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Background: Cervical cancer ranks fourth in incidence and mortality among women. Ubiquitin-specific protein 53 binds to damage-specific DNA binding protein 2 and affects the biological properties of colon cancer. Damage-specific DNA binding protein is involved in nucleotide excision repair, which can repair DNA damage. However, the mechanism by which ubiquitin-specific protein 53 regulates the radiosensitivity of cervical cancer through damage-specific DNA binding protein remains unclear. Methods: Tissue samples from 40 patients with cervical squamous cell carcinoma who received radiotherapy were examined by immunohistochemistry to detect the expression of ubiquitin-specific protein 53, and clinical data were collected for statistical analysis. The cell cycle was detected by flow cytometry in Siha cells transfected with Si-USP53 and exposed to 8 Gy irradiation. Cell viability was determined by the CCK8 method in cells transfected with Si-USP53 and exposed to 0, 2, 4, 6, 8, or 10 Gy. The expression of damage-specific DNA binding protein, cyclin-dependent kinase 1, and cell cycle checkpoint kinase 2 was detected in cells transfected with Si-USP53. Results: The expression of ubiquitin-specific protein 53 in the tissues of patients with cervical squamous cell carcinoma was correlated with the sensitivity to radiotherapy. Knockdown of ubiquitin-specific protein 53 in Siha cells downregulated damage-specific DNA binding protein and caused G2/M cell cycle arrest and decreased the survival rate of cells in response to radiation. Conclusion: Ubiquitin-specific protein 53–induced cell cycle arrest and affected the radiotherapy sensitivity of tumors through damage-specific DNA binding protein.

Background: This case mainly describes a relatively rare case of an old mineral-like corneal foreign body that existed for up to 20 years, and did not significantly affect the visual quality of the patient., Case Presentation: A 56-year-old male miner complained of right eye vision loss for 3 years, swollen and painful for 4 months. Admission examination: Best corrected visual acuity was no light perception in the right eye and 20/20 in the left eye. Anterior segment examination: A large number of spot-like grayish-brown mineral foreign bodies in the conjunctiva of the nasal conjunctiva, emulsified silicone oil floating in the anterior chamber, Corneal foreign bodies in the right eye were widely distributed in the upper cortex and the proelastic layer. There were fewer foreign bodies in the left cornea. Previous medical history, 20 years ago due to forging and burning sulphur mine explosion, resulting in a large number of ore foreign bodies in the conjunctiva of both eyes. As these corneal foreign bodies did not affect the visual quality of the patient, we adopted a conservative treatment plan, did not remove these foreign bodies, and only carried out symptomatic treatment for the patient's secondary ocular hypertension. The patient was followed up normally in the outpatient department, and no cornea-related complications occurred up to now., Conclusions: First of all, it is necessary to understand the source and nature of the foreign body in patients with corneal and conjunctival foreign body injuries. In the second, for the old corneal metal foreign body, when the patient's visual acuity is stable and there are no symptoms of corneal irritation and inflammatory reaction, it can be Conservative treatment or outpatient follow-up observation. In the end, corneal Optical coherence tomography imaging should not be ignored, which is very important for determining the depth of embedding and the location of the corneal foreign body., (© 2024. The Author(s).)

Single-cell expression dynamics, from differentiation trajectories or RNA velocity, have the potential to reveal causal links between transcription factors (TFs) and their target genes in gene regulatory networks (GRNs). However, existing methods either overlook these expression dynamics or necessitate that cells be ordered along a linear pseudotemporal axis, which is incompatible with branching trajectories. We introduce Velorama, an approach to causal GRN inference that represents single-cell differentiation dynamics as a directed acyclic graph of cells, constructed from pseudotime or RNA velocity measurements. Additionally, Velorama enables the estimation of the speed at which TFs influence target genes. Applying Velorama, we uncover evidence that the speed of a TF's interactions is tied to its regulatory function. For human corticogenesis, we find that slow TFs are linked to gliomas, while fast TFs are associated with neuropsychiatric diseases. We expect Velorama to become a critical part of the RNA velocity toolkit for investigating the causal drivers of differentiation and disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Zika virus (ZIKV) infection during pregnancy threatens pregnancy and fetal health. However, the infectivity and pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using human trophoblast stem cells (hTSCs), we demonstrated that hTSCs were permissive to ZIKV infection, and resistance to ZIKV increased with hTSC differentiation. Combining gene knockout and transcriptome analysis, we demonstrated that the intrinsic expression of AXL and TIM-1, and the absence of potent interferon (IFN)-stimulated genes (ISGs) and IFNs contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived trophoblast organoid (hTSC-organoid), we demonstrated that ZIKV infection disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further demonstrated that ZIKV infection of hTSC-organoids disrupted the stemness of hTSCs and the proliferation of cytotrophoblast cells (CTBs) and probably led to a preeclampsia (PE) phenotype. Overall, our results clearly demonstrate that hTSCs represent the major target cells of ZIKV, and a reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepen our understanding of the characteristics and consequences of ZIKV infection of hTSCs in early human embryos., (© 2023. Springer Nature Limited.)

Single-wall carbon nanotubes (SWCNTs) with excellent physicochemical properties are considered a promising candidate for the electrical and mechanical reinforcements of polymers. However, the poor dispersion of SWCNTs in plastics seriously limits their application and their achieved performance enhancement. Here, we coat a freestanding, highly conductive SWCNT film onto the surface of a polyethylene terephthalate (PET) film by a hot-pressing method. Due to the uniform SWCNT network structure and strong interfacial interaction, the SWCNT/PET hybrid film showed notably enhanced electrical and mechanical properties even though with a very low SWCNT weight fraction of 0.066%. The surface square resistance of the SWCNT/PET film decreased to 120-140 Ω/□ from 10 16 Ω. In addition, Young's modulus and tensile strength of the SWCNT/PET film reached 4.6 GPa and 148 MPa, which are 31.3 and 24.4%, respectively, higher than the pure PET film. The SWCNT/PET film shows excellent mechanical durability and thermal stability, demonstrating its potential use as an antistatic material.

Carbon nanotube (CNT)/Cu core-shell fibers are a promising material for lightweight conductors due to their higher conductivity than pure CNT fibers and lower density than traditional Cu wires. However, the electrical properties of the hybrid fiber have been unsatisfactory, mainly because of the weak CNT-Cu interfacial interaction. Here we report the fabrication of a single-walled CNT (SWCNT)/Cu core-shell fiber that outperforms commercial Cu wires in terms of specific electrical conductivity and current carrying capacity. A dense and uniform Cu shell was coated on the surface of wet-spun SWCNT fibers using a combination of magnetron sputtering and electrochemical deposition. Our SWCNT/Cu core-shell fibers had an ultrahigh specific electrical conductivity of (1.01 ± 0.04) × 10 4 S m 2 kg -1 , 56% higher than Cu. Experimental and simulation results show that oxygen-containing functional groups on the surface of a wet-spun SWCNT fiber interact with the sputtered Cu atoms to produce strong bonding. Our hybrid fiber preserved its integrity and conductivity well after more than 5000 bending cycles. Furthermore, the current carrying capacity of the coaxial fiber reached 3.14 × 10 5 A cm -2 , three times that of commercial Cu wires.

