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1.
J Hazard Mater ; 477: 135380, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39088944

ABSTRACT

The enzymatic degradation of plastic offers a green, sustainable strategy and scalable circular carbon route for solving polyester waste. Among the earlies discovered plastic-degrading enzymes are PET hydrolase (PETase) and MHET hydrolase (MHETase), which act synergistically. To promote the adsorption of enzymes on PET surfaces, increase their robustness, and enable directly depolymerization, we designed hydrophobin HFBI fused-PETase and MHETase. A customized self-assembled synergistic biocatalyst (MC@CaZn-MOF) was further developed to promote the two-step depolymerization process. The tailored catalysts showed better adhesion to the PET surface and desirable durability, retaining over 70% relative activity after incubation at pH 8.0 and 60 °C for 120 h. Importantly, MC@CaZn-MOF could directly decompose untreated AGf-PET to generate 9.5 mM TPA with weight loss over 90%. The successful implementation of a bifunctional customized catalyst makes the large-scale biocatalytic degradation of PET feasible, contributing to polymer upcycling and environmental sustainability.

2.
Skin Res Technol ; 30(8): e13895, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39096181

ABSTRACT

BACKGROUND: Bromhidrosis, characterized by foul-smelling sweat, is a prevalent condition that significantly affects patients' social and psychological well-being. METHODS: This review presents novel treatment approaches and discusses the pros and cons of various treatment options for axillary bromhidrosis. RESULTS: Extensive research has explored numerous treatment modalities for bromhidrosis. This article systematically reviews both surgical and nonsurgical interventions utilized in clinical practice. CONCLUSION: By synthesizing available evidence, this review aims to offer evidence-based recommendations for effectively managing bromhidrosis, considering factors such as treatment efficacy, safety profiles, patient preferences, and clinical outcomes.


Subject(s)
Axilla , Humans , Hyperhidrosis/therapy , Treatment Outcome , Sweat Gland Diseases/therapy , Sweat Gland Diseases/physiopathology , Odorants
3.
Clin Biomech (Bristol, Avon) ; 118: 106316, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39059102

ABSTRACT

BACKGROUND: Falls are a serious health threat for people with Parkinson's disease. Dynamic gait stability has been associated with fall risk. Developing effective fall prevention interventions requires a sound understanding of how Parkinson's disease affects dynamic gait stability. This study compared dynamic gait stability within the Feasible Stability Region framework between people with and without Parkinson's disease during level walking at a self-selected speed. METHODS: Twenty adults with Parkinson's disease and twenty age- and gender-matched healthy individuals were recruited. Dynamic gait stability at two gait instants: touchdown and liftoff, was assessed as the primary outcome measurement. Spatiotemporal gait parameters, including stance phase duration, step length, gait speed, and cadence were determined as explanatory variables. FINDINGS: People with Parkinson's disease walked more slowly (p < 0.001) with a shorter step (p = 0.05), and prolonged stance phase (p = 0.04) than their healthy peers with moderate to large effect sizes. Dynamic gait stability did not show any group-associated differences (p > 0.36). INTERPRETATION: Despite the different gait parameters between groups, people with Parkinson's disease exhibited similar dynamic gait stability to their healthy counterparts. To compensate for the potential dynamic gait stability deficit resulting from slow gait speed, individuals with Parkinson's disease adopted a short step length to shift the center of mass motion state closer to the Feasible Stability Region. Our findings could provide insight into the impact of Parkinson's disease on the control of dynamic gait stability.

