SASH1 contributes to glial cell migration in the early development of the central nervous system.

SAM and SH3 domain-containing 1 (SASH1), a member of the SLy protein family, is a tumor suppressor gene that has been studied for its association with various cancers. SASH1 is highly expressed in the mammalian central nervous system, particularly in glial cells, and is expressed in the central nervous system during zebrafish embryo development. However, SASH1's role in brain development has rarely been investigated. In this study, Morpholino oligonucleotides (MO) were used to down-regulate sash1a expression in zebrafish to observe morphological changes in the brain. Three transgenic zebrafish lines, Tg(gfap:eGFP), Tg(hb9:eGFP), and Tg(coro1a:eGFP) were selected to observe changes in glial cells, neurons, and immune cells after sash1a knockdown. Our results showed that the number of microglia residing in the developmental brain was reduced, whereas the axonal growth of caudal primary motor neurons was unaffected by sash1a downregulation. And more significantly, the gfap + glia presented abnormal arrangements and disordered orientations in sash1a morphants. The similar phenotype was verified in the mutation induced by the injection of cas9 mRNA and sash1a sgRNA. We further performed behavioral experiments in zebrafish larvae that had been injected with sash1a MO at one-cell stage, and found them exhibiting abnormal behavior trajectories. Moreover, injecting the human SASH1 mRNA rescued these phenomena in sash1a MO zebrafish. In summary, our study revealed that the downregulation of SASH1 leads to malformations in the embryonic brain and disorganization of glial cell marshalling, suggesting that SASH1 plays an important role in the migration of glial cells during embryonic brain development.

Histone acetyltransferase KAT2A modulates neural stem cell differentiation and proliferation by inducing degradation of the transcription factor PAX6.

Neural stem cells (NSCs) proliferation and differentiation rely on proper expression and posttranslational modification of transcription factors involved in the determination of cell fate. Further characterization is needed to connect modifying enzymes with their transcription factor substrates in the regulation of these processes. Here, we demonstrated that the inhibition of KAT2A, a histone acetyltransferase, leads to a phenotype of small eyes in the developing embryo of zebrafish, which is associated with enhanced proliferation and apoptosis of NSCs in zebrafish eyes. We confirmed that this phenotype is mediated by the elevated level of PAX6 protein. We further verified that KAT2A negatively regulates PAX6 at the protein level in cultured neural stem cells of rat cerebral cortex. We revealed that PAX6 is a novel acetylation substrate of KAT2A and the acetylation of PAX6 promotes its ubiquitination mediated by the E3 ligase RNF8 that facilitated PAX6 degradation. Our study proposes that KAT2A inhibition results in accelerated proliferation, delayed differentiation, or apoptosis, depending on the context of PAX6 dosage. Thus, the KAT2A/PAX6 axis plays an essential role to keep a balance between the self-renewal and differentiation of NSCs.

MEF2C contributes to axonal branching by regulating Kif2c transcription.

Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.

HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

Efficient manipulation of gene expression using Natronobacterium gregoryi Argonaute in zebrafish.

BACKGROUND: Natronobacterium gregoryi Argonaute (NgAgo) was found to reduce mRNA without generating detectable DNA double-strand breaks in a couple of endogenous genes in zebrafish, suggesting its potential as a tool for gene knockdown. However, little is known about how it interacts with nucleic acid molecules to interfere with gene expression. RESULTS: In this study, we first confirmed that coinjection of NgAgo and gDNA downregulated target genes, generated gene-specific phenotypes and verified some factors (including 5' phosphorylation, GC ratio, and target positions) of gDNAs affecting gene downregulation. Therein, the sense and antisense gDNAs were equally effective, suggesting that NgAgo possibly binds to DNA. NgAgo-VP64 with gDNAs targeting promoters upregulated the target genes, further providing evidence that NgAgo interacts with genomic DNA and controls gene transcription. Finally, we explain the downregulation of NgAgo/gDNA target genes by interference with the process of gene transcription, which differs from that of morpholino oligonucleotides. CONCLUSIONS: The present study provides conclusions that NgAgo may target genomic DNA and that target positions and the gDNA GC ratio influence its regulation efficiency.