The mammalian SWI/SNF (mSWI/SNF or BAF) family of chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression. The three final-form subcomplexes-cBAF, PBAF, and ncBAF-are distinct in biochemical componentry, chromatin targeting, and roles in disease; however, the contributions of their constituent subunits to gene expression remain incompletely defined. Here, we performed Perturb-seq-based CRISPR-Cas9 knockout screens targeting mSWI/SNF subunits individually and in select combinations, followed by single-cell RNA-seq and SHARE-seq. We uncovered complex-, module-, and subunit-specific contributions to distinct regulatory networks and defined paralog subunit relationships and shifted subcomplex functions upon perturbations. Synergistic, intra-complex genetic interactions between subunits reveal functional redundancy and modularity. Importantly, single-cell subunit perturbation signatures mapped across bulk primary human tumor expression profiles both mirror and predict cBAF loss-of-function status in cancer. Our findings highlight the utility of Perturb-seq to dissect disease-relevant gene regulatory impacts of heterogeneous, multi-component master regulatory complexes., Competing Interests: Declaration of interests C.K. is the Scientific Founder, Scientific Advisor to the Board of Directors, Scientific Advisory Board member, shareholder, and consultant for Foghorn Therapeutics, Inc. (Cambridge, MA); serves on the Scientific Advisory Boards of Nereid Therapeutics, Nested Therapeutics, and Fibrogen, Inc.; and is a consultant for Cell Signaling Technologies and Google Ventures. C.K. is also a member of the Molecular Cell advisory board. A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics, and until July 31, 2020 was an SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and ThermoFisher Scientific. Since August 1, 2020, A.R. has been an employee of Genentech and has equity in Roche. Since May 24, 2021, O.U. has been an employee of Genentech and has equity in Roche. J.E.O. is an employee and equity holder of Flagship Labs 84, Inc., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Water level rise is considered an environmental filter for the growth and reproduction of aquatic plants in lakes. Some emergent macrophytes can form floating mats, enabling them to escape from the negative effects of deep water. However, an understanding of which species can be uprooted and form floating mats easily and what factors affect these tendencies remains greatly elusive. We conducted an experiment to determine whether the monodominance of Zizania latifolia in the emergent vegetation community in Lake Erhai was related to its floating mat formation ability and to try to find the reasons for its floating mat formation ability during the continuous increase in water level over the past few decades. Our results showed that both the frequency and biomass proportion of Z. latifolia were greater among the plants on the floating mats. Furthermore, Z. latifolia was more likely to be uprooted than the other three previously dominant emergent species due to its smaller angle between the plant and the horizontal plane, rather than the root:shoot or volume:mass ratios. The dominance of Z. latifolia in the emergent community in Lake Erhai is due to its easier ability to become uprooted, allowing it to outperform other emergent species and become the single dominant emergent species under the environmental filter of deep water. The ability to uproot and form floating mats may be a competitive survival strategy for emergent species under the conditions of continuous significant water level rise.

Allelopathy has been considered a good explanation for the successful invasion of some invasive plants. However, the real latitudinal and longitudinal allelopathic effects on native species have rarely been documented since many exotics have spread widely. We conducted a Petri dish experiment to determine the latitudinal and longitudinal allelopathic patterns of an invasive alligator weed (Alternanthera philoxeroides) on a common crop (Lactuca sativa) in China, and find what determines the allelopathic intensity. The results showed that the allelopathic effects of A. philoxeroides increased with the latitude while decreased with the longitude. This indicated that A. philoxeroides used its allelopathy to gain competitive advantages more in its recent invaded communities than that in its early invaded ones as A. philoxeroides is expanding from southeast China to northwest China. Furthermore, we found that the allelopathic intensity of A. philoxeroide was negatively correlated to the leaf contents of soluble carbohydrate (SC), carbon (C) and nitrogen (N), but that was positively correlated to the leaf contents of soluble protein (SP), free amino acids (FAA), plant polyphenol (PP), phosphorus (P) and potassium (K). These results suggested that the allelopathic intensity of A. philoxeroide was more determined by the limited P and K nutrients as well as the intermediate allelochemicals (SP, FAA, PP) rather than the unlimited C, N and SC. Thus, we can speculate that the negative or positive effects of plant aqueous extracts are a function of not only the extract concentrations but also the trade-offs between inhibition and promotion of all components in the extracts. Then we could reduce the allelopathic effects of A. philoxeroide by controlling the component contents in the plant tissues, by fertilization or other managements, especially in the plant recent invaded communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plant invasive success is attributed to invaders' ecological advantages over their native neighbors. However, increasing evidence suggests that these advantages are expected to attenuate over time because of natural enemy accumulation, ecological evolution of native species and autotoxicity. We determined how an invasive Ageratina adenophora could remain its competitive advantages over time by avoiding its autotoxicity. Our results highlighted that the autotoxicity of A. adenophora in its invaded soil was reduced by some microbes. Moreover, an autotoxic allelochemical, 2-coumaric acid glucoside, detected in the invaded soil, demonstrated distinctly autotoxic effects on its seed germination and seedling growth . However, the autotoxic effects were greatly alleviated by a bacterium Bacillus cereus , accumulated by A. adenophora. Furthermore, the allelochemical could be almost completely degraded by B. cereus within 96 h. Accordingly, we speculate that A. adenophora could aggregate B. cereus to release its autotoxicity maintaining its competitive advantages over time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

In order to explore the characteristics of PM 2.5 oxidation potential and its impact sources in the suburbs of Baoding City in the winter of 2018, the dithiothreitol (DTT) method was used to determine the reactive oxygen species in PM 2.5 . Pearson correlation was used to analyze the relationship between the chemical components in PM 2.5 and the oxidation potential. PMF was used to analyze the pollution source of DTT v . Firstly, the results showed that the average value of ρ (PM 2.5 ) in Baoding in winter was (140.96±70.67) μg·m -3 higher than the concentration of PM 2.5 in Beijing during the same period. Secondly, both the DTT v and DTT m values of the oxidation potential were higher during the day than those at night[DTT v was (2.37±0.76) nmol·(min·m 3 ) -1 during the day and (2.14±1.17) nmol·(min·m 3 ) -1 at night; DTT m was (0.96±0.60) pmol·(min·μg) -1 during the day and (0.76±0.41) pmol·(min·μg) -1 at night]. This showed that the atmospheric environment during the day was more conducive to the generation and survival of active oxygen. In addition, through the analysis of the correlation between DTT v and carbohydrates, inorganic salt ions, OC, EC, and water-soluble metals, it was found that metal Fe, oxalate, and NH 4 + had a high correlation with DTT v both day and night (during the day: r =0.790, P <0.01, at night: r =0.960, P <0.01; during the day: r =0.609, P <0.01, at night: r =0.577, P <0.01; during the day: r =0.627, P <0.01, at night: r =0.586, P <0.01), and OC, levoglucan, mannan, and galactan were only highly correlated with DTT v in the daytime ( r =0.675, P <0.01; r =0.701, P <0.01; r =0.662, P <0.01; r =0.671, P <0.01). Finally, according to the PMF source analysis, there were five main pollution sources that affected DTT v :secondary sources (29.9%), biomass combustion (29.2%), dust (11.2%), mineral dust and industrial sources (8.6%), and traffic sources (21.1%). The influence of secondary sources and biomass combustion on DTT v was dominant.

