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Abstract Background Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . Results The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. Conclusions Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Graphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied.

Abstract Background The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. Methods Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. Results Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. Conclusion Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.

Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.

Cell-type-specific recording and manipulation is important for understanding neural circuits. Here the authors describe molecular tools to access cell types based on genetics and connectivity in the brain, and demonstrated the utility of these tools in neural recording and manipulations.

Fast and accurately characterizing animal behaviors is crucial for neuroscience research. Deep learning models are efficiently used in laboratories for behavior analysis. However, it has not been achieved to use an end-to-end unsupervised neural network to extract comprehensive and discriminative features directly from social behavior video frames for annotation and analysis purposes. Here, we report a self-supervised feature extraction (Selfee) convolutional neural network with multiple downstream applications to process video frames of animal behavior in an end-to-end way. Visualization and classification of the extracted features (Meta-representations) validate that Selfee processes animal behaviors in a way similar to human perception. We demonstrate that Meta-representations can be efficiently used to detect anomalous behaviors that are indiscernible to human observation and hint in-depth analysis. Furthermore, time-series analyses of Meta-representations reveal the temporal dynamics of animal behaviors. In conclusion, we present a self-supervised learning approach to extract comprehensive and discriminative features directly from raw video recordings of animal behaviors and demonstrate its potential usage for various downstream applications.

Abstract Background The prognostic significance of diabetic retinopathy (DR) for cardiovascular diseases (CVD) remained unclear. Therefore, we performed this meta-analysis to assess whether DR predicted CVD mortality in diabetic patients. Methods We searched PubMed, Embase, Web of Science and Cochrane Library for cohort studies reporting the association of DR and CVD mortality. Then we pooled the data for analysis. Results After screening the literature, 10 eligible studies with 11,239 diabetic subjects were finally included in quantitative synthesis. The pooled risk ratio (RR) of DR, mild DR, and severe DR for CVD mortality was 1.83 (95% confidence interval (CI): 1.42, 2.36; p 1; all P values

Summary: Drinking behavior in rodents is characterized by stereotyped, rhythmic licking movement, which is regulated by the basal ganglia. It is unclear how direct and indirect pathways control the lick bout and individual spout contact. We find that inactivating D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the ventrolateral striatum (VLS) oppositely alters the number of licks in a bout. D1- and D2-MSNs exhibit different patterns of lick-sequence-related activity and different phases of oscillation time-locked to the lick cycle. On the timescale of a lick cycle, transient inactivation of D1-MSNs during tongue protrusion reduces spout contact probability, whereas transiently inactivating D2-MSNs has no effect. On the timescale of a lick bout, inactivation of D1-MSNs (D2-MSNs) causes rate increase (decrease) in a subset of basal ganglia output neurons that decrease firing during licking. Our results reveal the distinct roles of D1- and D2-MSNs in regulating licking at both coarse and fine timescales.

AIM:To retrospectively analyze the effect of Qiming Granules combined with Deproteinized Calfblood Extract Eye Gel in the treatment of diabetes phaeoemulsification postoperative xerophthalmia.METHODS:From June 2017 to June 2018, 147 diabetics 269 eyes were diagnosed with phaeoemulsification postoperative xerophthalmia were enrolled in our study. The control group was given the Tobramycin Dexamethasone Eye Drops and Diclofenac Sodium Eye Drops, the Sugaojie group was given Deproteinized Calfblood Extract Eye Gel on the basic of the control group, the combined group was given the Qiming Granules on the basic of the Sugaojie group. The courses all last 4wk. The corneal fluorescence staining, BUT and SⅠt were analyzed before, and post 1mo after treatment, and the clinical efficacy of each group was analyzed.RESULTS: There was no difference among three groups on BUT and SⅠt before treatment(P>0.05). After 1 mo treatment, BUT and SⅠt of the Sugaojie group and the combined group were significantly improved compared to the control group(P vs 89.0%, P=0.013).CONCLUSION: Qiming Granules combined with Deproteinized Calf blood Extract Eye Gel could improve xerophthalmia after phaeoemulsification surgery. It is a positive and effective treatment, which has good clinical application significance.

Objective: Currently, there is paucity of data on the rate of vaginal deliveries and cesarean section among women in Tibet. In this study, we carried out an observational study of 7365 consecutive pregnant women in Lhasa, Tibet who gave birth at our tertiary care institution between 2012 and 2015. Materials and methods: In this retrospective study, we reviewed the hospital records for demographic data, obstetric history, and the number of vaginal and emergency cesarean section deliveries. The overall and annual rate of vaginal and cesarean section deliveries was calculated. Causes, indications or risks for cesarean section were also analyzed. Results: During the review period, 7365 neonates were delivered at our hospital, including 1690 (23.0%) deliveries via cesarean section. The yearly rate of cesarean section progressively declined from 26.7% in 2012 to 18% in 2015 (P

Though designing conductive polymers for memory devices is attractive for future low-cost flexible electronics, a proof-of-concept device has yet to be realized. Here, the authors report a redox-gated polymer memristive processing unit with programmable multilevel storage and logic functionalities.

