Publications by authors named "Shan Liu"

693 Publications

Nanoparticle Delivery of CD147 Antagonistic Peptide-9 Protects against Acute Ischemic Brain Injury and tPA-Induced Intracerebral Hemorrhage in Mice.

ACS Appl Bio Mater 2020 Apr 3;3(4):1976-1985. Epub 2020 Mar 3.

Department of Neurosurgery, The Pennsylvania State, University College of Medicine, Hershey, Pennsylvania 17033, United States.

CD147 has emerged as a potential therapeutic target in many human diseases. We have demonstrated that inhibition of CD147 using its function-blocking antibody ameliorates acute ischemic brain injury and promotes long-term functional recovery in mice. Recently, peptide-nanoparticle conjugates have emerged as powerful tools for biomedical applications. The present study aimed to investigate the therapeutic potential of CD147 antagonist peptide-9 (AP9) in acute ischemic stroke in mice using nanomaterial as the drug delivery vehicles. AP9-conjugated nanoparticles (APN), with an average size of about 40 nm, were fabricated by maleimide linkage and characterized using dynamic light scattering and transmission electron microscopy. We found that APN specifically bound to CD147 in cultured mouse brain endothelial cells (bEnd.3) and to ischemia-induced CD147 in mouse cerebral microvessels. Using a mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated, for the first time, that systemic delivery of APN (2.5 mg/kg, I.V.) initiated at 1 h after tMCAO significantly reduced brain infarct size, improved functional outcome, and attenuated delayed (5 h after tMCAO) tPA-induced intracerebral hemorrhage in acute ischemic stroke. These protective effects were associated with profound inhibition of MMP-9 and MMP-3 in both ischemic brain and plasma. In conclusion, the CD147 antagonist peptide-9 represents a potentially promising therapeutic candidate for the treatment of ischemic stroke.
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http://dx.doi.org/10.1021/acsabm.9b01141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195622PMC
April 2020

The interpretation of human body in traditional Chinese medicine and its influence on the characteristics of TCM theory.

Anat Rec (Hoboken) 2021 Jun 11. Epub 2021 Jun 11.

Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, Shaoguan, China.

Traditional Chinese medicine (TCM) has a long history of serving the Chinese people's health since its birth, including playing an important role in treating and preventing COVID-19 in 2020. The fact that TCM has been used in China for thousands of years shows the value and reason why it must exist. Although TCM has been or is being questioned, there is no doubt about its importance in terms of efficacy. This article focuses on how TCM understands the human body in comparison with anatomy knowledge in western medicine and discusses the development and advances of TCM in terms of the body view and the theory innovation. The purpose is to let foreign scholars get better understanding of TCM from this perspective.
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http://dx.doi.org/10.1002/ar.24643DOI Listing
June 2021

Association of minimal residual disease levels with clinical outcomes in patients with mantle cell lymphoma: A meta-analysis.

Leuk Res 2021 May 3;108:106605. Epub 2021 May 3.

Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 West Second Section First Ring Road, Chengdu, 610072, Sichuan, China. Electronic address:

Some studies have elucidated that Minimal residual disease (MRD) in patient with Mantle Cell Lymphoma (MCL) was a significant prognostic factor, with potential value in assessing overall survival (OS) and progression-free survival (PFS). However, most studies were widely varied in included population, sample sources and MRD detection time points. Some studies even have conflicting results. In view of this, a meta-analysis was performed to evaluate association of MRD levels with clinical outcomes in patients with MCL. We identified 7 included articles, which were published in recent 20 years. Then, we extracted or calculated hazard ratios (HRs) and their 95 % confidence intervals (CIs). Our results reveal that patients with MRD negativity have improved OS (HR = 0.63; 95 % CI: 0.50-0.79) and PFS (HR = 0.40, 95 % CI: 0.21-0.76), comparing with patients with MRD positivity. There are also consistent results in subgroups based on sample sources and MRD detection time points. Our study also demonstrates that MRD level is a strong prognostic factor of clinical outcomes. Thus, MRD is expected to be an effective clinical indicator for assessing prognosis and guide treatment decisions in MCL patients.
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http://dx.doi.org/10.1016/j.leukres.2021.106605DOI Listing
May 2021

An Update Review on Listeria Infection in Pregnancy.

Infect Drug Resist 2021 26;14:1967-1978. Epub 2021 May 26.

Department of Obstetrics, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.

Listeria monocytogenes (LM) is an intracellular, aerobic and facultative anaerobic, Gram-positive bacterium, which is primarily transmitted to humans orally via food. LM could occur in asymptomatic pregnant women; however, fetal infection is a serious condition, entailing premature birth, abortion, sepsis, central nervous system (CNS) involvement, or even death. If a pregnant woman exhibits symptoms, the performance is almost like influenza, such as fever, headache, diarrhea, myalgia, or other digestive-related symptoms. This review collected clinical and empirical results regarding the mechanism, clinical manifestations, obstetrical outcome, diagnosis, treatment, vertical transmission, neonatal infection, and prevention of listeriosi according to articles published in PubMed from January 1, 1980, to March 20, 2021. The early detection and diagnosis of pregnancy-associated listeriosis are significant since sensitive antibiotics are effective at enhancing the prognosis of newborns. Listeriosis can be diagnosed using positive cultures from maternal or neonatal blood, neonatal cerebrospinal fluid (CSF), amniotic fluid, intrauterine mucosa, or the placenta. Two weeks of high-dose intravenous amoxicillin (more than 6 g/day) is recommended for LM pregnant women without allergy. Terminating the pregnancy to save the mother's life should be considered if maternal and fetal conditions aggravate. Neonatal Listeria infection is primarily transmitted through the placenta, which is a critical illness associated with a high mortality rate. The necessary dietary guidance for pregnant women can reduce the incidence rate of pregnancy-related listeriosis.
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http://dx.doi.org/10.2147/IDR.S313675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165209PMC
May 2021

Biochemical Characterization of a Novel Bacterial Laccase and Improvement of Its Efficiency by Directed Evolution on Dye Degradation.

Front Microbiol 2021 12;12:633004. Epub 2021 May 12.

Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, College of Life Science and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, China.

