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1.
Aging Dis ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39012662

ABSTRACT

The increasing studies indicated that cardiovascular diseases, such as coronary artery disease (CAD), usually induce and exacerbate psychological problems, including anxiety and depression. These psychological issues are admitted as independent risk factors of heart disease as well. The interaction between CAD and anxiety and depression deteriorates the development and prognosis of CAD, which severely threatens the quality of life of patients. Although the existing mechanisms revealed the pathological relationship between CAD and anxiety and depression, there are few studies investigating the correlation between CAD and anxiety and depression from the aspect of gut microbiota (GM) and its metabolites. Therefore, in this review, we summarized whether GM and its metabolites are the emergent bridge between CAD and anxiety and depression. The results showed that there are four kinds of jointly up-regulated bacteria (i.e., Staphylococcus, Escherichia coli, Helicobacter pylori, and Shigella) and five kinds of jointly down-regulated bacteria (i.e., Prevotella, Lactobacillus, Faecalibacterium prausnitzii, Collinsella, and Bifidobacterium) in CAD as well as anxiety and depression. In addition, in CAD and anxiety and depression, the dysbiosis of the former four kinds of bacterium frequently leads to the outburst of inflammatory response, and the dysbiosis of the latter five kinds of bacterium is usually related to the metabolic abnormality of short-chain fatty acids, bile acids, and branched-chain amino acids. Therefore, we believe that GM and its metabolites act as the emergent bridge between CAD and anxiety and depression. The findings of this review provide novel insights and approaches for the clinical treatment of patients with both CAD and anxiety and depression.

2.
Nat Commun ; 15(1): 5607, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965277

ABSTRACT

Reducing interface nonradiative recombination is important for realizing highly efficient perovskite solar cells. In this work, we develop a synergistic bimolecular interlayer (SBI) strategy via 4-methoxyphenylphosphonic acid (MPA) and 2-phenylethylammonium iodide (PEAI) to functionalize the perovskite interface. MPA induces an in-situ chemical reaction at the perovskite surface via forming strong P-O-Pb covalent bonds that diminish the surface defect density and upshift the surface Fermi level. PEAI further creates an additional negative surface dipole so that a more n-type perovskite surface is constructed, which enhances electron extraction at the top interface. With this cooperative surface treatment, we greatly minimize interface nonradiative recombination through both enhanced defect passivation and improved energetics. The resulting p-i-n device achieves a stabilized power conversion efficiency of 25.53% and one of the smallest nonradiative recombination induced Voc loss of only 59 mV reported to date. We also obtain a certified efficiency of 25.05%. This work sheds light on the synergistic interface engineering for further improvement of perovskite solar cells.

3.
Chemosphere ; 362: 142722, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950739

ABSTRACT

Glutathione S-transferases (GSTs) are multifunctional enzymes, and insect GSTs play a pivotal role in the metabolism of insecticides. Grapholita molesta is a worldwide pest that causes substantial economic losses to the fruit industry. However, it remains unclear how imidacloprid, a commonly used insecticide in orchards, is metabolized by G. molesta. In the present study, the synergist diethyl maleate (DEM), which inhibits the GST activity, exhibited a 22-fold synergistic ratio against imidacloprid. Two new GST genes, GmGSTD2 (OR096251) and GmGSTD3 (OR096252), were identified and successfully cloned, showing the highest expression in the Malpighian tubes. Knockdown of GmGSTD2 and GmGSTD3 by RNA interference, increased the mortality of G. molesta from 28% to 47% following imidacloprid treatment. Both recombinant GmGSTD2 and GmGSTD3 proteins exhibited 1-chloro-2,4-dinitrobenzene (CDNB) activity and could be inhibited by imidacloprid in vitro, with maximum inhibition was 60% for GmGSTD2 and 80% for GmGSTD3. These results suggested that GSTs participate in the metabolism of imidacloprid with GmGSTD2 and GmGSTD3 playing key roles in this process.

