Integration of deep learning and habitat radiomics for predicting the response to immunotherapy in NSCLC patients.

BACKGROUND: The non-invasive biomarkers for predicting immunotherapy response are urgently needed to prevent both premature cessation of treatment and ineffective extension. This study aimed to construct a non-invasive model for predicting immunotherapy response, based on the integration of deep learning and habitat radiomics in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Independent patient cohorts from three medical centers were enrolled for training (n = 164) and test (n = 82). Habitat imaging radiomics features were derived from sub-regions clustered from individual's tumor by K-means method. The deep learning features were extracted based on 3D ResNet algorithm. Pearson correlation coefficient, T test and least absolute shrinkage and selection operator regression were used to select features. Support vector machine was applied to implement deep learning and habitat radiomics, respectively. Then, a combination model was developed integrating both sources of data. RESULTS: The combination model obtained a strong well-performance, achieving area under receiver operating characteristics curve of 0.865 (95% CI 0.772-0.931). The model significantly discerned high and low-risk patients, and exhibited a significant benefit in the clinical use. CONCLUSION: The integration of deep-leaning and habitat radiomics contributed to predicting response to immunotherapy in patients with NSCLC. The developed integration model may be used as potential tool for individual immunotherapy management.

Pelargonidin inhibits cell growth and promotes oxidative stress-mediated apoptosis in lung cancer A549 cells.

Lung cancer has the worst prognosis with an average 5-year survival rate of only 10%-20%. Lung cancer has the highest prevalence rate and a second most common cause of cancer-associated mortalities worldwide. The present study was planned to explore the anticancer effects of pelargonidin against the lung cancer A549 cells via analyzing oxidative stress-mediated apoptosis. The viability of both control and pelargonidin-treated A549 cells was analyzed using the MTT cytotoxicity assay at different time periods. The levels of endogenous ROS generation, mitochondrial membrane potential (Δψm), and apoptosis were assessed using corresponding fluorescent staining assays. The levels of oxidative stress biomarkers, including TBARS, SOD, CAT, and GSH, in the cell lysates of control and pelargonidin-treated A549 cells were examined using the assay kits. The pelargonidin treatment substantially suppressed the A549 cell growth. Further, pelargonidin promoted the ROS production and depleted the Δψm levels in the A549 cells. The fluorescent staining assays witnessed the occurrence of increased apoptosis in the pelargonidin-treated A549 cells. The pelargonidin also boosted the TBARS and reduced the antioxidant levels thereby promoted the oxidative stress-regulated apoptosis in the A549 cells. In summary, the findings' results of the current study demonstrated an anticancer activity of pelargonidin on A549 cells. The pelargonidin treatment substantially decreased the growth and encouraged the oxidative stress-regulated apoptosis in A549 cells. Therefore, it was evident that the pelargonidin could be employed as an effective anticancer candidate to treat the lung cancer.

Calcium phosphate coating enhances osteointegration of melt electrowritten scaffold by regulating macrophage polarization.

The osteoimmune microenvironment induced by implants plays a significant role in bone regeneration. It is essential to efficiently and timely switch the macrophage phenotype from M1 to M2 for optimal bone healing. This study examined the impact of a calcium phosphate (CaP) coating on the physiochemical properties of highly ordered polycaprolactone (PCL) scaffolds fabricated using melt electrowritten (MEW). Additionally, it investigated the influence of these scaffolds on macrophage polarization and their immunomodulation on osteogenesis. The results revealed that the CaP coated PCL scaffold exhibited a rougher surface topography and higher hydrophilicity in comparison to the PCL scaffold without coating. Besides, the surface morphology of the coating and the release of Ca2+ from the CaP coating were crucial in regulating the transition of macrophages from M1 to M2 phenotypes. They might activate the PI3K/AKT and cAMP-PKA pathways, respectively, to facilitate M2 polarization. In addition, the osteoimmune microenvironment induced by CaP coated PCL could not only enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro but also promote the bone regeneration in vivo. Taken together, the CaP coating can be employed to control the phenotypic switching of macrophages, thereby creating a beneficial immunomodulatory microenvironment that promotes bone regeneration.

Characterization of myeloid signature genes for predicting prognosis and immune landscape in Ewing sarcoma.

