Prelimbic cortex-nucleus accumbens core projection positively regulates itch and itch-related aversion.

Itch is one of the most common clinical symptoms in patients with diseases of the skin, liver, or kidney, and it strongly triggers aversive emotion and scratching behavior. Previous studies have confirmed the role of the prelimbic cortex (Prl) and the nucleus accumbens core (NAcC), which are reward and motivation regulatory centers, in the regulation of itch. However, it is currently unclear whether the Prl-NAcC projection, an important pathway connecting these two brain regions, is involved in the regulation of itch and its associated negative emotions. In this study, rat models of acute neck and cheek itch were established by subcutaneous injection of 5-HT, compound 48/80, or chloroquine. Immunofluorescence experiments determined that the number of c-Fos-immunopositive neurons in the Prl increased during acute itch. Chemogenetic inhibition of Prl glutamatergic neurons or Prl-NAcC glutamatergic projections can inhibit both histaminergic and nonhistaminergic itch-scratching behaviors and rectify the itch-related conditioned place aversion (CPA) behavior associated with nonhistaminergic itch. The Prl-NAcC projection may play an important role in the positive regulation of itch-scratching behavior by mediating the negative emotions related to itch.

Comparison of midterm efficacy of Kirschner wires and elastic intramedullary nails after closed reduction of Judet type 3 radial neck fractures in children: a multicenter study.

Objective: The objective of this study was to compare the midterm efficacy of Kirschner wires and elastic intramedullary nails after the closed reduction treatment of Judet 3 radial neck fractures in children. Methods: This was a retrospective multicenter study of patients diagnosed with Judet type 3 radial neck fractures who underwent closed reduction and internal fixation at four tertiary hospitals from January 2019 to December 2021. Gender, age, fracture type, operation time, follow-up time, x-ray results and complications were collected. The recovery of elbow joint between the two internal fixation methods, elbow motion and complications at the last follow-up were compared. Results: The average operation time of EIN group was statistical significantly increased compared with KW group. There were no significant differences in MEPS score and ROM 3 months after surgery between the two groups, but the ROR Angle of EIN group was statistical significantly increased compared with KW group 3 months after surgery. There were no significant differences in MEPS score, ROM and ROR at the last follow-up. The incidence of complications in EIN group was significantly lower than that in KW group. Conclusion: The use of elastic intramedullary nails fixation or Kirschner wires fixation in the treatment of radial neck fractures in children can both achieve satisfactory fracture reduction and healing. Compared with elastic intramedullary nails, the operation time of Kirschner wires fixation is shorter, and the internal fixation does not need to be removed under anesthesia again, but the complication rate is higher.

Analysis of airway structural parameters in Han Chinese adults: a prospective cross-sectional study.

INTRODUCTION: Establishing reference ranges for central airway parameters and exploring their influencing factors in Han Chinese non-smoking adults. METHODS: This prospective cross-sectional study was conducted on Han Chinese non-smoking adults who underwent chest CT scans at the Tongzhou Campus of Dongzhimen Hospital Affiliated with the Beijing University of Chinese Medicine between September 2022 and November 2022. The SYNAPSE 3D image analysis software was utilized, enabling the extraction of critical parameters such as central airway length, airway wall thickness (AWT), airway lumen area (ALA), and subcarinal angle (SCA). Pearson's correlation coefficient analysis and multiple linear regression analysis methods were employed to evaluate the relationship between central airway parameters and age, sex, weight, and height. RESULTS: The study encompassed 888 Han Chinese non-smoking adults, comprising 456 females and 432 males. Significant sex differences were noted in central airway length, AWT, and ALA, with measurements in males exceeding those in females (p < 0.01) with no significant difference in SCA. Correlation analyses unveiled relationships between central airway parameters and age, sex, weight, and height. During multiple linear regression analyses, no conclusive evidence emerged to demonstrate the independent or combined explanatory or predictive capacity of the aforementioned variables for central airway length and SCA. Although sex has a significant impact on AWT and ALA, its capability in explanation or prediction remains limited. The conclusions drawn from the primary analysis receive reinforcement from the outcomes of sensitivity analyses. CONCLUSION: Establishing the distribution range of central airway parameters in non-smoking Han Chinese adults. It observed significant sex differences in these parameters, except for the SCA. However, the study found that the predictive or explanatory power of age, sex, weight, and height for central airway parameters was either limited or non-significant.

