A neural-mast cell axis regulates skin microcirculation in diabetes.

Changes in microcirculation lead to the progression of organ pathology in diabetes. Although neuroimmune interactions contribute to a variety of conditions, it is still unclear whether abnormal neural activities affect microcirculation related to diabetes. Using laser speckle contrast imaging, we examined the skin of patients with type 2 diabetes and found that their microvascular perfusion was significantly compromised. This phenomenon was recapitulated in a high-fat-diet-driven murine model of type 2 diabetes-like disease. In this setting, although both macrophages and mast cells were enriched in the skin, only mast cells and associated degranulation were critically required for the microvascular impairment. Sensory neurons exhibited enhanced TRPV1 activities, which triggered mast cells to degranulate and compromise skin microcirculation. Chemical and genetic ablation of TRPV1+ nociceptors robustly improve skin microcirculation status. Substance P (SP) is a neuropeptide and was elevated in the skin and sensory neurons in the context of type 2 diabetes. Exogenous administration of SP resulted in impaired skin microcirculation, whereas neuronal knockdown of SP dramatically prevented mast cell degranulation and consequently improved skin microcirculation. Overall, our findings indicate a neural-mast cell axis underlying skin microcirculation disturbance in diabetes and shed light on neuroimmune therapeutics for diabetes-related complications.

Dysregulation of LINC00324 promotes poor prognosis in patients with glioma.

BACKGROUND: LINC00324 is a long-stranded non-coding RNA, which is aberrantly expressed in various cancers and is associated with poor prognosis and clinical features. It involves multiple oncogenic molecular pathways affecting cell proliferation, migration, invasion, and apoptosis. However, the expression, function, and mechanism of LINC00324 in glioma have not been reported. MATERIAL AND METHODS: We assessed the expression of LINC00324 of LINC00324 in glioma patients based on data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify pathways involved in LINC00324-related glioma pathogenesis. RESULTS: Based on our findings, we observed differential expression of LINC00324 between tumor and normal tissues in glioma patients. Our analysis of overall survival (OS) and disease-specific survival (DSS) indicated that glioma patients with high LINC00324 expression had a poorer prognosis compared to those with low LINC00324 expression. By integrating clinical data and genetic signatures from TCGA patients, we developed a nomogram to predict OS and DSS in glioma patients. Gene set enrichment analysis (GSEA) revealed that several pathways, including JAK/STAT3 signaling, epithelial-mesenchymal transition, STAT5 signaling, NF-κB activation, and apoptosis, were differentially enriched in glioma samples with high LINC00324 expression. Furthermore, we observed significant correlations between LINC00324 expression, immune infiltration levels, and expression of immune checkpoint-related genes (HAVCR2: r = 0.627, P = 1.54e-77; CD40: r = 0.604, P = 1.36e-70; ITGB2: r = 0.612, P = 6.33e-7; CX3CL1: r = -0.307, P = 9.24e-17). These findings highlight the potential significance of LINC00324 in glioma progression and suggest avenues for further research and potential therapeutic targets. CONCLUSION: Indeed, our results confirm that the LINC00324 signature holds promise as a prognostic predictor in glioma patients. This finding opens up new possibilities for understanding the disease and may offer valuable insights for the development of targeted therapies.

Laser-Activatable In Situ Vaccine Enhances Cancer-Immunity Cycle.

The immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address a single key aspect to enhance anti-tumor immunity. In the present study, a nanoplatform (Fe3 O4 @IR820@CpG)-based immunotherapy strategy that targets the multiple key steps in cancer-immunity cycle is developed: 1) promotes the release of tumor-derived proteins (TDPs), including tumor-associated antigens and pro-immunostimulatory factors), in addition to the direct killing effect, by photothermal (PTT) and photodynamic therapy (PDT); 2) captures the released TDPs and delivers them, together with CpG (a Toll-like receptor 9 agonist) to antigen-presenting cells (APCs) to promote antigen presentation and T cell activation; 3) enhances the tumor-killing ability of T cells by combining with anti-programmed death ligand 1 antibody (α-PD-L1), which collectively advances the outstanding of the anti-tumor effects on colorectal, liver and breast cancers. The broad-spectrum anti-tumor activity of Fe3 O4 @IR820@CpG with α-PD-L1 demonstrates that optimally manipulating anti-cancer immunity not singly but as a group provides promising clinical strategies.

Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching.