Laccase is a copper-containing polyphenol oxidase with a wide range of substrates, possessing a good application prospect in wastewater treatment and dye degradation. The purpose of this research is to study the degradation of various industrial dyes by recombinant laccase rlac1338 and the mutant enzyme lac2-9 with the highest enzyme activity after modification by error-prone PCR. Four enzyme activities improved mutant enzymes were obtained through preliminary screening and rescreening, of which lac2-9 has the highest enzyme activity. There are four mutation sites, including V281A, V281A, P309L, S318G, and D232V. The results showed that the expression of the optimized mutant enzyme also increased by 22 ± 2% compared to the unoptimized enzyme and the optimal reaction temperature of the mutant enzyme lac2-9 was 5°C higher than that of the rlac1338, and the optimal pH increased by 0.5 units. The thermal stability and pH stability of mutant enzyme lac2-9 were also improved. With ABTS as the substrate, the k/K of rlac1338 and mutant strain lac2-9 are the largest than other substrates, 0.1638 and 0.618 sM, respectively, indicating that ABTS is the most suitable substrate for the recombinant enzyme and mutant enzyme. In addition, the K of the mutant strain lac2-9 (76 μM) was significantly lower, but the k/K (0.618 sM) was significantly higher, and the specific enzyme activity (79.8 U/mg) increased by 3.5 times compared with the recombinant laccase (22.8 U/mg). The dye degradation results showed that the use of rlac1338 and lac2-9 alone had no degradation effect on the industrial dyes [indigo, amaranth, bromophenol blue, acid violet 7, Congo red, coomassie brilliant blue (G250)], however, adding small molecular mediators Ca and ABTS at the same time can significantly improve the degradation ability. Compared to the rlac1338, the degradation rates with the simultaneous addition of Ca and ABTS of mutant enzyme lac2-9 for acid violet 7, bromophenol blue and coomassie brilliant blue significantly improved by 8.3; 3.4 and 3.4 times. Therefore, the results indicated that the error-prone PCR was a feasible method to improve the degradation activity of laccase for environmental pollutants, which provided a basis for the application of laccase on dye degradation and other environmental pollutants.
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http://dx.doi.org/10.3389/fmicb.2021.633004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149590PMC
May 2021

Circulating angiopoietin-like proteins in metabolic-associated fatty liver disease: a systematic review and meta-analysis.

Lipids Health Dis 2021 May 25;20(1):55. Epub 2021 May 25.

Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Hangzhou, 310006, Zhejiang Province, China.

Background: Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) (newly named metabolic-associated fatty liver disease (MAFLD)) is based on metabolic dysfunction. There may be some correlation between ANGPTLs and MAFLD, but the specific correlation is unclear. This study aims to explore the predictive role of ANGPTLs in MAFLD and its progression.

Methods: Seven databases (PubMed, EMBASE, Cochrane Library, CNKI, WANFANG, CBM and Clinicaltrials.gov ) were searched with free terms and MeSH terms. The random-effects model was used to pool the data, and Standardized Mean Difference (SMD) and 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the article selection. RevMan 5.3, Stata 16 and MetaXL software were applied to analyse the data and the GRADE system was utilized to assess the certainty of evidence.

Results: After reviewing 823 related articles, 13 studies (854 cases and 610 controls) met the inclusion criteria, and contributed to this meta-analysis. The results showed that circulating ANGPTL8 level was significantly elevated in the MAFLD group than in the healthy control group (SMD = 0.97 pg/mL, 95%CI: 0.77, 1.18). Conversely, there was no significant difference in the ANGPTL4 (SMD = 0.11 ng/mL, 95%CI: - 0.32, 0.54) and ANGPTL3 (SMD = - 0.95 ng/mL, 95%CI: - 4.38, 2.48) between the two groups. Subgroup analysis showed that: 1) the MAFLD group had significantly higher ANGPTL8 levels than the healthy control group in Asian and other races; 2) the ANGPTL8 levels in Body Mass Index (BMI) > 25 kg/m patients with MAFLD were higher than those in the healthy control group; 3) the higher ANGPTL8 levels were observed in moderate to severe MAFLD group than the healthy control group. Meta-regression demonstrated that BMI might effectively explain the high heterogeneity. No significant publication bias existed (P > 0.05). The certainty of evidence was assessed as very low by the GRADE system.

Conclusions: The ANGPTLs may be related to MAFLD. The increased ANGPTL8 level may be positively correlated with different situations of MAFLD, which may act as a potential indicator to monitor the development trends.
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http://dx.doi.org/10.1186/s12944-021-01481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152125PMC
May 2021

[Screening and Sequencing High-risk Antibiotics in China's Water Environment Based on Ecological Risks].

Huan Jing Ke Xue 2021 Jun;42(6):2748-2757

College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China.

In view of the lack of ecotoxicological data for most antibiotics in China's water environment, national-scale ecological risk assessment of antibiotics remains impossible. This study determined the exposure index values for antibiotic products in the National Medical Products Administration based on quantity and average daily dose data for all antibiotics in the market alongside exposure modeling. The risk scores were calculated using data on the ecotoxicological effects of the antibiotics, and the species sensitivity distributions (SSD) method and apical effects. Priorities for control were identified based on the findings. Approximately 105 antibiotics were screened, and 53 were identified as candidate drugs with high national usage. Twenty antibiotics were identified for priority risk evaluation using a joint probabilistic model, with clarithromycin, ciprofloxacin, amoxicillin, cefaclor, and oxyfloxacin highlighted as presenting a high ecological risk. This study provides a scientific basis for the quantitative assessment of antibiotic risk prevention and control in China's aquatic environment.
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http://dx.doi.org/10.13227/j.hjkx.202009275DOI Listing
June 2021

Common Strategy: Mounting the Rod-like Ni-Based MOF on Hydrangea-Shaped Nickel Hydroxide for Superior Electrocatalytic Methanol Oxidation Reaction.

ACS Appl Mater Interfaces 2021 Jun 24;13(22):26472-26481. Epub 2021 May 24.

College of Material and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang 443002, China.

Developing efficient metal-organic framework (MOF)-based electrocatalysts with improvable activity and persistence toward the methanol oxidation reaction (MOR) is attracting great research attention but still remains an enormous challenge. Herein, a facile strategy, hydrangea-shaped nickel hydroxide template-directed synthesis of the hierarchically structured Ni-MOF on the Ni(OH) heterocomposite (denoted as Ni-Ni) for efficient MOR, is developed. The unique hierarchical structure and synergistic effect of the heterocomposite afford more exposed active sites, a facile ion diffusion path, and improved conductivity, favorable for improving MOR catalytic performance. Remarkably, the optimized Ni-Ni-2 material delivers an excellent activity with a high peak current density (24.6 mA cm). Furthermore, to prove the universality of this strategy, NiCu(OH) isometallic hydroxide was used as the precursor, and a series of MOF-74/CuNi(OH) (denoted as Ni-NiCu) heterogeneous materials have been prepared and could be used as an effective electrocatalyst to catalyze MOR. The results indicate that this strategy can be used in the synthesis of other new composite materials with specific hierarchical structures for a more efficient electrocatalytic system.
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http://dx.doi.org/10.1021/acsami.1c04282DOI Listing
June 2021

APOBEC3B deletion polymorphism and lung cancer risk in the southern Chinese population.

