)/OCT angiography (OCTA) endoscopic system, whose probe features a shape identical to the laser treatment probe. This system can provide high-resolution OCT images to identify the microstructure of vaginal tissue and visualize the vasculature network in vivo. We conducted clinical research on 25 post-menopausal patients with GSM. OCT/OCTA scans were acquired at four different locations of the vagina (distal anterior, distal posterior, proximal anterior, and proximal posterior) during the whole laser treatment session. A U-Net deep learning model was applied to segment the vaginal epithelium for assessing vaginal epithelial thickness (VET). Blood vessel density and VET were quantified to monitor the efficacy of fractional-pixel CO2 laser therapy. Statistical correlation analyses between these metrics and other clinical scores were conducted, validating the utility of our system. This OCT/OCTA endoscopic system has great potential to serve as a noninvasive biopsy tool in gynecological studies to screen, evaluate, and guide laser treatment for GSM.

Current research on the interference of GNSS (Global Navigation Satellite System) array antennas focuses on the single interference effect and the improvement of interference hardware capability, while the multi-degree-of-freedom (DOF) interference model and mechanism remain to be fully studied. Aiming at this problem, this paper analyzes the preconditions for the definition of anti-jamming degrees of freedom and the characteristics of super-DOF interference through formula derivation and simulation. First, by analyzing the influence of the number of interfering signals on the angular resolution, the prerequisite of the definition of anti-interference degrees of freedom in the airspace is proposed. Second, the definition of anti-interference degrees of freedom is used to calculate the change rule of the critical power of the interference under different numbers of interfering signals. Finally, the influence of super-DOF interference on the array antenna is analyzed. The results show that the prerequisite for the anti-interference freedom of the array antenna is that the distribution interval of the interfering signal is greater than 15°, taking a four-array element uniform circular array antenna as an example. The critical interference power of the array antenna decreases by about 15 dB when the number of interfering signals exceeds the degrees of freedom of the array antenna’s interference immunity, provided that the interference resolution is satisfied. The conclusions of this paper give the critical power change rule of multi-DOF interference and the effect of super-DOF interference, as well as the prerequisites for the setting of interference signals, which can be used, for example, in the deployment of distributed interference sources and the development of anti-jamming algorithms.

Abstract Background Compared with optimal blood pressure (BP), the prehypertension increases the risk of incident hypertension, cardiovascular (CV) events, and death. Moderate intensity of regular physical activity can reduce BP. However, aerobic exercise has some limitations. As a safe, low-impact, enjoyable, and inexpensive form of exercise that requires minimal equipment and space, Tai Chi is expected as a viable alternative to aerobic exercise. The study aimed to assess the effect of Tai Chi intervention program, compared with aerobic exercise, on the BP in prehypertension patients. Methods This study is a 12-month, two-center, single-blind, parallel, randomized controlled trial. Three hundred forty-two patients with prehypertension [with a systolic blood pressure (SBP) in the range of 120 mmHg to 139 mmHg and/or a diastolic blood pressure (DBP) in the range of 80 mmHg to 89 mmHg] are randomized to one of two intervention groups in a 1:1 ratio: Tai Chi or aerobic exercise. BP monitoring methods of office blood pressure, ambulatory blood pressure monitoring (ABPM), and home blood pressure monitoring (HBPM) are used at the same time to detect BP in multiple dimensions. The primary outcome is the comparison of SBP change from baseline to 12 months in Tai Chi group and SBP change from baseline to 12 months in aerobic exercise group. The secondary endpoints are as following: (1) the comparison of DBP of office blood pressure change from baseline to 12 months between Tai Chi group and aerobic exercise group, (2) the comparison of BP and the variability of BP assessed through ABPM change from baseline to 12 months between Tai Chi group and aerobic exercise group, (3) the comparison of BP assessed through HBPM change from baseline to 12 months between Tai Chi group and aerobic exercise group. Discussion This will be the first randomized controlled trial to specifically study the benefits of Tai Chi on the blood pressure control in patients with prehypertension. The successful completion of this study will help to provide evidence for whether Tai Chi is more desirable than aerobic exercise. Trial registration Trial registration number: Chinese Clinical Trial Registry, ChiCTR1900024368. Registered on 7 July 2019, http://www.chictr.org.cn/edit.aspx?pid=39478&htm=4

Abstract Background In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. Objective This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. Methods A total of 53,269 participants aged 30–79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004–2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. Results During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81–0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60–0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55–1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.

