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Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host's innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during T. gondii infection. In this study, the ROP5 from the PRU strain of T. gondii was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates T. gondii infection and provides new clues for strategies to prevent and control toxoplasmosis.

The fluorosulfonyldifluoromethylation of unactivated alkenes and (hetero)arenes with iododifluoromethanesulfonyl fluoride (ICF 2 SO 2 F) under visible light photoredox catalysis was successfully developed. Key to the successful fluorosulfonyldifluoromethylation of aromatic compounds was the usage of AgOTf as an additive to promote the formation of the CF 2 SO 2 F radical. The protocol provided a straightforward way to introduce the interesting and useful CF 2 SO 2 F group on sp 3 and sp 2 carbons.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

C - N axially chiral compounds have recently attracted significant interest among synthetic chemistry community due to their widespread application in pharmaceuticals, advanced materials and organic synthesis. Although the emerging asymmetric Catellani reaction offers great opportunity for their modular and efficient preparation, the only operative chiral NBE strategy to date requires using half stoichiometric amount of chiral NBE and 2,6-disubstituted bromoarenes as electrophiles. We herein report an efficient assembly of C-N axially chiral scaffolds through a distinct chiral ligand strategy. The crucial chiral source, a biimidazoline (BiIM) chiral dinitrogen ligand, is used in relatively low loading and permits the use of less bulky bromoarenes. The method also features the use of feedstock plain NBE, high reactivity, good enantioselectivity, ease of operation and scale-up. Applications in the preparation of chiral optoelectronic material candidates featuring two C-N chiral axes and a chiral ligand for asymmetric C-H activation have also been demonstrated., (© 2024. The Author(s).)

Objective: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway., Methods: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway., Results: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator., Conclusion: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA., (© 2024. The Author(s).)

Over the past few years, there has been a significant focus on air pollution due to its various detrimental effects on human health. However, its influence on people's tendency to have children remains uncertain, as only a few studies have examined the correlation between public perception of air pollution and the desire to start a family. This article introduces a theoretical framework utilizing a two-stage interval iteration model to explore the connection between children's relative utility and the perception of air pollution. Data for this study were gathered from the "Chinese General Social Survey" (CGSS 2013). The CGSS 2013 project employed a four-stage stratified random sampling technique and conducted household interviews using questionnaires. The sample covered 28 provincial-level cities across China. The hypothesis was tested using a Probit regression model. The findings indicate that individuals considering air pollution a significant issue are 8.62% less likely to have more than one child. The variation in fertility desire sensitivity to air pollution points to heterogeneity among residents, such as registered residents and those living in various residential areas, as well as individuals with different characteristics like education levels. The study concludes that air quality significantly influences human fertility desire, highlighting the urgent necessity to raise awareness of environmental protection issues among both the public and authorities. In particular, there are two key steps to address this issue. Firstly, the government should establish clear air pollution control objectives and refine policies to enhance governance efficiency. Secondly, there is a need to encourage environmentally friendly behaviours among the public, promote more significant involvement in public environmental matters, and ensure effective oversight of the government's responsibilities in managing air pollution., (© 2023. The Author(s) under exclusive licence to International Society of Biometeorology.)

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10  TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60  TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

Objective: To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial., Methods: This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments., Results: During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group., Conclusions: CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Sexual dimorphism exists widely in animals, manifesting in different forms, such as body size, color, shape, unique characteristics, behavior, and sound. Of these, body mass dimorphism is the most obvious. Studies of evolutionary and ontogenetic development and adaptation mechanisms of animals' sexual dimorphism in body mass (SDBM), allow us to understand how environment, social group size, diet, and other external factors have driven the selection of sexual dimorphism. There are fewer reports of the ontogenetic development of sexual dimorphism in body mass in Rhinopithecus . This study explores the ontogenetic development pattern of SDBM in wild black-and-white snub-nosed monkeys ( R. bieti ), and the causes resulting in extreme sexual dimorphism compared to other colobines. A significant dimorphism with a ratio of 1.27 ( p < 0.001) appears when females enter the reproductive period around six years old, reaching a peak (1.85, p < 0.001) when males become sexually mature. After the age of eight, the SDBM falls to 1.78, but is still significant ( p < 0.001). The results also indicate that males had a longer body mass growth period than females (8 years vs. 5 years); females in larger breeding units had a significantly higher SDBM than those in smaller ones (2.12 vs. 1.93, p < 0.01). A comparative analysis with other colobines further clarifies that Rhinopithecus and Nasalis , which both have multilevel social organization, have the highest degree of SDBM among all colobines. The large SDBM in R. bieti can be explained through Bergman's and Rensch's rules. Overall, environmental adaptation, a distinctive alimentary system, and a complex social structure contribute to R. bieti having such a remarkable SDBM compared to other colobines. In addition, we found that females' choice for males may not be significantly related to the development of SDBM.

Guanylate binding protein 5 (GBP5) is a member of the interferon (IFN)-inducible large guanosine triphosphate hydrolases (GTPase) family that regulates cell-autonomous immunity and malignant tumor transformation. However, its specific roles and underlying mechanisms GBP5 in gastric cancer (GC) remain unknown. In this study, we aimed to determine the role GBP5 and underlying mechanism of GBP5 in GC cell progression. Potential oncogenic roles of GBP5 in GC as well as its relationship with the tumor immune microenvironment (TIME) were comprehensively evaluated using bioinformatics analysis. Protein expression levels of GBP5 and their correlation with clinicopathological features of patients were assessed using immunohistochemistry. In addition, diverse in vitro functional experiments were performed to identify the functions of GBP5 in GC. Downstream targets of GBP5 were identified using RNA-sequencing analysis and verified using western blotting or quantitative polymerase chain reaction analysis in different cell lines. GBP5 expression is commonly upregulated and promotes the proliferation and migration of GC cells. Mechanistically, GBP5 was regulated by the IFNγ-Janus kinase (JAK1)-signal transducer and activator of transcription 1 (STAT1) axis and induced CXCL8 expression. Interestingly, GBP5 -induced CXCL8 regulated the JAK1-STAT1 signaling pathway to form a positive feedback loop. Moreover, GBP5 is closely related to the TIME and may be used as a biomarker for predicting the efficacy of immunotherapy. Our findings revealed a new JAK1-STAT1/GBP5/CXCL8 pathway and highlighted the value of GBP5 as a predictive biomarker and novel target for GC intervention., Competing Interests: None., (AJCR Copyright © 2023.)

