Distinct glutamatergic projections of the posteroventral medial amygdala play different roles in arousal and anxiety.

Sleep disturbance usually accompanies anxiety disorders and exacerbates their incidence rates. The precise circuit mechanisms remain poorly understood. Here, we found that glutamatergic neurons in the posteroventral medial amygdala (MePVGlu) are involved in arousal and anxiety-like behaviors. Excitation of MePVGlu neurons not only promoted wakefulness but also increased anxiety-like behaviors. Different projections of MePVGlu neurons played various roles in regulating anxiety-like behaviors and sleep-wakefulness. MePVGlu neurons promoted wakefulness through the MePVGlu-posteromedial cortical amygdaloid area (PMCo) pathway and the MePVGlu-bed nucleus of the stria terminals (BNST) pathway. In contrast, MePVGlu neurons increased anxiety-like behaviors through the MePVGlu-ventromedial hypothalamus (VMH) pathway. Chronic sleep disturbance increased anxiety levels and reduced reparative sleep, accompanied by the enhanced excitability of MePVGlu-PMCo and MePVGlu-VMH circuits but suppressed responses of glutamatergic neurons in the BNST. Inhibition of the MePVGlu neurons could rescue chronic sleep deprivation-induced phenotypes. Our findings provide important circuit mechanisms for chronic sleep disturbance-induced hyperarousal response and obsessive anxiety-like behavior, and are expected to provide a promising strategy for treating sleep-related psychiatric disorders and insomnia.

Dynamic root microbiome sustains soybean productivity under unbalanced fertilization.

Root-associated microbiomes contribute to plant growth and health, and are dynamically affected by plant development and changes in the soil environment. However, how different fertilizer regimes affect quantitative changes in microbial assembly to effect plant growth remains obscure. Here, we explore the temporal dynamics of the root-associated bacteria of soybean using quantitative microbiome profiling (QMP) to examine its response to unbalanced fertilizer treatments (i.e., lacking either N, P or K) and its role in sustaining plant growth after four decades of unbalanced fertilization. We show that the root-associated bacteria exhibit strong succession during plant development, and bacterial loads largely increase at later stages, particularly for Bacteroidetes. Unbalanced fertilization has a significant effect on the assembly of the soybean rhizosphere bacteria, and in the absence of N fertilizer the bacterial community diverges from that of fertilized plants, while lacking P fertilizer impedes the total load and turnover of rhizosphere bacteria. Importantly, a SynCom derived from the low-nitrogen-enriched cluster is capable of stimulating plant growth, corresponding with the stabilized soybean productivity in the absence of N fertilizer. These findings provide new insights in the quantitative dynamics of the root-associated microbiome and highlight a key ecological cluster with prospects for sustainable agricultural management.

Confining the Growth of AgNPs onto Epigallocatechin Gallate-Decorated Zein Nanoparticles for Constructing Potent Protein-Based Antibacterial Nanocomposites.

Sliver nanoparticles (AgNPs) have attracted tremendous interest as an alternative to commercially available antibiotics due to their low microbial resistance and broad-spectrum antimicrobial activity. However, AgNPs are highly reactive and unstable and are susceptible to fast oxidation. Synthesizing stable and efficient AgNPs using green chemistry principles remains a major challenge. To address this issue, we establish a facile route to form AgNP-doped zein nanoparticle core-satellite superstructures with ultralow minimum bactericidal concentration (MBC). In brief, polyphenol surface-functionalization of zein nanoparticles was performed, and the epigallocatechin gallate (EGCG) layer on zein nanoparticles served as a reducing-cum-stabilizing agent. We used EGCG-decorated zein nanoparticles (ZE) as a template to direct the nucleation and growth of AgNPs to develop metallized hybrid nanoparticles (ZE-Ag). The highly monodispersed core-satellite nanoparticles (∼150 nm) decorated with ∼4.9 nm AgNPs were synthesized successfully. The spatial restriction of EGCG by zein nanoparticles confined the nucleation and growth of AgNPs only on the surface of the particles, which prevented the formation of entangled clusters of polyphenols and AgNPs and concomitantly inhibited the coalescence and oxidation of AgNPs. Thus, this strategy improved the effective specific surface area of AgNPs, and as a result, ZE-Ag efficiently killed the indicator bacteria, Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus(MRSA) after 20 min of incubation, with MBCs of 2 and 4 µg/mL, respectively. This situation indicated that as-prepared core-satellite nanoparticles possessed potent short-term sterilization capability. Moreover, the simulated wound infection model also confirmed the promising application of ZE-Ag as an efficient antimicrobial composite. This work provides new insights into the synthesis and emerging application of AgNPs in food preservation, packaging, biomedicine, and catalysis.