4.
Eur J Pharm Sci ; 201: 106851, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39009286

ABSTRACT

Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), is an effective drug in treating patients infected with human immunodeficiency virus (HIV). Previous population pharmacokinetics (PPK) studies have showed the large variabilities in PK of TFV. Furthermore, limited information was known in Chinese populations. Therefore, the aim of this study was to characterize PPK of TDF in Chinese and identify factors that may affect its PK. TFV concentrations (n = 552) from 30 healthy subjects and 162 HIV-infected Chinese adult patients were pooled for PPK analysis by a nonlinear mixed-effects method. The PK of TFV was adequately described as a two-compartment model with first order absorption and elimination. The typical apparent clearance (CL/F) of TFV in 70-kg adults was 137 L/h, higher than that reported in Caucasians and Blacks (45.8-93 L/h). Estimated glomerular filtration rate was identified to be a significant factor influencing CL/F. Monte Carlo simulation showed that the exposure of standard dosing regimen of TDF 300 mg every 24 h in Chinese people with mild renal impairment (60 to 90 ml/min/1.73 m2) was close to that in individuals with normal renal function (90 mL/min). Dose adjustment is not required for patients with mild renal impairment. Our study might offer new clues for optimal dosing strategies in Chinese patients with HIV-infected.

5.
Pharmacol Res ; 206: 107289, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960011

ABSTRACT

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.


Subject(s)
Atherosclerosis , Mice, Inbred C57BL , STAT3 Transcription Factor , STAT3 Transcription Factor/metabolism , Animals , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Atherosclerosis/prevention & control , Mice , Male , Diet, High-Fat/adverse effects , Humans , RAW 264.7 Cells , Mice, Knockout , Protein Binding , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Foam Cells/drug effects , Foam Cells/metabolism
6.
Anal Methods ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39041298

ABSTRACT

Saxitoxin (STX) is a cyanotoxin with high toxicity, and therefore, there is an urgent need to develop a facile detection method for STX. In this study, an ordered nanopillar array-based electrochemical aptasensor was fabricated for the high-performance detection of STX. The anti-STX aptamer with methylene blue (MB) incorporated at the 3'-end (MB-Apt) was immobilized at the surface of an Au@PAN nanopillar array electrode and used as the recognition element. The proposed aptasensor demonstrated highly sensitive and selective STX detection because of synergistic catalysis effects of MB and ordered nanopillar arrays along with the selection of MB-Apt. The nanopillar array-based electrochemical aptasensor exhibited high sensitivity over a wide linear concentration range of 1 pM-3 nM with a linear regression equation of ΔI (µA) = 28.0 + 6.9 × log[STX] (R2 = 0.98079) and 3-100 nM with a linear regression equation of ΔI (µA) = 10.7 + 43.4 × log[STX] (R2 = 0.98772), where R is the correlation coefficient. In addition, the limit of detection (LOD) was as low as 1 pM. Furthermore, the designed aptasensor demonstrated excellent selectivity toward STX, preventing interference from neo-STX, okadaic acid, and common metal ions. The presented orderly nanopillar array-based strategy to develop an electrochemical aptasensor for STX detection offers a promising method for developing high-performance electrochemical sensors, and the presented aptasensor should find useful application in the detection of shellfish poison.

7.
J Insect Sci ; 24(4)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39023176

ABSTRACT

Tephritis angustipennis (Diptera: Tephritidae) and Campiglossa loewiana (Diptera: Tephritidae) are phytophagous pests in China. Their damage has significantly impacted the collection and cultivation of germplasm resources of native Asteraceae plants. However, the genetic characteristics and structure of their population are unclear. This study focused on the highly damaging species of T. angustipennis and C. loewiana collected from the three-river source region (TRSR). We amplified the mitochondrial cytochrome C oxidase subunit I (mtCOI) gene sequences of these pests collected from this area and compared them with COI sequences from GenBank. We also analyzed their genetic diversity and structure. In T. angustipennis, 5 haplotypes were identified from 5 geographic locations; the genetic differentiation between France population FRPY (from Nylandia, Uusimaa) and China populations GLJZ (from Dehe Longwa Village, Maqin County), GLDR (from Zhique Village, Dari County), and GLMQ (from Rijin Village, Maqin County) was the strongest. GLJZ exhibited strong genetic differentiation from GLDR and GLMQ, with relatively low gene flow. For C. loewiana, 11 haplotypes were identified from 5 geographic locations; the genetic differentiation between the Chinese population GLMQ-YY (from Yangyu Forest Farm, Maqin County) and Finnish population FDNL (from Nylandia, Uusimaa) was the strongest, with relatively low gene flow, possibly due to geographical barriers in the Qinghai-Tibet plateau. Only 1 haplotype was identified across GLDR, GLMQ, and GLBM. High gene flow between distant locations indicates that human activities or wind dispersal may facilitate the dispersal of fruit flies and across different geographic. Geostatistical analysis suggested a recent population expansion of these 2 species in TRSR. Our findings provide technical references for identifying pests in the TRSR region and theoretical support for managing resistance, monitoring pest occurrences, analyzing environmental adaptability, and formulating biological control strategies for Tephritidae pests on Asteraceae plants.