Impact of time-to-treatment initiation on survival in single primary non-small cell lung Cancer: A population-based study.

Background: Understanding the effects of a delayed time-to-treatment initiation(TTI) for non-small cell lung cancer (NSCLC) is vital. Methods: We analyzed NSCLC data from the Surveillance, Epidemiology, and End Results database, focusing on lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). TTI was studied as both continuous and dichotomous variables. Restricted cubic splines were employed to identify potential nonlinear dependency between the hazard ratio (HR) and TTI. Propensity score matching was used to ensure a balanced patient allocation, and then survival differences between groups were assessed using Kaplan-Meier analysis and competing risk models. We used overall survival (OS) as the primary outcome and cancer-specific cumulative mortality (CSCM) as a complementary indicator. Finally, sensitivity analyses were performed on censored data. Results: A total of 80,020 with NSCLC were analyzed. TTI was assessed as a continuous variable, showing a noticeable increase in the HR for stage I to II NSCLC with TTI >1 month. Conversely, the trend for stage III to IV NSCLC was the opposite. In stage I LUAD, the 'early' group demonstrated a higher OS compared to the 'delayed' group (Log-rank P = 0.002), while there was no significant difference in CSCM (Fine-gray P = 0.321). In stage I LUSC, there was no significant difference in OS(Log-rank P = 0.260), but the 'early' group had a lower CSCM (Fine-gray P = 0.018). For stage II-IV NSCLC, the 'delayed' group did not exhibit a negative impact on OS or CSCM. The sensitivity analysis further supported the results of the main analysis. Conclusion: Prolongation of TTI ≥31 days has a negative impact on OS or CSCM in stage I NSCLC only. Further exploration and validation are needed to determine whether these results can be used as evidence for a 'safe' TTI threshold setting for future NSCLC.

Linezolid-Induced Pancytopenia in Patients Using Dapagliflozin: A Case Series.

Background: Linezolid is classed as oxazolidinone antibiotics which can be used to treat severe infections caused by vancomycin-resistant Enterococcus faecium, hospital-acquired pneumonia caused by Staphylococcus aureus, complicated skin, and uncomplicated skin structure infections (SSSIs) caused by methicillin-susceptible S. aureus or Streptococcus pyogenes, and community-acquired pneumonia caused by Streptococcus pneumoniae. However, many studies have suggested it can also cause thrombocytopenia and pancytopenia. Patients and Methods: We report on three patients with linezolid-pancytopenia. Patients in cases 1 and 2 were diagnosed with heart failure with preserved ejection fraction (HFpEF) and were both administered with dapagliflozin, one of the sodium-dependent glucose transporters 2 inhibitors (SHLT-2i). Results: Two patients were diagnosed with type 2 diabetes, pneumonia, and hyponatremia. Severe myelosuppression occurred in both patients, with a severe decrease in leukocytes and platelets and a moderate decrease in hemoglobin, who eventually passed away despite the discontinuation of linezolid and adopting appropriate treatment measures. The patient in case 3 was diagnosed with pneumonia, type 2 diabetes, and sequelae of cerebral thrombosis. After twelve days of treatment, the patient developed moderate thrombocytopenia and anemia. She recovered without any additional treatment after the discontinuation of linezolid. Conclusion: In this case series, two patients with irreversible myelosuppression were treated with both linezolid and SGLT-2i, and one diabetic patient with single linezolid use presented with reversible pancytopenia, suggesting that SGLT-2i may exacerbate myelosuppression of linezolid. Linezolid should be used with caution in infectious patients with a history of SGLT-2i. We will conduct relevant animal experiments to clarify the interaction between the two drugs.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

[Clinical observation of different surgical methods for metaphyseal sequelae of ulna].

