Low NT5DC2 expression predicts favorable prognosis and suppresses soft tissue sarcoma progression via ECM-receptor interaction pathway.

BACKGROUND: Soft tissue sarcoma, a malignant tumor arising from mesenchymal tissues with poor prognosis. 5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncogene, and the precise involvement of NT5DC2 in soft tissue sarcoma were still undefined. Hence, our study aims to investigate NT5DC2 functions in soft tissue sarcoma progression. METHODS: The tumor immune single-cell hub 2 (TISCH2) website, The Cancer Genome Atlas (TCGA) pan-cancer or sarcoma and Gene Expression Omnibus (GEO, GSE21122) databases were applied to visualize the NT5DC2 status in the sarcoma databases. The NT5DC2 protein expression in sarcoma tissues in our hospital was detected by using immunohistochemistry (IHC) and analyzed the associations between NT5DC2 expression and clinicopathological parameters. Real-time quantitative polymerase chain reaction (RT-qPCR), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing, transwell, flow cytometry and xenograft model were used to elucidate the effects of NT5DC2 downregulated by lentivirus in sarcoma cell. RESULTS: The TISCH2 website detection found that NT5DC2 expression is enriched in malignant cells in sarcoma single-cell database. Furthermore, the TCGA-sarcoma database indicated that NT5DC2 expression correlates with metastasis, positive margin status, prognosis, and diagnostic value. Additionally, IHC staining showed that 40 % of soft tissue sarcoma patients present high expression of NT5DC2, and NT5DC2 upregulation is closely associated with poor prognosis. Functional verification analysis further revealed that downregulating NT5DC2 expression can suppress sarcoma progression through the ECM-receptor interaction pathway. CONCLUSION: Low expression of NT5DC2 predicts a favorable prognosis in soft tissue sarcoma, and downregulated NT5DC2 expression can suppress sarcoma cell progression through the ECM-receptor interaction pathway.

Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread.

Background: The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably ß-lactams, constitutes a formidable challenge for healthcare and global public health management. Methods: This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features. Results: The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments. Conclusion: In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

Identifying squalene epoxidase as a metabolic vulnerability in high-risk osteosarcoma using an artificial intelligence-derived prognostic index.

BACKGROUND: Osteosarcoma (OSA) presents a clinical challenge and has a low 5-year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers to stratify high-risk OSA patients and guide treatment. METHODS: We combined 10 machine-learning algorithms into 101 combinations, from which the optimal model was established for predicting overall survival based on transcriptomic profiles for 254 samples. Alterations in transcriptomic, genomic and epigenomic landscapes were assessed to elucidate mechanisms driving poor prognosis. Single-cell RNA sequencing (scRNA-seq) unveiled genes overexpressed in OSA cells as potential therapeutic targets, one of which was validated via tissue staining, knockdown and pharmacological inhibition. We characterized changes in multiple phenotypes, including proliferation, colony formation, migration, invasion, apoptosis, chemosensitivity and in vivo tumourigenicity. RNA-seq and Western blotting elucidated the impact of squalene epoxidase (SQLE) suppression on signalling pathways. RESULTS: The artificial intelligence-derived prognostic index (AIDPI), generated by our model, was an independent prognostic biomarker, outperforming clinicopathological factors and previously published signatures. Incorporating the AIDPI with clinical factors into a nomogram improved predictive accuracy. For user convenience, both the model and nomogram are accessible online. Patients in the high-AIDPI group exhibited chemoresistance, coupled with overexpression of MYC and SQLE, increased mTORC1 signalling, disrupted PI3K-Akt signalling, and diminished immune infiltration. ScRNA-seq revealed high expression of MYC and SQLE in OSA cells. Elevated SQLE expression correlated with chemoresistance and worse outcomes in OSA patients. Therapeutically, silencing SQLE suppressed OSA malignancy and enhanced chemosensitivity, mediated by cholesterol depletion and suppression of the FAK/PI3K/Akt/mTOR pathway. Furthermore, the SQLE-specific inhibitor FR194738 demonstrated anti-OSA effects in vivo and exhibited synergistic effects with chemotherapeutic agents. CONCLUSIONS: AIDPI is a robust biomarker for identifying the high-risk subset of OSA patients. The SQLE protein emerges as a metabolic vulnerability in these patients, providing a target with translational potential.