Abstract Background Erosion is one of the most common and basic lesions of oral mucosal diseases. Long-term refractory oral erosions, induced by autoimmune blistering diseases, infectious diseases, malignant diseases, and some rare conditions, may substantially reduce the quality of life of patients or even constitute a life-threatening condition, resulting in a clinical dilemma regarding the accurate diagnosis and precise management of these diseases. As a special type of malignant lymphoma, most lesions of follicular lymphoma (FL) in the oral mucosa present as masses or swelling of the oral mucosa, while emerging novel presentations lead to intractable diagnoses. Hence, diagnostic algorithms for such diseases are clinically required. Case presentation A 55-year-old female patient presented to the clinic with long-lasting oral mucosal erosions and proliferative lesions. Blood tests, pathological examinations of oral lesions including haematoxylin–eosin (HE) staining, and direct immunofluorescence precluded all of the potential diagnoses described previously. Unexpectedly, positron emission tomography/computed tomography (PET/CT) and abdominal CT of the patient revealed a dense mass in the retroperitoneal area, and the final diagnosis of the retroperitoneal mass was FL. After three courses of chemotherapy conducted by the haematologist, the erosion and proliferative lesions in the patient's oral mucosa had significantly improved. HE and immunohistochemical staining results of intraoral lesions also confirmed it as oral FL. The successful diagnosis of FL in this case is of great clinical significance, as the oral and abdominal FL were treated in a timely manner to avoid unfavourable outcomes. Conclusions To the best of our knowledge, this is the first case of FL that exhibited widespread erosions interspersed with proliferative lesions. Clinicians should be aware of oral FL or seek systemic factors in the presence of similar refractory oral erosions when treatment is non-responsive and the diagnosis is intractable.

Abstract Background Lung cancer is currently the most frequent cancer in Jiangsu Province, China, and the features of cancer distribution have changed continuously in the last decade. The aim of this study was to analyse the trend of the incidence of lung cancer in Jiangsu from 2009 to 2018 and predict the incidence from 2019 to 2030. Methods Data on lung cancer incidence in Jiangsu from 2009 to 2018 were retrieved from the Jiangsu Cancer Registry. The average annual percentage change (AAPC) was used to quantify the trend of the lung cancer age-standardized rate (ASR) using Joinpoint software. Bayesian age-period-cohort models were used to predict lung cancer incidence up to 2030. Results In Jiangsu, the lung cancer crude rate increased from 45.73 per 100,000 in 2009 to 69.93 per 100,000 in 2018. The lung cancer ASR increased from 29.03 per 100,000 to 34.22 per 100,000 during the same period (AAPC = 2.17%, 95% confidence interval [CI], 1.54%, 2.80%). Between 2019 and 2030, the lung cancer ASR is predicted to decrease slightly to 32.14 per 100,000 (95% highest density interval [HDI], 24.99, 40.22). Meanwhile, the ASR showed a downward trend in males and rural regions while remaining stable in females and urban regions. Conclusion We predict that the incidence of lung cancer in Jiangsu will decrease in the next 12 years, mainly due to the decrease in males and rural areas. Therefore, future lung cancer prevention and control efforts should be focused on females and urban regions.

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics. Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs, but the mass proportion of carriers generally exceeds 90% of the nano-drug, resulting in low drug loading and limited therapeutic output. Herein, we fabricated a nanocarrier using antibiotics as the building blocks, minimizing the use of carrier materials, significantly increasing the drug loading content and treatment effect. Firstly, we conjugated betaine carboxylate with ciprofloxacin (CIP) through an ester bond to form the amphiphilic conjugate (CIP-CB), which self-assembled into micelles (CIP-CBMs) in aqueous solutions, with a CIP loading content as high as 65.4% and pH-induced surface charge reversal properties. Secondly, a model photosensitizer (5, 10, 15, 20-tetraphenylporphyrin (TPP)) was encapsulated in CIP-CBMs, generating infection-targeted photodynamic/antibiotic combined nanomedicines (denoted as TPP@CIP-CBMs). Upon accumulation at infection sites or in deep bacterial biofilms, the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP, leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