Myeloid cells as a highly heterogeneous subpopulation of the tumor microenvironment (TME) are intimately associated with tumor development. Ewing sarcoma (EWS) is characterized by abundant myeloid cell infiltration in the TME. However, the correlation between myeloid signature genes (MSGs) and the prognosis of EWS patients was unclear. In this research, we synthetically characterized the expression of MSGs in a training cohort and classified EWS patients into two subtypes. Immune cell infiltration analysis revealed that MSGs subtypes correlated closely with different immune statuses. Furthermore, a three-gene prognostic model (CTSD, SIRPA, and FN1) was constructed by univariate, LASSO, and multivariate Cox analysis, and it showed excellent prognostic accuracy in EWS patients. We also developed a nomogram for better predicting the long-term survival of EWS. Functional enrichment analysis showed immune-related pathways were distinctly different in the high- and low-risk groups. Further analysis revealed that patients in the high-risk group were tightly associated with an immunosuppressive microenvironment. Finally, we validated the expression of these candidate genes by Western blot (WB), qPCR, and immunohistochemistry (IHC) analysis. To sum up, our study identified that the MSGs model was strongly linked to prognostic prediction and immune infiltration in EWS patients, providing novel insights into the clinical treatment and management of EWS patients.

The new insights into autophagy in thyroid cancer progression.

In recent decades, the incidence of thyroid cancer keeps growing at a shocking rate, which has aroused increasing concerns worldwide. Autophagy is a fundamental and ubiquitous biological event conserved in mammals including humans. Basically, autophagy is a catabolic process that cellular components including small molecules and damaged organelles are degraded for recycle to meet the energy needs, especially under the extreme conditions. The dysregulated autophagy has indicated to be involved in thyroid cancer progression. The enhancement of autophagy can lead to autophagic cell death during the degradation while the produced energies can be utilized by the rest of the cancerous tissue, thus this influence could be bidirectional, which plays either a tumor-suppressive or oncogenic role. Accordingly, autophagy can be suppressed by therapeutic agents and is thus regarded as a drug target for thyroid cancer treatments. In the present review, a brief description of autophagy and roles of autophagy in tumor context are given. We have addressed summary of the mechanisms and functions of autophagy in thyroid cancer. Some potential autophagy-targeted treatments are also summarized. The aim of the review is linking autophagy to thyroid cancer, so as to develop novel approaches to better control cancer progression.

Identification of key biomarkers related to epithelial-mesenchymal transition and immune infiltration in ameloblastoma using integrated bioinformatics analysis.

OBJECTIVE: This study aimed to elucidate the underlying mechanisms of ameloblastoma (AM) through integrated bioinformatics analysis. METHODS: We downloaded two microarrays of AMs from the GEO database and identified differentially expressed genes (DEGs) by integrated bioinformatics analysis. The enrichment analysis of DEGs was conducted to characterize GO and KEGG pathways. Protein-protein interaction (PPI) network and hub genes were screened via STRING and Cytoscape. CIBERSORT algorithm was utilized to analyze immune infiltration in AMs. We also verified the diagnostic and therapeutic value of hub genes. RESULTS: Overall, 776 DEGs were identified in AMs through bioinformatics analysis. The function enrichment analysis shed light on pathways involved in AMs. Subsequently, we screened six hub genes via PPI network. Furthermore, we evaluated immune infiltration in AMs and found that macrophages may be participating in the progression of AMs. The upregulated expression of FN1 was related to the macrophages M2 polarization. Finally, ROC analysis indicated that six hub genes had high diagnostic value for AMs and 11 drugs interacted with upregulated hub genes were identified by screening the DGIdb database. CONCLUSION: This study revealed the underlying mechanisms of pathogenesis and biological behavior of AMs and provided candidate targets for the diagnosis and treatment of AMs.

Silencing long non-coding RNA LINC00960 inhibits osteosarcoma proliferation by sponging miR-107 to downregulate SALL4.

long non-coding RNAs (lncRNAs), as tumor suppressors or oncogenes, have been identified to play key roles in tumorigenesis. The present study explored the roles and potential mechanisms of LINC00960 in osteosarcoma (OS). In vitro study showed that silencing LINC00960 inhibited proliferation, migration and invasion of 143B and MG63. In vivo study demonstrated that knockdown of LINC00960 repressed tumor growth. Further investigation revealed that LINC00960 could regulate SALL4 by sponging miR-107 to promote the progression of OS. Together, LINC00960 is a tumor oncogene in the development and prognosis of OS, which may be a new therapeutic target for OS.

Comparison of the effectiveness of high-flow nasal oxygen vs. standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: a systematic review and meta-analysis.

