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The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma (GBM) patients. The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein, facilitating tumor immune evasion. This study presents a pH-adapted excited state intramolecular proton transfer (ESIPT)-isomerized β-ketoamide-based covalent organic framework (COF) nanoplatform (denoted as OT@COF-RVG). Temozolomide (TMZ) and OSMI-4 (O-GlcNAc transferase inhibitor) were integrated into COF cavities, then modified on the surface with polyethylene glycol and the rabies virus peptide RVG-29, showing potential for sensitizing TMZ chemotherapy and initiating photodynamic therapy (PDT). By inhibiting O-GlcNAc and promoting lysosomal degradation of PD-L1, OT@COF-RVG enhanced the effectiveness of immune checkpoint blockade (ICB) therapy. Additionally, treatment with OT@COF-RVG led to a notable elevation in reactive oxygen species (ROS) levels, thereby re-establishing an immunostimulatory state, inducing immunogenic cell death (ICD). In summary, our research unveiled a correlation between O-GlcNAc in GBM and the evasion of immune responses by tumors, while showcasing the potential of OT@COF-RVG in reshaping the immunosuppressive microenvironment of GBM and offering a more effective approach to immunotherapy in clinical settings.

Abstract Purpose Previous research has documented cognitive deficits in survivors of papillary thyroid carcinoma (PTC).Our longitudinal study with large sample size, aims to assess the impact of menopausal status on cognitive function, elucidate related factors of cognitive impairment, and chart the trajectory of cognitive changes over time in female PTC patients. Methods In this longitudinal study, we administered the Montreal Cognitive Assessment (MoCA) to 322 female PTC patients over 40 years old, before surgery and at 3 and 6 months after surgery. Propensity score matching (PSM) was used to adjust for baseline disparities, leading to a final analysis of 228 patients (114 premenopausal and 114 postmenopausal). Cognitive scores were compared between groups using the Mann–Whitney U test, and univariate and multivariate logistic regression analyses were performed to identify independent predictors of cognitive impairment. Results Postmenopausal women demonstrated a significantly higher susceptibility to impairment in delayed recall (p = 0.004) and global cognition (p = 0.006) when compared with premenopausal women. Multivariate analysis identified menopause (p

Dental pulp stem cells (DPSCs) have demonstrated remarkable potential in enhancing peripheral nerve regeneration, though the precise mechanisms remain largely unknown. This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer. In a crab-eating macaque model, we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration, facilitating tissue proliferation and myelin recovery. We further established a rat facial nerve injury (FNI) model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells. A pivotal mitochondrial protective mechanism, resembling the effects of a ROS-targeted inhibitor, involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes, while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects. TNFα secreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs, enhancing mitochondrial transfer and adaptive stress responses, thereby promoting mitochondrial protection against pyroptosis in Schwann cells, as reflected in the improved therapeutic efficacy of TNFα-preconditioned DPSCs in the FNI model. These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer, presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.

Abstract The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy. The nanoreactors can catalyze the oxidation of glutathione (GSH) to glutathione disulfide (GSSG) in hypoxic cancer cells. This initiates the buildup of reactive oxygen species (ROS) and lipid peroxides, leading to the demise of cancer cells. It also stimulates the overexpression of the transient receptor potential melastatin 2 (TRPM2) ion channels, triggering macrophage activation, leading to a systemic immune response. Upon intravenous injection, the nanoreactors can systemically activate the immune system, and nearly fully eradicate an aggressive osteosarcoma tumor inside a mouse model.

ABSTRACT Background Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. JAM2, a member of the Junctional adhesion molecule (JAM) family, plays diverse roles in cell–cell contacts and tumor development. Although JAM2's expression and functions have been reported in various cancers, its clinical and biological significance in LUAD remains unclear. Aims The aim of this study was to investigate the expression and function of JAM2 in LUAD, and to assess its potential as a prognostic gene and a molecular target for early diagnosis and targeted therapy. Materials Immunohistochemistry (IHC) was performed on 37 pairs of LUAD tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted among co‐expression genes in different JAM2 subgroups. In vitro experiments were also conducted to study the migratory and invasive capabilities of LUAD cells when JAM2 was overexpressed. Results The study confirmed that JAM2 was downregulated in LUAD, possibly due to methylation. JAM2 emerged as an independent prognostic gene for predicting the outcomes of patients with LUAD. IHC analysis revealed the significance of JAM2 with clinicopathological parameters in LUAD. GO and KEGG analyses provided insights into the biological processes and pathways associated with JAM2. In vitro experiments showed that overexpressing JAM2 significantly suppressed the migratory and invasive capabilities of LUAD cells. Additionally, JAM2 played a crucial role in LUAD inflammatory infiltration, and higher JAM2 expression predicted a better immunotherapy response. Conclusion JAM2 may serve as a promising molecular target for early diagnosis and targeted therapy of LUAD. Its downregulation in LUAD, potential role as a prognostic gene, and influence on cell migration, invasion, and inflammatory infiltration make it a valuable target for further research and development of therapeutic strategies.

