Multichannel Multijunction Droplet Microfluidic Device to Synthesize Hydrogel Microcapsules with Different Core-Shell Structures and Adjustable Core Positions.

Core-shell hydrogel microcapsules have sparked great interest due to their unique characteristics and prospective applications in the medical, pharmaceutical, and cosmetic fields. However, complex synthetic procedures and expensive costs have limited their practical application. Herein, we designed and prepared several multichannel and multijunctional droplet microfluidic devices based on soft lithography for the effective synthesis of core-shell hydrogel microcapsules for different purposes. Additionally, two different cross-linking processes (ultraviolet (UV) exposure and interfacial polymerization) were used to synthesize different types of core-shell structured hydrogel microcapsules. Hydrogel microcapsules with gelatin methacryloyl (GelMA) as the core and polyacrylamide (PAM) as the thin shell were synthesized using UV cross-linking. Using an interfacial polymerization process, another core-shell structured microcapsule with GelMA as the core and Ca2+ cross-linked alginate with polyethylenimine (PEI) as the shell was constructed, and the core diameter and total droplet diameter were flexibly controlled by carving. Noteworthy, these hydrogel microcapsules exhibit stimuli-responsiveness and controlled release ability. Overall, a novel technique was developed to successfully synthesize various hydrogel microcapsules with core-shell microstructures. The hydrogel microcapsules possess a multilayered structure that facilitates the coassembly of cells and drugs, as well as the layered assembly of multiple drugs, to develop synergistic therapeutic regimens. These adaptable and controllable hydrogel microdroplets shall held great promise for multicell or multidrug administration as well as for high-throughput drug screening.

Spatial transcriptomics reveals gene interactions and signaling pathway dynamics in rat embryos with anorectal malformation.

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.

CircJag1 promotes apoptosis of ethylene thiourea-exposed anorectal malformations through sponging miR-137-3p by regulating Sox9 and suppressing Wnt/ß-catenin pathway during the hindgut development of rat embryos.

Anorectal malformations (ARMs) are common birth defects involving congenital structural anomalies of the gastrointestinal tract. As an important component of non-coding RNAs, circular RNAs (circRNAs) widely participate in the digestive system development; however, the specific molecular mechanism of their involvement in ARM occurrence remains obscure. Herein, we generated rat models of ARMs induced by ethylene thiourea. A novel circRNA (circJag1) was screened and identified by RNA-Seq, which is remarkably upregulated in hindgut tissues of ARM rat embryos. In vivo experiments, colocation analysis via fluorescence in situ hybridization, and immunofluorescence further demonstrated that the disordered circJag1/miR-137-3p/Sox9 expression caused a spatiotemporal imbalance in the urorectal septum (URS) of ARMs. In vitro, functional assays confirmed that circJag1 upregulation resulted in the degradation of nuclear ß-catenin, C-myc, and Cyclin D1 in rat intestinal epithelial cells, as well as the promotion of apoptosis and suppression of cell proliferation. Mechanistically, dual-luciferase reporter assay and RNA immunoprecipitation assay indicated that circJag1 acted as a miR-137-3p sponge, thereby inhibiting its repressive effect on its target Sox9. Further experiments showed that a loss of Sox9 abolished the circJag1-mediated increase in apoptosis. In conclusion, aberrantly high circJag1 expression promotes epithelial apoptosis by suppressing the canonical Wnt/ß-catenin pathway via the miR-137-3p/Sox9 axis, which leads to fusion failure of the URS and cloacal membrane, and eventually contributed to ARMs. Our achievements might boost the comprehension of ARM pathogenesis and could provide a novel candidate target for the development of therapies for ARMs to complement surgical treatment.

Synergistic Adsorption and In Situ Catalytic Conversion of SO2 by Transformed Bimetal-Phenolic Functionalized Biomass.

