Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.

Association between preoperative sarcopenia and prognosis of pancreatic cancer after curative-intent surgery: a updated systematic review and meta-analysis.

BACKGROUND: Sarcopenia is associated with poor outcomes in many malignancies. However, the relationship between sarcopenia and the prognosis of pancreatic cancer has not been well understood. The aim of this meta-analysis was to identify the prognostic value of preoperative sarcopenia in patients with pancreatic cancer after curative-intent surgery. METHODS: Database from PubMed, Embase, and Web of Science were searched from its inception to July 2023. The primary outcomes were overall survival (OS), progression-free survival (PFS), and the incidence of major complications. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were used to assess the relationship between preoperative sarcopenia and the prognosis of patients with pancreatic cancer. All statistical analyses were conducted by Review Manager 5.3 and STATA 17.0 software. RESULTS: A total of 23 retrospective studies involving 5888 patients were included in this meta-analysis. The pooled results demonstrated that sarcopenia was significantly associated with worse OS (HR = 1.53, P < 0.00001) and PFS (HR = 1.55, P < 0.00001). However, this association was not obvious in regard to the incidence of major complications (OR = 1.33, P = 0.11). CONCLUSION: Preoperative sarcopenia was preliminarily proved to be associated with the terrible prognosis of pancreatic cancer after surgery. However, this relationship needs to be further validated in more prospective studies.

Integrated transcriptomics and proteomics analyses reveal the ameliorative effect of hepatic damage in tilapia caused by polystyrene microplastics with chlorella addition.

Fish exhibit varying responses to polystyrene microplastics (MPs) depending on particle size. Previous studies suggested that microorganisms adhering to the surface of MPs can induce toxic effects. In this study, Tilapia were exposed to MPs of control (group A), 75 nm (B), 7.5 µm (C), 750 µm (D), as well as combinations of all sizes (E) and 75 nm MPs with Chlorella vulgaris addition (F) for 7, 10 and 14 days. Histopathological changes in liver of tilapia were assessed using enzyme activities, transcriptomics and proteomics. The results showed that in groups combined MPs of different particle sizes and those supplemented with chlorella, MPs were localized on the surface of goblet cells, leading to vacuoles, constricted hepatic sinuses and nuclei displacement. Exposure to 7.5 and 750 µm MPs significantly increased the contents of fatty acid synthase (FAS), adenosine triphosphate (ATP), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), total cholesterol (TC), total triglyceride (TG) contents at 7 and 10 days. In particular, cytochrome p450 1a1 (EROD), reactive oxygen species (ROS) and superoxide dismutase (SOD) were markedly elevated following exposure to MPs. Apoptotic markers caspase-3, and inflammatory markers, including tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß), had a similar upward trend in comparisons of group C vs A at 7 d, group D vs A at 14 d. The peroxisome proliferator activated receptor (PPAR) signaling pathway, spliceosome, was highly enriched during the 7-day exposure of medium sized MPs, while largest MPs in the comparison of group D vs A at 14 d activated pathways such as phagosome, apoptosis, salmonella infection. Transcriptomic analysis revealed that after 14 days, the kyoto encyclopedia of genes and genomes (KEGG) pathways associated with protein processing in endoplasmic reticulum and the PPAR signaling has been significantly enriched in the Chlorella-supplemented group, which was further confirmed via the proteomic analysis. Overall, the findings highlight the size-dependent effects of MPs on histopathological changes, gene and protein expression in the liver of tilapia, and C. vulgaris effectively attenuated liver damages, likely through modulation of endoplasmic reticulum protein processing and PPAR signaling pathways.

Ultrahigh-Q Lead Halide Perovskite Microlasers.

Lead halide perovskites have been promising platforms for micro- and nanolasers. However, the fragile nature of perovskites poses an extreme challenge to engineering a cavity boundary and achieving high-quality (Q) modes, severely hindering their practical applications. Here, we combine an etchless bound state in the continuum (BIC) and a chemically synthesized single-crystalline CsPbBr3 microplate to demonstrate on-chip integrated perovskite microlasers with ultrahigh Q factors. By pattering polymer microdisks on CsPbBr3 microplates, we show that record high-Q BIC modes can be formed by destructive interference between different in-plane radiation from whispering gallery modes. Consequently, a record high Q-factor of 1.04 × 105 was achieved in our experiment. The high repeatability and high controllability of such ultrahigh Q BIC microlasers have also been experimentally confirmed. This research provides a new paradigm for perovskite nanophotonics.

Interaction gene set between osteoclasts and regulatory CD4+ T cells can accurately predict the prognosis of patients with osteosarcoma.

