LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.

BACKGROUND AND PURPOSE: Long noncoding RNA (lncRNA) dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitro and in vivo. METHODS: Bioinformatics analysis was conducted to identify differentially expressed lncRNAs between control and OSCC samples. Quantitative real-time-polymerase chain reaction was employed to detect the expression of differentially expressed lncRNAs in human tongue squamous cell carcinoma and human oral keratinocytes cell lines. The biological function of lncRNA and its mechanism were examined via the experimental assessment of the cell lines with the lncRNA overexpressed and silenced. Additionally, to further explore the function of lncRNA in the progression of OSCC, xenograft tumour mouse models were established using 25 mice (5 groups, each with 5 mice). Tumour formation was observed at 2 weeks after the cell injection, and the tumours were resected at 5 weeks post-implantation. RESULTS: Two lncRNAs, LINC00958 and AFAP1-AS1, were found to be correlated with the prognosis of OSCC. The results of the quantitative real-time-polymerase chain reaction indicated that the 2 lncRNAs were highly expressed in OSCC. In combination with the previous literature, we found AFAP1-AS1 to be a potentially important biomarker for OSCC. Thus, we further investigated its biological function and found that AFAP1-AS1 silencing inhibited cell proliferation, migration, and invasion whereas AFAP1-AS1 overexpression reversed the effect of AFAP1-AS1 silencing (P < .05). Mechanism analysis revealed that AFAP1-AS1 regulated the development of OSCC through the ubiquitin-mediated proteolysis pathway. CONCLUSIONS: AFAP1-AS1 is an oncogene that aggravates the development of OSCC via the ubiquitin-mediated proteolysis pathway. It also provides a novel potential therapy for OSCC.

Atomic-Site-Dependent Pairing Gap in Monolayer FeSe/SrTiO3(001)-(√13 × âˆš13).

The interfacial FeSe/TiO2-δ coupling induces high-temperature superconductivity in monolayer FeSe films. Using cryogenic atomically resolved scanning tunneling microscopy/spectroscopy, we obtained atomic-site dependent surface density of states, work function, and the pairing gap in the monolayer FeSe on the SrTiO3(001)-(√13 × âˆš13)-R33.7° surface. Our results disclosed the out-of-plane Se-Fe-Se triple layer gradient variation, switched DOS for Fe sites on and off TiO5□, and inequivalent Fe sublattices, which gives global spatial modulation of pairing gap contaminants with the (√13 × âˆš13) pattern. Moreover, the coherent lattice coupling induces strong inversion asymmetry and in-plane anisotropy in the monolayer FeSe, which is demonstrated to correlate with the particle-hole asymmetry in coherence peaks. These results disclose delicate atomic-scale correlations between pairing and lattice-electronic coupling in the Bardeen-Cooper-Schrieffer to Bose-Einstein condensation crossover regime, providing insights into understanding the pairing mechanism of multiorbital superconductivity.

A planar electronic acceptor motif contributing to NIR-II AIEgen with combined imaging and therapeutic applications.

Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.

Treatment outcomes in patients with acute thromboembolic occlusion of the superior mesenteric artery.

OBJECTIVES: The goals of this study were to investigate the treatment outcomes of acute thromboembolic occlusion of the superior mesenteric artery (ATOS) and identify prognostic factors after treatment. METHODS: The clinical data of 62 patients with ATOS between 2013 and 2021 were retrospectively reviewed. Patients were stratified by the treatment strategy, complications and mortality were compared in different group. RESULTS: Sixty-two consecutive patients were identified with ATOS. The median patient age was 69 years (interquartile range 58-79 years). Endovascular therapy was initiated in 21 patients, and 4 patients received conservative treatment. Open surgery was performed first in the remaining 37 patients. The technical success rates of the endovascular first group and open surgery group were 90.5% and 97.3%, respectively. One patient in the conservative treatment group had progression of ischemia to extensive bowel necrosis. There was no difference in 30-day mortality between these groups. Predictors of 30-day mortality included initial neutrophil count > 12* 103/dL, age over 60 years old and history of chronic renal insufficiency. CONCLUSIONS: Endovascular treatment or conservative treatment may be adopted in selected patients who do not exhibit signs and symptoms of bowel necrosis, and close monitoring for bowel necrosis is important. The increase in preoperative neutrophil count, age over 60 years old and history of chronic renal insufficiency were poor prognostic factors.