SO2 removal is critical to flue gas purification. However, based on performance and cost, materials under development are hardly adequate substitutes for active carbon-based materials. Here, we engineered biomass-derived nanostructured carbon nanofibers integrated with highly dispersed bimetallic Ti/CoOx nanoparticles through the thermal transition of metal-phenolic functionalized industrial leather wastes for synergistic SO2 adsorption and in situ catalytic conversion. The generation of surface-SO32- and peroxide species (O22-) by Ti/CoOx achieved catalytic conversion of adsorbed SO2 into value-added liquid H2SO4, which can be discharged from porous nanofibers. This approach can also avoid the accumulation of the adsorbed SO2, thereby achieving high desulfurization activity and a long operating life over 6000 min, preceding current state-of-the-art active carbon-based desulfurization materials. Combined with the techno-economic and carbon footprint analysis from 36 areas in China, we demonstrated an economically viable and scalable solution for real-world SO2 removal on the industrial scale.

Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.

Formononetin is a flavonoid compound with anti-tumor and anti-inflammatory properties. However, its low solubility limits its clinical use. We employed microfluidic technology to prepare formononetin-loaded PLGA-PEGDA microspheres (Degradable polymer PLGA, Crosslinking agent PEGDA), which can encapsulate and release drugs in a controlled manner. We optimized and characterized the microspheres, and evaluated their antitumor effects. The microspheres had uniform size, high drug loading efficiency, high encapsulation efficiency, and stable release for 35 days. They also inhibited the proliferation, migration, and apoptosis. The antitumor mechanism involved the induction of reactive oxygen species and modulation of Bcl-2 family proteins. These findings suggested that formononetin-loaded PLGA-PEGDA microspheres, created using microfluidic technology, could be a novel drug delivery system that can overcome the limitations of formononetin and enhance its antitumor activity.

[A case report of neonatal severe coronavirus disease 2019]. / æ–°ç”Ÿå„¿é‡åž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Ž1例报告.

A 7-day-old male neonate was admitted due to testing positive for SARS-CoV-2. The neonate was born through cesarian section at 40 weeks and 2 days of gestation. His mother was diagnosed with coronavirus disease 2019 (COVID-19) caused by Omicron variant infection 1 day before delivery. The neonate was separated from his mother after birth and was taken care of by his father. Three days after the neonate was born, his father was also diagnosed with COVID-19. The neonate was diagnosed with COVID-19 on day 7 of life. The neonate presented with hyperpyrexia, dyspnea, hypoxia, and feeding difficulties, and the chest CT showed the coexistence of consolidation and ground glass-like changes mainly located below the posterior pleura. He was given symptomatic support treatment such as low flow oxygen therapy and posture management after admission. He was cured and discharged after 10 days of hospitalization. This is the first reported case of neonatal severe COVID-19 caused by Omicron variant infection in China. It is necessary to take appropriate protective measures for the neonate to prevent infection when the mother or caregiver of the neonate is a suspected or confirmed cases of COVID-19.

Deep Learning-Enabled Resolution-Enhancement in Mini- and Regular Microscopy for Biomedical Imaging.

Artificial intelligence algorithms that aid mini-microscope imaging are attractive for numerous applications. In this paper, we optimize artificial intelligence techniques to provide clear, and natural biomedical imaging. We demonstrate that a deep learning-enabled super-resolution method can significantly enhance the spatial resolution of mini-microscopy and regular-microscopy. This data-driven approach trains a generative adversarial network to transform low-resolution images into super-resolved ones. Mini-microscopic images and regular-microscopic images acquired with different optical microscopes under various magnifications are collected as our experimental benchmark datasets. The only input to this generative-adversarial-network-based method are images from the datasets down-sampled by the Bicubic interpolation. We use independent test set to evaluate this deep learning approach with other deep learning-based algorithms through qualitative and quantitative comparisons. To clearly present the improvements achieved by this generative-adversarial-network-based method, we zoom into the local features to explore and highlight the qualitative differences. We also employ the peak signal-to-noise ratio and the structural similarity, to quantitatively compare alternative super-resolution methods. The quantitative results illustrate that super-resolution images obtained from our approach with interpolation parameter α=0.25 more closely match those of the original high-resolution images than to those obtained by any of the alternative state-of-the-art method. These results are significant for fields that use microscopy tools, such as biomedical imaging of engineered living systems. We also utilize this generative adversarial network-based algorithm to optimize the resolution of biomedical specimen images and then generate three-dimensional reconstruction, so as to enhance the ability of three-dimensional imaging throughout the entire volumes for spatial-temporal analyses of specimen structures.