Objectives To evaluate the effectiveness of nurse-led coaching in self-care (SC) interventions for elderly patients undergoing total laryngectomy (TL) using multidimensional parameters.Design This was a double-arm randomised, single-centre trial that met the requirements of the CONSORT statement.Setting Head and neck department in a tertiary A-level hospital.Intervention Elderly patients scheduled for TL were randomly allocated to either the control group (n=24) or the intervention group (n=23). Patients in the control group received routine nursing care during hospitalisation and, subsequently, at home after discharge, received conventional family care without the regular supervision of nurses. Patients in the intervention group received a series of SC interventions led by nurses during hospitalisation and discharge and implemented SC practice using the home SC manual (SC knowledge and SC diary), nurses regularly supervised and evaluated the SC effect. The primary outcome was the SC ability. Secondary outcomes were self- efficacy, quality of life (QoL) and nutritional status.Results The SC intervention improved the SC ability, self-efficacy, QoL and nutritional status scores of patients in the intervention group compared with that of patients in the control group (p

Abstract Human fibrinogen (FIB) has been clinically proven to be considerably effective for the treatment of postoperative bleeding, with reported cases of allergic reactions to human FIB being rare. Here, we report a case of an anaphylactic shock in 27-year-old patients with rheumatic heart valve disease who received a human FIB infusion during mitral valve replacement, aortic valve replacement, and tricuspid valve-shaping surgery. The patients showed generalised profuse sweating, a barely noticeable skin rash, faint pulse, systolic pressure

Abstract Objective This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS). Methods Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (

Abstract Background Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. Methods We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. Results Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. Conclusion TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy. Graphical Abstract

Abstract Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.

Abstract Background Pleural solitary fibrous tumors (pSFTs) are rare mesenchymal pleural tumors with rich vascularity. Surgical resection is the cornerstone of pSFTs treatment, requiring careful preoperative imaging to delineate lesion extent and vascular supply including contrast-enhanced computed tomography and other examinations depending on its size and characteristics. Case presentation The patient was a 34-year-old female with a mass measuring approximately 67 × 42 × 65 mm in the left posterior mediastinum. Intraoperatively, the mass demonstrated rich vascularity. Two veins originating from the abdominal cavity entered the lower pole, one converged from the superior pole, draining into the brachiocephalic vein. Additionally, two arteries arose directly from the descending aorta, while several veins drained into the intercostal veins. In response to unexpected intraoperative vascular findings, vascular clips and silk threads were used to ligate them. Subsequently, the tumor was successfully dissected, with approximately 600 ml of blood loss recorded during the 4-hour surgery. The patient exhibited a satisfactory postoperative recovery, and follow-up spanning over six months revealed no indications of recurrence or metastasis. Conclusions We firstly present a case of successful resection of a pSFT in a 34-year-old woman with a distinct feeding vessel arising from the descending aorta and describe the related surgical procedures. This case highlights preoperative evaluation of mass vascularity based on contrast-enhanced computed tomography. When blood supply is challenging to clarify, angiography can offer additional details, especially for giant pSFTs. Despite this, thorough intraoperative exploration remains essential to detect unexpected vessels. Appropriate interventions should be customized based on the vascular origins and the surrounding anatomical structures.

Abstract Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS‐responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self‐assembled into nanoparticles (uhOLN‐NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN‐NPs to form nanoparticles with hypoxic and ROS responses (HOLN‐NPs). Under hypoxia in RGCs, the azo bond of HOLN‐NPs breaks and releases uhOLN‐NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano‐prodrug. The released nicotinamide and oleic acid co‐scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN‐NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN‐NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN‐NPs provide a new therapeutic approach for patients with neurodegenerative disease.

Shrimp allergy, the most common food allergy in the United States, affects up to 2% of the population. Its etiology is multi-factorial with the combination of genetic predisposition and environmental exposures. This review summarizes the latest diagnosis and management strategies for shrimp allergy. Currently, the double-blind, placebo-controlled food challenge is the gold standard for diagnosis. Moreover, mainstream and experimental management strategies include food allergen avoidance, the FDA-approved omalizumab, and oral immunotherapy. Herein, we emphasize the urgent need to develop more effective diagnostic tools and therapies for shrimp allergy.

IntroductionPredicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy.MethodsWe retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model’s performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort.ResultsWe enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil–Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram’s superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model.ConclusionThe nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients.