Palm-Sized Wireless Transient Elastography System with Real-Time B-Mode Ultrasound Imaging Guidance: Toward Point-of-Care Liver Fibrosis Assessment.

Transient elastography (TE), recommended by the WHO, is an established method for characterizing liver fibrosis via liver stiffness measurement (LSM). However, technical barriers remain towards point-of-care application, as conventional TE requires wired connections, possesses a bulky size, and lacks adequate imaging guidance for precise liver localization. In this work, we report the design, phantom validation, and clinical evaluation of a palm-sized TE system that enables simultaneous B-mode imaging and LSM. The performance of this system was validated experimentally using tissue-equivalent reference phantoms (1.45-75 kPa). Comparative studies against other liver elastography techniques, including conventional TE and two-dimensional shear wave elastography (2D-SWE), were performed to evaluate its reliability and validity in adults with various chronic liver diseases. Intra- and inter-operator reliability of LSM were established by an elastography expert and a novice. A good agreement was observed between the Young's modulus reported by the phantom manufacturer and this system (bias: 1.1-8.6%). Among 121 patients, liver stiffness measured by this system and conventional TE were highly correlated (r = 0.975) and strongly agreed with each other (mean difference: -0.77 kPa). Inter-correlation of this system with conventional TE and 2D-SWE was observed. Excellent-to-good operator reliability was demonstrated in 60 patients (ICCs: 0.824-0.913). We demonstrated the feasibility of employing a fully integrated phased array probe for reliable and valid LSM, guided by real-time B-mode imaging of liver anatomy. This system represents the first technical advancement toward point-of-care liver fibrosis assessment. Its small footprint, along with B-mode guidance capability, improves examination efficiency and scales up screening for liver fibrosis.

Facile Synthesis and Multiple Application of Ultralong-Afterglow Room Temperature Phosphorescence Aggregate Carbon Dots from Simple Raw Materials.

Owing to the ultralong afterglow, room temperature decay phosphorescence nanomaterials have aroused enough attention. In the work, by simple one-pot solid-state thermal decomposition reaction, aggregate carbon dots (CDs) was prepared from trimesic and boric acid. Based on the intermolecular hydrogen bonds and intramolecular π-π stacking weak interaction from precursors, CDs was encapsulated in boron oxide matrix and formed aggregation. The aggregate state of CDs facilitated the triplet excited states (Tn), which could induce the room temperature decay phosphorescence properties. By careful investigation, under different excitation wavelengths at 254 and 365 nm, the aggregate CDs showed > 15 s and > 3 s room temperature phosphorescence emission in the naked eye, which was associated with 1516.12 ms and 718.62 ms lifetime respectively. And the aggregate CDs exhibited widespread application in encoding encryption, optical anti-counterfeiting and fingerprint identification etc. The interesting aggregate CDs revealed unexpected ultralong-afterglow room temperature decay phosphorescence properties and the work opened a window for constructing ultralong-afterglow room temperature decay phosphorescence aggregate CDs nanomaterials.

Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice.