4.
J Am Chem Soc ; 146(29): 20193-20204, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39004825

ABSTRACT

High-entropy intermetallic (HEI) nanocrystals, composed of multiple elements with an ordered structure, are of immense interest in heterogeneous catalysis due to their unique geometric and electronic structures and the cocktail effect. Despite tremendous efforts dedicated to regulating the metal composition and structures with advanced synthetic methodologies to improve the performance, the surface structure, and local chemical order of HEI and their correlation with activity at the atomic level remain obscure yet challenging. Herein, by determining the three-dimensional (3D) atomic structure of quinary PdFeCoNiCu (PdM) HEI using atomic-resolution electron tomography, we reveal that the local chemical order of HEI regulates the surface electronic structures, which further mediates the alkyl-substitution-dependent alkyne semihydrogenation. The 3D structures of HEI PdM nanocrystals feature an ordered (intermetallic) core enclosed by a disordered (solid-solution) shell rather than an ordered surface. The lattice mismatch between the core and shell results in apparent near-surface distortion. The chemical order of the intermetallic core increases with annealing temperature, driving the electron redistribution between Pd and M at the surface, but the surface geometrical (chemically disordered) configurations and compositions are essentially unchanged. We investigate the catalytic performance of HEI PdM with different local chemical orders toward semihydrogenation across a broad range of alkynes, finding that the electron density of surface Pd and the hindrance effect of alkyl substitutions on alkynes are two key factors regulating selective semihydrogenation. We anticipate that these findings on surface atomic structure will clarify the controversy regarding the geometric and/or electronic effects of HEI catalysts and inspire future studies on tuning local chemical order and surface engineering toward enhanced catalysts.

5.
BMC Public Health ; 24(1): 1989, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054517

ABSTRACT

BACKGROUND: Psychological resilience has been associated with increased longevity in the oldest old; however, its significance in the broader older adult population has not been thoroughly explored. There is a lack of understanding regarding its relationship with cause-specific mortality in older adults. This study aims to address these gaps by investigating the association between psychological resilience and both overall mortality and cause-specific mortality in individuals aged 65 and older. METHODS: We enrolled 4,935 participants aged 65 and older in the Chinese Longitudinal Healthy Longevity Survey, with baseline assessments conducted in 2014 and follow-up surveys in 2018. To evaluate the associations between psychological resilience and mortality, we used Cox proportional hazards models. Additionally, we employed restricted cubic spline plots to illustrate the dose-response relationships between these variables. RESULTS: During a mean (Standard Deviation) follow-up of 3.2 years (1.2), 1726 participants died. Higher psychological resilience was independently associated with lower all-cause mortality risk (Hazard ratio [HR] 0.74, 95% confidence interval [CI]: 0.67-0.82) and cause-specific mortality from cardiovascular disease (HR 0.74, 95% CI: 0.59-0.93), respiratory diseases (HR 0.63, 95% CI:0.45-0.87), and other causes (HR 0.69, 95% CI: 0.60-0.78), excluding cancer-related mortality. Similar effects were evident when examining the psychological resilience score. The dose-response analysis further indicated a gradual decrease in mortality risk corresponding to higher psychological resilience scores. Interaction analyses revealed that psychological resilience has a more pronounced effect on mortality from other causes among economically independent older adults (P-interaction = 0.02). CONCLUSIONS: Enhanced psychological resilience is independently associated with reduced all-cause and some cause-specific mortality in older adults. These findings underscore the importance of addressing psychological factors in the promotion of healthy aging and longevity.


Subject(s)
Cause of Death , Resilience, Psychological , Humans , Male , Aged , Female , Longitudinal Studies , Aged, 80 and over , China/epidemiology , Proportional Hazards Models , Mortality/trends , Cohort Studies
6.
Cancer Med ; 13(14): e70018, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39045904

ABSTRACT

BACKGROUND: The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. METHODS: Stage II non-small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier analysis with log-rank testing compared overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)-based Cox analyses identified prognostic factors. RESULTS: Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO-based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). CONCLUSIONS: The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplasm Staging , SEER Program , White People , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Male , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Female , Aged , Middle Aged , Lymphatic Metastasis , Prognosis , Kaplan-Meier Estimate , Propensity Score
7.
Environ Pollut ; 358: 124486, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972563