Abstract Purpose In VATS surgery, precise preoperative localization is particularly crucial when dealing with small-diameter pulmonary nodules located deep within the lung parenchyma. The purpose of this study was to compare the efficacy and safety of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules. Methods This retrospective study was conducted on 164 patients who received either laser guidance or freehand hook-wire localization prior to Uni-port VATS from September 1st, 2022 to September 30th, 2023 at The First Affiliated Hospital of Soochow University. Patients were divided into laser guidance group and freehand group based on which technology was used. Preoperative localization data from all patients were compiled. The localization success and complication rates associated with the two groups were compared. The risk factors for common complications were analyzed. Results The average time of the localization duration in the laser guidance group was shorter than the freehand group (p

Abstract The main purpose of vital pulp therapy (VPT) is to preserve the integrity and function of the pulp. A wide variety of materials and techniques have been proposed to improve treatment outcomes, and among them, the utilization of lasers has gained significant attention. The application of lasers in different stages of VPT has witnessed remarkable growth in recent years, surpassing previous approaches. This study aimed to review the applications of lasers in different steps of VPT and evaluate associated clinical and radiographic outcomes. An electronic search using Scopus, MEDLINE, Web of Science and Google Scholar databases from 2000 to 2023 was carried out by two independent researchers. The focus was on human studies that examined the clinical and/or radiographic effects of different laser types in VPT. A total of 4243 studies were included in this narrative review article. Based on the compiled data, it can be concluded that although current literature suggests laser may be proposed as an adjunct modality for some procedural steps in VPT, more research with standardized methodologies and criteria is needed to obtain more reliable and conclusive results.

Rock mass in tunnel, underground chamber and other underground engineering is inevitably affected by multiple blasting impact, rock mass cracking and failure are often affected by these damaged rock mass, so it is meaningful to study the rock mass affected by dynamic damage. To explore the influence of cyclic impact on the internal structure of marble, NMR (Nuclear Magnetic Resonance) technique was adopted to test the marble. It was found that the impact would rise the porosity of marble, and the pore size distribution would also change greatly. Then uniaxial compression experiments were conducted on core samples. The results show that the impact will cause significant damage to the marble, and the mechanical properties of the marble will be obviously degraded. With the increase of impact times, the peak strength and tangential deformation modulus tend to decrease. The impact effect promotes the initiation and development of rock microcracks, pushes forward the development of the compaction stage, and increases the strain at the full compaction point. In addition, the damage constitutive model with the combination of different disturbances and loads was constructed in stages according to the principle of statistics, and the experimental results were used to verify the damage constitutive model. The crack closure and failure of the samples subjected to different impact times were well reflected in the model, and the practical significance of the parameters in the model was analyzed. The failure mode of the sample subjected to different impact times is discussed and verified by acoustic emission technology.

Abstract The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development. Graphical Abstract

GRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, including blood, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a scarcity of data linking both intracellular and extracellular GRP78/Bip to disease activity and progression of RA. This study was undertaken to investigate the differential expression of GRP78/Bip in blood, SF, and synovium, and to determine their association with disease activity and progression of RA. Patients with RA, osteoarthritis (OA), and traumatic meniscal injury (TMI) without radiographic OA were consecutively recruited for the study. Among patients with RA, six different subgroups were established based on their disease activity and progression. Disease activity was measured using the DAS28 (Disease activity scores in 28 joints) criterion, while disease progression was evaluated using the Steinbrocker classification grade. The levels of GRP78/Bip, TNF-α, and IL-10 were significantly elevated in the serum, SF, and synovium of patients with RA when compared to both the control (CON, TMI Patients) and the inflammation control (iCON, OA Patients) groups (p < 0.05). In terms of disease activity status, as opposed to remission status in RA, the levels of GRP78/Bip, TNF-α, and IL-10 were all elevated in serum and synovium (p < 0.05). However, GRP78/Bip and IL-10 levels were found to be reduced in SF, while TNF-α levels remained elevated. With respect to disease progression in RA, GRP78/Bip levels exhibited a positive correlation with both the stage of RA and the levels of TNF-α and IL-10 in serum and synovium. Nonetheless, a negative correlation was observed between GRP78/Bip levels and the stage of RA in SF, while positive correlations with the levels of TNF-α and IL-10 persisted. The differential expression of GRP78/Bip in blood, SF, and synovium indicated that the potential role and function of GRP78/Bip might vary depending on its specific location within these biological fluids and tissues. The presence of intracellular and extracellular GRP78/Bip was associated with disease activity and progression of RA, suggesting the involvement of GRP78/Bip in the pathogenesis and development of this debilitating autoimmune disorder, as well as its potential as a biomarker for monitoring disease activity and progression of RA.

Objective: Understanding the characteristics of alveolar bone resorption in an East Asian population after maxillary incisor extraction and providing a reference for implant treatment plans. Study design: Cone-beam computerized tomography (CBCT) data of 125 East Asian patients with unilateral extraction of maxillary incisors for 3 months were collected. The alveolar bone width and height in the extraction sites were measured and compared with the corresponding contralateral sites. Results: The differences in alveolar bone width between the extraction site and contralateral site were as follows: 4.11 mm, 2.68 mm, and 2.09 mm (3 mm, 5 mm, 7 mm apical from CEJ of the contralateral tooth). Data are expressed as the median. The horizontal resorption ratio of alveolar bone was 49.94 %, 31.5 %, and 24.46 %. The difference in alveolar bone height was 0.78 mm. The vertical resorption ratio was 7.78 %. The resorption did not differ significantly between sexes and was not significantly affected by tooth positions. Conclusions: In the studied East Asian population, significant horizontal and vertical alveolar bone resorption occurs after natural healing of maxillary incisor extraction for 3 months. The closer to the alveolar ridge crest, the more significant the horizontal resorption, resulting in an “inverted triangle” shape residual alveolar bone.

