Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective To investigate the inhibitory effect and mechanism of lentinan on colitis-associated colorectal cancer (CAC) induced by azomethane (AOM)/dextran sulfate sodium salt (DSS) through the IL-6/ STAT3 pathway. Methods C57BL/6 mice were randomly divided into a control group, a model group, a low-dose group (0.865 mg/kg lentinan), a medium-dose group (1.73 mg/kg lentinan), and a high-dose group (3.46 mg/kg lentinan). Except the control group, CAC was induced by AOM/DSS in the other groups, and corresponding drugs were injected intraperitoneally during the modeling process. Body mass, disease activity index (DAI) score, colon length, and tumor number were compared among all groups. Hematoxylin–eosin staining was used to observe the pathological morphology of colon. ELISA was utilized to detect the IL-6, IL-1β, and IL-18 contents in serum. Western blot analysis was conducted to detect the expression levels of IL-6, p-STAT3, and c-Myc in colon tissues. Results The tumor number, DAI score, serum IL-6, IL-1β, and IL-18 contents and the expression levels of IL-6, p-STAT3, and c-Myc in the colon tissue of the model group were higher than those of the control group, while the body mass and colon length were lower than those of the control group (P<0.05). The pathological morphology of colon tissues showed adenocarcinoma formation. After different doses of lentinan intervention, the tumor number, DAI score, serum IL-6, IL-1β, and IL-18 contents and the expression levels of IL-6, p-STAT3, and c-Myc in colon tissues were all lower than those in the model group, while body mass and colon length were higher than those in the model group (P<0.05). The pathological morphology of colon tissues showed adenomas of different grades but no adenocarcinoma was found. Conclusion Lentinan inhibits CAC formation, and its anticancer effect is related to the inhibition of the IL-6/STAT3 pathway.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

ObjectiveTo investigate the infection and genotypes of Wolbachia in Aedes albopictus. MethodsAdult and larval samples of Aedes albopictus were collected from different residential and wild areas from 2020 to 2021， Wolbachia surface protein （wsp） gene was amplified and genotyped for wAlbA and wAlbB by PCR， and sequenced for phylogenetic analysis. The difference of detection rate among different habitats， male and female adult mosquitoes， adult and larvae was compared by χ² analysis. ResultsThe detection rate of Wolbachia in adult and larvae of Aedes albopictus were 43.5% （77/177） and 70.4% （190/270）， respectively， with a statistically significant difference （χ²=32.086，P<0.001）， and wAlbA and wAlbB were mainly detected together. The detection rate of Wolbachia in female and male Aedes albopictus were 50.7% （76/150） and 3.7% （1/27）， respectively， with a statistically significant difference（χ²=20.533，P<0.001）. The detection rate of adult Aedes albopictus in Songjiang wild area， residential area and Hongkou residential area were 91.7% （55/60）， 18.8% （22/117） and 41.7% （30/72）， respectively， with a statistically significant difference （χ²=54.322，P<0.001）. Genotyping and phylogenetic analysis showed that adult and larvae of Aedes albopictus infected with Wolbachia were mainly wAlb A and wAlb B. In addition， some sequences formed clades independently， and the genetic distance from other sequences was relatively large. ConclusionInfection of Wolbachia in Aedes albopictus is relatively common in Songjiang District. The main genotypes are wAlb A and wAlb B and there may be other subtypes， which are worthy of further exploration and research.