OBJECTIVE: To investigate the effect and safety of ulnar osteochondroma resection, ulnar minimally invasive osteotomy, external fixation and ulnar lengthening in the treatment of forearm deformity of metaphyseal extension of ulna. METHODS: From August 2005 to December 2013, there were 20 cases of ulnar metaphyseal sequelae, including 15 males and 5 females, aged from 7 to 13(10.00±2.34) years, the course of disease ranged for 6 to 11(8.10±1.52) months. The clinical manifestations were shortening of the affected forearm and bending to the ulnar side. The postoperative evaluation included pain, activities of daily living, orthopedic effect and the range of motion of wrist, elbow and forearm. The radiological evaluation included ulnar length, radial joint inclination angle and wrist epiphysis growth. RESULTS: All patients healed without infection. The only operation related to complications was ulnar lengthening, including 1 case of nonunion, 2 cases of ulnar lengthening callus fracture and 1 case of temporary radial nerve palsy. All patients were followed up for 4 to 7.5 years, with an average of (6.03±1.33) years. There were statistically significant differences in changes of wrist radial deviation, ulnar deviation, forearm pronation and supination in all cases (P<0.05). Radiological evaluation parameters (ulnar variance, radial joint angle, wrist slip) were improved, and the differences were statistically significant(P<0.05). The modified Green and O'Brien wrist function scores at the last follow-up were significantly different from those before operation (P<0.05). The clinical effect of wrist joint was significantly different from that before operation (P<0.05). The Mayo elbow function scoreat the latest follow-up was significantly different from that before operation (P<0.05). The clinical effect of elbow joint was significantly different from that before operation (P<0.05). CONCLUSION: Ulnar lengthening is not beneficial to prevent the development of long-term deformity. Simple resection of osteochondroma of distal ulna is beneficial to prevent the development of deformity. Patients with limited rotation of wrist joint and forearm and strong demand for improvement of appearance can be actively treated.

Chronic colchicine poisoning with neuromyopathy, gastric ulcers and myelosuppression in a gout patient: A case report.

BACKGROUND: Colchicine has been widely used as an anti-gout medication over the past decades. However, it is less commonly used due to its narrow therapeutic range, meaning that its lethal dose is close to its therapeutic dose. The lethal dose of colchicine is considered to be 0.8 mg/kg. As chronic colchicine poisoning has multiple manifestations, it poses a challenge in the clinician's differential diagnosis. Historically, the drug was important in treating gout; however, clinical studies are currently underway regarding the use of colchicine in patients with coronavirus disease 2019 as well as its use in coronary artery disease, making this drug more important in clinical practice. CASE SUMMARY: A 61-year-old male with a history of gout and chronic colchicine intake was admitted to our Emergency Department due to numbness and weakness of the lower limbs. The patient reported a history of colchicine intake for 23 years. After thorough examination, he was diagnosed with colchicine poisoning, manifesting as neuromyopathy, multiple gastric ulcers and myelosuppression. We advised him to stop taking colchicine and drinking alcohol. We also provided a prescription of lansoprazole and mecobalamin, and then asked him to return to the clinic for re-examination. The patient was followed up for 3-mo during which time his gout symptoms were controlled to the point where he was asymptomatic. CONCLUSION: Colchicine overdose can mimic the clinical manifestations of several conditions. Physicians easily pay attention to the disease while ignoring the cause of the disease. Thus, the patient's medication history should never be ignored.

Acute myocarditis presenting as accelerated junctional rhythm in Graves' disease: A case report.