Abstract Background The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors. Methods Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not. Results In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not. Conclusion In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Background: Extracellular vesicles (EVs) derived from stem cells demonstrate significant potential in bone regeneration. Adipose tissue is regarded as a stem cell reservoir with abundant reserves and easy accessibility. Compared to adipose-derived stem cells (ASCs), dedifferentiated fat cells (DFATs) possess similar stem cell characteristics but exhibit greater proliferative capacity, higher homogeneity, and an enhanced osteogenic differentiation potential. This study is the first to examine the effect of DFATs-derived EVs on bone regeneration and elucidate their potential mechanisms of action. Methods: Primary DFATs were cultured using the “ceiling culture” method and EVs were isolated by ultracentrifugation and characterized. Experiments were performed to assess the impact of the EVs on the proliferation, migration, and osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Subsequently, high-throughput miRNA sequencing was conducted on the EVs derived from DFATs that had undergone 0 days (0d-EVs) and 14 days (14d-EVs) of osteogenic differentiation. Results: The results indicated that the EVs derived from DFATs which experienced 14 days of osteogenic induction significantly promoted the proliferation, migration, and osteogenic differentiation of BMSCs. High-throughput sequencing results revealed that up-regulated miRNAs in the 14d-EVs were primarily involved in biological processes such as the Notch signaling pathway and the positive regulation of cell movement and migration. The target genes of these differently expressed miRNAs were enriched in osteogenesis-related signaling pathways. Conclusion: This study innovatively demonstrated that conditioned EVs (14d-EVs) derived from DFATs promoted the osteogenic differentiation of BMSCs via miRNAs, offering a promising cell-free therapeutic option for bone defect.

Abstract Purpose The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. Methods A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. Results The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson–Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and joint cartilage destruction. The severity of OA is highly associated with the imbalance between M1 and M2 synovial macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A ROS‐responsive polymer is synthesized to self‐assemble with astaxanthin and autophagy activator rapamycin to form nanoparticles (NP@PolyRHAPM). In vitro experiments show that NP@PolyRHAPM significantly reduced intracellular ROS levels. Furthermore, NP@PolyRHAPM restored mitochondrial membrane potential, increased glutathione (GSH) levels, and promoted intracellular autophagy, hence successfully repolarizing M1 macrophages into the M2 phenotype. This repolarization enhanced chondrocyte proliferation and vitality while inhibiting apoptosis. In vivo experiments utilizing an anterior cruciate ligament transection (ACLT)‐induced OA mouse model revealed the anti‐inflammatory and cartilage‐protective effects of NP@PolyRHAPM, effectively mitigating OA progression. Consequently, the findings suggest that intra‐articular delivery of ROS‐responsive nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for OA treatment.

Abstract Background Postoperative patients with lung cancer mostly experience different degrees of dyspnea and decreased activity tolerance, and these symptoms all significantly affect postoperative quality of life. The concept of pulmonary rehabilitation applicable to patients with chronic respiratory diseases is also applicable to patients with postoperative lung cancer. The current application of postoperative pulmonary rehabilitation for lung cancer is inconsistent, and reliable guidelines are lacking. The purpose of this study was to further verify the efficacy and feasibility of postoperative pulmonary rehabilitation for lung cancer patients, and to find a suitable local pulmonary rehabilitation program for postoperative patients with lung cancer that is clinically promoted in our department through this study. Methods We collected the clinical data of patients undergoing video-assisted thoracoscopic surgery (VATS) wedge resection or lobectomy. The patients were divided into rehabilitation group (using three-ball breathing apparatus after discharge) and control group (routine follow-up after discharge) according to whether the patients were trained with three-ball breathing apparatus after operation. The detailed method using three-ball apparatus is as follows. To begin with, patients are required to put themselves in a comfortable position. Then, after the three-ball breathing apparatus put on the same plane of their eyes, patients hold the tube in their mouth closely and control their breath slowly. When patients inhale to their largest extent, the balls will rise up accordingly. Then they exhale. The evaluation results of pulmonary function, activity tolerance, anxiety scores and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. The effects of pulmonary rehabilitation training on wedge resection and lobectomy were compared. Results A total of 210 patients were included in this study, including 126 patients with VATS wedge resection and 84 patients with VATS lobectomies. No discrepancy was noticed when FEV1 loss between two groups were compared in the wedge resection patients, and the same results were also shown in patients undergoing lobectomy (12.8% ± 2.0% vs. 12.7% ± 1.9%, P = 0.84, wedge resection; 12.6% ± 2.9% vs. 12.1% ± 1.8%, P = 0.37, lobectomy). The loss of FVC in the control group was greater than that in the rehabilitation group for patients undergoing lobectomy (11.7% ± 5.2%, vs. 17.1% ± 5.6%, P

