Accurate Detection of G-Series Agent Simulants by Pseudo-Multiple Reaction Monitoring on Miniature LIT-MS.

Rapid and accurate on-site detection of chemical warfare agents (CWAs) could defend military and civilian populations against current and emerging chemical weapons. With the development of ambient ionization and linear ion trap technology, the rapid and accurate quantitative determination method of CWAs based on direct ionization and multistage mass spectrometry has attracted widespread attention. In this study, a microliter electrospray ionization-miniature linear ion trap mass spectrometry (LIT-MS) instrument was designed and constructed, and the effects of quadrupole enhanced dipole resonance excitation on the resolution and sensitivity were investigated; consequently, the parameters of CWAs detection were optimized. Based on the broad time-frequency ion excitation technology, accurate multiple reaction monitoring (MRM) quantitative analysis of DMMP (G-series agent simulants, m/z 125 → m/z 93) was obtained. The linear correlation coefficient in the concentration range of 1 to 20 µg/mL could reach 99.02%, and the relative standard deviations (RSD) of continuous repeatability, interday repeatability, and intraday repeatability were all less than 10%. The results showed that the accurate pseudo-MRM detection method based on miniature linear ion trap mass spectrometry for CWAs detection was feasible.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence.

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.

Clinical Approach to Inconclusive Subscapularis Tear Diagnosis: a Meta-analysis.

To identify factors associated with subscapularis (SSC) tears and provide a theoretical basis for clinical diagnosis, we included studies related to subscapularis tears published before February 1, 2023. We screened for six predictors across previous studies for the meta-analysis. The predictors included age, sex, coracoid overlap (CO), coracohumeral distance (CHD), impairment of the long head of the biceps tendon (LHB), and dominant arm. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. The risk ratios (RRs) and the weighted mean differences (WMDs) were used to evaluate the effect size of categorical variables and continuous variables, respectively. The Egger test was used to assess the publication bias of the studies. Ten studies were included from seven countries. A total of 2 126 patients were enrolled, of whom 1 041 had subscapularis tears and 1 085 did not. The study showed that age (WMD, 4.23 [95% CI, 2.32-6.15]; P<.00001), coracoid overlap (WMD, 1.98 [95% CI, 1.55-2.41]; P<.00001), coracohumeral distance(WMD, -1.03 [95% CI, -1.17- -0.88]; P<.00001), and an injury of the long head of the biceps tendon (RR, 4.98 [95% CI, 3.75-6.61]; P<.00001) were risk factors for subscapularis tears. These risk factors can help clinicians identify subscapularis tears early and select appropriate interventions. The level of evidence is 3.

Photothermal Carbon Dots Chelated Hydroxyapatite Filler: High Photothermal Conversion Efficiency and Enhancing Adhesion of Hydrogel.

The synthesis of photothermal carbon/hydroxyapatite composites poses challenges due to the binding modes and relatively low photothermal conversion efficiency. To address these challenges, the calcium ions chelated by photothermal carbon dots (PTC-CDs) served as the calcium source for the synthesis of photothermal carbon dots chelated hydroxyapatite (PTC-HA) filler via the coprecipitation method. The coordination constant K and chelation sites of PTC-HA were 7.20 × 102 and 1.61, respectively. Compared to PTC-CDs, the coordination constant K and chelation sites of PTC-HA decreased by 88 and 35% due to chelating to hydroxyapatite, respectively. PTC-HA possesses fluorescence and photothermal performance with a 62.4% photothermal conversion efficiency. The incorporation of PTC-HA filler significantly enhances as high as 76% the adhesion performance of the adhesive hydrogel. PTC-HA with high photothermal conversion efficiency and enhancing adhesion performance holds promise for applications in high photothermal conversion efficiency, offering tissue adhesive properties and fluorescence capabilities to the hydrogel.

EGTA-Derived Carbon Dots with Bone-Targeting Ability: Target-Oriented Synthesis and Calcium Affinity.