Obesity increases the severity of airway hyperresponsiveness (AHR) in individuals with asthma, but the mechanism is not well elucidated. G-protein coupled receptor 40 (GPR40) has been found to induce airway smooth muscle contraction after activated by long-chain fatty acids (LC-FFAs), suggesting a close correlation between GPR40 and AHR in obese. In this study, C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization, the regulatory effects of GPR40 on AHR, inflammatory cells infiltration, and the expression of Th1/Th2 cytokines were evaluated by using a small-molecule antagonist of GPR40, DC260126. We found that the free fatty acids (FFAs) level and GPR40 expression were greatly elevated in the pulmonary tissues of obese asthmatic mice. DC260126 greatly reduced methacholine-induced AHR, ameliorated pulmonary pathological changes and decreased inflammatory cell infiltration in the airways in obese asthma. In addition, DC260126 could down-regulate the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and pro-inflammatory cytokines (IL-1ß, TNF-α), but elevated Th1 cytokine (IFN-γ) expression. In vitro, DC260126 could remarkedly reduce oleic acid (OA)-induced cell proliferation and migration in HASM cells. Mechanistically, the effects that DC260126 alleviated obese asthma was correlated with the down-regulation of GTP-RhoA and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1). Herein, we proved that targeting of GPR40 with its antagonist helped to mitigate multiple parameters of obese asthma effectively.

Intestinal Microflora Altered by Vancomycin Exposure in Early Life Up-regulates Type 2 Innate Lymphocyte and Aggravates Airway Inflammation in Asthmatic Mice.

Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Exposure to antibiotics during early life is associated with an increased risk of allergic asthma, although the exact mechanism is not fully understood. In this study, mice were randomly divided into a normal saline control group (NS group), an OVA-induced asthma group (OVA group), a vancomycin treatment control group (VAN.NS group), and a vancomycin treatment the OVA-induced asthma group (VAN.OVA group). The results showed that vancomycin altered dominant species in experimental mice. The phylum level histogram showed that Bacteroides abundance was increased, and Firmicutes abundance was decreased in the OVA group. Airway inflammation and airway hyperresponsiveness (AHR) were aggravated in the vancomycin-exposed group. Enzyme-linked immunosorbent assay (ELISA) showed that the serum levels of IL-5, IL-13, and IL-33 in the OVA group were higher than those in the NS group, especially in the VAN.OVA group. The expression of GATA binding protein-3(GATA3) and retinoid acid receptor-related orphan receptor alpha (RORa) increased in the OVA group, even more so in the VAN.OVA group. Group 2 innate lymphoid cells (ILC2s) in the lung detected by flow cytometry was increased in OVA mice more than those in control mice, with a more remarkable increase in the VAN.OVA. Our results demonstrated that vancomycin used in early life could alter the intestinal microecology of mice, which, in turn, aggravates airway inflammation and upregulate type 2 innate lymphocytes.

High-Output Lotus-Leaf-Bionic Triboelectric Nanogenerators Based on 2D MXene for Health Monitoring of Human Feet.

As versatile energy harvesters, triboelectric nanogenerators (TENGs) have attracted considerable attention in developing portable and self-powered energy suppliers. The question of how to improve the output power of TENGs using cost-effective means is still under vigorous investigation. In this paper, high-output TENGs were successfully produced by using a simple and low-cost lotus-leaf-bionic (LLB) method. Well-distributed microstructures were fabricated via the LLB method on the surface of a polydimethylsiloxane (PDMS) negative triboelectric layer. 2D MXene (Ti3C2Tx) and graphene were doped into the structured PDMS to evaluate their effects on the performance of TENG. Owing to merits of the MXene doping and microstructures on the PDMS surface, the output power of MXene-doped LLB TENGs reached as high as 104.87 W/m2, which was about 10 times higher than that of graphene-doped devices. The MXene-doped LLB TENGs can be used as humidity sensors, with a sensitivity of 4.4 V per RH%. In addition, the MXene-doped LLB TENGs were also sensitive to human body motions; hence, a foot health monitoring system constructed by the MXene-doped LLB TENGs was successfully demonstrated. The results in this work introduce a way to produce cost-effective TENGs using bionic means and suggest the promising applications of TENGs in the smart monitoring system of human health.