BACKGROUND: Acute myocarditis is an acute myocardium injury that manifests as arrhythmia, dyspnea, and elevated cardiac enzymes. Acute myocarditis is usually caused by a viral infection but can sometimes be caused by autoimmunity. Graves' disease is an autoimmune disease that is a rare etiology of acute myocarditis. Accelerated junctional rhythm is also a rare manifestation of acute myocarditis in adults. CASE SUMMARY: A rare case of new-onset Graves' disease combined with acute myocarditis and thyrotoxic periodic paralysis is reported. The patient was a 25-year-old young man who suddenly became paralyzed and felt palpitations and dyspnea. He was then sent to our emergency department (ED). Upon arrival, electrocardiography revealed an accelerated junctional rhythm and ST-segment depression in all leads, and laboratory findings showed extreme hypokalemia and elevated troponin I, with the troponin I level being 0.32 ng/mL (reference range, 0-0.06 ng/mL). Coronary computer tomography angiography was performed, and there were no abnormal findings in the coronary arteries. Subsequently, the patient was admitted to the ED ward, where further testing revealed Graves' disease, along with continued elevated cardiac enzyme levels and B-type natriuretic peptide (BNP) levels. The troponin I level was 0.24 ng/mL after admission. All of the echocardiography results were normal: Left atrium 35 mm, left ventricle 48 mm, end-diastolic volume 102 mL, right atrium 39 mm × 47 mm, right ventricle 25 mm, and ejection fraction 60%. Cardiac magnetic resonance was performed on the fifth day of admission, revealing myocardial edema in the lateral wall and intramyocardial and subepicardial late gadolinium enhancement in the lateral apex, anterior lateral, and inferior lateral segments of the ventricle. The patient refused to undergo an endomyocardial biopsy. After 6 d, the patient's cardiac enzymes, BNP, potassium, and electrocardiography returned to normal. After the patient's symptoms were relieved, he was discharged from the hospital. During a 6-mo follow-up, the patient was asymptomatic and subjected to thyroid function, liver function, kidney function, troponin I, and electrocardiograph routine tests for medicine adjustments. The hyperthyroid state was controlled. CONCLUSION: Acute myocarditis is a rare manifestation of Graves' disease. Accelerated junctional rhythm is also a rare manifestation of acute myocarditis in adults. When the reason for hypokalemia and elevated cardiac enzymes in patients is unknown, cardiologists should consider Graves' disease and also pay attention to accelerated junctional rhythm.

Study of Combined Multi-Point Constraint Multi-Scale Modeling Strategy for Ultra-High-Performance Steel Fiber-Reinforced Concrete Structures.

Compared with normal strength concrete (NSC), ultra-high-performance steel fiber-reinforced concrete (UHPFRC) shows superior performance. The concrete damage plasticity (CDP) model in ABAQUS can predict the mechanical properties of UHPFRC components well after calibration. However, the simulation of the whole structure is seriously restricted by the computational capability. In this study, a novel multi-scale modeling strategy for UHPFRC structure was proposed, which used a calibrated CDP model. A novel combined multi-point constraint (CMPC) was established by the simultaneous equations of displacement coordination and energy balance in different degrees of freedom of interface nodes. The advantage is to eliminate the problem of the tangential over-constraint of displacement coordination equation at the interface and to avoid stress iteration of the energy balance equation in the plastic stage. The expressions of CMPC equations of typical multi-scale interface connection were derived. The multi-scale models of UHPFRC components under several load cases were established. The results show that the proposed strategy can well predict the strain distribution and damage distribution of UHPFRC while significantly reducing the number of model elements and improving the computational efficiency. This study provides an accurate and efficient finite element modeling strategy for the design and analysis of UHPFRC structures.

[Correlation between Gut Microbiota and Lung Cancer].