Summary: Despite being innate, displays of aggression are influenced by cortical activities. Here, using Vglut1 as a marker for inputs from cortical structures, we identify a small population of excitatory neurons located in the posterior amygdala (PA) that project to the ventrolateral division of ventromedial nucleus of the hypothalamus (VMHvl), a region that critically regulates territorial aggression. Indeed, activities of PA Vglut1+ (PAVglut1) neurons, as analyzed by post hoc c-Fos expression, differentiate trials in which attacks occur, or not, during resident-intruder assays. More importantly, chemogenetic activation of VMHvl-projecting PAVglut1 neurons robustly promote aggression while inhibition of these neurons reduces attacks. Finally, a connectivity map places VMHvl-projecting PAVglut1 neurons at the interface between emotion regulation and aggression as they receive broad inputs from limbic structures and project collaterally to the VMHvl and other targets. Taken together, these results point to VMHvl-projecting PAVglut1 neurons as a potential site for cortical gating of territorial aggression. : While innate, displays of aggression are influenced by cortical activity. Using Vglut1 as a marker for cortical structures, Zha et al. identify a population of Vglut1+ neurons in the posterior amygdala (PA) that project to the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) and bidirectionally modulate territorial attacks. Keywords: aggression, Vglut1, posterior amygdala, VMHvl, emotion regulation, aggression circuit, cortical gating, innate behavior

Background: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. Methods: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. Results: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Conclusions: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.

The medial preoptic area (mPOA) in a mammalian brain is sexually dimorphic, and yet its exact function in mediating gender-specific behavior remains unclear. Here, Xu and colleagues show that optogenetic manipulation of the mPOA in male mice induce female-stereotyped behaviors and vice versa.

Abstract Recent theoretical studies indicated that the Curie temperature of perovskite manganite thin films can be increased by more than an order of magnitude by applying appropriate interfacial strain to control orbital ordering. In this work, we demonstrate that the regular intercalation of BaTiO3 layers between La0.67Sr0.33MnO3 layers effectively enhances ferromagnetic order and increases the Curie temperature of La0.67Sr0.33MnO3/BaTiO3 superlattices. The preferential orbital occupancy of eg(x 2 –y 2 ) in La0.67Sr0.33MnO3 layers induced by the tensile strain of BaTiO3 layers is identified by X-ray linear dichroism measurements. Our results reveal that controlling orbital ordering can effectively improve the Curie temperature of La0.67Sr0.33MnO3 films and that in-plane orbital occupancy is beneficial to the double exchange ferromagnetic coupling of thin-film samples. These findings create new opportunities for the design and control of magnetism in artificial structures and pave the way to a variety of novel magnetoelectronic applications that operate far above room temperature.

Abstract We study the magnetic properties of an epitaxial growth bilayer composed of ferromagnetic La0.7Sr0.3MnO3 (LSMO) and paramagnetic LaNiO3 (LNO) on SrTiO3 (STO) substrates. We find that the stack order of the bilayer heterostructure plays a key role in the interfacial coupling strength, and the coupling at the LSMO(top)/LNO(bottom) interface is much stronger than that at the LNO(top)/LSMO(bottom). Moreover, a strong spin glass state has been observed at the LSMO/LNO interface, which is further confirmed by two facts: first, that the dependence of the irreversible temperature on the cooling magnetic field follows the Almeida-Thouless line and, second, that the relaxation of the thermal remnant magnetization can be fitted by a stretched exponential function. Interestingly, we also find an exchange bias effect at the LSMO/LNO bilayer below the spin glass freezing temperature, indicating that the exchange bias is strongly correlated with the spin glass state at its interface.

Abstract Background Colistin has been considered as a last-line treatment option in severe infections caused by multidrug-resistant (MDR) gram-negative pathogens. However, the emergence of the mobile colistin resistance gene (mcr-1) has challenged this viewpoint. The aim of this study is to explore the prevalence of mcr-1 in Escherichia coli (E. coli) in a Chinese teaching hospital, and investigate their molecular characteristics. Methods A total of 700 E. coli isolates were used to screen mcr-1 by PCR and sequencing in a Chinese university hospital from August 2014 to August 2015. Susceptibility test of mcr-1-producing isolates was determined by Vitek -2 Compact system. 26 virulence factors (VFs), phylogenetic groups, Multi-locus sequence typing (MLST), and DNA Fingerprinting (ERIC-PCR) of strains were investigated by PCR. Results Four (0.6%) mcr-1 producing E. coli isolates were found in this study. The results of antibiotic susceptibility test showed that all four isolates were resistant to colistin, ciprofloxacin, levofloxacin, cefazolin, and trimethoprim/sulfamethoxazole, and were susceptible to amikacin, ertapenem and imipenem. In addition, all 4 isolates exhibited high-level resistance to aztreonam, cefotaxime and gentamicin. The numbers of VFs contained in mcr-1 positive isolates were no more than 4 in our study. MLST result demonstrated that these isolates were assigned to two sequence types: ST156 and ST167. The result of phylogenetic analysis showed that four mcr-1-positive isolates belong to two phylogenetic groups: A and B1 group. ERIC-PCR showed that four mcr-1 positive strains were categorized into three different genotypes. Conclusions Our study demonstrated a low prevalence of mcr-1 in E. coli clinical isolates in a Chinese teaching hospital, and we have gained insights into the molecular characteristics of these mcr-1-positive strains. Increasing the surveillance of these infections, as well as taking effective infection control measures are urgently needed to take to control the transmission of mcr-1 gene.