Whole-plant microbiome profiling reveals a novel geminivirus associated with soybean stay-green disease.

Microbiota colonize every accessible plant tissue and play fundamental roles in plant growth and health. Soybean stay-green syndrome (SGS), a condition that causes delayed leaf senescence (stay-green), flat pods and abnormal seeds of soybean, has become the most serious disease of soybean in China. However, the direct cause of SGS is highly debated, and little is known about how SGS affect soybean microbiome dynamics, particularly the seed microbiome. We studied the bacterial, fungal, and viral communities associated with different soybean tissues with and without SGS using a multi-omics approach, and investigated the possible pathogenic agents associated with SGS and how SGS affects the assembly and functions of plant-associated microbiomes. We obtained a comprehensive view of the composition, function, loads, diversity, and dynamics of soybean microbiomes in the rhizosphere, root, stem, leaf, pod, and seed compartments, and discovered that soybean SGS was associated with dramatically increased microbial loads and dysbiosis of the bacterial microbiota in seeds. Furthermore, we identified a novel geminivirus that was strongly associated with soybean SGS, regardless of plant cultivar, sampling location, or harvest year. This whole-plant microbiome profiling of soybean provides the first demonstration of geminivirus infection associated with microbiota dysbiosis, which might represent a general microbiological symptom of plant diseases.

Measuring Human Corneal Stromal Biomechanical Properties Using Tensile Testing Combined With Optical Coherence Tomography.

Purpose: To investigate the ex vivo elastic modulus of human corneal stroma using tensile testing with optical coherence tomography (OCT) imaging and its correlation with in vivo measurements using corneal visualization Scheimpflug technology. Methods: Twenty-four corneal specimens extracted from stromal lenticules through small incision lenticule extraction were cut into strips for uniaxial tensile tests. In vivo corneal biomechanical responses were evaluated preoperatively using the corneal visualization Scheimpflug technology (CorVis ST). The correlation of the elastic modulus with clinical characteristics and dynamic corneal response parameters were analyzed using Spearman's correlation analysis. Results: The mean low strain tangent modulus (LSTM) of the human corneal stroma was 0.204 ± 0.189 (range 0.010-0.641) MPa, and high strain tangent modulus (HSTM) 5.114 ± 1.958 (range 2.755-9.976) MPa. Both LSTM (r = 0.447, p = 0.029) and HSTM (r = 0.557, p = 0.005) were positively correlated with the stress-strain index (SSI). LSTM was also positively correlated with the A1 deflection length (r = 0.427, p = 0.037) and A1 deflection area (r = 0.441, p = 0.031). HSTM was positively correlated with spherical equivalent (r = 0.425, p = 0.038). Conclusions: The correlation of corneal elastic modulus with A1 deflection parameters and SSI may indicate a relationship between these parameters and tissue elasticity. The HSTM decreased with the degree of myopia. Combining tensile test with OCT may be a promising approach to assess corneal biomechanical properties.

How Paretic and Non-Paretic Ankle Muscles Contract during Walking in Stroke Survivors: New Insight Using Novel Wearable Ultrasound Imaging and Sensing Technology.