Design of 3D-printed prostheses for reconstruction of periacetabular bone tumors using topology optimization.

Background: Prostheses for the reconstruction of periacetabular bone tumors are prone to instigate stress shielding. The purpose of this study is to design 3D-printed prostheses with topology optimization (TO) for the reconstruction of periacetabular bone tumors and to add porous structures to reduce stress shielding and facilitate integration between prostheses and host bone. Methods: Utilizing patient CT data, we constructed a finite element analysis (FEA) model. Subsequent phases encompassed carrying out TO on the designated area, utilizing the solid isotropic material penalization model (SIMP), and this optimized removal area was replaced with a porous structure. Further analyses included preoperative FEA simulations to comparatively evaluate parameters, including maximum stress, stress distribution, strain energy density (SED), and the relative micromotion of prostheses before and after TO. Furthermore, FEA based on patients' postoperative CT data was conducted again to assess the potential risk of stress shielding subsequent to implantation. Ultimately, preliminary follow-up findings from two patients were documented. Results: In both prostheses, the SED before and after TO increased by 143.61% (from 0.10322 to 0.25145 mJ/mm3) and 35.050% (from 0.30964 to 0.41817 mJ/mm3) respectively, showing significant differences (p < 0.001). The peak stress in the Type II prosthesis decreased by 10.494% (from 77.227 to 69.123 MPa), while there was no significant change in peak stress for the Type I prosthesis. There were no significant changes in stress distribution or the proportion of regions with micromotion less than 28 µm before and after TO for either prosthesis. Postoperative FEA verified results showed that the stress in the pelvis and prostheses remained at relatively low levels. The results of follow-up showed that the patients had successful osseointegration and their MSTS scores at the 12th month after surgery were both 100%. Conclusion: These two types of 3D-printed porous prostheses using TO for periacetabular bone tumor reconstruction offer advantages over traditional prostheses by reducing stress shielding and promoting osseointegration, while maintaining the original stiffness of the prosthesis. Furthermore, in vivo experiments show that these prostheses meet the requirements for daily activities of patients. This study provides a valuable reference for the design of future periacetabular bone tumor reconstruction prostheses.

(E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment.

Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single-cell hub 2 website was used for graph-based visualization of Smad3 status in osteosarcoma single-cell database. Western Blot was applied to detect the expression of Smad3 protein in cell lines. Colony formation and cell counting kit-8 assays were used to evaluate cell proliferation. Transwell and wound healing assays were used to detect the migration and invasion abilities of cells. Cell apoptosis rates and cell cycle changes were explored by using flow cytometry analysis. The xenograft tumor growth model was applied to explore the effect in tumor growth after Smad3 blockage in vivo. Moreover, to confirm the potential mechanism of Smad3's effects on osteosarcoma, bioinformatics analysis was performed in TARGET-Osteosarcoma and GSE19276 databases. Our study found that the Smad3 protein is overexpressed in 143B and U2OS cells, suppressing the expression of Smad3 protein in osteosarcoma cells by Smad3 target inhibitor (E)-SIS3 or lentivirus can inhibit the proliferation, migration, invasion, promote cell apoptosis, arrest cell G1 cycle in osteosarcoma cells in vitro, and suppress tumor growth in vivo. Furthermore, the bioinformatics analysis demonstrated that high expression of Smad3 is closely associated with low immune status in TARGET-Osteosarcoma and GSE19276 databases. Our study suggested that Smad3 could contribute positively to osteosarcoma progression via the regulation of tumor immune microenvironment, and Smad3 may represent as an valuable potential therapeutic target in osteosarcoma therapy.

Genetic characterization of a Salmonella enterica serovar Typhimurium isolated from an infant with concurrent resistance to ceftriaxone, ciprofloxacin and azithromycin.

