Neural radiance fields-based multi-view endoscopic scene reconstruction for surgical simulation.

PURPOSE: In virtual surgery, the appearance of 3D models constructed from CT images lacks realism, leading to potential misunderstandings among residents. Therefore, it is crucial to reconstruct realistic endoscopic scene using multi-view images captured by an endoscope. METHODS: We propose an Endoscope-NeRF network for implicit radiance fields reconstruction of endoscopic scene under non-fixed light source, and synthesize novel views using volume rendering. Endoscope-NeRF network with multiple MLP networks and a ray transformer network represents endoscopic scene as implicit field function with color and volume density at continuous 5D vectors (3D position and 2D direction). The final synthesized image is obtained by aggregating all sampling points on each ray of the target camera using volume rendering. Our method considers the effect of distance from the light source to the sampling point on the scene radiance. RESULTS: Our network is validated on the lung, liver, kidney and heart of pig collected by our device. The results show that the novel views of endoscopic scene synthesized by our method outperform existing methods (NeRF and IBRNet) in terms of PSNR, SSIM, and LPIPS metrics. CONCLUSION: Our network can effectively learn a radiance field function with generalization ability. Fine-tuning the pre-trained model on a new endoscopic scene to further optimize the neural radiance fields of the scene, which can provide more realistic, high-resolution rendered images for surgical simulation.

3D Bioprinting of Induced Pluripotent Stem Cells and Disease Modeling.

Patient-derived induced pluripotent stem cells (iPSCs), carrying the genetic information of the disease and capable of differentiating into multilineages in vitro, are valuable for disease modeling. 3D bioprinting enables the assembly of the cell-laden hydrogel into hierarchically three-dimensional architectures that recapitulate the natural tissues and organs. Investigation of iPSC-derived physiological and pathological models constructed by 3D bioprinting is a fast-growing field still in its infancy. Distinctly from cell lines and adult stem cells, iPSCs and iPSC-derived cells are more susceptible to external stimuli which can disturb the differentiation, maturation, and organization of iPSCs and their progeny. Here we discuss the fitness of iPSCs and 3D bioprinting from the perspective of bioinks and printing technologies. We provide a timely review of the progress of 3D bioprinting iPSC-derived physiological and pathological models by exemplifying the relatively prosperous cardiac and neurological fields. We also discuss scientific rigors and highlight the remaining issues to offer a guiding framework for bioprinting-assisted personalized medicine.

Data-driven fault diagnosis of FW-UAVs with consideration of multiple operation conditions.

Fixed-wing Unmanned Aerial Vehicles (FW-UAVs) are intelligent aircrafts. It is of significance to carry out fault diagnosis of FW-UAVs to improve reliability and safety. An entire mission of FW-UAVs contains couple of phases; correspondingly, this paper treats FW-UAVs as multiple operation condition processes. An innovative framework is then proposed for fault diagnosis of FW-UAVs, where the process dynamics, multiple operation conditions, variable data density, and process disturbance are considered. Firstly, augmented matrixes are constructed with the data samples to involve the dynamic characteristic of FW-UAVs. Secondly, a modified DBSCAN algorithm employing Shared Nearest Neighbor based Distance (SNND-DBSCAN) and a K Nearest Neighbor algorithm employing SNND (SNND-KNN) are proposed respectively. They cooperate with each other to realize offline operation condition classification and online recognition. Thirdly, Multiple condition oriented Dynamic KPCA (M-DKPCA) algorithms incorporated with Weighted sliding window denoising (WM-DKPCA) is proposed for fault diagnosis. Finally, the proposed algorithms are tested with real flight data sets in terms of linear and nonlinear faults; and the comparisons between KPCA, DKPCA, M-DKPCA and WM-DKPCA are presented. The results confirm that the multiple condition oriented M-DKPCA and WM-DKPA algorithms are more suitable for fault diagnosis of FW-UAVs; and WSW denoising can indeed improve the fault diagnosis performance.

Silver nanoparticles (AgNPs) and AgNO3 perturb the specification of human hepatocyte-like cells and cardiomyocytes.

