Effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy / 中华内分泌代谢杂志

Objective:To investigate the effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy.Methods:A retrospective analysis was conducted in 784 pregnant women including 111 cases of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy and 673 pregnant women with normal thyroid function as control group. All women were registered and delivered in the Department of Obstetrics of our hospital from April 2016 to April 2017. The complications and adverse outcomes of pregnancy in the two groups were analyzed.Results:Age, body weight before pregnancy, body mass index(BMI), 1 h plasma glucose and 2 h plasma glucose during oral glucose tolerance test in persistent isolated hypothyroxinemia group were higher than those in control group( P<0.05), with increased incidence of anemia during pregnancy( P<0.05). However, there were no significant differences in the incidences of gestational diabetes mellitus and gestational hypertension between the two groups( P>0.05). No significant statistical differences were found in macrosomia, stillbirth, neonatal malformation, postpartum hemorrhage, acute delivery, premature delivery, fetal intrauterine development delay, and small full-term infants between the two groups( P>0.05). Logistic regression analysis showed that age( OR=1.1, 95% CI 1.0-1.1, P=0.002) and pre-pregnancy body weight( OR=1.0, 95% CI 1.0-1.1, P=0.046) were risk factors for the occurrence of persistent isolated hypothyroxinemia in the first and second trimesters of pregnancy. Persistent isolated hypothyroxinemia in the first and second trimesters was associated with anemia during pregnancy( OR=1.9, 95% CI 1.1-3.2, P=0.024). Conclusions:Pregnant women who are older and heavier before pregnancy should pay more attention to their thyroid function. Pregnant women with persistent isolated hypothyroxinemia in the first and second trimesters should be concerned for anemia.

Effects of proton pump inhibitors on outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors / 国际肿瘤学杂志

Objective:To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs).Methods:A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group ( n=73) and Non-PPIs group ( n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients′ prognosis. Results:During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients′ gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ2=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ2=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group ( χ2=9.563, P=0.002; χ2=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS ( HR=1.85, 95% CI: 1.24-2.76, P=0.003); PPIs uses( HR=1.65, 95% CI: 1.09-2.51, P=0.019) and age ( HR=1.56, 95% CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS ( HR=1.90, 95% CI: 1.27-2.85, P=0.002) and PFS ( HR=1.73, 95% CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group ( n=64) were shorter than those in the Non-PPIs group ( n=34) ( χ2=16.187, P<0.001; χ2=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS ( HR=2.97, 95% CI: 1.70-5.22, P<0.001) and PFS ( HR=1.97, 95% CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS ( HR=3.38, 95% CI: 1.87-6.11, P<0.001) and PFS ( HR=2.31, 95% CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion:The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Changes of intestinal microflora and expression of intestinal and renal AGEs/SGLT-1 in diabetic kidney disease mouse model / 中华内分泌代谢杂志

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Clinical influencing factors of immunotherapy for non-small cell lung cancer / 国际肿瘤学杂志

In the treatment of non-small cell lung cancer (NSCLC), immunotherapies represented by immune checkpoint inhibitors are developing rapidly. It is the premise of precise treatment to clarify the influencing factors of NSCLC immunotherapy. In the course of immunotherapy for advanced NSCLC, elderly patients can obtain specific effect from immunotherapy; male patients benefit more from monotherapy; when steroid hormones are used for related symptoms caused by tumors, they are poor prognostic factors for patients. The occurrence of immune-related adverse events is a favorable prognostic factor while driving gene mutations and the use of antibiotics will reduce the efficacy of immunotherapy.

Role of antibiotics in tumor development and immunotherapy / 国际肿瘤学杂志

In recent years, immunotherapy with immune checkpoint inhibitor (ICI) as the representative drug has become an important treatment method for advanced malignant tumors. Preclinical studies have found that disorders of the gut microbiota can reduce the clinical benefit of patients treated with ICI. The latest data indicate that antibiotics may further affect the occurrence and development of tumors and the efficacy of immunotherapy by changing the abundance and composition of intestinal microbiota. To sum up the role of anti-biotics in the immunotherapy of advanced malignant tumor may provide a new idea for the optimization of treatment strategies for patients with advanced cancer.