OBJECTIVES: To investigate the resistance mechanism of a Salmonella Typhimurium (S. Typhimurium) isolated from a faecal sample of an infant, which exhibited concurrent resistance to ceftriaxone, ciprofloxacin and azithromycin. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution in two kinds of drug-sensitive plates. Antimicrobial resistance (AMR) genes were identified by whole genome sequencing and bioinformatics analysis. Genotyping of the strain was performed by multilocus sequence typing (MLST). Plasmid DNA was sequenced and analysed using plasmid bioinformatics tools. RESULTS: The SH11G993 strain was resistant to 28 antibiotics and carried 54 AMR genes. MLST results showed that the strain belonged to a rare genotype. The plasmid profile and plasmid sequencing showed that the strain carried two resistance plasmids. The pSH11G993-1 carried 14 AMR genes (especially co-harboured blaCMY-2, mphA and ermB) and a variety of insertion sequences, belonging to the IncC. The pSH11G993-2 carried 3 AMR genes and 9 virulence genes, belonging to the IncFIB-FII, forming a novel resistance and virulence co-harbouring plasmid. CONCLUSIONS: Our findings highlight that continuously monitor the changes in antibiotic resistance patterns and research on the resistance mechanisms in potential human pathogens are imperative.

Physics-informed Gaussian process for tool wear prediction.

The tool wear monitoring (TWM) system plays an increasingly important role to ensure high quality finishing and system safety in advanced CNC machining process. The pure data-based TWM approaches generally needs to develop complex machine learning models and require massive sensory data to learn the models to reach high monitoring accuracy, while the physics-based tool wear models are simple but hard to adapt to varied working conditions. In order to incorporate the benefits of both methods, a novel physics-informed Gaussian process model is developed to predict the tool wear. Different from the traditional approaches, three tool wear physical models are introduced to develop the physics-informed Gaussian process regression (PB-GPR) model. The wear model is applied to constrain the mean function of the Gaussian process, so that the PB-GPR is more in line with the actual tool wear. At the same time, the model can initiate small data training to meet limited tool wear labels in practice, and then update the model with new measurements. Multi-sensor signals are collected and multi-domain features are extracted for the model learning. The proposed approach is validated from high speed milling experiments. The results show a significant performance improvement including tool wear prediction accuracy and robustness in extrapolation compared to the conventional machine learning methods.

Bacteroides xylanisolvens possesses a potent anti-hyperuricemia effect in goslings fed on a high-protein diet.

Introduction: Hyperuricemia is widespread in humans and birds which is a necessary physiological factor leading to gout. Studies have shown an inextricable relationship between gut microbiota and hyperuricemia. This study explored the association between intestinal flora and hyperuricemia in Goslings. Methods and results: The hyperuricemia model was established in gosling by a high protein diet (HPD). 16S rDNA sequencing showed that the cecal microbiota differed significantly between the HPD and control groups (fed with the normal protein). The abundance of Firmicutes was higher in the HPD group, while the Bacteroidetes were lower than in controls. To investigate the role of intestinal flora in hyperuricemia, the cecum microbiotas from the HPD group and the control group were transplanted to the newly born goslings by gavage. The serum uric acid levels of the goslings that transplanted the cecal microbiota of the HPD group were significantly higher than the goslings that transplanted the cecal microbiota of the controls. Furthermore, the transplantation of cecal microbiota also affects the production and excretion of uric acid in goslings. Then we identify the gut bacterium Bacteroides xylanisolvens as an effective anti-hyperuricemia in the Goslings. B. xylanisolvens reduces serum uric acid concentrations in hyperuricemia in the Goslings' model, and it can up-regulation ABCG2 mRNA expression in the kidney and down-regulation XDH mRNA expression in the liver. Discussion: The intestinal flora acts as a novel target for the therapeutic approach to hyperuricemia and gout, suggest Bacteroides xylanisolvens is a possible route to therapy for hyperuricemia and gout in goslings.

Surgical robot-assisted tripod percutaneous reconstruction technique combined with bone cement filling technique for the treatment of acetabular metastasis.

Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms. Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot's guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells. Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery. Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis.

Combination of hsa_circ_0004674 and lncRNA OIP5­AS1 as a novel clinical biomarker used to predict prognosis in patients with osteosarcoma.

Osteosarcoma is a malignant tumor that predominantly occurs in children or adolescents under the age of 20 years old. Metastasis and chemotherapy resistance are two problems in the treatment of osteosarcoma, and the lack of definite biomarkers impairs the course of treatment. In recent years, non-coding RNA, as a biomarker of osteosarcoma, has become an area of research focus. The role of long non-coding RNAs (lncRNAs), such as lncRNA OIP5-AS1, and circular RNAs, such as hsa_circ_0004674, in osteosarcoma have previously been revealed, and the present study investigated their clinical significance. A total of 20 samples were collected from patients with osteosarcoma. The expression levels of lncRNA OIP5-AS1 and hsa_circ_0004674 were analyzed in tumor tissues and patient serum, and their associations with chemotherapy sensitivity, lung metastasis and prognosis were assessed. The results revealed that these two non-coding RNAs were significantly upregulated in the osteosarcoma tissues of patients compared with those in the adjacent tumor tissues. In addition, the expression levels of the two non-coding RNAs were increased in the serum of patients with osteosarcoma compared with those in patients with bone fractures (P<0.01). In patients with lung metastasis or chemotherapy resistance (tumor necrosis rate <90%), the expression levels of the two non-coding RNAs were similarly increased. By plotting the receiver operating characteristic curve, it was revealed that the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 was better than ALP or either non-coding RNA alone in predicting chemotherapy sensitivity and metastasis. Kaplan-Meier survival analysis showed that, in patients with osteosarcoma, higher expression of both non-coding RNAs was associated with worse survival time (log-rank test P=0.006). In conclusion, the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 may be used as a better biomarker than traditional biomarkers, such as ALP, in a clinical setting.

Refracture after plate removal of midshaft clavicle fractures after bone union-incidence, risk factors, management and outcomes.

INTRODUCTION: There is a great debate on the routine use of open reduction and internal fixation (ORIF) for midshaft clavicle fractures, and one concern is the adverse events after ORIF, such as implant removal after bone union. In this retrospective study, we assessed the incidence, risk factors, management and outcomes of refracture after plate removal of midshaft clavicle fractures after bone union. MATERIALS AND METHODS: Three hundred fifty-two patients diagnosed with acute midshaft clavicle fractures who had complete medical records from primary fractures to refracture were recruited. Details of imaging materials and clinical characteristics were carefully reviewed and analysed. RESULTS: The incidence rate of refracture was 6.5% (23/352), and the average interval from implant removal to refracture was 25.6 days. Multivariate analysis showed that the risk factors were Robinson type-2B2 and fair/poor reduction. Females were 2.4 times more likely to have refracture, although it was not significant in multivariate analysis (p = 0.134). Postmenopausal females with a short interval (≤ 12 months) from primary surgery to implant removal had a significant risk for refracture. Tobacco use and alcohol use during bone healing were potential risk factors for male patients, although they were not significant in multivariate analysis. Ten patients received reoperation with or without bone graft, and they had a higher rate of bone union than 13 patients who refused reoperation. CONCLUSION: The incidence of refracture following implant removal after bone union is underestimated, and severe comminute fractures and unsatisfactory reduction during primary surgery are risk factors. Implant removal for postmenopausal female patients is not recommended due to a high rate of refracture.

Generic Cutting Force Modeling with Comprehensively Considering Tool Edge Radius, Tool Flank Wear and Tool Runout in Micro-End Milling.