Silver nanoparticles (AgNPs) are commonly utilized industrial compounds mostly because of their antimicrobial properties. Nevertheless, our understanding of their potential developmental toxicity in humans is still limited. Embryonic stem cells (ESCs) are powerful in vitro tools for developmental toxicity assessments of chemicals. Here, we evaluated the potential developmental toxicity during early embryogenesis of AgNPs and AgNO3 with human ESC (hESC)-based differentiation systems in vitro. We found that human relevant concentrations of AgNPs and Ag ions affected the specification of two of the three primary germ layers, endoderm and mesoderm, without drastically affecting ectoderm. Furthermore, the two forms of Ag impaired the generation and functions of hepatocytes-like cells derived from endoderm, by decreasing the expression of important liver markers such as AFP, ALB, and HNF4A, and altering glycogen storage. When considering cardiac development, AgNPs and AgNO3 manifested opposite adverse effects, in that AgNPs increased while AgNO3 decreased the expression of typical cardiac markers (NKX2.5, MYH6, and ISL) in hESC-derived cardiomyocytes. In conclusion, our findings argue for a potential developmental toxicity of AgNP doses we are exposed to, or levels detected in the human body, especially at very early stages during embryogenesis, and which may not be just due to Ag leakage. Moreover, mesendoderm-derived cell types, tissues and organs may be more prone to AgNP toxicity than ectoderm lineages.

Non-cytotoxic silver nanoparticle levels perturb human embryonic stem cell-dependent specification of the cranial placode in part via FGF signaling.

Silver nanoparticles (AgNPs) are compounds used in numerous consumer products because of their desirable optical, conductive and antibacterial properties. However, several in vivo and in vitro studies have raised concerns about their potential developmental toxicity. Here, we employed a human embryonic stem cell model to evaluate the potential ectodermal toxicity of AgNPs, at human relevant concentrations. Among the four major ectodermal lineages tested, only cranial placode specification was significantly affected by AgNPs and AgNO3, morphology-wise and in the expression of specific markers, such as SIX3 and PAX6. Mechanistically, we found that the effects of AgNPs on the cranial placode differentiation were probably due to Ag ion leakage and mediated by the FGF signaling. Thus, AgNPs may have the ability to alter the early stages of embryonic development.

Three-Dimensional Printing of Hydrogel Scaffolds with Hierarchical Structure for Scalable Stem Cell Culture.

The expansion and harvest of stem cells at clinically relevant scales is critical for cell-based therapies. These approaches need to be robust and cost-effective, support the functional maintenance of desired cell behaviors, and allow for simple harvest. Here, we introduce a real-time monitoring 3D printing approach to fabricate scaffolds with quadruple hierarchical structure that meet these design goals for stem cell expansion. Specifically, a versatile strategy was developed to produce scaffolds from alginate and gelatin with approximately 102 µm interconnected macropores, 300 µm microfilaments, 1.3 mm hollow channels, and centimeter-scale overall dimensions. The scaffolds exhibited good pattern fidelity and stable mechanical properties (compressive modulus value was 22-fold that of hydrogels from the same materials), facilitating uniform and efficient cell seeding with high viability (98.9%). The utility of the scaffold was shown with the 3D culture of HepaRG cells and embryonic stem cells (ESCs) with aggregated morphology, and significantly enhanced cell proliferation was observed compared to those of cultures on flat surfaces, obtaining approximately 2 × 108 cells within a single culture. Interestingly, the functional behavior of the cells was dependent on the cell type, as ESCs maintained their pluripotency, while HepaRG cells improved their hepatic differentiation. Cells were harmlessly harvested through chelating the calcium ions in the cross-linked alginate and de-cross-linking the scaffolds, indicating the potential of this study for scalable stem cell culture for numerous downstream applications.

A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis.