Behçet’s disease (BD) behaves similarly to Crohn’s disease (CD) when the bowel is involved. Computed tomography enterography (CTE) can accurately show intestinal involvement and obtain body composition data. The objective of this study was to evaluate whether CTE could improve the ability to distinguish between intestinal BD and CD. This study evaluated clinical, laboratory, endoscopic, and CTE features on first admission. Body composition analysis was based on the CTE arterial phase. The middle layers of the L1–L5 vertebral body were selected. The indicators assessed included: the area ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) (VSR) in each layer, the total volume ratio of VAT/SAT, the quartile of VAT attenuation in each layer and the coefficient of variation (CV) of the VAT area for each patient was also calculated. Two models were developed based on the above indicators: one was a traditional model (age, gender, ulcer distribution) and the other was a comprehensive model (age, gender, ulcer distribution, proximal ileum involvement, asymmetrical thickening of bowel wall, intestinal stenosis, VSRL4, and CV). The areas under the receiver operating characteristic (ROC) curve of the traditional (sensitivity: 80.0%, specificity: 81.0%) and comprehensive (sensitivity: 95.0%, specificity: 87.2%) models were 0.862 and 0.941, respectively (p = 0.005).

Abstract Intravascular polarization-sensitive optical coherence tomography (IV-PSOCT) provides depth-resolved tissue birefringence which can be used to evaluate the mechanical stability of a plaque. In our previous study, we reported a new strategy to construct polarization-sensitive optical coherence tomography in a microscope platform. Here, we demonstrated that this technology can be implemented in an endoscope platform, which has many clinical applications. A conventional intravascular OCT system can be modified for IV-PSOCT by introducing a 12-m polarization-maintaining fiber-based imaging probe. Its two polarization modes separately produce OCT images of polarization detection channels spatially distinguished by an image separation of 2.7 mm. We experimentally validated our IV-PSOCT with chicken tendon, chicken breast, and coronary artery as the image samples. We found that the birefringent properties can be successfully visualized by our IV-PSOCT.

Abstract Glutathione S‐transferase pi (GSTP1), a phase II detoxification enzyme, is known to be overexpressed and mediates chemotherapeutic resistance in lung cancer. However, whether GSTP1 supports cancer stem cells (CSCs) and the underlying mechanisms in lung adenocarcinoma (LUAD) remain largely unknown. This study unveiled that GSTP1 is upregulated in lung CSCs and supports tumor self‐renewal, metastasis, and resistance to targeted tyrosine kinase inhibitors of LUAD both in vitro and in vivo. Mechanistically, CaMK2A (calcium/calmodulin‐dependent protein kinase 2 isoform A)/NRF2 (nuclear factor erythroid 2‐related factor 2)/GSTP1 is uncovered as a regulatory axis under hypoxia. CaMK2A increased GSTP1 expression through phosphorylating the Sersine558 residue of NRF2 and promoting its nuclear translocation, a novel mechanism for NRF2 activation apart from conventional oxidization‐dependent activation. Upregulation of GSTP1 in turn suppressed reactive oxygen species levels and supported CSC phenotypes. Clinically, GSTP1 analyzed by immunohistochemistry is upregulated in a proportion of LUAD and serves as a prognostic marker for survival. Using patient‐derived organoids from an ALK‐translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long‐term control of LUAD through targeting CSCs.

ObjectiveOral potentially malignant disorders (OPMDs) are a spectrum of diseases that harbor the potential of malignant transformation and developing into oral squamous cell carcinoma (OSCC). Narrow band imaging (NBI) has been clinically utilized for the adjuvant diagnosis of OPMD and OSCC. This study aimed to comprehensively evaluate the diagnostic accuracy of NBI for malignant transformations of OPMD by applying the intraepithelial papillary capillary loop (IPCL) classification approach.MethodsStudies reporting the diagnostic validity of NBI in the detection of OPMD/OSCC were selected. Four databases were searched and 11 articles were included in the meta-analysis. We performed four subgroup analyses by defining IPCL I/II as negative diagnostic results and no/mild dysplasia as negative pathological outcome. Pooled data were analyzed using random-effects models. Meta-regression analysis was performed to explore heterogeneity.ResultsAfter pooled analysis of the four subgroups, we found that subgroup 1, defining IPCL II and above as a clinically positive result, demonstrated the most optimal overall diagnostic accuracy for the malignant transformation of OPMDs, with a sensitivity and specificity of NBI of 0.87 (95% confidence interval (CI) [0.67, 0.96], p