ABSTRACT

Chlorinated volatile organic compounds (Cl-VOCs) have dramatically biotoxicity and environmental persistence due to the presence of chlorine atoms, seriously jeopardizing ecological security and human health. Dichloromethane (DCM) as a model pollutant, is widely applied in solvents, extractants and cleaning agents in the pharmaceutical, chemical and food industries. In this study, highly biocompatible and conductive carbon cloth-titanium nitride-polyaniline (CC-TiN-PANI) bioelectrodes were obtained for DCM degradation in microbial electrolysis cell (MEC). The good adhesion of TiN and PANI on the electrode surface was demonstrated. The degradation kinetics were fitted by the Haldane model, compared to the CC bioelectrode (0.8 h-1), the proportion of maximum degradation rates to half-saturation concentration (Vmax/Km) of CC-TiN (1.4 h-1) and CC-TiN-PANI (2.2 h-1) bioelectrodes were enhanced by 1.8 and 2.8 times, respectively. Microbial community structure analysis illuminated that the dominant genera on the biofilm were Alicycliphilus and Hyphomicrobium, and the abundance was enhanced significantly with the modification of TiN and PANI. The dechlorination of DCM to formaldehyde could be catalyzed by DCM dehalogenase (DcmA) or by haloalkane dehalogenase (DhlA). And further oxidized to formate: 1) direct catalyzed by formaldehyde dehydrogenase (FdhA); 2) conjugated with glutathione by S-(hydroxymethyl)-glutathione synthase (Gfa), S-(hydroxymethyl)-glutathione dehydrogenase (FrmA) and S-formyl-glutathione hydrolase (FrmB); 3) conjugation with tetrahydrofolate (H4F) and/or tetrahydromethanopterin.

8.
Angew Chem Int Ed Engl ; : e202407658, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982589

ABSTRACT

Metallene is considered as an emerging family of electrocatalysts due to its atomically layered structure and unique surface stress. Here we propose a strategy to modulate the Bader charge transfer (BCT) between Pd surface and oxygenated intermediates via p-d electronic interaction by introducing single-atomp-block metal (M = In, Sn, Pb, Bi) into Pd metallene nanosheets towards efficient oxygen reduction reaction (ORR). X-ray absorption and photoelectron spectroscopy suggests that doping p-block metals could facilitate electron transfer to Pd sites and thus downshift the d-band center of Pd and weaken the adsorption energy of O intermediates. Among them, the developed Bi-Pd metallene shows extraordinarily high ORR mass activity of 11.34 A mgPd-1 and 0.86 A mgPd-1 at 0.9 V and 0.95 V in alkaline solution, respectively, representing the best Pd-based ORR electrocatalysts ever reported. In the cathode of a Zinc-air battery, Bi-Pd metallene could achieve an open-circuit voltage of 1.546 V and keep stable for 760 h at 10 mA cm-2. Theoretical calculations suggest that the BCT between Pd surface and *OO intermediates greatly affects the bond length between them (dPd-*OO) and Bi doping could appropriately reduce the amount of BCT and stretch the dPd-*OO, thus enhancing the ORR activity.

9.
ESC Heart Fail ; 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39034632

ABSTRACT

AIMS: To assess the stage of acute kidney injury (AKI), as an index of organ perfusion, combined with shock severity, measured by the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification, to stratify the risk of mortality in patients diagnosed with cardiogenic shock (CS) and supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). METHODS ANS RESULTS: From January 2018 to December 2020, consecutive adult patients diagnosed with CS and received VA ECMO were retrospectively evaluated. The highest AKI stage within 48 h after ECMO initiation was assessed using the Kidney Disease: Improving Global Outcomes criteria. We included 216 patients with a mean age of 58.8 years and 31.0% were females. 88.4% of patients received ECMO for postcardiotomy, while 11.6% for medical CS. The total in-hospital mortality was 53.2%. AKI occurred in 182 (84.3%) patients receiving ECMO for CS. AKI stage 0, 1, 2, and 3 were present in 15.7%, 17.6%, 18.1%, and 48.6% of patients with in-hospital mortality of 26.5%, 26.3%, 61.5%, and 68.6%, respectively (P < 0.001). The AKI stage (P < 0.001), SCAI shock stage before ECMO (P = 0.008), and NYHA ≥ Class III on admission (P = 0.044) were independent predictors of in-hospital mortality. The area under the receiver operating characteristic curve of 0.754 (95% confidence interval: 0.690 to 0.811) for AKI stage combined with SCAI shock stage was better than those for AKI stage (0.676), SCAI shock stage (0.657), serum lactate level (0.682), SOFA score (0.644), SVAE score (0.582), and VIS score (0.530) prior to ECMO. CONCLUSIONS: In this single-center CS population who received VA ECMO for circulatory support, predominantly postcardiotomy cases, AKI occurred in 84.3% of the patients. AKI stage, as an index of organ perfusion combined with shock severity measured by the SCAI shock classification, demonstrates a good correlation with in-hospital mortality.