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9}  GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

A variety of nereidid species have been reported from the South China Sea, although little is known about the deep-sea species in this area. Recently, two specimens belonging to a novel nereidid polychaete were collected from a sedimentary habitat during an environmental survey to a deep-sea basin where cold seeps occur. This new species, Nereistricirrata sp. nov. , is described herein, based on morphological and molecular analyses. The most noteworthy feature is the absence of eyes on the prostomium; it can be distinguished from other eyeless Nereis species by the arrangement of conical paragnaths on the pharynx, the nature of homogomph falcigers and the shape of notopodial lobes in posterior chaetigers. The reconstructed phylogenetic tree, using concatenated sequences of mtCOI, 16S, and 18S rRNA, showed that all Nereis species included in this study form a monophyletic clade with full support. The mtCOI-based interspecific comparisons revealed a high genetic divergence (23.1%-37.3% K2P) from four-eyed Nereis species with the available sequences. This is the first record of an eyeless Nereis species in the South China Sea., (Jun-Hui Lin, Ya-Qin Huang, Qian-Yong Liang, Xue-Bao He.)

Midbrain dopamine (DA) neurons are associated with locomotor and psychiatric disorders. DA phenotype is specified in ancestral neural precursor cells (NPCs) and maintained throughout neuronal differentiation. Here we show that endogenous expression of MeCP2 coincides with DA phenotype specification in mouse mesencephalon, and premature expression of MeCP2 prevents in vitro cultured NPCs from acquiring DA phenotype through interfering NURR1 transactivation of DA phenotype genes. By contrast, ectopic MeCP2 expression does not disturb DA phenotype in the DA neurons. By analyzing the dynamic change of DNA methylation along DA neuronal differentiation at the promoter of DA phenotype gene tyrosine hydroxylase (Th), we show that Th expression is determined by TET1-mediated de-methylation of NURR1 binding sites within Th promoter. Chromatin immunoprecipitation assays demonstrate that premature MeCP2 dominates the DNA binding of the corresponding sites thereby blocking TET1 function in DA NPCs, whereas TET1-mediated de-methylation prevents excessive MeCP2 binding in DA neurons. The significance of temporal DNA methylation status is further confirmed by targeted methylation/demethylation experiments showing that targeted de-methylation in DA NPCs protects DA phenotype specification from ectopic MeCP2 expression, whereas targeted methylation disturbs phenotype maintenance in MeCP2-overexpressed DA neurons. These findings suggest the appropriate timing of MeCP2 expression as a novel determining factor for guiding NPCs into DA lineage., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Antibody development is the integral process of generating and characterizing an antibody. It commences by inoculating the antigen of interest into laboratory animals, allowing the immune system develops large quantities of antibodies. This was aimed at developing antibodies against the virion of Goatpox and Sheeppox virus vaccines. The ability of Goatpox and Sheeppox vaccines was assessed. Regarding this study, the antibody titers against both Goatpox and Sheeppox viruses was increased in the same manner. The amount of IgG was determined to be 2.29 μg/μl and 2.18 μg/μl against virions of Goatpox virus and Sheeppox respectively. The purified IgG was analyzed by SDS-PAGE. Different bands of the purified antibodies were clearly visualized, and the molecular weight of IgG was estimated to be 67 kDa and 25 kDa. Additionally, antigen/antibody binding was confirmed by Western blot using GTPV A27 antigen. No significant differences in antibody titers were observed between the two groups (p < 0, 05)., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Plasmonic demultiplexers hold promise for the realization of the subwavelength and high-splitting ratio dichroic splitter and have a wide range of applications from optical communication, and manipulation to ultrafast data treatment. However, this vision has not been realized for a long time due to lacking the suitable splitting structure design, which limits its further development of integrated photonic circuits. Here, we demonstrate a plasmonic demultiplexer with subwavelength feature size (0.54 µm) and broadband spectral (620-870 nm) range, and high-splitting ratio (17 dB in experiments and 20 dB in calculations). It consists of two adjacent Fabry-Perot cavities (covered by PMMA polymer) and coupling gratings, which are integrated with the Au waveguide. The relatively simple double cavities design of our device has a simple theoretical analysis and fabrication process. Our work has relevance for various optical applications, such as multiple wavelength photodetectors and optical multichannel interconnects.

Trichiurus nanhaiensis is one of the most important commercial fish species in the South China Sea. This study aimed to investigate the level of genetic variation and population genetic structure of T. nanhaiensis in the South China Sea for the first time, using 281 individuals collected from seven locations along the coast of mainland China, Taiwan, and Hainan Island. A high level of haplotype diversity and low nucleotide diversity were detected in the mitochondrial DNA cyt b gene and nuDNA RYR 3 gene. The overall expected heterozygosity (He = 0.693) among the seven populations ranged from 0.681 to 0.706 in microsatellite DNA data, which revealed high levels of genetic diversity. Significant genetic differentiation was found in Taidong populations in Taiwan, revealing the prevention of gene flow caused by the Kuroshio Current. Two major lineages based on the cyt b gene suggested that the Taiwan Strait acted as a geographic barrier for T. nanhaiensis during the glacier periods in the late Pleistocene. The Bayesian skyline plot also revealed that population demographic expansion of T. nanhaiensis was estimated to have occurred in 0.1 Mya. Our results indicated that all populations of T. nanhaiensis had experienced a recent genetic bottleneck following recent expansion based on ABC analysis., (© 2022. The Author(s).)

