A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid.

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.

Interface-Stabilized Fiber Sensor for Real-Time Monitoring of Amniotic Fluid During Pregnancy.

Diseases in pregnancy endanger millions of fetuses worldwide every year. The onset of these diseases can be early warned by the dynamic abnormalities of biochemicals in amniotic fluid, thus requiring real-time monitoring. However, when continuously penetrated by detection devices, the amnion is prone to loss of robustness and rupture, which is difficult to regenerate. Here, an interface-stabilized fiber sensor is presented for real-time monitoring of biochemical dynamics in amniotic fluid during pregnancy. The sensor is seamlessly integrated into the amnion through tissue adhesion, amniotic regeneration, and uniform stress distribution, posing no risk to the amniotic fluid environment. The sensor demonstrates a response performance of less than 0.3% fluctuation under complex dynamic conditions and an accuracy of more than 98% from the second to the third trimester. By applying it to early warning of diseases such as intrauterine hypoxia, intrauterine infection, and fetal growth restriction, fetal survival increases to 95% with timely intervention.

A Mitochondrion-Inspired Magnesium-Oxygen Biobattery with High Energy Density In Vivo.

Implantable batteries are urgently needed as a power source to meet the demands of the next generation of biomedical electronic devices. However, existing implantable batteries suffer from unsatisfactory energy density, hindering the miniaturization of these devices. Here, a mitochondrion-inspired magnesium-oxygen biobattery that achieves both high energy density and biocompatibility in vivo is reported. The resulting biobattery exhibits a recorded energy density of 2517 Wh L-1 /1491 Wh kg-1 based on the total volume/mass of the device in vivo, which is ≈2.5 times higher than the current state-of-the-art, and can adapt to different environments for stable discharges. The volume of the magnesium-oxygen biobattery can be as thin as 0.015 mm3 and can be scaled up to 400 times larger without reducing the energy density. Additionally, it shows a stable biobattery/tissue interface, significantly reducing foreign body reactions. This work presents an effective strategy for the development of high-performance implantable batteries.

Implantable Zinc-Oxygen Battery for In Situ Electrical Stimulation-Promoted Neural Regeneration.

Electrical stimulation is a promising strategy for treating neural diseases. However, current energy suppliers cannot provide effective power for in situ electrical stimulation. Here, an implantable tubular zinc-oxygen battery is reported as the power source for in situ electrical stimulation during the neural repair. The battery exhibited a high volumetric energy density of 231.4 mWh cm-3 based on the entire anode and cathode in vivo. Due to its superior electrochemical properties and biosafety, the battery can be directly wrapped around the nerve to provide in situ electrical stimulation with a minimal size of 0.86 mm3 . The cell and animal experiments demonstrated that the zinc-oxygen battery-based nerve tissue engineering conduit effectively promoted regeneration of the injured long-segment sciatic nerve, proving its promising applications for powering implantable neural electronics in the future.

Diagnostic efficiency on ultrasound shear wave elastography in evaluation of steatosis severity for non-alcoholic fatty liver disease: a rat model.

BACKGROUND: The pathological feature of steatosis affects the elasticity values measured by shear wave elastography (SWE) is still controversial in non-alcoholic fatty liver disease (NAFLD). The aim of this study is to demonstrate the influence of steatosis on liver stiffness measured by SWE on a rat model with NAFLD and analyze feasibility of SWE for grading steatosis in absence of fibrosis. METHODS: Sixty-six rats were fed with methionine choline deficient diet or standard diet to produce various stages of steatosis; 48 rats were available for final analysis. Rats underwent abdominal ultrasound SWE examination and pathological assessment. Liver histopathology was analyzed to assess the degree of steatosis, inflammation, ballooning, and fibrosis according to the non-alcoholic fatty liver disease activity score. The diagnostic performance of SWE for differentiating steatosis stages was estimated according to the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was conducted to determine clinical usefulness and the areas under DCA (AUDCAs) calculated. RESULTS: In multivariate analysis, steatosis was an independent factor affecting the mean elastic modules (B = 1.558, P < 0.001), but not inflammation (B = - 0.031, P = 0.920) and ballooning (B = 0.216, P = 0.458). After adjusting for inflammation and ballooning, the AUROC of the mean elasticity for identifying S ≥ S1 was 0.956 (95%CI: 0.872-0.998) and the AUDCA, 0.621. The AUROC for distinguishing S ≥ S2 and S = S3 was 0.987 (95%CI: 0.951-1.000) and 0.920 (95%CI: 0.816-0.986) and the AUDCA was 0.506 and 0.256, respectively. CONCLUSIONS: Steatosis is associated with liver stiffness and SWE may have the feasibility to be introduced as an assistive technology in grading steatosis for patients with NAFLD in absence of fibrosis.

How Does Government Efficiency Affect Health Outcomes? The Empirical Evidence from 156 Countries.