10.
Biomed Rep ; 21(2): 124, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39006508

ABSTRACT

Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.

11.
Nat Commun ; 15(1): 5628, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965215

ABSTRACT

The control of a molecule's geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.

12.
Heliyon ; 10(11): e32616, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961961

ABSTRACT

The study aimed to evaluate the impact of varying modulus of elasticity (MOE) values of dental implants on the deformation and von Mises stress distribution in implant systems and peri-implant bone tissues under dynamic cyclic loading. The implant-bone interface was characterised as frictional contact, and the initial stress was induced using the interference fit method to effectively develop a finite element model for an immediately loaded implant-supported denture. Using the Ansys Workbench 2021 R2 software, an analysis was conducted to examine the deformation and von Mises stress experienced by the implant-supported dentures, peri-implant bone tissue, and implants under dynamic loading across three simulated masticatory cycles. These findings were subsequently evaluated through a comparative analysis. The suprastructures showed varying degrees of maximum deformation across zirconia (Zr), titanium (Ti), low-MOE-Ti, and polyetheretherketone (PEEK) implant systems, registering values of 103.1 µm, 125.68 µm, 169.52 µm, and 844.06 µm, respectively. The Zr implant system demonstrated the lowest values for both maximum deformation and von Mises stress (14.96 µm, 86.71 MPa) in cortical bone. As the MOE increased, the maximum deformation in cancellous bone decreased. The PEEK implant system exhibited the highest maximum von Mises stress (59.12 MPa), whereas the Ti implant system exhibited the lowest stress (22.48 MPa). Elevating the MOE resulted in reductions in both maximum deformation and maximum von Mises stress experienced by the implant. Based on this research, adjusting the MOE of the implant emerged as a viable approach to effectively modify the biomechanical characteristics of the implant system. The Zr implant system demonstrated the least maximum von Mises stress and deformation, presenting a more favourable quality for preserving the stability of the implant-bone interface under immediate loading.

13.
Dev Neurosci ; : 1-15, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38955163

ABSTRACT

INTRODUCTION: Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation. METHODS: Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology. RESULTS: We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There was significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, the number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the Western blot analysis revealed decreased PSD-95 expression levels in the knockout mice compared to the wild type at P15. CONCLUSION: These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.

14.
Anal Methods ; 16(29): 4981-4994, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38973656

ABSTRACT

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

15.
Colloids Surf B Biointerfaces ; 242: 114079, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39029247

ABSTRACT

Water-in-water (W/W) Pickering emulsions, exhibit considerable potential in the food and pharmaceutical fields owing to their compartmentalization and high biocompatibility. However, constrained by the non-uniform distribution of shear forces during emulsification or the spatial obstruction in polydimethylsiloxane (PDMS) passive microfluidic platform, the existing methods cannot generate monodisperse W/W Pickering emulsions with high particle coverage rate, thereby limiting their applications. Herein, a novel microfluidic system is designed for the preparation of monodisperse and highly particle-covered W/W Pickering emulsions under mild conditions. pH-responsive Polyethylene glycol (PEG)/phosphate aqueous two-phase system (ATPS) is used for the emulsions' preparation. Notably, a coverage rate of 96 ± 3 % is obtained by adjusting the length of the helical coiled tube, as well as the size and contact angle of genipin cross-linked BSA (BSA-GP) particles. Moreover, these W/W Pickering emulsions, with surfaces almost completely covered, can maintain monodisperse (Ncoal = 1.18 ± 0.03) for one day. Furthermore, the results of ranitidine hydrochloride (RH) release demonstrated that the drug release rate of W/W Pickering emulsions in the simulated gastric fluid (SGF) was 10 times faster than that in the neutral solution. We believe that the highly particle-covered monodisperse W/W Pickering emulsions possess great potential applications in bioencapsulation for foods and drug delivery.

