Near-Infrared, Organic Chiroptic Switch with High Dissymmetry Factors.

Here we unveil a chiral molecular redox switch derived from PDI-based twistacenes─chPDI[2] that has the remarkable attributes of high-intensity and a broadband chiral response. This material exhibits facile, stable, and reversible multistate chiroptical switching behavior over a broad active wavelength range close to 700 nm, encompassing ultraviolet, visible, and near-infrared regions. Upon reduction, chPDI[2] exhibits a substantial increase in the amplitude of its circular dichroic response, with an outstanding |ΔΔε| > 300 M-1 cm-1 and a high dissymmetry factor of 3 × 10-2 at 960 nm. DFT calculations suggest that the long wavelength CD signal for doubly reduced chPDI[2] originates from excitation of the PDI backbone to the π* orbital of the bridging alkene. Importantly, the dimer's molecular contortion facilitates ionic diffusion, enabling chiral switching in solid state films. The high dissymmetry factors and near-infrared response establish chPDI[2] as a unique chiroptic switch.

Type H vessels in osteogenesis, homeostasis, and related disorders.

The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have identified three types of capillaries in the skeletal system. Compared with type L and E vessels, type H vessels express high levels of CD31 and endomucin, and function to couple angiogenesis and osteogenesis. Endothelial cells in type H vessels interact with osteolineage cells (e.g., osteoblasts, osteoclasts, and osteocytes) through cytokines or signaling pathways to maintain bone growth and homeostasis. In imbalanced bone homeostases, such as osteoporosis and osteoarthritis, it may be a new therapeutic strategy to regulate the endothelial cell activity in type H vessels to repair the imbalance. Here, we reviewed the latest progress in relevant factors or signaling pathways in coupling angiogenesis and osteogenesis. This review would contribute to further understanding the role and mechanisms of type H vessels in coupling angiogenic and osteogenic processes. Furthermore, it will facilitate the development of therapeutic approaches for bone disorders by targeting type H vessels.

Selective Detection of Functionalized Carbon Particles based on Polymer Semiconducting and Conducting Devices as Potential Particulate Matter Sensors.

This paper reports a new mechanism for particulate matter detection and identification. Three types of carbon particles are synthesized with different functional groups to mimic the real particulates in atmospheric aerosol. After exposing polymer-based organic devices in organic field effect transistor (OFET) architectures to the particle mist, the sensitivity and selectivity of the detection of different types of particles are shown by the current changes extracted from the transfer curves. The results indicate that the sensitivity of the devices is related to the structure and functional groups of the organic semiconducting layers, as well as the morphology. The predominant response is simulated by a model that yielded values of charge carrier density increase and charge carriers delivered per unit mass of particles. The research points out that polymer semiconductor devices have the ability to selectively detect particles with multiple functional groups, which reveals a future direction for selective detection of particulate matter.

An Electrochemical Strategy to Synthesize Disilanes and Oligosilanes from Chlorosilanes.

Silanes are important compounds in industrial and synthetic chemistry. Here, we develop a general approach for the synthesis of disilanes as well as linear and cyclic oligosilanes via the reductive activation of readily available chlorosilanes. The efficient and selective generation of silyl anion intermediates, which are arduous to achieve by other means, allows for the synthesis of various novel oligosilanes by heterocoupling. In particular, this work presents a modular synthesis for a variety of functionalized cyclosilanes, which may give rise to materials with distinct properties from linear silanes but remain challenging synthetic targets. In comparison to the traditional Wurtz coupling, our method features milder conditions and improved chemoselectivity, broadening the functional groups that are compatible in oligosilane preparation. Computational studies support a mechanism whereby differential activation of sterically and electronically distinct chlorosilanes are achieved in an electrochemically driven radical-polar crossover mechanism.

Poly(cyclosilane) Connectivity Tunes Optical Absorbance.