Osteoclasts (OCs) and regulatory CD4+ T cells (CD4+ Tregs) are important components in the tumor microenvironment (TME) of osteosarcoma. In this study, we collected six osteosarcoma samples from our previous study (GSE162454). We also integrated a public database (GSE152048), which included single cell sequencing data of 11 osteosarcoma patients. We obtained 138,192 cells and then successfully identified OCs and CD4+ Tregs. Based on the interaction gene set between OCs and CD4+ Tregs, patients from GSE21257 were distinguished into two clusters by consensus clustering analysis. Both the tumor immune microenvironment and survival prognosis between the two clusters were significantly different. Subsequently, five model genes were identified by protein-protein interaction network based on differentially upregulated genes of cluster 2. Quantitative RT-PCR was used to detect their expression in human osteoblast and osteosarcoma cells. A prognostic model was successfully established using these five genes. Kaplan-Meier survival analysis found that patients in the high-risk group had worse survival (p = 0.029). Therefore, our study first found that cell-cell communication between OCs and CD4+ Tregs significantly alters TME and is connected to poor prognosis of OS. The model we constructed can accurately predict prognosis for osteosarcoma patients.

Significance of the neutrophil-to-lymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity osteosarcoma: a multicentre retrospective study.

BACKGROUND: At present, no predictive factor has been validated for the early efficacy of neoadjuvant chemotherapy (NACT) in osteosarcoma. The purpose of this study was to investigate the significance of the neutrophil-to-lymphocyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma. METHODS: Pathological complete response (pCR) was used to assess the efficacy of NACT. Receiver operating characteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR. Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT. RESULTS: The optimal NLR cut-off value was 2.36 (sensitivity, 80.0%; specificity, 71.3%). Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR. Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR. Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI 1.36-5.17, p = 0.02). CONCLUSION: The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients. Patients with a higher NLR showed a lower percentage of pCR after NACT.

Multidimensional jagged SnSb/C/DLC nanofibers fabricated by AP-PECVD method for Li-ion battery anode.

The atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD) method has been shown to have dramatic effects on the morphology and structure of nanomaterials. For the sake of solving the capacity decline caused by alloy expansion and improving the electrode performance of SnSb/C nanofiber anodes in Li-ion batteries, the self-designed AP-PECVD device was first used to deposit large numbers of diamond-like carbon (DLC) nanoparticles on nanofibers to construct a special 3D structure. Interestingly, after the AP-PECVD and carbonization treatment, we found that most DLC nanoparticles had a single crystal structure and nanofibers reacted with a high energy hydrogen plasma to generate a special jagged morphology. The special jagged grooves provided an excellent channel for the Li ions' insertion/extraction, and the 3D structure provided a buffer space for the volume expansion of SnSb alloy during the electrochemical cycle. Compared with the SnSb/C nanofibers, SnSb/C/DLC nanofibers exhibited a much better electrochemical performance with a high reversible capacity of 583.54 mAh g-1 at the 100th cycle, and excellent rate capability. This paper proved that the AP-PECVD device can successfully deposit a DLC nanoparticle layer and the construction of nanofiber morphology was a valid method to improve the electrochemical properties of the nanofiber anode in Li-ion batteries.

Multiple Diffused Cavernous Hemangiomas Associated with Venous Calculi Formation in the Right Upper Limb and Back: A Case Report.

Cavernous hemangioma, a benign soft tissue and intramuscular tumor, is commonly located in the head, neck, and maxillofacial regions. They can sometimes occur in the limbs and trunk, although rarely. Treatment of cavernous hemangiomas includes surgical and nonsurgical means. Cases of extensive diffused cavernous hemangiomas of an entire limb are rare. In this case presentation, we report the case of chronic diffused cavernous hemangioma associated with venous calculi of the right upper limb and back in a 31-year-old Chinese man. Due to the long history, chronic articular impairments and extensive damage to the skeletal and musculature, surgical amputation of the limb was performed. The aim of this report is to provide further understanding of treatment prioritization and the risks of delayed treatment of cavernous hemangiomas.

Intraperitoneal extraosseous osteosarcoma: a case report and literatures review.

BACKGROUND: To investigate the clinical imaging manifestations, diagnosis and treatment of intraperitoneal extraosseous osteosarcoma. CASE PRESENTATION: A 52-year-old male patient with intraperitoneal extraosseous osteosarcoma was retrospectively analyzed. He suffered from left lower abdominal pain accompanied by mass for 6 months. On abdominal CT scan, multiple patchy and banded calcification were found. The largest is about six centimeters in diameter and underwent mass resection. Postoperative pathology revealed retroperitoneal osteosarcoma. The reported intraperitoneal extraosseous osteosarcoma was analyzed and the related literature was reviewed. Two years after operation, the patients had recurrence of the tumors and invaded sigmoid colon, peritoneum and bladder. Palliative operation was performed to remove the tumors in the bladder and transverse colostomy was performed. The patients were followed up by telephone and died 2 months after the second operation. CONCLUSIONS: Intraperitoneal extraosseous osteosarcoma has a low incidence and has no specific imaging features. Surgical resection is the main treatment and the prognosis is poor.

Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates.

A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of ß-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.

Giant cell tumors combined with secondary aneurysmal bone cysts are more likely to develop postoperative recurrence: A retrospective study of 256 cases.

PURPOSE: The epidemiology and clinicopathology of aneurysmal bone cysts (ABCs) secondary to giant cell tumors of bone (GCTBs) have been well documented in the previous literature. However, reports on whether secondary ABCs could affect the postoperative recurrence of GCTBs are rare. This study analyzed the effects of secondary ABCs and other relevant clinical factors on the postoperative recurrence of GCTBs of the extremities. METHODS: We retrospectively analyzed 256 cases of GCTBs of the extremities that were treated surgically at our institution. Among them, there were 60 patients diagnosed with GCTBs combined with secondary ABCs and 196 patients diagnosed with simple GCTBs. Intralesional curettage and tumor resection were performed in 136 and 120 cases, respectively. Univariate analysis, Kaplan-Meier survival analysis, and multivariate regression analysis were used to assess the factors for postoperative recurrence. The follow-up period was at least 24 months. RESULTS: The total postoperative recurrence rate was 32%. The recurrence rate in the secondary ABCs group was significantly higher than that in the simple GCTBs group (53.3% vs 25.5%, P < 0.05). Curettage was associated with a higher recurrence rate than tumor resection (42.5% vs 20%, P < 0.05). Kaplan-Meier survival analysis showed that patients with GCTBs combined with secondary ABCs and who were treated by intralesional curettage had a decreased disease-free survival rate. The hazard ratio was 2.18 (95% confidence interval [CI], 1.15-4.13) for the group of GCTB combined with ABCs ( P = 0.01) and 1.97 (95% CI, 1.22-7.50) for the curettage group ( P = 0.01), respectively. Multivariate regression analysis revealed that the presence of secondary ABCs and curettage were independent factors for recurrence of GCTBs. CONCLUSION: According to the results of this study, the presence of secondary ABCs is a potential risk factor for postoperative relapse of GCTBs.

Intermolecular Carboamination of Unactivated Alkenes.

Herein, we report the first example of group transfer radical addition of O-vinylhydroxylamine derivatives onto unactivated alkenes. By utilizing O-vinylhydroxylamine derivatives as both the N- and C-donors, this reaction enables intermolecular carboamination of unactivated alkenes in an atom economical fashion. As the process is initiated through N-radical addition followed by C-transfer, linear carboamination products are afforded. This differs from canonical radical carbofunctionalization of olefins, which typically favors branched product owing to initiation by C-radical addition.

Investigation of multi-bunching by generating multi-order fluorescence of NV center in diamond.

Fabricating electronics from solid-state quantum emitters is a promising strategy for the miniaturization and integration of electronic devices. However, the practical realization of solid-state quantum devices and circuits for signal transmission and processing at room temperature has remained challenging. Herein, we investigated the multi-bunching phenomenon by generating multi-order fluorescence from a pseudo-thermal source at room temperature using the nitrogen-vacancy (NV) center in diamond. We demonstrate the shift in time of multi-bunching by controlling the effect of dressing to realize logical gates and transistor switching operations. We also suggest the optimization of the time propagation delay (TPD) of the gate circuit by changing the boxcar gate position.

Residual bone fragments in tibiofibular joint and postoperative local recurrence: an analysis of 21 cases of proximal fibular giant cell tumour.

BACKGROUND: Currently, there are no known reports on the aetiology of local giant cell tumour (GCT) recurrence in the proximal fibula following en bloc resection. We analysed 21 cases of proximal fibular GCT, focusing on the presence of residual bone in the tibiofibular joint, its causes and its impact on postoperative recurrence. METHODS: We retrospectively analysed 21 cases with proximal fibular GCT occurring between 2000 and 2017. RESULTS: There were 14 males and 7 females. The average patient age was 25.0 years. Seventeen patients were diagnosed and treated at our facility, while 4 were referred after local recurrence. Six patients presented with residual bone fragments in the tibiofibular joint during their first month of follow-up. Patients with residual bone fragments had a higher local recurrence rate (83.3%) than those without (0%, p = 0.0003). Upon further analysis, patients with a preoperative Campanacci grade III tumour (p = 0.0055) and pathological fractures (p = 0.0109) were at a higher risk of exhibiting postoperative residual bone fragments. CONCLUSIONS: The presence of residual bone fragments in the tibiofibular joint was the main cause of postoperative local recurrence. The presence of residual bone fragments may be related to the preoperative Campanacci grade and pathological fractures. Therefore, close attention should be paid to postoperative follow-up examinations, and if recurrence is suspected, surgical resection should be planned.