Research advances of m 6A methylation modification in digestive system neoplasms / 国际肿瘤学杂志

N 6-methyladenosine (m 6A) methylation modification is defined as the methylation at the N 6 position of adenosine. This dynamic process is regulated by writer, eraser and reader. Accumulating evidence indicates that m 6A methylation modification is involved in the initiation and development of various digestive system neoplasms including proliferation, invasion, metastasis and chemoresistance. A further understanding about the role of m 6A methylation modification in digestive system neoplasms will benefit the development of a novel precise diagnostic and therapeutic strategy and finally improve the overall prognosis of patients.

Identification of Nonylphenol and Glucolipid Metabolism-Related Proteins in the Serum of Type 2 Diabetes Patients.

BACKGROUND: To identify serum nonylphenol (NP) and glucolipid metabolism-related proteins in Type 2 diabetes (T2D) patients. METHODS: We performed a hospital-based, case-control study in patients admitted to the Department of Endocrinology, Hospital of Zunyi Medical University, Zunyi City, China from Mar to Nov of 2014. The study included 112 T2D cases diagnosed in accordance with the 2013 WHO Expert Committee Diabetes Diagnosing Criteria, and 125 healthy individuals with normal fasting blood glucose (FBG) when receiving physical examination in the same period in the Municipal Physical Examination Center. Blood samples from subjects in the 2 groups underwent detection of biochemical indices, including FBG, blood fat, and NP. Glucolipid metabolism-related proteins, including estrogen receptor (ER), sterol regulatory element-binding protein-1c (SREBP-1c), wingless-type MMTV integration site family member 5a (Wnt5a), and peroxisome proliferator-activated receptor-γ (PPAR-γ). These indices were compared between the 2 groups to analyze the correlation between serum NP levels and glucolipid metabolic proteins. RESULTS: The subjects in the diabetes group had higher triglycerides (TG), total cholesterol (TC), NP, ER, SREBP-1c, Wnt5a, FBG, and TG levels than the healthy group, but lower levels of low-density lipoprotein cholesterol (LDL-C) and PPAR-γ than the healthy group. No significant differences in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found between the two groups. The serum NP levels were shown to be positively correlated with SREBP-1c but negatively correlated with PPAR-γ. CONCLUSION: The serum NP levels of T2D patients is higher than the levels in healthy controls, and its levels correlate with SREBP-1c and PPAR-γ levels.

The adverse effects of chronic low-dose exposure to nonylphenol on type 2 diabetes mellitus in high sucrose-high fat diet-treated rats.

OBJECTIVES: Although it has been shown that exposure to environmental endocrine disruptors (EDCs) has been implicated as a potential risk factor for metabolic disease, information on adverse effect of chronic low-dose exposure to nonylphenol (NP), on the development and progress of type 2 diabetes mellitus (T2DM) is scarce. NP, as an EDC, is a ubiquitous degradation product of nonylphenol polyethoxylate (NPE) that is primarily used in cleaning and industrial processes. METHOD: Eighty Sprague-Dawley rats were assigned into 8 groups (n = 10 per group): rats fed a normal-diet (ND) as the control (C-ND); rats fed a normal diet and were gavaged with NP at a dose level of 0.02 µg/kg/day (NP-L-ND), 0.2 µg/kg/day (NP-M-ND) or 2 µg/kg/day (NP-H-ND), respectively; rats fed a high-sucrose/high-fat diet (HSHFD) as the HSHFD control (C-HSHFD); rats fed a HSHFD and were gavaged with NP at a dose level of 0.02 µg/kg/day (NP-L-HSHFD), 0.2 µg/kg/day (NP-M-HSHFD) or 2 µg/kg/day (NP-H-HSHFD), respectively. RESULT: On day 180, the rats in the groups treated with NP-M-HSHFD and NP-H-HSHFD showed significant increases in body weight (p < 0.05) in comparison with the C-ND group. Fast blood glucose (FBG) level in the NP-M-HSHFD and NP-H-HSHFD groups was higher than that in the C-ND group (F = 96.17, p < 0.001). The fast serum insulin (FINS) level of rats was lower in both the NP-M-HSHFD and NP-H-HSHFD groups compared with the C-ND group (F = 145.56, p < 0.001). Serum leptin (LEP) level in both the NP-M-HSHFD and NP-H-HSHFD groups was lower when compared with the C-ND group (F = 34.62, p < 0.001). The effect of NP at the dose level of 0.2 µg/kg/day on FBG, serum FINS and LEP levels in rats was greatest among the treatment groups (p < 0.05). Oral glucose tolerance test showed increased area under the curve (AUC) in treatment groups at week 12 (p < 0.05). A decrease of pancreatic islet numbers and size was exhibited in the pancreatic tissue of NP-M-HSHFD and NP-H-HSHFD treated rats compared with C-ND treated rats. Co-exposure to NP and HSHFD causes inflammatory changes histologically. CONCLUSION: Chronic low-dose exposure to NP might induce impaired glucose tolerance, which further lead to insulin resistance, and pancreatic ß cell insulin secretion deficiency, ultimately increase the risk of T2DM. Moreover, additive toxic effects of NP and HSHFD on pancreatic beta-cell function and glucose metabolism have been identified in rats as well.