BACKGROUND: In recent years, high flow nasal oxygen (HFNO) has been widely used in clinic, especially in perioperative period. Many studies have discussed the role of HFNO in pre- and apneic oxygenation, but their results are controversial. Our study aimed to examine the effectiveness of HFNO in pre- and apneic oxygenation by a meta-analysis of RCTs. METHODS: EMBASE, PUBMED, and COCHRANE LIBRARY databases were searched from inception to July 2021 for relevant randomized controlled trails (RCTs) on the effectiveness of HFNO versus standard facemask ventilation (FMV) in pre- and apenic oxygenation. Studies involving one of the following six indicators: (1) Arterial oxygen partial pressure (PaO2), (2) End expiratory oxygen concentration (EtO2), (3) Safe apnoea time, (4) Minimum pulse oxygen saturation (SpO2min), (5) Oxygenation (O2) desaturation, (6) End expiratory carbon dioxide (EtCO2) or Arterial carbon dioxide partial pressure(PaCO2) were included. Due to the source of clinical heterogeneity in the observed indicators in this study, we adopt random-effects model for analysis, and express it as the mean difference (MD) or risk ratio (RR) with a confidence interval of 95% (95%CI). We conducted a risk assessment of bias for eligible studies and assessed the overall quality of evidence for each outcome. RESULTS: Fourteen RCTs and 1012 participants were finally included. We found the PaO2 was higher in HFNO group than FMV group with a MD (95% CI) of 57.38 mmHg (25.65 to 89.10; p = 0.0004) after preoxygenation and the safe apnoea time was significantly longer with a MD (95% CI) of 86.93 s (44.35 to 129.51; p < 0.0001) during anesthesia induction. There were no significant statistical difference in the minimum SpO2, CO2 accumulation, EtO2 and O2 desaturation rate during anesthesia induction between the two groups. CONCLUSIONS: This systematic review and meta-analysis suggests that HFNO should be considered as an oxygenation tool for patients during anesthesia induction. Compared with FMV, continuous use of HFNO during anesthesia induction can significantly improve oxygenation and prolong safe apnoea time in surgical patients.

Eikenella corrodens infections in human: Reports of six cases and review of literatures.

PURPOSE: To investigate clinical characteristics of six cases of Eikenella corrodens infection in Ningbo First Hospital in China in recent 2 years. METHODS: We retrospectively analyze medical records of six cases of E. corrodens infection in Ningbo First Hospital from 2020 to 2021. And we describe the gender, age, clinical manifestations, antimicrobial administration, and treatment of the six patients. RESULTS: Five of the patients had deep infection and they were treated with surgical drainage or abscess resection plus antimicrobial administration. After treatment, five patients were discharged and recovered well, and another patient was transferred to another hospital for further treatment. All the six cases were in line with the reports on the clinical characteristics of patients infected with E. corrodens at home and abroad before 2021. CONCLUSION: Eikenella corrodens is a part of the normal flora of human oropharynx, but it can migrate to other parts of the human body to cause severe invasive disease in humans. Although it is susceptible to most antimicrobials, it needs debridement in the treatment of deep infection.

Clinical features of patients with talaromycosis marneffei and microbiological characteristics of the causative strains.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a temperature-dependent dimorphic fungus that is mainly prevalent in Southeast Asia and South China and often causes disseminated life-threatening infections. This study aimed to investigate the clinical features and improve the early diagnosis of talaromycosis marneffei in nonendemic areas. METHODS: We retrospectively analyzed the medical records of six cases of T. marneffei infection. We describe the clinical manifestations, laboratory tests, and imaging manifestations of the six patients. RESULTS: Talaromyces marneffei infection was confirmed by sputum culture, blood culture, tissue biopsy, and metagenomic next-generation sequencing (mNGS). In this study, there were five disseminated-type patients and two HIV patients. One patient died within 24 h, and the others demonstrated considerable improvement after definitive diagnosis. CONCLUSIONS: Due to the lack of significant clinical presentations of talaromycosis marneffei, many cases may be easily misdiagnosed in nonendemic areas. It is particularly important to analyze the imaging manifestations and laboratory findings of infected patients. With the rapid development of molecular biology, mNGS may be a rapid and effective diagnostic method.

Downregulation of Circ_0088196 Contributes to the Development of Trophoblastic Cells through miR-133b Sponging Function to Affect the AHNAK Expression.

