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Melophagus ovinus (sheep ked) is a hematophagous ectoparasite that mainly parasitizes sheep. In addition to causing inflammation, wool loss, and skin damage to the animal hosts, M. ovinus also serves as a vector for a variety of pathogens and is highly likely to participate in the life and transmission cycle of pathogenic organisms. Herein, we investigated the presence and molecular characterization of vector-borne pathogens in M. ovinus from Qinghai-Tibet Plateau, China. A total of 92 M. ovinus pools collected from the Qinghai province of China were screened for the presence of selected vector-borne pathogens. The overall positive rate of A. ovis, A. bovis, A. phagocytophilum, and T. ovis in M. ovinus was 39.1%, 17.4%, 9.8%, and 89.1%, respectively. All of the samples were negative for Border disease virus (BDV), other Anaplasma species, Babesia spp., Rickettsia spp., and Borrelia spp. Co-infection of different Anaplasma species and T. ovis occurred in 51.2% of all samples with T. ovis. The positive rates of A. ovis, A. bovis, and A. phagocytophilum in different regions and altitudes of the sampling sites were significantly different. Sequence and phylogenetic analysis of target genes confirmed their identity with corresponding pathogens. Our results elucidate the occurrence and molecular characterization of Anaplasma spp. and Theileria spp. in M. ovinus, which could act as potential zoonotic reservoirs. To the best of our knowledge, this is the first report of the detection of A. bovis and A. phagocytophilum DNA in M. ovinus. This study gives the first extensive molecular survey of vector-borne pathogens with veterinary and public health significance in M. ovinus from the Qinghai-Tibet Plateau, China.

The Qinghai–Tibet Plateau Area (QTPA) has a complex natural ecosystem, causing a greatly increased risk of spreading various tick-borne diseases including rickettsial infections, which are regarded as one of the oldest known vector-borne zoonoses. However, the information of one of its pathogen, spotted fever group Rickettsia (SFG Rickettsia ), is limited in tick vectors and animals in this area. Therefore, this study focused on the investigation of SFG Rickettsia in tick vectors, yaks ( Bos grunniens ), and Tibetan sheep ( Ovis aries ) in the QTPA. A total of 1,000 samples were collected from nine sampling sites, including 425 of yaks, 309 of Tibetan sheep, 266 of ticks. By morphological examination, PCR, and sequencing, we confirmed the species of all collected ticks. All tick samples, all yak and Tibetan sheep blood samples were detected based on SFG Rickettsia ompA and sca4 gene. The results showed that all tick samples were identified to be Haemaphysalis qinghaiensis , and the positive rates of SFG Rickettsia were 5.9% (25/425), 0.3% (1/309), and 54.1% (144/266) in yaks, Tibetan sheep, and ticks, respectively. All positive samples were sequenced, and BLASTn analysis of the ompA gene sequences of SFG Rickettsia showed that all positive samples from animals and ticks had 99.04–100% identity with yak and horse isolates from Qinghai Province, China. BLASTn analysis of the sca4 gene sequences of SFG Rickettsia showed that all positive samples had 97.60–98.72% identity with tick isolates from Ukraine. In addition, the phylogenetic analysis showed that all the SFG Rickettsia ompA and sca4 sequences obtained from this study belong to the same clade as Rickettsia raoultii isolated from livestock and ticks from China and other countries. Molecularly, this study detected and characterized SFG Rickettsia both in the tick vectors and animals, suggesting that the relationship between SFG Rickettsia , tick species and animal hosts should be explored to understand their interrelationships, which provide a theoretical basis for preventing control of this pathogen.

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow (Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and antipathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Background：Little attention has been paid to the role of subcortical deep gray matter （SDGM） structures in type 2 diabetes mellitus （T2DM）-induced cognitive impairment,especially hippocampal subfields.Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging （MRI） and to test their associations with cognitive performance in T2DM.Methods：A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age,sex and education level was enrolled in this study.We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry.We used Mini-Mental State Examination and Montreal Cognitive Assessment （MoCA） scores as measures of cognitive performance.The association of glycosylated hemoglobin （HbAlc） with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.Results：Bilaterally,the hippocampal volumes were smaller in T2DM patients,mainly in the CA1 and subiculum subfields.Partial correlation analysis showed that the MoCA scores,particularly those regarding delayed memory,were significantly positively correlated with reduced hippocampal CA 1 and subiculum volumes in T2DM patients.Additionally,higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.Conclusions：These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM.These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction,suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.

In this paper we formulate a continuous-time behavioral （4 la cumulative prospect theory） portfolio selection model where the losses are constrained by a pre-specified upper bound. Economically the model is motivated by the previously proved fact that the losses Occurring in a bad state of the world can be catastrophic for an unconstrained model. Mathematically solving the model boils down to solving a concave Choquet minimization problem with an additional upper bound. We derive the optimal solution explicitly for such a loss control model. The optimal terminal wealth profile is in general characterized by three pieces： the agent has gains in the good states of the world, gets a moderate, endogenously constant loss in the intermediate states, and suffers the maximal loss （which is the given bound for losses） in the bad states. Examples are given to illustrate the general results.