Abnormal muscle tone and muscle weakness are related to gait asymmetry in stroke survivors. However, the internal muscle morphological changes that occur during walking remain unclear. To address this issue, this study investigated the muscle activity of the tibialis anterior (TA) and medial gastrocnemius (MG) of both the paretic and non-paretic sides during walking in nine stroke survivors, by simultaneously capturing electromyography (EMG), mechanomyography (MMG), and ultrasound images, and using a validated novel wearable ultrasound imaging and sensing system. Statistical analysis was performed to examine the test−retest reliability of the collected data, and both the main and interaction effects of each "side" (paretic vs. non-paretic) and "gait" factors, in stroke survivors. This study observed significantly good test−retest reliability in the collected data (0.794 ≤ ICC ≤ 0.985), and significant differences existed in both the side and gait factors of the average TA muscle thickness from ultrasound images, and in the gait factors of TA and MG muscle's MMG and EMG signals (p < 0.05). The muscle morphological characteristics also appeared to be different between the paretic and non-paretic sides on ultrasound images. This study uncovered significantly different internal muscle contraction patterns between paretic and non-paretic sides during walking for TA (7.2% ± 1.6%) and MG (5.3% ± 4.9%) muscles in stroke survivors.

Preparation, characterization and cell labelling of strong pH-controlled bicolor fluorescence carbonized polymer dots.

As a class of important carbon nanomaterial, carbonized polymer dots (CPDs), also called carbon dots (CDs), have aroused wide interest owing to their unique water solubility, fluorescence properties, and rich surface functional groups. However, the directional tuning of the fluorescence properties of CPDs remains incomplete because of the influence of many factors like diameter, solvent and surface groups. Particularly, most carbonized polymer dots are synthesized in a neutral pH environment. Herein, by modulating the pH (strongly acidic or alkaline) of dextrin water solution, bicolor fluorescence emission (blue and yellow) CPDs were prepared by a hydrothermal reaction. Through systematic characterization, it was found that the different fluorescence properties are regulated by the diameters and surface groups of the carbon cores. Simultaneously, the pH value affected the nucleation process. Based on the excellent fluorescence properties, cell fluorescence imaging and cytotoxicity were tested. The bicolor fluorescence CPDs obtained by tuning the pH provide an important theoretical basis for the design of broadband CPDs.

ICS/LABA Combined With Subcutaneous Immunotherapy Modulates the Th17/Treg Imbalance in Asthmatic Children.

Rationale: The imbalance of T helper (Th17) cell and regulatory T (Treg) cell are involved in allergic asthma pathogenesis. We hypothesized that ICS/LABA could modulate the Th17/Treg imbalance and that subcutaneous immunotherapy (SCIT) could coordinate with ICS/LABA to rebalance the dysfunction of Th17/Treg. Methods: Thirty house dust mites (HDM) allergic asthmatic children and fifteen healthy control subjects were enrolled in this study. Fifteen asthmatic children were treated by ICS/LABA powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with HDM-SCIT. Asthmatic subjects were followed up for 6 months, but 2 asthmatics treated with ICS/LABA were lost to follow-up. Flow cytometry was used to determine the proportions of Th17 and Treg in CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Serum levels of IL-17A and IL-10 were assessed by ELISA. Result: ICS/LABA treatment significantly reduced the percentage of Th17 cells (1.252 ± 0.134% vs. 2.567 ± 0.386%), serum IL-17A (49.42 ± 2.643 pg/ml vs. 66.75 ± 3.442 pg/ml) and Th17/Treg ratio (0.194 ± 0.025 vs. 0.439 ± 0.072) compared to baseline (P<0.01). The ICS/LABA+HDM-SCIT treatment group showed similar reduction in the percentage of Th17 cells (1.11 ± 0.114% vs. 2.654 ± 0.276%), serum IL-17A (49.23 ± 2.131 pg/ml vs. 66.41 ± 2.616 pg/ml) and the Th17/Treg ratio (0.133 ± 0.015 vs. 0.4193 ± 0.050) (P<0.01). ICS/LABA+HDM-SCIT treatment group demonstrated elevated Treg percentages (8.483 ± 0.408% vs. 6.549 ± 0.299%) and serum IL-10 levels (127.4 ± 4.423 pg/ml vs. 93.15 ± 4.046 pg/ml), resulting in a lower Th17/Treg ratio than the ICS/LABA group. Conclusion: ICS/LABA treatment regulates Th17/Treg imbalance mainly by mitigating Th17-induced inflammation in asthma patients. The addition of SCIT further enhanced such effect by upregulating Treg cells.