Effect of high hydrostatic pressure on the edible quality, health and safety attributes of plant-based foods represented by cereals and legumes: a review.

Consumers today are increasingly willing to reduce their meat consumption and adopt plant-based alternatives in their diet. As a main source of plant-based foods, cereals and legumes (CLs) together could make up for all the essential nutrients that humans consume daily. However, the consumption of CLs and their derivatives is facing many challenges, such as the poor palatability of coarse grains and vegetarian meat, the presence of anti-nutritional factors, and allergenic proteins in CLs, and the vulnerability of plant-based foods to microbial contamination. Recently, high hydrostatic pressure (HHP) technology has been used to tailor the techno-functionality of plant proteins and induce cold gelatinization of starch in CLs to improve the edible quality of plant-based products. The nutritional value (e.g., the bioavailability of vitamins and minerals, reduction of anti-nutritional factors of legume proteins) and bio-functional properties (e.g., production of bioactive peptides, increasing the content of γ-aminobutyric acid) of CLs were significantly improved as affected by HHP. Moreover, the food safety of plant-based products could be significantly improved as well. HHP lowered the risk of microbial contamination through the inactivation of numerous microorganisms, spores, and enzymes in CLs and alleviated the allergy symptoms from consumption of plant-based foods.

Digital histopathological images of biopsy predict response to neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been recognized as an effective therapeutic option for locally advanced gastric cancer as it is expected to reduce tumor size, increase the resection rate, and improve overall survival. However, for patients who are not responsive to NAC, the best operation timing may be missed together with suffering from side effects. Therefore, it is paramount to differentiate potential respondents from non-respondents. Histopathological images contain rich and complex data that can be exploited to study cancers. We assessed the ability of a novel deep learning (DL)-based biomarker to predict pathological responses from images of hematoxylin and eosin (H&E)-stained tissue. METHODS: In this multicentre observational study, H&E-stained biopsy sections of patients with gastric cancer were collected from four hospitals. All patients underwent NAC followed by gastrectomy. The Becker tumor regression grading (TRG) system was used to evaluate the pathologic chemotherapy response. Based on H&E-stained slides of biopsies, DL methods (Inception-V3, Xception, EfficientNet-B5, and ensemble CRSNet models) were employed to predict the pathological response by scoring the tumor tissue to obtain a histopathological biomarker, the chemotherapy response score (CRS). The predictive performance of the CRSNet was evaluated. RESULTS: 69,564 patches from 230 whole-slide images of 213 patients with gastric cancer were obtained in this study. Based on the F1 score and area under the curve (AUC), an optimal model was finally chosen, named the CRSNet model. Using the ensemble CRSNet model, the response score derived from H&E staining images reached an AUC of 0.936 in the internal test cohort and 0.923 in the external validation cohort for predicting pathological response. The CRS of major responders was significantly higher than that of minor responders in both internal and external test cohorts (both p < 0.001). CONCLUSION: In this study, the proposed DL-based biomarker (CRSNet model) derived from histopathological images of the biopsy showed potential as a clinical aid for predicting the response to NAC in patients with locally advanced GC. Therefore, the CRSNet model provides a novel tool for the individualized management of locally advanced gastric cancer.

Associations of healthful and unhealthful plant-based diets with plasma markers of cardiometabolic risk.