The Below-the-Knee Approach to Percutaneous Mechanical Thrombectomy for Lower Extremity Deep Venous Thrombosis: A Retrospective Single-Centre, Single-Arm Study.

PURPOSE: The objective of this study was to evaluate the safety, efficacy, and feasibility of percutaneous mechanical thrombectomy (PMT) through a below-the-knee (BTK) approach for acute lower extremity deep venous thrombosis (DVT). METHODS: A retrospective review of DVT patients treated with PMT by the BTK approach at our center from April 2022 to August 2023 was performed. Their preoperative demographics, intraoperative data, and postoperative outpatient outcomes were analyzed. RESULTS: A total of 12 patients (67% men; mean age, 63 years) met the inclusion criteria. The BTK approach was successfully achieved in all patients through the posterior tibial vein (n = 1), anterior tibial vein (n = 2), and peroneal vein (n = 9). PMTs were achieved in 11 (92%) patients. Successful lysis (grade II and grade III lysis) was achieved in all patients with PMT. Four (33%) patients had residual venous occlusion over the popliteal vein. No intraoperative complications or bleeding events occurred in any of the patients. CONCLUSION: PMT via BTK puncture seems to be a safe and effective approach for treating lower extremity DVT. It is reserved for highly select patients with a low risk of bleeding and is performed at centers that have experience with this procedure.

Bibliometric and visualized analysis of hydrogels in organoids research.

Over the past decades, there has been ongoing effort to develop complex biomimetic tissue engineering strategies for in vitro cultivation and maintenance of organoids. The defined hydrogels can create organoid models for various organs by changing their properties and various active molecules. An increasing number of researches has been done on the application of hydrogels in organoids, and a large number of articles have been published on the topic. Although there have been existing reviews describing the application of hydrogels in the field of organoids, there is still a lack of comprehensive studies summarizing and analyzing the overall research trends in this field. The citation can be used as an indicator of the scientific influence of an article in its field. This study aims to evaluate the application of hydrogels in organoids through bibliometric analysis, and to predict the hotspots and developing trends in this field.

Late-onset Cholestasis with Paucity of Portal Area Secondary to HNF1ß Deficiency in Adulthood: A Case Report.

Hepatocyte nuclear factor 1ß (HNF1ß) is essential for biliary development, while its genetic defect triggers the dysplasia of interlobular bile ducts, leading to life-threatening hepatitis and cholestasis. To date, this disorder has mainly been documented in neonates. Here, we report a case of cholestasis in an adult patient caused by a de novo HNF1ß mutation. A liver biopsy revealed remarkable shrinkage of the portal area accompanied by a decrease or absence of interlobular bile ducts, veins, and arteries in the portal area. Our case showed that an HNF1ß defect could induce late-onset cholestasis with paucity of the portal area in adulthood.

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study.

BACKGROUND: To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery. In this study, the correlation between preoperative frailty and POD, one-year mortality will be investigated in noncardiac Chinese geriatric surgery patients. METHODS: This study is a prospective, observational, cohort study conducted at a single center with Chinese geriatric patients. Patients who undergo noncardiac surgery and are older than 70 years will be included. A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study. The Barthel Index (BI) rating will be used to assess the patient's ability to carry out everyday activities on the 1st preoperative day. The modified frailty index (mFI) will be used to assess frailty. Patients in the nonfrailty group will have an mFI < 0.21, and patients in the frailty group will have an mFI ≥ 0.21. The primary outcome is the incidence of POD. Three-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) will be conducted twice daily during the 1st-7th postoperative days, or just before discharge. The secondary outcomes will include one-year mortality, in-hospital cardiopulmonary events, infections, acute renal injury, and cerebrovascular events. DISCUSSION: This study will clarify the correlation of preoperative frailty with POD and one-year all-cause mortality in Chinese geriatric patients undergoing noncardiac surgery. Can preoperative frailty predict POD or one-year mortality? In the face of China's serious aging social problems, this result may have important clinical value for the surgical treatment of geriatric patients. TRIAL REGISTRATION: This protocol has been registered with ClinicalTrials. Gov on 12 January 2022 (https://clinicaltrials.gov/ct2/show/NCT05189678).