Net micromineral requirements for maintenance and growth of ewe lambs at the latter fattening period.

OBJECTIVE: The objective of this study was to investigate the net micromineral (Cu, Fe, Mn, Zn) requirements for maintenance and growth of Dorper×Jinzhong crossbred ewe lambs at their latter fattening period. METHODS: Thirty 1/2 Dorper × 1/2 Jinzhong crossed F1 ewe lambs (35±0.5 kg of body weight [BW]) were used and divided into five groups in a randomized design for a comparative slaughter trial. At the beginning of the experiment, six lambs were randomly selected and slaughtered at 35 kg BW to determine their initial body composition. When their BWs reached 43 kg, another six lambs fed ad libitum were slaughtered to serve as an intermediate slaughter group. The retained eighteen lambs were randomly distributed into three groups and offered one type of feed at 100%, 65%, and 40% of the ad libitum intake. When the lambs fed ad libitum reached a BW of 50 kg, the three groups were slaughtered. The body composition (muscle, fat, bone, blood with viscera, skin, and wool) were weighted, ground, mixed, and subsampled for mineral content analysis. RESULTS: The net maintenance requirements of Cu, Fe, Mn, and Zn were 0.017, 0.160, 0.004, and 0.067 mg/kg BW/d, respectively, and the net growth requirements per 100 grams of average daily gain ranged from 0.48 to 0.51 mg of Cu, 2.63 to 2.17 mg of Fe, 0.12 to 0.15 mg of Mn, and 2.07 to 2.00 mg of Zn, respectively, for Dorper × Jinzhong crossed ewes from 35 to 50 kg BW. CONCLUSION: Our results suggest that the micromineral requirements for both maintenance and growth of Dorper × Jinzhong crossbred ewe lambs were quite different from the recommendations of NRC (2007), except for Zn.

Fabrication of Ag2O/Ag decorated ZnAl-layered double hydroxide with enhanced visible light photocatalytic activity for tetracycline degradation.

The photocatalytic performance of layered double hydroxides (LDH) is usually confined to the slow interface mobility and high recombination rate of photogenerated electron-hole pairs in material. To overcome the low photocatalytic efficiency, novel Ag2O/Ag decorated LDH (LDH-Ag2O/Ag) was successfully synthesized by depositing Ag2O on the surface of LDH and then converted to Ag° nanoparticles in the right position after heat treatment. The as-synthesized LDH-Ag2O/Ag composites were characterized by Powder X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflectance spectra (UV-vis DRS), photoluminescence spectra (PL) and transient photocurrent (TPC) analysis. Compared with virgin LDH, the photocatalytic activities of LDH-Ag2O/Ag composites were enhanced significantly. The optimum photocatalytic efficiency of LDH-Ag10 (0.0184 min-1) was nearly 46 times higher than that of virgin LDH (0.0004 min-1). The result of active species trapping experiments indicated that •OH, h+, and •O2- have an effect on the TC degradation, where •OH played the predominant role during the photocatalytic process. The possible photocatalytic mechanisms involving the charge transfer pathway and reactive species generation during the process of TC degradation were also discussed. The improved photocatalytic activity of LDH-Ag2O/Ag could be attributed to the synergetic effect between LDH and Ag2O/Ag that extended visible light range and reduced photogenerated charge carriers recombination.

Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug Delivery.

Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment to gain a more stable material (a-LDH) in acid medium for oral administration. It demonstrated that the a-LDH had smaller crystal size, particle sizes and higher permanent charge density (σp) compared with that of the p-LDH by means of XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH and FU/p-LDH delivery systems were obtained using anion-exchange method. The in vitro 5-FU drug release studies showed that no burst release phenomenon was observed at the beginning of release tests. The in vitro 5-FU release behaviors of the delivery systems at initial pH 4.6 and 7.5 were studied which could be described by first-order and Bhaskas models. Combined with the XRD and FT-IR analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it was found that the dissolution mechanism was mainly responsible for the release behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5-FU.