Gene-environment interactions underlie cancer susceptibility and progression. The human body is exposed to and affected by the microenvironment seiscasts of various microorganisms and their metabolites, such as the microenvironment of gut microbiota. The relative abundance of some intestinal microbes in lung cancer patients was significantly different from that in the control group. These studies suggest that gut microbiota may be associated with lung cancer through some ways. At the same time, gut microbiota is relatively manageable environmental variables compared to the external environment we are exposed to, as they are highly quantifiable and relatively stable in the individual. Just as some measures of diagnosis, intervention and treatment of lung cancer targeting gut microbiota have achieved some results in clinical practice. In this review, we mainly discuss the role of gut microbiota and its metabolites in the progression and treatment of lung cancer through certain ways, such as regulation of metabolism, inflammation, and immune response. Finally, based on current research progress, it is inferred that research on gut microbiota may be an effective approach to the precise and personalized medical treatment of lung cancer.
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Influence of Uniaxial Stress on the Shear-Wave Spectrum Propagating in Steel Members.

Structural health monitoring technologies have provided extensive methods to sense the stress of steel structures. However, monitored stress is a relative value rather than an absolute value in the structure's current state. Among all the stress measurement methods, ultrasonic methods have shown great promise. The shear-wave amplitude spectrum and phase spectrum contain stress information along the propagation path. In this study, the influence of uniaxial stress on the amplitude and phase spectra of a shear wave propagating in steel members was investigated. Furthermore, the shear-wave amplitude spectrum and phase spectrum were compared in terms of characteristic frequency (CF) collection, parametric calibration, and absolute stress measurement principles. Specifically, the theoretical expressions of the shear-wave amplitude and phase spectra were derived. Three steel members were used to investigate the effect of the uniaxial stress on the shear-wave amplitude and phase spectra. CFs were extracted and used to calibrate the parameters in the stress measurement formula. A linear relationship was established between the inverse of the CF and its corresponding stress value. The test results show that both the shear-wave amplitude and phase spectra can be used to evaluate uniaxial stress in structural steel members.

Overexpression of Egr2 and Egr4 protects rat brains against ischemic stroke by downregulating JNK signaling pathway.

OBJECTIVE: The purpose of this study was to investigate the effect of Egr2 and Egr4 upregulation on ischemic stroke recovery of rats. METHODS: In this study, Sprague Dawley (SD) rats assigned at random into control, sham and MCAO (middle cerebral artery occlusion) group were treated accordingly to build MCAO models. The neurological severity scores (NSS) test was applied to assess rats' behavior. Triphenyltetrazolium chloride (TTC) staining reflected infarct areas while Nissl staining revealed the number of neurons. Levels of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6 and tumor necrosis factor [TNF]-α) were judged by enzyme-linked immunosorbent assay (ELISA) in brain and serum tissues. We applied western blot to check the expression of Egr2, Egr4 and JNK/c-JUN (c-Jun N-terminal kinase) pathway. Further grouping of rats were based on various transfection, requiring control, sham, MCAO, MCAO + Egr2 cDNA (complementary DNA), MCAO + Egr4 cDNA, MCAO + Egr2 cDNA + Egr4 cDNA group to observe difference in MCAO recovery and JNK/c-JUN-pathway-related protein expression. RESULTS: Under successful modeling of MCAO, western blot results suggested down-regulation of Egr2 and Egr4 and overexpression of pro-inflammatory cytokines. The JNK/c-JUN pathway was activated. On upregulation of Egr2 and Egr4 in infarct areas, neurological function of SD rats recovered along with repressed JNK/c-JUN pathway activation and increased neuron number. CONCLUSION: Upregulation of Egr2 and Egr4 could demote the activation of JNK/c-JUN pathway and the expression of pro-inflammatory cytokines in MCAO rats, so that Egr2 and Egr4 might be potential targets for ischemic stroke in future.

Investigation of Binding Behavior between Drug Molecule 5-Fluoracil and M4 L4 -Type Tetrahedral Cages: Selectivity, Capture, and Release.

Two analogous M4 L4 -type tetrahedral cages (smaller: MOC-19; larger: MOC-22) were synthesized and investigated for their interactions with the anticancer drug 5-fluoracil (5-FU) by NMR spectroscopy, high-resolution electrospray-ionization mass spectrometry (HR-ESI-MS), and molecular simulation. The cage's size and window are of importance for the host-guest binding, and consequently the smaller MOC-19 with a more suitable size of cavity window was found to have much stronger hydrogen-bond interactions with 5-FU. The porous nanoparticles of MOC-19 exhibited outstanding behavior for the controlled release of 5-FU in a simulated human body with liquid phosphate-buffered saline solution.