Background: The predictive value of red blood cell distribution width (RDW) for mortality in patients with sepsis-induced acute kidney injury (SI-AKI) remains unclear. The present study aimed to investigate the potential association between RDW at admission and outcomes in patients with SI-AKI. Methods: The Medical Information Mart for Intensive Care (MIMIC)-IV (version 2.0) database, released in June of 2022, provides medical data of SI-AKI patients to conduct our related research. Based on propensity score matching (PSM) method, the main risk factors associated with mortality in SI-AKI were evaluated using Cox proportional hazards regression analysis to construct a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability and clinical utility of this model. Patients with SI-AKI were classified into the high- and low-RDW groups according to the best cut-off value obtained by calculating the maximum value of the Youden index. Results: A total of 7574 patients with SI-AKI were identified according to the filter criteria. Compared with the low-RDW group, the high-RDW group had higher 28-day (9.49% vs. 31.40%, respectively, P <0.001) and 7-day (3.96% vs. 13.93%, respectively, P <0.001) mortality rates. Patients in the high-RDW group were more prone to AKI progression than those in the low-RDW group (20.80% vs. 13.60%, respectively, P <0.001). Based on matched patients, we developed a nomogram model that included age, white blood cells, RDW, combined hypertension and presence of a malignant tumor, treatment with vasopressor, dialysis, and invasive ventilation, sequential organ failure assessment, and AKI stages. The C-index for predicting the probability of 28-day survival was 0.799. Decision curve analysis revealed that the model with RDW offered greater net benefit than that without RDW. Conclusion: The present findings demonstrated the importance of RDW, which improved the predictive ability of the nomogram model for the probability of survival in patients with SI-AKI.

Preparation and characterisation of a novel silk fibroin/hyaluronic acid/sodium alginate scaffold for skin repair.

To mimic the natural structure of tissue extracellular matrix, a novel silk fibroin (SF)/hyaluronic acid (HA)/sodium alginate (SA) composite scaffold (92% in porosity) was prepared by freeze-drying. Fourier-transform infrared spectroscopy and Raman spectra indicated interactions among SF, HA, and SA molecules. Scanning electron microscopy showed that the prepared SF/HA/SA scaffold had soft, elastic characteristics, with an average pore diameter of 93 µm. Mechanical property, thermogravimetric analyses and degradation results indicated that the SF/HA/SA scaffold had good physical stability in body fluid and mechanical movement-related environments. Cell proliferation, morphological, and live-dead analyses showed that NIH-3T3 fibroblast cells were better able to attach, grow, and proliferate on the SF/HA/SA scaffold compared with SF, SF/HA, and SF/SA scaffolds. We evaluated the wound healing effects in a rat full-thickness burn model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results from SF/HA/SA scaffold showed that improved re-epithelialization, enhanced extracellular matrix remodeling. Our findings showed that the prepared SF/HA/SA scaffold can provide a potential way as a wound dressing for skin repair.

Identification of biomarkers associated with progression and prognosis in bladder cancer via co-expression analysis.

BACKGROUND: Bladder cancer is one of the most common genitourinary malignancies, with a high rate of recurrence and progression. The prognosis for patients with bladder cancer, especially muscle-invasive bladder cancer, remains poor despite systemic therapy. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers for bladder cancer. METHODS: Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were applied to identify hub genes correlated with the bladder cancer progression. Survival analyses were then conducted to identify potential biomarkers correlated with the prognosis of bladder cancer. Finally, validation and analysis of these potential biomarkers were conducted by a series of bioinformatics analyses. RESULTS: Based on the results of weighted gene co-expression network analysis and protein-protein interaction network analysis, ten hub genes closely correlated with bladder cancer progression were identified in the relevant module. Survival analyses of these genes indicated that elevated expressions of six potential biomarkers (COL3A1, FN1, COL5A1, FBN1, COL6A1 and THBS2) were significantly associated with a worse overall survival. Furthermore, these 6 potential biomarkers were validated in association with the progression of bladder cancer. Bladder cancer samples with higher expression of these genes were most significantly enriched in gene set associated with ECM-receptor interaction. CONCLUSIONS: This study identified several biomarkers associated with bladder cancer progression and prognosis. As novel findings, these may have important clinical implications for diagnosis, treatment and prognosis prediction.

A Novel Well Drill Assisted with High-Frequency Vibration Using the Bending Mode.