Gaussian Process Based Bayesian Inference System for Intelligent Surface Measurement.

This paper presents a Gaussian process based Bayesian inference system for the realization of intelligent surface measurement on multi-sensor instruments. The system considers the surface measurement as a time series data collection process, and the Gaussian process is used as mathematical foundation to establish an inferring plausible model to aid the measurement process via multi-feature classification and multi-dataset regression. Multi-feature classification extracts and classifies the geometric features of the measured surfaces at different scales to design an appropriate composite covariance kernel and corresponding initial sampling strategy. Multi-dataset regression takes the designed covariance kernel as input to fuse the multi-sensor measured datasets with Gaussian process model, which is further used to adaptively refine the initial sampling strategy by taking the credibility of the fused model as the critical sampling criteria. Hence, intelligent sampling can be realized with consecutive learning process with full Bayesian treatment. The statistical nature of the Gaussian process model combined with various powerful covariance kernel functions offer the system great flexibility for different kinds of complex surfaces.

Low NKD1 expression predicts adverse prognosis in cytogenetically normal acute myeloid leukemia.

Dysregulation of NKD1 has been identified in several solid tumors. However, the status of NKD1 expression and its clinical implication in acute myeloid leukemia remain largely elusive. NKD1 transcript level in bone marrow mononuclear cells was detected by real-time quantitative polymerase chain reaction in 126 de novo acute myeloid leukemia patients and 30 controls. Clinical significance of NKD1 expression was obtained by the comparison between the patients with low and high NKD1 expression. NKD1 messenger RNA level was significantly decreased in acute myeloid leukemia patients compared with controls ( p = 0.019). There were no significant differences between patients with low and high NKD1 expression in sex, age, peripheral blood cells, bone marrow blasts, French-American-British/World Health Organization subtypes, and karyotypes/karyotypic classifications ( p > 0.05). Although no significant difference was observed in complete remission rate between NKD1low and NKD1high patients ( p > 0.05), Kaplan-Meier analysis revealed that NKD1low patients showed shorter overall survival time than NKD1high patients in whole-cohort acute myeloid leukemia, non-M3 acute myeloid leukemia, and cytogenetically normal acute myeloid leukemia ( p = 0.014, 0.063, and 0.020). Multivariate analyses disclosed the low NKD1 expression was an independent risk factor in cytogenetically normal acute myeloid leukemia patients (hazard ratio = 0.397, p = 0.017). Moreover, the prognostic value of NKD1 expression was confirmed by gene expression profile data in cytogenetically normal acute myeloid leukemia patients ( p = 0.028 and 0.011). NKD1 showed significantly increased level after induction chemotherapy achieved complete remission in follow-up paired acute myeloid leukemia patients ( p < 0.001). These findings indicated that reduced NKD1 expression is associated with unfavorable clinical outcome in cytogenetically normal acute myeloid leukemia.

The prognostic implication of SRSF2 mutations in Chinese patients with acute myeloid leukemia.

Recently, somatic mutations in SRSF2 gene have been discovered in a proportion of hematologic malignancies including acute myeloid leukemia (AML). This study was aimed to investigate SRSF2 mutations in Chinese AML patients. High-resolution melting analysis (HRMA) was developed to screen SRSF2 mutations in 249 cases with AML, and then direct DNA sequencing was used to verify the results of HRMA. In this study, 3.6 % (9/249) of Chinese AML patients were found with heterozygous SRSF2 mutations. Patients with SRSF2 mutations were older than those with wild-type SRSF2 (P = 0.014). No differences in the sex, blood parameters, French-American-British classification (FAB) subtypes, and karyotypes were observed between AML patients with and without SRSF2 mutations. Although the overall survival (OS) of SRSF2-mutated patients was inferior to those without mutations in both whole AML patients (median 4 vs. 11 months, respectively; P = 0.006) and cytogenetically normal patients (median 2 vs. 12 months, respectively; P = 0.008), multiple analysis disclosed that SRSF2 mutation was not an independent prognostic factor in AML patients. These results suggest that SRSF2 mutation occurs at a low frequency in aged AML patients and might not be associated with adverse prognosis in Chinese AML patients.

Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis.

Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk.

[Human papillomavirus genotypes in male patients attending the STD clinic in Zhenjiang area].

OBJECTIVE: To investigate the status of human papillomavirus ( HPV) infection and its genotypes in male patients in Zhenjiang area. METHODS: Using PCR and reverse dot blot hybridization, we determined the genotypes of HPV DNA in 245 male patients at our Clinic of Dermatology and STD. RESULTS: The total rate of HPV infection was 43.67% (107/245), and 18 subtypes were detected. Among the 107 HPV-positive cases, low-risk, high-risk, and combined high- and low-risk infections accounted for 39.25% (42/107), 38.32% (41/107), and 22.43% (24/107), respectively. The most notable low-risk HPV types were HPV6 and HPV11, and the most notable high-risk HPV types were HPV16, HPV52, and HPV58. The rates of single infection and multi-infection were 53.27% (57/107) and 46.73% (50/107), respectively. One case had the most types, infected with 8 genotypes. No statistically significant differences were observed in the total rate of HPV infection among different age groups (Χ2 = 7.999, P > 0.05). CONCLUSION: The dominant subtypes of HPV infection in male patients in Zhenjiang area were HPV6, HPV11, and HPV16. The most common subtypes were HPV6 and HPV11 in low-risk infection, and HPV16, HPV52, and HPV58 in high-risk infection.

Preparation of strong, tough and conductive soy protein isolate/poly(vinyl alcohol)-based hydrogel via the synergy of biomineralization and salting out.

Conductive hydrogels have shown a great potential in the field of flexible electronic devices. However, conductive hydrogels prepare by traditional methods are difficult to combine high strength and toughness, which limits their application in various fields. In this study, a strategy for preparing conductive hydrogels with high strength and toughness by using the synergistic effect of biomineralization and salting-out was pioneered. In simple terms, by immersing the CaCl2 doped soy protein isolate/poly(vinyl alcohol)/dimethyl sulfoxide (SPI/PVA/DMSO) hydrogel in Na2CO3 and Na3Cit complex solution, the biomineralization aroused by Ca2+ and CO32-, and the salting-out effect of both NaCl and Na3Cit would enhance the mechanical properties of SPI/PVA/DMSO hydrogel. Meanwhile, the ionic conductivity of the hydrogel would also increase due the introduction of cation and anion. The mechanical and electrical properties of SPI/PVA/DMSO/CaCO3/Na3Cit hydrogels were significantly enhanced by the synergistic effect of biomineralization and salting-out. The optimum tensile strength, toughness, Young's modulus and ionic conductivity of the hydrogel were 1.4 ± 0.08 MPa, 0.51 ± 0.04 MPa and 1.46 ± 0.01 S/m, respectively. The SPI/PVA/DMSO/CaCO3/Na3Cit hydrogel was assembled into a strain sensor. The strain sensor had good sensitivity (GF = 3.18, strain in 20 %-500 %) and could be used to accurately detect various human movements.

Rack1-mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights.

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C-Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM-affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14-16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM-affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co-localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38-MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset.

The Synergy between Deep Learning and Organs-on-Chips for High-Throughput Drug Screening: A Review.

Organs-on-chips (OoCs) are miniature microfluidic systems that have arguably become a class of advanced in vitro models. Deep learning, as an emerging topic in machine learning, has the ability to extract a hidden statistical relationship from the input data. Recently, these two areas have become integrated to achieve synergy for accelerating drug screening. This review provides a brief description of the basic concepts of deep learning used in OoCs and exemplifies the successful use cases for different types of OoCs. These microfluidic chips are of potential to be assembled as highly potent human-on-chips with complex physiological or pathological functions. Finally, we discuss the future supply with perspectives and potential challenges in terms of combining OoCs and deep learning for image processing and automation designs.