PURPOSE: Plant-based diets, particularly when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes and cardiovascular disease. However, the impact of plant-based diets that distinguish between healthy and unhealthy plant foods on cardiometabolic biomarkers remains unclear. METHODS: Dietary information was collected by two 24-h recalls among 34,785 adults from a nationwide cross-sectional study. Plasma levels of insulin, C-peptide, glucose, C-reactive protein (CRP), white blood cell (WBC) count, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) were measured. Linear regression was used to evaluate the percentage difference in plasma marker concentrations by three plant-based diet indices, namely the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). RESULTS: Greater hPDI-adherence scores (comparing extreme quartiles) were associated with lower levels of insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), TG/HDL-C ratio, CRP, WBC count, and TG, and higher levels of HDL-C, with the percentage differences of - 14.55, - 15.72, - 11.57, - 14.95, - 5.26, - 7.10, and 5.01, respectively (all Ptrend ≤ 0.001). Conversely, uPDI was associated with higher levels of insulin, C-peptide, HOMA-IR, TG/HDL-C ratio, CRP, WBC count, and TG, but lower HDL-C, with the percentage differences of 13.71, 14.00, 14.10, 10.43, 3.32, 8.00, and - 4.98 (all Ptrend ≤ 0.001), respectively. Overall PDI was only associated with lower levels of CRP and WBC count (all Ptrend ≤ 0.001). CONCLUSION: Our findings suggest that hPDI may have positive, whereas uPDI may have negative impacts on multiple cardiometabolic risk markers, and underscore the need to consider the quality of plant foods in future PDI studies.

Large field-of-view thermal imaging via all-silicon meta-optics.

A broad range of imaging and sensing technologies in the infrared require large field-of-view (FoV) operation. To achieve this, traditional refractive systems often employ multiple elements to compensate for aberrations, which leads to excess size, weight, and cost. For many applications, including night vision eye-wear, air-borne surveillance, and autonomous navigation for unmanned aerial vehicles, size and weight are highly constrained. Sub-wavelength diffractive optics, also known as meta-optics, can dramatically reduce the size, weight, and cost of these imaging systems, as meta-optics are significantly thinner and lighter than traditional refractive lenses. Here, we demonstrate 80° FoV thermal imaging in the long-wavelength infrared regime (8-12 µm) using an all-silicon meta-optic with an entrance aperture and lens focal length of 1 cm.

Dysregulation of MiR-199a/IL8 pathway in chronic Cr (VI)-induced tumor growth and angiogenesis.

Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.

Circular RNA circRNF169 functions as a miR-30c-5p sponge to promote cellular senescence.

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.

Thermally stable gold nanorod dispersed silicone composite with plasmonic resonance in the optical communication window.

Gold nanorods (AuNRs) possess a high optical nonlinear coefficient, ultrafast optical response speed and widely tunable localized surface plasmon resonance (LSPR) wavelength covering the visible and near infrared region. Therefore, they are extensively investigated for many optical applications. However, the poor thermal stability of the AuNRs seriously restricts their practical performance. In addition, for many applications, such as optical communication or laser modulation, AuNRs have to be combined with transparent solids, for example polymers, glass or crystals to make devices. Here, we report on the preparation of 0.23 mg AuNR dispersed methyl silicone resin (MSR) with longitudinal LSPR (L-LSPR) wavelength (1450 nm) in the optical communication window. We found that AuNR-silicone composites possess high thermal stability. After calcination in ambient environment at a temperature of 250 °C for 10 h, the L-LSPR peak of the sample can remain longer than 1380 nm, implying that the NR shape of the Au particles was well maintained. Using the open-aperture Z-scan technique, the nonlinear absorption coefficient of the composites was measured as -11.71 cm GW-1, higher than many nonlinear materials. Thus, the thermally stable AuNR@SiO2-MSR composite with high nonlinearity is promising for practical applications in the optical communication window.

Comparison of CT values in traditional trajectory, traditional cortical bone trajectory, and modified cortical bone trajectory.