Bacillus Thuringiensis (Bt) protein has a strong ability to complex with metal ions, which may increase the transport of metal ions in the soil multi-media system. In this study, the interactions between Cry1Ac protein and metal ions (Zn 2+ and Cd 2+ ) were investigated through spectroscopies and molecular docking methods. The spectra results showed that both Zn 2+ and Cd 2+ quenched the fluorescence intensity of Cry1Ac protein through the static quenching. The binding constants with 4-5 orders of magnitude also indicated the interactions between the ions and the Cry1Ac protein. The thermodynamic analysis showed that hydrogen bonds and van der Waals forces were predominant during the processes. In terms of the Förster non-radiation energy transfer theory, the binding distances between metal ions and Cry1Ac protein were approximately 0.21-0.24 nm, indicating the existence of a non-radiative energy transfer between them. Furthermore, molecular docking revealed that the metal ions participated in ligand binding with the Cry1Ac at the locations Asp569, Thr560, Asn564 and Gln566. The present work provided reasonable models helping us further understand the transport effect of heavy metals in the presence of Cry1Ac. The results could provide mechanistic insights into the nature of metal ions-Cry1Ac interactions and offer important information on the toxicity risk of metal ions-Cry1Ac binding interactions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The negative effects, caused by high light, on algae, terrestrial and marine aquatic plants are well documented; those negative effects on freshwater submerged plants are, however, not well known. We determined the negative effects of two common submerged species, Myriophyllum spicatum and Vallisneria natans , on their growth and reproduction in a shallow water experiment along an irradiance gradient. Our results highlighted that the plant mass, relative growth rate and shoot height of V. natans and M. spicatum , and root mass and root length:root mass of M. spicatum and leaf mass and shoot height:shoot mass of V. natans were significantly negatively affected in shallow water with high-light regime (>50 % of full light). While the ramet number of the two species was stimulated by from 20.0 to 36.4 %, and root length, root:shoot, chlorophyll (a:b), chlorophyll (a + b), leaf carbon, nitrogen and phosphorus contents of the two studied macrophytes were not significantly impacted by light. Our results indicated that the high-light inhibition of plant growth was greater on the shoots than on the roots of the plants, although these effects were significantly different between the two studied submerged species and among the measured traits. Accordingly, we should avoid negative effects caused by high light to improve the performance of submerged species when we conduct submerged aquatic vegetation restoration programmes in eutrophic lakes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Motivation: Recent advances in single-cell RNA-sequencing (scRNA-seq) technologies promise to enable the study of gene regulatory associations at unprecedented resolution in diverse cellular contexts. However, identifying unique regulatory associations observed only in specific cell types or conditions remains a key challenge; this is particularly so for rare transcriptional states whose sample sizes are too small for existing gene regulatory network inference methods to be effective., Results: We present ShareNet, a Bayesian framework for boosting the accuracy of cell type-specific gene regulatory networks by propagating information across related cell types via an information sharing structure that is adaptively optimized for a given single-cell dataset. The techniques we introduce can be used with a range of general network inference algorithms to enhance the output for each cell type. We demonstrate the enhanced accuracy of our approach on three benchmark scRNA-seq datasets. We find that our inferred cell type-specific networks also uncover key changes in gene associations that underpin the complex rewiring of regulatory networks across cell types, tissues and dynamic biological processes. Our work presents a path toward extracting deeper insights about cell type-specific gene regulation in the rapidly growing compendium of scRNA-seq datasets., Supplementary Information: Supplementary data are available at Bioinformatics online., Availability and Implementation: The code for ShareNet is available at http://sharenet.csail.mit.edu and https://github.com/alexw16/sharenet., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is a high incidence of leprosy among house-contacts compared with the general population. We aimed to establish a predictive model using these genetic factors along with epidemiological factors to predict leprosy risk of leprosy household contacts (HHCs)., Methods: Weighted genetic risk score (wGRS) encompassing genome wide association studies (GWAS) variants and five non-genetic factors were examined in a case-control design associated with leprosy risk including 589 cases and 647 controls from leprosy HHCs. We constructed a risk prediction nomogram and evaluated its performance by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling with 1000 resamples and a prospective design including 1100 HHCs of leprosy patients., Finding: The C-index for the risk model was 0·792 (95% confidence interval [CI] 0·768-0·817), and was confirmed to be 0·780 through bootstrapping validation. The calibration curve for the probability of leprosy showed good agreement between the prediction of the nomogram and actual observation. HHCs were then divided into the low-risk group (nomogram score ≤ 81) and the high-risk group (nomogram score > 81). In prospective analysis, 12 of 1100 participants had leprosy during 63 months' follow-up. We generated the nomogram for leprosy in the validation cohort (C-index 0·773 [95%CI 0·658-0·888], sensitivity75·0%, specificity 66·8%). Interpretation The nomogram achieved an effective prediction of leprosy in HHCs. Using the model, the risk of an individual contact developing leprosy can be determined, which can lead to a rational preventive choice for tracing higher-risk leprosy contacts., Funding: The ministry of health of China, ministry of science and technology of China, Chinese academy of medical sciences, Jiangsu provincial department of science and technology, Nanjing municipal science and technology bureau., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Arbuscular mycorrhizal fungi (AMF) are often considered bioameliorators. AMF can promote plant growth under various stressful conditions; however, differences between male and female clones in mycorrhizal strategies that protect plants from the detrimental effects of salinity are not well studied. In this study, we aimed to examine the interactive effects of salinity and AMF on the growth, photosynthetic traits, nutrient uptake, and biochemical responses of Morus alba males and females. In a factorial setup, male and female M. alba clones were subjected to three salinity regimes (0, 50, and 200 mM NaCl) and planted in soil with or without Funneliformis mosseae inoculation. The results showed that NaCl alone conferred negative effects on the growth, salinity tolerance, photosynthetic performance, and shoot and root ionic ratios (K + /Na + , Ca 2+ /Na + , and Mg 2+ /Na + ) in both sexes; in contrast, mycorrhizal inoculation mitigated the detrimental effects of salinity. Furthermore, the mycorrhizal effects were closely correlated with Mn 2+ , proline, and N concentrations. Females benefited more from AMF inoculation as shown by the enhancements in their biomass accumulation, and N, proline, K + , Mg 2+ , Fe 2+ , Zn 2+ , and Mn 2+ concentrations than males with mycorrhizal inoculation under saline conditions. In comparison, male plants inoculated with AMF showed improvements in biomass allocated to the roots, P, and peroxidase concentrations under saline conditions. These sex-specific differences suggest that male and female mulberry clones adopted different mycorrhizal strategies when growing under saline conditions. Overall, our results provide insight into the sex-specific difference in the performance of AMF-associated mulberry clones, suggesting that female mulberry could be more suitable for vegetation remediation than the male one, due to its higher salinity tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhang, Wang, He, Lv, Wei, Su, Wu and Li.)