The close association between astrocytes and microglia causes great difficulties to distinguish their individual roles in innate immune responses in central nervous system. Current chemical-based methods to eliminate microglia in glial cell culture introduce various molecular and functional alterations to astrocytes. Here, we describe a novel two-step approach to achieve a complete elimination of microglia without affecting the biological properties of co-cultured astrocytes by temporal treatment of histone deacetylase inhibitor trichostatin A (TSA). We verify TSA as a potent inducer for microglial-specific apoptotic cell death, which also causes comprehensive gene expression changes in astrocytes. However, withdrawal of TSA not only ensures no microglia repopulation, but also restores all the gene expression changes in terms of astrocyte functions, including neurotrophic factors, glutamate and potassium transporters, and reactive astrocyte subtypes. By contrast, withdrawal of PLX5622, the commonly used colony-stimulating factor 1 receptor inhibitor neither prevents microglia repopulation nor restores the gene expression changes mentioned above. Using this method, we are able to discriminate differential roles of microglia and astrocytes in the induced expression of antiviral and pro-inflammatory cytokines upon various pathological stimuli including the spike protein of SARS-CoV-2. This simple and efficient method can be customized for the understanding of microglia-astrocyte interaction and the development of epigenetic therapies that target over-activated microglia in neuroinflammation-related diseases., (© 2022 International Society for Neurochemistry.)

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M&#95;{Pl} and that the second-order LIV scale is >10^{-3}M&#95;{Pl}. Both limits improve by at least one order of magnitude the previous results.

Four Trichiurus species, T.japonicus , T.lepturus , T.nanhaiensis , and T.brevis , from the coasts of the China Seas, have been identified and their entire mitochondrial genomes (mitogenomes) have been sequenced by next-generation sequencing technology. A comparative analysis of five mitogenomes was conducted, including the mitogenome of T.gangeticus . The mitogenomes contained 16.568-16.840 bp and encoded 36 typical mitochondrial genes (13 protein-coding, 2 ribosomal RNA-coding, and 21 transfer RNA-coding genes) and two typical noncoding control regions. Although tRNA Pro is absent from Trichiurus mitogenomes, when compared with the 22 tRNAs reported in other vertebrates, the gene arrangements in the mitogenomes of the studied species are consistent with those in most teleost mitogenomes. The full-length sequences and protein-coding genes (PCGs) in the mitogenomes of the five species had obvious AT biases and negative GC skew values. Our study indicate that the specimens in the Indian Ocean are neither T.lepturus nor T.nanhaiensis but they are T.gangeticus ; the Trichiurus species composition in the Indian Ocean is totally different from that in Pacific and Atlantic oceans; there are at least two Trichiurus species in Indian Ocean; and the worldwide systematics and diversity of the genus Trichiurus need to be reviewed., (Mu-Rong Yi, Kui-Ching Hsu, Sui Gu, Xiong-Bo He, Zhi-Sen Luo, Hung-Du Lin, Yun-Rong Yan.)

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10 -4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 10 36 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25  TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17&#95;{stat}±0.02&#95;{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160  TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 15 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays 1 . The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2 ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane 3-6 , unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

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.)

We measured stable carbon and nitrogen isotopes and calculated trophic level and trophic niche of Trichiurus japonicus , with samples collected from the Beibu Gulf from 2008 to 2009 and 2018. The differences between two periods were compared and analyzed to explore the changes of its ecological adaptation. The results showed that value of δ 13 C varied substantially between the two periods. The narrowed range and the smaller mean value of δ 13 C in 2018 suggested that their food source changed from upper-middle to lower-middle waters. The values of δ 15 N were stable, and the range and mean values of trophic level (3.38-3.43) did not change significantly, which indicated a stable trophic level of T. japonicas in the past decade. The correlation between δ 13 C and preanal length was not significant, but a positive correlation between δ 15 N and preanal length. In terms of trophic niche, the indicators had decreased in different degrees in 2018 with 1.1%-32.1%. The value of total area and standard ellipse area decreased from 20.20 and 4.68 to 14.20 and 3.18, respectively, indicating that the niches of T. japonicas in the Beibu Gulf had varied obviously and that their ability to use resources and adapt to the environment had declined. It was speculated that in the past decade, the mean trophic level of T. japonicas in the Beibu Gulf had not changed significantly. Due to the change of food sources, however, the diversity of trophic sources had decreased, and the trophic niche had become smaller.