Air pollution has been linked to many health issues, including skin conditions, especially in children. Among all the atmospheric pollutants, ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin, and be absorbed into the bloodstream. Here, we employed a human embryonic stem cell (hESC)-based differentiation system towards keratinocytes, to test the effects of ultrafine carbon particles, which mimic ambient ultrafine particles, at environment related concentrations. We found that 10 ng/mL to 10 µg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in hESCs. Moreover, 1 µg/mL to 10 µg/mL carbon particle treatments disrupted the keratinocyte differentiation, and up-regulated inflammation- and psoriasis-related genes, such as IL-1ß, IL-6, CXCL1, CXCL2, CXCL3, CCL20, CXCL8, and S100A7 and S100A9, respectively. Overall, our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.

Typical halogenated flame retardants affect human neural stem cell gene expression during proliferation and differentiation via glycogen synthase kinase 3 beta and T3 signaling.

2',2',4,4'-tetrabromo diphenyl ether (BDE-47), one of the most abundant congeners of commercial pentaBDE utilized as flame retardants, has been phased out of production due to its potential neural toxicity and endocrine disrupting activities, and yet still present in the environment. Several alternatives to BDE-47, including tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), tetrachlorobisphenol A (TCBPA) and decabromodiphenyl ether (BDE-209), are presently employed without restrictions and their potential toxic effects on human neural development are still unclear. In this study, we utilized a human neural stem cell (hNSC)-based system to evaluate the potential developmental neurotoxic effects of the above-mentioned five chemicals, at environment and human exposure relevant concentrations. We found that those compounds slightly altered the expression of hNSC identity markers (SOX2, SOX3 and NES), without impairing cell viability or proliferation, in part by either modulating glycogen synthase kinase 3 beta (GSK3ß) signaling (TBBPS, TCBPA and BDE-47), and slightly disturbing the NOTCH pathway (TBBPA, TBBPS and TCBPA). Moreover, the five chemicals seemed to alter hNSC differentiation by perturbing triiodothyronine (T3) cellular signaling. Thus, our findings suggest that the five compounds, especially TBBPS, TCBPA, and BDE-47, may affect hNSC self-renewal and differentiation abilities and potentially elicit neural developmental toxicity.

Toxicogenomic analyses of the effects of BDE-47/209, TBBPA/S and TCBPA on early neural development with a human embryonic stem cell in vitro differentiation system.

Flame retardants are detected in the environment worldwide, and thus pose great risks to human health. The potential effects of these chemicals on the development of the central nervous system, have recently raised public concern. In this study, to explore the toxicity of these chemicals during the early developmental stages of the human central nervous system, we induced human embryonic stem cells to differentiate into neural ectoderm in the presence of five halogenated flame retardants, BDE-47, BDE-209, TBBPA, TBBPS and TCBPA, individually or in combination. We identified a set of neural development-related biological processes that responded to these chemicals, by analyzing the whole transcriptional changes. We confirmed the RNA-seq results by qRT-PCR and found that transcription factors crucial for neural development, such as ZIC1, ZIC3, HES3, IGFBP3 and DLX5, were dysregulated by those chemicals. In addition, the five flame retardants might also influence axon growth/guidance and neuron transmission-related processes, by dysregulating genes including CNTN2, SLIT1, LRRC4C, RELN, CBLN1, CHRNB4 and GDF7. Furthermore, the chemical treatments seemed to interfere with the WNT and AHR signaling pathways. Overall, our findings revealed that BDE-209 had similar toxicity as BDE-47, whereas TBBPS and TCBPA might not be safe alternatives to TBBPA. Interestingly, we observed no obvious synergistic effects when we mixed those five flame retardants together.

Embryoid body-based RNA-seq analyses reveal a potential TBBPA multifaceted developmental toxicity.

The frequent detection of tetrabromobisphenol A (TBBPA) in the human body, especially in umbilical cord serum and breast milk, has raised concerns about TBBPA potential effects on embryonic development. The differentiation of embryonic stem cells (ESCs) in vitro can serve as a model for the early stages of embryonic development. In this study, we differentiated mouse ESCs via 3D aggregates called embryoid bodies in presence of environment and human relevant TBPPA concentrations for 28 days. We collected samples at different time points and analyzed TBBPA-dependent global gene expression changes by RNA-seq. Our analyses revealed a potential TBBPA multifaceted developmental toxicity with effects on the nervous and cardiac/skeletal muscle systems. Mechanistically, our findings suggest TBBPA endocrine disrupting activities in part via prolactin signaling.