Abstract The study of artificial intelligence (AI) has been a continuous endeavor of scientists and engineers for over 65 years. The simple contention is that human-created machines can do more than just labor-intensive work; they can develop human-like intelligence. Being aware or not, AI has penetrated into our daily lives, playing novel roles in industry, healthcare, transportation, education, and many more areas that are close to the general public. AI is believed to be one of the major drives to change socio-economical lives. In another aspect, AI contributes to the advancement of state-of-the-art technologies in many fields of study, as helpful tools for groundbreaking research. However, the prosperity of AI as we witness today was not established smoothly. During the past decades, AI has struggled through historical stages with several winters. Therefore, at this juncture, to enlighten future development, it is time to discuss the past, present, and have an outlook on AI. In this article, we will discuss from a historical perspective how challenges were faced on the path of revolution of both the AI tools and the AI systems. Especially, in addition to the technical development of AI in the short to mid-term, thoughts and insights are also presented regarding the symbiotic relationship of AI and humans in the long run.

As a result of ongoing breakthroughs in cancer therapy, cancer patients' survival rates have grown considerably. However, cardiotoxicity has emerged as the most dangerous toxic side effect of cancer treatment, negatively impacting cancer patients' prognosis. In recent years, the link between non-coding RNAs (ncRNAs) and cancer therapy-induced cardiotoxicity has received much attention and investigation. NcRNAs are non-protein-coding RNAs that impact gene expression post-transcriptionally. They include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In several cancer treatments, such as chemotherapy, radiotherapy, and targeted therapy-induced cardiotoxicity, ncRNAs play a significant role in the onset and progression of cardiotoxicity. This review focuses on the mechanisms of ncRNAs in cancer therapy-induced cardiotoxicity, including apoptosis, mitochondrial damage, oxidative stress, DNA damage, inflammation, autophagy, aging, calcium homeostasis, vascular homeostasis, and fibrosis. In addition, this review explores potential ncRNAs-based biomarkers and therapeutic strategies, which may help to convert ncRNAs research into clinical practice in the future for early detection and improvement of cancer therapy-induced cardiotoxicity.

BackgroundProstate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransferase for m5c RNA modification, the role of the NSUN members (NSUN1-7) in prostate cancer is unclear.MethodsWe obtained sequencing data of genes and related clinical data of prostate cancer from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database and analyzed the correlation between NSUN members’ expression and prognosis. we found that NSUN2 was closely implicated in the prognosis of prostate cancer, then verified the expression of NSUN2 in clinical samples, and obtained the correlation between NSUN2 and immune cell infiltration through CIBERSORT algorithm and ESTIMATE method. The relationship between NSUN2 copy number variation and immune cell infiltration was further analyzed in the TIMER database and identified signaling pathways associated with NSUN2 expression by GO, KEGG, and GSEA analysis. Finally, we verified the expression of NSUN2 in prostate cancer cell lines and confirmed the role of NSUN2 on the biological behavior of prostate cancer cells by proliferation and migration-related assays.ResultsNOP2 and NSUN2 were upregulated in prostate tumor tissues. NSUN2 expression is closely associated with tumor prognosis. NSUN2 high expression implies poor clinical features, and the NSUN family is significantly associated with tumor stromal score and immune score. Besides, NSUN2 is associated with a variety of immune infiltrating cells (B cells memory, T cells CD4 memory resting, T cells CD4 memory activated, NK cells resting, and so on). High NSUN2 expression lowers the sensitivity of many chemotherapy drugs, such as docetaxel, doxorubicin, fluorouracil, cisplatin, and etoposide. In prostate cancer, the most common type of mutation in NSUN2 is amplification, and NSUN2 copy number variation is closely associated with NSUN2 expression and immune cell infiltration. GSEA analysis showed that the related genes were mainly enriched in ubiquitin-mediated protein hydrolysis, cell cycle, RNA degradation, endometrial cancer, prostate cancer, p53 signaling pathway, and NSUN2 potentiated the proliferation and migration of prostate cancer cells.ConclusionsNSUN2 is highly expressed in prostate cancer, which contributes to the progression of prostate cancer, and is closely implicated in immune cell infiltration and chemotherapy drugs. NSUN2 is expected to be a prospective marker and a new treatment target for prostate cancer.