Accumulating studies have shown that the dysregulation of microRNAs is related to the carcinogenesis and development of gastric cancer (GC), and the role of miR-635 in GC remains largely unknown. miR-635 and Kinesin Family Member C1 (KIFC1) mRNA expression in GC tissues and paracancerous tissues and cells were detected by quantitative real-time PCR. KIFC1 protein expression in GC tissues and paracancerous normal tissues and cells was detected by immunohistochemistry and western blot. Cell proliferation was monitored by Cell Counting Kit-8 assay and 5-bromo-2'-deoxyuridine assay. Transwell assay was employed to detect the migration and invasion of GC cells. The dual-luciferase reporter gene assay was adopted to detect the targeting relationship between miR-635 and KIFC1. Compared with paracancerous tissues, miR-635 expression was remarkably decreased in GC tissues; conversely, KIFC1 expression was significantly increased. Compared with human normal gastric epithelial cell GSE-1, miR-635 expression was markedly decreased in GC cell lines. Meanwhile, KIFC1 expression was significantly increased, and the Kaplan-Meier Plotter database showed that its high expression was remarkably associated with poor prognosis. Additionally, miR-635 can negatively regulate KIFC1. miR-635 can target KIFC1 to inhibit proliferation, migration and invasion of GC cells. Collectively, miR-635 is lowly expressed in GC, and it inhibits proliferation, migration and invasion of GC cells via regulating KIFC1., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Heart is a multi-cellular organ made up of various cell types interacting with each other. Cardiomyocytes may benefit or suffer from crosstalk with noncardiomyocytes in response to diverse kinds of cardiac stresses. Proteasome dysfunction is a common cardiac stress which causes cardiac proteotoxicity and contributes to cardiac diseases such as heart failure and myocardial infarction. The role of crosstalk between cardiomyocytes and noncardiomyocytes in defense of cardiac proteotoxicity remains unknown. Here, we report a cardiomyocyte-specific survival upon proteasome inhibition in a heterogeneous culture consisting of cardiomyocytes and other three major cardiac cell types. Conversely, cardiomyocyte apoptosis is remarkably induced by proteasome inhibition in a homogeneous culture consisting of a majority of cardiomyocytes, demonstrating an indispensable role of noncardiomyocytes in the prevention of cardiomyocyte apoptosis resulting from proteasome inhibition. We further show that cardiomyocytes express brain natriuretic peptide (BNP) as an extracellular molecule in response to proteasome inhibition. Blockade of BNP receptor on noncardiomyocytes significantly exacerbated the cardiomyocyte apoptosis, indicating a paracrine function of cardiomyocyte-released extracellular BNP in activation of a protective feedback from noncardiomyocytes. Finally, we demonstrate that proteasome inhibition-activated transcriptional up-regulation of BNP in cardiomyocytes was associated with the dissociation of repressor element 1 silencing transcription factor (REST)/ histone deacetylase 1 (HDAC1) repressor complex from BNP gene promoter. Consistently, the induction of BNP could be further augmented by the treatment of HDAC inhibitors. We conclude that the crosstalk between cardiomyocytes and noncardiomyocytes plays a crucial role in the protection of cardiomyocytes from proteotoxicity stress, and identify cardiomyocyte-released BNP as a novel paracrine signaling molecule mediating this crosstalk. These findings provide new insights into the key regulators and cardioprotective mechanism in proteasome dysfunction-related cardiac diseases.

Cancer has always been an enormous threat to human health and survival. Surgery, radiotherapy, and chemotherapy could improve the survival of cancer patients, but most patients with advanced cancer usually have a poor survival or could not afford the high cost of chemotherapy. The emergence of oncolytic viruses provided a new strategy for us to alleviate or even cure malignant tumors. An oncolytic virus can be described as a genetically engineered or naturally existing virus that can selectively replicate in cancer cells and then kill them without damaging the healthy cells. There have been many kinds of oncolytic viruses, such as herpes simplex virus, adenovirus, and Coxsackievirus. Moreover, they have different clinical applications in cancer treatment. This review focused on the clinical application of oncolytic virus and predicted the prospect by analyzing the advantages and disadvantages of oncolytic virotherapy., (Copyright © 2020 Cao, He, Sun, Chen, Wan, Xu, Feng, Li, Chen and Xiong.)

Background: Flavonoid monomers are proved to have an anti-inflammatory effect and may also be promising for chronic pain treatment. In the present study, the analgesic effect and the relevant mechanisms of luteoloside, one of the flavonoid monomers, were investigated., Methods: The analgesic effect of luteoloside was first evaluated in complete Freud's adjuvant induced inflammatory model by von Frey test and Hargreaves test in both male and female mice. The interleukin-1β levels in plantar tissue, serum, dorsal root ganglion, and the dorsal horn of the spinal cord were determined by enzyme-linked immunosorbent assay or immunofluorescence. The activation of macrophage/microglia was tested by Iba-1 staining., Results: Our data showed that luteoloside exhibited both acute and chronic analgesic phenotypes. Every single dose of luteoloside solution reached the peak transient analgesic effect 2 h after administration and lasted less than 6 h. About 14 consecutive days administration (one dose per day) later, luteoloside showed a sustained analgesic effect which lasted more than 24 h. Celecoxib 20 mg/kg combined with luteoloside 40 mg/kg achieved a similar analgesic effect as celecoxib 40 mg/kg alone. Luteoloside inhibited interleukin-1β expression in plantar tissue, dorsal root ganglion, the dorsal horn of spinal cord, and serum, after 14 days of continuous administration. Furthermore, our results also showed that the activation of macrophage/microglia in dorsal root ganglions were significantly inhibited 2 h after each single dose in daily luteoloside administration and recovered to a higher level 6 h later. These findings might be involved in the mechanisms of the acute analgesic effect of luteoloside., Conclusion: Luteoloside presents an analgesic effect via anti-inflammatory and other mechanisms such as inhibiting the activation of macrophage/microglia., (Copyright © 2020 Shi, He, Zhao and Wang.)