Embryonic stem cell- and transcriptomics-based in vitro analyses reveal that bisphenols A, F and S have similar and very complex potential developmental toxicities.

Bisphenol A (BPA) is a very versatile industrial chemical. Many reports have associated BPA with several health effects. Some bisphenol alternatives have been introduced to replace BPA in its many applications. However, comprehensive toxicological evaluations for these replacements are still lacking. In this study, we examined the potential effects of BPA, bisphenol F (BPF) and bisphenol S (BPS), on embryonic development with an in vitro stem cell toxicology system and transcriptomics analyses. Mouse embryonic stem cells (mESCs) were differentiated via embryoid body formation, either globally towards the three primary germ layers and their lineages, or specifically into neuroectoderm/neural progenitor cells. During the differentiation, cells were treated with BPA, BPF, BPS, or DMSO control. Samples were collected at different time points, for qRT-PCR and RNA-seq analyses. BPA, BPF and BPS disrupted many processes, during mESC global and neural differentiations, in very similar manners. In fact, at each time point the three chemicals differentially regulated analogous gene categories, particularly the ones involved in cell-matrix and cell-cell adhesion, signal transduction pathways, and medical conditions such as cardiovascular diseases and cancer. Our findings demonstrate once more then BPA substitutes may not be very safe. They potentially have a very complex developmental toxicity, similarly to BPA, and seem more toxic than BPA itself. In addition, our results reveal that stem cell-based developmental toxicity assays can be very comprehensive.

Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations.

The liver is one of the major targets of hormones, including thyroid hormones (THs), and many industrial chemicals, such as endocrine-disrupting chemicals. Those compounds may permeate the placenta barrier and pose a risk for embryonic development. Therefore, it is necessary to assess the toxic effects of those kind of industrial chemicals during liver development. In this study, to mimic liver specification in vitro, we differentiated human embryonic stem cells (ESCs) into functional hepatocyte-like cells. We performed this differentiation process in presence of two THs, triiodothyronine (T3) and thyroxine (T4), with the purpose of identifying biomarkers for toxicity screening. TH exposure (3, 30 and 300 nM) yielded to hepatocytes with impaired glycogen storage ability and abnormal lipid droplets' accumulation. Global gene expression analysis by RNA-seq identified a number of genes responsible for hepatic differentiation and function which were affected by 30 nM T3 and T4. Those differentially expressed genes were used to assess the potential developmental liver toxicity of two famous environmental pollutants, 2, 2, 4, 4-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), at 10 nM to 1 µM treatments. Our findings demonstrate that BDE-47 and BDE-209, dysregulated pathways such as "chemical carcinogenesis", "steroid hormone biosynthesis" and "drug metabolism-cytochrome P450". Moreover, we were able to identify a set of 17 biomarkers, very useful to predict the potential developmental hepatotoxicity of industrial chemicals.

TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways.

Tetrabromobisphenol A (TBBPA), as well as its alternatives Tetrabromobisphenol S (TBBPS) and Tetrachlorobisphenol A (TCBPA), are widely used halogenated flame retardants. Their high detection rates in human breast milk and umbilical cord serum have raised wide concerns about their adverse effects on human fetal development. In this study, we evaluated the cytotoxicity and neural developmental toxicity of TBBPA, TBBPS, and TCBPA with a mouse embryonic stem cell (mESC) system, at human body fluid and environmental relevant doses. All the three compounds showed similar trends in their cytotoxic effects. However, while TBBPA and TBBPS stimulated ESC neural differentiation, TCBPA significantly inhibited neurogenesis. Mechanistically, we demonstrated that, as far as the NOTCH (positive regulator) and WNT (negative regulator) pathways were concerned, TBBPA only partially and slightly disturbed them, whereas TBBPS significantly inhibited the WNT pathway, and TCBPA down-regulated the expression of NOTCH effectors but increased the WNT signaling, actions which both inhibited neural specification. In conclusion, our findings suggest that TBBPS and TCBPA may not be safe alternatives to TBBPA, and their toxicity need to be comprehensively evaluated.