Objective: The objective of this study is to develop a novel automatic convolutional neural network (CNN) that aids in the diagnosis of meniscus injury, while enabling the visualization of lesion characteristics. This will improve the accuracy and reduce diagnosis times. Methods: We presented a cascaded-progressive convolutional neural network (C-PCNN) method for diagnosing meniscus injuries using magnetic resonance imaging (MRI). A total of 1396 images collected in the hospital were used for training and testing. The method used for training and testing was 5-fold cross validation. Using intraoperative arthroscopic diagnosis and MRI diagnosis as criteria, the C-PCNN was evaluated based on accuracy, sensitivity, specificity, receiver operating characteristic (ROC), and evaluation performance. At the same time, the diagnostic accuracy of doctors with the assistance of cascade- progressive convolutional neural networks was evaluated. The diagnostic accuracy of a C-PCNN assistant with an attending doctor and chief doctor was compared to evaluate the clinical significance. Results: C-PCNN showed 85.6% accuracy in diagnosing and identifying anterior horn injury, and 92% accuracy in diagnosing and identifying posterior horn injury. The average accuracy of C-PCNN was 89.8%, AUC = 0.86. The diagnosis accuracy of the attending physician with the aid of the C-PCNN was comparable to that of the chief physician. Conclusion: The C-PCNN-based MRI technique for diagnosing knee meniscus injuries has significant practical value in clinical practice. With a high rate of accuracy, clinical auxiliary physicians can increase the speed and accuracy of diagnosis and decrease the number of incorrect diagnoses.

(1) Background: pathological changes in hepatic Langerhans cell histiocytosis (LCH) have been observed; however, corresponding imaging findings can appear vague to physicians and radiologists. The present study aimed to comprehensively illustrate the imaging findings of hepatic LCH and to investigate the evolution of LCH-associated lesions. (2) Methods: LCH patients with liver involvement treated at our institution were retrospectively reviewed along with prior studies in PubMed. Initial and follow-up computed tomography (CT) and magnetic resonance imaging (MRI) were systematically reviewed, and three imaging phenotypes were created based on the lesion distribution pattern. Clinical features and prognoses were compared among the three phenotypes. Liver fibrosis was evaluated visually on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values of the fibrotic areas were measured. Descriptive statistics and a comparative analysis were used to analyze the data. (3) Results: based on the lesion distribution pattern on CT/MRI scans, patients with liver involvement were categorized as the disseminated lesion phenotype, scattered lesion phenotype, and central periportal lesion phenotype. Patients with scattered lesion phenotype were typically adults, and only a few of them had hepatomegaly (npresent = 1, 1/6, 16.7%) and liver biochemical abnormalities (npresent = 2, 2/6, 33.3%); patients with central periportal lesion phenotype were typically young children, and hepatomegaly and biochemical abnormalities were more apparent in these patients than those with another phenotype; and those with the disseminated lesion phenotype were found in all age groups, and the lesions evolved rapidly on medical imaging. Follow-up MRI scans show more details and can better document the evolution of lesions than CT. T2-hypointense fibrotic changes, including the periportal halo sign (npresent = 2, 2/9, 22.2%), patchy liver parenchyma changes (npresent = 6, 6/9, 66.7%), and giant hepatic nodules close to the central portal vein (npresent = 1, 1/9, 11.1%), were found, while fibrotic changes were not observed in patients with the scattered lesion phenotype. The mean ADC value for the area of liver fibrosis in each patient was lower than the optimal cutoff for significant fibrosis (METAVIR Fibrosis Stage ≥ 2) in a previous study that assessed liver fibrosis in chronic viral hepatitis. (4) Conclusions: The infiltrative lesions and liver fibrosis of hepatic LCH can be well characterized on MRI scans with DWI. The evolution of these lesions was well demonstrated on follow-up MRI scans.

The intensive research and development efforts directed towards large-scale complex industrial systems in the context of Industry 4.0 indicate that safety and reliability issues pose significant challenges. During online operation, system performance degradation will lead, not only to economic losses, but also potential safety hazards. In the existing research and technical routes, the target of the fault diagnosis systems is to trigger alarms to report the fact of the existence of malfunctions as well as the underlying reasons accurately. However, it remains unanswered how urgent it is to fix it, and what degrees of fault-tolerance, maintenance, and fault recovery are needed. Further analyses are necessary to evaluate the impact of the detected fault on the plant-wide performance. In this article, to enable a more comprehensive and precise description of the plant-wide operational status, the roles of the commonly used performance metrics, the state-of-the-art performance evaluation approaches, as well as the performance-oriented and plant-wide process monitoring techniques are investigated. On this basis, an alternative straightforward technical route, embedded in the cyber-physical-social system framework is proposed. A roadmap including the key research questions, the future research directions, and an outlook about the future vision is presented.