Palladium-Catalyzed Fluoroarylation of gem-Difluoroalkenes.

A Pd-catalyzed fluoroarylation of gem-difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α-CF3 -benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem-difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non-symmetric α,α-disubstituted trifluoroethane derivatives.

Ultrafast optical transistor and router of multi-order fluorescence and spontaneous parametric four-wave mixing in Pr³âº:YSO.

We study the realization of an optical transistor (switch and amplifier) and router in multi-order fluorescence (FL) and spontaneous parametric four-wave mixing (SP-FWM). We estimate that the switching speed is about 15 ns. The router action results from the Autler-Townes splitting in spectral or time domain. The switch and amplifier are realized by dressing suppression and enhancement in FL and SP-FWM. The optical transistor and router can be controlled by multi-parameters (i.e., power, detuning, or polarization).

A Two-Layer Graphene Nonwoven Fabric for Effective Electromagnetic Interference Shielding.

Rapid advancements and proliferation of electronic devices in the past decades have significantly intensified electromagnetic interference (EMI) issues, driving the demand for more effective shielding materials. Herein, we introduce a novel two-layer graphene nonwoven fabric (2-gNWF) that shows excellent EMI shielding properties. The 2-gNWF fabric comprises a porous fibrous upper layer and a dense conductive film-like lower layer, specifically designed to enhance EMI shielding through the combined mechanisms of reflection, multiple internal reflections, and absorption of electromagnetic waves. The 2-gNWF exhibits a remarkable EMI shielding effectiveness (SE) of 80 dB while maintaining an impressively low density of 0.039 g/cm3, surpassing the performance of many existing graphene-based materials. The excellent EMI shielding performance of 2-gNWF is attributed to the multiple interactions of incident electromagnetic waves with its highly conductive network and porous structure, leading to efficient energy dissipation. The combination of high EMI SE and low density makes 2-gNWF ideal for applications that require lightweight yet effective shielding properties, demonstrating the significant potential for advanced EMI shielding applications.

Primary hepatic mucosa-associated lymphoid tissue lymphoma complicated with atrial fibrillation: A case report and literature review.

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignant primary hepatic lymphoma. The sensible choice of treatment for patients with primary lymphoma combined with atrial fibrillation (AF) is controversial and challenging. PATIENT CONCERNS: The patient presented with both primary hepatic MALT lymphoma and AF, which was difficult to manage. DIAGNOSES: Pathological and immunohistochemical examination are helpful for definitive diagnosis. INTERVENTIONS: Surgical resection and subsequent anticoagulant therapy are main treatment methods, and adjuvant therapy depends on the situation. OUTCOMES: Primary hepatic MALT lymphoma is easy to misdiagnosis due to a lack of typical symptoms and imaging signs. LESSONS: This case highlights for patients with primary hepatic MALT lymphoma combined with AF, toxicity caused by adjuvant chemotherapy should be fully considered, and careful selection should be made based on the general conditions and complications of patients.

Development and validation of neutrophil extracellular traps-derived signature to predict the prognosis for osteosarcoma patients.

Neutrophil extracellular traps (NETs) have been reported to be crucial in tumorigenesis and malignant progression. However, their prognostic significance, association with tumor immune microenvironment (TIME), and therapeutic response in osteosarcoma (OS) stills remain unclear. Hence, TARGET and GSE21257 cohorts were included for analysis. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were conducted to extract NETs-derived genes. Subsequently, the NETs score (NETScore) model, consisting of 4 signature genes, was established and validated with the least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. Our results indicated that NETScore has satisfactory predictability of the patient's overall survival, with AUC values at 1-, 3- and 5-year in the training cohort of 0.798, 0.792 and 0.804, respectively; similar prominent prediction performance was obtained in three validation cohorts. Further, real-time quantitative PCR (RT-qPCR) assay was conducted to determine the expression of signature genes in human osteoblasts and OS cells. Besides, NETScore and clinical factors (age, gender, metastatic status) were integrated to construct a nomogram. C-index and AUC values at 1-, 3-, and 5-year were above 0.800, displaying robust predictive performance. Patients with high and low NETScore had different immune statuses and drug sensitivity. Meanwhile, several positive regulatory immune function pathways, including T cell proliferation, activation and migration, were significantly suppressed among patients with high NETScore. Summarily, we established a novel NETScore that can accurately predict OS patients' prognosis, which correlated closely with the immune landscape and therapeutic response and might help to guide clinical decision-making.