Early detection of Dementia in Type 2 Diabetes population: Predictive analytics using Machine learning approach.

BACKGROUND: The possible association between diabetes mellitus and dementia has raised concerns, given the observed coincidental occurrences. OBJECTIVE: This study aims to develop a personalized predictive model, utilizing artificial intelligence, to assess the 5-year and 10-year dementia risk among patients with Type 2 Diabetes Mellitus (T2DM) who are prescribed antidiabetic medications. METHODS: This retrospective multicenter study used data from Taipei Medical University Clinical Research Database, which comprises electronic medical records from three hospitals in Taiwan. This study applied eight machine learning algorithms to develop prediction models, including logistic regression (LR), linear discriminant analysis (LDA), gradient boosting machine (GBM), lightGBM (LBGM), AdaBoost, random forest, extreme gradient boosting (XGBoost), and artificial neural network (ANN). These models incorporated a range of variables, encompassing patient characteristics, comorbidities, medication usage, laboratory results, and examination data. RESULTS: This study involved a cohort of 43,068 patients diagnosed with T2DM, which accounted for a total of 1,937,692 visits. For model development and validation, 1,300,829 visits were utilized, while an additional 636,863 visits were reserved for external testing. The area under the curve (AUC) of the prediction models range from 0.67 for the logistic regression to 0.98 for the artificial neural networks. Based on the external test results, the model built using the ANN algorithm has the best AUC: 0.97 (5-year follow-up period) and 0.98 (10-year follow-up period). Based on the best model (ANN), age, gender, triglyceride, HbA1c, anti-diabetic agents, stroke history, and other long-term medications were the most important predictors. CONCLUSIONS: We have successfully developed a novel computer-aided dementia risk prediction model that can facilitate the clinical diagnosis and management of patients prescribed with antidiabetic medications. However, further investigation is required to assess the model's feasibility and external validity.

Dietary nitrate, nitrite, and nitrosamine in association with diabetes: a systematic review and meta-analysis.

CONTEXT: Diabetes is a global health concern, and diet is a contributing factor to diabetes. Findings regarding the connection between nitrate, nitrite, and nitrosamine and diabetes risk are inconsistent. OBJECTIVE: The aim was to examine the effects of these dietary compounds on diabetes risk. DATA SOURCES: The data were sourced from PubMed, EMBASE, Scopus, and Web of Science until February 28, 2023. Studies that reported individual-level consumption of these compounds were included. Review articles or ecological studies were excluded. DATA EXTRACTION: The number of events and total observations were recorded. DATA ANALYSIS: The pooled odds ratio (OR) was calculated and displayed in a forest plot. Subgroup and sensitivity analyses were predefined. A dose-response meta-analysis was conducted to determine the exposure intervals that may increase the risk of disease. Six observational reports that met the inclusion criteria were included, involving 108 615 individuals. Participants in the highest quantile of nitrite intake had a greater risk of diabetes compared with those in the lowest quantile (OR, 1.61; 95% confidence interval [CI], 1.08-2.39; I2 = 74%, P = 0.02). Higher nitrosamine consumption tended to increase diabetes risk (OR, 1.52; 95% CI, 0.76-3.04; I2 = 76%; P = 0.24). The relationship was stronger for type 1 (OR, 1.79; 95% CI, 1.20-2.67; I2 = 58%; P < 0.01) than for type 2 diabetes (OR, 1.42; 95% CI, 0.86-2.37; I2 = 71%; P = 0.17). Additionally, nitrite consumption had a dose-dependent association with both phenotypes. No association was found between diabetes risk and high nitrate intake (OR, 1.01; 95% CI, 0.87-1.18; I2 = 28%; P = 0.87). CONCLUSION: Attention should be paid to the consumption of nitrite-containing foods. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023394462 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394462).

Pre-operative Factors Predicting Mortality in Six Months and Functional Recovery in Elderly Patients with Hip Fractures.