Ann Transl Med 2021 Apr;9(8):656

Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China.

Background: Approximately 80-85% of lung cancer is the non-small cell lung cancer (NSCLC) subtype, which ranks as the leading cause of cancer deaths worldwide. (A3B) was reported to be a key source of mutations in NSCLC. However, the role of the A3B deletion polymorphism in the etiology of NSCLC has not been well-documented.

Methods: A case-control study with 317 NSCLC patients and 334 healthy controls was conducted to explore the association between the A3B deletion polymorphism and the risk of NSCLC. The unconditional logistic regression model was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI), and the confounding factors were adjusted, including age, gender, and smoking status, to estimate the risk. An analysis of gene-environment interactions was performed using multifactor dimensionality reduction (MDR) software.

Results: We found that the del/del genotype of A3B deletion significantly increased NSCLC risk. Compared with individuals carrying the ins/ins genotype of A3B deletion, individuals with the del/del genotype had a 2.36 times increased risk of developing NSCLC after adjusting for confounding factors (OR =2.71, 95% CI: 1.67-4.42, P<0.001). A 3-factor gene-environment (A3B deletion, gender, and smoking) interaction model was found for NSCLC (OR =4.407, 95% CI: 1.174-16.549, P=0.028).

Conclusions: We propose that the A3B deletion polymorphism can increase the risk of developing NSCLC, and their interactions with gender and smoking may contribute to the risk of NSCLC in the southern Chinese population.
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http://dx.doi.org/10.21037/atm-21-989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105993PMC
April 2021

Simultaneous measurement of temperature and relative humidity based on a twisted microfiber coated with nanomaterials.

Appl Opt 2021 May;60(13):3849-3855

We propose a twisted microfiber interferometer sensor coated with boron nitride (BN) nanosheets for simultaneous measurement of relative humidity (RH) and temperature ($ T $). Sensitive material characteristics (BN nanosheets) enhance refractive index (RI) sensing sensitivity of proposed devices. A twisting process on the microfiber surely improves the evanescent field interaction with the deposited layer. The experimental results show that the RH sensitivities are ${-}{121.6}\;{\rm pm}/\% {\rm RH}$ and 0.26 dBm/%RH for humidity range from 46% to 72% and $ T $ sensitivities of 23.5 pm/°C and ${-}{0.045}\;{\rm dBm}/^\circ {\rm C}$ from 50°C to 90°C. The twisted microfiber interferometer has the advantages of compact structure, high sensitivity, and multiparameter measurement, which has certain potential for more applications.
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http://dx.doi.org/10.1364/AO.423341DOI Listing
May 2021

Moving the needle on fall prevention: A Geriatric Emergency Care Applied Research (GEAR) Network scoping review and consensus statement.

Acad Emerg Med 2021 May 11. Epub 2021 May 11.

Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island, USA.

Background: Although falls are common, costly, and often preventable, emergency department (ED)-initiated fall screening and prevention efforts are rare. The Geriatric Emergency Medicine Applied Research Falls core (GEAR-Falls) was created to identify existing research gaps and to prioritize future fall research foci.

Methods: GEAR's 49 transdisciplinary stakeholders included patients, geriatricians, ED physicians, epidemiologists, health services researchers, and nursing scientists. We derived relevant clinical fall ED questions and summarized the applicable research evidence, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. The highest-priority research foci were identified at the GEAR Consensus Conference.

Results: We identified two clinical questions for our review (1) fall prevention interventions (32 studies) and (2) risk stratification and falls care plan (19 studies). For (1) 21 of 32 (66%) of interventions were a falls risk screening assessment and 15 of 21 (71%) of these were combined with an exercise program or physical therapy. For (2) 11 fall screening tools were identified, but none were feasible and sufficiently accurate for ED patients. For both questions, the most frequently reported study outcome was recurrent falls, but various process and patient/clinician-centered outcomes were used. Outcome ascertainment relied on self-reported falls in 18 of 32 (56%) studies for (1) and nine of 19 (47%) studies for (2).

Conclusion: Harmonizing definitions, research methods, and outcomes is needed for direct comparison of studies. The need to identify ED-appropriate fall risk assessment tools and role of emergency medical services (EMS) personnel persists. Multifactorial interventions, especially involving exercise, are more efficacious in reducing recurrent falls, but more studies are needed to compare appropriate bundle combinations. GEAR prioritizes five research priorities: (1) EMS role in improving fall-related outcomes, (2) identifying optimal ED fall assessment tools, (3) clarifying patient-prioritized fall interventions and outcomes, (4) standardizing uniform fall ascertainment and measured outcomes, and (5) exploring ideal intervention components.
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http://dx.doi.org/10.1111/acem.14279DOI Listing
May 2021

Low Serum LH Levels During Ovarian Stimulation With GnRH Antagonist Protocol Decrease the Live Birth Rate After Fresh Embryo Transfers but Have No Impact in Freeze-All Cycles.

Front Endocrinol (Lausanne) 2021 23;12:640047. Epub 2021 Apr 23.

Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Objective: To explore the association between serum LH levels and the cumulative live birth rate (CLBR) within one complete cycle, and the impact of serum LH levels on the live birth rate (LBR) after the initial embryo transfer (ET) considering different ET strategies (fresh or freeze-all).

Design: A retrospective cohort study.

Setting: University-affiliated reproductive center.

Patients: 1480 normogonadotrophic women who underwent COS with GnRH antagonist protocol for the first IVF/ICSI attempt.

Interventions: The sample was stratified into low and higher LH groups according to serum LH peak levels of <4 (Group A) and ≥4 IU/L (Group B) during COS. Patients were also sub-grouped into conventional fresh/frozen ET cycles and freeze-all cycles.

Main Outcome Measures: The LBR after the initial embryo transfer and the CLBR within one complete cycle.

Secondary Outcome Measures: The numbers of day-3 high-quality embryos, the numbers of embryos available, and the other pregnancy outcomes after the initial ET.

