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Multiscale investigation of collagen structure in human skin and gel matrices using polarization resolved second harmonic generation microscopy
Abstract Collagen is critical to the structure and function of skin tissues, with the collagen I/III ratios influencing fibrillogenesis, fiber organization, and skin mechanics. Abnormal collagen organization, such as in fibrosis or scar tissue, compromises both skin functionality and aesthetics. In this study, we employed label-free polarization resolved second harmonic generation (PSHG) microscopy to investigate collagen structure in artificial collagen matrices with various Col I/III ratios at the fibril scale ( $$\sim$$ ∼ 1 to $$3\,\upmu \hbox {m}$$ 3 μ m ) and in ex vivo human healthy and scarred skin at the fiber scale ( $$\sim 10$$ ∼ 10 to $$20\,\upmu \hbox {m}$$ 20 μ m ). Complementary third harmonic generation (THG) microscopy provided additional structural information. Our results indicate that an increasing Col I/III ratio is associated with longer fibril length, higher PSHG intensity, and a reduced effective $$\alpha$$ α -helix pitch angle of fibrils. In pure Col I, the effective $$\alpha$$ α -helix pitch angle is determined to be $$47.72^{\circ }$$ 47 . 72 ∘ . These observations indicate alterations in fibril assembly. Furthermore, although the $$\alpha$$ α -helix pitch angle of fibers in both healthy and scarred skin was approximately $$46.7^{\circ }$$ 46 . 7 ∘ , healthy skin exhibited $$24\%$$ 24 % greater variability in fiber orientation, suggesting a more randomized organization compared to scar tissue. THG imaging further revealed a higher cellular density in scar tissue, consistent with the inflammatory activity associated with wound healing. Immunohistochemical (IHC) staining using dermatansulphate and Col III-specific antibodies confirmed that the Col I/III ratio is higher in healthy skin (2.2) than in scarred skin (1.6). These findings underscore the potential of PSHG microscopy for label-free, quantitative assessment of collagen structure across multiple scales, with THG offering complementary cellular insights. This integrated approach represents a promising strategy for real-time, in vivo monitoring and automated quantification of collagen organization in clinical applications, including dermatology, burn treatment, and fibrosis monitoring.
Native globular ferritin nanopore sensor
Abstract High-resolution nanopore analysis technology relies on the design of novel transmembrane protein platforms. Traditional barrel-shaped protein channels are preferred for constructing nanopore sensors, which may miss protein candidates in non-barrel structures. Here, we demonstrate the globular ferritin displays excellent membrane-insertion capacity and stable transmembrane ionic current owing to its hydrophobic four-fold channels and hydrophilic three-fold channels. The ionic current rectification and voltage-gating characteristics are discovered in single-ferritin ionic current measurement. Notably, the ferritin is used as a nanopore sensor, by which we achieve the high resolution discrimination of L-cysteine, L-homocysteine, and cysteine-containing dipeptides with the assistance of equivalent Cu2+. The mechanistic studies by multiple controlled experiments and quantum mechanics/all-atom/coarse-grained multiscale MD simulations reveal that analytes are synergistically captured by His114, Cys126, and Glu130 within C3 channel, causing the current blockage signals. The promising ferritin nanopore sensor provides a guide to discovering new protein nanopores without shape restrictions.
A multi-strategy improved crow search algorithm for multi-level thresholding image segmentation
Chemoselective dual functionalization of proteins via 1,6-addition of thiols to trifunctional N-alkylpyridinium
Abstract Chemoselective dual functionalization of proteins has emerged as an invaluable tool to introduce two distinct payloads to proteins, thus greatly expanding their structural and functional repertoire for more advanced biomedical applications. Here, we introduce N-alkylpyridinium reagents as soft electrophiles for chemoselective dual modification of cysteine residues in peptides or proteins via a 1,6-addition reaction. The N-alkylpyridinium derivatives can be synthesized in two reaction steps revealing good water solubility, high labelling efficiency and chemoselectivity towards cysteine over lysine/N-terminal amine residues, even when used in large excess. This reaction can be combined with strain-promoted azide-alkyne click (SPAAC) and inverse-electron-demand Diels−Alder (iEDDA) reactions to achieve dual functionalization of proteins in a sequential simple one-pot reaction. As a proof-of-concept, the Rho-inhibiting enzyme Clostridium botulinum C3 is functionalized with a cancer cell-targeting peptide and a fluorescent dye for the inhibition of specific Rho-mediated intracellular pathways. The high stability, ease of synthesis, fast reaction kinetics, high water-solubility and chemoselectivity make N-alkylpyridinium reagents unique for dual modification of peptides and proteins to increase their functional diversities for medical applications.