Introduction: This study aimed to determine on-admission and perioperative factors predicting six-month mortality and functional recovery in Vietnamese patients with hip fracture. Materials and methods: Between April 2020 and July 2021, 118 patients participated in this prospective study. Patients' data were collected from medical records. Harris hip score (HHS) was used to evaluate the functional recovery six months after fractures. The obtained data were analysed using a univariate and multivariate model. Results: The mean age of the participants was 79.5±9.4 years and 68.6% of the patients were female. The six-month mortality rate was 5.9% and independently associated with age (odds ratio (OR): 3.512, 95% confidence interval (CI) 1.538 - 8.019; P<0.001, patients aged >80 years vs those aged ≤80 years) and hypoproteinemia (OR: 2.859, 95% CI: 1.001 - 8.166, P=0.049). Among 111 survivors there were 66 (59.5%) of patients with a good functional recovery. Patients aged >80 years had a higher risk of poor functional outcome (OR: 3.167, 95% CI: 1.386 - 7.235, P: 0.006) compared to those aged ≤ 80 years. No significant correlations between other clinical (gender, body mass index, comorbidities, type of fractures or surgery, time until surgery) or laboratory parameters (anaemia, hyperglycemia, marked elevation of C reactive protein level, electrolyte abnormalities, elevated urea) and mortality or functional outcome were found. Conclusion: Advanced age is the most important factor affecting both mortality and functional outcome while hypoproteinemia is associated with a higher risk of mortality in elderly patients with hip fractures.

Space farming: Horticulture systems on spacecraft and outlook to planetary space exploration.

Successful human space exploration requires more products than can be taken as payload. There is a need, therefore, for in-space circular manufacturing. Requirements for this include limited resource inflow, from either Earth or other planets and the generation of minimal waste. The provision of nutritious food is a clear need for human survival on the Moon or Mars and is one of the most complex to solve. Demand in large quantities, constant and reliable provision of food requires the development of specialist agricultural technologies. Here, we first review the history of space farming over the past five decades. This survey assesses the technologies which have been tested under the harsh conditions of space, identifying which modern horticultural components are applicable for in-space plant growth. We then outline which plants have been grown and under what conditions, and speculate upon the types of plants that could be selected to best nourish astronauts. Current systems are focussed on experimentation and exploration, but do not yet provide turn-key solutions for efficient food production within a long-term space exploration scenario. With that take, this review aims to provide a perspective on how an engineered closed circular environmental life-support system (ECCLES) might be constructed. To exemplify the latter, nutrient auto accumulation by biofortification is proposed through the integration of space farming and space mining, which is uncharted on Earth.

Electrocatalytic CO2 Reduction by [Re(CO)3Cl(3-(pyridin-2-yl)-5-phenyl-1,2,4-triazole)] and [Re(CO)3Cl(3-(2-pyridyl)-1,2,4-triazole)].

The exploration of novel electrocatalysts for CO2 reduction is necessary to overcome global warming and the depletion of fossil fuels. In the current study, the electrocatalytic CO2 reduction of [Re(CO)3Cl(N-N)], where N-N represents 3-(2-pyridyl)-1,2,4-triazole (Hpy), 3-(pyridin-2-yl)-5-phenyl-l,2,4-triazole (Hph), and 2,2'-bipyridine-4,4' dicarboxylic acidic (bpy-COOH) ligands, was investigated. In CO2-saturated electrolytes, cyclic voltammograms showed an enhancement of the current at the second reduction wave for all complexes. In the presence of triethanolamine (TEOA), the currents of Re(Hpy), Re(Hph), and Re(bpy-COOH) enhanced significantly by approximately 4-, 2-, and 5-fold at peak potentials of -1.60, -150, and -1.69 VAg/Ag+, respectively (in comparison to without TEOA). The reduction potential of Re(Hph) was less negative than those of Re(Hpy) and Re(COOH), which was suggested to cause its least efficiency for CO2 reduction. Chronoamperometry measurements showed the stability of the cathodic current at the second reduction wave for at least 300 s, and Re(COOH) was the most stable in the CO2-catalyzed reduction. The appearance and disappearance of the absorption band in the UV/vis spectra indicated the reaction of the catalyst with molecular CO2 and its conversion to new species, which were proposed to be Re-DMF + and Re-TEOA and were supposed to react with CO2 molecules. The CO2 molecules were claimed to be captured and inserted into the oxygen bond of Re-TEOA, resulting in the enhancement of the CO2 reduction efficiency. The results indicate a new way of using these complexes in electrocatalytic CO2 reduction.

Enhancing the remarkable adsorption of Pb2+ in a series of sulfonic-functionalized Zr-based MOFs: a combined theoretical and experimental study for elucidating the adsorption mechanism.