Results: In the whole cohort, the CLBRs decreased significantly in the low (63.1% vs. 68.3%, =.034) LH group compared to the higher LH group. Subgroup analysis revealed that patients with low LH levels had lower LBR after fresh ET (38.0% vs. 51.5%, =.005) but comparable LBR after the first frozen-thawed ET (FET) in freeze-all cycles (49.8% vs. 51.8%, =.517) than patients with higher LH peak levels. Likewise, patients with low LH levels had lower CLBR for conventional fresh/frozen ET cycles (54.8% vs. 66.1%, =.015) but comparable CLBR for the freeze-all cycles (66.8% vs. 69.2%, =.414) than those with higher LH levels. Following confounder adjustment, multivariable regression analyses showed that low LH level was an independent risk factor for the CLBR in the whole cohort (odds ratio (OR): 0.756, 95% confidence interval (CI): 0.604-0.965, =.014) and in patients who underwent the conventional ET strategy (OR: 0.596, 95% CI: 0.408-0.917, =.017). Moreover, the adverse impact of low LH levels on LBRs maintained statistically significant after fresh transfers (OR: 0.532, 95% CI: 0.353-0.800, =.002) but not after the first FETs in freeze-all cycles (OR: 0.918, 95% CI: 0.711-1.183,=.508).

Conclusions: In comparison with higher LH levels, low LH levels decrease the CLBRs per oocyte retrieval cycle for normogonadotrophic women who underwent COS using GnRH antagonists. This discrepancy may arise due to the significant detrimental effect of low LH levels on the LBRs after fresh embryo transfers.
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http://dx.doi.org/10.3389/fendo.2021.640047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104121PMC
April 2021

Xiao-Xu-Ming decoction prevented hemorrhagic transformation induced by acute hyperglycemia through inhibiting AGE-RAGE-mediated neuroinflammation.

Pharmacol Res 2021 May 5;169:105650. Epub 2021 May 5.

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 280 Waihuan East Road, Panyu District, Guangdong 510006, PR China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address:

Stroke is one of the leading causes of death worldwide. Hemorrhagic transformation (HT) is a common serious complication of ischemic stroke (IS) and is related to poor prognosis. Hyperglycemia after stroke is associated with the occurrence of HT and seriously affects the clinical treatment of stroke. Our previous experiments demonstrated that the Xiao-Xu-Ming decoction effective components group (XXMD), which is a Chinese medicine formula reconstituted by active ingredients, has multiple pharmacological effects in the treatment of IS. However, the effects of XXMD on HT after IS remain unclear. Thus, we investigated the preventive effects of XXMD on hyperglycemia-induced HT and further explored the underlying mechanism. Acute hyperglycemia combined with the electrocoagulation cerebral ischemia model was used to establish the HT model. XXMD (37.5, 75, 150 mg/kg/d) was given by gavage for 5 days. Network pharmacology was used to predict potential targets and pathways of XXMD in HT occurrence, and further studies confirmed the related targets. The results showed that hyperglycemia aggravated neurological deficits and blood-brain barrier (BBB) disruption, leading to intracerebral hemorrhage. Pretreatment with XXMD improved neurological function and BBB integrity and inhibited HT occurrence. Network pharmacology revealed that AGE-RAGE-mediated neuroinflammation may be associated with hyperglycemia-induced HT. Further studies confirmed that hyperglycemia activated the AGE-RAGE signaling pathway, increased the expression of HMGB1, TLR4 and p-p65, and induced the release of inflammatory factors and neutrophil infiltration, leading to HT. XXMD could inhibit AGE-RAGE-mediated neuroinflammation. These findings indicated that pretreatment with XXMD alleviated hyperglycemia-induced HT, which may be associated with the inhibition of AGE-RAGE-mediated neuroinflammation. Therefore, XXMD may be a potential therapeutic drug for HT.
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http://dx.doi.org/10.1016/j.phrs.2021.105650DOI Listing
May 2021

Occurrence, bioaccumulation, fate, and risk assessment of novel brominated flame retardants (NBFRs) in aquatic environments - A critical review.

Water Res 2021 Jun 21;198:117168. Epub 2021 Apr 21.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Novel brominated flame retardants (NBFRs), which have been developed as replacements for legacy flame retardants such as polybrominated diphenyl ethers (PBDEs), are a class of alternative flame retardants with emerging and widespread applications. The ubiquitous occurrence of NBFRs in the aquatic environments and the potential adverse effects on aquatic organisms have initiated intense global concerns. The present article, therefore, identifies and analyzes the current state of knowledge on the occurrence, bioaccumulation, fates, and environmental and health risks of NBFRs in aquatic environments. The key findings from this review are that (1) the distribution of NBFRs are source-dependent in the global aquatic environments, and several NBFRs have been reported at higher concentrations than that of the legacy flame retardants; (2) high bioaccumulative properties have been found for all of the discussed NBFRs due to their strong hydrophobic characteristics and weak metabolic rates; (3) the limited information available suggests that NBFRs are resistant to biotic and abiotic degradation processes and that sorption to sludge and sediments are the main fate of NBFRs in the aquatic environments; (4) the results of ecological risk assessments have indicated the potential risks of NBFRs and have suggested that source areas are the most vulnerable environmental compartments. Knowledge gaps and perspectives for future research regarding the monitoring, toxicokinetics, transformation processes, and development of ecological risk assessments of NBFRs in aquatic environments are proposed.
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http://dx.doi.org/10.1016/j.watres.2021.117168DOI Listing
June 2021

Case Report: Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease) Concurrent With Aseptic Meningitis.

Front Neurol 2021 20;12:565387. Epub 2021 Apr 20.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, self-limiting disease characterized by local lymphadenopathy. Central nervous system involvement in KFD is extremely rare and remains a diagnostic challenge. Only 41 cases of aseptic meningitis associated with KFD have been reported worldwide, with just four cases (including our case) of KFD with meningitis as the first symptom. We report a case of KFD accompanied by aseptic meningitis with severely high intracranial pressure (400 mmHO), increased white blood cell count (56 × 10/L), and moderately elevated protein level (0.52 g/L). This case is unique in the delayed appearance of lymphadenopathy. After 1 month of treatment with steroids, fever, headache, and lymphadenopathy gradually disappeared, and the result of cerebrospinal fluid examination gradually became normal. In conclusion, based on our case findings and our literature review on KFD with aseptic meningitis, a diagnosis of KFD should be considered when delayed appearance of lymphadenopathy is observed in patients with aseptic meningitis.
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http://dx.doi.org/10.3389/fneur.2021.565387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093430PMC
April 2021

Identification of an 11-Autophagy-Related-Gene Signature as Promising Prognostic Biomarker for Bladder Cancer Patients.

