An endoscopically compatible fast-gelation powder forms Janus-adhesive hydrogel barrier to prevent postoperative adhesions.

Postoperative adhesions occur widely in various tissues, bringing the risk of secondary surgery and increased medical burden. Hydrogel barriers with Janus-adhesive ability can achieve physical isolation of adjacent tissues and are therefore considered an ideal solution. However, integrating endoscopic delivery convenience and viscoelastic Janus hydrogel formation remains a great challenge. Here, we present a report of the in situ formation of Janus-adhesive hydrogel barrier using a sprayable fast-Janus-gelation (FJG) powder. We first methacrylate the polysaccharide macromolecules to break the intermolecular hydrogen bonds and impart the ability of rapid hydration. FJG powder can rapidly absorb interfacial water and crosslink through borate ester bonds, forming a toughly adhesive viscoelastic hydrogel. The Janus barrier can be simply formed by further hydrating the upper powder with cationic solution. We construct rat models to demonstrate the antiadhesions efficiency of viscoelastic FJG hydrogels in organs with different motion modalities (e.g., intestine, heart, liver). We also developed a low-cost delivery device with a standardized surgical procedure and further validated the feasibility and effectiveness of FJG powder in minimally invasive surgery using a preclinical translational porcine model. Considering the advantages in terms of therapeutic efficacy, clinical convenience, and commercialization, our results reveal the great potential of Janus-gelation powder materials as a next-generation antiadhesions barrier.

Oxygen Isotope Analysis of Nanomole Phosphate Using PO3- Fragment in ESI-Orbitrap-MS.

The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current Ag3PO4 method is not only tedious in PO43- extraction and purification but also requires a large-sized sample at the micromole level, thereby limiting its application. Here, we present an approach to measuring the oxygen isotope composition, δ18O, of dissolved phosphate at the nanomole level using electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap-MS). We compared the reproducibility of δ18O measurements using the H2PO4- ions (m/z = 97 and 99 for H2P16O4- and H2P18O16O3-, respectively) and using the PO3- fragment ions (m/z = 79 and 81 for P16O3- and P18O16O2-, respectively) generated by source fragmentation and by higher-energy collisional dissociation, respectively. The results demonstrate that phosphate δ18O can be more reliably measured by the PO3- ions than by the H2PO4- ions. PO3- generated by source fragmentation at 40 V achieved the highest reproducibility for δ18O based on precision tests. Furthermore, the mass spectrum for a 50:50 µM mixed solution of phosphate and sulfate revealed that PO3- ions resulting from source fragmentation at 40 V are the predominant species in the Orbitrap analyzer. Notably, P16O3- ions (m/z: 79) are not interfered with by 32S16O3- (m/z: 80) ions. This is in contrast to the case for 1H2P16O4- ions, which share the same m/z value with 1H32S16O4- ions and exhibit much lower signal intensity than HSO4- ions. Using the PO3- fragment method and six phosphate standards with a wide range of δ18O values, we obtained a calibration line with a slope of 0.94 (R2 = 0.98). The overall uncertainty for ESI-Orbitrap-MS phosphate δ18O measurement was 0.8‰ (n = 30; 1 SD). With much room for improvement, the PO3- fragment method presents a better approach to measuring the phosphate oxygen isotope composition, applicable to nanomole sample sizes in a liquid phase.

Matrix Nonlinear Viscoelasticity Regulates Skeletal Myogenesis through MRTF Nuclear Localization and Nuclear Mechanotransduction.

Mechanically sensitive tissues (e.g., skeletal muscles) greatly need mechanical stimuli during the development and maturation. The extracellular matrix (ECM) mediates these signals through nonlinear viscoelasticity of collagen networks that are predominant components of the ECM. However, the interactions between cells and ECM form a feedback loop, and it has not yet been possible to determine the degree to which, if any, of the features of matrix nonlinear viscoelasticity affect skeletal muscle development and regeneration. In this study, a nonlinear viscoelastic feature (i.e., strain-enhanced stress relaxation (SESR)) in normal skeletal muscles is observed, which however is almost absent in diseased muscles from Duchenne muscular dystrophy mice. It is recapitulated such SESR feature in vitro and separated the effects of mechanical strain and ECM viscoelasticity on myoblast response by developing a collagen-based hydrogel platform. Both strain and stress relaxation induce myogenic differentiation and myotube formation by C2C12 myoblasts, and myogenesis is more promoted by applying SESR. This promotion can be explained by the effects of SESR on actin polymerization-mediated myocardin related transcription factor (MRTF) nuclear localization and nuclear mechanotransduction. This study represents the first attempt to investigate the SESR phenomenon in skeletal muscles and reveal underlying mechanobiology, which will provide new opportunities for the tissue injury treatments.

Evaluation of gadolinium deposition in cortical bone using three-dimensional ultrashort echo time quantitative susceptibility mapping: A preliminary study.