BACKGROUND: To compare the CT values and length of the screw tracks of traditional trajectory (TT), cortical bone trajectory (CBT), and modified cortical bone trajectory (MCBT) screws and investigate the effects on the biomechanics of lumbar fixation. METHODS: CT scan data of 60 L4 and L5 lumbar spine were retrieved and divided into 4 groups (10 male and 10 female cases in the 20-30 years old group and 20 male and 20 female cases in the 30-40 years old group). 3-dimentional (3D) model were established using Mimics 19.0 for each group and the placement of three techniques was simulated on the L4 and L5, and the part of the bone occupied by the screw track was set as the region of interest (ROI). The mean CT value and the actual length of the screw track were measured by Mimics 19.0. RESULTS: The CT values of ROI for the three techniques were significantly different between the same gander in each age group (P < 0.05). The difference of screw track lengths for CBT and MCBT in the male and female is significant (P < 0.05). CONCLUSIONS: According to the CT values of the three screw tracks: MCBT > CBT > TT, the MCBT screw track has greater bone-screw surface strength and longer screw tracks than CBT, which is easier to reach the anterior column of the vertebral body contributing to superior biomechanical properties.

Highly Stretchable and Sensitive Flexible Strain Sensor Based on Fe NWs/Graphene/PEDOT:PSS with a Porous Structure.

With the rapid development of wearable smart electronic products, high-performance wearable flexible strain sensors are urgently needed. In this paper, a flexible strain sensor device with Fe NWs/Graphene/PEDOT:PSS material added under a porous structure was designed and prepared. The effects of adding different sensing materials and a different number of dips with PEDOT:PSS on the device performance were investigated. The experiments show that the flexible strain sensor obtained by using Fe NWs, graphene, and PEDOT:PSS composite is dipped in polyurethane foam once and vacuum dried in turn with a local linearity of 98.8%, and the device was stable up to 3500 times at 80% strain. The high linearity and good stability are based on the three-dimensional network structure of polyurethane foam, combined with the excellent electrical conductivity of Fe NWs, the bridging and passivation effects of graphene, and the stabilization effect of PEDOT:PSS, which force the graphene-coated Fe NWs to adhere to the porous skeleton under the action of PEDOT:PSS to form a stable three-dimensional conductive network. Flexible strain sensor devices can be applied to smart robots and other fields and show broad application prospects in intelligent wearable devices.

Experimental study on the washing characteristics of fly ash from municipal solid waste incineration.

The disposal of fly ash with high salt content has become an important bottleneck for the further application of municipal solid waste incineration (MSWI). In this study, the soluble salt content and composition of fly ash from different MSWI were analysed. The composition of fly ash was affected by incinerator type and flue gas cleaning system, especially the type of deacidification solvent. The soluble salt content in fly ash from MSW grate incinerator can be over 35.16%. Most of the soluble salt was calcium salt and chloride salt. The effect of washing parameters including liquid/solid (L/S) ratio and washing time on salt removal from fly ash were studied. Raw fly ash contained high chlorine (Cl) with the maximum of 19.83% and it can be significantly reduced by washing. Double-washing and secondary-washing had better performance than single-washing on salt removal. The secondary-washing did not only save water, but also reduced the energy cost during evaporation for crystallising soluble salt. Based on the analysis of variance (ANOVA), L/S ratio was the most principal factor for salt and Cl removal of fly ash by washing.

[function of the patients' male partners].