OBJECTIVE: Preeclampsia (PE) is the most common gestational disease related to various biomolecules, including circular RNA. Hsa_circ_0088196 (circ_0088196) was aberrantly upregulated in PE tissues. DESIGN: This study focused on the further exploration of circ_0088196 in PE. METHODS: Circ_0088196, microRNA-133b (miR-133b), and AHNAK Nucleoprotein (AHNAK) levels were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). EDU assay was used for proliferation detection. Cell cycle and apoptosis were analyzed using flow cytometry. Wound healing assay and transwell assay were performed to assess migration and invasion. The protein levels were determined via Western blot. Target analysis was conducted through dual-luciferase reporter assay and RNA pull-down assay. RESULTS: Circ_0088196 upregulation was detected in PE patients. The knockdown of circ_0088196 induced the promotion of proliferation, cell cycle, migration, and invasion but not the inhibition of apoptosis in trophoblastic cells. Then, circ_0088196 was found to act as a sponge of miR-133b in HTR-8/SVneo cells. The inhibition of miR-133b abolished the regulation of si-circ_0088196 in trophoblastic cells. In addition, miR-133b targeted AHNAK and circ_0088196 evoked the expression change of AHNAK by sponging miR-133b. The function of circ_0088196 was also achieved by regulating AHNAK in trophoblastic cells. LIMITATIONS: The role of circ_0088196 in PE was not verified by in vivo experiments. CONCLUSION: The current evidence demonstrated that circ_0088196 knockdown facilitated trophoblastic cell development by regulating the levels of miR-133b and AHNAK, suggesting that circ_0088196 promoted the PE progression via the miR-133b/AHNAK axis.

Customized three dimensional printed prosthesis as a novel intercalary reconstruction for resection of extremity bone tumours: a retrospective cohort study.

AIMS: The 3D-printed prosthesis (3DP) is a novel treatment for massive bone defect reconstruction after tumor resection. This study was aiming to explore the clinical efficacy of customized 3DP for intercalary reconstruction by comparing the clinical outcomes after implanting customized 3DP or conventional allograft in limb salvage surgery. METHODS: A total of 28 patients with extremity bone tumors who underwent customized 3DP or conventional allograft reconstruction between 2011 and 2018 at our institution were analyzed retrospectively. Among them, 14 cases received customized 3DP reconstruction (3DP group), and 14 cases received conventional allograft reconstruction (control group). Demographics, surgical outcomes, radiographical assessments, limb functions, and post-operative complications between these two groups were collected to evaluate clinical outcomes. RESULTS: No significant difference was observed in the demographics, mean intra-operative blood loss, MOSI scores, and MSTS scores between the two groups. Patients in 3DP group had a shorter operative time (157.9 vs 199.6 min, p = 0.03) and lesser number of fluoroscopy (4.1 vs 8.1, p < 0.001) compared to control group. The mean time to osseointegration at bone-implant interfaces in 3DP group was significantly earlier than that in control group (6.1 vs 12.2 months, p < 0.001). Moreover, the 3DP group had a significantly lower post-operative complication rate than the control group (7% vs 50%, p = 0.03). CONCLUSIONS: The customized 3DP might provide a promising strategy for intercalary reconstruction in limb salvage surgery with more precise reconstruction, higher surgical efficiency, and comparable satisfactory clinical outcomes.

The Characterization of OXA-232 Carbapenemase-Producing ST437 Klebsiella pneumoniae in China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) was epidemic around the world and become a global threat to public health. The most important carbapenem-resistant mechanism is producing carbapenemases, especially Klebsiella pneumoniae carbapenemase (KPC), which is prevalent in the international clonal complex CC11. The high-risk multidrug-resistant CC11 is widespread worldwide, and KPC-producing and (New Delhi metallo) NDM-producing strains had been reported in this clonal complex before; moreover, cases with the CC11 strain faced more severe forms of drug resistance and treatment challenges than other clonal complexes. In this study, we identified an OXA-232-producing ST437 Klebsiella pneumoniae isolate in China, which belonged to CC11. The isolate was resistant to ß-lactams, aminoglycosides, and fluoroquinolones but susceptible to fosfomycin, tigecycline, and colistin. The bla OXA-232 gene was located on a 6141 bp ColKP3-type nonconjugative plasmid, and the plasmid was transformed by chemical transformation successfully. This is the first report of OXA-232-producing ST437 K. pneumoniae in China, a new clone of high-risk multidrug-resistant CC11.

The complete chloroplast genome of Dianella ensifolia (Asphodelaceae).

Dianella ensifolia (L.) Redouté 1802 is a plant known for its significant medicinal values. In this study, we presented its chloroplast genome. The length of the chloroplast genome was found to be 156,571 bp, with a GC content of 37.86%. It consisted of a large single-copy (LSC) of 85,318 bp and a small single-copy (SSC) of 18,307 bp, a pair of inverted repeats (IRs) of 26,473 bp each that separated the LSC and SSC regions. The chloroplast genome of D. ensifolia consisted of 114 unique genes, including 80 protein-coding genes, four rRNA genes, and 30 tRNA genes. Through phylogenetic analysis, we identified a close relationship between D. ensifolia and D. nigra. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Dianella, but also provides valuable insights for the evolutionary study of the family Asphodelaceae.