OPG and RANKL expression in alveolar bone of type 2 diabetic rats with periodontitis / 实用口腔医学杂志

Objective:To investigate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in type 2 diabetic rats with periodontitis.Methods:46 male Wistar rats were randomly divided into the healthy group(n =10),the periodontitis group(n =12),the type 2 diabetes mellitus group(n =12) and the type 2 diabetic periodontitis group(n =12).Animal models were prepared respectively.The expression of OPG and RANKL protein in alveolar bone was detected by immunohistochemistry(IHC).Results:Compared with the healthy group,the expression of OPG in the type 2 diabetes mellitus group,the periodontitis group,the type 2 diabetes mellitus with periodontitis group decreased in turn,however the expression of RANKL increased in turn.The expression of OPG and RANKL had no significant difference between periodontitis group and type 2 diabetes periodontitis group,while there was statistically significant difference among the other groups (P ＜ 0.05).Conclusion:Inflammation may lcad to upregulation of RANKL in osteoclasts and immune cells,and downregulation of OPG in osteoblasts.

Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity.

OBJECTIVE: The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats. METHODS: Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21. RESULTS: At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100 mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100 mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100 mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100 mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100 mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP-43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100 mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05). CONCLUSION: High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43.

A new method for quantifying mitochondrial axonal transport

Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial transport using microfluidic-chamber-cultured neurons together with a newly developed analysis package named "MitoQuant". This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms (temperature changes, drug treatment and genetic manipulation) that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mitochondrial transport that were not detected by traditional kymographic analyses.

The expression of visfatin in liver of diabetic rats and it′s relationship with type 2 diabetic / 重庆医学

Objective To explore the effects of visfatin in glucose metabolism by testing the expression of visfatin in liver of rats in different glucose metabolic statuses .Methods SD rats were randomly divided into five groups :normal control group (NC group) ,diet induce obesity group (DIO group) ,diabetes mellitus group (DM group) ,diabetes controlled by insulin group (INS group)and diabetes controlled by metformin group (MET group) .Tested the data of blood glucose (FPG) ,triglyceride(TG) ,total cholesterol(TC) ,free fat acid(FFA) ,fasting insulin(Fins) .The liver of rats was used to test visfatin ,glucose‐6‐phosphatase(G‐6‐pase) mRNA by RT‐PCR and visfatin ,AMP‐activated protein kinase‐α (AMPKα) ,phosphor‐AMP‐activated protein kinase‐α (p‐AMPKα) protein by Western blot .Results FBG of group DM increased than group NC and DIO (P< 0 .01) ;FBG of group INS and MET decresed than group DM (P < 0 .01) ;HOMA‐IR of group DIO and DM increased than group NC (P < 0 .01) ;HOMA‐IR of group DM increased than group DIO (P< 0 .01) .ISI of group DIO and DM decresed than group NC (P< 0 .01) ;ISI of group DM de‐creased than group DIO(P< 0 .01) .TG of group DIO increased than group NC (P< 0 .01) .TG of group INS and MET decreased than group DM (P< 0 .05) .The level of TG and TC of group DM ,INS and MET increased than group NC (P< 0 .05) .The level of serum FFA of group DM ,INS and MET were significantly higher than group NC (P < 0 .05) ;FFA of group DM increased than group DIO(P< 0 .05) .The expression of visfatin mRNA of group DM increased than group NC and DIO (P< 0 .05) ;visfatin mRNA of group INS and MET decreased than group DM (P< 0 .01) .Group DM ,INS and MET had a significantly higher level of G‐6‐Pase mRNA of than group DIO( P < 0 .05) ;Group MET had a significantly lower level of G‐6‐Pase mRNA of than group DM (P <0 .05) .The expression of visfatin protein of group DM ,INS and MET increased than group NC ( P < 0 .05) .The expression of AMPKα protein of group DM ,INS and MET decresed than group NC(P< 0 .05) ;AMPKα of group DM decresed than group DIO (P<0 .05) .The expression of p‐AMPKα protein of group DIO ,DM ,INS and MET decresed than group NC (P< 0 .01) .Conclusion The ex‐pression of visfatin in liver of SD rats might have something to do with insulin resistance and diabetes .We could′t consider that visfatin can affect the pathway of metformin activated AMPK to decrease blood glucose .