Evaluation of the early developmental neural toxicity of F-53B, as compared to PFOS, with an in vitro mouse stem cell differentiation model.

F-53B, as an alternative to the persistent organic pollutant perfluorooctane sulfonate (PFOS), is amply used in the electric plating industry. F-53B and PFOS have similar physicochemical, biochemical and physiological properties, due to the similarity in their chemical structure. Thus, they may also possess similar toxicities. Although epidemiological studies and in vivo assays have shown that prenatal exposure to PFOS may impair the development of the nervous system, toxicity data for F-53B are still scarce. In this study, we employed an embryonic stem cell (ESC) in vitro differentiation system, to detect the potential developmental neural toxicity of F-53B and PFOS, at human exposure relevant doses. We demonstrated that during early mouse ESC (mESC) neural differentiation, F-53B and PFOS disrupted the expression of neural marker genes and affected the morphology of the differentiated cells. However, the very same treatments did not cause any cytotoxic effects. In conclusion, our ESC in vitro differentiation system was able to prove for the first time that F-53B and PFOS at human exposure relevant concentrations, could alter the expression of differentiation biomarkers, indicating a potential developmental neural toxicity. Based on our findings, it is reasonable to deduce that excessive exposure to F-53B and PFOS may cause severe dysfunctions during early stages of embryo development.

DEP and DBP induce cytotoxicity in mouse embryonic stem cells and abnormally enhance neural ectoderm development.

Diethyl phthalate (DEP) and dibutyl phthalate (DBP) are two typical small phthalate esters, extensively used in personal care and consumer products. Although previous studies have linked phthalate esters to several health issues, it is still unclear whether they can affects the early stages of embryonic development. In this study, we evaluated the early developmental neurotoxicity as well as the cytotoxicity of DEP and DBP, using mouse embryonic stem cells (mESCs). Our results showed that both DEP and DBP could decrease mESC viability in a dose-dependent manner. Moreover, while DBP could activate the caspase-3/7 enzymes and cause cell membrane damage as well as intracellular ROS accumulation, interestingly DEP treatment only showed stimulation of ROS production. In addition, DEP and DBP treatment at non-cytotoxic concentrations, abnormally altered the expression levels of several vitally important regulators of embryo development. For instance, neural ectoderm markers, such as Pax6, Nestin, Sox1 and Sox3, were significantly up-regulated upon DEP and DBP exposure. In conclusion, our work suggests a potential developmental toxicity of DEP and DBP on mammals, especially for neural ectoderm specification. Our findings help better understand the association between health problems and DEP/DBP exposure and most significantly remind us of the importance of additional health risk tests for these two largely used chemicals.

Early detection of Zika virus infection among travellers from areas of ongoing transmission in China.

Nine imported Zika virus (ZIKV) infections (four through temperature monitoring and epidemiological investigation at entry and five by active surveillance tracking of index case contacts during follow-up; from Venezuela [n = 5], Samoa [n = 3] and both Samoa and Fiji [n = 1]) were detected in mainland China from February 1 to 29, 2016. The minimal incubation period lasted 5.2 days, with mean lag time to diagnosis of 2.6 days. Diagnosis relied on positive real-time reverse transcriptase polymerase chain reaction for ZIKV RNA in serum (n = 7), urine (n = 4) or saliva (n = 3), respectively. All cases recovered rapidly without serious complications.

Inhibition of cell proliferation and migration by chondroitin sulfate-g-polyethylenimine-mediated miR-34a delivery.