It is important for companies to increase the efficiency of drilling as well as prolong the lifetime of the drilling tool. Since some previous investigations indicated that a superposition of well drilling with an additional vibration increases the drilling efficiency, this paper introduces a novel well drill which is assisted with additional vibrations by means of piezoelectric sandwich bending vibration transducer. The proposed drill uses bending vibrations in two different directions to from an elliptical trajectory movement, which can help the drill to break the surface of hard material more efficiently and clean away the lithic fragments more easily. The proposed well drill with bending vibration transducer is designed to have a resonance frequency of the first bending vibration mode of about 1779 Hz. The motion equation of the particle on the edge of the drill bit is developed and analyzed. The vibration trajectory of the particle on the edge of the drill bit is calculated by using finite element method. A prototype of the proposed drill using bending vibrations is fabricated and tested to verify the aim of drilling efficiency increase. The feed speed of the vibration assisted drilling is tested to be about 0.296 mm/s when the excitation voltage of the transducer is 300 V, while this speed decreases to about 0.195 mm/s when no vibration is added. This comparison shows that the feed speed of the vibration assisted drilling is about 52% higher than that of the normal drilling, which means the proposed drill has a better efficiency and it is important to consider vibration superimposition in well drilling. In addition, the surface of the drill hole gained by the vibration assisted drilling is smoother than that of the normal drilling, which makes the clearance easier.

Development of a bi-directional standing wave linear piezoelectric actuator with four driving feet.

A bi-directional standing wave linear piezoelectric ultrasonic actuator with four driving feet is proposed in this work. Two sandwich type transducers operated in longitudinal-bending hybrid modes are set parallelly. The working mode of the transducer is not simple hybrid vibrations of a longitudinal one and a bending one, but a special coupling vibration mode contained both longitudinal and bending components. Two transducers with the same structure and unsymmetrical boundary conditions are set parallelly to accomplish the bi-directional driving: the first transducer can push the runner forward, while the other one produces the backward driving. In the experiments, two voltages with different amplitudes are applied on the two transducers, respectively: the one with higher voltage serves as the actuator, whereas the other one applied with lower voltage is used to reduce the frictional force. The prototype achieves maximum no-load speed and thrust force of 244 mm/s and 9.8 N. This work gives a new idea for the construction of standing wave piezoelectric ultrasonic actuator with bi-directional driving ability.

Research on a Novel Exciting Method for a Sandwich Transducer Operating in Longitudinal-Bending Hybrid Modes.

A novel exciting method for a sandwich type piezoelectric transducer operating in longitudinal-bending hybrid vibration modes is proposed and discussed, in which the piezoelectric elements for the excitations of the longitudinal and bending vibrations share the same axial location, but correspond to different partitions. Whole-piece type piezoelectric plates with three separated partitions are used, in which the center partitions generate the first longitudinal vibration, while the upper and lower partitions produce the second bending vibration. Detailed comparisons between the proposed exciting method and the traditional one were accomplished by finite element method (FEM) calculations, which were further verified by experiments. Compared with the traditional exciting method using independent longitudinal ceramics and bending ceramics, the proposed method achieves higher electromechanical coupling factors and larger vibration amplitudes, especially for the bending vibration mode. This novel exciting method for longitudinal-bending hybrid vibrations has not changed the structural dimensions of the sandwich transducer, but markedly improves the mechanical output ability, which makes it very helpful and meaningful in designing new piezoelectric actuators operated in longitudinal-bending hybrid vibration modes.

A ring-type multi-DOF ultrasonic motor with four feet driving consistently.

A new type of multiple-degree-of-freedom (multi-DOF) ultrasonic motor was developed aiming at high output torque and compact structure. To reach this purpose, a ring type composite stator was proposed with four driving feet uniformly arranged in the inner circumference of the ring stator. The stator employs two orthogonal axial bending modes and a radial bending mode, by exciting two of them simultaneously, to generate elliptic trajectories on driving feet tips and to push sphere rotor around x, y and z axis respectively. Based on the deduced criteria, a specific combination of the A(0,5) axial bending modes and R(0,2) radial bending mode were chosen to realize that the rotating directions of the elliptical driving trajectories on four feet tips can push the sphere rotor to spin in the same direction consistently, thus the efficiency and output performance will be improved by decreasing the slip between feet and rotor. FEM was used to design the motor including selecting key parameters to tune the resonant frequencies by sensitivity analysis, and a prototype was fabricated and tested. The experiment results showed that the maximum output torque of the motor is 0.118Nm and the maximum speed is 55r/min.

An electromechanical coupling model of a bending vibration type piezoelectric ultrasonic transducer.