Sound vibrations generate electrical signals called cochlear potentials, which can reflect cochlear stereocilia movement and outer hair cells (OHC) mechanical activity. However, because the cochlear structure is delicate and complex, it is difficult for existing measurement techniques to pinpoint the origin of potentials. This limitation in measurement capability makes it difficult to fully understand the contribution of stereocilia and transduction channels to cochlear potentials. In view of this, firstly, this article obtains the stereocilia movement generated by basilar membrane (BM) vibration based on the positional relationship between the various structures of the organ Corti. Secondly, Kirchhoff’s law is used to establish an electric field model of the cochlear cavity, and the stereocilia movement is embedded in the electric field by combining the gated spring model. Finally, a force-electric coupling mathematical model of the cochlea is established. The results indicated that the resistance variation between different cavities in the cochlea leads to a sharp tuning curve. As the displacement of the BM increased, the longitudinal potential along the cochlea continued to move toward the base. The decrease in stereocilia stiffness reduced the deflection angle, thereby reducing the transduction current and lymphatic potential.

Thermal runaway characteristics and hazards of lithium-ion batteries under low ambient pressure in-flight conditions are studied in a dynamic pressure chamber. The influence of ambient pressures (95 kPa and 20 kPa) and packaging forms (cylindrical and pouch commercial batteries) were especially investigated. The results show that the values of heat release, temperature, and CO2 concentration decrease with the reduction in pressure from 95 kPa to 20 kPa, while the total hydrocarbon and CO increase. Without violent fire, explosion, and huge jet flames, the thermal hazards of TR fire under 20 kPa are lower, but the amount of toxic/flammable gas emissions increases greatly. The amount of CO and hydrocarbons varies inversely with the thermal hazards of fire. Under low-pressure environments of cruise altitude, the thermal hazards of TR fire for pouch cells and the toxic/potentially explosive hazards of gas emissions of cylindrical cells need more attention. The performance of TR hazards for two packaging types of battery is also different. Pouch cells have higher thermal hazards of fire and lower combustible/toxic emitted gases than cylindrical cells. The thermal runaway intensity of individual cells decreases under lower ambient pressure, but the burning intensity increases dramatically when thermal runaway occurs in a battery pack. The open time of a safety valve (rupture of the bag) is shortened, but the trigger time for a thermal runaway varies for different formats of batteries under 20 kPa. Those results may be helpful for the safety warning and hazard protection design of Li batteries under low-pressure conditions.

Objective: The objective of this study is to assess the impact of low-intensity pulsed ultrasound (LIPUS) therapy on the peri-implant osteogenesis in a Type II diabetes mellitus (T2DM) rat model.Methods: A total of twenty male Sprague-Dawley (SD) rats were randomly allocated into four groups: Control group, T2DM group, Control-LIPUS group, and T2DM-LIPUS group. Implants were placed at the rats’ bilateral maxillary first molar sites. The LIPUS treatment was carried out on the rats in Control-LIPUS group and T2DM-LIPUS group, immediately after the placement of the implants, over three consecutive weeks. Three weeks after implantation, the rats’ maxillae were extracted for micro-CT, removal torque value (RTV), and histologic analysis.Results: Micro-CT analysis showed that T2DM rats experienced more bone loss around implant cervical margins compared with the non-T2DM rats, while the LIPUS treated T2DM rats showed similar bone heights to the non-T2DM rats. Bone-implant contact ratio (BIC) were lower in T2DM rats but significantly improved in the LIPUS treated T2DM rats. Bone formation parameters including bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone mineral density (BMD) and RTV were all positively influenced by LIPUS treatment. Histological staining further confirmed LIPUS’s positive effects on peri-implant new bone formation in T2DM rats.Conclusion: As an effective and safe treatment in promoting osteogenesis, LIPUS has a great potential for T2DM patients to attain improved peri-implant osteogenesis. To confirm its clinical efficacy and to explore the underlying mechanism, further prospective cohort studies or randomized controlled trials are needed in the future.

Background. Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. Methods. A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0–85), intermediate III and IV (85–125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). Results. We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8–96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. Conclusions. PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.

Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted.Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C17H18N2O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk.Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.

Tissue engineering (TE) has been widely proposed as a potential solution to the global shortage of donor organs for transplantation. Organic and biocompatible materials have been explored as potential candidates to mimic natural extracellular matrices for regenerative applications. Biomimetic environments have been created using these materials, and hydrogels have shown promise in tissue regeneration due to their rapid gel-forming ability and excellent biocompatibility. Therefore, achieving comparisons between studies utilizing identical materials can prove arduous, as variations in material concentrations, sample preparation techniques, and laboratory conditions significantly influence the physicochemical characteristics of hydrogel systems. To ensure their promotion for clinical purposes, stable variables are crucial. In this regard, we have created an amalgamated and simplified device to assist in hydrogel-based systems using hyaluronic acid and alginate-loaded exosomes for regenerative medicine. The objective of this study is to examine the porosity, injectability, release of loaded exosomes, mechanical properties, and the rate of dissolution and degradation of well-known biomaterials, including alginate and hyaluronic acid, at different concentrations in a stable and controlled setting provided by a simplified integrated device. Furthermore, it aims to comprehensively assess their ex vivo and in vivo osteogenesis and vascularity-related metrics.