Biology (Basel) 2021 Apr 27;10(5). Epub 2021 Apr 27.

Department of Environmental Medicine, New York University School of Medicine, 341 East 25 Street, New York, NY 10010, USA.

Background: Survival rates for highly invasive bladder cancer (BC) patients have been very low, with a 5-year survival rate of 6%. Accurate prediction of tumor progression and survival is important for diagnosis and therapeutic decisions for BC patients. Our study aims to develop an autophagy-related-gene (ARG) signature that helps to predict the survival of BC patients.

Methods: RNA-seq data of 403 BC patients were retrieved from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) database. Univariate Cox regression analysis was performed to identify overall survival (OS)-related ARGs. The Lasso Cox regression model was applied to establish an ARG signature in the TCGA training cohort (N = 203). The performance of the 11-gene ARG signature was further evaluated in a training cohort and an independent validation cohort (N = 200) using Kaplan-Meier OS curve analysis, receiver operating characteristic (ROC) analysis, as well as univariate and multivariate Cox regression analysis.

Results: Our study identified an 11-gene ARG signature that is significantly associated with OS, including , , , , , , , , , , and . The ARGs-derived high-risk bladder cancer patients exhibited significantly poor OS in both training and validation cohorts. The prognostic model showed good predictive efficacy, with the area under the ROC curve (AUCs) for 1-year, 3-year, and 5-year overall survival of 0.702 (0.695), 0.744 (0.640), and 0.794 (0.658) in the training and validation cohorts, respectively. A prognostic nomogram, which included the ARGs-derived risk factor, age and stage for eventual clinical translation, was established.

Conclusion: We identified a novel ARG signature for risk-stratification and robust prediction of overall survival for BC patients.
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http://dx.doi.org/10.3390/biology10050375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146553PMC
April 2021

Impact of Teamwork and Communication Training Interventions on Safety Culture and Patient Safety in Emergency Departments: A Systematic Review.

J Patient Saf 2020 Sep 7. Epub 2020 Sep 7.

From the Department of *Emergency Medicine, Beth Israel Deaconess Medical Center, Teaching Hospital of Harvard Medical School, Harvard Medical School, Boston, Massachusetts †Department of Emergency Medicine, Dr Sulaiman Alhabib Hospital, Dubai, United Arab Emirates ‡Department of Emergency Medicine, Purpan Hospital and Toulouse III University, Toulouse, France §STRATUS Center for Medical Simulation, Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School ∥MS Knowledge Services, Beth Israel Deaconess Medical Center, Boston, Massachusetts ¶The National Medical Library, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates **Hamad Medical Corporation Ambulance Service, Doha, Qatar ††School of Health and Social Work, University of Hertfordshire, Hatfield, United Kingdom ‡‡Department of Health Quality, University Hospital, Hospices Civils §§Health Services and Performance Research Laboratory, EA 7425, University Lyon 1, Lyon, France ∥∥Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts ¶¶Division of Emergency and Acute Medicine (CVK, CCM), Charité University Medicine, Berlin, Germany ***Department of Healthcare Quality, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts †††Emergency Medicine Department, University Hospital, Hospices Civils, Lyon, University Lyon 1, Lyon, France ‡‡‡Department of Medicine, Division of Primary Care, Stanford University School of Medicine, Stanford, California §§§Department of Emergency Medicine, Union Hospital Terre Haute and Clinton IN, Simulation Center for Health Care Education, Indiana State University, Terre Haute, Indiana ∥∥∥Research Innovation Department, Global Health Care Network and Research Innovation Institute LLC, Brookline, MA, Massachusetts.

Objectives: This study aimed to narratively summarize the literature reporting on the effect of teamwork and communication training interventions on culture and patient safety in emergency department (ED) settings.

Methods: We searched PubMed, EMBASE, Psych Info CINAHL, Cochrane, Science Citation Inc, the Web of Science, and Educational Resources Information Centre for peer-reviewed journal articles published from January 1, 1988, to June 8, 2018, that assessed teamwork and communication interventions focusing on how they influence patient safety in the ED. One additional search update was performed in July 2019.

Results: Sixteen studies were included from 8700 screened publications. The studies' design, interventions, and evaluation methods varied widely. The most impactful ED training interventions were End-of-Course Critique, Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), and crisis resource management (CRM)-based training. Crisis resource management and TeamSTEPPS CRM-based training curriculum were used in most of the studies. Multiple tools, including the Kirkpatrick evaluation model, the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture, the TeamSTEPPS Teamwork Attitudes Questionnaire, the Safety Attitudes Questionnaire, and the Communication and Teamwork Skills Assessment, were used to assess the impact of such interventions. Improvements in one of the domains of safety culture and related domains were found in all studies. Four empirical studies established improvements in patient health outcomes that occurred after simulation CRM training (Kirkpatrick 4), but there was no effect on mortality.

Conclusions: Overall, teamwork and communication training interventions improve the safety culture in ED settings and may positively affect patient outcome. The implementation of safety culture programs may be considered to reduce incidence of medical errors and adverse events.
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http://dx.doi.org/10.1097/PTS.0000000000000782DOI Listing
September 2020

Coupling stable isotopes to evaluate sources and transformations of nitrate in groundwater and inflowing rivers around the Caohai karst wetland, Southwest China.

Environ Sci Pollut Res Int 2021 Apr 21. Epub 2021 Apr 21.

College of Resource and Environmental Engineering, Guizhou University, Guiyang, 550025, Guizhou, China.