We report herein the influence of skeletal connectivity on the conformation-dependent optical properties of cyclosilane homo- and copolymers. 1,3-Linked cyclosilanes were bathochromically shifted by 20 nm in solution relative to 1,4-linked cyclosilanes, an effect reproduced by quantum chemical calculations on oligomeric model systems. Polysilane optical properties are conformation-dependent, and 1,3-linked cyclosilanes were hypothesized to adopt a favorable conformation unavailable to 1,4-linked cyclosilanes constrained to an endocyclic gauche conformation. Copolymerization of the isomeric cyclosilanes 1,3Si6 and 1,4Si6 afforded linear statistical copolymers, as characterized by 1H and 29Si NMR spectroscopies. The distinct connectivity of each comonomer was found to give rise to tunable absorption spectra, where the position of the absorption band systematically increased with the increased corporation of 1,3Si6. Computational studies pointed to conformation-dependent changes in orbital symmetry in shifting the most intense transition from the low-energy highest occupied molecular orbital (HOMO) → lowest unoccupied molecular orbital (LUMO) transition to a higher-energy HOMO → LUMO + n transition. The results of these studies demonstrate for the first time the role of silicon skeletal connectivity in controlling conformation and optoelectronic properties and provide new insight into the structure-based design of solution-processable silicon-based polymeric materials.

Azaborine benzylic ion stability and reactivity in ionic polymerization.

Benzylic cations and anions are implicated in the mechanism of critical organic transformations, such as styrene polymerization. We investigate the influence of BN for CC bond substitution on the reactivity of benzylic ions and the effect on BN 2-vinylnaphthalene (BN2VN) ionic polymerization. Calculations suggest that the proximity of a N donor to a cation influences the stability of a BN benzylic cation, rationalizing unsuccessful protonation of BN2VN. Organolithium reagents undergo clean nucleophilic aromatic substitution with BN2VN and related BN naphthalenes via a hypothesized associative mechanism. These results suggest design principles for main group aromatic substitution.

Electron-Dense Deposition Patterns and the Outcomes of Nephrotic Idiopathic Membranous Nephropathy Treated with Tacrolimus in Chinese Adults.

BACKGROUND Tacrolimus may be effective in the short-term treatment of idiopathic membranous nephropathy (IMN). However, it is not clear whether an electron microscopic classification of the homogeneous and heterogeneous types of nephrotic IMN is related to the efficacy of tacrolimus in patients with IMN. This study aimed to explore this question and to provide evidence for individualized patient treatment. MATERIAL AND METHODS This 6-month retrospective study included 61 Chinese patients previously diagnosed with IMN. Patients received treatment was tacrolimus plus glucocorticoid. The patients were divided into a homogeneous group and a heterogeneous group based on the evaluation of electron-dense deposits. The initial clinicopathologic factors in the 2 groups were analyzed, and the difference in efficacy of tacrolimus in the 2 groups was assessed. The factors predicting remission were also studied. RESULTS No significant alteration in the initial clinicopathologic status was found between the 2 groups, except for proteinuria, serum albumin levels, systolic blood pressure, and renal biopsy results (stages I/II/III/IV). After 3 months of treatment, the difference in remission was not significant between the 2 groups. However, after 6 months of treatment, a significant difference in remission rates was observed between the 2 groups. The binary logistic model showed that the homogeneous nephrotic IMN was independently associated with total remission (partial plus complete remission), and was also related to complete remission. CONCLUSIONS The results of our study revealed that the homogeneous type of nephrotic IMN had a higher short-term remission rate and a predictive value for partial or complete remission, and it might be a meaningful marker of the short-term response to tacrolimus.

Modified arteriosclerosis score predicts the outcomes of diabetic kidney disease.