Real-Time Visual Biofeedback via Wearable Ultrasound Imaging Can Enhance the Muscle Contraction Training Outcome of Young Adults.

ABSTRACT: Huang, Z-H, Ma, CZ-H, Wang, L-K, Wang, X-Y, Fu, S-N, and Zheng, Y-P. Real-time visual biofeedback via wearable ultrasound imaging can enhance the muscle contraction training outcome of young adults. J Strength Cond Res 36(4): 941-947, 2022-Real-time ultrasound imaging (RUSI) can serve as visual biofeedback to train deep muscle contraction in clinical rehabilitative settings. However, its effectiveness in resistance training in sports/fitness fields remains unexplored. This article introduced a newly developed wearable RUSI system that provided visual biofeedback of muscle thickening and movement and reported its effectiveness in improving the training outcomes of muscle thickness change (%) during dynamic contraction. Twenty-five healthy young men participated and performed pec fly exercise both with and without RUSI biofeedback. Statistical analysis was conducted to examine the reliability of the measurements and the immediate effects of (a) RUSI biofeedback of muscle contraction and (b) training intensity (50 vs. 80% of 1-repetition maximum [1RM]) on the pectoralis major (PMaj) thickness change measured by ultrasound images. In addition to significantly high inter-contraction reliability (ICC3,1 > 0.97), we observed significantly increased PMaj thickness change for both training intensities upon receiving biofeedback in subjects, compared with without biofeedback (p < 0.001). We also observed significantly larger PMaj thickness change at 80% of 1RM compared with 50% of 1RM (p = 0.023). The provision of visual biofeedback using RUSI significantly enlarged the magnitude of PMaj thickness change during pec fly exercises, potentially indicating that RUSI biofeedback could improve the ability of targeted muscle contraction of PMaj in healthy young adults. To our knowledge, this study has pioneered in applying RUSI as a form of biofeedback during weight training and observed positive effectiveness. Future iterations of the technique will benefit more subject groups, such as athletes and patients with neuromuscular disorders.

Mycorrhizal symbiosis modulates the rhizosphere microbiota to promote rhizobia-legume symbiosis.

Plants establish symbioses with mutualistic fungi, such as arbuscular mycorrhizal (AM) fungi, and bacteria, such as rhizobia, to exchange key nutrients and thrive. Plants and symbionts have coevolved and represent vital components of terrestrial ecosystems. Plants employ an ancestral AM signaling pathway to establish intracellular symbioses, including the legume-rhizobia symbiosis, in their roots. Nevertheless, the relationship between the AM and rhizobial symbioses in native soil is poorly understood. Here, we examined how these distinct symbioses affect root-associated bacterial communities in Medicago truncatula by performing quantitative microbiota profiling (QMP) of 16S rRNA genes. We found that M. truncatula mutants that cannot establish AM or rhizobia symbiosis have an altered microbial load (quantitative abundance) in the rhizosphere and roots, and in particular that AM symbiosis is required to assemble a normal quantitative root-associated microbiota in native soil. Moreover, quantitative microbial co-abundance network analyses revealed that AM symbiosis affects Rhizobiales hubs among plant microbiota and benefits the plant holobiont. Through QMP of rhizobial rpoB and AM fungal SSU rRNA genes, we revealed a new layer of interaction whereby AM symbiosis promotes rhizobia accumulation in the rhizosphere of M. truncatula. We further showed that AM symbiosis-conditioned microbial communities within the M. truncatula rhizosphere could promote nodulation in different legume plants in native soil. Given that the AM and rhizobial symbioses are critical for crop growth, our findings might inform strategies to improve agricultural management. Moreover, our work sheds light on the co-evolution of these intracellular symbioses during plant adaptation to native soil conditions.