The aim of the current study was to investigate the feasibility of three-dimensional ultrashort echo time quantitative susceptibility mapping (3D UTE-QSM) for the assessment of gadolinium (Gd) deposition in cortical bone. To this end, 40 tibial bovine cortical bone specimens were divided into five groups then soaked in phosphate-buffered saline (PBS) solutions with five different Gd concentrations of 0, 0.4, 0.8, 1.2, and 1.6 mmol/L for 48 h. Additionally, eight rabbits were randomly allocated into three groups, consisting of a normal-dose macrocyclic gadolinium-based contrast agent (GBCA) group (n = 3), a high-dose macrocyclic GBCA group (n = 3), and a control group (n = 2). All bovine and rabbit tibial bone samples underwent magnetic resonance imaging (MRI) on a 3-T clinical MR system. A 3D UTE-Cones sequence was utilized to acquire images with five different echo times (i.e., 0.032, 0.2, 0.4, 0.8, and 1.2 ms). The UTE images were subsequently processed with the morphology-enabled dipole inversion algorithm to yield a susceptibility map. The average susceptibility was calculated in three regions of interest in the middle of each specimen, and the Pearson's correlation between the estimated susceptibility and Gd concentration was calculated. The bone samples soaked in PBS with higher Gd concentrations exhibited elevated susceptibility values. A mean susceptibility value of -2.47 ± 0.23 ppm was observed for bovine bone soaked in regular PBS, while the mean QSM value increased to -1.75 ± 0.24 ppm for bone soaked in PBS with the highest Gd concentration of 1.6 mmol/L. A strong positive correlation was observed between Gd concentrations and QSM values. The mean susceptibility values of rabbit tibial specimens in the control group, normal-dose GBCA group, and high-dose GBCA group were -4.11 ± 1.52, -3.85 ± 1.33, and -3.39 ± 1.35 ppm, respectively. In conclusion, a significant linear correlation between Gd in cortical bone and QSM values was observed. The preliminary results suggest that 3D UTE-QSM may provide sensitive noninvasive assessment of Gd deposition in cortical bone.

Qualitative and Quantitative MR Imaging of the Cartilaginous Endplate: A Review.

The cartilaginous endplate (CEP) plays a pivotal role in facilitating the supply of nutrients and, transport of metabolic waste, as well as providing mechanical support for the intervertebral disc (IVD). Recent technological advances have led to a surge in MR imaging studies focused on the CEP. This article describes the anatomy and functions of the CEP as well as MRI techniques for both qualitative and quantitative assessment of the CEP. Effective CEP MR imaging sequences require two key features: high spatial resolution and relatively short echo time. High spatial resolution spoiled gradient echo (SPGR) and ultrashort echo time (UTE) sequences, fulfilling these requirements, are the basis for most of the sequences employed in CEP imaging. This article reviews existing sequences for qualitative CEP imaging, such as the fat-suppressed SPGR and UTE, dual-echo subtraction UTE, inversion recovery prepared and fat-suppressed UTE, and dual inversion recovery prepared UTE sequences. These sequences are employed together with other techniques for quantitative CEP imaging, including measurements of T2*, T2, T1, T1ρ, magnetization transfer, perfusion, and diffusion tensor parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1+ (CD8+ T cell/Treg) and promoted the levels of IFN-γ+ CD8+ T cells and TNF-α+ CD8+ T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1+ (CD8+ T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.

Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-a]pyrimidine for the Synthesis of Zanubrutinib.

A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.

Selenium Treatment Ameliorates the Adverse Effects Caused by Dynamin Gene Knockdown in Bombyx mori.

Our previous research reported the influence of 50 µM selenium (Se) on the cytosolization (endocytosis) pathway, which in turn stimulates the growth and development of Bombyx mori. Lately, dynamin is recognized as one of the key proteins in endocytosis. To explore the underlying mechanisms of Se impact, the dynamin gene was knocked down by injecting siRNAs (Dynamin-1, Dynamin-2, and Dynamin-3). This was followed by an analysis of the target gene and levels of silk protein genes, as well as growth and developmental indices, Se-enrichment capacity, degree of oxidative damage, and antioxidant capacity of B. mori. Our findings showed a considerable decrease in the relative expression of the dynamin gene in all tissues 24 h after the interference and a dramatic decrease in the silkworm body after 48 h. RNAi dynamin gene decreased the silkworm body weight, cocoon shell weight, and the ratio of cocoon. In the meantime, malondialdehyde level increased and glutathione level and superoxide dismutase/catalase activities decreased. 50 µM Se markedly ameliorated these growth and physiological deficits as well as decreases in dynamin gene expression. On the other hand, there were no significant effects on fertility (including produced eggs and laid eggs) between the interference and Se treatments. Additionally, the Se content in the B. mori increased after the dynamin gene interference. The dynamin gene was highly expressed in the silk gland and declined significantly after interference. Among the three siRNAs (Dynamin-1, Dynamin-2, and Dynamin-3), the dynamin-2 displayed the highest interference effects to target gene expression. Our results demonstrated that 50 µM Se was effective to prevent any adverse effects caused by dynamin knockdown in silkworms. This provides practical implications for B. mori breeding industry.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.