Subject(s)
DNA Barcoding, Taxonomic , Electron Transport Complex IV , Genetic Variation , Tephritidae , Animals , Tephritidae/genetics , China , Electron Transport Complex IV/genetics , Haplotypes , Phylogeny , Insect Proteins/genetics
8.
Micromachines (Basel) ; 15(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39064361

ABSTRACT

A miniaturized and wideband four-port multiple-input multiple-output (MIMO) antenna pair for Wi-Fi mobile terminals application is proposed. The proposed antenna pair consists of four multi-branch antenna elements arranged orthogonally, with an overall size of 40 × 40 × 3.5 mm3 and each antenna element size of 15.2 × 3.5 mm × 0.8 mm3. The performance of the proposed antenna shows the advantages of a wide frequency band, low mutual coupling, high efficiency, and a compact structure. The wideband characteristics of the antenna elements are achieved through multi-mode resonance. The suppression of coupling is accomplished by strategically positioning the four compact antenna elements to ensure their maximum radiation directions are orthogonal, thus eliminating the need for an additional decoupling structure. In this paper, the proposed antenna is optimized in terms of the parameters then simulated and measured. The simulated results illustrate that an impedance bandwidth of the antenna is about 15% (5.06~5.88 GHz) with S11 < -10 dB, excellent port isolation exceeds 20 dB between all ports, a high radiation efficiency ranges from 51.2% to 89.9%, the maximum gain is 4.5 dBi, and the ECCs are less than 0.04. The measured results show that the -10 dB impedance bandwidth of the antenna is about 13% (5.13~5.80 GHz), the isolation between the antenna elements is better than 21 dB, the radiation efficiency ranges from 51.8% to 92.3%, the maximum gain is 5.3 dBi, and the ECCs are less than 0.05. The proposed four-port MIMO antenna works on the 5G LTE band 46 and Wi-Fi 6E operating bands. As a mobile terminal antenna, the proposed design scheme demonstrates excellent performance and applicability, fulfilling the requirements for 5G mobile terminal applications.

9.
Phys Chem Chem Phys ; 26(28): 19554-19563, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38979978

ABSTRACT

Monitoring of reactive oxygen species (ROS), such as O2˙-, etc., in organisms is of great significance, not only for their essential role in biological processes, but their excessive production may also result in many diseases. Flavin (FL) is a fluorophore that naturally exists in flavoenzymes, and its fluorescent emission (FE) becomes negligible when reduced. This enables the application of FL derivatives as fluorescent sensors for ROS. We presented a theoretical investigation to address the impact of amino substitution on the photophysical properties of aminoflavins (AmFLs). Resulting from the interplay of electronic and positional effects, amination at C8 enhances the electronic coupling between the ground state and the first singlet excited state by enlarging the adiabatic energy change of the electronic transitions and the emission transition dipole moments, weakens the vibronic coupling by decreasing the contribution of isoalloxazine to the frontier molecular orbitals, redshifts the absorption band, and enhances the fluorescent emission drastically in 8AmFL. The theoretically estimated fluorescent emission intensity of 8AmFL is ∼40 times that of FL, suggesting its potential application as a fluorescent sensor.

10.
Discov Oncol ; 15(1): 314, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39073672

ABSTRACT

OBJECTIVE: To assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed. RESULTS: A high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3-T4, N+, III-IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040). CONCLUSION: High infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target.