The intracellular membrane trafficking is a complicated pathway network. Rab GTPases are key regulators of membrane trafficking that are generally considered as specific markers and indicators of various organelles and membrane trafficking in endocytic and secretory pathways. Dysfunction in axonal and endosomal transport related to Rab proteins is one of the most important causes of neurodegenerative diseases. In this review, we mainly introduce how the Rab proteins change in different neurodegenerative diseases and their regulatory roles in the pathological mechanisms of related diseases. We also discuss the relationships between mitochondrial and glial cell dysfunctions and Rab proteins. Further exploration of the regulatory roles of Rab proteins will shed lights on revealing the pathogenic mechanisms of neurological diseases and providing potential targets for the early diagnosis and treatment of neurological diseases.

A piscicide, rotenone (RT), is frequently used for clear and management of aquatic systems such as fish pond, and even for illegal fishing throughout the world. The effects of RT on submerged macrophytes remain elusive although the effects of RT on many kinds of animals are well documented. We wanted to determine the effects of RT on the growth and metabolism of three submerged plants (Vallisneria natans, Myriophyllum spicatum, Potamogeton maackianus) and try to find the reasons of these effects. The results showed that the shoot height, shoot dry weight, root dry weight, root:shoot ratios, contents of soluble protein and soluble carbohydrate of the three tested submerged plants were significantly negatively affected by RT and the effects were different among the studied species. Furthermore, pH rised a little and light transmission was greatly reduced in the water with RT treatment. We think that the negative effects of RT on the growth and metabolism of submerged species is partially attributing to the lower light caused by RT application. Accordingly, we highlight that submerged species may be greatly suppressed by RT, and we should apply RT in water ecosystems with great caution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Long-term, in vivo, fluorescent cell tracking probes are useful for understanding complex cellular processes including tissue regeneration, communication, development, invasion, and cancer metastasis. A near-infrared fluorescent, water-soluble probe is particularly important for studying these biological events and processes. Herein, a lysosome specific, near-infrared Bodipy probe with increased fluorescent intensity in the acidic, lysosome environment is reported. This Bodipy probe is packaged in a nanoparticle using DSPE-PEG 2000 . The resulting nanoparticle is intravenously delivered to a tumor xenograft, where the fluorescent Bodipy becomes useful for non-invasive, long-term, in vivo fluorescent tumor imaging for periods greater than 36 days. These long-term, in vitro and in vitro tracking data indicate that the described Bodipy nanoparticles hold great potential for monitoring biological processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS)., Methods: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [ 18 F]-IR783-AMBF 3 . [ 18 F]-IR783-AMBF 3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes., Results: IR783-AMBF 3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF 3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF 3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF 3 was safe under the tested dosage both in vitro and in vivo., Conclusion: The superior imaging properties of IR783-AMBF 3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats. We tested this probe in models relevant to the clinical diagnosis and treatment of central nervous system (CNS) diseases that affect CSF flow. In this study, fluorescein was radiolabeled with fluorine-18 to produce Fc-AMBF 3 . [ 18/19 F]-Fc-AMBF 3 was introduced at trace quantities (13.2 nmols, 100 μCi) intrathecally (between L5 and L6) in rats to observe the dynamic distribution and clearance of small molecules in the CSF by both [ 18 F]-PET and fluorescence (FL) imaging. Murine models were used to demonstrate the following utilities of Fc-AMBF 3 : (1) utility in monitoring the spontaneous CSFL repair of a compression fracture of the cribriform plate and (2) utility in quantifying CSF flow velocity during neurosurgical lumboperitoneal shunt placement. Fc-AMBF 3 clearly delineated CSF-containing volumes based on noninvasive PET imaging and in ex vivo FL histology. In vivo morbidity ( n = 16 rats, <2.7 mg/kg, 77 times the PET dose) was not observed. The clearance of the contrast agent from the CNS was rapid and quantitative ( t 1/2 = 33.8 ± 0.6 min by FL and t 1/2 = 26.0 ± 0.5 min by PET). Fc-AMBF 3 was cleared from the CSF through the vasculature and/or lymphatic system that supplies the cribriform plate and the temporal bone. Fc-AMBF 3 can be used to diagnose CSFLs, image CSFL repair, and determine the CSF flow velocity in the CNS or through lumboperitoneal shunts by PET/FL imaging. In conclusion, Fc-AMBF 3 PET imaging has been demonstrated to safely and dynamically quantitate CSF flow, diagnose fistulas associated with the CSF space, and approximate the clearance of small molecules in the CSF.

Clinical trials involving genome-edited cells are growing in popularity, where CAR-T immunotherapy and CRISPR/Cas9 editing are more recognized strategies. Genetic reporters are needed to localize the molecular events inside these cells in patients. Specifically, a nonimmunogenic genetic reporter is urgently needed as current reporters are immunogenic due to derivation from nonhuman sources. Prostate-specific membrane antigen (PSMA) is potentially nonimmunogenic due to its natural, low-level expression in select tissues (self-MHC display). PSMA overexpression on human prostate adenocarcinoma is also visible with excellent contrast. We exploit these properties in a transduced, two-component, H uman- D erived, G enetic, P ositron-emitting, and F luorescent (HD-GPF) reporter system. Mechanistically analogous to the luciferase and luciferin reporter, PSMA is genetically encoded into non-PSMA expressing 8505C cells and tracked with ACUPA-Cy3-BF3, a single, systemically injected small molecule that delivers positron emitting fluoride ( 18 F) and a fluorophore (Cy3) to report on cells expressing PSMA. PSMA-lentivirus transduced tissues become visible by Cy3 fluorescence, [ 18 F]-positron emission tomography (PET), and γ-scintillated biodistribution. HD-GPF fluorescence is visible at subcellular resolution, while a reduced PET background is achieved in vivo , due to rapid ACUPA-Cy3-BF3 renal excretion. Co-transduction with luciferase and GFP show specific advantages over popular genetic reporters in advanced murine models including, a "mosaic" model of solid-tumor intratumoral heterogeneity and a survival model for observing postsurgical recurrence. We report an advanced genetic reporter that tracks genetically modified cells in entire animals and with subcellular resolution with PET and fluorescence, respectively. This reporter system is potentially nonimmunogenic and will therefore be useful in human studies. PSMA is a biomarker of prostate adenocarcinoma and ACUPA-Cy3-BF3 potential in radical prostatectomy is demonstrated.

In weed management, using native parasites to control exotic weeds is considered a better alternative than classical biological control. But the risk must be assessed because of the potential damage caused by these agents. We conducted this project to investigate the mechanism driving the choice of a native obligate parasite, Cuscuta australis, between the exotic, Humulus scandens, and native plants as its host through field and pot experiments. The results showed that C. australis preferred the exotic weed over native (naturalized) hosts and caused a notable reduction in the biomass of H. scandens in the field. In contrast, the results of the pot experimentindicated that C. australis preferred a mix of native (naturalized) hosts over the exotic weed. Both texperiments indicated that the parasitic preference of C. australis was induced more by light irradiance than plant water, carbon (C), nitrogen (N) and phosphorus (P) contents, indicating that the native parasite can only be used to control H. scandens when the exotic weed forms mono-cultures or dominates the community. Accordingly, induction and release of C. australis to control H. scandens should be conducted with great caution.