An electromechanical coupling model of a bending vibration type piezoelectric ultrasonic transducer is proposed. The transducer is a Langevin type transducer which is composed of an exponential horn, four groups of PZT ceramics and a back beam. The exponential horn can focus the vibration energy, and can enlarge vibration amplitude and velocity efficiently. A bending vibration model of the transducer is first constructed, and subsequently an electromechanical coupling model is constructed based on the vibration model. In order to obtain the most suitable excitation position of the PZT ceramics, the effective electromechanical coupling coefficient is optimized by means of the quadratic interpolation method. When the effective electromechanical coupling coefficient reaches the peak value of 42.59%, the optimal excitation position (L1=22.52 mm) is found. The FEM method and the experimental method are used to validate the developed analytical model. Two groups of the FEM model (the Group A center bolt is not considered, and but the Group B center bolt is considered) are constructed and separately compared with the analytical model and the experimental model. Four prototype transducers around the peak value are fabricated and tested to validate the analytical model. A scanning laser Doppler vibrometer is employed to test the bending vibration shape and resonance frequency. Finally, the electromechanical coupling coefficient is tested indirectly through an impedance analyzer. Comparisons of the analytical results, FEM results and experiment results are presented, and the results show good agreement.

Surface Chemical Gradient Affects the Differentiation of Human Adipose-Derived Stem Cells via ERK1/2 Signaling Pathway.

To understand the role of surface chemistry on cell behavior and the associated molecular mechanisms, we developed and utilized a surface chemical gradient of amine functional groups by carefully adjusting the gas composition of 1,7-octadiene (OD) and allylamine (AA) of the plasma phase above a moving substrate. The chemical gradient surface used in the present work shows an increasing N/C ratio and wettability from the OD side toward the AA side with no change in surface topography. Under standard culture conditions (with serum), human adipose-derived stem cells (hASCs) adhesion and spreading area increased toward the AA side of the gradient. However, there were no differences in cell behavior in the absence of serum. These results, supported by the trends in proteins adsorption on the gradient surface, demonstrated that surface chemistry affects the response of hASCs through cell-adhesive serum proteins, rather than interacting directly with the cells. The expression of p-ERK and the osteogenic differentiation increased toward the AA side of the gradient, while adipogenic differentiation decreased in the same direction; however, when the activation of ERK1/2 was blocked by PD98059, the levels of osteogenic or adipogenic differentiation on different regions of the chemical gradient were the same. This indicates that ERK1/2 may be an important downstream signaling pathway of surface chemistry directed stem cell fate.

Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for skin regeneration.

Inspired from the sophisticated bilayer structures of natural dermis, here, we reported collagen/chitosan based two-compartment and bi-functional dermal scaffolds. Two functions refer to mediating rapid angiogenesis based on recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and rhVEGF encapsulated PLGA microspheres were further combined with collagen/chitosan mixtures in low (lower layer) and high (upper layer) concentrations, and molded to generate the two-compartment and bi-functional scaffolds. Based on morphology and pore structure analyses, it was found that the scaffold has a distinct double layered porous and connective structure with PLGA microspheres encapsulated. Statistical analysis indicated that the pores in the upper layer and in the lower layer have great variations in diameter, indicative of a two-compartment structure. The release profiles of gentamicin and rhVEGF exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts showed that the scaffold can facilitate cell adhesion and proliferation. Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The two-compartment and bi-functional dermal scaffolds can be a promising candidate for skin regeneration.

Accelerated regeneration of skin injury by co-transplantation of mesenchymal stem cells from Wharton's jelly of the human umbilical cord mixed with microparticles.

This study was set to explore a new strategy for repairing skin wounds, co-transplantation of mesenchymal stem cells from Wharton's Jelly of the human umbilical cord (hUC-Wharton's jelly-MSCs) and microparticles. A mixture of hUC-Wharton's jelly-MSCs and microparticles was co-transplanted to 10-mm diameter, full-thickness, mid-dorsal, excisional skin wounds of mice. After 7, 14, and 21 days, the tissue sections were sampled for reconstruction analysis and histological examination. Our results showed that hUC-Wharton's jelly-MSCs possess the potentials for multi-directional differentiation. After co-transplantation, there was remarkable development of newborn skin and its appendages. Newly generated layers of epidermis, sebaceous glands, hair follicle, and sweat glands were observed. This promising innovative strategy could significantly increase the quality of repair and regeneration of skin after injuries.

Continuous renal replacement therapy as a supportive treatment for acute pediatric necrotizing fasciitis.