Accurate cutting force prediction is crucial in improving machining precision and surface quality in the micro-milling process, in which tool wear and runout are essential factors. A generic analytic cutting force model considering the effect of tool edge radius on tool flank wear and tool runout in the micro-end milling process is proposed. Based on the analytic modeling of the cutting part of the cutting edge in the end face of the micro-end mill bottom, the actual radius model of the worn tool is established, considering the tool edge radius and tool flank wear. The tool edge radius, tool wear, tool runout, trochoidal trajectories of the current cutting edge, and all cutting edges in the previous cycle are comprehensively considered in the instantaneous uncut chip thickness calculation and the cutter-workpiece engagement determination. The cutting force coefficient model including tool wear is established. A series of milling experiments are performed to verify the accuracy and effectiveness of the proposed cutting force model. The results show that the predicted cutting forces are in good agreement with the experimental cutting forces, and it is necessary to consider tool wear in the micro-milling force modeling. The results indicate that tool wear has a significant influence on the cutting forces and cutting force coefficients in the three directions, and the influences of tool wear on the axial cutting force and axial force coefficient are the largest, respectively. The proposed cutting force model can contribute to real-time machining process monitoring, cutting parameters optimization and ensuring machining quality.

A Shigella sonnei clone with extensive drug resistance associated with waterborne outbreaks in China.

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health.

A Review of Spatter in Laser Powder Bed Fusion Additive Manufacturing: In Situ Detection, Generation, Effects, and Countermeasures.

Spatter is an inherent, unpreventable, and undesired phenomenon in laser powder bed fusion (L-PBF) additive manufacturing. Spatter behavior has an intrinsic correlation with the forming quality in L-PBF because it leads to metallurgical defects and the degradation of mechanical properties. This impact becomes more severe in the fabrication of large-sized parts during the multi-laser L-PBF process. Therefore, investigations of spatter generation and countermeasures have become more urgent. Although much research has provided insights into the melt pool, microstructure, and mechanical property, reviews of spatter in L-PBF are still limited. This work reviews the literature on the in situ detection, generation, effects, and countermeasures of spatter in L-PBF. It is expected to pave the way towards a novel generation of highly efficient and intelligent L-PBF systems.

Corrigendum: A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

[This corrects the article DOI: 10.3389/fmicb.2021.779749.].

LncRNA ODRUL regulates progression of osteosarcoma by regulating IL-6 via sponging miR-6874-3p.

Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.

Biomineralization-inspired synthesis of amorphous manganese phosphates for GLUT5-targeted drug-free catalytic therapy of osteosarcoma.

Osteosarcoma, occurring most frequently in children, teens, and young adults, is a lethal bone cancer with a high incidence of distant metastases and drug resistance. Developing a therapeutic platform that integrates targeting, curing and imaging is highly desirable for enhanced osteosarcoma therapy, yet quite challenging. In this work, we demonstrate a novel biomineralization-inspired strategy for the synthesis of a fructose incorporated manganese phosphate (Fru-MnP) nanoplatform for tumour targeting, drug-free therapy, and MRI imaging. Benefitting from the glucose transporter 5 (GLUT5)-mediated endocytosis, our Fru-MnP nanoplatform produces a high level of reactive oxygen species (ROS) via the Mn2+-driven Fenton reaction within osteosarcoma cells, leading to efficient cancer cell killing due to caspase-mediated apoptosis. By virtue of the T1 signal enhancement of Mn2+, our Fru-MnP nanoplatform also acts as an effective tumour-specific MRI contrast agent, realizing the MRI-monitored chemodynamic therapy. The proposed synergistic therapeutic platform opens new possibilities for high efficacy therapy for osteosarcoma.

Metal-based additive manufacturing condition monitoring methods: From measurement to control.

Compared with other additive manufacturing processes, the metal-based additive manufacturing (MAM) can build higher precision and higher density parts, and have unique advantages in the applications to automotive, medical, and aerospace industries. However, the quality defects of builds, such as dimensional accuracy, layer morphology, mechanical and metallurgical defects, have been hindering the wide applications of MAM technologies. These decrease the repeatability and consistency of build quality. In order to overcome these shortcomings and to produce high-quality parts, it is very important to carry out online monitoring and process control in the building process. A process monitoring system is demanded which can automatically optimize the process parameters to eliminate incipient defects, improve the process stability and the final build quality. In this paper, the current representative studies are selected from the literature, and the research progress of MAM process monitoring and control are surveyed. Taking the key components of the MAM monitoring system as the mainstream, this study investigates the MAM monitoring system, measurement and signal acquisition, signal and image processing, as well as machine learning methods for the process monitoring and quality classification. The advantages and disadvantages of their algorithmic implementations and applications are discussed and summarized. Finally, the prospects of MAM process monitoring researches are advised.