Objective: To discuss the correlation between shock index (SI) and severity and the values to forecast the prognosis in patients with septic shock., Methods: 127 patients with septic shock admitted to intensive care unit (ICU) of Zhejiang Provincial People's Hospital from January 1st, 2016 to October 31st, 2017 were enrolled, and they were divided into survival group and death group according to the outcomes after 28-day hospitalized. The vital signs, laboratory indexes, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), lactate clearance rate (LCR) of 3 hours after fluid resuscitation, and shock index on admission (SI 1 ) and shock index of 3 hours after fluid resuscitation (SI 2 ) were compared between the two groups. The correlation among SI and APACHE II, SOFA, LCR was analyzed. The receiver operating characteristic curve (ROC) was drawn to evaluate the prognostic value of SI in patients with septic shock., Results: A total of 127 patients were included, 52 in survival group (40.9%) and 75 in death group (59.1%). The SI 1 , SI 2 , APACHE II and SOFA in the death group were significantly higher than those in the survival group (SI 1 : 1.62±0.46 vs. 1.35±0.32, SI 2 : 1.36±0.24 vs. 0.93±0.15, APACHE II: 17.5±4.0 vs. 13.6±3.5,SOFA: 9.5±2.3 vs. 6.3±1.5), and LCR was significantly lower than that in the survival group [(14.4±5.2)% vs. (28.6±8.6)%], with statistically significant differences (all P < 0.01). The correlation analysis showed that SI 1 was significantly positively correlated with APACHE II (r = 0.458, P = 0.000) and SOFA (r = 0.535, P = 0.000), SI 2 was also significantly positively correlated with APACHE II (r = 0.624, P = 0.000) and SOFA (r = 0.656, P = 0.000), while SI 1 and SI 2 were significantly negatively correlated with LCR (r values were -0.348, -0.435, both P = 0.000), and the SI 2 were more remarkable. ROC curve analysis showed that the area under ROC curve (AUC) of SI 1 for predicting the prognosis of septic shock was 0.720 [95% confidence interval (95%CI) = 0.620-0.831, P < 0.05]; when SI 1 = 1.68, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 79.5%, 65.6%, 0.451, 0.759 and 0.636, respectively. The AUC of the SI 2 to predict prognosis of septic shock was 0.826 (95%CI = 0.739-0.826, P < 0.05); when SI 2 = 1.37, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 85.7%, 87.6%, 0.733, 0.893 and 0.902, respectively., Conclusions: Compared with SI 1 , SI 2 was more correlated with the severity in patients with septic shock and it had more values to predict prognosis.

The hexagonal and monoclinic phase LaPO 4 and LaPO 4 :Eu nanostructures have been controllably synthesized by a citrate-induced hydrothermal process at 100 °C. The crystal growth of LaPO 4 nanostructures was investigated, and the phase transformation of nanostructured LaPO 4 was systematically studied by varying the citrate concentration, pH value and reaction temperature. When 0.8 mmol of citrate was added into the reaction system, the hexagonal phase LaPO 4 transformed into the monoclinic phase. High concentrations of citrate would lead to the formation of hexagonal phase LaPO 4 . The photoluminescence properties of the monoclinic phase LaPO 4 :Eu prepared using a citrate-induced process demonstrate that the electric dipole transition ( 5 D 0 → 7 F 2 ) is stronger than the magnetic dipole transition ( 5 D 0 → 7 F 1 ), which indicated that Eu 3+ is in a site with no inversion center. The strongest emission peak of hexagonal phase LaPO 4 :Eu comes from 5 D 0 → 7 F 1 . Furthermore, the citrate-induced hexagonal phase LaPO 4 :Eu has a stronger emission intensity than the hexagonal phase LaPO 4 :Eu prepared not using a citrate-induced process., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Contribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT., Methods: Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI., Results: The prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively., Conclusions: We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score., Competing Interests: There are no conflicts of interest

Objective: To investigate the effect of Rutin on the function and morphology of liver in type 1 diabetes mice induced by streptozotocin (STZ)., Methods: Type 1 diabetic mice model was established with the treatment of STZ by a 5 d intraperitoneal administration to male Kunming mice. Normal group had 12 mice without treatment of STZ,the mice with DM after STZ treated were randomly divided into DM group,low-dose (50 mg/kg) Rutin group and high-dose (100 mg/kg) Rutin group,each group had 12 mice. The mice in normal and DM group were given sodium carboxymethyl cellulose (10 mg/kg). Each mice was given above drugs by intragastric administration for 8 weeks. Postprandial random blood glucose was measured at 4 weeks and 8 weeks and the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),lactate dehydrogenase (LDH),total protein (TP) and albumin (ALB) in serum were detected by automatic biochemical analyzer after 8 weeks. The morphology of liver was observed by HE and Masson staining. The ultrastructure of liver tissue was observed by electron microscope., Results: After a continuous small-dose injection of STZ,the success rate of diabetes model mice were up to 98%. The blood glucose of the model group was significantly increased ( P <0.01),and the levels of ALT,AST and LDH in serum were significantly higher,and TP and ALB were lower than those in normal group ( P <0.05, P <0.01). Compared to the DM group,the levels of blood glucose were lower ( P <0.05) at 4 weeks and 8 weeks,the contents of ALT,AST and LDH were significantly decreased,and TP and ALB were improved in both Rutin dose group. High-dose group performed more obvious ( P <0.05, P <0.01). Morphological observation showed the tissue morphology of Rutin treatment group were improved obviously,and the effect was more significant in high-dose Rutin group., Conclusion: Rutin may improve the liver function and reduce the damage of liver tissue in STZ-induced type 1 diabetic mice., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Two novel core-shell structure ternary terbium composites SiO 2(600) @Tb(MABA-Si)·L(L:dipy/phen) nanometre luminescence materials were prepared by ternary terbium complexes Tb(MABA-Si)·L 2 ·(ClO 4 ) 3 ·2H 2 O shell grafted onto the surface of SiO 2 microspheres. And corresponding ternary terbium complexes were synthesized using (CONH(CH 2 ) 3 Si(OCH 2 CH 3 ) 3 ) 2 (denoted as MABA-Si) as first ligand and L as second ligand coordinated with terbium perchlorate. The as-synthesized products were characterized by means of IR spectra, 1 HNMR, element analysis, molar conductivity, SEM and TEM. It was found that the first ligand MABA-Si of terbium ternary complex hydrolysed to generate the Si-OH and the Si-OH condensate with the Si-OH on the surface of SiO 2 microspheres; then ligand MABA-Si grafted onto the surface of SiO 2 microspheres. The diameter of SiO 2 core of SiO 2(600) @Tb(MABA-Si)·L was approximately 600 nm. Interestingly, the luminescence properties demonstrate that the two core-shell structure ternary terbium composites SiO 2(600) Tb(MABA-Si)·L(dipy/phen) exhibit strong emission intensities, which are 2.49 and 3.35 times higher than that of the corresponding complexes Tb(MABA-Si)·L 2 ·(ClO 4 ) 3 ·2H 2 O, respectively. Luminescence decay curves show that core-shell structure ternary terbium composites have longer lifetime. Excellent luminescence properties enable the core-shell materials to have potential applications in medicine, industry, luminescent fibres and various biomaterials fields., Competing Interests: We declare we have no competing interests.