A series of Zr-based metal-organic frameworks was prepared via the solvothermal route using sulfonic-rich linkers for the efficient capture of Pb2+ ions from aqueous medium. The factors affecting adsorption such as the solution pH, adsorbent dosage, contact time, adsorption isotherms, and mechanism were studied. Consequently, the maximum adsorption capacity of Pb2+ on the acidified VNU-23 was determined to be 617.3 mg g-1, which is much higher than that of previously reported adsorbents and MOF materials. Furthermore, the adsorption isotherms and kinetics of the Pb2+ ion are in good accordance with the Langmuir and pseudo-second-order kinetic model, suggesting that the uptake of Pb2+ is a chemisorption process. The reusability experiments demonstrated the facile recovery of the H+⊂VNU-23 material through immersion in an HNO3 solution (pH = 3), where its Pb2+ adsorption efficiency still remained at about 90% of the initial uptake over seven cycles. Remarkably, the adsorption mechanism was elucidated through a combined theoretical and experimental investigation. Accordingly, the Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy connected to energy-dispersive X-ray mapping (SEM-EDX-mapping), and X-ray photoelectron spectroscopy (XPS) analysis of the Pb⊂VNU-23 sample and comparison with H+⊂VNU-23 confirmed that the electrostatic interaction occurs via the interaction between the SO3- moieties in the framework and the Pb2+ ion, leading to the formation of a Pb-O bond. In addition, the density functional theory (DFT) calculations showed the effective affinity of the MOF adsorbent toward the Pb2+ ion via the strong driving force mentioned in the experimental studies. Thus, these findings illustrate that H+⊂VNU-23 can be employed as a potential adsorbent to eliminate Pb2+ ions from wastewater.

Techno-environmental assessment of small-scale Haber-Bosch and plasma-assisted ammonia supply chains.

Haber-Bosch (HB) process, the main method for ammonia (NH3) production, contributes to near 2% of the global carbon emissions because the hydrogen input is obtained from fossil sources. NH3 production is concentrated in a few countries, adding emissions due to global distribution. Distributed plants next to farmers and fed by renewable energy can reduce these impacts, as well as NH3 storage, shortage risks, and price volatility. Distributed plants cannot reach low NH3 production costs as centralised plants, but they can be promoted by the environmental benefits of its products lifecycles. Therefore, life cycle assessments of NH3 production pathways and specific modelling for NH3 transport in Australia were performed, from cradle-to-site, to identify the influence of storage, transport, and energy sources in their environmental profiles. The carbon footprint of centralised production was up to 2.96 kg.CO2-eq/kg.NH3, from which 29.3% corresponded to transport. Local production demonstrated substantial avoided transport impacts and that CO2-eq can reach reductions over 100% when including co-product credits such as oxygen and carbon black. Local plants using electrolysers to supply mini-HB loops obtained rates of 0.12, -0.52, and -1.57 kg.CO2-eq/kg.NH3 using electricity from solar, wind, and biogas (other than manure) sources, respectively. The alternative using high temperature plasma reactor instead of electrolyser obtained its best rate of -0.65 kg.CO2-eq/kg using biogas different from manure. At farm electrolyser-based plants using novel non-thermal plasma reactors, considering potential energy yields and simplified NH3 separation technology, could reach a rate of -1.07 kg.CO2-eq/kg.NH3, using solar energy. Among the assessed pathways, the most notable impact was on freshwater eutrophication in the electrolyser-based plants generating reductions up to 290%, due to oxygen credits. Despite these results, the use of solar energy raises concerns on land use and terrestrial ecotoxicity due to the area needed for solar farms and the manufacture of their components.

Ligand-based discovery of new potential acetylcholinesterase inhibitors for Alzheimer's disease treatment.

The enzyme acetylcholinesterase (AChE) is currently a therapeutic target for the treatment of neurodegenerative diseases. These diseases have highly variable causes but irreversible evolutions. Although the treatments are palliative, they help relieve symptoms and allow a better quality of life, so the search for new therapeutic alternatives is the focus of many scientists worldwide. In this study, a QSAR-SVM classification model was developed by using the MATLAB numerical computation system and the molecular descriptors implemented in the Dragon software. The obtained parameters are adequate with accuracy of 88.63% for training set, 81.13% for cross-validation experiment and 81.15% for prediction set. In addition, its application domain was determined to guarantee the reliability of the predictions. Finally, the model was used to predict AChE inhibition by a group of quinazolinones and benzothiadiazine 1,1-dioxides obtained by chemical synthesis, resulting in 14 drug candidates with in silico activity comparable to acetylcholine.

Echocardiographic Reference Ranges of Non-invasive Myocardial Work Indices in Children.