BACKGROUND: The significance of renal arteriosclerosis in the prediction of the renal outcomes of diabetic kidney disease (DKD) remains undetermined. METHODS: We enrolled 174 patients with DKD from three centres from January 2010 to July 2017. The severity and extent of arteriosclerosis were analysed on sections based on dual immunohistochemical staining of CD31 and α-smooth muscle actin. An X-tile plot was used to determine the optimal cut-off value. The primary endpoint was renal survival (RS), defined as the duration from renal biopsy to end-stage renal disease or death. RESULTS: The baseline estimated glomerular filtration rate (eGFR) of 135 qualified patients was 45 (29 ~ 70) ml/min per 1.73 m2, and the average 24-h urine protein was 4.52 (2.45 ~ 7.66) g/24 h. The number of glomeruli in the biopsy specimens was 21.07 ± 9.7. The proportion of severe arteriosclerosis in the kidney positively correlated with the Renal Pathology Society glomerular classification (r = 0.28, P < 0.012), interstitial fibrosis and tubular atrophy (IFTA) (r = 0.39, P < 0.001), urine protein (r = 0.213, P = 0.013), systolic BP (r = 0.305, P = 0.000), and age (r = 0.220, P = 0.010) and significantly negatively correlated with baseline eGFR (r = - 0.285, P = 0.001). In the multivariable model, the primary outcomes were significantly correlated with glomerular class (HR: 1.72, CI: 1.15 ~ 2.57), IFTA (HR: 1.96, CI: 1.26 ~ 3.06) and the modified arteriosclerosis score (HR: 2.21, CI: 1.18 ~ 4.13). After risk adjustment, RS was independently associated with the baseline eGFR (HR: 0.97, CI: 0.96 ~ 0.98), urine proteinuria (HR: 1.10, CI: 1.04 ~ 1.17) and the modified arteriosclerosis score (HR: 2.01, CI: 1.10 ~ 3.67), and the nomogram exhibited good calibration and acceptable discrimination (C-index = 0.82, CI: 0.75 ~ 0.87). CONCLUSIONS: The severity and proportion of arteriosclerosis may be helpful prognostic indicators for DKD.

Detection of sulfadimethoxine using optical images of liquid crystals.

A label-free method for sulfadimethoxine (SDM) detection using an aptamer-based liquid crystal biosensor is developed. The sensor probe is fabricated by immobilizing amine-functionalized aptamers onto the glass slide decorating mixed self-assembled layers of triethoxysilylbutyraldehyde (TEA) and N,N-dimethyl-n-octadecyl-3-aminopropyltrimethoxysilylchloride (DMOAP). Liquid crystals (LCs) are supported on the surface and serve as response elements, which assume the homeotropic alignment and cause a dark optical appearance under crossed polarizers. In the presence of SDM, the formation of SDM-aptamer compounds induces a notable change in the topographical structure of the surface, which disturbs the original homeotropic orientation of LCs and results in a bright optical appearance. A detection limit of 10 µg L-1 is obtained, which is far lower than the maximum residue limit (100 µg L-1 in China). This facile method shows good specificity for SDM detection and may have great potential for detecting other small molecules.

Crystallinity dependency of the time-dependent mechanical response of polyethylene: application in total disc replacement.

Degeneration of the intervertebral disc (IVD) is a leading source of chronic low back pain or neck pain, and represents the main cause of long-term disability worldwide. In the aim to relieve pain, total disc replacement (TDR) is a valuable surgical treatment option, but the expected benefit strongly depends on the prosthesis itself. The present contribution is focused on the synthetic mimic of the native IVD in the aim to optimally restore its functional anatomy and biomechanics, and especially its time-dependency. Semi-crystalline polyethylene (PE) materials covering a wide spectrum of the crystallinity are used to propose new designs of TDR. The influence of the crystallinity on various features of the time-dependent mechanical response of the PE materials is reported over a large strain range by means of dynamic mechanical thermo-analysis and video-controlled tensile mechanical tests. The connection of the stiffness and the yield strength with the microstructure is reported in the aim to propose a model predicting the crystallinity dependency of the response variation with the frequency. New designs of TDR are proposed and implemented into an accurate computational model of a cervical spine segment in order to simulate the biomechanical response under physiological conditions. Predicted in-silico motions are found in excellent agreement with experimental data extracted from published in-vitro studies under compression and different neck movements, namely, rotation, flexion/extension and lateral bending. The simulation results are also criticized by analyzing the local stresses and the predicted biomechanical responses provided by the different prosthetic solutions in terms of time-dependency manifested by the hysteretic behavior under a cyclic movement and the frequency effect.

[Study on a new urine analysis core module based on semi-reflection mirror].

A new urine analysis core module based on high performance 32-bit microprocessor and high precision color sensor was presented. A novel optical structure and a specific circuit were applied to improve measurement precision and temperature was used to compensate for results in this core module. The information of urine test peice, such as all original data and color RGB value, reflectivity, semi-quantitative level, etc. can be output. The results showed that the measuring precision was about 95% or above with ideal stability and reliability using this presented core module, which can be conveniently applied in various urine analyzers, and can greatly decrease the cost of urine analyzers in development and production.