Nitrate is one of the most common pollutants in aquatic ecosystems, particularly in highly vulnerable karst aquifers. In Caohai Lake, an important karst wetland in southwestern China, karst surface water and groundwater are important recharge water sources, and nitrates flow into the wetland along with the surface water and groundwater, degrading the wetland water quality. Therefore, identifying the sources of nitrate in the surface water and groundwater in the Caohai catchment is of great significance to the protection of the wetland water environment. In this study, the nitrate concentrations, hydrochemistry and multiple stable isotope ratios (δO-HO, δD-HO, δN-NO and δO-NO) were used to identify the sources and fate of the NO in the groundwater and inflowing rivers around the Caohai wetland. The results showed that the NO concentrations in the groundwater samples from the southern side exceeded the WHO limit during the wet season, while other samples did not exceed the limit. The mean concentrations of NO in groundwater were higher than those in the inflowing river water, and NO concentrations decreased in the order of wet season>dry season>normal season in the groundwater and inflowing rivers. The hydrochemistry and multiple isotope ratios suggest that the nitrate transformation was dominated by nitrification processes, while denitrification had an influence on the transformation of NO (as evidenced by isotopes) in groundwater during the dry season. According to the analyses based on a stable isotope analysis in R (SIAR), sewage and manure were the main sources of NO in the groundwater, while sewage, manure and chemical fertilizer were the major sources of NO in the inflowing river water; therefore, the scientific use of farmland fertilizers and the treatment of domestic sewage should be strengthened to safeguard groundwater quality and control the NO concentrations in rivers.
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http://dx.doi.org/10.1007/s11356-021-13827-4DOI Listing
April 2021

The therapeutic effects of ginkgolides in Guillain-Barré syndrome and experimental autoimmune neuritis.

J Clin Neurosci 2021 May 11;87:44-49. Epub 2021 Mar 11.

Neuroscience Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China. Electronic address:

Background: Guillain-Barré syndrome (GBS) is an acquired immune-mediated inflammatory peripheral neuropathy. The immune regulation of ginkgolides have been revealed in recent years. We herein investigate the potential therapeutic effects of ginkgolides both on GBS and its animal model, experimental autoimmune neuritis (EAN).

Methods: EAN in C57BL/6 mice induced by subcutaneous injection with peripheral nerve myelin P0 protein peptide 180-199 (P0 peptide) were treated with ginkgolides at three different doses. GBS patients were randomly divided into two groups, the experimental group and the control group. The experimental group were treated with ginkgolides as soon as diagnosed.

Results: Our data indicated that ginkgolides administration daily ameliorated the score of EAN and delayed the peak of disease in EAN mice. Ginkgolides also down-regulated the proportions of T helper (Th) 17 cells in EAN spleens. Furthermore, we also found that administration of ginkgolides significantly decreased the levels of interferon (IFN)-γ and interleukin-12 (IL)-12 in GBS patients.

Conclusions: Our results suggested that ginkgolides ameliorated the clinical score of EAN through down-regulating the proportions of Th 17 cells. Ginkgolides also suppressed inflammation response by decreasing pro-inflammatory cytokines IFN-γ and IL-12, suggesting ginkgolides had potential therapeutic effects on GBS patients and EAN in the future.
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http://dx.doi.org/10.1016/j.jocn.2021.02.016DOI Listing
May 2021

The application of acupuncture in obstetrics and gynecology: a bibliometric analysis based on Web of Science.

Ann Palliat Med 2021 Mar;10(3):3194-3204

Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: Acupuncture therapy has a wide range of applications in obstetrics and gynecology, especially for patients with reproductive issues, irregular menstruation, dysmenorrhea, and pelvic inflammatory disease. In recent decades, acupuncture therapy has gradually attracted the attention of professionals in China and overseas due to its beneficial effects, and has been the focus of many studies. This study aimed to conduct a statistical analysis of the relevant literature to understand the current application and research status of acupuncture in obstetric and gynecologic diseases.

Methods: A search of the SCI-EXPANDED database in the Web of Science Core Collection (WOSCC) was performed. Search strategy included two formulas: #1 WC=Obstetrics & Gynecology, limited: index =SCI-EXPANDED time span=all years; #2 subject: (ACUPUNCTURE-MOXIBUSTION) OR subject: (ACUPUNCTURE) OR subject: (MOXIBUSTION), limited: index=SCI-EXPANDED time span=all years. The final result was acquired by searching #1 AND #2. CiteSpace software was used to analyze and visualize the annual distribution of articles, and the distributions of disciplines, countries/institutions, journals, and authors. Keywords were used to infer the application of acupuncture in obstetrics and gynecology.

Results: A total of 593 research literatures, including 323 original articles, were retrieved. Since 1972, the number of literatures has shown a general increase. Studies on reproductive medicine accounted for the highest proportion of the retrieved literatures (139, 23.44%). The United States (25.5%), China (14.0%), Germany (7.6%), Australia (7.3%), and Sweden (7.1%) were the main contributors. The centrality index showed that the United States (0.19), the United Kingdom (0.19), and Germany (0.16) had the closest cooperation. The retrieved literatures covered 15 subdivision areas, including menstruation, embryo transfer, production, and pelvic pain. Obstetrics & Gynecology, Cochrane Database of Systematic Reviews, and American Journal of Obstetrics and Gynecology were found to be the most influential journals. The most frequently cited keywords were acupuncture (intensity =5.5326), low back pain (intensity =5.0506), and pregnancy (intensity =4.7016).

Conclusions: Acupuncture is receiving an increasing amount of attention in obstetrics and gynecology, and international cooperation in research in this field is also increasing.
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http://dx.doi.org/10.21037/apm-21-477DOI Listing
March 2021

The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Crit Rev Food Sci Nutr 2021 Apr 13:1-18. Epub 2021 Apr 13.

Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.
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http://dx.doi.org/10.1080/10408398.2021.1898333DOI Listing
April 2021

Acupuncture, from the ancient to the current.

Anat Rec (Hoboken) 2021 Apr 6. Epub 2021 Apr 6.

Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Acupuncture is characterized by the insertion of a fine metal needle through the skin of the human body at an acupuncture point (acupoint) in Traditional Chinese Medicine (TCM). It is an ancient form of therapy, and has a long history of prosperity and decline. Due to the persistent efforts of TCM practitioners, a number of well-designed clinical trials regarding acupuncture have been published in the past decade. Besides, numerous basic researches aiming to reveal the mechanisms of acupuncture have also been conducted. Several scientific explanations have been obtained to interpret the arcane TCM theory. This review provides brief information of acupuncture, including its history, status, evidence, and mechanisms.
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http://dx.doi.org/10.1002/ar.24625DOI Listing
April 2021

Improving quality management of newborn screening in southwest China.

J Int Med Res 2021 Apr;49(4):3000605211002999

Center for Clinical Molecular Medicine & Newborn Screening, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing, China.

Objective: Newborn screening (NBS) programs benefit tens of millions of infants worldwide each year. However, the extremely large screening populations and number of laboratories involved pose great challenges to maintaining high screening quality. To achieve continuous quality improvement, we established a comprehensive quality management system (CQMS) in southwest China.

