Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats.

Cancer chemotherapy-induced neuropathic pain is a devastating pain syndrome without effective therapies. We previously reported that rats deficient in complement C3, the central component of complement activation cascade, showed a reduced degree of paclitaxel-induced mechanical allodynia (PIMA), suggesting that complement is integrally involved in the pathogenesis of this model. However, the underlying mechanism was unclear. Complement activation leads to the production of C3a, which mediates inflammation through its receptor C3aR1. In this article, we report that the administration of paclitaxel induced a significantly higher expression level of C3aR1 on dorsal root ganglion (DRG) macrophages and expansion of these macrophages in DRGs in wild-type (WT) compared with in C3aR1 knockout (KO) mice. We also found that paclitaxel induced less severe PIMA, along with a reduced DRG expression of transient receptor potential channels of the vanilloid subtype 4 (TRPV4), an essential mediator for PIMA, in C3aR1 KO than in WT mice. Treating WT mice or rats with a C3aR1 antagonist markedly attenuated PIMA in association with downregulated DRG TRPV4 expression, reduced DRG macrophages expansion, suppressed DRG neuron hyperexcitability, and alleviated peripheral intraepidermal nerve fiber loss. Administration of C3aR1 antagonist to TRPV4 KO mice further protected them from PIMA. These results suggest that complement regulates PIMA development through C3aR1 to upregulate TRPV4 on DRG neurons and promote DRG macrophage expansion. Targeting C3aR1 could be a novel therapeutic approach to alleviate this debilitating pain syndrome.

A nanobody-based complement inhibitor targeting complement component 2 reduces hemolysis in a complement humanized mouse model of autoimmune hemolytic anemia.

C2 is an attractive therapeutic target for many complement-mediated diseases. We developed Nab1B10, a new anti-C2 nanobody that potently and selectively inhibits both the classical and lectin pathways of complement activation. Mechanistically, Nab1B10 binds to the C2a portion of C2 and inhibits the assembly of C3 convertase C4b2a. Nab1B10 cross-reacts with monkey but not rodent C2 and inhibits classical pathway-mediated hemolysis. Using a new complement humanized mouse model of autoimmune hemolytic anemia (AIHA), we demonstrated that Nab1B10 abolished classical pathway complement activation-mediated hemolysis in vivo. We also developed C2-neutralizing bi- and tetra-valent antibodies based on Nab1B10 and found these antibodies significantly more potent than the other anti-C2 monoclonal antibody that is already in clinical trials. These data suggest that these novel C2-neutralizing nanobodies could be further developed as new therapeutics for many complement-mediated diseases, in which pathogenesis is dependent on the classical and/or lectin pathway of complement activation.

Plasmon-driven catalytic reactions in optoplasmonic sandwich hybrid structure.

As an interesting phenomenon in the field of surface enhanced Raman spectroscopy (SERS), the plasmon-driven catalytic reaction (PDSC) induced by plasmonic hot electrons has great value in the research of novel properties of surface plasmons and accuracy of SERS applications. In this work, an optoplasmonic sandwich hybrid structure is proposed for studying PDSC of p-aminothiophenol (PATP) molecules, which is composed of Au film, metal organic frameworks (MOFs) nanoparticles, zeolithic imidazolate (ZIF-8), and single S i O 2 microsphere (Au f i l m@M O F s@S i O 2). In order to analyze the novel, to the best of our knowledge, phenomenon of the PDSC in this micro-nano structure, the hot electron generation in the MOF without the plasmonic core is carried out by combining the plasmonic enhancement of gold film with the light concentration of microspheres. Experimental data show that the PDSC reactions is dependent on the size of the MOFs nanoparticle and the size of the S i O 2 microsphere, which is confirmed by the electromagnetic field simulation of the finite-difference time-domain method (FDTD). Our work not only strengthens the understanding of surface plasmon in optoplasmonic hybrid structures but also has broad application prospects in the SERS and plasmon-driven catalytic fields.

Hemorrhage Risk Profiles among Different Antithrombotic Regimens: Evidence from a Real-World Analysis of Postmarketing Surveillance Data.