The bone-targeting mechanism of clinic bisphosphonate-type drugs, such as alendronate, risedronate, and ibandronate, relies on chelated calcium ions on the surface of the bone mineralized matrix for the treatment of osteoporosis. EGTA with aminocarboxyl chelating ligands can specifically chelate calcium ions. Inspired by the bone-targeting mechanism of bisphosphonates, we hypothesize that EGTA-derived carbon dots (EGTA-CDs) hold bone-targeting ability. For the target-oriented synthesis of EGTA-CDs and to endow CDs with bone targeting, we designed calcium ion chelating agents as precursors, including aminocarboxyl chelating agents (EGTA and EDTA) and bisphosphonate agents (ALN and HEDP) for the target-oriented synthesis of aminocarboxyl-derived CDs (EGTA-CDs and EDTA-CDs) and bisphosphonate-derived CDs (ALN-CDs and HEDP-CDs) with high synthetic yield. The synthetic yield of EGTA-CDs reached 87.6%. Aminocarboxyl-derived CDs and bisphosphonate-derived CDs retain the chelation ability of calcium ions and can specifically bind calcium ions. The chemical environment bone-targeting value coordination constant K and chelation sites of EGTA-CDs were 6.48 × 104 M-1 and 4.12, respectively. A novel method was established to demonstrate the bone-targeting capability of chelate-functionalized carbon dots using fluorescence quenching in a simulated bone trauma microenvironment. EGTA-CDs exhibit superior bone-targeting ability compared with other aminocarboxyl-derived CDs and bisphosphonate-derived CDs. EGTA-CDs display exceptional specificity toward calcium ions and better bone affinity than ALN-CDs, suggesting their potential as novel bone-targeting drugs. EGTA-CDs with strong calcium ion chelating ability have calcium ion affinity in simulated body fluid and bone-targeting ability in a simulated bone trauma microenvironment. These findings offer new avenues for the development of advanced bone-targeting strategies.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.

Cortical microvascular blood flow velocity mapping by combining dynamic light scattering optical coherence tomography and two-photon microscopy.

Significance: The accurate large-scale mapping of cerebral microvascular blood flow velocity is crucial for a better understanding of cerebral blood flow (CBF) regulation. Although optical imaging techniques enable both high-resolution microvascular angiography and fast absolute CBF velocity measurements in the mouse cortex, they usually require different imaging techniques with independent system configurations to maximize their performances. Consequently, it is still a challenge to accurately combine functional and morphological measurements to co-register CBF speed distribution from hundreds of microvessels with high-resolution microvascular angiograms. Aim: We propose a data acquisition and processing framework to co-register a large set of microvascular blood flow velocity measurements from dynamic light scattering optical coherence tomography (DLS-OCT) with the corresponding microvascular angiogram obtained using two-photon microscopy (2PM). Approach: We used DLS-OCT to first rapidly acquire a large set of microvascular velocities through a sealed cranial window in mice and then to acquire high-resolution microvascular angiograms using 2PM. The acquired data were processed in three steps: (i) 2PM angiogram coregistration with the DLS-OCT angiogram, (ii) 2PM angiogram segmentation and graphing, and (iii) mapping of the CBF velocities to the graph representation of the 2PM angiogram. Results: We implemented the developed framework on the three datasets acquired from the mice cortices to facilitate the coregistration of the large sets of DLS-OCT flow velocity measurements with 2PM angiograms. We retrieved the distributions of red blood cell velocities in arterioles, venules, and capillaries as a function of the branching order from precapillary arterioles and postcapillary venules from more than 1000 microvascular segments. Conclusions: The proposed framework may serve as a useful tool for quantitative analysis of large microvascular datasets obtained by OCT and 2PM in studies involving normal brain functioning, progression of various diseases, and numerical modeling of the oxygen advection and diffusion in the realistic microvascular networks.

Differential reductions in the capillary red-blood-cell flux between retina and brain under chronic global hypoperfusion.

Significance: It has been hypothesized that abnormal microcirculation in the retina might predict the risk of ischemic damages in the brain. Direct comparison between the retinal and the cerebral microcirculation using similar animal preparation and under similar experimental conditions would help test this hypothesis. Aim: We investigated capillary red-blood-cell (RBC) flux changes under controlled conditions and bilateral-carotid-artery-stenosis (BCAS)-induced hypoperfusion, and then compared them with our previous measurements performed in the brain. Approach: We measured capillary RBC flux in mouse retina with two-photon microscopy using a fluorescence-labeled RBC-passage approach. Key physiological parameters were monitored during experiments to ensure stable physiology. Results: We found that under the controlled conditions, capillary RBC flux in the retina was much higher than in the brain (i.e., cerebral cortical gray matter and subcortical white matter), and that BCAS induced a much larger decrease in capillary RBC flux in the retina than in the brain. Conclusions: We demonstrated a two-photon microscopy-based technique to efficiently measure capillary RBC flux in the retina. Since cerebral subcortical white matter often exhibits early pathological developments due to global hypoperfusion, our results suggest that retinal microcirculation may be utilized as an early marker of brain diseases involving global hypoperfusion.

Intelligent convolution neural network-assisted SERS to realize highly accurate identification of six pathogenic Vibrio.

Based on label-free SERS technology, the relationship between the Raman signals of pathogenic Vibrio microorganisms and purine metabolites was analyzed in detail. A deep learning CNN model was successfully developed, achieving a high accuracy rate of 99.7% in the identification of six typical pathogenic Vibrio species within 15 minutes, providing a new method for pathogen identification.

