Propylene glycol alginate sodium sulfate suppressed lung metastasis by blocking P-selectin to recruit CD4 regulatory T cells.

P-selectin has been shown to enhance growth and metastasis of mouse tumors by promoting regulatory T cell (Treg) infiltration into the tumors. Theoretically, a P-selectin antagonist could suppress the process. Popylene glycol alginate sodium sulfate (PSS) is a heparin-like marine drug, which was originally approved to treat cardiovascular disease in China. Previously, we reported that PSS was an effective P-selectin antagonist in vitro. However, it is unknown whether PSS can regulate Treg infiltration and its effect on lung metastasis in vivo. Our results showed that PSS at 30 mg/kg significantly suppressed lung metastasis and improved overall survival, with potency comparable to the positive control LMWH. Mechanistic study indicated that PSS blocked tumor cells adhesion and activated platelets by directly binding with activated platelet's P-selectin. Compared to the model group, PSS decreased the percent of Tregs by 63 % in lungs after treating for 21 days while increasing CD8+ T cells (1.59-fold) and Granzyme B+ CD8 T cells (2.08-fold)' percentage for generating an adaptive response for systemic tumor suppression. The study indicated that the P-selectin antagonist, PSS, suppressed lung metastasis by inhibiting the infiltration of regulatory T cells (Treg) into the tumors.

Pyogenic liver abscess complicated with endogenous endophthalmitis caused by Klebsiella pneumoniae: A case report and Literature Review.

OBJECTIVE: Pyogenic liver abscess (PLA) is a common surgical infectious disease caused by various pathogens. Klebsiella pneumoniae is a relatively recent cause, often affecting patients with low immunity. Endogenous endophthalmitis (EE), a rare and serious complication of PLA, may appear with eye symptoms before PLA. By reviewing a case of Klebsiella pneumoniae-induced PLA complicated with EE, we want to summarize the information about the characteristics, causes, and complications of PLA based on the literature review. METHODS: This case report describes a 37-year-old male who had fever high to 39°C for 10 days experienced blurred vision followed by nonlight perception vision. He reported a history of diabetes irregularly taking oral medications and insulin therapy. Imaging examination found a large low-density area in the right lobe of the liver with an unclear border and vague surrounding fat gap. The blood culture was not positive. The culture of the drainage fluid from the liver puncture showed Klebsiella pneumonia. Blood and liver puncture drainage fluid were sent for microbial high-throughput gene detection with next-generation sequencing technology (NGS), which confirmed the diagnosis of Klebsiella pneumoniae-induced PLA complicated with EE. RESULTS: The patient's surgical incision had healed well at discharge, and he could feel light at his left eye. But the patient was lost to follow-up since the third month after discharge. CONCLUSION: By reviewing this case and summarize the information about the characteristics, causes, and complications of PLA based on the literature review, we concluded that it is necessary to promptly perform liver puncture drainage and empirically use antibiotics for patients with PLA, especially those with poor glycemic control, to avoid serious complications such as EE.

HDAC1 overexpression promoted by METTL3-IGF2BP2 inhibits FGF21 expression in metabolic syndrome-related liver injury.

Metabolic syndrome (MetS) represents a cluster of diseases that includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function. We hypothesized here that histone deacetylase 1 (HDAC1) inhibits fibroblast growth factor 21 (FGF21) expression through histone deacetylation, thereby accentuating liver injury in rats with MetS. MetS rats induced by a high-fat diet were monitored weekly for blood pressure and body weight measurement. The changes of hepatic injury parameters were also measured. The pathological changes in the liver were observed by HE staining and oil red O staining. We found that HDAC1 was increased in the liver of rats with MetS, while sh-HDAC1 reduced blood pressure, body weight, and hepatic injury parameters. Improvement of structural pathological alterations and reduction of lipid deposition were observed after HDAC1 inhibition. Notably, HDAC1 inhibited FGF21 expression through histone deacetylation. The hepatoprotective effects of sh-HDAC1 on rats were reversed by adenovirus-mediated knockdown of FGF21. Moreover, methyltransferase-like 3 (METTL3) mediated the N6-methyladenosine (m6A) modification of HDAC1 mRNA and increased its binding to IGF2BP2. Consistently, sh-METTL3 inhibited HDAC1 and increased FGF21 expression, thereby ameliorating liver injury in MetS rats. This study discovered that HDAC1 is capable of managing liver injury in MetS. Targeting HDAC1 may be an optimal treatment for MetS-related liver injury.

Emerging biotransduction strategies on soft interfaces for biosensing.

As a lab-on-soft biochip providing accurate and timely biomarker information, wearable biosensors can satisfy the increasing demand for intelligent e-health services, active disease diagnosis/therapy, and huge bioinformation data. As biomolecules generally could not directly produce detectable signals, biotransducers that specifically convert biomolecules to electrical or optical signals are involved, which determines the pivotal sensing performance including 3S (sensitivity, selectivity, and stability), reversibility, etc. The soft interface poses new requirements for biotransducers, especially equipment-free, facile operation, mechanical tolerance, and high sensing performance. In this review, we discussed the emerging electrochemical and optical biotransduction strategies on wearables from the aspects of the transduction mechanism, amplification strategies, biomaterial selection, and device fabrication procedures. Challenges and perspectives regarding future biotransducers for monitoring trace amounts of biomolecules with high fidelity, sensitivity, and multifunctionality are also discussed. It is expected that through fusion with functional electronics, wearable biosensors can provide possibilities to further decentralize the healthcare system and even build biomolecule-based intelligent cyber-physical systems and new modalities of cyborgs.