Prognostic value of peripheral blood lymphocyte-to-monocyte ratio in patients with solid tumors: a meta-analysis.

BACKGROUND: Although accumulating evidence suggests peripheral blood lymphocyte-to-monocyte ratio (LMR) could act as a prognosis predictor in various tumors, the prognostic value of LMR still remains controversial. We carried out this meta-analysis to evaluate the association of pretreatment LMR with survival outcomes in patients with solid tumors. METHODS: Eligible studies were collected and extracted by searching PubMed and Embase databases up to June 3, 2015. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed to assess the prognostic value of LMR quantitatively. RESULTS: Eighteen studies with a total of 8,377 participants were enrolled in this meta-analysis. Our findings indicated that elevated pre-treatment LMR predicted a significantly favorable overall survival (HR=0.59, 95% CI: 0.53-0.67) and disease-free survival (HR=0.74, 95% CI: 0.68-0.80) in solid tumor patients. Subgroup analyses revealed that enhanced LMR was significantly associated with favorable overall survival in patients with digestive system cancers (HR=0.63, 95% CI: 0.49-0.81), urinary tract tumors (HR=0.66, 95% CI: 0.52-0.84), lung cancer (HR=0.62, 95% CI: 0.54-0.72), and nasopharyngeal carcinoma (HR=0.50, 95% CI: 0.43-0.57). CONCLUSION: This meta-analysis showed that enhanced LMR may indicate a favorable prognosis in patients with solid tumors.

Internal Stress Monitoring of In-Service Structural Steel Members with Ultrasonic Method.

Internal stress in structural steel members is an important parameter for steel structures in their design, construction, and service stages. However, it is hard to measure via traditional approaches. Among the existing non-destructive testing (NDT) methods, the ultrasonic method has received the most research attention. Longitudinal critically refracted (Lcr) waves, which propagate parallel to the surface of the material within an effective depth, have shown great potential as an effective stress measurement approach. This paper presents a systematic non-destructive evaluation method to determine the internal stress in in-service structural steel members using Lcr waves. Based on theory of acoustoelasticity, a stress evaluation formula is derived. Factor of stress to acoustic time difference is used to describe the relationship between stress and measurable acoustic results. A testing facility is developed and used to demonstrate the performance of the proposed method. Two steel members are measured by using the proposed method and the traditional strain gauge method for verification. Parametric studies are performed on three steel members and the aluminum plate to investigate the factors that influence the testing results. The results show that the proposed method is effective and accurate for determining stress in in-service structural steel members.

Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the ß subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

MicroRNA-195 downregulates Alzheimer's disease amyloid-ß production by targeting BACE1.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by amyloid-beta (Aß) deposition and neurofibrillary tangles. Numerous microRNAs have been found to play crucial roles in regulating Aß production in the process of AD. Previous investigations have reported lower levels of many microRNAs in AD patients and animal models. Here, we examined the role of miR-195 in the process of Aß formation. Bioinformatics' algorithms predicted miR-195 binding sites within the beta-site APP cleaving enzyme 1 (BACE1) 3'-untranslated region (3'-UTR), and we found the level of miR-195 to be negatively related to the protein level of BACE1 in SAMP8 mice. We confirmed the target site in HEK293 cells by luciferase assay. Overexpression of miR-195 in N2a/WT cells decreased the BACE1 protein level, and inhibition of miR-195 resulted in increase of BACE1 protein level. Furthermore, overexpression of miR-195 in N2a/APP decreased the level of Aß, while inhibition of miR-195 resulted in an increase of Aß. Thus, we demonstrated that miR-195 could downregulate the level of Aß by inhibiting the translation of BACE1. We conclude that miR-195 might provide a therapeutic strategy for AD.