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

AIM: To compare the efficacy and complication of extra-trabeculotomy in combination with trabeculectomy and trabeculectomy and compound trabeculectomy in the treatment of primary infantile glaucoma. METHODS: Patients with primary infantile glaucoma undergone one of the three procedures from Jan 2006 to Jan 2014 were selected. Among them, group A(20 patients, 31 eyes)underwent extra-trabeculotomy in combination with trabeculectomy, group B(20 patients, 32 eyes)underwent trabeculectomy, while group C(20 patients, 30 eyes)underwent compound trabeculectomy RESULTS: The success rates in group A were 96.8% at the time of discharge and 90.3% during follow-up(mean 24mo); the rates in group B were 96.9% and 81.2%(mean 24mo)the rates in group C were 83.3% and 76.7%(mean 24mo)respectively, the differences being significant(P CONCLUSION: Extra-trabeculotomy in combination with trabeculectomy is more efficacious and safer than trabeculectomy and compound trabeculectomy in the treatment of primary infantile glaucoma. It should be the first choice for primary infantile glaucoma.

Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenic acids and only one methyl's position is different between them. OA and UA always exist in the same plant, so it is difficult to separate them when determining contents by RP-HPLC. In this study, a very simple mobile phase for HPLC was developed to simultaneously determine UA and OA, and the factors affecting separation were also discussed. The mobile phase is methanol: water (95:5) with flow rate 0.4 mL/min. The retention time for OA and UA was 20.58 and 21.57 min, respectively, the resolution was 1.61. The average contents of OA and UA of three Loquat leaves sets were 1.4 mg/g and 5.6 mg/g, respectively. Regarding the HPLC, we found that changing mobile phase, adjusting the pH value or adding ion-pairing agent could not affect the separation between UA and OA greatly. While adjustment of the flow rate and column temperature could improve the resolution greatly. Keywords: RP-HPLC, Oleanolic acid (OA), Ursolic acid (UA), Triterpenic acid

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

We report the results of a sequence of magnetisation and magneto-optical studies on laser ablated thin films of ZnCoAlO and ZnCoO that contain a small amount of metallic cobalt. The results are compared to those expected when all the magnetization is due to isolated metallic clusters of cobalt and with an oxide sample that is almost free from metallic inclusions. Using a variety of direct magnetic measurements and also magnetic circular dichroism we find that there is ferromagnetism within both the oxide and the metallic inclusions, and furthermore that these magnetic components are exchange-coupled when aluminium is included. This enhances both the coercive field and the remanence. Hence the presence of a controlled quantity of metallic nanoparticles in ZnAlO can improve the magnetic response of the oxide, thus giving great advantages for applications in spintronics.

In the title compound, [Fe(C8H5Cl2O3)2(H2O)2]n, the FeII atom is located on an inversion center. It is coordinated by four O atoms from four 2,4-dichlorophenoxyacetate ligands and two water molecules, displaying a distorted octahedral geometry. The carboxylate groups of the 2,4-dichlorophenoxyacetate ligands link the Fe atoms, forming a polymeric layered network in the bc plane. Intralayer O—H...O hydrogen bonds enhance the stability of the two-dimensional network.

In the title complex, [Nd(C10H13N2O8)(H2O)]n, each NdIII ion is coordinated by six O atoms and two N atoms from one N′-(carboxymethyl)ethylenediamine-N,N,N′-triacetate (edta) ligand and one water molecule, displaying a bicapped trigonal-prismatic geometry. The edta ligands link the neodymium metal centres, forming polymeric chains running along the a axis of the unit cell. These chains are further assembled via intermolecular O—H...O hydrogen-bonding interactions into a three-dimensional supramolecular network.

In the title complex, {[Tb(C6H5NO2)3(H2O)2](ClO4)3·H2O}n, the TbIII ion is coordinated by six O atoms from six isonicotinate (inic) ligands and two water molecules, displaying a bicapped trigonal-prismatic geometry. The inic ligands, which are protonated at the pyridine N atom, link the metal centres, forming a polymeric chain running parallel to the a axis. The chains are further assembled via intra- and intermolecular O—H...O and N—H...O hydrogen-bonding interactions into a three-dimensional supramolecular network involving the inic ligands, the water molecules and the perchlorate anions. One of the perchlorate ions is disordered over two sites with occupancies of 0.561 (17) and 0.439 (17).

We have observed room temperature ferromagnetism in In2O3 thin films doped with either 5 at.% Mn or Fe, prepared by pulsed laser deposition at substrate temperatures ranging from 300 to 600 °C. The dependence of saturation magnetization on grain size was investigated for both types of In2O3 films. It is revealed that, for the Mn-doped films, the magnetization was largest with small grains, indicating the importance of grain boundaries. In contrast, for Fe-doped films, the largest magnetization was observed with large grains.