Ground-based optical observation of GEO space debris plays an essential role in tracking, identifying, cataloging, and classifying space debris. The factors that affect the brightness of space debris include size, surface material, illumination geometry, attitude, shape, position, and so on. In order to better understand the influence of the above factors on the brightness of space debris, the synthetic light curves are analyzed. The Ashikhmin–Shirley model is chosen to simulate the light curves of space debris. The effects of orbit, attitude, model parameters, and the location of the observation station on the synthetic light curves are analyzed by the control variable method. Based on the Markov Chain Monte Carlo method (MCMC), the optimal model parameters that characterize the surface material of space debris can be obtained by comparing the synthetic light curves with the observed light curves under certain shape, orbit, and attitude characteristics. The results are roughly in good agreement with those measured in the laboratory.

As a new type of two-dimensional layered carbides, nitrides or carbonitrides, MXenes have attracted widespread attention due to their excellent physical/chemical properties and huge potential functions. This work theoretically investigates the compositional dependence of Mn+1XnT2 and their electronic properties; where the series of Mn+1XnT2 (M = Sc, Ti, V; X = C; n = 1, 2; T = O, OH, F, Cl, Br, I) is employed as a case study. It is found that the Sc-based MXenes have the largest lattice constants, illustrating the weak interactions between the surface functionalized groups and Sc atoms. According to the mechanical stability analysis, it is found that except for Ti3C2O2, all the others are stable. Mechanically, the halogen functionalized (F, Cl, Br, and I) M2CT2 series have relatively large c11 values; and the Ti3C2Br2 has the largest c11 value. It is also found that the band gaps of Sc2CCl2 and Sc2CBr2 are 0.8734 and 0.6976 eV, respectively; both of which show their potential applications as indirect band gaps semiconductors.

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.

Background: Stuttering is characterized by dysfluency and difficulty in speech production. Previous research has found abnormalities in the neural function of various brain areas during speech production tasks. However, the cognitive neural mechanism of stuttering has still not been fully determined. Method: Activation likelihood estimation analysis was performed to provide neural imaging evidence on neural bases by reanalyzing published studies. Results: Our analysis revealed overactivation in the bilateral posterior superior temporal gyrus, inferior frontal gyrus, medial frontal gyrus, precentral gyrus, postcentral gyrus, basal ganglia, and cerebellum, and deactivation in the anterior superior temporal gyrus and middle temporal gyrus among the stutterers. The overactivated regions might indicate a greater demand in feedforward planning in speech production, while the deactivated regions might indicate dysfunction in the auditory feedback system among stutterers. Conclusions: Our findings provide updated and direct evidence on the multi-level impairment (feedforward and feedback systems) of stutterers during speech production and show that the corresponding neural bases were differentiated.

Abstract Background The interaction between tumor cells and their immunosuppressive microenvironment promotes tumor progression and drug resistance. Thus, simultaneously targeting tumor cells and stromal cells is expected to have synergistic antitumor effects. Herein, we present for the first time a preclinical antitumor investigation of 3D185, a novel dual inhibitor targeting FGFRs, which are oncogenic drivers, and CSF-1R, which is the major survival factor for protumor macrophages. Methods The antitumor characteristics of 3D185 were assessed by a range of assays, including kinase profiling, cell viability, cell migration, immunoblotting, CD8+ T cell suppression, and in vivo antitumor efficacy, followed by flow cytometric and immunohistochemical analyses of tumor-infiltrating immune cells and endothelial cells in nude mice and immune-competent mice. Results 3D185 significantly inhibited the kinase activity of FGFR1/2/3 and CSF-1R, with equal potency and high selectivity over other kinases. 3D185 suppressed FGFR signaling and tumor cell growth in FGFR-driven models both in vitro and in vivo. In addition, 3D185 could inhibit the survival and M2-like polarization of macrophages, reversing the immunosuppressive effect of macrophages on CD8+ T cells as well as CSF1-differentiated macrophage induced-FGFR3-aberrant cancer cell migration. Furthermore, 3D185 inhibited tumor growth via remodeling the tumor microenvironment in TAM-dominated tumor models. Conclusions 3D185 is a promising antitumor candidate drug that simultaneously targets tumor cells and their immunosuppressive microenvironment and has therapeutic potential due to synergistic effects. Our study provides a solid foundation for the investigation of 3D185 in cancer patients, particularly in patients with aberrant FGFR and abundant macrophages, who respond poorly to classic pan-FGFRi treatment.