Incidence and predictors of postoperative acute kidney injury in older adults with hip fractures.

OBJECTIVES: Main Purpose: To clarify the incidence and predictors of acute kidney injury (AKI) after hip fracture surgery; Secondary Purpose: To investigate the impact of AKI on the length of stay (LOS) and mortality of patients. METHODS: We retrospectively evaluated data from 644 hip fracture patients at Peking University First Hospital from 2015 to 2021, and divided the patients into AKI and Non-AKI groups according to whether AKI occurred after surgery. Logistic regression was used to clarify the risk factors for AKI, draw ROC curves, and analyze the odds ratio (OR) for LOS and death at 30 days, 3 months, and 1 year for patients with AKI. RESULTS: The prevalence of AKI after hip fracture was 12.1%. Age, BMI, and postoperative brain natriuretic peptide (BNP) levels were risk factors for AKI after hip fracture surgery. The risk of AKI in underweight patients, overweight patients and obese patients was 2.24, 1.89, and 2.58 times. Compared to patients with BNP levels <800 pg/ml, the risk of AKI was 22.34-fold for postoperative BNP levels>1500 pg/ml. The risk of a one-grade increase in LOS was 2.84 times higher in the AKI group and the mortality of patients with AKI were higher. CONCLUSION: The incidence of AKI after hip fracture surgery was 12.1%. Advanced age, low BMI, and postoperative high level BNP were risk factors for AKI. Surgeons need to pay more attention to patients with older age, low BMI and high postoperative BNP levels in order to proactively prevent the development of postoperative AKI.

Measurements of cerebral microvascular blood flow, oxygenation, and morphology in a mouse model of whole-brain irradiation-induced cognitive impairment by two-photon microscopy and optical coherence tomography: evidence for microvascular injury in the cerebral white matter.

Whole-brain irradiation (WBI, also known as whole-brain radiation therapy) is a mainstay treatment modality for patients with multiple brain metastases. It is also used as a prophylactic treatment for microscopic tumors that cannot be detected by magnetic resonance imaging. WBI induces a progressive cognitive decline in ~ 50% of the patients surviving over 6 months, significantly compromising the quality of life. There is increasing preclinical evidence that radiation-induced injury to the cerebral microvasculature and accelerated neurovascular senescence plays a central role in this side effect of WBI. To better understand this side effect, male C57BL/6 mice were first subjected to a clinically relevant protocol of fractionated WBI (5 Gy, two doses per week, for 4 weeks). Nine months post the WBI treatment, we applied two-photon microscopy and Doppler optical coherence tomography to measure capillary red-blood-cell (RBC) flux, capillary morphology, and microvascular oxygen partial pressure (PO2) in the cerebral somatosensory cortex in the awake, head-restrained, WPI-treated mice and their age-matched controls, through a cover-glass-sealed chronic cranial window. Thanks to the extended penetration depth with the fluorophore - Alexa680, measurements of capillary blood flow properties (e.g., RBC flux, speed, and linear density) in the cerebral subcortical white matter were enabled. We found that the WBI-treated mice exhibited a significantly decreased capillary RBC flux in the white matter. WBI also caused a significant reduction in capillary diameter, as well as a large (although insignificant) reduction in segment density at the deeper cortical layers (e.g., 600-700 µm), while the other morphological properties (e.g., segment length and tortuosity) were not obviously affected. In addition, we found that PO2 measured in the arterioles and venules, as well as the calculated oxygen saturation and oxygen extraction fraction, were not obviously affected by WBI. Lastly, WBI was associated with a significant increase in the erythrocyte-associated transients of PO2, while the changes of other cerebral capillary PO2 properties (e.g., capillary mean-PO2, RBC-PO2, and InterRBC-PO2) were not significant. Collectively, our findings support the notion that WBI results in persistent cerebral white matter microvascular impairment, which likely contributes to the WBI-induced brain injury and cognitive decline. Further studies are warranted to assess the WBI-induced changes in brain tissue oxygenation and malfunction of the white matter microvasculature as well.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.

Baseline oxygen consumption decreases with cortical depth.

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase-the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.

Surface configuration of microarc oxidized Ti with regionally loaded chitosan hydrogel containing ciprofloxacin for improving biological performance.