11.
J Colloid Interface Sci ; 676: 1032-1043, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39074406

ABSTRACT

Traditional peroxymonosulfate (PMS) catalytic membranes dominated by radical pathways often face interference from complex components in water bodies. Herein, we employed a controlled electro-deposition technique to coat a Ni-Co metal-organic framework (MOF) precursor onto titanium hollow fiber membrane (THFM), followed by high-temperature calcination to synthesize a MOF-derived NiO-NiCo2O4/THFM (M-NNCO-THFM) PMS catalytic membrane. Then, the M-NNCO-THFM filtration integrated with PMS activation (MFPA process) for water treatment. Experimental results demonstrated that the M-NNCO-THFM MFPA process successfully achieved complete phenol (PE) removal via a non-radical-dominated degradation pathway, involving singlet oxygen (1O2) and electron transfer, while exhibiting wide pH adaptability and exceptional stability in complex water matrices. Mechanism analysis revealed that the electron transfer process was significantly enhanced by the MOF-derived heterojunction structure, which increased the flat-band potential from 0.39 eV to 0.56 eV, thereby facilitating efficient electron transfer for PE removal. The non-radical 1O2 pathway was primarily due to the cycling of metal valence states (Ni2+/Co3+), leading to the reduction of Co2+ and its reaction with PMS, resulting in the generation of reactive species. Furthermore, electrochemical measurements indicated that the M-NNCO-THFM exhibited lower charge transfer resistance and enhanced charge transfer efficiency compared to non-MOF-derived NNCO-THFM, corresponding to the superior catalytic performance and electrochemically active surface area of M-NNCO-THFM.

12.
Complement Ther Clin Pract ; 57: 101882, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38976965

ABSTRACT

OBJECTIVE: To systematically investigate the efficacy of aromatherapy in patients with acute coronary syndrome (ACS). METHODS: We conducted a comprehensive search for papers published until November 2023 using the following databases: PubMed, Embase, and Cochrane Library. This study was conducted following the PRISMA and Cochrane Guidelines. The inclusion criteria were randomized controlled trials (RCTs) performed to assess the comparative effectiveness of inhalation aromatherapy versus controls in individuals diagnosed with ACS. The Jadad rating method was used to assess the quality of the included studies, and a meta-analysis was performed using the RevMan 5.4 software. Heterogeneity was quantified using the Higgins I2 (%) test. RESULTS: A total of 12 RCTs with 476 patients with ACS were included. Aromatherapy has been shown to reduce anxiety scores significantly (standard mean difference [SMD]: -1.18, 95 % confidence interval [CI]: -1.33 to -1.03; P < 0.00001) along with reduction in systolic blood pressure (MD = -8.78, 95 % CI [-13.92, -3.65], P = 0.008); diastolic blood pressure (MD = -7.76, 95 % CI [-11.39, -4.12], P < 0.001); mean artery pressure MD = -9.68, 95 % CI [-13.93.-5.44]; P < 0.0001). However, no significant effects were reported on the heart rate (MD = -6.98, 95 % CI [-15.46, 1.50], P = 0.11) and respiratory rate (MD = -0.67, 95 % CI [-2.52, 1.19], P = 0.48). A greater frequency of aromatherapy was associated greater anxiety -1.80 incidence, with 95 % CI [-2.04, -1.56]. Citrus essential oils exhibited the strongest effect (SMD = -1.97, 95 % CI [-3.34, -0.60], P = 0.005) in reducing anxiety levels. CONCLUSION: Aromatherapy appears to be an effective non-pharmacological intervention for reducing blood pressure and anxiety in individuals with ACS. This suggests that aromatherapy more than twice a day is effective in reducing anxiety levels. However, aromatherapy had no statistically significant impact on the heart or respiratory rates. Moreover, additional high-quality RCTs should be conducted to verify these results and explore the efficacy and mechanism of aromatherapy in patients with ACS.

13.
BMC Cardiovasc Disord ; 24(1): 341, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969996

ABSTRACT

BACKGROUND: The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics. METHODS: The study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9. RESULTS: In males, the 97.5th centile NT-proBNP concentration at age < 45, 45 to 54, 55 to 64, 65 to 74 and ≧ 75 were 89.4 ng/L, 126 ng/L, 206 ng/L, 386 ng/L and 522 ng/L, respectively. In females, the concentration of NT-proBNP at the same age was 132 ng/L, 229 ng/L, 262 ng/L, 297 ng/L and 807 ng/L, respectively. The repeatability precision coefficient of variation (CV%) for NT-proBNP was between 0.86 and 1.65 in analytical performance. In contrast, the reproducibility precision (CV%) for NT-proBNP was between 1.52 and 3.22, respectively. The study found a bias of accuracy of 3.73% in low-value samples (concentration: 148.69) and 7.31% in high-value samples (concentration: 1939.08). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 125 ng/L were 96.6%, 92.3%, 84.2%, and 98.5%, respectively. In contrast, those of 300 ng/L were 94.0%, 98.2%, 95.7% and 97.5%, respectively. CONCLUSIONS: The Mindray NT-proBNP assay showed increased levels in both males and females with age, with higher levels in women. It performs well and aligns with manufacturer specifications. We recommend adjusting cutoff values based on demographic factors.