An epidemiological investigation of food allergy among children aged 3 to 6 in an urban area of Wenzhou, China.

BACKGROUND: The prevalence of food allergy (FA) has increased worldwide. In China, the prevalence of FA in infants and school-aged children is well known, but the prevalence in preschool children is unknown. METHODS: A total of 4151 preschool children aged 3 to 6 years in urban Wenzhou, China, were recruited for this cross-sectional study. Their parents completed a preliminary screening questionnaire, and a detailed FA questionnaire was given to parents whose children had suspected FA according to the preliminary screening. According to the results of the detailed FA questionnaires, some children underwent a skin prick test (SPT) and specific IgE (sIgE) measurement. Children with abnormal SPT and/or sIgE results who did not meet the diagnostic criteria and those with negative SPT and sIgE results whose histories strongly supported FA underwent an oral food challenge (OFC). RESULTS: Of the 4151 children's parents who completed the surveys, 534 (12.86%) indicated a positive medical history of FA. Among the 40 children who underwent an OFC, 24 were positive. According to SPT and sIgE measurements, 11 children were diagnosed with FA. The prevalence of FA was at least 0.84%; children who dropped out during the study were considered FA-negative. Among the 35 children with FA, the most common allergic manifestation was skin symptoms. The most common allergic foods were egg, fish and shrimp. CONCLUSIONS: The parent-reported rate of FA in preschool children in urban Wenzhou was 12.86%. The prevalence of FA was at least 0.84%. Among all cases, the most common allergic food was eggs, and the most common allergic manifestation was skin symptoms. TRIAL REGISTRATION: NCT03974555, registered on 30 May 2019 (www.clinicaltrials.gov).

Diplatin, a novel water-soluble platinum complex, inhibits lung cancer growth via augmentation of Fas-mediated apoptosis.

Platinum drugs, such as cisplatin (DDP) and carboplatin (CBP), are the main drugs for the treatment of lung cancer, but their practical clinical application is limited by severe toxicity and acquired drug resistance. Our previous study has indicated that diplatin, [2-(4-(diethyl-amino)butyl)malonate-O,O']-[(1R,2R)-cyclohexane-1,2-diamine N,N'] platinum (II) phosphate, a novel water-soluble platinum complex, could overcome DDP-resistant cells and was less toxic than comparable platinum drugs. In the present study, the effects and mechanisms of diplatin were further evaluated for its development as a novel anti-lung cancer platinum drug. Here, we found diplatin down-regulated the viability of H460 and LTEP-A-2 cells in a dose-dependent manner. Nude mice administrated with diplatin (30-120 mg/kg) via tail vein injection dose-dependently inhibited the growth of H460 and LTEP-A-2 xenograft tumors, whose action mainly correlated with the induction of tumor apoptosis. Particularly, the exposure of lung cancer cells or xenograft tumors to diplatin resulted in elevated Fas level, and knockdown of Fas ameliorated diplatin-induced cells apoptosis. Overall, we suggest that diplatin has potent anti-tumor activity, which probably acts through Fas-mediated signaling pathway.

Keratoconus Diagnosis: Validation of a Novel Parameter Set Derived from IOP-Matched Scenario.

