ObjectiveTo evaluate the effect of sex on phenotypic stability in mouse models of chemotherapy-induced alopecia (CIA) induced by cyclophosphamide (CYP) or paclitaxel (PTX), and to explore potential mechanisms underlying phenotypic heterogeneity in female mice. MethodsTwenty-eight wild-type specific pathogen-free (SPF) C57BL/6J mice (half male and half female) aged 6-8 weeks were selected for synchronous back hair removal. On the 9th day after hair removal (T0), the mice were randomly divided into a wild-type female CYP group, a wild-type male CYP group, a female negative control group and a male negative control group. Mice in the CYP groups were intraperitoneally injected with a single dose of 120 mg/kg CYP, and mice in the negative control groups were intraperitoneally injected with the same volume of normal saline. Subsequently, the phenotypic changes of the CIA model induced by CYP were continuously observed and photographed. Eleven 6-week-old SPF female C57BL/6J mice underwent bilateral ovariectomy (OVX group). Following successful surgery, these mice and five XY (Sry⁻) mice bred from Four Core Genotypes breeding stock were used to establish the chemotherapy-induced alopecia (CIA) model using the same protocol. Serum was collected from mice in the OVX group, wild-type female CYP group, and wild-type male CYP group on T7 after CYP administration for steroid hormone analysis by mass spectrometry to evaluate the effects of gonadal estrogen and sex chromosome background changes on the stability of the CYP-induced female alopecic phenotype. Finally, twenty SPF C57BL/6J mice aged 6-8 weeks (half male and half female) were randomly divided into a PTX low-dose group and a PTX high-dose group. On the 9th day after simultaneous hair removal, PTX was injected intraperitoneally at a single dose of 80 mg/kg or 120 mg/kg, respectively. Mice from the PTX low-dose group and the PTX high-dose group were continuously observed and photographed to compare the intra-group consistency of the phenotypes of female and male mice. Six SPF C57BL/6J mice (half male and half female) aged 6-8 weeks were used to repeat the construction method of the PTX low-dose group, and the hair follicle histological examination was performed at T0, T4, T7, T14 and T21, respectively, to observe the damage caused by PTX to hair follicle regeneration. ResultsThe phenotypes of CYP-induced male CIA mice are stable and reproducible. There are obvious individual differences in the alopecia phenotype in the CYP-induced female CIA model mice, which may be mainly caused by the differences in the relevant estrogens in the estrous cycle. The difference between OVX+CYP group and XY (Sry⁻) +CYP group disappeared, suggesting that ovarian-derived hormones and XY (Sry⁻) sex chromosome background may be involved in the formation of phenotypic heterogeneity of CYP-induced alopecia in female mice. The mice in the high-dose PTX group and the low-dose PTX group showed a relatively consistent alopecia and regrowth process, and there was no significant sex difference. ConclusionCYP-induced CIA is strongly influenced by sex, and ovariectomy or alteration of the sex chromosome background can improve the consistency of CYP-induced alopecic phenotypes in female mice. PTX-induced CIA shows good phenotypic consistency in both female and male mice, indicating broad applicability across sexes. Taken together, the choice of animal sex in CIA model construction, mechanistic studies, and evaluation of anti-alopecia interventions should take into account the type of chemotherapeutic agent, the study objective, and the required degree of phenotypic stability. Sex should therefore be considered an important variable in model standardization and interpretation of experimental findings.