BACKGROUND: Although the use of direct oral anticoagulants (DOACs) has been reported in patients with atrial fibrillation (AF), there is currently no consensus on the occurrence or characteristics of the hemorrhage risk in different antithrombotic regimens. METHODS: Disproportionality and Bayesian analyses were performed in mining data of suspected hemorrhagic events after antithrombotic drug use from the FDA Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset and fatality rate of hemorrhage following different antithrombotic regimens were also compared. RESULTS: A total of 84,998 reports of hemorrhage-related adverse events with the use of antithrombotic drugs were identified. The patients included were mostly from the Americas (80.87%) and Europe (13.22%), with most data submitted by nonhealthcare professionals. Among the seven antithrombotic drug monotherapies, betrixaban had the highest association with hemorrhage based on the highest reporting odds ratio (ROR, 829.95; 95% CI = 113.61-6063.15), proportional reporting ratio (PRR, 24.68, χ2 = 804.24), and multi-item gamma Poisson shrinker (MGPS, 24.68, 95% one-sided CI = 4.67). The combination therapies of clopidogrel plus new oral anticoagulants had higher RORs, PRRs, and empirical Bayesian geometric means (EBGMs) than the antithrombotic drug monotherapies. Hemorrhage associated with rivaroxaban plus clopidogrel appeared to have an earlier onset (171 days vs 219 days, 95% two-sided CI =68.68-27.34, p < 0.0001) and a lower fatality rate (15.30% vs 17.74%, p<0.05) than that associated with rivaroxaban monotherapy. CONCLUSION: This study provides a relevant overview of the hemorrhagic complications/fatalities associated with different antithrombotic regimens in their real-world use. Among the combination therapies, clopidogrel plus DOACs were found to have stronger associations with hemorrhage than traditional dual antithrombotic therapies. Rivaroxaban showed a stronger association with hemorrhage than other antithrombotic drug monotherapies, and apixaban monotherapy appeared to have weaker associations with hemorrhage than others.

ROS-Induced Oxidative Damage and Mitochondrial Dysfunction Mediated by Inhibition of SIRT3 in Cultured Cochlear Cells.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability worldwide. Previous evidence suggests that reactive oxygen species (ROS) may play an important role in the occurrence and development of SNHL, while its mechanism remains unclear. We cultured dissected organs of Corti in medium containing different concentrations (0, 0.25, 0.5, 0.75, 1, and 1.25 mM) of hydrogen peroxide (H2O2) and established a four-concentration model of 0, 0.5, 0.75, and 1 mM to study different degrees of damage. We examined ROS-induced mitochondrial damage and the role of sirtuin 3 (SIRT3). Our results revealed that the number of ribbon synapses and hair cells appeared significantly concentration-dependent decrease with exposure to H2O2. Outer hair cells (OHCs) and inner hair cells (IHCs) began to be lost, and activation of apoptosis of hair cells (HCs) was observed at 0.75 mM and 1 mM H2O2, respectively. In contrast with the control group, the accumulation of ROS was significantly higher, and the mitochondrial membrane potential (MMP) was lower in the H2O2-treated groups. Furthermore, the expression of SIRT3, FOXO3A, and SOD2 proteins declined, except for an initial elevation of SIRT3 between 0 and 0.75 mM H2O2. Administration of the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine resulted in increased damage to the cochlea, including loss of ribbon synapses and hair cells, apoptosis of hair cells, more production of ROS, and reduced mitochondrial membrane potential. Thoroughly, our results highlight that ROS-induced mitochondrial oxidative damage drives hair cell degeneration and apoptosis. Furthermore, SIRT3 is crucial for preserving mitochondrial function and protecting the cochlea from oxidative damage and may represent a possible therapeutic target for SNHL.

Rich Structural Index for Stereoscopic Image Quality Assessment.

The human visual system (HVS), affected by viewing distance when perceiving the stereo image information, is of great significance to study of stereoscopic image quality assessment. Many methods of stereoscopic image quality assessment do not have comprehensive consideration for human visual perception characteristics. In accordance with this, we propose a Rich Structural Index (RSI) for Stereoscopic Image objective Quality Assessment (SIQA) method based on multi-scale perception characteristics. To begin with, we put the stereo pair into the image pyramid based on Contrast Sensitivity Function (CSF) to obtain sensitive images of different resolution. Then, we obtain local Luminance and Structural Index (LSI) in a locally adaptive manner on gradient maps which consider the luminance masking and contrast masking. At the same time we use Singular Value Decomposition (SVD) to obtain the Sharpness and Intrinsic Structural Index (SISI) to effectively capture the changes introduced in the image (due to distortion). Meanwhile, considering the disparity edge structures, we use gradient cross-mapping algorithm to obtain Depth Texture Structural Index (DTSI). After that, we apply the standard deviation method for the above results to obtain contrast index of reference and distortion components. Finally, for the loss caused by the randomness of the parameters, we use Support Vector Machine Regression based on Genetic Algorithm (GA-SVR) training to obtain the final quality score. We conducted a comprehensive evaluation with state-of-the-art methods on four open databases. The experimental results show that the proposed method has stable performance and strong competitive advantage.

