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.

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*

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.

ObjectiveTo determine the protein and mRNA expression levels of interleukin-17 (IL-17) and proportions of Th17 cells in peripheral blood of patients with atopic dermatitis (AD),and to analyze their clinical significance.MethodsVenous blood samples were obtained from 63 patients with AD and 30 normal human controls.Enzyme linked immunosorbent assay was performed to measure the plasma level of IL-17 protein,real time fluorescence reverse transcription (RT)-PCR to detect the mRNA expression level of IL-17 in peripheral blood,flow cytometry to determine the percentage of Th17 cells in peripheral blood mononuclear cells(PBMCs).Spearman's rank correlation analysis was performed to assess the relationship of peripheral blood Th17 cell percentage and IL-17 levels with disease severity in patients with AD.Results The percentage of Th17 cells in PBMCs was 1.83％ ± 0.47％ in patients with acute AD,significantly higher than that in normal human controls (0.85％ ± 0.45％,t =4.128,P ＜ 0.01 ) and in patients with chronic AD ( 1.12％ ± 0.69％,t =2.439,P ＜ 0.05).There was a significant increase in the plasma level (98.37 vs.63.75 ng/L,U =168,P ＜ 0.05) and mRNA expression level of IL-17 in peripheral blood in patients with AD compared with normal controls.Both the Th17 cell percentage and plasma IL-17 level were positively correlated with eczema area and severity index(EASI) score in patients with AD (r =0.681,P ＜ 0.01;r =0.427,P ＜ 0.05).ConclusionsThere is an elevated proportion of Th17 cells and an abnormal expression of IL-17 protein and mRNA in peripheral blood from patients with acute AD,which are positively correlated with disease severity,implicating the possible roles of IL-17 and Th17 cells in the pathogenesis of AD.

A 54-year-old woman presented with a five-year history of malaise with weight loss and arthralgia of both knee joints. Six months prior to the presentation, an indurated nodule developed at the site of an old scar on the temporal side of left eyebrow. Subsequently, erythema and nodules spread over the trunk and extremities, especially at the sites of old scars on the hands. Physical examination showed bilateral axillary lymphadenectasis, a plaque at the site of an old scar on the temporal side of left eyebrow, a subcutaneous mass at the extensor aspect of the right upper arm, multiple dark-erythematous nodules at the site of scars on the left hand and both soles, few small erythematous papules scattered on the left forearm and trunk. The serum angiotensin converting enzyme concentration was high (82 kU/L). Computer tomography of thorax showed multiple obscure tubercles in both lungs and swollen lymph nodes in mediastina and axillary fossa, but no hilum pulmonis lymphadenectasis was observed. Histopathology revealed non-caseating granulomas with multinucleated giant cells. Neither acid-fast bacilli nor PAS staining was positive. A diagnosis of scar sarcoidosis was established. The lesions obviously improved after one-month treatment with oral methylprednisolone. This case represents a rare subtype of sarcoidosis that arose in old sears and clinically manifests as scar, nodules,plaques, subcutaneous masses and papules. The reactivation of old scars, which manifests as erythematous swelling and nodules, may highly suggest the diagnosis of sarcoidosis.