MOF@platelet-rich plasma antimicrobial GelMA dressing: structural characterization, bio-compatibility, and effect on wound healing efficacy.

In this study, a metal-organic framework (MOF) antimicrobial gel loaded with platelet-rich plasma (PRP) was prepared to improve the biological properties of gelatin gels and enhance their wound healing efficiency. PRP, MOF particles, and PRP-loaded MOF particles were each integrated into gelatin gels. The performance of the gels was evaluated for micro-structure, mechanical strength, in vitro bio-compatibility and pro-wound healing effects. The results revealed that the integration of PRP created a multi-cross-linked structure, increasing the ductility of the gels by over 40%. The addition of MOF particles significantly increased the strength of the gel from 13 kPa to 43 kPa. The combination of MOF and PRP further improved the cell induction and migration capabilities of the composite gel, and the scratches in the PRP/MOF@GelMA group had completely healed within 48 h. Due to the presence of MOF and PRP, the gel dressing exhibited inhibitory effects of 45.7% against Staphylococcus aureus (S. aureus) and 50.2% against Escherichia coli (E. coli). Different gels promoted tissue regeneration and wound healing ability of bacterial-infected wounds in C57 rats, while PRP/MOF@GelMA showed the strongest wound repair ability with 100% healing. This study provides a new strategy for the development and clinical application of gel dressings.

CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury.

Wnt/ß-catenin signaling is an attractive target for regenerative medicine. A powerful driver of stem cell activity and hence tissue regeneration, Wnt signaling can promote fibroblast proliferation and activation, leading to fibrosis, while prolonged Wnt signaling is potentially carcinogenic. Thus, to harness its therapeutic potential, the activation of Wnt signaling must be transient, reversible, and tissue specific. In the lung, Wnt signaling is essential for alveolar stem cell activity and alveolar regeneration, which is impaired in lung fibrosis. Activation of Wnt/ß-catenin signaling in lung epithelium may have anti-fibrotic effects. Here, we used intratracheal adeno-associated virus 6 injection to selectively deliver CasRx into the lung epithelium, where it reversibly activates Wnt signaling by simultaneously degrading mRNAs encoding Axin1 and Axin2, negative regulators of Wnt/ß-catenin signaling. Interestingly, CasRx-mediated Wnt activation specifically in lung epithelium not only promotes alveolar type II cell proliferation and alveolar regeneration but also inhibits lung fibrosis resulted from bleomycin-induced injury, relevant in both preventive and therapeutic settings. Our study offers an attractive strategy for treating pulmonary fibrosis, with general implications for regenerative medicine.

Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.

BACKGROUND: Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored. METHODS: Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM. RESULTS: 2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16circle in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16circle showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001). CONCLUSIONS: Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16circle, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker. TRIAL REGISTRATION: ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.

Multicellular 3D bioprinted human gallbladder carcinoma forin vitromimicry of tumor microenvironment and intratumoral heterogeneity.

Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by an intricate tumor microenvironments (TME) and heterogeneity. The traditional GBC 2D culture models cannot faithfully recapitulate the characteristics of the TME. Three-dimensional (3D) bioprinting enables the establishment of high-throughput and high-fidelity multicellular GBC models. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with the inner portion containing GBC cells, and the outer ring containing a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarker expression and gene expression profiles of GBC 3D tetra-culture models. Hematoxylin-eosin (HE) and immunofluorescence staining verified the morphology and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model, glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among variousin vitromodels revealed that cellular interactions and the TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of the TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future applications in tumor biology research and antitumor drug development.

Fluorinated Naphthalene Diimides as Buried Electron Transport Materials Achieve Over 23% Efficient Perovskite Solar Cells.

Naphthalene diimides (NDI) are widely serving as the skeleton to construct electron transport materials (ETMs) for optoelectronic devices. However, most of the reported NDI-based ETMs suffer from poor interfaces with the perovskite which deteriorates the carrier extraction and device stability. Here, a representative design concept for editing the peripheral groups of NDI molecules to achieve multifunctional properties is introduced. The resulting molecule 2,7-bis(2,2,3,3,4,4,4-heptafluorobutyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-C4F) incorporated with hydrophobic fluorine units contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability and the formation of strong chemical coordination with perovskite precursors. All these features favor retarding the perovskite crystallization and achieving superior buried interfaces, which subsequently promote charge collection and improve the structural compatibility between perovskite and ETMs. The corresponding PSCs based on low-temperature processed NDI-C4F yield a record efficiency of 23.21%, which is the highest reported value for organic ETMs in n-i-p PSCs. More encouragingly, the unencapsulated devices with NDI-C4F demonstrate extraordinary stability by retaining over 90% of their initial PCEs after 2600 h in air. This work provides an alternative molecular strategy to engineer the buried interfaces and can trigger further development of organic ETMs toward reliable PSCs.