Fluorescein is modified to bear 18 F so that it can act as both a positron emitter, and a fluorophore, allowing detection by positron emission tomography (PET), scintillation, and fluorescent imaging (FL). [ 18 F]- 2 is injected into the intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that bathes the brain and spine. Injury in three different applications is visualized with [ 18 F]- 2 : 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2) detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic brain injury. In all models, the location of injury is visualized with [ 18 F]- 2 at high resolution. [ 18 F]- 2 PET imaging may be a superior alternative to current clinical contrast myelography and 131 I, 111 In or 99m Tc radionuclide cisternography. Like fluorescein, [ 18 F]- 2 may also have other uses in diagnostic or fluorescence guided medicine., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Propofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients., Methods: Eight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony., Results: Increasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange., Conclusions: Propofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n =238), 34.2%(Ⅱ grade, n =161), 12.4%(Ⅲ grade, n =58) and 2.8%(Ⅳ, n =13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n =115), 49.4%(Ⅱ grade, n =232), 20.6%(Ⅲ grade, n =97) and 5.5%(Ⅳ, n =26), respectively. 28- and 60-day mortality rate was 29.3%( n =161) and 32.5%( n =179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P =0.025) and 60-day survival rate(34.7% vs 20.0%, P =0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality( P <0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly( P ≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P =0.04), diabete mellitus(χ(2)=3.96, P =0.05), the use of vasoactive drugs(χ(2)=6.55, P =0.01), serum lactate(χ(2)=4.73, P =0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P =0.008), and APACHE Ⅱ score(χ(2)=12.1, P <0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P =0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

Objective: To investigate the factors associated with positive results of blood culture and the impact of positive results on the prognosis of patients in ICU of Peking University People's Hospital., Methods: We retrospectively analyzed 1 008 blood culture results of 379 critical ill adult patients in ICU from July 1st, 2013 to June 30th, 2014. According to blood culture results, the patients were divided into positive and negative groups. The patients' maximal body temperature, sample collection times, number of bottles within 24 hours, routine hematological variables [(white blood cell count (WBC), percentage of neutrophils (NEU%), lymphocyte count (LYM), platelet count (PLT)], serum C-reactive protein (CRP), usage of antibiotics were compared between the two groups, as well as the patients' gender, age, duration of mechanical ventilation, length of ICU stay and hospital mortality rate., Results: The total positiverate of blood culture of our study was 15.38%, and the positive rate of patients was 24.27%.When compared between positive group and negative group, the medians of sample collection times were 3 and 1(P<0.000 1); the medians of sample bottles were 4 and 4(P=0.001 2); the medians of WBC were 8.61×10(9)/L and 9.95×10(9)/L(P=0.001 7); and the medians of mechanical ventilation time were 179.5 hours and 47 hours(P<0.000 1); the medians of length of ICU stay were 17 days and 7 days(P<0.000 1), respectively. Hospital mortality rates in positive patients and negative patients were 35.87% and 20.21%(P=0.002 2), respectively. There was no significant difference(P>0.05) between the two groups in body temperature, NEU%, LYM, PLT, CRP or usage of antibiotics., Conclusions: Increasing the frequency of sampling and the bottles of blood culture will improve the positive rate of blood culture. The body temperature, WBC, NEU%, LYM, PLT, CRP, us age of antibiotics, gender and age have no effect on the positive rate of blood culture. The patients with positive blood culture results have longer duration of mechanical ventilation, longer ICU stayand higher hospital mortality rate.

To screen allelochemical-resistant species of the alien invasive weed Mikania micrantha, we studied the allelopathic inhibition effects of the leaf aqueous extract (LAE) of Mikania on seed germination and seedling growth of the 26 species native or naturalized in the invaded region in South China. Seed germination was more strongly negatively affected by LAE than seedling growth. Responses of seed germination and seed growth to LAE differed differently among the target species. LAE more strongly negatively affected seed germination, but less strongly negatively affected seedling growth, in non-legume species than in legume species. LAE more strongly negatively affected seed germination and seedling growth in native species than naturalized exotic species. Therefore, naturalized exotic non-legume seedlings are more suitable than seeds of native legume species for restoration of Mikania-invaded habitats.

Objectives/hypothesis: No accepted standard exists for the diagnosis of vocal fold paresis (VFP). Laryngeal specialists are surveyed to establish expert opinion on diagnostic methodology and criteria., Study Design: Cross-sectional survey., Methods: Questionnaires were distributed at laryngology conferences in fall 2013. Responses were collated anonymously and subjected to cross-tabulated data analysis., Results: Fifty-eight responses completed by posttraining physicians whose practice focused in laryngology ≥ 75% were analyzed. One (1.7%) relied principally on laryngeal electromyography, one (1.7%) on history, 10 (17%) on laryngoscopy, and 42 (72%) on strobovideolaryngoscopy for diagnosis. Only 12 (21%) performed laryngeal electromyography on > 50% of vocal fold paresis patients. Laryngeal electromyography sensitivity was considered moderate (61 ± 3.7%, σ = 28). Laryngoscopic/stroboscopic findings considered to have the strongest positive predictive value for VFP were slow/sluggish vocal fold motion (75 ± 3.0%, σ = 23), decreased adduction (67 ± 3.5%, σ = 27), decreased abduction (65 ± 3.4%, σ = 26), and decreased vocal fold tone (61 ± 3.5%, σ = 26). Asymmetric mucosal wave amplitude (52 ± 4.2%, σ = 32), asymmetric mucosal wave phase (60 ± 4.1%, σ = 31), hemilaryngeal atrophy (60 ± 4.0%, σ = 31), and asymmetric mucosal wave frequency (49 ± 4.0%, σ = 30) generated greatest disagreement., Conclusions: Surveyed expert laryngologists diagnose vocal fold paresis predominantly on stroboscopic examination. Gross motion abnormalities had the highest positive predictive value. Laryngeal electromyography was infrequently used to assess for vocal fold paresis., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

While H2N2 viruses have been sporadically isolated from wild and domestic birds, H2N2 viruses have not been detected among human populations since 1968. Should H2N2 viruses adapt to domestic poultry they may pose a risk of infection to people, as most anyone born after 1968 would likely be susceptible to their infection. We report the isolation of a novel influenza A virus (H2N2) cultured in 2013 from a healthy domestic duck at a live poultry market in Wuxi City, China. Sequence data revealed that the novel H2N2 virus was similar to Eurasian avian lineage avian influenza viruses, the virus had been circulating for ≥ two years among poultry, had an increase in α2,6 binding affinity, and was not highly pathogenic. Approximately 9% of 100 healthy chickens sampled from the same area had elevated antibodies against the H2 antigen. Fortunately, there was sparse serological evidence that the virus was infecting poultry workers or had adapted to infect other mammals. These findings suggest that a novel H2N2 virus has been circulating among domestic poultry in Wuxi City, China and has some has increased human receptor affinity. It seems wise to conduct better surveillance for novel influenza viruses at Chinese live bird markets.