Global myocardial work (GMW) is an emerging method to characterize left ventricle (LV) function with potential advantages over both ejection fraction and global longitudinal strain (GLS). We aimed to determine the feasibility and reproducibility for echocardiographic-derived GMW in a healthy pediatric population; establish normal reference values; and investigate the influence of age, gender, and other clinical factor on normal reference ranges. We prospectively enrolled 212 individuals (median age of 9 years; interquartile range, 6 to 12 years, 112 female). Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured from LV pressure-strain loops. Quantification of GMW was performed using a GE Vivid E95 system and available software package (Echopac V.203, GE). The mean LV EF was 64 ± 3% with GLS of -21.3 ± 1.5%. GWI was 1688 ± 219 mmHg% with mean GWE of 96.5 ± 1.4%. The GCW was 1959 ± 207 mmHg%, and the mean GWW of 61.1 ± 30.9 mmHg%. No significant difference was found in MW indices across age group and gender (p > 0.05 for all). There were significant correlations between both GWI and GCW with GLS and systolic blood pressure (p < 0.001), but not with GWE and GWW. Linear regression model revealed that GWI and GCW were more closely correlated with systolic blood pressure than GLS. LV MW indices had good intra-observer and inter-observer reproducibility. This study establishes both the feasibility and reference ranges for non-invasive echocardiographic indices of GMW in healthy children. Myocardial work appears to be a complementary modality to assess LV performance in children.

Large renal arteriovenous fistula treated by embolization: a case report.

Renal arteriovenous fistula (RAVF) is an uncommon vascular malformation of the kidney, which can be congenital, acquired or idiopathic. Although most patients are asymptomatic, RAVF can lead to hypertension, heart failure, renal insufficiency, hematuria, and progressive increase in size of renal vessels. Diagnosis is aided by radiological studies, with digital subtraction angiography as a gold standard. Besides, ultrasound with color Doppler and computed tomography angiography are noninvasive imaging techniques and can be useful for planning the treatment. A large fistula are generally treated by nephrectomy. Intervention can ameliorate the hemodynamic effects of high flow and to preserve the renal parenchymal function. Although endovascular therapy may be challenging due to the large size and high flow of fistula, this report describes a case of huge RAVF was successfully treated by embolization instead of surgery.

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

PURPOSE: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress. METHODS: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1ß. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate. RESULTS: IL-1ß stimulation activated NFκB demonstrating that IL-1ß was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1ß increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1ß stimulation. hTIMP1 expression was comparable between IL-1ß stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1ß. CONCLUSION: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.

Correction: Sensitive MnFe2O4-Ag hybrid nanoparticles with photothermal and magnetothermal properties for hyperthermia applications.

[This corrects the article DOI: 10.1039/D1RA03216J.].

Sensitive MnFe2O4-Ag hybrid nanoparticles with photothermal and magnetothermal properties for hyperthermia applications.

In this study, we present an experiment showing that designing multifunctional MnFe2O4-Ag nanoparticles to act as a dual hyperthermia agent is an efficient route for enhancing their heating ability. Interestingly, the specific absorption rate of the heteromeric MnFe2O4-Ag nanoparticles increased 2.7 times under simultaneous irradiation of a 100 Oe magnetic field and 0.14 W cm-2 laser compared to the action by the magnetic field alone, and more interestingly, is 30% higher than the sum of the two individual actions. The synergistic benefit of the magneto- and photo-thermal properties of the heteromeric structure can reduce the strengths of the magnetic field and laser intensities as well as their irradiation time to levels lower than those required in their hyperthermia applications individually. In vitro cytotoxicity analysis performed on HepG2 liver cancer and Hela cervical cancer cell lines showed that IC50 values were 83 ± 5.6 µg mL-1 (for HepG2) and 122.6 ± 19.8 µg mL-1 (for Hela cells) after 48 h of incubation, therefore, the nanoparticles are moderately cytotoxic and nontoxic to HepG2 and Hela cells, respectively; which offers the potential of safe therapy.

Attenuation of ataxia telangiectasia mutated signalling mitigates age-associated intervertebral disc degeneration.

Previously, we reported that persistent DNA damage accelerates ageing of the spine, but the mechanisms behind this process are not well understood. Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the human intervertebral disc, we exposed human nucleus pulposus (hNP) cells directly to the DNA damaging agent cisplatin. Cisplatin-treated hNP cells exhibited rapid phosphorylation of ATM and subsequent increased NF-κB activation, aggrecanolysis, decreased total proteoglycan production and increased expression of markers of senescence, including p21, γH2 AX and SA-ß-gal. Treating cisplatin-exposed hNP cells with an ATM-specific inhibitor negated these effects. In addition, genetic reduction of ATM reduced disc cellular senescence and matrix proteoglycan loss in the progeroid Ercc1-/∆ mouse model of accelerated ageing. These findings suggest that activation of ATM signalling under persistent genotoxic stress promotes disc cellular senescence and matrix homeostatic perturbation. Thus, the ATM signalling pathway represents a therapeutic target to delay the progression of age-associated spine pathologies.