Effects of serum from the obesity patients with diabetic mellitus on TLR4/NF-κB pathway in human THP-1 monocytes / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of serum from the obesity patients and obesity patients with Diabetic mellitus on toll-like receptor 4/Nuclear factor -κB p65 (TLR/NF-κB) pathway in human THP-1 monocytes and to explore the inflammatory immune response in obesity.@*METHODS@#Peripheral serum was isolated from healthy volunteers (the control group), the obesity patients (Ob group) and the obesity patients with diabetic mellitus (the Ob with DM group), respectively, 20 in each group. THP-1 monocytes were incubated with the serum for 48 h. The monocytes and culture supernatant were collected. The phosphorylation level of NF-κB p65 protein in THP-1 monocytes was evaluated by Western blot as well as immunofluorescence assay. The TLR4 mRNA expression was evaluated by RT-PCR. ELISA was used to measure the monocyte chemotactic protein-1 (MCP-1) levels in the culture supernatant.@*RESULTS@#In the presence of serum, the obesity group and the obesity with diabetic mellitus group showed the up-regulated phosphorylation level of NF-κB p65 protein and TLR4 mRNA expression in THP-1 monocytes compared with the healthy control group (both P<0.05), and the MCP-1 levels in the obesity patients were up-regulated significantly compared with the healthy control group [healthy control group (26.4 ± 3.9) pg/mL, Ob group (45.8 ± 10.0) pg/mL, Ob with DM group (58.0 ± 15.3) pg/mL; P<0.05]. These parameters were further up-regulated in the obesity patients with diabetic mellitus patients.@*CONCLUSION@#The serum from the obesity patients or the obesity patients with diabetes can induce monocyte dysfunction, which might be related to the activation of TLR4/NF-κB signaling pathway.

Effect of LPS on the level of TLR4 and on the expression of NF-κB and Notch1 in monocytes from patients with type 2 diabetic nephropathy / 中南大学学报(医学版)

OBJECTIVE@#To characterize the expression of Toll-like receptor 4 (TLR4) in monocytes of diabetic nephropathy (DN) patients and the response of TLR4 to lipopolysaccharide (LPS), and, further, to explore the potential effects of inflammatory immune response in DN.@*METHODS@#Thirty DN patients with uremia, ten early-type 2 DN patients, and twenty healthy volunteers were enrolled for the determination of TLR4 expression in monocytes by using peripheral blood flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated and subjected to 1 μg/mL LPS for 24 h. Monocytes were collected to assay NF-κB p65 and Notch1 expression by Western blot, with immuneofluorescence detection. Serum and supernatants were sampled for the determination of interleukin-6 (IL-6) concentration by using ELISA. Serum C-reactive protein (CRP) level was determined by using the immunoturbidimetry.@*RESULTS@#Compared with the normal control, type 2 DN uremic patients had a significantly higher TLR4 fluorescence-blot intensities (FI), and serum CRP and IL-6 levels [TLR4 FI: DN uremia patients 2.8±0.9; early type 2 DN patients 3.4 ±0.7; healthy subjects 1.6±0.7. IL-6 concentration: DN uremia patients (84.8±20.7) pg/mL; early type 2 DN patients (63.20±14.4) pg/mL; healthy subjects (11.0±2.0) pg/mL. CRP concentraton: DN uremia patients (5.4±2.8) mg/L; early type 2 DN patients (3.7±1.7) mg/L; healthy subjects (1.7±0.7) mg/L. P<0.01 for any DN-group vs control]. In early type 2 DN patients, following exposure to LPS, PBMCs showed a significant upregulation in TLR4 and NF-κB p65 expression and a remarked increase in serum IL-6 level (all P<0.05), and NF-κB p65 transfer to the nucleus is enhanced. Notch1 protein expression was not significantly altered in any group.@*CONCLUSION@#A disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in type 2 DN patients. Such immunological dysfunction may be related to activation in NF-κB/TLR4 signaling pathways, and have nothing to do with the Notch1 signaling pathway.

Expression of human FUS protein in Drosophila leads to progressive neurodegeneration

Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.