Oxidized ATP Suppresses B Lymphocyte Activity to Attenuate Antibody-mediated Rejection of Kidney Allografts in Mice.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. METHODS: Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. RESULTS: Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. CONCLUSIONS: These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

A multiplex real-time fluorescence-based quantitative PCR assay for calf diarrhea viruses.

Introduction: Calf diarrhea is a significant condition that has a strong effect on the cattle industry, resulting in huge economic losses annually. Bovine torovirus (BToV), bovine enterovirus (BEV), bovine norovirus (BNoV), bovine coronavirus (BCoV), bovine rotavirus (BRV), and bovine viral diarrhea virus (BVDV) are key pathogens that have been implicated in calf diarrhea. Among these viruses, there remains limited research on BToV, BEV, and BNoV, with no available vaccines or drugs for their prevention and control. Although commercial vaccines exist for BCoV, BRV, and BVDV, the prevalence of these diseases remains high. Methods: To address this issue, we developed a multiplex real-time fluorescence quantitative PCR method for detecting BToV, BEV, BNoV, BCoV, BRV, and BVDV. This method can be used to effectively monitor the prevalence of these six viruses and serve as a reference for future prevention and control strategies. In this study, we specifically designed primers and probes for the BNoV Rdrp, BEV 5'UTR, BToV M, BCoV N, BRV NSP5, and BVDV 5'UTR genes. Results: This method was determined to be efficient, stable, and sensitive. The lowest detectable levels of plasmids for BNoV, BEV, BToV, BRV, BCoV, and BVDV were 1.91 copies/µL, 96.0 copies/µL, 12.8 copies/µL, 16.4 copies/µL, 18.2 copies/µL, and 65.3 copies/µL, respectively. Moreover, the coefficients of variation for all six detection methods were < 3%; they also exhibited a strong linear relationship (R2 ≥ 0.98), and an amplification efficiency of 90%-110%. A total of 295 fecal and anal swabs were collected from calves with diarrhea in Guangdong, China. The positive rates for BToV, BEV, BNoV, BCoV, BR, and BVDV were determined to be 0.34% (1/295), 6.10% (18/295), 0.68% (2/295), 1.36% (4/295), 10.85% (32/295), and 2.03% (6/295), respectively. Notably, BEV and BRV exhibited the highest prevalence. Discussion: Additionally, this study identified the occurrence of BToV and BNoV in Guangdong for the first time. In summary, this study successfully established an effective method for detecting several important bovine viruses; ultimately, this holds strong implications for the future development of the cattle industry.

Evaluation of safety and efficacy of the bone marrow mesenchymal stem cell and gelatin-nano-hydroxyapatite combination in canine femoral defect repair.

Femoral shaft fracture is a common bone trauma in dogs. The limitation of mesenchymal stem cells in bone defect applications is that the cell suspension cannot be fixed to the bone defect site. In the study, our objective was to substantiate the combined application of canine bone marrow mesenchymal stem cells (cBMSCs) and gelatin-nano-hydroxyapatite (Gel-nHAP) and evaluate its therapeutic effect on bone defect diseases in dogs. Experiments were performed to evaluate the following: (1) the porosity of Gel-nHAP; (2) the adhesion of cBMSCs to Gel-nHAP; and (3) the effect of Gel-nHAP on cBMSC proliferation. The efficacy and safety of the combination of cBMSC and Gel-nHAP in the repair of femoral shaft defects were evaluated in animal experiments. The results showed that Gel-nHAP supported the attachment of cBMSCs and exhibited good biocompatibility. In the animal bone defect repair experiment, significant cortical bone growth was observed in the Gel-nHAP group at week 8 (p < 0.05) and in the cBMSCs-Gel-nHAP group at week 4 (p < 0.01). We demonstrated that Gel-nHAP could promote the repair of bone defects, and the effect of cBMSC-Gel-nHAP on the repair of bone defects was profound.

Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C.

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation.