In situ Blending For Co-Deposition of Electron Transport and Perovskite Layers Enables Over 24% Efficiency Stable Conventional Solar Cells.

Simplifying the manufacturing processes of multilayered high-performance perovskite solar cells (PSCs) is yet of vital importance for their cost-effective production. Herein, an in situ blending strategy is presented for co-deposition of electron transport layer (ETL) and perovskite absorber by incorporating (3-(7-butyl-1,3,6,8-tetraoxo-3,6,7,8-tetrahydrobenzo- [lmn][3,8]phenanthrolin-2(1H)-yl)propyl)phosphonic acid (NDP) into the perovskite precursor solutions. The phosphonic acid-like anchoring group coupled with its large molecular size drives the migration of NDP toward indium tin oxide (ITO) surface to form a distinct ETL during perovskite film forming. This strategy circumvents the critical wetting issue and simultaneously improves the interfacial charge collection efficiencies. Consequently, n-i-p PSCs based on in situ blended NDP achieve a champion power conversion efficiency (PCE) of 24.01%, which is one of the highest values for PSCs using organic ETLs. This performance is notably higher than that of ETL-free (21.19%) and independently spin-coated (21.42%) counterparts. More encouragingly, the in situ blending strategy dramatically enhances the device stability under harsh conditions by retaining over 90% of initial efficiencies after 250 h in 100 °C or 65% humidity storage. Moreover, this strategy is universally adaptable to various perovskite compositions, device architectures, and electron transport materials (ETMs), showing great potential for applications in diverse optoelectronic devices.

Acoustic-holography-patterned primary hepatocytes possess liver functions.

Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel invitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.

Liver bioprinting within a novel support medium with functionalized spheroids, hepatic vein structures, and enhanced post-transplantation vascularization.

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

Revitalizing liver function in mice with liver failure through transplantation of 3D-bioprinted liver with expanded primary hepatocytes.

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro-expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.

A step towards 6D WAXD tensor tomography.

X-ray scattering/diffraction tensor tomography techniques are promising methods to acquire the 3D texture information of heterogeneous biological tissues at micrometre resolution. However, the methods suffer from a long overall acquisition time due to multi-dimensional scanning across real and reciprocal space. Here, a new approach is introduced to obtain 3D reciprocal information of each illuminated scanning volume using mathematic modeling, which is equivalent to a physical scanning procedure for collecting the full reciprocal information required for voxel reconstruction. The virtual reciprocal scanning scheme was validated by a simulated 6D wide-angle X-ray diffraction tomography experiment. The theoretical validation of the method represents an important technological advancement for 6D diffraction tensor tomography and a crucial step towards pervasive applications in the characterization of heterogeneous materials.

Value of quantitative microsurface structure analysis for evaluating the invasion depth of type 0-II early gastric cancer.

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

Plasmonic Alloys Enhanced Metabolic Fingerprints for the Diagnosis of COPD and Exacerbations.

Accurate diagnosis of chronic obstructive pulmonary disease (COPD) and exacerbations by metabolic biomarkers enables individualized treatment. Advanced metabolic detection platforms rely on designed materials. Here, we design mesoporous PdPt alloys to characterize metabolic fingerprints for diagnosing COPD and exacerbations. As a result, the optimized PdPt alloys enable the acquisition of metabolic fingerprints within seconds, requiring only 0.5 µL of native plasma by laser desorption/ionization mass spectrometry owing to the enhanced electric field, photothermal conversion, and photocurrent response. Machine learning decodes metabolic profiles acquired from 431 individuals, achieving a precise diagnosis of COPD with an area under the curve (AUC) of 0.904 and an accurate distinction between stable COPD and acute exacerbations of COPD (AECOPD) with an AUC of 0.951. Notably, eight metabolic biomarkers identified accurately discriminate AECOPD from stable COPD while providing valuable information on disease progress. Our platform will offer an advanced nanoplatform for the management of COPD, complementing standard clinical techniques.

Rapid Self-Assembly Mini-Livers Protect Mice Against Severe Hepatectomy-Induced Liver Failure.

