The landscape of pathophysiology guided therapeutic strategies for gout treatment.

INTRODUCTION: Gout is a common autoinflammatory disease caused by hyperuricemia with acute and/or chronic inflammation as well as tissue damage. Currently, urate-lowering therapy (ULT) and anti-inflammatory therapy are used as first-line strategies for gout treatment. However, traditional drugs for gout treatment exhibit some unexpected side effects and are not suitable for certain patients due to their comorbidity with other chronic disease. AREAS COVERED: In this review, we described the pathophysiology of hyperuricemia and monosodium urate (MSU) crystal induced inflammatory response during gout development in depth and comprehensively summarized the advances in the investigation of promising ULT drugs as well as anti-inflammatory drugs that might be safer and more effective for gout treatment. EXPERT OPINION: New drugs that are developed based on these molecular mechanisms exhibited great efficacy on reduction of disease burden both in vitro and in vivo, implying their potential for clinical application. Moreover, hyperthermia also showed regulation effect on MSU crystals formation and the signaling pathways involved in inflammation.

[Electroacupuncture combined with bone marrow mesenchymal stem cell transplantation promotes repair of thin endometrium by regulating SDF-1/CXCR4 signaling].

OBJECTIVE: It is to explore, based on stromal cell derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis, whether the electroacupuncture (EA) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation can promote thin endometrium regeneration and improve endometrial receptivity, so as to further study its mechanisms underlying improvement of promoting BMSCs homing to repair thin endometrium. METHODS: Thirty matured female SD rats were randomly divided into normal control , model , BMSCs transplantation (BMSCs), BMSCs+AMD3100 (a specific antagonist of CXCR4, BMSCs+AMD3100), BMSCs+EA, and BMSCs+EA+AMD3100 groups, with 5 rats in each group. The thin endometrial model was established by intrauterine injection of 95% ethanol during the period of estrus. Rats of the model group received intravenous injection of PBS solution (tail vein) on day 1, 3 and 7 of modeling and intraperitoneal injection of normal saline once daily for 3 estrous cycles. Rats of the BMSCs group received intravenous injection of BMSCs suspension on day 1,3 and 7 of modeling, and those of the BMSCs+EA group received BMSCs transplantation and EA stimulation. EA (2 Hz/15 Hz, 1 mA) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao"(SP9), "Zigong" (EX-CA1) for 15 min, once daily for 3 estrous cycles. Rats of the BMSCs+AMD3100 group received intravenous injection of BMSCs suspension (1×106/mL) and intraperitoneal injection of AMD3100 (5 mg/kg), and those of the BMSCs+EA+AMD3100 group received administration of BMSCs, AMD3100 and EA, with both groups being once daily for 3 estrous cycles. H.E. staining was used to observe histopathological changes of endometrium tissues, and immunohistochemistry was used to detect the expressions of cytokeratin (CK19) and vimentin in endometrium (for evaluating the damage and repair of endometrium). The expression levels of homeobox A10 (HOXA10), leukemia inhibitory factor (LIF), SDF-1 and CXCR4 proteins were detected by Western blot, and those of SDF-1 and CXCR4 mRNAs in the endometrium detected by real-time PCR. RESULTS: In comparison with the normal control group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression leve-ls of HOXA10, LIF and CXCR4 proteins and CXCR4 mRNA were significantly down-regulated (P<0.01), and the expression levels of SDF-1 protein and mRNA significantly up-regulated (P<0.05) in the model group. Compared with the model group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, and the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs group, and the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA, and SDF-1 protein and mRNA in the BMSCs+EA group were significantly up-regulated (P<0.05, P<0.01). Compared to the BMSCs group, the number of endometrial glands, and the expression levels of LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA group were up-regulated (P<0.01, P<0.05)； the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+AMD3100 group were down-regulated (P<0.01). Compared to the BMSCs+EA group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA+AMD3100 group were down-regulated (P<0.01). Results of H.E. staining showed thin endometrium with absence of epithelial cells, and sparse glands and blood vessels, with smaller glandular cavity in the model group, which was relative milder in BMSCs and BMSCs+EA groups. CONCLUSION: EA can promote the transfer of transplanted BMSCs to the damaged site through SDF-1/CXCR4 signaling related stem cell homing, thereby promoting thin endometrial regeneration, repairing endometrial injury, and improving endometrial tolerance in rats with thin endometrium.

Aptamers: an emerging navigation tool of therapeutic agents for targeted cancer therapy.

Chemotherapeutic agents have been used for the treatment of numerous cancers, but due to poor selectivity and severe systemic side effects, their clinical application is limited. Single-stranded DNA (ssDNA) or RNA aptamers could conjugate with highly toxic chemotherapy drugs, toxins, therapeutic RNAs or other molecules as novel aptamer-drug conjugates (ApDCs), which are capable of significantly improving the therapeutic efficacy and reducing the systemic toxicity of drugs and have great potential in clinics for targeted cancer therapy. In this review, we have comprehensively discussed and summarized the current advances in the screening approaches of aptamers for specific cancer biomarker targeting and development of the aptamer-drug conjugate strategy for targeted drug delivery. Moreover, considering the huge progress in artificial intelligence (AI) for protein and RNA structure predictions, automatic design of aptamers using deep/machine learning techniques could be a powerful approach for rapid and precise construction of biopharmaceutics (i.e., ApDCs) for application in cancer targeted therapy.

Resonant-type inertial impact piezoelectric motor based on a cam locking mechanism.