Recent advancements in nanotechnology have introduced a myriad of potential applications in dentistry, with nanomaterials playing an increasing role in endodontics. These nanomaterials exhibit distinctive mechanical and chemical properties, rendering them suitable for various dental applications in endodontics, including obturating materials, sealers, retro-filling agents, and root-repair materials. Certain nanomaterials demonstrate versatile functionalities in endodontics, such as antimicrobial properties that bolster the eradication of bacteria within root canals during endodontic procedures. Moreover, they offer promise in drug delivery, facilitating targeted and controlled release of therapeutic agents to enhance tissue regeneration and repair, which can be used for endodontic tissue repair or regeneration. This review outlines the diverse applications of nanomaterials in endodontics, encompassing endodontic medicaments, irrigants, obturating materials, sealers, retro-filling agents, root-repair materials, as well as pulpal repair and regeneration. The integration of nanomaterials into endodontics stands poised to revolutionize treatment methodologies, presenting substantial potential advancements in the field. Our review aims to provide guidance for the effective translation of nanotechnologies into endodontic practice, serving as an invaluable resource for researchers, clinicians, and professionals in the fields of materials science and dentistry.

The stability of nano-TATB in an environment of long-term storage or service is currently one concern since it will affect the reliability of weapon systems. To explore the effects of the residual dimethyl sulfoxide (DMSO) solvent generated during synthesis on the storage performance of nano-TATB, this study proposed a new strategy that utilized solvent atmosphere induction to simulate the effects of residual solvents for the first time and quantified the residual solvents using the equilibrium adsorption capacity (Qe) obtained from the pseudo-first-order adsorption kinetic model. Moreover, this study investigated the storage performance of nano-TATB in the DMSO atmosphere using techniques of scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy (Raman), and infrared (IR) spectroscopy. The results show that the residual DMSO can induce nano-TATB growth more significantly than stimuli in a hot and humid environment. After aging at 60 ​°C for 1 ​d in the DMSO atmosphere, a large number of particles with relatively a regular shape and a particle size of about 1 ​μm were generated in the DMSO atmosphere, with a Qe of DMSO of (1.045 ​± ​0.026) mg·g−1. After aging for 5 ​d, some nano-TATB particles grew and had a particle size of up to 5–6 ​μm, and the average density and cohesive strength of nano-TATB greatly increased. As shown by the analysis of the growth mechanism of nano-TATB in the DMSO atmosphere based on the above experimental results, the main reason for the self-assembly of nano-TATB is the surface DMSO induction caused by the interactions between nano-TATB and DMSO molecules. These results show that the key to improving the storage stability of nano-TATB is to reduce the content of residual solvents.

Abstract Background About 20–30% of patients with schizophrenia develop tardive dyskinesia (TD). Oxidative stress is one potential causes of TD. CYP2E1 is considered as an oxidative stress-related gene, however, no study has been reported on the DNA methylation levels of the CYP2E1 in schizophrenia or TD. Methods A total of 35 schizophrenia patients with TD, 35 schizophrenia patients without TD (NTD), and 35 health controls (HCs) were collected in Beijing, China. DNA was extracted from peripheral blood samples. The promoter methylation levels of CYP2E1 were detected using pyrosequencing. The generalized linear model (GLM) was used to examine the methylation levels of three CpG sites among three diagnostic groups (TD vs. NTD vs. HC). Results The average methylation levels were 8.8 ± 10.0, 14.5 ± 11.9 and 15.1 ± 11.3 in TD, NTD and HC groups, respectively. The F-test in GLM revealed overall differences in the average of methylation levels of three CpG sites among three diagnostic groups (p = 0.0227) and in the third CpG site (p = 0.0026). Furthermore, the TD group had lower average methylation levels than HC and NTD groups (p = 0.0115 and 0.0268, respectively). Specifically, TD group showed lower methylation levels in the third CpG site than HC and NTD groups (p = 0.0012 and 0.0072, respectively). Additionally, associations of the methylation levels with clinical features in the TD group were observed using Spearman correlation analysis. Conclusion This study provides the first evidence of DNA methylation levels in the promoter of CYP2E1 gene associated with schizophrenia and TD. The abnormal DNA methylation might serve as a potential mechanism for TD.

Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.