Correlations of cardiovascular autonomic neuropathy with urinary albumin excretion rate and cardiac function in patients with type 2 diabetes mellitus.

BACKGROUND: The associations of cardiovascular autonomic neuropathy (CAN) with diabetic nephropathy and heart disease remain elusive. The aim of this study was to explore the correlations of CAN with urinary albumin excretion rate (UAER) and cardiac function in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 225 T2DM patients were assigned into CAN and non-CAN groups using cardiovascular reflex tests (CARTs). They were divided into macroalbuminuria, microalbuminuria and normoalbuminuria groups according to urinary albumin/creatinine ratio (UACR), or left ventricular diastolic dysfunction and normal groups based on left ventricular peak E/A velocity ratio (E/A). The correlations of CAN with albuminuria and left ventricular diastolic dysfunction, and the predictive values of UACR and E/A were analyzed. RESULTS: Compared with non-CAN group, CAN group had older age, longer T2DM duration, higher serum urine acid (SUA) level, UACR, systolic and diastolic pressure differences between supine and standing positions, and lower other CARTs parameters and E/A (P<0.001). Macroalbuminuria group had largest positional systolic and diastolic pressure differences, and lowest other CARTs parameters (P<0.001). Compared with normal group, left ventricular diastolic dysfunction group had larger positional systolic and diastolic pressure differences, and lower other CARTs parameters (P<0.001). CAN in T2DM patients was positively correlated with albuminuria and left ventricular diastolic dysfunction (P<0.001). Age, SUA, UACR and E/A were independent predictive factors (P=0.031, 0.005, <0.001, <0.001). UACR and E/A had high predictive values. CONCLUSIONS: In T2DM patients, CAN is positively correlated with declined UAER and cardiac function. UACR and E/A have high predictive values.

Fabricating of high-performance functional graphene fibers for micro-capacitive energy storage.

Although graphene is a typical two dimensional materials, it has converted to multi-dimensional materials with many unique properties. As an example, the one dimensional graphene fiber is fabricated by utilizing ionic liquid as coagulation and functional diamines as cross-linkers to connect graphene oxide layers. The fibers show excellent mechanical properties and superior electrical performance. The tensile strength of the resultant fibers reaches ~729 MPa after a super high temperature thermal annealing treatment at 2800 °C. Additionally, quasi-solid-state flexible micro-capacitors are fabricated with promising result on energy storage. The device show a specific volumetric capacity as high as ~225 F/cm(3) (measured at 103.5 mA cm(-3) in a three-electrode cell), as well as a long cycle life of 2000 times. The initial results indicate that these fibers will be a good candidate to replace energy storage devices for miniaturized portable electronic applications.

Fabrication of high-quality graphene oxide nanoscrolls and application in supercapacitor.

We reported a simple and effective way of fabricating one-dimensional (1D) graphene oxide nanoscrolls (GONS) from graphene oxide (GO) sheets through shock cooling by liquid nitrogen. The corresponding mechanism of rolling was proposed. One possibility is the formation of ice crystals during the shock cooling process in liquid nitrogen to be the driving force. The other might be due to the uneven stress of the sheets inside or outside ice during the lyophilization. After reducing, graphene nanoscrolls (GNS) exhibited good structural stability, high specific surface area, and high specific capacitance. The capacitance properties were investigated by cyclic voltammetry, galvanostatic charge-discharge, and electrical impedance spectroscopy. A specific capacity of 156 F/g for the GNS at the current density of 1.0 A/g was obtained comparing with the specific capacity of 108 F/g for graphene sheets. Those results indicated that GNS-based rolling structure could be a kind of promising electrode material for supercapacitors and batteries.

Controllable size-selective method to prepare graphene quantum dots from graphene oxide.

We demonstrated one-step method to fabricate two different sizes of graphene quantum dots (GQDs) through chemical cutting from graphene oxide (GO), which had many advantages in terms of simple process, low cost, and large scale in manufacturing with higher production yield comparing to the reported methods. Several analytical methods were employed to characterize the composition and morphology of the resultants. Bright blue luminescent GQDs were obtained with a produced yield as high as 34.8%. Moreover, how the different sizes affect fluorescence wavelength mechanism was investigated in details.

[Clinical factors relating to the arterial elastic function measured by PWV, C1/C2 and AI in hypertensive patients].

OBJECTIVE: To analyze the clinical factors relating to arterial elastic function measured with pulse wave velocity (PWV), large and small arterial elastic indexes (C(1) and C(2)) and augmentation index (AI) in hypertensive patients. METHODS: A total of 2176 hypertensive patients were enrolled and divided into three groups: Elastic function was measured in 1100 subjects by (PWV), in 647 subjects by C(1) and C(2) and in 429 by AI. RESULTS: PWV was positively correlated with age, systolic pressure, pulse pressure and negatively correlated with body height and weights (all P < 0.05). C(1) and C(2) values were higher in male than that in female patients (P < 0.01) and negatively correlated with age, systolic pressure, pulse pressure and heart rate while positively correlated with body height, weight and body mass index. In hypercholesterolemia patients (n = 168), C(1) and C(2) were negatively correlated with serum cholesterol level (P < 0.05). AI value was higher in female than that in male patients (P < 0.01) and positively correlated with age, systolic pressure, diastolic pressure, pulse pressure while negatively correlated with body height, weight and heart rate. CONCLUSION: Age, systolic and pulse pressure as well as body height and weights are the main factors correlated to arterial elastic function measured by PWV, C(1) and C(2) and AI.