Mandibular Movement Analysis to Assess Efficacy of Oral Appliance Therapy in OSA.

RATIONALE: The respiratory effort index derived from vertical mandibular movements (MM-REI) is a potential marker of increased respiratory effort during sleep. We evaluated the effectiveness of mandibular advancement splint therapy using MM-REI, in comparison with the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). METHODS: Fifty-six subjects (median age, 47 years) with OSA treated with a custom mandibular advancement splint (Herbst appliance) were evaluated at the end of the titration procedure when snoring was reported absent by the sleep partner. We employed a magnetometer to capture mandibular movements (Brizzy; Nomics). Mandibular advancement splint efficacy was assessed as the percent change from baseline, using Bayesian multilevel models. RESULTS: At the end of titration, all indices of OSA severity decreased compared with baseline: AHI (-48.9% to -71.1%), ODI (-49.5% to -77.2%), with obstructive hypopnea index and MM-REI showing the largest responses (-70.6% to -88.5% and -69.5% to -96.3%, respectively). MM-REI normalization via reductions in both mandibular movement event rate and duration accurately reflected efficacy of the appliance. CONCLUSIONS: The reduction of vertical respiratory mandibular movements estimated by MM-REI and sleep respiratory effort duration accompanied the decrease in obstructive hypopneas, AHI, and ODI when snoring resolved in subjects with OSA treated with an optimally titrated mandibular advancement splint.

Nanoporous anodic aluminum oxide internalized with gold nanoparticles for on-chip PCR and direct detection by surface-enhanced Raman scattering.

Nanoporous anodic aluminum oxide internalized with gold nanoparticles was utilized as an integrated platform miniaturized for consecutively performing on-chip PCR and downstream detection of the amplified product of a 183 bp eaeA gene fragment from Escherichia coli O157:H7 using surface-enhanced Raman scattering (SERS).

Online Reviews as Health Data: Examining the Association Between Availability of Health Care Services and Patient Star Ratings Exemplified by the Yelp Academic Dataset.

BACKGROUND: There have been public health interventions that aim to reduce barriers to health care access by extending opening hours of health care facilities. However, the impact of opening hours from the patient's perspective is not well understood. OBJECTIVE: This study aims to investigate the relationship between temporal accessibility of health care services and how patients rate the providers on Yelp, an online review website that is popular in the United States. Using crowdsourced open Internet data, such as Yelp, can help circumvent the traditional survey method. METHODS: From Yelp's limited academic dataset, this study examined the pattern of visits to health care providers and performed a secondary analysis to examine the association between patient rating (measured by Yelp's rating) and temporal accessibility of health care services (measured by opening hours) using ordinal logistic regression models. Other covariates included were whether an appointment was required, the type of health care service, the region of the health care service provider, the number of reviews the health care service provider received in the past, the number of nearby competitors, the mean rating of competitors, and the standard deviation of competitors' ratings. RESULTS: From the 2085 health care service providers identified, opening hours during certain periods, the type of health care service, and the variability of competitors' ratings showed an association with patient rating. Most of the visits to health care service providers took place between normal working hours (9 AM-5 PM) from Sunday to Thursday, and the least on Saturday. A model fitted to the entire sample showed that increasing hours during normal working hours on Monday (OR 0.926, 95% CI 0.880-0.973, P=0.03), Saturday (OR 0.897, 95% CI 0.860-0.935, P<0.001), Sunday (OR 0.904, 95% CI 0.841-0.970, P=0.005), and outside normal working hours on Friday (OR 0.872, 95% CI 0.760-0.998, P=0.048) was associated with receiving lower ratings. But increasing hours during outside normal working hours on Sunday was associated with receiving higher ratings (OR 1.400, 95% CI 1.036-1.924, P=0.03). There were also observed differences in patient ratings among the health care services types, but not geographically or by appointment requirement. CONCLUSIONS: This study shows that public health interventions, especially those involving opening hours, could use crowdsourced open Internet data to enhance the evidence base for decision making and evaluation in the future. This study illustrates one example of how Yelp data could be used to understand patient experiences with health care services, making a case for future research for exploring online reviews as a health dataset.

Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.