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1β, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.

Atrial fibrillation (AF) occurs in up to 11% of cancer patients treated with ibrutinib. The pathophysiology of ibrutinib promoted AF is complicated, as there are multiple interactions involved; the detailed molecular mechanisms underlying this are still unclear. Here, we aimed to determine the electrophysiological and molecular mechanisms of burst-pacing-induced AF in ibrutinib-treated mice. The results indicated differentially expressed proteins in ibrutinib-treated mice, identified through proteomic analysis, were found to play a role in oxidative stress-related pathways. Finally, treatment with an inhibitor of NADPH oxidase (NOX) prevented and reversed AF development in ibrutinib-treated mice. It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-β protein expression. It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca2+ release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins. Ibrutinib-treated mice were also more likely to develop AF, and AF occurred over longer periods. In conclusion, our study has established a pathophysiological role for ROS signaling in atrial cardiomyocytes, and it may be that ox-CaMKII and p-CaMKII (Thr-286) are activated by ROS to increase AF susceptibility following ibrutinib treatment. We have also identified the inhibition of NOX as a potential novel AF therapy approach. Keywords: Reactive oxygen species, Ibrutinib, Atrial fibrillation, Electrical remodeling, Structural remodeling

Industrial cyber-physical systems (ICPSs) are the backbones of Industry 4.0 and as such, have become a core transdisciplinary area of research, both in industry and academia. New challenges brought about by the growing scale and complexity of systems, insufficient information exchange, and the exploitation of knowledge available have started threatening the overall system safety and stability. This work is motivated by these challenges and the strategic and practical demands of developing ICPSs for safety critical systems such as the intelligent factory and the smart grid. It investigates the current status of research in ICPS monitoring and control, and reviews the recent advances in monitoring, fault diagnosis, and control approaches based on data-driven realization, which can take full advantage of the abundant data available from past observations and those collected online in realtime. The practical requirements in the typical ICPS applications are summarized as the major issues to be addressed for the monitoring and the safety control tasks. The key challenges and the research directions are proposed as references to the future work.

Abstract Head and neck cancer (HNC) ranks as the 6th most common malignancy across the world. Metastasis is a hallmark of cancer, primarily contributing to the relapse and poor prognosis of HNC. Recently, long noncoding RNAs (lncRNAs), previously considered as non-functional, are increasingly appreciated by scholars to play crucial roles in mediating HNC metastasis. LncRNAs, which are located in the nucleus and cytoplasm, mainly exert their function via epigenetic modification, transcriptional control and translational regulation. As several lncRNAs are presently demonstrated to participate in HNC metastasis, we make a summary of the functions and mechanisms regarding these lncRNAs. As shown in the literature, most lncRNAs appear to promote the metastasis of HNC. Hence, we primarily discuss the lncRNAs involved in enhancing metastasis. Additionally, more studies are needed to understand those lncRNAs without clear mechanisms. Furthermore, we introduced the upstream regulator for the aberrant expression of lncRNAs in HNC. Finally, we concisely addressed future research prospects of lncRNAs, particularly the interplay between lncRNAs and tumor immunity as well as lncRNA-targeted therapeutic techniques, and we introduced clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possibly transformative tool to study lncRNAs. Although lncRNA research is still in the initial stage, it holds great promise to be applied as a prognosticator of HNC and a therapeutic target to inhibit HNC metastasis, which could significantly enhance the outcome of HNC patients.

Antiferromagnetic Ising model on Husimi lattice of polygons with odd number of sides are exactly solved to investigate the frustration of spins. Recursive lattices of pentagon, heptagon and nonagon were studied. The spontaneous magnetizations of these systems can easily be located from the solution and entropy curve. The solutions present N branches from 0 to 1 below TC, and the asymmetric arrangement of solutions confirms the frustration, which also can be identified by the non-zero residual entropy at T = 0. As expected, the TC increases with the number of sides, while ST=0 decreases as a measure of the degree of frustration.