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

Deep learning algorithm-based multimodal MRI radiomics and pathomics data improve prediction of bone metastases in primary prostate cancer.

PURPOSE: Bone metastasis is a significant contributor to morbidity and mortality in advanced prostate cancer, and early diagnosis is challenging due to its insidious onset. The use of machine learning to obtain prognostic information from pathological images has been highlighted. However, there is a limited understanding of the potential of early prediction of bone metastasis through the feature combination method from various sources. This study presents a method of integrating multimodal data to enhance the feasibility of early diagnosis of bone metastasis in prostate cancer. METHODS AND MATERIALS: Overall, 211 patients diagnosed with prostate cancer (PCa) at Gansu Provincial Hospital between January 2017 and February 2023 were included in this study. The patients were randomized (8:2) into a training group (n = 169) and a validation group (n = 42). The region of interest (ROI) were segmented from the three magnetic resonance imaging (MRI) sequences (T2WI, DWI, and ADC), and pathological features were extracted from tissue sections (hematoxylin and eosin [H&E] staining, 10 × 20). A deep learning (DL) model using ResNet 50 was employed to extract deep transfer learning (DTL) features. The least absolute shrinkage and selection operator (LASSO) regression method was utilized for feature selection, feature construction, and reducing feature dimensions. Different machine learning classifiers were used to build predictive models. The performance of the models was evaluated using receiver operating characteristic curves. The net clinical benefit was assessed using decision curve analysis (DCA). The goodness of fit was evaluated using calibration curves. A joint model nomogram was eventually developed by combining clinically independent risk factors. RESULTS: The best prediction models based on DTL and pathomics features showed area under the curve (AUC) values of 0.89 (95% confidence interval [CI], 0.799-0.989) and 0.85 (95% CI, 0.714-0.989), respectively. The AUC for the best prediction model based on radiomics features and combining radiomics features, DTL features, and pathomics features were 0.86 (95% CI, 0.735-0.979) and 0.93 (95% CI, 0.854-1.000), respectively. Based on DCA and calibration curves, the model demonstrated good net clinical benefit and fit. CONCLUSION: Multimodal radiomics and pathomics serve as valuable predictors of the risk of bone metastases in patients with primary PCa.

Bufalin suppresses hepatocellular carcinogenesis by targeting M2 macrophage-governed Wnt1/ß-catenin signaling.

BACKGROUND: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role in the development of hepatocellular carcinoma (HCC) and provides an important target for HCC therapy. The communication between them is still on the investigation. Bufalin, the active component derived from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor cells, while its immunomodulatory effect on the tumor microenvironment (TME) is unclear. PURPOSE: To explore the mechanism of M2 TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting M2 macrophages. METHODS: Morphology and marker proteins were detected to evaluate macrophage polarization via microscopy and flow cytometry. Cellular proliferation and malignant transformation of HCC cells cultured with macrophage conditioned medium (CM) or bufalin-primed M2-CM, were assessed by cell viability, colony formation and soft agar assays. Regulations of gene transcription and protein expression and release were determined by RT-qPCR, immunoblotting, immunoprecipitation, ELISA and immunofluorescence. Tumorigenicity upon bufalin treatment was verified in orthotopic and diethylnitrosamine-induced HCC mouse model. RESULTS: In this study, we first verified that M2 macrophages secreted Wnt1, which acted as a mediator to trigger ß-catenin activation in HCC cells, leading to cellular proliferation. Bufalin suppressed HCC cell proliferation and malignant transformation by inhibiting Wnt1 release in M2 macrophages, and dose-dependently inhibited HCC progression in mice. Mechanistically, bufalin specially targeted to block Wnt1 transcription, thus inactivating ß-catenin signaling cascade in HCC cells and leading to tumor regression in HCC mouse model. CONCLUSION: These results clearly reveal a novel potential of bufalin to suppress HCC through immunomodulation, and shed light on a new M2 macrophage-based modality of HCC immunotherapy, which additively enhances direct tumor-inhibitory efficacy of bufalin.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.

Temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) may present as comorbid conditions, but treatment options are ineffective. The purpose of this study was to investigate whether valproate (VPA) attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress, which represents a model of pain associated with TMD and FMS comorbidity, and to explore the potential mechanisms. The results showed that VPA inhibited somatic hyperalgesia induced by orofacial inflammation combined with stress, and down-regulated the interleukin-6 (IL-6) expression in the L4-L5 spinal dorsal horn of female rats. The anti-nociceptive effect of VPA was blocked by single or 5 consecutive day intrathecal administration of recombinant rat IL-6. Orofacial inflammation combined with stress up-regulated the ratio of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) to STAT1 (p-STAT1/STAT1) in the spinal cord. VPA did not affect the STAT1 expression, while it down-regulated the ratio of p-STAT1/STAT1. The expression of STAT3 and the ratio of p-STAT3/STAT3 were not affected by orofacial inflammation combined with stress and VPA treatment. Intrathecal administration of exogenous IL-6 up-regulated the ratio of p-STAT1/STAT1. These data indicate that VPA attenuated somatic hyperalgesia induced by orofacial inflammation combined with stress via inhibiting spinal IL-6 in female rats, and the mechanism may involve the alteration of activation status of spinal STAT1. Thus, VPA may be a new candidate analgesic that targets IL-6 and STAT1 for the treatment of pain associated with the comorbidity of TMD and FMS.

Effect of the new video laryngeal mask airway SaCoVLM on airway management in lateral laparoscopic urological surgery: A single center randomized controlled trial.

There are few pertinent studies about the application of laryngeal mask airways (LMAs) in lateral decubitus surgery. Therefore, the aim of our study was to evaluate the effects of lateral position and pneumoperitoneum on oropharyngeal leak pressure (OLP) and ventilation efficiency for the LMA SaCoVLM. Patients undergoing elective retroperitoneal laparoscopic urological surgery were randomized 1:1 to the Supreme group or SaCoVLM group. The primary outcome was the OLP with LMA insertion. The secondary outcomes were the first-attempt success rate, insertion time, adjustment times, gastric tube success rate, LMA alignment accuracy, LMA removal time, regurgitation or aspiration, LMA blood staining, and incidence of adverse events 24 h after surgery. We recruited 70 patients to complete the study. Regardless of lateral position and pneumoperitoneum, the OLP was greater in the SaCoVLM group (n = 35) than in the Supreme group (n = 35), with a median difference of 4-7 cmH2O. The first-attempt success rate of the SaCoVLM group was higher than that of the Supreme group (91.4% vs. 77.1%, risk ratio (RR): 1.19; 95% CI 0.96 to 1.46, P = 0.188). Thus, in the lateral position with pneumoperitoneum, although the new video LMA SaCoVLM has a higher OLP than the LMA Supreme, both devices provide sufficient ventilation efficiency.

A protocol for the stereoselective synthesis of a Star of David [2]catenane.

Most complex prime links exhibit inherent topological chirality, yet their high stereoinduction remains a rare occurrence. Here, we present a protocol for the stereoselective synthesis of a molecular link comprising two triple entwined rings. We describe steps for constructing the precursor circular helicate, performing ring closure metathesis, and demetallation. We also outline procedures for bio-beads separation and data analysis. This protocol holds promise for applications in molecular nanotopology. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.

A ratiometric fluorescent probe for rapid and specific detection of hypochlorite.

Hypochlorite (ClO- ), as a kind of essential reactive oxygen species, plays a crucial role in vitro and in vivo. Here, a ratiometric fluorescent probe (TPAM) was designed and constructed for sensing ClO- based on substituted triphenylamine and malononitrile, which exhibited obvious colour transfer from orange to colourless under daylight accompanied by noticeable fluorescence change from red to green in response to ClO- . TPAM could effectively monitor ClO- with the merits of fast response, excellent selectivity, high sensitivity and a low detection limit of 0.1014 µM. 1 H NMR, mass spectra and theoretical calculations proved that ClO- caused the oxidation of the carbon-carbon double bond in TPAM, resulting in compound 1 and marked changes in colour and fluorescence. In addition, TPAM was utilized for imaging ClO- in living cells successfully with good photostability and biocompatibility.