Inhibitory effect of ficin on Candida albicans biofilm formation and pre-formed biofilms.

BACKGROUND: To investigate the effect of ficin, a type of proteases, on Candida albicans (C. albicans) biofilm, including forming and pre-formed biofilms. METHODS: Crystal violet tests together with colony forming unit (CFU) counts were used to detect fungal biofilm biomass. Live/dead staining of biofilms observed by confocal laser scanning microscopy was used to monitor fungal activity. Finally, gene expression of C. albicans within biofilms was assessed by qRT-PCR. RESULTS: According to our results, biofilm biomass was dramatically reduced by ficin in both biofilm formation and pre-formed biofilms, as revealed by the crystal violet assay and CFU count (p < 0.05). Fungal activity in biofilm formation and pre-formed biofilms was not significantly influenced by ficin according to live/dead staining. Fungal polymorphism and biofilm associated gene expression were influenced by ficin, especially in groups with prominent antibiofilm effects. CONCLUSIONS: In summary, ficin effectively inhibited C. albicans biofilm formation and detached its preformed biofilm, and it might be used to treat C. albicans biofilm associated problems.

Plasmon-Driven Interfacial Catalytic Reactions in Plasmonic MOF Nanoparticles.

Benefiting from the noble metal nanoparticle core and organic porous nanoshell, plasmonic metal-organic frameworks (MOFs) become a nanostructure with great enhancement of the electromagnetic field and a high density of reaction sites, which has fantastic optical properties in surface plasmon-related fields. In this work, the plasmon-driven interfacial catalytic reactions involving p-aminothiophenol to 4,4'-dimercaptoazobenzene (trans-DMAB) in both the liquid and gaseous phases are studied in plasmonic MOF nanoparticles, which consist of a Ag nanoparticle core and an organic shell (ZIF-8). The surface-enhanced Raman spectroscopy (SERS) spectra recorded at the plasmonic MOF in an aqueous environment demonstrate that the reversible plasmon-driven interfacial catalytic reactions could be modulated by a reductant (NaBH4) or oxidant (H2O2). Also, the situ SERS spectra also point out that plasmonic MOF (AgNP@ZIF-8) nanoparticles exhibit much better catalytic performance in the H2O2 solution compared to pure Ag nanoparticles for the anti-oxidation caused by the MOF shell. It is surprising that although there is greater SERS enhancement obtained at pure Ag nanoparticles, the plasmon-driven interfacial catalytic reactions only occur at plasmonic AgNP@ZIF-8 nanoparticles in the gaseous phase. This interesting phenomenon is further confirmed and analyzed by simulated electromagnetic field distributions, which could be understood by the effective capture of gaseous molecules by the organic porous nanoshell. Our work not only explores the plasmonic MOF nanoparticles with unique optical properties but also strengthens the understanding of plasmon-driven interfacial catalytic reactions.

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease.

Nanowire assisted repeatable DEP-SERS detection in microfluidics.

Surface enhanced Raman spectroscopy (SERS) detection in microfluidics is an interesting topic for its high sensitivity, miniaturization and online detection. In this work, a SERS detection in microfluidics with the help of the Ag nanowire aggregating based on dielectrophoresis (DEP) is reported. The Raman intensities of molecule in microfluidics is greatly enhanced in the naturally generated nanogaps of Ag nanowire aggregating modulated by DEP. Firstly, the influence of DEP voltage and time on Ag nanowire aggregating is investigated to figure out the optimal condition for SERS. And then, the SERS intensities of methylene blue and rhodamine6G at various concentration with high reproducibility and uniformity are studied. Furthermore, the experiment data demonstrate this DEP-SERS system could be repeated used for different molecule detections. At last, the SERS of melamine is measured to explore its application on food safety. Our work anticipates this nanowire assisted repeatable DEP-SERS detection in microfluidics with high sensitivity could meet the emerging needs in environmental pollution monitoring, food safety evaluation, and so on.

Targeting CD6 for the treatment of experimental autoimmune uveitis.

OBJECTIVE: CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. METHODS: After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. RESULTS: In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells. CONCLUSIONS: Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases.

Microstructures in striato-thalamo-orbitofrontal circuit in methamphetamine users.