Acute necrotizing fasciitis (NF) in children is a dangerous illness characterized by progressive necrosis of the skin and subcutaneous tissue. The present study summarizes our recent experience with the treatment of pediatric patients with severe NF. Between 2000 and 2009, eight children suffering from NF were admitted to our department. Four of the children received an active treatment strategy including continuous renal replacement therapy (CRRT), radical debridement, and broad-spectrum antibiotics. Another four children presented at a late stage of illness, and did not complete treatment. Clinical data for these two patient groups were retrospectively analyzed. The four patients that completed CRRT, radical debridement, and a course of broad-spectrum antibiotics were cured without any significant residual morbidity. The other four infants died shortly after admission. Early diagnosis, timely debridement, and aggressive use of broad-spectrum antibiotics are key factors for achieving a satisfactory outcome for cases of acute NF. Early intervention with CRRT to prevent septic shock may also improve patient outcome.

A rectangle-type linear ultrasonic motor using longitudinal vibration transducers with four driving feet.

To make full use of the vibrational energy of a longitudinal transducer, a rectangle-type linear ultrasonic motor with four driving feet is proposed in this paper. This new motor consists of four longitudinal vibration transducers which are arranged in a rectangle and form an enclosed construction. Lead zirconate titanate ceramics are embedded into the middle of the transducer and fastened by a wedge-caulking mechanism. Each transducer includes an exponentially shaped horn located on each end. The horns of the vertical transducers intersect at the base of the horizontal transducers' horns; the tip ends of the horizontal transducers' horns are used as the driving feet. Longitudinal vibrations are superimposed in the motor and generate elliptical movements at the tip ends of the horns. The working principle of the proposed motor is analyzed. The resonance frequencies of two working modes are tuned to be close to each other by adjusting the structural parameters. Transient analysis is developed to gain the vibration characteristics of the motor. A prototype motor is fabricated and measured. The vibration test results verify the feasibility of the proposed design. Typical output of the prototype is a no-load speed of 928 mm/s and maximum thrust force of 60 N at a voltage of 200 Vrms.

A U-shaped linear ultrasonic motor using longitudinal vibration transducers with double feet.

A U-shaped linear ultrasonic motor using longitudinal vibration transducers with double feet was proposed in this paper. The proposed motor contains a horizontal transducer and two vertical transducers. The horizontal transducer includes two exponential shape horns located at the leading ends, and each vertical transducer contains one exponential shape horn. The horns of the horizontal transducer and the vertical transducer intersect at the tip ends where the driving feet are located. Longitudinal vibrations are superimposed in the motor and generate elliptical motions at the driving feet. The two vibration modes of the motor are discussed, and the motion trajectories of driving feet are deduced. By adjusting the structural parameters, the resonance frequencies of two vibration modes were degenerated. A prototype motor was fabricated and measured. Typical output of the prototype is no-load speed of 854 mm/s and maximum thrust force of 40 N at a voltage of 200 V(rms).

A cylindrical standing wave ultrasonic motor using bending vibration transducer.

A cylindrical standing wave ultrasonic motor using bending vibration transducer was proposed in this paper. The proposed stator contains a cylinder and a bending vibration transducer. The two combining sites between the cylinder and the transducer locate at the adjacent wave loops of bending vibration of the transducer and have a distance that equal to the half wave length of bending standing wave excited in the cylinder. Thus, the bending mode of the cylinder can be excited by the bending vibration of the transducer. Two circular cone type rotors are pressed in contact to the end rims of the teeth, and the preload between the rotors and stator is accomplished by a spring and nut system. The working principle of the proposed motor was analyzed. The motion trajectories of teeth were deduced. The stator was designed and analyzed with FEM. A prototype motor was fabricated and measured. Typical output of the prototype is no-load speed of 165rpm and maximum torque of 0.45Nm at an exciting voltage of 200V(rms).

A rotary ultrasonic motor using bending vibration transducers.

A rotary ultrasonic motor using bending vibration transducers is proposed. In each transducer, two orthogonal bending vibrations are superimposed and an elliptical trajectory is generated at the driving foot. Typical output of the prototype is a no-load speed of 58 rpm and maximum torque of 9·5 Nm under an exciting voltage of 200 V(rms).

A high-power linear ultrasonic motor using longitudinal vibration transducers with single foot.

A high-power linear ultrasonic motor using longitudinal vibration transducers with single foot was proposed in this paper. The stator of proposed motor contains a horizontal transducer and a vertical transducer. Longitudinal vibrations are superimposed in the stator and generate an elliptical trajectory at the driving foot. The sensitivity analysis of structural parameters to the resonance frequencies of two working modes of the stator was performed using the finite element method. The resonance frequencies of two working modes were degenerated by adjusting the structural parameters. The vibration characteristics of stator were studied and discussed. A prototype motor was fabricated and measured. Typical output of the prototype is a no-load speed of 1160 mm/s and maximum thrust force of 20 N at a voltage of 200 V(rms).