This paper uses the unbalanced panel data of 156 countries during the period of 2002 to 2018 to explore the possible impact of government efficiency on health outcomes. Firstly, we used the fixed-effect model to examine the relationship between government efficiency and health outcomes and found that the increase in government efficiency can significantly improve health outcomes. Then, a series of robustness checks were carried out, which confirmed the reliability of the above result. Thirdly, this paper conducted a heterogeneity analysis from the perspective of life cycle. Fourthly, this paper investigated the mechanisms of the impact of government efficiency on health outcomes from the perspectives of economic growth, health innovation, education and corruption control. Finally, this paper studied the moderating effects of the ruling party's ideology and democracy on the relationship between government efficiency and health outcomes. The findings of this study provide some references for governments to improve health outcomes.

A Tissue-Like Soft All-Hydrogel Battery.

To develop wearable and implantable bioelectronics accommodating the dynamic and uneven biological tissues and reducing undesired immune responses, it is critical to adopt batteries with matched mechanical properties with tissues as power sources. However, the batteries available cannot reach the softness of tissues due to the high Young's moduli of components (e.g., metals, carbon materials, conductive polymers, or composite materials). The fabrication of tissue-like soft batteries thus remains a challenge. Here, the first ultrasoft batteries totally based on hydrogels are reported. The ultrasoft batteries exhibit Young's moduli of 80 kPa, perfectly matching skin and organs (e.g., heart). The high specific capacities of 82 mAh g-1 in all-hydrogel lithium-ion batteries and 370 mAh g-1 in all-hydrogel zinc-ion batteries at a current density of 0.5 A g-1 are achieved. Both high stability and biocompatibility of the all-hydrogel batteries have been demonstrated upon the applications of wearable and implantable. This work illuminates a pathway for designing power sources for wearable and implantable electronics with matched mechanical properties.

An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria.

Scorpion venoms are rich resources of antimicrobial peptides (AMPs). While the short-chain noncysteine-containing AMPs have attracted much attention as templates for drug development, the antimicrobial potential of long-chain noncysteine-containing AMPs has been largely overlooked. Here, by using the online HeliQuest server, we designed and analyzed a series of 14-residue fragments of Smp43, a 43-residue long-chain noncysteine-containing AMP identified from the venom of Scorpio maurus palmatus. We found that Smp43(1-14) shows high antimicrobial activity against both Gram-positive and Gram-negative bacteria and is nontoxic to mammalian cells at the antimicrobial dosage. Sequence alignments showed that the designed Smp43(1-14) displays a unique primary structure that is different from other natural short-chain noncysteine-containing AMPs from scorpions, such as Uy17, Uy192 and IsCT. Moreover, the peptide Smp43(1-14) caused concentration-dependent fluorescence increases in the bacteria for all of the tested dyes, propidium iodide, SYTOXTM Green and DiSC3-5, suggesting that the peptide may kill the bacteria through the formation of pore structures in the plasma membrane. Taken together, our work sheds light on a new avenue for the design of novel short-chain noncysteine-containing AMPs and provides a good peptide template with a unique sequence for the development of novel drugs for use against bacterial infectious diseases.

Two new cationic α-helical peptides identified from the venom gland of Liocheles australasiae possess antimicrobial activity against methicillin-resistant staphylococci.

Methicillin-resistant staphylococci have become growing threats to human health, and novel antimicrobials are urgently needed. Natural antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics. Here, two novel cationic α-helical antimicrobial peptides, Lausporin-1 and Lausporin-2, were identified from the venom gland of the scorpion L. australasiae through a cDNA library screening strategy. Biochemical analyses demonstrated that Lausporin-1 and Lausporin-2 are cationic α-helical amphipathic molecules. Antimicrobial assays demonstrated that the two peptides possess antibacterial activities against several species of antibiotic-resistant staphylococci. Importantly, they are active against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus capitis, with the minimum inhibitory concentrations ranging from 2.5 to 10 µg/ml. Moreover, both peptides can induce dose-dependent plasma membrane disruptions of the bacteria. In short, our work expands the knowledge of the scorpion L. australasiae venom-derived AMPs and sheds light on the potential of Lausporin-1 and Lausporin-2 in the development of novel drugs against methicillin-resistant staphylococci.

Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer.

PURPOSE: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. METHODS: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. RESULTS: The median follow-up time was 57 months and the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with blood type A had a poorer 5-year OS than patients with blood type non-A (55.0% vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs. 62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was significantly associated with OS than those with non-A types (hazard ratio (HR) 2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A remained an independent prognostic factor for OS than those with non-A blood types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002). CONCLUSION: ABO blood group is associated with survival in patients with ovarian cancer, patients with blood type A had a significantly worse OS than patients with non-A blood types, especially in patients with age > 50 years.

Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

OBJECTIVES: The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node. METHODS: We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients). RESULTS: The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients. CONCLUSIONS: PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.