Objective: To investigate the sexual behavior and sexual function of the male partners of breast cancer patients and their potential relationship with socio-demographic and clinical variables. METHODS: In this cross-sectional study, we conducted an investigation among 196 male partners (aged 23－59 years) of breast cancer patients between May 2020 and October 2020. We completed the Male Sexual Function Questionnaire (BSFI) by online and telephone interview with the subjects and collected relevant socio-demographic and clinical variables. RESULTS: The average age of the interviewees was (46.13 ± 7.75) years old, and the mean duration of the patients' breast cancer was (1.58 ± 0.48) years at the time of the investigation. The incidence rate of sexual dysfunction in the male partners of the patients was dramatically higher after the onset of breast cancer than before it (49.76% vs 9.68%, P < 0.01). Low libido was found to be the main type of sexual dysfunction (38.3%) among the male subjects, with an even high incidence rate among those whose wives received mastectomy (OR = 5.533, P = 0.017, 95% CI: 1.366－22.412) and radiotherapy (OR = 3.439, P < 0.044, 95% CI: 1.058－11.171) and significantly correlated with age (OR = 1.134, P = 0.001, 95% CI: 1.053－1.222). CONCLUSIONS: Breast cancer and its treatment methods may affect the sexual function of the male partners of the patients. It is necessary for doctors to pay attention to the factors affecting the sexual function of the patients and their partners so as to take appropriate intervention measures.

Imaging through dynamical scattering media by two-photon absorption detectors.

Imaging through a dynamical opaque scattering medium is an almost impossible task, where strong multiple light scattering from moving scatters dynamically prevents imaging formations even with state-of-art techniques like correlation imaging or adaptive optics. Meanwhile, a small number of ballistic photons can still penetrate through but require demanding detection in terms of a ultrashort time gate and high sensitivity. However, visible light is strongly scattered for most of scattering media. Here we experimentally demonstrate a non-invasive coherent imaging scheme based on two-photon absorption capable of imaging through dynamical scattering media with a length equivalent to 28 times mean free paths for single photon transport, where two-photon absorption in a conventional semiconductor photodetector when phase matching is not required works over a wide bandwidth so it can support a fast time gate down to femtosecond level, short enough to distinguish ballistic photons from scattering background, and allows accessing longer wavelengths for deeper penetration. This technique combined with successful optical coherence tomography may pave a new way for imaging through fog, storm, and rain as well as biomedical imaging applications.

Label-free plasmonic assisted optical trapping of single DNA molecules.

DNA molecules are hard to catch using traditional optical trapping due to the nanometer width of their chains. Here we experimentally demonstrate a label-free optical trapping of a single micrometer λ-DNA in solution by the aid of plasmonic gold nanoparticles (GNPs), where a double-laser trap induces strong optical interparticle forces for the tweezer. We examine such sub-resolved interparticle forces by tracking the GNP dynamics in solution. Moreover, surface-enhanced Raman scattering signals of trapped λ-DNA have also been measured simultaneously in the same setup. In comparison with prior works, ours benefit from the excitation in a dynamic configuration without fabrication. This technique opens a new avenue for all-optical manipulation of biomolecules, as well as ultra-sensitive bio-medical sensing applications.

Vibrational modes in an optically levitated droplet.

Levitation by optical tweezers provides a unique non-invasive tool for investigating a microscale object without external perturbations. Here we experimentally levitate a micrometer-sized water droplet in the air using an optical tweezer. Meanwhile, vibrational modes of a levitated water droplet are excited by modulating the trapping laser. From their backscattered light, vibrational modes with mode numbers are observed in the spectra. Additionally, their corresponding free spectral ranges are analyzed and compared with theory and numerical simulations. This Letter, establishing a non-invasive and all-optical detection technique of optomechanical properties of levitated droplets, paves the way for their practical applications in aerosol and biomedical science.

Broadband achromatic metalens design based on deep neural networks.

For the design of achromatic metalenses, one key challenge is to accurately realize the wavelength dependent phase profile. Because of the demand of tremendous simulations, traditional methods are laborious and time consuming. Here, a novel deep neural network (DNN) is proposed and applied to the achromatic metalens design, which turns complex design processes into regression tasks through fitting the target phase curves. During training, x-y projection pairs are put forward to solve the phase jump problem, and some additional phase curves are manually generated to optimize the DNN performance. To demonstrate the validity of our DNN, two achromatic metalenses in the near-infrared region are designed and simulated. Their average focal length shifts are 2.6% and 1.7%, while their average relative focusing efficiencies reach 59.18% and 77.88%.