Background Striato-thalamo-orbitofrontal (STO) circuit plays a key role in the development of drug addiction. Few studies have investigated its microstructural abnormalities in methamphetamine (MA) users. Purpose To evaluate the microstructural changes and relevant clinical relevance of the STO circuit in MA users using diffusion tensor imaging (DTI). Material and Methods Twenty-eight MA users and 28 age-matched normal volunteers were enrolled. 3T magnetic resonance imaging (MRI) was employed to obtain structural T1-weighted (T1W) imaging and diffusion-tensor imaging (DTI) data. Freesurfer software was used for automated segmentation of the bilateral nucleus accumbens (NAc), thalami, and orbitofrontal cortex (OFC). Four DTI measures maps, fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) were generated and non-linearly co-registered to structural space. Comparisons of DTI measures of the STO circuit were carried out between MA and controls using repeated measures analysis of variance. Correlation analyses were performed between STO circuit DTI measures and clinical characteristics. Results The MA group had significant FA reduction in the bilateral NAc, OFC, and right thalamus ( P < 0.05). Lower left OFC FA and right NAc FA/AD were associated with longer duration of MA use. Lower right OFC FA was associated with younger age at first MA use. Higher FA and lower MD/RD in the thalamus, as well as higher left OFC RD, were associated with increased psychiatric symptoms. Conclusion The STO circuit has reduced microstructural integrity in MA users. Microstructural changes in the thalamus may compensate for dysfunction in functionally connected cortices, which needs further investigation.

Therapeutic effect of bone marrow mesenchymal stem cells on laser-induced retinal injury in mice.

Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment.

Effect of dissolved ozone flotation thickening process on coliform bacteria and antibiotics simultaneous abatement: A pilot-scale study.

This study focused on the removal of the total coliforms, fecal coliforms and four target antibiotics in the dissolved ozone flotation (DOF) thickening sludge process. Additionally, the thickened effluent chromaticity and its effect on thickened sludge hydrolysis process were investigated. Ozonation in the DOF process could inactivate coliforms by oxidizing cellular components and destroying genetic material, as well as altering the chemical structure of antibiotics, leading to the degradation of antibiotics. At an O3 dosage of 16 mg/g TS, the concentration of total coliforms and fecal coliforms decreased by 2.2 log and 2.4 log, corresponding to an overall removal rate of 99.4 % and 99.7 %, respectively. The total degradation rate of four target antibiotics (tetracycline (TC), oxytetracycline (OTC), norfloxacin (NOR), ofloxacin (OFL)) were 66.5 %, 68.8 %, 53.3 % and 57.5 %, respectively. The chromaticity removal rate of the thickened effluent reached 95 %. Analysis of fluorescence spectra indicated alterations in the fluorescence properties of dissolved organic matter, resulting in a decrease in fluorescence intensity by ozonation. The thickened sludge had higher hydrolysis rates, resulting in a greater production of volatile fatty acids (VFAs). This was mainly attributed to the increased amount of soluble protein and carbohydrate in the substrate after DOF treatment, which was more conducive for the rapid conversion of hydrolysis into VFAs during the initial stage. These results provided new ideas for upgrading and transforming the thickening process of wastewater treatment plants (WWTPs).

Development of a C3 Humanized Rat as a New Model for Evaluating Novel C3 Inhibitors.

INTRODUCTION: C3 is central for all complement activation pathways, thus making it an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or nonhuman primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. METHODS: We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats. RESULTS: We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat factor H or compstatin, suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo. CONCLUSION: The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.

Humanization of a mouse anti-human complement C6 monoclonal antibody as a potential therapeutic for certain complement-mediated diseases.

The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.

Complete genome sequence of a J subgroup avian leukosis virus isolated from local commercial broilers.

Subgroup J avian leukosis virus (ALV-J) isolate GDKP1202 was isolated from a 50-day-old local yellow commercial broiler in the Guangdong province of China in 2012. Here we report the complete genomic sequence of the GDKP1202 isolate, which caused high mortality, serious growth suppression, thymic atrophy, and liver enlargement in commercial broilers. A novel potential binding site (5'-GGCACCTCC-3') for c-myb was identified in the GDKP1202 genome. These findings will provide additional insights into the molecular characteristics in the genomes and pathogenicity of ALV-J.

Discriminative analysis of early-stage Alzheimer's disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study.