Methods: External quality assessment (EQA) and internal quality control were carried out for basic quality management. We used 16 quality indicators (QIs) to monitor the entire screening process, with external supervision from the China National Accreditation Service for Conformity Assessment. All retrospective data for quality assessment were collected consecutively from laboratory management and patient follow-up systems.

Results: From 2015 to 2019, satisfactory EQA performance was achieved, with an average score greater than 97 for each screening item. QI monitoring showed that NBS quality improved continuously. The rate of health education provision increased from 90.9% to 100% and the recall rate after a positive primary screening increased from 85.4% to 99.2%. The unsatisfactory specimen rate and rate of newborns lost to follow-up decreased to 0.38% and 0.08%, respectively.

Conclusions: Implementing a CQMS and monitoring the whole screening process using QIs may yield continuous quality improvement of NBS.
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http://dx.doi.org/10.1177/03000605211002999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033469PMC
April 2021

Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old.

Diagnostics (Basel) 2021 Mar 21;11(3). Epub 2021 Mar 21.

Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA 98105, USA.

Improvement of antiretroviral therapy (ART) regimen switching practices and implementation of pretreatment drug resistance (PDR) testing are two potential approaches to improve health outcomes for children living with HIV. We developed a microsimulation model of disease progression and treatment focused on children with perinatally acquired HIV in sub-Saharan Africa who initiate ART at 3 years of age. We evaluated the cost-effectiveness of diagnostic-based strategies ( and ), over a 10-year time horizon, in settings without and with pediatric dolutegravir (DTG) availability as first-line ART. The strategy increases the probability of switching to second-line ART when virologic failure is diagnosed through viral load testing. The strategy involves a one-time PDR test prior to ART initiation to guide choice of initial regimen. When DTG is not available, PDR testing is dominated by the improved switching strategy, which has an incremental cost-effectiveness ratio (ICER) of USD 579/life-year gained (LY), relative to the status quo. If DTG is available, has a similar ICER (USD 591/LY) relative to the . Even when substantial financial investment is needed to achieve improved regimen switching practices, the strategy still has the potential to be cost-effective in a wide range of sub-Saharan African countries. Our analysis highlights the importance of strengthening existing laboratory monitoring systems to improve the health of children living with HIV.
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http://dx.doi.org/10.3390/diagnostics11030567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004076PMC
March 2021

Dragon's Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity.

Int J Mol Sci 2021 Mar 8;22(5). Epub 2021 Mar 8.

School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing 100081, China.

Dragon's Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has shown protective effects on intestinal disorders. Microgravity could alter intestinal homeostasis. However, the potential herbal drugs for preventing intestine epithelial barrier (IEB) dysfunction under microgravity are not available. This study aimed to investigate the effects of Dragon's Blood (DB) on microgravity-induced IEB injury and explore its underlying mechanism. A rat tail-suspension model was used to simulate microgravity (SMG). Histomorphology, ultrastructure, permeability, and expression of junction proteins in jejunum, ileum, and colon of SMG rats were determined. Proteomic analysis was used to identify differentially expressed proteins (DEPs) in rat ileum mucosa altered by DB. The potential mechanism of DB to protect IEB dysfunction was validated by western blotting. The effects of several components in DB were evaluated in SMG-treated Caco-2 cells. DB protected against IEB disruption by repairing microvilli and crypts, inhibiting inflammatory factors, lowering the permeability and upregulating the expression of tight and adherens junction proteins in the ileum of SMG rats. Proteomic analysis showed that DB regulated 1080 DEPs in rat ileum mucosa. DEPs were significantly annotated in cell-cell adhesion, focal adhesion, and cytoskeleton regulation. DB increased the expression of Rac1-WAVE2-Arp2/3 pathway proteins and F-actin to G-actin ratio, which promoted the formation of focal adhesions. Loureirin C in DB showed a protective effect on epithelial barrier injury in SMG-treated Caco-2 cells. DB could protect against IEB dysfunction induced by SMG, and its mechanism is associated with the formation of focal adhesions mediated by the Rac1-WAVE2-Arp2/3 pathway, which benefits intestinal epithelial cell migration and barrier repair.
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http://dx.doi.org/10.3390/ijms22052722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962842PMC
March 2021

Co-existing siderite alleviates the Fe(II) oxidation-induced inactivation of Fe(III)-reducing bacteria.

Sci Total Environ 2021 Aug 27;781:146489. Epub 2021 Mar 27.

School of Environmental Studies, China University of Geosciences, Wuhan 430074, PR China.

Abiotic Fe (II) oxidation widely occurs in the natural subsurface environment and engineered dynamic processes, which possibly impacts the growth of indigenous microbes. As previously discovered, the oxidation of aqueous Fe at neutral pH effectively inactivates iron-reducing bacteria Shewanella oneidensis strain MR-1 (MR-1). Herein, the impacts of co-existing iron mineral on the oxidation of aqueous Fe and the subsequent disinfection activity on MR-1 were investigated with siderite selected as a representative iron mineral in the subsurface environment. The oxidation rate of aqueous Fe and the amount of generated OH radical increased as the content of siderite increased, while the MR-1 inactivation was alleviated. An initial concentration of 2.0 × 10 CFU/mL MR-1 was inactivated by about 2.7 orders of magnitude during oxidation of 0.2 mM FeSO alone for 30 min, which was reduced to only about 0.6 orders of magnitude in the presence of 4.3 mM co-existing siderite. ROS scavenging results confirmed that the OH radical generated in the bulk solution was not the leading role for the inactivation of MR-1. Morphological changes of the cells observed by SEM demonstrated that the disruption of the cell membrane was alleviated by siderite, which was further supported by the XRD and FTIR spectra. The underlying mechanism was proposed to be the reduced contact time of Fe and MR-1 cells due to the accelerated oxidation. This work provides new insights into the disinfection behavior of heterogeneous Fe (II) oxidation on iron cycling bacterial in the natural environment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146489DOI Listing
August 2021

The Antimicrobial Peptide Melectin Shows Both Antimicrobial and Antitumor Activity via Membrane Interference and DNA Binding.

Drug Des Devel Ther 2021 19;15:1261-1273. Epub 2021 Mar 19.

The Key Laboratory, The First Hospital of Lanzhou University, Lanzhou, People's Republic of China.

Purpose: Increasingly complex diseases require novel drugs for their treatment. Antimicrobial peptides (AMPs) are promising candidate treatments due to their broad existence and special characteristics. However, the current understanding of AMPs is not sufficient to allow them to be produced commercially for clinical use.