Background：Neuroimaging studies have found that functional changes exist in patients with Parkinson＇s disease （PD）.However,the majority of functional magnetic resonance imaging （fMRI） studies in patients with PD are task-related and cross-sectional.This study investigated the functional changes observed in patients with PD,at both baseline and after 2 years,using resting-state fMRI.It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.Methods：Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI.In addition,20 age-and sex-matched,healthy controls were examined using resting-state fMRI.The fractional amplitude of low-frequency fluctuation （fALFF） approach was used to analyze the fMRI data.Nonlinear registration was used to model within-subject changes over the scanning interval,as well as changes between the patients with PD and the healthy controls.A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.Results：Compared to the control subjects,the patients with PD showed increased fALFF values in the left inferior temporal gyrus,right inferior parietal lobule （IPL） and right middle frontal gyrus.Compared to the baseline in the 2 years follow-up,the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum,right thalamus,right striatum,left superior parietal lobule,left IPL,left precentral gyrus,and left postcentral gyrus （P 〈 0.01,after correction with AlphaSim）.In addition,the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale （UPDRS） motor scores （r =0.5 l,P 〈 0.05,uncorrected） and the change in the UPDRS motor score （r =0.61,P 〈 0.05,uncorrected）.Conclusions：The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease＇s progression in patients with PD.

Herein, a novel pyrrolo[2,3- ]pyridine-based glycogen synthase kinase 3β (GSK-3β) inhibitor, , was rationally designed and synthesised to target Alzheimer's disease (AD). inhibited GSK-3β, with an IC of 0.35 ± 0.06 nM, and had an acceptable kinase selectivity for 24 structurally similar kinases. Western blotting assays indicated that efficiently increased the expression of p-GSK-3β-Ser9 and decreased p-tau-Ser396 levels in a dose-dependent manner. In vitro cell experiments, showed low cytotoxicity to SH-SY5Y cells, significantly upregulated the expression of β-catenin and neurogenesis-related biomarkers, and effectively promoted the outgrowth of differentiated neuronal neurites. Moreover, substantially ameliorated dyskinesia in AlCl -induced zebrafish AD models at a concentration of 0.12 μM, which was more potent than Donepezil (8 μM) under identical conditions. Acute toxicity experiments further confirmed the safety of in vivo. Our findings suggested that is a prospective GSK-3β inhibitor and can be tested as a candidate for treating AD.

Aim： We previously reported a novel triptolide （TP）-glucosamine conjugate （TPG） that specifically accumulated in kidneys and protected renal function from acute ischemia/reperfusion （I/R） injury in rats. In this study we further examined the molecular mechanisms underlying the renoprotective action of TPG. Methods： The renal-targeting of TPG was investigated in a human proximal renal tubular epithelial cell line （HK-2） by measuring cell uptake of TP or TPG. The effects of TP or TPG on cell cycle distribution and apoptosis rate of HK-2 cells were assessed, and the activities of caspase-3 and caspase-9 were also measured. SD rats were subjected to bilateral renal ischemia by temporarily clamping both renal pedicles. The rats were administered TP （4.17 μmol·kg^-1·d^-1, iv） or TPG （4.17 μmol·kg^-1·d^-1, iv） for 3 d before the renal surgery. The kidneys were harvested after 24 h of recovery from the surgery. The levels of oxidative stress, proinflammatory cytokines, chemotactic cytokines and intracellular adhesion molecules in kidneys were examined. Results： The uptake of TPG in HK-2 cells was 2-3 times higher than that of TP at the concentrations tested. Furthermore, TPG targeting the proximal tubules was mediated through interactions with megalin receptors. TP （40-160 nmol/L） concentration-dependently increased GJM arrest, apoptosis and caspase-3/caspase-9 activity in HK-2 cells, whereas the same concentrations of TPG did not show those features when compared with the control group. In I/R-treated rats, TPG administration caused more robust down-regulation of proinflammatory cytokines （TNF-α, IL-6, IL-1, TGF-β） and chemotactic cytokines （MCP-1） in the kidneys compared with TP administration, suggesting the inhibition of the proliferation and accumulation of lymphocytes. And TPG administration also caused more prominent inhibition on the levels of oxidative stress and intracellular adhesion molecules in the kidneys, compared with TP administration. Conclusion： The renal-targeting TPG is more effective and less toxic than TP, in amelioration of I/R-induced rat renal injury, which may provide a new avenue for the treatment of acute kidney injury.

The effect of processing parameters on the flow response and microstructural evolution of the a＋b titanium alloy Ti-6.5Al-3.5Mo-1.5Zr-0.3Si has been studied by conducting isothermal hot compressive tests at a strain rate of 0.01-10 s-1 at 860-1100°C. The true stress-true strain curves of the sample hot-compressed in the a＋b phase region exhibit a peak stress followed by continuous flow softening, whereas in the b region, the flow stress attains a steady-state regime. At a strain rate of 10 s-1, the alloy exhibits plastic flow insta-bilities. According to the kinetic rate equation, the apparent activation energies are estimated to be about 674-705 kJ/mol in the a＋b region and 308-335 kJ/mol in the b region, respectively. When deformed in the a＋b region, the globularization process of the a colony structure occurs, and a dynamic recrystallized microstructures are observed to show bimodal. Dynamic recrystallization can take place in the b region irrespective of starting deformed structures.

Several ionic liquids were used as reaction media for penicillin G acylase catalysis. In all the assayed ionic liquids, [bmim]PF6 proved good media for PGA-catalyzed hydrolysis. A novel [bmim]PF6/water two-phase system is provided for 6-aminopenicillanic acid (APA) production, which will be more benefical than aquous batch systems used widely in industrial production of APA.