The bacterial colonization and poor osseointegration of Ti implants significantly compromise their applications in load-bearing bone repair and replacement. To endorse the Ti with both excellent bioactivity and antibacterial ability, we developed a microarc oxidation coating that was modified uniformly by hydroxyapatite (HA) nanodots arrays and loaded regionally with chitosan hydrogel containing ciprofloxacin. The bonding between the HA nanodots covered coating and the chitosan hydrogel is further enhanced via silanization and chemical grafting of glutaraldehyde. Benefiting from the regionally loaded structure of the chitosan hydrogel, the chitosan hydrogel unloaded area can promote the cell adhesion and proliferation with excellent bioactivity, though relatively low OD value of cck8 has been observed at the beginning of the cell culturing. Whereas, the OD value of cck8 rises with the prolongation of the cell culturing time due to the degradation of the regionally loaded chitosan hydrogel. With the help of the laden ciprofloxacin in chitosan hydrogels, the sample effectively sterilizes the bacterial with a bacteriostatic ring. Therefore, regional loading of chitosan hydrogel containing ciprofloxacin on the modified microarc oxidation coating is a good approach to endorse Ti with both excellent bioactivity and antibacterial ability.

N-Doped sp2 /sp3 Carbon Derived from Carbon Dots to Boost the Performance of Ruthenium for Efficient Hydrogen Evolution Reaction.

The structure and properties of the carrier significantly affect the catalytic activity of the active centers for supported electrocatalysts. Therefore, elaborate design and regulation of the physicochemical properties of carbon carriers are essential to improve the activity and stability of the carbon-supported ruthenium-based catalysts. Herein, enlightened by the unique characteristics of coexisting sp2 and sp3 carbon nuclei in N-doped carbon dots (NCDs), a hybrid structure of N-doped carbon substrates featuring N-doped sp2 /sp3 carbon interfaces loaded with Ru nanoparticles (Ru/NCDs) is obtained. Spectroscopic analysis and density functional theory calculations illustrate that the interaction between Ru and NCDs effectively modulates the electronic structure of the active center Ru, and the formed N-doped sp2 /sp3 carbon interface lowers the energy barrier of the intermediates in hydrogen evolution reaction (HER) and balances the hydrogen adsorption and desorption and, thereby, greatly improves the activity of Ru/NCDs. Remarkably, Ru/NCDs exhibit excellent HER activity and stability in comparison to Pt/C, which merely requires overpotentials as low as 37 and 14 mV at 10 mA cm-2 in alkaline and acidic electrolytes, respectively. This finding will provide more thoughts about the influence of substrate properties on the catalytic activity and rational design of carbon-loaded electrocatalysts.

Molecular insight into the systematic affinity and selectivity of partner recognition sites between the WW1 and WW2 domains of human KIBRA neuroprotein.

Human KIBRA, a member of the WWC family proteins, is an upstream regulator of the Salvador/Warts/Hippo (SWH) signaling pathway and predominately expressed in nervous system. The protein has two functionally regulatory domains WW1 and WW2 at N-terminal region, which recognize and bind to the PY-motif segments of their partner proteins to serve as a signaling scaffold role in the SWH pathway. The two domains are highly conserved, but their downstream ligands and biological functions may not be fully consistent. In this study, we attempted to systematically profile the PY-motif affinity to and selectivity between KIBRA WW1 and WW2 domains involved in partner recognition sites. Ontology mining was used to enrich the KIBRA-interacting proteins in literature libraries, from which a variety of PY-motif peptide segments were identified, and their binding behavior to each domain was then analyzed by integrating computational modeling and experimental assay. Most PY-motif peptides were found to interact potently with WW1 and WW2, but they generally only exhibit a moderate or modest selectivity between the two domains. Subsequently, several representative peptides were further examined in detail to elucidate the molecular mechanism underlying their affinity and selectivity. It is revealed that the middle motif region of PY-motif peptides is primarily responsible for the affinity and stability of peptide binding, but only contributes marginally to peptide selectivity. Instead, the N-terminal region and, particularly, C-terminal region of PY-motif peptides play a crucial role in the selectivity. Hydrophobic contacts and hydrogen bonds confer stability and specificity to the domain-peptide interaction, respectively.

Stretchable Electronic Facial Masks for Sonophoresis.

We introduce a stretchable electronic facial mask (SEFM) as a platform for facial healthcare, which can integrate with various sensors and actuators. As a demonstration, an SEFM for sonophoresis enabling the promotion of the delivery effect of a drug mask is developed. To overcome the technique challenges, several approaches including the design of the joined silicone layer by two planar half-face portions and the single-side soft pressing (SSSP) technique for encapsulation are exploited in this work, which could be extended to the design and fabrication of other stretchable electronics. The mechanical, thermal, electrical, and ultrasonic characteristics of the SEFM are all verified by the finite element analysis and experiments. Finally, we prove the effect of the SEFM on accelerating the delivery of hyaluronic acid (HA) through animal experiments and confirm that the SEFM can enhance the skin moisture content by 20% via human facial experiments.