Objective: To evaluate the feasibility and efficacy of partial superficial parotidectomy with V-shaped incision by comparing with the Blair incision and hairline N-shaped incision. Methods: From January 2015 to January 2016, 60 patients (47 males and 13 females, with an age range of 25- 63 years) required for superficial partial parotid gland resection were randomly divided into three groups: V-shaped incision (VI) group, Blair incision (BI) group and hairline N-shaped incision (NI) group, with 20 cases in each group.Intraoperative, postoperative and follow-up indexes were compared between three groups. Operative time and drainage volume in the surgery of tumors at different sites in VI group were compared. SPSS18.0 software was used for statistic analysis. Results: There were no statistically significant differences among the three groups in operative time, drainage volume, postoperative hospital stay, periauricular numbness, fistulas, pain score, facial palsy, and scar score at the 3rd month after surgery ( P >0.05). For appearance satisfaction score at the 6th month after surgery, VI group was better than BI group or NI group, with significant differences(VI group vs. BI group: 9.00[8.00, 9.00] vs. 5.00[4.00, 5.25], χ(2)=6.629, P <0.001; VI group vs. NI group: 9.00[8.00, 9.00] vs. 7.00[6.00, 8.00], χ(2)=2.942, P =0.010; BI group vs. NI group: 5.00[4.00, 5.25] vs. 7.00[6.00, 8.00], χ(2)=-3.687, P =0.001). For tumors located in the front, upper and middle of parotid gland, there were no statistically significant differences in operative time and drainage volume between the three groups ( P >0.05). For tumors located at the lower part of parotid gland, the difference in operative time between the three groups was statistically significant ( F =7.278, P =0.01). With pairwise comparison, operative time in VI group was longer than that in BI group or NI group, but there was no significant difference between BI group and NI group (VI group vs. BI group: (181.00±22.89) min vs. (132.50±9.01) min, t =3.694, P =0.004; VI group vs. NI group:(181.00±22.89) min vs. (149.00±15.94) min, t =2.585, P =0.025; BIgroup vs. NI group, (132.50±9.01) min vs. (149.00±15.94) min, t =1.257, P =0.235). For tumors located at the lower part of parotid gland, the differences in intraoperative drainage volume were not statistically significant between three groups ( P >0.05). There were no statistically significant differences in operative time and drainage volume in the surgery of tumors at different sites in VI group ( P >0.05). Conclusions: By use of V-shaped incision for the surgery of benign parotid gland tumors, the operation time of tumors located only in the lower part of the parotid gland will be prolonged. For tumors in different sites without increasing surgical complications, this modality can get good cosmetic effect.

Purpose: To investigate the clinical efficacy and safety of ultrasound-guided percutaneous nephrolithotomy (PCNL) assisted by a puncture frame., Materials and Methods: Clinical data of 106 patients with nephrolithiasis who underwent ultrasound-guided percutaneous nephrolithotomy from October 2016 to December 2017 in our hospital were analyzed retrospectively. The channels were established by the assistance of the puncture frame., Results: The mean puncture time was 35 ± 18 seconds, the puncture was performed 1.3 ± 0.9 times on average. The puncture was successfully performed at first attempt in 73 cases. The mean operation time was 67.3 ± 39.2 min, and the mean intraoperative blood loss was 48 ± 22 mL. The stones were located on the left in 50 (47.2%) cases, and on the right in 56 (52.8%) cases. Channels were established through the upper, middle and lower calyces of the kidney in 78 (73.6%), 20 (18.9%), and 8 (7.5%) cases, respectively. The puncture sites were located on the upper and lower of 12th rib in 81 (76.4%) and 25 (23.6%) cases. Intraoperative and postoperative blood transfusion was given in four cases. Pleural injury occurred in two cases, and hydropneumothorax occurred in one case in whom closed thoracic drainage was performed. The stone free rate after a single surgery was 87.7% (93/106)., Conclusion: Establishing a percutaneous nephrolithotomy access tract under ultrasound guidance using the puncture frame is an efficacious and safe approach.

Introduction: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study., Methods: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared., Results: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05)., Conclusions: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

General anesthesia with double-lumen endobronchial intubation is considered mandatory for thoracoscopic bullectomy. We assessed the safety and feasibility of thoracoscopic bullectomy for treatment of primary spontaneous pneumothorax (PSP) under intubating laryngeal mask airway (ILMA) with spontaneous breathing sevoflurane anesthesia combined with thoracic paravertebral block (TPB).From January 2018 to December 2018, some 34 consecutive patients with PSP were treated by thoracoscopic bullectomy under ILMA with spontaneous breathing sevoflurane anesthesia combined with TPB (study group). To evaluate the safety and feasibility of this new technique, these patients were compared with the control group consisting of 34 consecutive patients with PSP who underwent thoracoscopic bullectomy using tracheal intubation with controlled ventilation from January 2017 to December 2017. The demographic characteristics, intraoperative surgical and anesthetic results, and postoperative results were assessed.The 2 groups had comparable anesthetic time, operation time, chest drainage time, postoperative hospital stays, and hospitalization cost. Visual analogue score (VAS) scores at 3 hours at rest and at coughing were significantly lower in the study group than in the control group (mean, 0.9 vs 2.0 and 1.8 vs 4.0, P = .024 and P = .006, respectively). No differences were seen in PaO2 values between the 2 groups in the intraoperative stage and postoperative stage (P > .05, respectively). The pH value was significantly lower in the intraoperative stage (mean, 7.28 vs 7.40, P = .01) and higher in the postoperative stage (mean, 7.35 vs 7.33, P = .014) in the study group than in the control group. The PaCO2 value was significantly higher in the intraoperative stage in the study group than in the control group (mean, 57.0 mm Hg vs 42.0 mm Hg, P = .015). In the study group, no cough reflex was found, and the level of collapse of the operative lung was excellent in 31 cases and good in 3 cases.Our study demonstrated that thoracoscopic bullectomy for treatment of PSP can be safely and feasibly performed in highly selected patients under ILMA with spontaneous breathing sevoflurane anesthesia combined with TPB.