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

Objective:To explore the clinical effect of continuous transfer of sural neurovascular flap and free-style perforator flap for repairing soft tissue defect of foot and ankle.Methods:Clinical data of patients with skin and soft tissue defects of the foot and ankle from Ningbo HwaMei Hospital, University of Chinese Academy of Sciences were enrolled in this study from February 2011 to February 2020. The sural neurovascular flap was used to repair the soft tissue defect of the ankle and foot, and the free-style perforator flap was designed to cover the donor site in the proximal lower leg. The survival of the flaps in the recipient and donor sites were observed after surgery, and the morphology, sensation, and foot and ankle movement were followed up in the later period.Results:A total of 11 patients with soft tissue defects in the ankle and foot were enrolled, including 7 males and 4 females, average aged 41±3 years old. The area of the wound defect was 3.0 cm×5.0 cm-7.0 cm×10.0 cm; the size of sural neurovascular flap was 4.0 cm×10.0 cm-9.0 cm×17.0 cm; and the size of perforator flap of the proximal lower leg was 4.5 cm×6.5 cm-5.5 cm×10.5 cm on average, respectively. All flaps were survived primarily without infection, vascular crisis, and flap necrosis. Patients were followed up for 2-36 months in this study, with an average of 10.2 months. There was no scar contracture being observed, and the shape and sensation of the flap of patients were recovered well. Two-point distance discrimination of the flap of ankle and foot was 13-18 mm. The angle of ankle dorsiflexion, plantar flexion, inversion, and eversion were 30°-45°, 35°-45°, 30°-40°, respectively.Conclusions:We found that the wound of the foot and ankle could be safely and effectively repaired by the sural neurovascular flap, and the donor site on the proximal lower leg could be well repaired by free-style perforator flaps, with no sacrifice with the main blood vessel. Overall, these two methods can not only obtain a good appearance but also reduce functional damage.

Objective:To explore the clinical effect of continuous transfer of sural neurovascular flap and free-style perforator flap for repairing soft tissue defect of foot and ankle.Methods:Clinical data of patients with skin and soft tissue defects of the foot and ankle from Ningbo HwaMei Hospital, University of Chinese Academy of Sciences were enrolled in this study from February 2011 to February 2020. The sural neurovascular flap was used to repair the soft tissue defect of the ankle and foot, and the free-style perforator flap was designed to cover the donor site in the proximal lower leg. The survival of the flaps in the recipient and donor sites were observed after surgery, and the morphology, sensation, and foot and ankle movement were followed up in the later period.Results:A total of 11 patients with soft tissue defects in the ankle and foot were enrolled, including 7 males and 4 females, average aged 41±3 years old. The area of the wound defect was 3.0 cm×5.0 cm-7.0 cm×10.0 cm; the size of sural neurovascular flap was 4.0 cm×10.0 cm-9.0 cm×17.0 cm; and the size of perforator flap of the proximal lower leg was 4.5 cm×6.5 cm-5.5 cm×10.5 cm on average, respectively. All flaps were survived primarily without infection, vascular crisis, and flap necrosis. Patients were followed up for 2-36 months in this study, with an average of 10.2 months. There was no scar contracture being observed, and the shape and sensation of the flap of patients were recovered well. Two-point distance discrimination of the flap of ankle and foot was 13-18 mm. The angle of ankle dorsiflexion, plantar flexion, inversion, and eversion were 30°-45°, 35°-45°, 30°-40°, respectively.Conclusions:We found that the wound of the foot and ankle could be safely and effectively repaired by the sural neurovascular flap, and the donor site on the proximal lower leg could be well repaired by free-style perforator flaps, with no sacrifice with the main blood vessel. Overall, these two methods can not only obtain a good appearance but also reduce functional damage.

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e′ was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e′ (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e′, and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.

Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P＜0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) ％ in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

Objective To study effects of oxycodone post-operative early analgesia on stress re-sponse with in diabetics undergoing uvulopalatopharyngoplasty (UPPP).Methods Eighty patients undergoing UPPP,53 males,27 females,aged 28-65 years,ASA Ⅰ or Ⅱ were randomly divided in-to two groups(n =40).1 5 minutes before the end of the operation,group O was intravenously given oxycodone 0.07 mg/kg;Group F fentanyl 0.7 μg/kg.The patients of the two groups were sampled venous blood 3 ml in the morning of operation (T1 ),postoperative 1 hour (T2 ),postoperative 3 hours (T3 )for determination of serum cortisol (Cor),serum insulin(Ins),serum C-peptide(C-P)u-sing electrochemical luminescence method.Results Cor at T2 ,T3 was lower than that at T1 , C-P was higher than that at T1 (P <0.05)in group O,respectively;Cor at T2 ,T3 was higher than that at T1 , respectively,C-P was lower than that at T1 (P <0.05);Cor in group F was higher than that in group O,C-P in group F was lower than that in group O(P <0.05).Ins at T2 ,T3 was lower than that at T1 and was lower than that in group O(P <0.05).Conclusion Oxycodone 0.07 mg/kg early analgesia for UPPP significantly inhibits the occurrence of stress response.