Abstract Background In the treatment of peripheral early-staged lung cancer and benign lesions, segmentectomy and wedge resection are both reliable treatment methods. It is debatable that how much pulmonary function will be lost after different sublobar resection in the treatment of early-staged deep-located peripheral NSCLC (non-small cell lung cancer). The purpose of this study was to explore postoperative pulmonary function changes of sublobar resection in enrolled patients with non-subpleural peripheral nodules. Methods We collected clinical data of patients undergoing VATS (video-assisted thoracoscopic surgery) segmentectomy or wedge resection for single nodule. These nodules were confirmed as peripheral non-subpleural nodules by preoperative 3D imaging. Patients were divided into two groups according to the operation procedure. Demographic characteristics, pulmonary function, postoperative outcomes, and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. Outcomes after wedge resection were compared with those after segmentectomy resection. Results A total of 88 patients were included in this study, including 46 patients with VATS wedge resection and 42 patients with VATS segmentectomy. No difference was detected when comparing FEV1 (forced expiratory volume in 1 s) loss between these two groups (17.6 ± 2.1%, wedge resection vs. 19.4 ± 5.4%, segmentectomy, P = 0.176). FVC (forced vital capacity) loss (8.7 ± 2.3%, wedge resection vs. 17.1 ± 2.2%, segmentectomy, P

Abstract Aims/Introduction To estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China. Materials and Methods Hospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ2‐test was used to evaluate differences between groups regarding the prevalence, and demographic and other clinical parameters. Results A total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5/h), moderate‐to‐severe (apnea hypopnea index ≥15/h) and severe (apnea hypopnea index ≥30/h) OSAS was 66.3% (95% confidence interval 60.8–71.6%), 35.6% (95% confidence interval 30.3–41.2%) and 16.5% (95% confidence interval 12.5–21.1%), respectively. Central and mixed apnea contributed 12% to all sleep‐disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self‐reported snoring and apnea, and diabetes complications. Conclusions Guidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.

Abstract Background Lung adenocarcinoma (LUAD) is the most common subtype of non‐small cell lung cancer and has a poor prognosis. RBR E3 ubiquitin ligases are a special class of E3 ubiquitin ligases which contain three zinc‐bing domains that catalyze ubiquitin to substrate proteins. The RBR family of E3 ubiquitin ligases has been reported in various human malignancies, but the roles of RBR E3 ubiquitin ligases in LUAD remain unclear. Methods By using TCGA and Kaplan–Meier plotter databases, we examined the expression and prognostic value of RBR E3 ubiquitin ligases. cBioPortal was used to analyze genetic mutations. The STRING database was used to build a protein interactive network. GO, KEGG, and GSEA were performed to investigate the potential biological functions of RBR E3 ubiquitin ligases. Results The expression of ARIH2, RNF144B, RNF216, and RNF217 was significantly related to the clinicopathological parameters and prognosis in LUAD patients. GSEA enrichment result showed ARIH2, RNF144B, RNF216, and RNF217 were all associated with NADH dehydrogenase complex assembly. GO functional enrichment analysis revealed that four RBR E3 ubiquitin ligases and their interactors were most correlated with ubiquitin‐protein transferase activity. KEGG pathway analysis indicated they were associated with cytosolic DNA‐sensing pathway, RIG‐I‐like receptor signaling pathway and NF‐kappa B signaling pathway. Conclusions Our comprehensive bioinformatic analysis revealed that ARIH2, RNF144B, RNF216, and RNF217 may be new prognostic biomarkers and these findings will help to better understand the distinct roles of RBR E3 ubiquitin ligases in LUAD.

Fluorescent tracers facilitate the identification and subsequent collection of tumour draining lymph node biopsies, enabling important clinical assessment. Here, the authors present a molecular gold nanocluster NIR-II fluorescent imaging probe and demonstrate its utility to visualise draining lymph nodes in breast and colon cancer mouse models.

Summary: Temporal associative learning binds discontiguous conditional stimuli (CSs) and unconditional stimuli (USs), possibly by maintaining CS information in the hippocampus after its offset. Yet, how learning regulates such maintenance of CS information in hippocampal circuits remains largely unclear. Using the auditory trace fear conditioning (TFC) paradigm, we identify a projection from the CA1 to the subiculum critical for TFC. Deep-brain calcium imaging shows that the peak of trace activity in the CA1 and subiculum is extended toward the US and that the CS representation during the trace period is enhanced during learning. Interestingly, such plasticity is consolidated only in the CA1, not the subiculum, after training. Moreover, CA1 neurons, but not subiculum neurons, increasingly become active during CS-and-trace and shock periods, respectively, and correlate with CS-evoked fear retrieval afterward. These results indicate that learning dynamically enhances stimulus information maintenance in the CA1-subiculum circuit during learning while storing CS and US memories primarily in the CA1 area.

A two-step temperature-controlled magnetron sputtering procedure was adopted to obtain a bilayer hierarchical Fe25.2Co25.2Ni27.4Cr22.2 high entropy alloy (HEA) thin film consisting of the external nano-lamellar layer and internal equiaxed zone, which displayed combined advantages of high hardness, good modulus and excellent corrosion resistance. The roles of heterogeneous nanostructure on the mechanical and corrosion behavior were revealed by nano-indentation and Scanning Kelvin probe (SKP) methods. Compared to the substrate 304 ASS, the hierarchical HEA film not only shows much higher nano-hardness and modulus values, but also possesses a higher electron transfer resistance (12158 vs 4567 Ω.cm2) and lower overall corrosion rate (6.28*10−4 vs 6.84*10−3 mm·year−1). Moreover, the outer nano-lamellar layer shows higher nano-hardness (∼8.1 GPa) but lower surface potential values (∼-261 mV) than those of the inter equiaxed zone (∼5.9 GPa and ∼−150 mV). The former arises from the significant grain refinement strengthening effect, while the latter is attributed to an obvious increase in the high energy and chemically active areas such as grain boundaries and triple junctions. This work demonstrates the capability of hierarchy to adjust the comprehensive performance of multi-functional films, which possess superior mechanical property and comparable corrosion performance than those of the as-cast bulk HEA alloys.