Objective: To study the role of high-mobility group protein 1 (HMGB1) in the promotion of diethylnitrosamine-induced liver cancer formation in C57BL/6 mice and its mechanism. Methods: HMGB1(loxp/loxp)/Alb-Cre(+/-) were used as a liver-specific knockout (KO) of HMGB1 gene in mice. HMGB1(loxp/loxp)/Alb-Cre(-/-), HMGB1(loxp/WT)/Alb-Cre(+/-) and HMGB1(loxp/WT)/Alb-Cre(-/-) born in the same litter were wild-type mice. Six 12-day-old male WT and KO mice were separated and given a single intraperitoneal injection of diethylnitrosamine (25 mg/kg). Six months later, HE staining was used to evaluate the histopathological changes and then the incidence of liver cancer in each mice group was calculated. Serum samples were taken from each mice group to determine alanine aminotransferase levels. Immunohistochemical staining was used to detect the expression and intracellular localizations of HMGB1 protein status in tumor tissue of the two groups of mice. Western blot was used to detect the expressional condition of mitochondrial biogenesis in tumor tissue of the two groups of mice. RT-PCR was used to detect mitochondrial DNA copy number of tumor tissue and normal liver tissue in the two groups of mice. Intra and inter group data comparison was compared using t-tests and one one-way analysis of variance. Results: Compared with WT mice, the liver/body weight ratio of KO mice was decreased significantly ( t = 2.634, P = 0.0225). Serum alanine aminotransferase levels in both groups of mice were increased, and the difference was not statistically significant ( t = 0.4062, P = 0.6932). There were many visible gray-white nodules of different sizes on the liver surface of WT mice, and the histological type was hepatocellular carcinoma. There was no statistically significant difference in the incidence of liver cancer among different genotypes of WT mice ( P > 0.05). The incidence rate of liver cancer in KO mice was significantly reduced ( t = 8.521, P < 0.001). Compared with WT mice, the expression levels of HMGB1 and mitochondrial biogenesis (PGC-1α and NRF1) was significantly reduced ( t = 6.238, 4.852, P = 0.0335, 0.041) in tumor tissue of KO mice. Mitochondrial DNA copy number was decreased significantly ( t = 9.211, P < 0.01). Mitochondrial DNA copy number in tumor tissue of WT mice was significantly higher than that in normal liver tissue ( t = 8.305, P = 0.0142). Conclusion: HMGB1 promotes the formation of diethylnitrosamine-induced liver cancer by inducing mitochondrial biogenesis.

This study aims to investigate the neuroprotective effects of Pyrola incarnata against β-amyloid-induced memory impairment in mice. Ethanol extract of Pyrola incarnata (EPI) was obtained and led to eleven phytochemicals successfully by isolation and purification, which were elucidated by spectroscopic analysis ( 1 H NMR, 13 C NMR and HR-ESI-MS). Thereinto, ursolic acid was gained as most abundant monomer. C57BL/6 mice were intracerebroventricular injected with aggregated Aβ 25-35 . Open-field test, Barnes maze test and Morris water maze were conducted for evaluating cognition processes of EPI and ursolic acid. EPI significantly improved learning and memory deficits, attenuated the Aβ 25-35 level of deposition immunohistochemically. Further studies revealed that ursolic acid as bioactive phytochemical of P. incarnata improved spatial memory performance and ameliorated Aβ 25-35 accumulation by activating microglia cells and up-regulating Iba1 level in the hippocampus. These findings suggest P. incarnata could improve the cognition of mice and be a promising natural source for the treatment of neurodegenerative disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We use 84 rainfall samples collected during June to September 2017 from the Dongkemadi basin, source region of the Yangtze River, China, to analyze the characteristics and influencing factors of stable isotopes in groundwater, and further discuss the groundwater recharge sources. The results showed that the range of groundwater δ 18 O values in this permafrost region varied from -15.3‰ to -12.5‰ (mean -14.0‰). The range of δ D values in groundwater varied from -108.9‰ to -91.7‰ (mean -100.2‰). Compared with local atmospheric precipitation, groundwater isotopes were relatively enriched. The slope and intercept of the groundwater line (GL) in the study area were both lower than of those of the global and local meteoric water lines (GMWL and LMWL), thus indicating that groundwater in the study area was subjected to evaporation during rainfall recharge of groundwater. The d -excess values of groundwater varied from 4.9‰ to 25.0‰ (mean 11.6‰), which was close to the average d -excess value determined for global average rainfall (10‰), but lower than that of rainfall in the study area (15.1‰). The influencing factors on the composition and variation of groundwater isotopes were different in different periods. The permafrost active layer was relatively thin during periods of increasing air temperature, and groundwater isotopes were significantly affected by air temperature. A temperature decrease during the latter part of the sampling period, when the thickness of the permafrost active layer was still increasing, further increased the retention time of infiltrating rainfall in the soil, thereby eventually leading to evaporation that strengthened the enrichment of heavy isotopes in the groundwater. According to the topographic characteristics of the Dongkemadi basin, the isotopic characteristics of the groundwater, and the factors influencing the isotopic composition, we conclude that rainfall was the main source of groundwater recharge. The results of this study provide a scientific basis for studying water cycle processes in the permafrost regions of the source region of the Yangtze River.