Materials And Methods: Melectin, from the venom of the cleptoparasitic bee , does not exhibit sequence homology with other wasp venom peptides. To investigate this more deeply, we explored the antibacterial and antitumor activities of Melectin and related mechanisms.

Results: Our results demonstrate that Melectin possesses antimicrobial properties against standard sensitive/clinical drug-resistant bacteria strains as well as antitumor activity. It has an α-helix form and exhibits moderate cytotoxicity. Its action mechanisms are involved with membrane interfering and DNA binding. The membrane interfering effect was distinct between different phospholipid compositions.

Conclusion: We found that Melectin may serve as a new potential template in the battle against multidrug resistance, and our study indicated that there are promising prospects for medically applicable drugs based on AMPs.
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http://dx.doi.org/10.2147/DDDT.S288219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989573PMC
March 2021

Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Cardiovascular Surgical ICU, Tianjin Chest Hospital, Nankai University, Tianjin 300222, P.R. China.

Sepsis is a life‑threatening organ dysfunction caused by a dysregulated host response to infection, and is a leading cause of mortality worldwide. Myocardial dysfunction is associated with poor prognosis in patients with sepsis and contributes to a high risk of mortality. However, the pathophysiological mechanisms underlying sepsis‑induced myocardial dysfunction are not completely understood. The aim of the present study was to investigate the role of toll‑like receptor 4 (TLR4)/c‑Jun N‑terminal kinase (JNK) signaling in pro‑inflammatory cytokine expression and cardiac dysfunction during lipopolysaccharide (LPS)‑induced sepsis in mice. C57BL/6 mice were pretreated with TAK‑242 or saline for 1 h and then subjected to LPS (12 mg/kg, intraperitoneal) treatment. Cardiac function was assessed using an echocardiogram. The morphological changes of the myocardium were examined by hematoxylin and eosin staining and transmission electron microscopy. The serum protein levels of cardiac troponin I (cTnI) and tumor necrosis factor‑α (TNF‑α) were determined by an enzyme‑linked immunosorbent assay (ELISA). The TLR4 and JNK mRNA levels were analyzed via reverse transcription‑quantitative PCR. TLR4, JNK and phosphorylated‑JNK protein levels were measured by western blotting. In response to LPS, the activation of TLR4 and JNK in the myocardium was upregulated. There were significant increases in the serum levels of TNF‑α and cTnI, as well as histopathological changes in the myocardium and suppressed cardiac function, following LPS stimulation. Inhibition of TLR4 activation using TAK‑242 led to a decrease in the activation of JNK and reduced the protein expression of TNF‑α in plasma, and alleviated histological myocardial injury and improved cardiac function during sepsis in mice. The present data suggested that the TLR4/JNK signaling pathway played a critical role in regulating the production of pro‑inflammatory cytokines and myocardial dysfunction induced by LPS.
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http://dx.doi.org/10.3892/mmr.2021.11973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974310PMC
May 2021

[Hydrochemistry Characteristics and Estimation of the Dissolved Inorganic Carbon Flux in the Caohai Lake Wetland Catchment of Guizhou Province].

Huan Jing Ke Xue 2021 Apr;42(4):1761-1771

Key Laboratory of Karst Georesources and Environment, Ministry of Education, College of Resource and Environmental Engineering, Guizhou University, Guiyang 550025, China.

The Caohai Lake wetland in Weining County, Guizhou Province, is the largest karst wetland in China, and karst groundwater is an essential source of recharge and material. This study collected groundwater from the Caohai Lake catchment during the wet season, dry season, and flat season, and the main ion components of the groundwater were analyzed. The hydrochemistry characteristics and main ion sources of the groundwater were revealed, and the preliminary estimates of the karst carbon sink flux in the Caohai Lake catchment were calculated based on the solute load method. The results indicated that the water chemistry of the groundwater in the Caohai Lake catchment is primarily the HCO-Ca type, and individual groundwater points in the southeast are the SO-Ca type during the flat season. The dominant ions in the groundwater are Ca, Mg, and HCO. Seasonally, the average concentrations of SO and Mg decreased in the order of flat season>dry season>wet season, while the average concentration of NO decreased in the order of wet season>dry season>flat season, and the seasonal variation of the other ions were not significant. Spatially, the concentrations of Ca and HCO in the groundwater in the northern part of Caohai Lake, of K, Na, and Cl in the southwest, and of Mg, NO, and SO in the southeast were relatively high. Ca, Mg, and HCO in the groundwater were primarily controlled by the dissolution of carbonate rocks, and carbonic acid, sulfuric acid and nitric acid were all involved in the weathering of carbonate rocks in the catchment. Most of the NO in the groundwater was affected mostly by the soil nitrogen and domestic sewage, while NO in the southeast groundwater was primarily affected by agricultural activities. The sources of K, Na, Cl, and SO exhibited no obvious temporal and spatial differences, and the K, Na, and Cl were mainly affected by human activities, while SO was mostly derived from the dissolution of sulfur compounds in the formation. The studied area has a high proportion of allogenic acids (sulfuric acid and nitric acid) participating in the weathering of carbonate rocks, which is the highest in the flat season and the lowest in wet season. After deducting the proportion of allogenic acids participating in the weathering of carbonate rocks, the average inorganic carbon flux in the Caohai Lake catchment is preliminarily estimated to be approximately 181.5 t·a, and the average karst groundwater transport of HCO to Caohai Lake is approximately 1144.1 t·a.
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http://dx.doi.org/10.13227/j.hjkx.202007163DOI Listing
April 2021

COVID-19 Pandemic Response Simulation in a Large City: Impact of Nonpharmaceutical Interventions on Reopening Society.

Med Decis Making 2021 05 18;41(4):419-429. Epub 2021 Mar 18.

Department of Industrial & Systems Engineering, University of Washington, Seattle, WA, USA.

As the novel coronavirus (COVID-19) pandemic continues to expand, policymakers are striving to balance the combinations of nonpharmaceutical interventions (NPIs) to keep people safe and minimize social disruptions. We developed and calibrated an agent-based simulation to model COVID-19 outbreaks in the greater Seattle area. The model simulated NPIs, including social distancing, face mask use, school closure, testing, and contact tracing with variable compliance and effectiveness to identify optimal NPI combinations that can control the spread of the virus in a large urban area. Results highlight the importance of at least 75% face mask use to relax social distancing and school closure measures while keeping infections low. It is important to relax NPIs cautiously during vaccine rollout in 2021.
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http://dx.doi.org/10.1177/0272989X211003081DOI Listing
May 2021