A new resonant-type inertial impact piezoelectric motor based on a cam locking mechanism was designed, assembled, and tested. The motor is composed of a stator, a rotor, and other auxiliary components. The cam clamping foot of the stator in contact with the inner surface of the rotor forms a cam locking mechanism, which can make the resonant vibration of the stator effective in a half cycle. By receiving sinusoidal signals, the stator generates bending deformation due to the regular deformation of the piezoelectric plate, which drives the cam clamping foot to move and subsequently causes the rotor to rotate. COMSOL5.4 finite element analysis software was used to design the structure of the piezoelectric motor, and an experimental device was built to evaluate and verify the performance of the motor. The maximum no-load speed of the prototype reached 21.61 rpm and the maximum load torque of the motor was 84 N mm under a driving voltage of 360 Vp-p and a driving frequency of 388 Hz. The motor achieved a net efficiency of 5.6% under a preload torque of 2 N mm with the same condition. The maximum resolution of the motion angle of the new motor prototype was 0.0748° with a driving voltage of 160 Vp-p and the same frequency.

Resonant-type piezoelectric linear motor driven by harmonic synthesized mechanical square wave.

In this study, a novel resonant piezoelectric linear motor driven by harmonic synthesized mechanical square waves was designed, fabricated, and tested. The motor consists of a stator, a mover, and auxiliary parts. Periodic square wave motions of the stator and the mover were generated by composing two sinusoidal resonant bending vibrations with a frequency ratio of 1:3. Piezoelectric plates were deformed with a certain regularity to drive the piezoelectric motor. The finite element method software COMSOL was used to design the structure of the motor. An experimental device was established to validate the working principle and evaluate the performance of the motor. The prototype motor reached the maximum no-load velocity of 22.5 mm/s with the stator driven voltage of 140 Vp-p and the mover driven voltage of 180 Vp-p for a base frequency. The maximum traction force of 3.8 N was obtained under a stator driving voltage of 140 Vp-p and a mover driving voltage of 100 Vp-p for the base frequency. The motor achieved a net efficiency of 12.2% with a load of 0.3 N.

Correction to: The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

In the original article, there was some error in Table 2. The correct table is given below.

The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

INTRODUCTION: Small fiber neuropathy (SFN)-the early stage of diabetic peripheral neuropathy (DPN)-progresses gradually and is difficult to diagnose using neurophysiological tests. To facilitate the early diagnosis of SFN, biomarkers for SFN must be identified. The purpose of this study was to investigate the characteristics of SFN in prediabetic patients and the relationship between pNF-H and SFN. METHODS: 44 IGT patients (inpatients and outpatients) were selected at random. 33 healthy subjects served as controls. Data on clinical characteristics and laboratory parameters were collected. Quantitative sensory testing (QST), electromyography (EMG), and Sudoscan were performed, and pNF-H was measured by ELISA. RESULTS: 24 of the 44 patients with impaired glucose tolerance (IGT) were diagnosed with SFN according to the modified Toronto Diabetic Neuropathy Expert Group consensus criteria. The thermal sensory thresholds of the IGT-SFN group were significantly different from those of the CTRL group (p < 0.05), except for the heat pain threshold. The sensory nerve action potential (SNAP) of the sural nerve was 12.39 in the IGT-SFN group, which was significantly lower than those in the other groups. No significant difference in nerve conduction velocity (NCV) was observed among the three groups. The electrochemical skin conductance (ESC) in the IGT-SFN group was 69.78 ± 14.03uS, which was significantly lower than that in the CTRL group. The pNF-H in the IGT-SFN group was 170.6 (140.0, 223.6) pg/ml, which was significantly higher than those in the CTRL and IGT-non-SFN groups (76.55 and 64.7 pg/ml, respectively). Multivariate regression analysis demonstrated that pNF-H and 2h plasma glucose were independently correlated with SFN; the ORs (95% CI) were 1.429 (1.315, 1.924) and 2.375 (1.157, 4.837), respectively. CONCLUSIONS: Serum pNF-H may be associated with SFN in IGT patients, and serum pNF-H could therefore serve as a sensitive biomarker for the detection of SFN.

Inertial piezoelectric linear motor driven by a single-phase harmonic wave with automatic clamping mechanism.

A novel, single-phase, harmonic-driven, inertial piezoelectric linear motor using an automatic clamping mechanism was designed, fabricated, and tested to reduce the sliding friction and simplify the drive mechanism and power supply control of the inertial motor. A piezoelectric bimorph and a flexible hinge were connected in series to form the automatic clamping mechanism. The automatic clamping mechanism was used as the driving and clamping elements. A dynamic simulation by Simulink was performed to prove the feasibility of the motor. The finite element method software COMSOL was used to design the structure of the motor. An experimental setup was built to validate the working principle and evaluate the performance of the motor. The prototype motor outputted a no-load velocity of 3.178 mm/s at a voltage of 220 Vp-p and a maximum traction force of 4.25 N under a preload force of 8 N. The minimum resolution of 1.14 µm was achieved at a driving frequency of 74 Hz, a driving voltage of 50 Vp-p, and a preload force of 0 N.

On the mechanisms of the recurvature of super typhoon Megi.

Tropical cyclones (TC) are one of the most threatening natural hazards to human beings. Although significant improvements have been made in the track prediction of TCs during the past several decades, considerable uncertainties still exist, especially for recurving tracks. In this study, we explore the physical mechanisms that drove the large recurvature of super typhoon Megi through numerical sensitivity experiments using a regional atmospheric model. The results indicate that the cold air intrusion from the northwest to the southeast of China is the main cause of the sharp turning of Megi. This finding suggests that a cold air intrusion could be taken as an indicator for predicting the recurvature of a tropical cyclone in the future.