Multiresponsive hydrogels have attracted tremendous interest due to their promising applications in tissue engineering, wearable devices, and flexible electronics. In this work, we report a multiresponsive upper critical solution temperature (UCST) composite hydrogel based on poly (acrylic acid-co-acrylamide), PAAc-co-PAAm, sequentially cross-linked by acid-hydrolysis cellulose nanocrystals (CNCs). Scanning electron microscopy (SEM) observations demonstrated that the hydrogels are formed by densely cross-linked porous structures. The PAAc/PAAm/CNC hybrid hydrogels exhibit swelling and shrinking properties that can be induced by multiple stimuli, including temperature, pH, and salt concentration. The driving force of the volume transition is the formation and dissociation of hydrogen bonds in the hydrogels. A certain content of CNCs can greatly enhance the shrinkage capability and mechanical strength of the hybrid hydrogels, but an excess addition may impair the contractility of the hydrogel. Furthermore, the hydrogels can be used as a matrix to adsorb dyes, such as methylene blue (MB), for water purification. MB may be partly discharged from hydrogels by saline solutions, especially by those with high ionic strength. Notably, through temperature-controlled hydrogel swelling and shrinking, doxorubicin hydrochloride (DOX-HCl) can be controllably adsorbed and released from the prepared hydrogels.

Abstract Background The objective of this study is to evaluate the value of computed tomography (CT) post-processing images in postoperative assessment of Lisfranc injuries compared with plain radiographs. Methods A total of 79 cases with closed Lisfranc injuries that were treated with conventional open reduction and internal fixation from January 2010 to June 2016 were analyzed. Postoperative assessment was performed by two independent orthopedic surgeons with both plain radiographs and CT post-processing images. Inter- and intra-observer agreement were analyzed by kappa statistics while the differences between the two postoperative imaging assessments were assessed using the χ 2 test (McNemar’s test). Significance was assumed when p

A circularly polarized (CP) wearable antenna based on the FDM (fused deposition modeling) technology is proposed. Conductive fabric is used to realize conductive parts of the patch antenna on the NinjaFlex substrate. The antenna is encapsulated with additional layers of NinjaFlex. Modified patch ensures the CP character at 2.45 GHz. Bending and washing tests are conducted to check the performance stability, and good agreement between simulated and measured results is observed. The experimental results illustrate that the antenna holds 11% 10 dB S11 bandwidth and around 70 MHz 3 dB axial ratio bandwidth. In addition, surface current analysis is also given to understand the operating mechanism of CP wave.

The proper utilization of road information can improve the performance of relay-node selection methods. However, the existing schemes are only applicable to a specific road structure, and this limits their application in real-world scenarios where mostly more than one road structure exists in the Region of Interest (RoI), even in the communication range of a sender. In this paper, we propose an adaptive relay-node selection (ARNS) method based on the exponential partition to implement message broadcasting in complex scenarios. First, we improved a relay-node selection method in the curved road scenarios through the re-definition of the optimal position considering the distribution of the obstacles. Then, we proposed a criterion of classifying road structures based on their broadcast characteristics. Finally, ARNS is designed to adaptively apply the appropriate relay-node selection method based on the exponential partition in realistic scenarios. Simulation results on a real-world map show that the end-to-end broadcast delay of ARNS is reduced by at least 13.8% compared to the beacon-based relay-node selection method, and at least 14.0% compared to the trinary partitioned black-burst-based broadcast protocol (3P3B)-based relay-node selection method. The broadcast coverage is increased by 3.6−7% in curved road scenarios, with obstacles benefitting from the consideration of the distribution of obstacles. Moreover, ARNS achieves a higher and more stable packet delivery ratio (PDR) than existing methods profiting from the adaptive selection mechanism.

An output-only method for structural diagnosis based on passing vehicle response is proposed in this article. Theoretical derivation reveals that the area of displacement response from only one sensor when vehicle loads pass over a bridge is in relation to global bending stiffness. Therefore, it can be preliminarily ascertained whether damage occurs in structure by comparison of the area of displacement responses before and after damage. Then, in order to localize damage, a damage index composed of displacement responses from several sensors is presented. The damage index has corresponding relationship with local bending stiffness and it is irrelevant to vehicle load parameters. Meanwhile, the method is suitable for both dynamic moving load and static vehicular load test. Case study of a box-girder bridge and experimental data verify the accuracy of the method, and different kinds of vehicle loads at different speeds basically have no influence on the method. In addition, the comparison between the method of curvature of displacement influence line and the presented method is also made, and the results show that the presented damage index is free from the effect of vehicle speeds while the damage index of curvature of displacement influence line is susceptible to vehicle speed.