Chondroitin sulfate was chemically conjugated to PEI25K through Michael addition to construct a non-viral gene carrier CS-PEI, and then the carrier was employed in miR-34a delivery to achieve the inhibition of cell proliferation and migration, using prostate tumor cell PC-3 as a model. The nanoparticle from CS-PEI and miR-34a at a mass ratio of 10 was prepared with particle size and zeta potential of 170.7 nm and +42.2 mV, respectively. Flow cytometry and fluorescence microscopy revealed that CS-PEI could efficiently induce the cellular uptake of miR-34a in a CD44-mediated endocytosis manner. Through CS-PEI-mediated miR-34a transfection, obvious cell apoptosis was observed with early apoptotic cells of 47.49%, and meanwhile the activation of caspase-3, -8 and -9, and decreased expression level of Bcl-2 were detected. Moreover, wound healing assay showed that CS-PEI/miR-34a transfection could inhibit the cell migration. Overall, CS-PEI is potentially employed as a promising tumor-targeting system for miR-34a delivery in tumor gene therapy.

USA's expanded overseas tuberculosis screening program: a retrospective study in China.

BACKGROUND: To address increasing tuberculosis (TB) incidence in foreign-born populations, immigrant TB screening programs have been implemented in the USA. These programs are modified periodically, the effectiveness of which have been disputed. The aim of this retrospective study was to assess the value of the 2009 Technical Instructions for Tuberculosis Screening and Treatment Using Cultures and Directly Observed Therapy (CDOT TB TI) in a cohort of the USA permanent-resident applicants from China. METHODS: Standardized forms were used to collect demographic, clinical, and laboratory data of Chinese individuals screened at the Guangdong International Travel Healthcare Center for permanent residence in the USA between October 08, 2009 and December 31, 2012. Applicants' data were further retrospectively evaluated by three experienced panel physicians and radiologists according to the 1991 Technical Instructions for Tuberculosis Screening and Treatment (TI). TB cases and characteristics identified by the 1991 and expanded 2009 programs were compared. RESULTS: The CDOT TB TI identified more than twice as many TB cases that required treatment completion before clearance for travel than the 1991 TI (270 vs. 131). In addition, the expanded screening program identified more cases of negative sputum smear but positive culture (181 vs. 44), and more cases of radiography suggestive of inactive (22 vs. 3) and active (248 vs. 128) TB. Specifically, the 1991 TI screening program failed to identify 25/38 (65.79%) cases carrying drug-resistant isolates, and 13/131 (9.92%) would have been inappropriately treated. Moreover, 220/270 (81.48%) of the cases were asymptomatic, which were identified by screening and subsequently treated. Improved chest radiograph and sputum negative conversion occurred in all treated cases. CONCLUSION: CDOT TB TI, a screening program that includes sputum culture and drug susceptibility tests, identifies a greater number of TB cases, likely contributing to the overall decrease in TB prevalence in host (USA) and origin (China) countries.

N-Isopropylacrylamide-modified polyethylenimine-mediated p53 gene delivery to prevent the proliferation of cancer cells.

In this paper, N-isopropylacrylamide-modified polyethylenimine (PEN) was constructed through Michael addition and employed as a carrier to achieve the p53 gene delivery, using HeLa (p53wt) and PC-3 cells (p53null) as models. After PEN-mediated p53 transfection, expression level of p53 in HeLa and PC3 cells was up-regulated at both mRNA and protein levels. Due to the exogenous p53 expression, the inhibition of cell proliferation was observed through MTT analysis, attributing to the activation of apoptosis and cell cycle arrest. Using flow cytometric analysis, early apoptotic ratios of 54.95% and 27.06% after PEN-mediated p53 transfection were detected in PC-3 and HeLa cells, respectively, indicating that PC-3 cells were more sensitive to the exogenous p53 transfection than HeLa cells. Meanwhile, G1 phase arrest was detected in PC-3 cells while a unique G2 phase arrest was identified in HeLa cells after p53 transfection. Through Western blotting, activity analysis of caspase-3, caspase-8 and caspase-9 and mitochondrial membrane potential measurement, the apoptosis induced by PEN-mediated p53 transfection was conducted in a mitochondria-dependent apoptosis pathway. These results demonstrated that PEN could successfully mediate the p53 gene delivery and up-regulate the cellular p53 expression level, triggering a significant p53-dependent anti-proliferative effect on tumor cells.