Hollow ZnO nanorod in PVDF matrix for high-performance sensing, vibration energy harvesting and wearable application
Extreme potential photocatalysis enabled by spin-exchange Auger processes in magnetic-doped quantum dots
Abstract Visible-light-absorbing semiconductor nanocrystals have shown great promise as photocatalysts for promoting photoredox chemistry. However, their utilization in organic synthesis remains considerably limited compared to small molecule photosensitizers. Recently, the generation of hot electrons from quantum-confined systems has emerged as a powerful means of photoreduction, yet the efficiencies remain limited under mild conditions. In this study, we present an efficient hot-electron generation system facilitated by the spin-exchange Auger process in Mn2+-doped CdS/ZnS quantum dots. These hot electrons can be effectively utilized in a wide range of organic reactions, such as the Birch reduction and reductive cleavage of C-Cl, C-Br, C-I, C-O, C-C, and N-S bonds. Notably, these reactions accommodate substrate reduction potentials as low as −3.4 V versus the saturated calomel electrode. Through two-photon excitation, we achieve the generation of a “super” photoreductant using visible-light irradiation power that is only 1% of that previously reported for molecular and quantum dot systems. By modulating the intensity of light output, the spin-exchange Auger process enables the on/off generation of hot electrons, allowing for programmable assembly-point cross-coupling cascades. Our findings demonstrate the potential of quantum-confined semiconductors in facilitating challenging organic transformations that were unattainable with molecular photocatalysts.
Double effects of O2 on passive film of super 13Cr stainless steel in CO2 saturated environment
Abstract Herein, a comprehensive suite of electrochemical methods, including cyclic polarization, Mott-Schottky (M-S), and electrochemical impedance spectroscopy (EIS) tests, were employed to investigate the effects of O2 on passivation and pitting behavior of Super 13Cr in CO2-saturated environment. Our findings reveal that O2 plays a dual role: O2 substantially enhances the stability of passive film by diminishing point defeat density, thereby improving the resistance to local corrosive attacks. Conversely, within the stable pitting domain, O2 exacerbates the severity of the corrosive environment, undermining the repassivation capabilities of super 13Cr stainless steel. The study elucidates the intricate interplay of O2 and the passive film, offering valuable insights for the strategic application of Super 13Cr in the demanding conditions of modern oil and gas extraction processes where CO2 and O2 coexist.
Leaf-based energy harvesting and storage utilizing hygroscopic iron hydrogel for continuous power generation
Abstract In the era of big data, developing next-generation self-powered continuous energy harvesting systems is of great importance. Taking advantage of fallen leaves’ specific structural advantage gifted by nature, we propose a facile approach to convert fallen leaves into energy harvesters from ubiquitous moisture, based on surface treatments and asymmetric coating of hygroscopic iron hydrogels. Upon moisture absorption, a water gradient is established between areas with/without hydrogel coating, and maintained due to gel-like behaviors and leaf veins for water retention and diffusion restriction, thus forming electrical double layers over the leaf surface and showing capacitance-like behavior for energy charging and discharging. Besides, the specific leaf cell structures with small grooves enabled uniform carbon coatings instead of aggregations, and high electrical conductivity, resulting in 49 μA/cm2 and 497 μW/cm3 electrical output, achieving competitive performance with the state-of-art and potential for lower environmental impact compared to other types of energy harvesters.