PURPOSE: Considering that intraocular pressure (IOP) is an important confounding factor in corneal biomechanical evaluation, the notion of matching IOP should be introduced to eliminate any potential bias. This study aimed to assess the capability of a novel parameter set (NPS) derived from IOP-matched scenario to diagnose keratoconus. METHODS: Seventy samples (training set; 35 keratoconus and 35 normal corneas; pairwise matching for IOP) were used to determine NPS by forward logistic regression. A large validation dataset comprising 62 matching samples (31 keratoconus and 31 normal corneas) and 203 unmatching samples (112 keratoconus and 91 normal corneas) was used to evaluate its clinical significance. To further assess its diagnosis capability, NPS was compared with the other two prior biomechanical indexes. RESULTS: NPS was comprised of three biomechanical parameters, namely, DA Ratio Max 1 mm (DRM1), the first applanation time (AT1), and an energy loading parameter (Eload). NPS was successfully applied to the validation dataset, with a higher accuracy of 96.8% and 95.6% in the IOP-matched and -unmatched scenarios, respectively. More surprisingly, accuracy of NPS was 95.5% in the combined validation, an improvement compared to the two prior biomechanical indexes. CONCLUSIONS: This is the first study taking IOP bias into consideration to determine a biomechanical parameter set. Our study shows that NPS indeed offers comparable performance in keratoconus diagnosis. Translational Relevance. Determining a parameter set after eliminating the influence from IOP is useful in revealing the essential differences between keratoconus and normal corneas and possibly facilitating further progress in keratoconus diagnosis.

Provincial analysis and zoning of atmospheric pollution in China from the atmospheric transmission and the trade transfer perspective.

The "Joint Prevention and Control of Regional Air Pollution in China" has been put forward to solve serious regional air pollution. However, there is no geographical division covering the whole country that could reveal the similarities and differences among regions to support implementing this policy. This paper applied an air quality model and a multiregional input-output model to analyze the impacts and patterns of atmospheric transmission and trade transfer of regional air pollution, then compared the differences among typical provinces in the northern, central and southern regions. The social network analysis method was used to analyze the interacting pattern of regional atmospheric transmission and trade transfer, and 31 provinces in mainland China were divided into 5 clusters to reveal the interprovincial relationship of atmospheric transmission; then, the 31 provinces were divided into 3 clusters to reveal the interprovincial relationship of trade transfer. Based on these results, the provincial geographical division of "Nine Atmospheric Environmental Transmission Zones" covering mainland China was carried out. In addition, the key regions linking atmospheric transmission and trade transfer were also found. For example, Inner Mongolia is a typical key linkage region. From an atmospheric transmission perspective, it is linked to the northeast area. However, from a trade transfer perspective, it has a close relationship with the southern provinces. The linkage among provinces provides support for the interregional interaction mechanism of air pollution and the formulation of "Joint Prevention and Control of Regional Air Pollution in China".

Hormesis effect of hydrogen peroxide on the promoter activity of neuropeptide receptor PAC1-R.

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 1 (PAC1-R) is the neuropeptide PACAP-preferring receptor-mediating neuroprotective activity. In order to clarify the biological mechanism of its expression, we cloned the 2,526 bp promoter fragment from -2,500 to +26 of the transcription initiation site of human ADCYAP1R1 gene and constructed the novel promotor reporter system named pYr-PromDetect-PAC1p. It was found in SH-SY5Y cells low concentration (<10 nM) of hydrogen peroxide (H2 O2 ) significantly promoted the activity of PAC1-R promoter in dose-dependent way, which was significantly inhibited by the transcription factor specificity protein 1 (SP1) inhibitor mithramycin A and was further confirmed in the deletion mutation of the predicted SP1 binding sites. Moreover, higher concentration of H2 O2 (>10 nM) inhibited the activity of PAC1-R in dose-dependent way. The hormesis effect of H2 O2 on PAC1-R promoter would help to further clarify the physiological effect of low-dose reactive oxygen on nervous system. PRACTICAL APPLICATIONS: PAC1-R mediates well-known neuroprotective, neurotrophic, and neurogenesis effects, which is an important drug target for neurodegenerative diseases. The hormesis effects of oxidative stress on PAC1-R expression not only help to explain the hormesis effects of oxidative stress on nerve system, but also offer a novel strategy to increase the expression of PAC1-R for the nerve protection or nerve generation. For example, taking advantage of low degree of oxidative stress to increases the expression of PAC1-R might help prevent subsequent surgical serious injury on the nervous system. The activation of PAC1-R promoter by low concentration of H2 O2 would help to further clarify the physiological effect of low-dose reactive oxygen on nervous system.