BACKGROUND: Previous studies have revealed that amyloid depositions exist in not only the hippocampus but in other subcortical gray matter structures as well. Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional magnetic resonance imaging (MRI) techniques. PURPOSE: To evaluate the significance of the volumes and the mean diffusivity (MD) values of subcortical gray matter structures in discrimination between early-stage AD and normal subjects using the Integrated Registration and Segmentation Tool in FMRIB's Software Library. MATERIAL AND METHODS: Fifty-three cases of early-stage AD and 30 normal aging volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences using two similar 1.5T MR systems. The mean relative volumes and mean MD values of subcortical gray matter structures were compared between early-stage AD and control groups. Binary logistic regression analysis and receiver-operating characteristic (ROC) curves were applied to assess the diagnostic significance of every structure's relative volume, MD value, and combination of both. RESULTS: The relative volumes of the left hippocampus, right amygdala, bilateral thalamus, right caudate, left putamen, and bilateral pallidum were significantly lower in the early-stage AD group than in the control group (P < 0.05). The MD values of the bilateral hippocampus and pallidum, and of the right thalamus and caudate were significantly elevated in the early-stage AD group (P < 0.05). In binary logistic regression analysis, the relative volume of left hippocampus and age entered the final model of volumetric analysis. The MD values of bilateral hippocampi and pallidums entered the final model of MD analysis. The MD values of bilateral hippocampi and pallidums, and the relative volume of left pallidum, entered the final model of combination analysis. The accuracy of three models was 84.7%, 88.9%, and 93.1%, respectively. CONCLUSION: Pathological changes takes place in the hippocampus and other subcortical gray matter structures in early-stage AD. Diffusive imaging has great diagnostic significance in early-stage AD. The combination of both imaging modalities can lead to better discrimination between early-stage AD and normal aging.

[Association between degree of pulmonary artery hypertension and cardiac structural and functional changes in chronic high altitude heart disease patients].

OBJECTIVE: To compare the cardiac structural and functional changes in high altitude heart disease (HAHD) patients with various grade of pulmonary artery hypertension (PAH). METHODS: Pulmonary artery systolic pressure (PASP) was evaluated by Doppler echocardiography in 100 patients with HAHD and patients were divided into 3 groups: mild (PASP: 30-49 mm Hg), moderate (PASP: 50-69 mm Hg) and severe (PASP ≥ 70 mm Hg) PAH and 50 patients without organic heart disease served as control group. Data on heart structure and function, heart rhythm and whole blood NT-proBNP were compared among groups. RESULTS: Right ventricular free wall was significantly thicker in moderate and severe PAH groups than in the control group [(5.10 ± 2.23) mm, (7.00 ± 2.29 ) mm vs.(3.70 ± 0.92)mm, P < 0.05], and in the severe PAH group than in mild and moderate PAH groups [ (7.00 ± 2.29) mm vs.(4.58 ± 1.80) mm, (5.10 ± 2.23) mm, all P < 0.05] and which was similar between the mild PAH group and the control group. Right ventricular inter diameter and right ventricular outflow tract inter diameter were significantly increased in all HAHD groups compared to the control group (all P < 0.01), and were also significantly increased in moderate and severe PAH groups than in the mild PAH group (P < 0.01). Thickness of interventricular septum was also significantly increased in HAHD patients than control group and in moderate and severe PAH groups than in moderate PAH group. Left atrium anterior-posterior diameter was significantly increased in HAHD patients than in control group and was similar among HAHD patients with various degree of PAH. Left ventricular ejection fraction (LVEF) was remarkably decreased in all HAHD groups than in the control group (P < 0.05) , moreover, LVEF was remarkably decreased in the moderate PAH group than in the mild PAH group (P < 0.05) . EF was similar between severe PAH group and moderate PAH group (P > 0.05) . There was no significant correlation between lgPASP and EF (R = -0.103, P = 0.298) . Compared with the control group, the incidences of decompensated heart failure and arrhythmia were remarkably increased in HAHD patients (P < 0.05) . The level of whole blood NT-proBNP increased in proportion to increasing PASP in HAHD patients (P < 0.05). CONCLUSION: Increased PASP correlates with whole blood NT-proBNP and is an important determinant affecting the right ventricular structure and left and right ventricular function in HAHD patients.

Mechano-Driven Tribo-Electrophoresis Enabled Human-Droplet Interaction in 3D Space.

Electronically controlled droplet manipulation has widespread applications in biochemistry, life sciences, and industry. However, current technologies such as electrowetting, electrostatics, and surface charge printing rely on complex electrode arrays and external power supplies, leading to inefficient manipulation. In light of these limitations, a novel method is proposed, which leverages tribo-electrophoresis (TEP) to pipette in an oil medium, thereby enabling human-droplet interactions to be constructed with greater efficiency. The approach involves the rational design of a triboelectric nanogenerator-electrostatic tweezer that generates an electric field to charge the droplet and improves the maneuverability of the charged droplet, including aligned/non-aligned pipetting and stable transport in the clamped state, which can be accomplished solely by hand motion. The TEP method not only provides droplets with freedom to move in three dimensions but also offers a feasibility case for chemical reactions in the liquid phase and non-invasive sample extraction. This breakthrough establishes a cornerstone for human-droplet interactions capitalized on triboelectric nanogenerators, opening new avenues for research in droplet manipulation.