Plant fungal pathogens secrete numerous proteins into the apoplast at the plant-fungus contact sites to facilitate colonization.However,only a few secretory proteins were functionally characterized in Magnaporthe oryzae,the fungal pathogen causing rice blast disease worldwide.Asparagine-linked glycosylation 3(Alg3)is an a-l,3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins.Fungal pathogenicity and cell wall integrity are impaired in Aalg3 mutants,but the secreted proteins affected in Aalg3 mutants are largely unknown.In this study,we compared the secretomes of the wild-type strain and the Aalg3 mutant and identified 51 proteins that require Alg3 for proper secretion.These proteins were predicted to be involved in metabolic processes,interspecies interactions,cell wall organization,and response to chemicals.Nine proteins were selected for further validation.We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae.Moreover,the N-glycosylation of these proteins was significantly changed in the Aalg3 mutant,leading to the decreased protein secretion and abnormal protein localization.Furthermore,we tested the biological functions of two genes,INV1(encoding invertase 1,a secreted invertase)and AMCase(encoding acid mammalian chinitase,a secreted chitinase).The fungal virulence was significantly reduced,and the cell wall integrity was altered in the Ainv1 and Aamcase mutant strains.Moreover,the N-glycosylation was essential for the function and secretion of AMCase.Taken together,our study provides new insight into the role of N-glycosylated secretory proteins in fungal virulence and cell wall integrity.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective To investigate the influence of Leptin on the proliferation of peripheral blood regulatory T cells in patients with rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 6 RA patients.RA PBMCs were stimulated with anti-CD3 (3 μg/ml)/anti-CD28(2 μg/ml) antibody for 72 h,anti-CD3 (3 μg/ml)/anti-CD28 (2 μg/ml) antibody and Leptin (100 ng/ml) for 72 h,anti-CD3 (3 μg/ml)/anti-CD28 (2 μg/ml) antibody and Leptin (100 ng/ml) and interleukin (IL)-6 receptor antagonist (0.5 μg/ml) for 72 h.Regulatory T cells (Treg) were detected by flow cetometry.IL-6 level and TGF-βlevels in the supernatants of RA PBMCs culture were detected by Enzyme linked immunosorbent assay(ELISA).Statistical analysis between the two groups were performed by Wilcoxon Signed Rank Test.Results ①) Our results suggested that compared to the control group,RA PBMCs were stimulated by leptin for 72 h had lower percentage of Treg[13.6(11.6,14.8)％ vs 9.8(7.0,10.0)％,Z=-2.201,P＜0.05];Compared to the control group,the level of IL-6 and TGF-β were elevated when RA PBMCs treated with leptin for 72 h [548.9(508.6,608.4)ng/L vs 631.8(538.4,672.6) ng/L,Z=-1.992,P＜0.05;1175.0(1 045.4,1 373.1) ng/L vs 1 580.2(1 315.3,1 906.5) ng/L,Z=-2.201,P＜0.05];② The percentage of Peripheral Treg was increased [9.8(7.0,10.0)％ vs 12.3(9.7,13.8)％,Z=-1.997,P＜0.05] and the level of IL-6 was decreased [631.8(538.4,672.6) ng/L vs 522.7(339.3,593.3) ng/L,Z=-2.201,P＜0.05] when RA PBMCs was stimulated with IL-6 receptor antagonist and anti-CD3/anti-CD28 antibody and Leptin for 72 h.Conclusion The study has shown that Leptin can down-regulate the percentage of RA peripheral blood Treg via increasing IL-6 secretion.

Plants provide an immense reservoir of natural secondary metabolites. Secondary metabolites and those involved enzymes accumulate in various compartments in specific plant tissues. The biosynthesis of diverse groups of secondary metabolites is often complicated, tightly controlled via network interconnections, metabolite levels, metabolite channeling and multi-enzyme complexes, and so on. Secondary metabolite profiles could be genetically altered by two strategies, i.e. single gene modification and multiple gene modification; which thus has opened a feasible and prospective platform for secondary chemicals production in plant.
Gene Expression Regulation, Plant ; Phytochemicals ; biosynthesis ; genetics ; Plants ; genetics ; metabolism ; Plants, Genetically Modified ; genetics ; metabolism ; Secondary Metabolism ; genetics ; Transformation, Genetic

Objective To determine the urine parameters,body temperature and main organ coefficient of Fujian rabbits.Methods In this experiment,we selected twenty healthy Fujian rabbits with weight of about 2.5kg.Both male and female rabbits were ten.Before experiment,the rabbits drunk water freely.We collected fresh urine before breeding in the morning,and then determined the ten items urine parameters soon.Under the room temperature,we used electricity thermometer into the rabbits' rectum to determine the body temperature.Being fasting for 12h,the rabbits were anesthetized by 3% pentobarbital sodium,and then were put to death after bloodletting.The dissection took various internal organs immediately.The clean organs were weighed by electronic analytical balance.Results The results showed that the majority of the urine was yellow opacity,and the ten items urine parameters between male and female had no significant difference.The average body temperature of Fujian rabbits was 39.67℃ above other ones.There was no significant difference in main organ coefficient between male and female expect the lung and spleen.Conclusion In a word,it was objective to determine the body temperature,urine parameters,mainly organ coefficient of Fujian rabbits which were fed in conventional environment.It is valuable for the appliation of Fujian rabbits in life science sphere.

Objective The establish a bioassay method to luteinizing hormone in serum for rhesus monkey.Methods With the technique method of bioassay,we measured the content of luteinizing hormone(LH)in serum for the rhesus monkey.Results The sensitivity of the assay was 0.05ng LH/per tube.The intra and inter assay variations were(3.18?1.52)% and(7.56?3.41)%,which proved that the method accuracy was higher.Both the dose-response curve of LH in serum for rhesus monkey and hLH of standard showed the method could be used to examine LH in serum of biology activity for rhesus monkey,which reflected the physiological status of the animals.The recoverable rates of 10,20 and 40ng hLH added to the diluted ram serum were(99.12?4.56)%,(99.31?6.49)% and(101.02?7.58)% respectively,which demonstrated the veracity of the bioassay results.Conclusion The bioactive LH level in pituitary extract is by far higher than that in circulation.