Evaluating the feasibility of region-of-interest X-ray phase contrast imaging for lung cancer diagnostics
Understanding indirect assortative mating and its intergenerational consequences for educational attainment
Abstract We develop a framework for understanding indirect assortative mating and provide updated definitions of key terms. We then develop family models that use partners of twins and siblings to freely estimate the degree of genetic and social homogamy, and account for it when investigating sources of parent-offspring similarity. We applied the models to educational attainment using 1,545,444 individuals in 212,070 extended families in the Norwegian population and Norwegian Twin Registry. Partner similarity in education was better explained by indirect assortment than direct assortment on observed educational attainment, with social homogamy being particularly important. The implied genotypic partner correlation ( r = 0.34) was comparable to earlier studies, and higher than expected under direct assortment. About 38% of the parent-offspring correlation ( r = 0.34) was attributable to various forms of environmental transmission. Alternative models that assumed direct assortment estimated environmental transmission to be lower, but these did not fit the data well.
Femoral strength after cephalomedullary nail removal can be predicted preoperatively using CT based FE models
Abstract Removals of cephalomedullary nails (CMNs) after healed pertrochanteric femur fractures are sometimes requested by patients or medically indicated due to pain or screw cut-out. However, CMN removal carries a high risk of secondary femoral neck fracture, even in the absence of trauma. Consequently, decisions on nail removal and establishing a safe post-operative loading regimen can be challenging. This study investigated if finite element (FE) models can pre-operatively predict femoral strength after CMN removal to support these clinical decisions. Nine proximal femora of body donors who were treated with a CMN during their lifetime were included. Computed tomography (CT) scans were acquired with the CMN still in place, followed by virtual implant removal using image processing. Based on this scan, non-linear voxel-based FE models were created and femoral strength was predicted for a one-legged stance configuration. For validation, the CMNs were physically removed and femoral strength was assessed in a material testing machine. The FE models predicted the femoral strength accurately relative to the experiments (R 2 = 0.94, CCC = 0.97). In conclusion, CT-based FE models demonstrate potential to predict femoral strength after CMN removal pre-operatively. This could help patients and clinicians to make an informed decision on implant removal and permissible post-operative weight-bearing.
Multiple exciton generation boosting over 100% quantum efficiency photoelectrochemical photodetection
Abstract The self-powered photoelectrochemical components themselves featured advancements in operating independently without external supply. Ultimately, due to lack of assistance from the external bias, the photoelectrochemical response is commonly restricted by the deficient photo-quantum efficiency for the absence of carrier multiplication. This work demonstrates a self-powered photoelectrochemical photodetector based on CuOx/AlGaN nanowires with staggered band structure and enhanced built-in potential for efficient exciton extraction. The generated multiple excitons within reach-through CuOx layer could be speedily separated before Auger recombination. This yields a 131.5% external quantum efficiency and 270.6 mA W−1 responsivity at 255 nm. The work confirms the role of multiple exciton generation in photoelectrochemical systems, offering a solution on paving path of advance for self-powered optoelectronics and weak-light UV imaging applications.
The effect of Effort-Reward imbalance on job performance among primary healthcare professionals: the mediating roles of social support and resilience
TANGO2 binds crystallin alpha B and its loss causes desminopathy
Abstract Mutations in the TANGO2 gene cause an autosomal recessive disorder characterised by developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias along with severe metabolic crises. Although TANGO2 mutations result in a well characterised disease pathology, the function of TANGO2 is still unknown. To investigate the function of TANGO2, we knocked out the TANGO2 gene in human cells and mice. We identify that loss of TANGO2 impairs intermediate filament structure, resulting in fragmented mitochondrial networks and formation of cup-like mitochondria. In male mice, loss of TANGO2 caused heart defects, reduced muscle function and glucose intolerance by remodelling of intermediate filaments, which altered the mitochondrial and cytoplasmic proteomes, N-glycosylation and nucleocytoplasmic O-GlcNAcylation. We identify that TANGO2 binds the small heat shock protein crystallin alpha B (CRYAB) to prevent the aggregation of the intermediate filament desmin and in the absence of TANGO2, mice develop desminopathy, which is consistent with features found in patients carrying mutations in either desmin or CRYAB.