The Complete Mitochondrial Genome Sequence of Eimeria kongi (Apicomplexa: Coccidia).

Rabbit coccidiosis is caused by infection with one or, more commonly, several Eimeria species that parasitize the hepatobiliary ducts or intestinal epithelium of rabbits. Currently, there are eleven internationally recognized species of rabbit coccidia, with the complete mitochondrial (mt) genomes of six species commonly infecting rabbits having been sequenced and annotated. Eimeria kongi was initially discovered in 2011 and prompted a preliminary study on this species. Through traditional morphological analysis, E. kongi was identified as a novel species of rabbit coccidia. To further validate this classification, we sequenced and annotated its mitochondrial genome. The complete mt genome of E. kongi spans 6258 bp and comprises three cytochrome genes (cytb, cox1, cox3), fourteen gene fragments for the large subunit (LSU) rRNA, and nine gene fragments for the small subunit (SSU) rRNA, lacking transfer RNA (tRNA) genes. Moreover, phylogenetic analysis of the mitochondrial genome sequence of E. kongi revealed its clustering with six other species of rabbit coccidia into a monophyletic group. Additionally, E. irresidua and E. flavescens were grouped within the lineage lacking oocyst residuum, consistent with their morphological characteristics. Consistent with multiple molecular phylogenies, in this investigation, E. kongi was further confirmed as a new species of rabbit coccidia. Our research findings are of great significance for the classification of coccidia and for coccidiosis prevention and control in rabbits.

Bioactive 3D Electrohydrodynamic Printed Lattice Architectures Augment Tenogenesis of Tendon Stem/Progenitor Cells.

Tendon defect repair remains a tough clinical procedure that hinders functional motion in patients. Electrohydrodynamic (EHD) three-dimensional (3D) printing, as a novel strategy, can controllably fabricate biomimetic micro/nanoscale architecture, but the hydrophobic and bioinert nature of polymers might be adverse to cell-material interplay. In this work, 3D EHD printed polycaprolactone (PCL) was immobilized on basic fibroblast growth factor (bFGF) using polydopamine (PDA), and the proliferation and tenogenic differentiation of tendon stem/progenitor cells (TSPCs) in vitro was researched. A subcutaneous model was established to evaluate the effects of tenogenesis and immunomodulation. We then investigated the in situ implantation and immunomodulation effects in an Achilles tendon defect model. After immobilization of bFGF, the scaffolds profoundly facilitated proliferation and tenogenic differentiation; however, PDA had only a proliferative effect. Intriguingly, the bFGF immobilized on EHD printed PCL indicated a synergistic effect on the highest expression of tenogenic gene and protein markers at 14 days, and the tenogenesis may be induced by activating the transforming growth factor-ß (TGF-ß) signal pathway in vitro. The subcutaneous engraftment study confirmed a tendon-like structure, similar to that of the native tendon, as well as an M2 macrophage polarization effect. Additionally, the bioactive scaffold exhibited superior efficacy in new collagen formation and repair of Achilles tendon defects. Our study revealed that the topographic cues alone were insufficient to trigger tenogenic differentiation, requiring appropriate chemical signals, and that appropriate immunomodulation was conducive to tenogenesis. The tenogenesis of TSPCs on the bioactive scaffold may be correlated with the TGF-ß signal pathway and M2 macrophage polarization.

An asynchronous response fluorescence sensor combines machine learning theory to qualitatively and quantitatively detect tetracyclines.

Excess use of tetracyclines poses significant health risks arising from animal-derived foods, meaning simple and sensitive methods to detect tetracyclines would be beneficial given current laboratory methods are complex and expensive. Herein, we describe an asynchronous response fluorescence sensor constructed based on Zn-based metal-organic framework and Ru(bpy)32+ (denoted as Ru@Zn-BTEC) for the qualitative and quantitative detection of tetracyclines in foods. Under excitation at 365 nm, the sensor emitted red fluorescence at 609 nm. When tetracyclines were present, these molecules aggregated in the Ru@Zn-BTEC framework, causing green fluorescence emission at 528 nm. The developed sensing system accurately distinguished the different categories of tetracyclines with a classifier accuracy of 94 %. The Ru@Zn-BTEC sensor demonstrated a detection limit of 0.012 µM and satisfactory recovery (87.81 %-113.84 %) for tetracyclines in food samples. This work provides a pathway for constructing asynchronous response fluorescence sensors for food analysis.