Subject(s)
Biomarkers , Natriuretic Peptide, Brain , Peptide Fragments , Predictive Value of Tests , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Male , Female , Middle Aged , Aged , Biomarkers/blood , Reproducibility of Results , Adult , China , Reference Values , Sex Factors , Age Factors , Healthy Volunteers , Aged, 80 and over , Young Adult , Limit of Detection
14.
Biointerphases ; 19(4)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38984804

ABSTRACT

Topical ophthalmic solutions (eye drops) are becoming increasingly popular in treating and preventing ocular diseases for their safety, noninvasiveness, and ease of handling. However, the static and dynamic barriers of eyes cause the extremely low bioavailability (<5%) of eye drops, making ocular therapy challenging. Thus, drug-eluting corneal contact lenses (DECLs) have been intensively investigated as a drug delivery device for their attractive properties, such as sustained drug release and improved bioavailability. In order to promote the clinical application of DECLs, multiple aspects, i.e., drug release and penetration, safety, and biocompatibility, of these drug delivery systems were thoroughly examined. In this review, we systematically discussed advances in DECLs, including types of preparation materials, drug-loading strategies, drug release mechanisms, strategies for penetrating ocular barriers, in vitro and in vivo drug delivery and penetration detection, safety, and biocompatibility validation methods, as well as challenges and future perspectives.


Subject(s)
Contact Lenses , Drug Delivery Systems , Ophthalmic Solutions , Humans , Animals , Cornea/metabolism , Biological Availability
15.
Elife ; 132024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012339

ABSTRACT

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).


Subject(s)
COVID-19 , Influenza, Human , Pneumonia , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , Influenza, Human/drug therapy , Male , Female , COVID-19/epidemiology , Middle Aged , Aged , Cohort Studies , Pneumonia/epidemiology , Histamine H2 Antagonists/adverse effects , Histamine H2 Antagonists/therapeutic use , SARS-CoV-2 , Adult , United Kingdom/epidemiology , Disease Susceptibility , Proportional Hazards Models
16.
J Med Chem ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018526

ABSTRACT

Acute respiratory viral infections, such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1), a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV (EC50 = 3-46 nM), human metapneumovirus (EC50 = 210 nM), human rhinovirus (EC50 = 54-61 nM), and enterovirus (EC50 = 83-90 nM). Prodrug optimization for cellular potency and lung cell metabolism identified 5'-methyl [(S)-hydroxy(phenoxy)phosphoryl]-l-alaninate in combination with 2',3'-diisobutyrate promoieties as being optimal for high levels of intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together, these findings support additional evaluation of 1 and its analogues as potential therapeutics for pneumo- and picornaviruses.

17.
Biointerphases ; 19(4)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39023091

ABSTRACT

Biofilms are groups of microorganisms protected by self-secreted extracellular substances. Biofilm formation on the surface of biomaterial or engineering materials becomes a severe challenge. It has caused significant health, environmental, and societal concerns. It is believed that biofilms lead to life-threatening infection, medical implant failure, foodborne disease, and marine biofouling. To address these issues, tremendous effort has been made to inhibit biofilm formation on materials. Biofilms are extremely difficult to treat once formed, so designing material and coating bearing functional groups that are capable of resisting biofilm formation has attracted increasing attention for the last two decades. Many types of antibiofilm strategies have been designed to target different stages of biofilm formation. Development of the antibiofilm material can be classified into antifouling material, antimicrobial material, fouling release material, and integrated antifouling/antimicrobial material. This review summarizes relevant research utilizing these four approaches and comments on their antibiofilm properties. The feature of each method was compared to reveal the research trend. Antibiofilm strategies in fundamental research and industrial applications were summarized.