Stromal cell-derived factor 1 (SDF-1) is a critical regulator of endothelial progenitor cells (EPCs) mediated physiological and pathologic angiogenesis. It was considered to act via its unique receptor CXCR4 for a long time. CXCR7 is a second, recently identified receptor for SDF-1, and its role in human EPCs is unclear. In present study, CXCR7 was found to be scarcely expressed on the surface of human EPCs derived from cord blood, but considerable intracellular CXCR7 was detected, which differs from that on EPCs derived from rat bone marrow. CXCR7 failed to support SDF-1 induced human EPCs migration, proliferation, or nitric oxide (NO) production, but mediated human EPCs survival exclusively. Besides that, CXCR7 mediated EPCs tube formation along with CXCR4. Blocking CXCR7 with its antagonist CCX733 impaired SDF-1/CXCR4 induced EPCs adhesion to active HUVECs and trans-endothelial migration. Those results suggested that CXCR7 plays an important role in human cord blood derived EPCs in response to SDF-1.

Highly selective addition of cyclosilanes to alkynes enabling new conjugated materials.

Main group organometallic compounds can exhibit unusual optical properties arising from hybrid σ,π-conjugation. While linear silanes are extensively studied, the shortage of methods for the controlled synthesis of well-defined cyclic materials has precluded the study of cyclic conjugation. Herein we report that Ru-catalyzed addition of cyclosilanes to aryl acetylenes (hydrosilylation) proceeds with high chemoselectivity, regioselectivity, and diastereoselectivity, affording complex organosilanes that absorb visible light. We further show that the hydrosilylation products are useful building blocks towards novel conjugated polymers.

Microstructure and Mechanical Properties of Severely Deformed Polypropylene in ECAE (Equal Channel Angular Extrusion) via Routes A and C.

Equal channel angular extrusion (ECAE) is a solid-state extrusion process for modifying microstructures via severe plastic deformation without modifying the specimen cross section. In this study, changes in the microstructure and mechanical properties of polypropylene resulting from extrusion orientation route A (no rotation between extrusions) and extrusion orientation route C (a rotation of 180° between extrusions) are investigated using a 90° die-angle tooling outfitted with back pressure. Important differences are reported for the ECAE-induced deformation behavior between the two processing routes. A focus is made on the occurrence of heterogeneous plastic deformations (periodic shear banding and warping) for both routes and the control and inhibition of the plastic instabilities via regulated back pressure and ram velocity. Wide-angle X-ray scattering is carried out to characterize the structural evolution as a function of the processing conditions including route, extrusion velocity and BP application. The mechanical properties of the specimens machined from the ECAE pieces are examined under different loading paths including uniaxial tension/compression and simple shear. Full-field displacements converted to volumetric strains revealed the profound impacts of the processing route on the deformation mechanisms during tensile deformation.

Cuff Anastomosis of Both Renal Artery and Vein to Minimize Thrombosis: A Novel Method of Kidney Transplantation in Mice.

OBJECTIVES: Anastomosis of renal artery and renal vein in mouse models of kidney transplantation is technically challenging. Conventional technique using suture may result in vascular thrombosis. We developed a simple cuff method to anastomose both renal artery and vein. MATERIALS AND METHODS: Briefly, the left renal artery was occluded at the junction with abdominal aorta using a small vessel clip, transected at the renal hilum, irrigated with heparinized saline, and passed through the lumen of a seamless tubing made of polyimide. The loose end of the artery was everted over the cuff and secured using an 8-0 silk suture. The cuffed artery was inserted into the donor renal artery and secured with an 8-0 suture. Anastomosis of the renal vein was performed similarly. Isograft transplantation was conducted using BALB/c mice as donor and recipient mice (n = 20). The total operative time was 77 ± 3 min, and the cold ischemic time of the graft kidney was minimized to 20 min. One animal was excluded due to anatomic variant vessels and another one died at three day after surgery without thrombosis. RESULTS: Serum creatinine increased insignificantly after transplantation and remained stable over 12 weeks posttransplant. Five recipient mice were sacrificed for histologic examination at 12 weeks after transplantation. No vascular thrombosis was observed at the site of anastomosis. The isografts showed no evidence of acute and chronic lesions such as extinctive ischemic sclerosis and interstitial fibrosis. CONCLUSION: In summary, cuff anastomosis can be used to eliminate thrombosis formation in the mouse model of kidney transplantation.