A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

Salmonella contamination of eggs and egg shells has been identified as a public health problem worldwide. Here, we reported an outbreak of severe gastrointestinal symptoms caused by Salmonella enterica serovar Enteritidis (S. enteritidis) in China. We evaluated the outbreak by using epidemiological surveys, routine laboratory testing methods, and whole genome sequencing (WGS). This outbreak occurred in a canteen in Beijing, during March 9-11, 2021, 225 of the 324 diners who have eaten at the canteen showed gastrointestinal symptoms. The outbreak had characteristical epidemiological and clinical features. It caused a very high attack rate (69.4%) in a short incubation time. All patients developed diarrhea and high fever, accompanied by abdominal pain (62.3%), nausea (50.4%), and vomiting (62.7%). The average frequency of diarrhea was 12.4 times/day, and the highest frequency of diarrhea was as high as 50 times/day. The average fever temperature was 39.4°C, and the highest fever temperature was 42°C. Twenty strains of S. enteritidis were recovered, including 19 from the patients samples, and one from remained egg fried rice. Antibiotic susceptibility test showed that the 20 outbreak strains all had the same resistance pattern. PFGE results demonstrated that all 20 strains bore completely identical bands. Phylogenetic analysis based on WGS revealed that all 20 outbreak strains were tightly clustered together. So the pathogenic source of this food poisoning incident may was contaminated egg fried rice. Resistance gene analysis showed that the outbreak strains are all multi-drug resistant strains. Virulence gene analysis indicated that these outbreak strains carried a large number of virulence genes, including 2 types of Salmonella pathogenicity islands (SPI-1 and SPI-2). Other important virulence genes were also carried by the outbreak strains, such as pefABCD, rck and shdA. And the shdA gene was not in other strains located in the same evolutionary branch as the outbreak strain. We speculated that this is a significant reason for the serious symptoms of gastroenteritis in this outbreak. This outbreak caused by S. enteritidis suggested government should strengthen monitoring of the prevalence of outbreak clone strains, and take measures to mitigate the public health threat posed by contaminated eggs.

Doxorubicin-induced novel circRNA_0004674 facilitates osteosarcoma progression and chemoresistance by upregulating MCL1 through miR-142-5p.

Accumulating evidence has shown that circular RNA (circRNA) dysregulation is involved in various types of cancer, including osteosarcoma (OS). Nevertheless, the role and mechanism of circRNAs in OS progression and chemoresistance remain elusive. We found that a novel doxorubicin-induced circular RNA, hsa_circ_0004674, screened by whole total transcriptome RNA sequencing in our previous study, was upregulated in OS chemoresistant cell lines and tissues and also connected with patients' poor prognosis. Circ_0004674 knockdown remarkably suppressed OS cell chemoresistance, proliferation, migration, invasion, OS tumor growth, and enhanced cell cycle arrest and apoptosis in vitro and in vivo through control the expression of the antiapoptotic protein MCL1, a member of the Bcl-2 gene family. Further online bioinformatics analysis revealed that miR-142-5p had potential binding sites that can bind circ_0004674 and the 3'UTR of MCL1 mRNA. Moreover, the expression and function of miR-142-5p were conversely correlated with circ_0004674 in vitro. RIP, pull-down, luciferase assay, and RNA FISH demonstrated that circ_0004674 could compete with MCL1 for miR-142-5p binding to counteract miR-142-5p-mediated repression of MCL1 at the post-transcriptional level. To sum up, our study sheds light on the critical role of the oncogenic circ_0004674/miR-142-5p/MCL1 axis in OS progression and chemoresistance, providing a novel potential target for OS therapy.