Objective: Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People's Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P >0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation. Results: In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively ( F =54.868, P <0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively ( F =95.016, P <0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively ( F =79.409, P <0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days ( F =177.677, P <0.001), respectively, whose differences were all statistically significant (all P <0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant ( H =52.915, P <0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant ( H =91.709, P <0.001; H =79.692, P <0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well ( H =86.543, P <0.001; H =78.667, P <0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion: The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Using 64 precipitation samples collected from June to September 2013 in the Dongkemadi Basin in the source region of the Yangtze River, the pH, conductivity, and main ionic concentration characteristics of precipitation were analyzed. The main ionic sources of precipitation and their relationships with atmospheric circulation were examined using factor analysis, correlation analysis, enrichment factor analysis, and backward trajectory analysis. The results showed that the range of precipitation pH values varied from 5.26 to 9.25 with a weighted average of 6.70, and conductivity ranged from 0.23 to 28.70 μS·cm -1 with a weighted average of 3.45 μS·cm -1 . The conductivity of precipitation was lower than for the Mt. Waliguan basin (China Global Atmosphere Watch baseline observatory). The total ionic concentrations in the precipitation ranged from 7.0 to 376.9 μeq·L -1 with a weighted average of 40.8 μeq·L -1 . The ranked order of ionic concentrations was HCO 3 - > NH 4 + > Ca 2+ > NO 3 - > SO 4 2- > Na + > Cl - > K + > Mg 2+ . HCO 3 - , NH 4 + ,Ca 2+ , and NO 3 - were the dominant ions, which accounted for 74.75% of the total ionic concentration. Fractional acidity (FA) analysis showed that 97.8% of the precipitation acidity was neutralized by alkaline constituents. Neutral factor (NF) analysis indicated that NH 4 + and Ca 2+ were the dominant neutralization constituents in the precipitation. The precipitation ions in this study area were mainly derived from terrestrial material, while input from marine sources was relatively low. Backward trajectory analysis revealed that the total ionic concentrations varied significantly between the different sources, which followed the order of local sources>westerly sources>monsoon sources. This indicates that different atmospheric circulation conditions and air mass sources have a significant influence on the chemical composition of precipitation in this area. To some extent, the chemical characteristics of precipitation could reflect the air quality and background values for remote areas due to the limited effect of human activities. The results of this study provide a scientific basis for the protection of water quality and the assessment of the impact of human activities on the atmospheric environment in the source region of the Yangtze River.

Based on samples collected by bottom trawl in May, August, November and December 2016 in the Minjiang Estuary, species richness and functional diversity of fishes, as well as their spatial-temporal variations, were quantified by a trait-based approach. The functional diversity varied with the changes of species richness. The species richness averaged across all stations were (17.8±5.1) species in spring, (22.4±5.6) in summer, (17.7±6.3) in autumn, and (12.1±2.3) in winter. Functional diversity also showed seasonal variation, with the highest in summer as (33.94±28.70), followed by (9.93±8.83) in winter, (11.30±7.55) in spring and (19.05±19.32) in autumn. The key functional species varied seasonally, as Setipinna taty contributing to 26% of the total functional value in spring, Polydactylus sextarius at 26% in summer, Harpadon nehereus climbing to 69% in autumn, and Collichthys lucidus at 38% in winter. The seasonal variations of fish species function were determined by life history and its interaction with other species.

The differentiation characteristics of landscape pattern affect the urban thermal environment. In this study, temperature characteristics of nine types of landscape in a national forest city, Longquan City, were analyzed by temperature inversion method and spatial analysis. The landscape pattern analysis method was used to explore the correlation of landscape metrics and the thermal environment from 1 km to 3.5 km. The results showed that the high and sub-high temperature zones of Longquan City were distributed in northeast-southwest, mainly composed of urban and rural residential areas. The low and sub-low temperature zone were mainly distributed in the northwest and southeast areas, mainly composed of public welfare forests. By calculating the mean land surface temperature of each landscape type in the area below 700 m above sea level, the temperature of coniferous forest, broadleaf forest, conifer-broadleaf forest, bamboo forest and water was relatively low, whereas that of shrub land, other forest land, cultivated land and construction land was relatively high. Through the analysis of landscape pattern and thermal environment, it was found that the class pattern index was more practical than the landscape pattern index. The correlation between thermal environment effect and construction land distribution reached 0.835, coniferous forest land, broadleaf forest land, coniferous-broadleaf forest land and water were the second, up to -0.5 to -0.4. The cooling effects of different forest types vaied across different spatial scales. Broadleaved forests and coniferous-broadleaved forests were more conducive to cooling at large scales. The larger the area and volume stock of forest land, the more likely it had the lowest land surface temperature.

Based on the stable isotopes of 73 precipitation samples continuously collected from May to October 2014 and related meteorological statistics in the Dongkemaldi Basin, the characteristics of δ D, δ 18 O, and d -excess of precipitation, as well as the correlations between δ 18 O and the rainfall amount and air temperature were analyzed. The moisture sources were tracked by the HYSPLIT model to further estimate the contribution of different water vapor sources to the rainfall amount. The results showed that the range of δ 18 O and δ D values varied from -26.5‰ to 1.9‰ and -195.2‰ to 34.0‰, respectively; meanwhile, the δ 18 O and δ D values in precipitation fluctuated greatly with time in response to water vapor transport from different moisture sources of the Qinghai-Tibet Plateau. The slope and intercept of the Local Meteoric Water Line (LMWL) were both higher than those of the Global Meteoric Water Line (GMWL) and close to the LMWL in the northern area of the Qinghai-Tibet Plateau. The relationship between δ 18 O and δ D in different precipitation types showed significant differences, which were mainly related to the source of water vapor and meteorological conditions during the process of precipitation formation. Because of the influence of local evaporation and the transport process of water vapor, the d -excess values of atmospheric precipitation were relatively large; the δ 18 O in precipitation had a significant amount effect, but had no temperature effect, thus indicating that the rainfall amount was more effective in controlling the stable isotope content of atmospheric precipitation than temperature. The modeled trajectory of vapor sources showed that water vapor of precipitation was mainly derived from the marine vapor carried by the southwest monsoon, local moisture, and the westerly water vapor, and their contributions to the rainfall amount were 43%, 36%, and 21%, respectively. The results of this study can contribute to further understanding of the atmospheric circulation characteristics and water cycle process of the Dongkemadi basin in the headwaters of the Yangtze River.

Flight, an active fear response to imminent threat, is dependent on the rapid risk assessment of sensory information processed by the cortex. The thalamic reticular nucleus (TRN) filters information between the cortex and the thalamus, but whether it participates in the regulation of flight behavior remains largely unknown. Here, we report that activation of parvalbumin-expressing neurons in the limbic TRN, but not those in the sensory TRN, mediates flight. Glutamatergic inputs from the cingulate cortex (Cg) selectively activate the limbic TRN, which in turn inhibits the intermediodorsal thalamic nucleus (IMD). Activation of this Cg→limbic TRN→IMD circuit results in inhibition of the IMD and produces flight behavior. Conversely, removal of inhibition onto the IMD results in more freezing and less flight, suggesting that the IMD may function as a pro-freeze center. Overall, these findings reveal a novel corticothalamic circuit through the TRN that controls the flight response.