To pursue an effective way to control freshwater algae, four extracts from a submerged macrophyte Hydrilla verticillata (Linn.f.) Royle were tested to study its inhibitory effects on Anabaena flos-aquae FACHB-245 and Chlorella pyrenoidosa Chick FACHB-9. Extract with the highest inhibiting ability was further studied in order to reveal the inhibitory mechanism. The results demonstrated that H. verticillata extracts inhibited the growth of A. flos-aquae and C. pyrenoidosa, and methanol extract had the highest inhibiting ability. The mechanism underlying the algal growth inhibition involves the superoxide anion radical generation that induces the damage of cell wall and release of intracellular components.

Objective: To evaluate the predictive performance of neuro-mechanical coupling (NMC) and neuro-ventilatory coupling (NVC) in the weaning outcome in patients with chronic obstructive pulmonary disease (COPD)., Methods: Sixteen patients were enrolled when the criteria for their first spontaneous breathing trial (SBT) was met. A 30-minute SBT was attempted, with the measurement of electrical activity of the diaphragm (Edi), NMC, NVC, NVC × NMC, index of rapid shallow breathing (f/Vt), airway occlusion pressure (P(0.1)) and f/Vt × P(0.1) at 0, 5 and 30 min. The receiver operating characteristic (ROC) curve was calculated to evaluate the predictive performance of each index., Results: Successful weaning (S group) was observed in 6 patients while weaning failure (F group) in 10 patients. (1) The predictive capacity of Edi: at 30 min of SBT, Edi showed higher values in the F group (P < 0.05), the area under the ROC curves (AUC) was 0.817(P < 0.05). (2) The predictive capacity of NVC and NMC: at 5, 30 min of SBT, NVC and NMC showed higher values in the S group (P < 0.05); at 30 min of SBT NVC presented the largest AUC than any other time of SBT (0.822, P < 0.05), while the AUC of NMC was 0.800(P > 0.05). (3) The predictive capacity of NVC × NMC: at 30 min of SBT, the AUC of NVC × NMC was larger than NVC (0.864, P < 0.05), showing greater sensitivity (100.0%) and specificity (83.3%). (4) The predictive capacity of f/Vt and P(0.1): f/Vt and f/Vt × P(0.1) presented poor predictive performance in the failed patients., Conclusions: Edi, NVC and NVC × NMC were good predictor for the weaning outcome in patients with COPD.

Objective: To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits., Methods: Twenty New Zealand white rabbits were randomly divided into 4 groups: (1) control group (n = 5); (2) Volume control (VC) group (n = 5); (3) Pressure support (PSV) group (n = 5); (4) NAVA group (n = 5). In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation. Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing. In all rabbits, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) of diaphragm were measured. Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber., Results: (1) MDA: Compared with the control [(0.15 ± 0.06) nmol/mg], PSV group [(0.30 ± 0.11) nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [(0.28 ± 0.19) nmol/mg] (F = 2.730, P > 0.05). MDA in VC group [(0.40 ± 0.16) nmol/mg] was significantly higher than the control group (P < 0.05). (2) SOD: Compared with control [(111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [(94 ± 9) U/mg] (F = 4.422, P > 0.05). SOD in VC group [(80 ± 21) U/mg] was significantly lower than the control group (P < 0.05). (3) GSH: Compared with control [(5.3 ± 1.0) mg/g] and PSV group [(4.5 ± 1.2) mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g] (F = 3.001, P > 0.05). GSH in VC group [(3.3 ± 1.7) mg/g] is significantly lower than control and NAVA groups (P < 0.05). (4) Light microscope: In VC group, many changes were observed in the muscle, such as myelofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups. (5) Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal. Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria. (6) CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group (P > 0.05); The CSA of type II fibers in VC group was markedly lower than control group (P < 0.05)., Conclusions: Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.

Objectives/hypothesis: By phage display, we have developed a novel peptide (NP41) that binds selectively to nerves following systemic administration. We evaluated the pattern of facial nerve labeling with fluorescently-labeled NP41 (F-NP41). We also tested whether F-NP41 highlights facial nerves well enough to identify nerve stumps accurately several weeks after nerve transection., Study Design: Forty-seven wild-type mice were studied prospectively. One surgeon performed the nerve transection, reanastomosis, and monitoring of functional recovery., Methods: Fluorescent labeling: F-NP41 was administered intravenously (20 mice). Nerve labeling was studied with fluorescence microscopy. Transection and reanastomosis: the right facial nerve was transected (25 mice). Three weeks after transection, F-NP41 was administered intravenously and fluorescence microscopy was used to identify the nerve stumps and reanastomosis in one group. Nerve identification and reanastomosis was performed with white light in another group without F-NP41. The control group underwent sham surgery. Time to nerve identification was recorded. Functional recovery was monitored for at least 8 weeks., Results: We found excellent labeling of intact and transected facial nerves following F-NP41 administration. Several weeks following nerve transection, F-NP41 provided accurate identification of the proximal and distal nerve stumps. Following reanastomosis, time to recovery and level of functional recovery was similar in the absence and presence of F-NP41., Conclusions: We show improved visualization of facial nerves with a novel systemically applied fluorescently labeled probe. Use of F-NP41 resulted in accurate identification of facial nerve stumps several weeks following transection. Functional recovery was similar with and without the use of F-NP41., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: To study the proliferation effect of the AM supernatant incubated activation of p38 mitogen activated protein kinases (p38MAPK) signal transduction pathway in human embryonic lung fibroblasts, and to participate in the development of fibrosis in silicosis., Methods: The silicotic alveolar macrophages were collected by bronchoalveolar lavage and incubated in vitro in the DMEM medium containing SiO₂ (50 µg/ml) and DMEM medium without SiO₂ for 18 h. Then the AM supernatant incubated for 18 h was collected. HELFs were isolated by organize paste block method, and incubated with AM supernatants. HELFs were divided into four groups: blank control groups, AM groups, SiO₂ + AM groups, SB203580 + SiO₂ + AM groups. The proliferation in the HELF was detected with MTT method and Flow cytometry., Results: The proliferation in the HELF acted with the conditioned AM supernatant fluid were more than blank control groups, AM groups and SB203580 + SiO₂ + AM groups [average optical density: (0.48 ± 0.03) vs (0.29 ± 0.01), (0.38 ± 0.02), (0.33 ± 0.03)], the values with MTT method were statistically different (P < 0.05); Proliferous index with flow cytometry in SiO₂ + AM groups (18.12 ± 0.82) was bigger than blank control groups (9.24 ± 0.48), AM groups (14.76 ± 0.43) and SB203580 + SiO₂ + AM groups (11.71 ± 0.70) and the values were statistically different(P < 0.05)., Conclusions: The AM supernatant stimulated by silicon dioxide can accelerate the proliferation in the HELF by activation of p38MAPK signal transduction pathway.