The construction of bioartificial livers, such as liver organoids, offers significant promise for disease modeling, drug development, and regenerative medicine. However, existing methods for generating liver organoids have limitations, including lengthy and complex processes (taking 6-8 weeks or longer), safety concerns associated with pluripotency, limited functionality of pluripotent stem cell-derived hepatocytes, and small, highly variable sizes (typically ≈50-500 µm in diameter). Prolonged culture also leads to the formation of necrotic cores, further restricting size and function. In this study, a straightforward and time-efficient approach is developed for creating rapid self-assembly mini-livers (RSALs) within 12 h. Additionally, primary hepatocytes are significantly expanded in vitro for use as seeding cells. RSALs exhibit consistent larger sizes (5.5 mm in diameter), improved cell viability (99%), and enhanced liver functionality. Notably, RSALs are functionally vascularized within 2 weeks post-transplantation into the mesentery of mice. These authentic hepatocyte-based RSALs effectively protect mice from 90%-hepatectomy-induced liver failure, demonstrating the potential of bioartificial liver-based therapy.

Advancements of 3D bioprinting in regenerative medicine: Exploring cell sources for organ fabrication.

3D bioprinting has unlocked new possibilities for generating complex and functional tissues and organs. However, one of the greatest challenges lies in selecting the appropriate seed cells for constructing fully functional 3D artificial organs. Currently, there are no cell sources available that can fulfill all requirements of 3D bioprinting technologies, and each cell source possesses unique characteristics suitable for specific applications. In this review, we explore the impact of different 3D bioprinting technologies and bioink materials on seed cells, providing a comprehensive overview of the current landscape of cell sources that have been used or hold potential in 3D bioprinting. We also summarized key points to guide the selection of seed cells for 3D bioprinting. Moreover, we offer insights into the prospects of seed cell sources in 3D bioprinted organs, highlighting their potential to revolutionize the fields of tissue engineering and regenerative medicine.

Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases.

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

Conjugated Phosphonic Acids Enable Robust Hole Transport Layers for Efficient and Intrinsically Stable Perovskite Solar Cells.

High efficiency and long-term stability are the prerequisites for the commercialization of perovskite solar cells (PSCs). However, inadequate and non-uniform doping of hole transport layers (HTLs) still limits the efficiency improvements, while the intrinsic instability of HTLs caused by ion migration and accumulation is difficult to be addressed by external encapsulation. Here it is shown that the addition of a conjugated phosphonic acid (CPA) to the Spiro-OMeTAD benchmark HTL can greatly enhance the device efficiency and intrinsic stability. Featuring an optimal diprotic-acid structure, indolo(3,2-b)carbazole-5,11-diylbis(butane-4,1-diyl) bis(phosphonic acid) (BCZ) is developed to promote morphological uniformity and mitigate ion migration across both perovskite/HTL and HTL/Ag interfaces, leading to superior charge conductivity, reinforced ion immobilization, and remarkable film stability. The dramatically improved interfacial charge collection endows BCZ-based n-i-p PSCs with a champion power conversion efficiency of 24.51%. More encouragingly, the BCZ-based devices demonstrate remarkable stability under harsh environmental conditions by retaining 90% of initial efficiency after 3000 h in air storage. This work paves the way for further developing robust organic HTLs for optoelectronic devices.

Gas Sensor Array Fault Diagnosis Based on Multi-Dimensional Fusion, an Attention Mechanism, and Multi-Task Learning.

With the development of gas sensor arrays and computational technology, machine olfactory systems have been widely used in environmental monitoring, medical diagnosis, and other fields. The reliable and stable operation of gas sensing systems depends heavily on the accuracy of the sensors outputs. Therefore, the realization of accurate gas sensor array fault diagnosis is essential to monitor the working status of sensor arrays and ensure the normal operation of the whole system. The existing methods extract features from a single dimension and require the separate training of models for multiple diagnosis tasks, which limits diagnostic accuracy and efficiency. To address these limitations, for this study, a novel fault diagnosis network based on multi-dimensional feature fusion, an attention mechanism, and multi-task learning, MAM-Net, was developed and applied to gas sensor arrays. First, feature fusion models were applied to extract deep and comprehensive features from the original data in multiple dimensions. A residual network equipped with convolutional block attention modules and a Bi-LSTM network were designed for two-dimensional and one-dimensional signals to capture spatial and temporal features simultaneously. Subsequently, a concatenation layer was constructed using feature stitching to integrate the fault details of different dimensions and avoid ignoring useful information. Finally, a multi-task learning module was designed for the parallel learning of the sensor fault diagnosis to effectively improve the diagnosis capability. The experimental results derived from using the proposed framework on gas sensor datasets across different amounts of data, balanced and unbalanced datasets, and different experimental settings show that the proposed framework outperforms the other available methods and demonstrates good recognition accuracy and robustness.

Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility.

Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.