Subject(s)
Anti-Infective Agents , Biofilms , Biofouling , Biofilms/drug effects , Biofilms/growth & development , Biofouling/prevention & control , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
18.
Ecol Evol ; 14(7): e70015, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39026959

ABSTRACT

Reaumuria songarica, a drought-resistant shrub, is widely distributed and plays a crucial role in the northern deserts of China. It is a key species for desert rehabilitation and afforestation efforts. Using the Maxent model to predict suitable planting areas for R. songarica is an important strategy for combating desertification. With 184 occurrence points of R. songarica and 13 environmental variables, the optimized Maxent model has identified the main limiting factors for its distribution. Distribution patterns and variation trends of R. songarica were projected for current and future climates (2030s, 2050s, 2070s, and 2090s) and different scenarios (ssp_126, ssp_370, and ssp_585). Results show that setting parameters to RM (regulation multiplier) = 4 and FC (feature combination) = LQHPT yields a model with good accuracy and high reliability. Currently, R. songarica is primarily suitable for desert control in eight provinces and autonomous regions, including Inner Mongolia, Xinjiang, Qinghai, and Ningxia. The total suitable planting area is 148.80 × 104 km2, representing 15.45% of China's land area. Precipitation (Precipitation of the wettest month, Precipitation of the warmest quarter, and Annual precipitation) and Ultraviolet-B seasonality are the primary environmental factors limiting the growth and distribution of R. songarica. Mean temperature of the warmest quarter is the primary factor driving changes in the distribution of suitable areas for R. songarica under future climate scenarios. In future climate scenarios, the suitable planting area of R. songarica will shrink, and the distribution center will shift towards higher latitude, potentially indicate further desertification. The area of highly suitable habitat has increased, while moderately and less suitable habitat areas have decreased. Increased precipitation within R. songarica's water tolerance range is favorable for its growth and reproduction. With changes in the suitable cultivation area for R. songarica, priority should be given to exploring and utilizing its germplasm resources. Introduction and cultivation can be conducted in expanding regions, while scientifically effective measures should be implemented to protect germplasm resources in contracting regions. The findings of this study provide a theoretical basis for addressing desertification resulting from climate change and offer practical insights for the development, utilization, introduction, and cultivation of R. songarica germplasm resources.

19.
Colloids Surf B Biointerfaces ; 242: 114086, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39038410

ABSTRACT

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

20.
Int J Surg ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38896866

ABSTRACT

BACKGROUND: Despite the growing evidence of an association between inflammatory bowel disease (IBD) and psychiatric disorders, there has been limited research exploring the underlying mediating role of blood biomarkers on the gut-brain axis. This study aimed to examine the association between IBD and the risk of incident psychiatric disorders and investigate whether and how blood biomarkers mediate this association. METHODS: This prospective cohort study using data from the UK Biobank included participants without psychiatric diagnoses at baseline. The case cohort consisted of participants with a hospital-based diagnosis of IBD at baseline. The primary outcome was all psychiatric disorders. Secondary outcomes included 11 major psychiatric disorders. Cox regression models estimated adjusted hazard ratios (HRs) for psychiatric outcomes. Causal mediation models investigated the potential mediation effects of blood biomarkers. RESULTS: Among 491,131 participants, patients with IBD exhibited higher risks of overall psychiatric disorders (HR 1.23 [95% CI 1.13-1.33]), substance misuse (1.23 [1.09-1.38]), depression (1.36 [1.22-1.52]), anxiety (1.15 [1.01-1.30]) and post-traumatic stress disorder (1.87 [1.00-3.51]) compared with non-IBD participants. The association with incident substance misuse was only among patients with Crohn's disease (CD, 1.47 [1.23-1.76]), but not ulcerative colitis (UC, 1.01 [0.84-1.21]). Mediation analysis revealed 16, 14, 15, and 6 biomarkers partially mediated the associations for all psychiatric disorders, substance misuse, depression, and anxiety, respectively. Six blood markers showed the strongest mediating effects: neutrophil count (12.04%), C-reactive protein (10.29%), systemic immune-inflammatory index (8.94%), erythrocyte distribution width (16.51%), erythrocyte count (9.76%), and albumin (9.15%). Moreover, several blood mediators of CD identified in association with incident substance misuse may explain the risk discrepancy between IBD subtype. CONCLUSION: The blood biomarkers of inflammation, blood oxygen-carrying capacity, and metabolism mediate the effect of IBD on the risk of psychiatric outcomes and could be considered as a therapeutic target.

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