Background & Aims: Integrin contact with basement membrane is a major determinant of epithelial cell polarity. beta1 integrin heterodimers are the primary receptors for basement membrane in pancreatic acinar cells, which function to synthesize and directionally secrete digestive enzymes into a central lumen. Aberrant acinar secretion and exposure of the parenchyma to digestive enzyme activity lead to organ damage and pancreatitis., Methods: beta1 integrin conditional knockout mice were crossed to Ptf1a-Cre mice to ablate beta1 integrin in the pancreas. Histopathology of aged and cerulein-treated mice were assessed by histology and immunocytochemistry. Directional secretion was determined in vitro by FM1-43 loading with cerulein stimulation., Results: Pancreas-specific ablation of beta1 integrin led to progressive organ degeneration, associated with focal acinar cell necrosis and ductal metaplasia along with widespread inflammation and collagen deposition. beta1 Integrin-null pancreata were highly susceptible to cerulein-induced acute pancreatitis, displaying an enhanced level of damage with no loss in regeneration. Degenerating beta1 integrin-null pancreata were marked by disruption of acinar cell polarity. Protein kinase C epsilon, normally localized apically, was found in the cytoplasm where it can lead to intracellular digestive enzyme activation. beta1 Integrin-null acinar cells displayed indiscriminate secretion to all membrane surfaces, consistent with an observed loss of basolateral membrane localization of Munc18c, which normally prevents basal secretion of digestive enzymes., Conclusions: Ablation of beta1 integrin induces organ atrophy by disrupting acinar cell polarity and exposing the pancreatic parenchyma to digestive enzymes., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

A limnological study was carried out to determine the responses of superoxide dismutase (SOD) activities and soluble protein (SP) contents of 11 common aquatic plants to eutrophication stress. Field investigation in 12 lakes in the middle and lower reaches of the Yangtze River was carried out from March to September 2004. Our results indicated that non-submersed (emergent and floating-leafed) plants and submersed plants showed different responses to eutrophication stress. Both SOD activities of the non-submersed and submersed plants were negatively correlated with their SP contents (P < 0.000 1). SP contents of non-submersed plants were significantly correlated with all nitrogen variables in the water (P < 0.05), whereas SP contents of submersed plants were only significantly correlated with carbon variables as well as ammonium and Secchi depth (SD) in water (P < 0.05). Only SOD activities of submersed plants were decreased with decline of SD in water (P < 0.001). Our results indicate that the decline of SOD activities of submersed plants were mainly caused by light limitation, this showed a coincidence with the decline of macrophytes in eutrophic lakes, which might imply that the antioxidant system of the submersed plants were impaired under eutrophication stress.

Background: The presumed pathogenesis of posttraumatic anosmia is stretching or shearing of the olfactory nerves in a coup-contracoup head contusion. Direct injury to the brain is an alternate mechanism of injury. In this study we report a case where direct injury to the brain is the probable mechanism of injury., Methods: A case report was performed., Results: A 55-year-old man presented with loss of smell beginning 1 month after a closed head injury with loss of consciousness. The MRI showed posttraumatic scarring in the region of the olfactory bulbs., Conclusion: This case suggests that central nervous system injury to the olfactory bulbs and tracts may be a mechanism of posttraumatic anosmia.

Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role in invasion of many tumor types. EGF receptor ligands increase invasiveness in vivo, but it remains unclear how consequent effects on intrinsic cell motility behavior versus effects on extrinsic matrix properties integrate to result in net increase of translational speed and/or directional persistence of migration in a 3D environment. Understanding this convolution is important for therapeutic targeting of tumor invasion, as key regulatory pathways for intrinsic versus extrinsic effects may not be coincident. Accordingly, we have undertaken a quantitative single-cell imaging study of glioblastoma cell movement in 3D matrices and on 2D substrata across a range of collagen densities with systematic variation of protease-mediated matrix degradation. In 3D, EGF induced a mild increase in cell speed and a strong increase in directional persistence, the latter depending heavily on matrix density and EGF-stimulated protease activity. In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely a decrease in directional persistence (both independent of protease activity). Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance.

In this report, we describe an unusual patient with a choreiform movement disorder, misdiagnosed as Huntington disease, who later developed dense vitreitis leading to the identification of Treponema pallidum as the underlying pathogen of both abnormalities.

Toll-like receptors (TLRs) are a group of sensors on the surface of antigen-presenting cells, such as dendritic cells and macrophages, which recognize microbial pathogens and induce innate and adaptive immune responses. Periodontitis is an inflammatory disease characterized by the destruction of tooth-supporting structures. In order to address whether TLR4 signaling plays a role in periodontitis, we studied the gene expression change in human periodontal ligament cells (HPDLCs) in response to TLR4 ligand, lipopolysaccharide treatment by microarray analysis. Expression of TLR4 was detected in HPDLCs. Lipopolysaccharide treatment increased the expression of 12 genes (more than twofold), including TLR4, TLR5, TLR7, Pellino 1, colony stimulating factor 2 (CSF2) and IL-6. In addition, the expression of 15 genes (less than equal to twofold) was decreased, including Fos, LY64 and LY86. In addition, real-time PCR was used to confirm the change of gene expression of TLR4, IL-6 and Fos. We also showed that the upregulation of IL-6 by lipopolysaccharide treatment was TLR4-dependent. This pattern of gene expression indicates that pathogens may trigger TLR4 signaling and cause periodontitis. Manipulating TLR4 signaling may potentially become one of the recognized therapies for periodontitis.

A combination of targeted probes and new imaging technologies provides a powerful set of tools with the potential to improve the early detection of cancer. To develop a probe for detecting colon cancer, we screened phage display peptide libraries against fresh human colonic adenomas for high-affinity ligands with preferential binding to premalignant tissue. We identified a specific heptapeptide sequence, VRPMPLQ, which we synthesized, conjugated with fluorescein and tested in patients undergoing colonoscopy. We imaged topically administered peptide using a fluorescence confocal microendoscope delivered through the instrument channel of a standard colonoscope. In vivo images were acquired at 12 frames per second with 50-microm working distance and 2.5-microm (transverse) and 20-microm (axial) resolution. The fluorescein-conjugated peptide bound more strongly to dysplastic colonocytes than to adjacent normal cells with 81% sensitivity and 82% specificity. This methodology represents a promising diagnostic imaging approach for the early detection of colorectal cancer and potentially of other epithelial malignancies.

Objective: To determine the biomechanical characteristics of mandibular fractures in different site., Methods: Nine adult mandibular specimens were measured precisely. The data was used to establish a three-dimensional model. When mandibular was under functional loading, the bending and torsion moment as well as shear force of angle, body and symphyseal fracture was calculated. The data were analyzed by Origin 6.0 software., Results: Angle fracture had relatively high positive bending moment and high shear force. Body fracture had positive as well as negative bending moment and the highest torsion moments. Symphyseal fracture had only negative bending moment and relatively low shear force., Conclusion: Angle, body and symphyseal fractures each have a biomechanics characteristic. These biomechanics characteristic should have an important meaning in the treatment of mandibular fractures and instructing patient how to bite correctly.