Purpose: To explore which restoration strategy generates the most favorable stress distribution in an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect. Methods: Models with one post in palatal canal (PP), each post in palatal and distobuccal canals (PDP), each post in palatal and mesiobuccal canals (PMP), and each post in all canals (PDMP) were established for an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect either with fiber-reinforced composite (FRC) post or gold alloy cast (GAC) post. A 400-N vertical force and a 225-N lateral force were respectively applied. The Mohr-Coulomb stress ratio (σMC ratio) in the residual tooth structure (RTS), the resin cement, and the crowns, the tensile stress (σt) and compressive stress (σc) in the FRC posts, the von-Mises stress ratio (σvM ratio) in the GAC post-and-cores, and the σt and shear stress (σs) at the adhesive interfaces were calculated using finite element analysis. Results: FRC posts generated lower σMC ratio than GAC posts in the RTS (0.3274–0.3643 vs. 0.3399–0.4118). Among the FRC post groups, the PDMP group got the lowest σs at the dentin-post interface (14.92 MPa) and the abutment-crown interface (8.242 MPa) under vertical loading, as well as the lowest σMC ratio in the RTS (0.3381) and the lowest σs at the dentin-post interface (38.00 MPa) under lateral loading. Conclusions: From the point of stress distribution, placing FRC posts in the palatal, distobuccal, and mesiobuccal canals is the optimal strategy in restoring a severely damaged maxillary first molar, provided that lateral occlusal force is reduced.

Abstract Background Esophageal carcinosarcoma (ECS) is a rare malignant tumor that often presents as an intraluminal polypoid lesion in the esophageal lumen. The pathogenesis of esophageal carcinosarcoma is not clear and its etiology is still being discussed. Case presentation We report the case of a 68-year-old male who had dysphagia for approximately three months. Contrast-enhanced computed tomography showed an irregular enhancing mass in the lower esophagus. Endoscopy showed a gray-white mass with a smooth surface that almost filled the esophageal lumen at a location 28 cm from the incisor tooth. Considering the location of the tumor, we opted for Ivor-Lewis esophagectomy with intrathoracic anastomosis through a 5-port laparoscope and uniport video-assisted thoracic surgery (VATS). Pathological analysis showed that the mass comprised carcinoma in situ and pleomorphic sarcoma, without lymphatic metastasis. The postoperative pathological stage was T1bN0M0, stage I (Japanese Classification of Esophageal Cancer 11th Edition). The latest follow-up of the patient was 14 months after the surgery, and no signs of recurrence or metastasis were found. Conclusion This case demonstrates a rare esophageal malignancy with a peculiar histological composition. Successful VATS esophagectomy with intrathoracic anastomosis was conducted without recurrence or metastasis at the 14-month follow-up.

Abstract Identification of novel molecular signaling targets for non-small cell lung cancer (NSCLC) is important. The present study examined expression, functions and possible underlying mechanisms of the sodium/myo-inositol co-transporter SLC5A3 in NSCLC. The Cancer Genome Atlas (TCGA) database and local NSCLC tissue results demonstrated that SLC5A3 expression in NSCLC tissues (including patient-derived primary NSCLC cells) was significantly higher than that in normal lung tissues and lung epithelial cells. In primary NSCLC cells and immortalized lines, SLC5A3 depletion, using small hairpin RNA (shRNA) and CRSIRP/Cas9 methods, robustly impeded cell proliferation and migration, simultaneously provoking cell cycle arrest and apoptosis. Conversely, ectopic overexpression of SLC5A3 further enhanced proliferation and migration in primary NSCLC cells. The intracellular myo-inositol contents and Akt-mTOR activation were largely inhibited by SLC5A3 silencing or knockout (KO), but were augmented following SLC5A3 overexpression in primary NSCLC cells. Significantly, SLC5A3 KO-induced anti-NSCLC cell activity was largely ameliorated by exogenously adding myo-inositol or by a constitutively-active Akt construct. By employing the patient-derived xenograft (PDX) model, we found that the growth of subcutaneous NSCLC xenografts in nude mice was largely inhibited by intratumoral injection SLC5A3 shRNA adeno-associated virus (AAV). SLC5A3 silencing, myo-inositol depletion, Akt-mTOR inactivation and apoptosis induction were detected in SLC5A3 shRNA virus-injected NSCLC xenograft tissues. Together, elevated SLC5A3 promotes NSCLC cell growth possibly by maintaining myo-inositol contents and promoting Akt-mTOR activation.