With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers. In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the in silico analysis and the reported experimental validations. Based on the network analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5-hydroxytryptamine receptor 1 A (5HT 1A ), delta-type opioid receptor (OPRD) and G protein-coupled receptor 55 (GPR55), were selected for close evaluation. Integrated computational methodologies, including homology modeling, molecular docking, and molecular dynamics simulation, were used to evaluate the protein-CBD binding modes. A CBD-preferred pocket consisting of a hydrophobic cavity and backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally, the neurophysiological effects of CBD were illustrated at the molecular level, and dopamine receptor 3 (DRD3) was further predicted to be an active target for CBD.

Both the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) are involved in affective control and reward-related behaviors. Moreover, the neuronal activities of the VTA and DRN are modulated by opioids. However, the precise circuits from the VTA to DRN and how opioids modulate these circuits remain unknown. Here, we found that neurons projecting from the VTA to DRN are primarily GABAergic. Rostral VTA (rVTA) GABAergic neurons preferentially innervate DRN GABAergic neurons, thus disinhibiting DRN serotonergic neurons. Optogenetic activation of this circuit induces aversion. In contrast, caudal VTA (cVTA) GABAergic neurons mainly target DRN serotonergic neurons, and activation of this circuit promotes reward. Importantly, μ-opioid receptors (MOPs) are selectively expressed at rVTA→DRN GABAergic synapses, and morphine depresses the synaptic transmission. Chronically elevating the activity of the rVTA→DRN pathway specifically interrupts morphine-induced conditioned place preference. This opioid-modulated inhibitory circuit may yield insights into morphine reward and dependence pathogenesis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Previous studies have reported that vitamin C (VC) promotes neural stem/precursor cell (NSC) differentiation toward dopamine (DA) neurons via DNA hydroxymethylation-induced transcriptional activation of DA neuron-specific genes. To further understand the VC effects on NSC differentiation, we profiled the transcriptome and DNA methylome/hydroxymethylome using high-throughput sequencing. Interestingly, RNA sequencing analyses have shown that, in addition to DA neuronal genes, astrocytic genes Gfap, Slc1a3, and S100a16 were also upregulated in NSC cultures differentiated with VC treatment. Consistently, enhanced GFAP+ astrocytic yields were manifested in the differentiated cultures with VC treatment, collectively indicating that VC promotes astrocytic differentiation. In genome-wide hydroxymethylome analyses, VC treatment induces enrichment of DNA hydroxymethylation (5-hydroxymethyl cytosine; 5hmC) near the consensus binding motifs of nuclear factor I (NFI). Furthermore, we showed that VC significantly enhanced recruitment of NFI and STAT3, key transcription factors for astrogenesis, in the 5hmC-enriched regions of the astrocyte-specific genes. These findings suggest that VC play important roles in astrocytogenesis during brain development. Stem Cells 2018;36:1578-1588., (© AlphaMed Press 2018.)

To study the trophic structure of fish community in Minjiang Estuary, we measured the carbon and nitrogen stable isotope ratios (δ 13 C and δ 15 N) of common fish species sampled in winter (January), spring (May), summer (August) and autumn (November) of 2015 by trawling, as well as seven quantitative metrics (ratios range of δ 15 N, NR; ratios range of δ 13 C, CR; total area, TA; standard ellipse area, SEAc; average distance of centroid, CD; mean nearest neighbor distance, MNND; standard deviation of nearest neighbor distance, SDNND). The results showed significant differences of δ 13 C values among all the seasons except between summer and autumn. There were significant differences of δ 15 N values between spring and other three seasons but no significant difference among summer, autumn, and winter. According to the results of the seven quantitative metrics, trophic structure of common fish community remarkably varied among the four seasons, as TA, SEAc, CR, NR, CD and MNND increased in succession from summer, autumn, winter to spring. Our results indicated that seasonal differences in trophic structure of common fish community were related to the fish spawning migration and the diversity of food source.

Based on the seasonal bottom trawl surveys in the Minjiang River Estuary in 2015, the breadth and overlap of ecological niche of major fish species were analyzed. Those fish species were identified based on the index of relative importance (IRI). A total of 137 species belonging to 37 families and 16 orders were collected. Fifteen major fish species were determined by the IRI, including six dominant species Polydactylus sextarius, Harpadon nehereus, Pennahia argentata, Secutor ruconius, Cynoglossus abbreviates, Coilia mystus, and nine important species Collichthys lucidus, Amblychaeturichthys hexanema, Upeneus japonicas, Lagocephalus spadiceus, Pampus argenteus, Larimichthys crocea, Thryssa kammalensis, Takifugu oblongus, Lepturacanthus savala. Seven species whose spatio-temporal niche breadth was higher than 1 in a declining order were C. abbreviates, C. lucidus, S. ruconius, A. hexanema, T. kammalensis, C. mystus, H. nehereus. The ecological niche of major fish species in the Minjiang River Estuary showed obvious seasonal dynamics. The percentage of species pairs with spatio-temporal niche overlap at the meaningful level was as high as 81.9%. Six species pairs reached significant ecological niche overlap, indicating that major fish species had similar distribution at the spatial and temporal scales and the existence of resource utilization competition. The species pairs of U. japonicus-L. savalawas had the highest spatio-temporal niche overlap value, whereas U. japonicus-C. lucidus had the lowest niche overlap value. The spatio-temporal niche overlap of major fish species in the Minjiang River Estuary had substantial seasonal variation.