16.
Molecules ; 29(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39064954

ABSTRACT

Chiral molecules have similar physicochemical properties, which are different in terms of physiological activities and toxicities, rendering their differentiation and recognition highly significant. Nanozymes, which are nanomaterials with inherent enzyme-like activities, have garnered significant interest owing to their high cost-effectiveness, enhanced stability, and straightforward synthesis. However, constructing nanozymes with high activity and enantioselectivity remains a significant challenge. This review briefly introduces the synthesis methods of chiral nanozymes and systematically summarizes the latest research progress in enantioselective recognition of chiral molecules based on electrochemical methods and ultraviolet-visible absorption spectroscopy. Moreover, the challenges and development trends in developing enantioselective nanozymes are discussed. It is expected that this review will provide new ideas for the design of multifunctional chiral nanozymes and broaden the application field of nanozymes.


Subject(s)
Electrochemical Techniques , Nanostructures , Spectrophotometry, Ultraviolet , Stereoisomerism , Nanostructures/chemistry
17.
Front Cell Infect Microbiol ; 14: 1397724, 2024.
Article in English | MEDLINE | ID: mdl-38966251

ABSTRACT

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.


Subject(s)
Aneuploidy , Antifungal Agents , Brefeldin A , Cryptococcus neoformans , Drug Resistance, Fungal , Cryptococcus neoformans/drug effects , Cryptococcus neoformans/genetics , Brefeldin A/pharmacology , Antifungal Agents/pharmacology , Drug Resistance, Fungal/genetics , Fluconazole/pharmacology , Amphotericin B/pharmacology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Microbial Sensitivity Tests , Flucytosine/pharmacology , Humans , Endoplasmic Reticulum Stress/drug effects
18.
Aging Med (Milton) ; 7(3): 350-359, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975311

ABSTRACT

Objective: The objective of the present study was to explore the correlation between the advanced lung cancer inflammation index (ALI) and in-hospital mortality among patients diagnosed with community-acquired pneumonia (CAP). Methods: Data from the Medical Information Mart for Intensive Care-IV database were adopted to analyze the in-hospital mortality of ICU patients with CAP. Upon admission to the ICU, fundamental data including vital signs, critical illness scores, comorbidities, and laboratory results, were collected. The in-hospital mortality of all CAP patients was documented. Multivariate logistic regression (MLR) models and restricted cubic spline (RCS) analysis together with subgroup analyses were conducted. Results: This study includes 311 CAP individuals, involving 218 survivors as well as 93 nonsurvivors. The participants had an average age of 63.57 years, and the females accounted for approximately 45.33%. The in-hospital mortality was documented to be 29.90%. MLR analysis found that ALI was identified as an independent predictor for in-hospital mortality among patients with CAP solely in the Q1 group with ALI ≤ 39.38 (HR: 2.227, 95% CI: 1.026-4.831, P = 0.043). RCS analysis showed a nonlinear relationship between the ALI and in-hospital mortality, with a turning point at 81, and on the left side of the inflection point, a negative correlation was observed between ALI and in-hospital mortality (HR: 0.984, 95% CI: 0.975-0.994, P = 0.002). The subgroup with high blood pressure showed significant interaction with the ALI. Conclusion: The present study demonstrated a nonlinear correlation of the ALI with in-hospital mortality among individuals with CAP. Additional confirmation of these findings requires conducting larger prospective investigations.

20.
Sci Rep ; 14(1): 17410, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075197

ABSTRACT

Improving the green electricity efficiency (GEE), is an important issue for China's high-quality economic development. This study presents a spatial correlation network of urban GEE in the Yellow River Basin from 2012 to 2021, constructed using an improved gravity model. Social network analysis and the quadratic assignment procedure method are employed to analyze the spatial correlation characteristics and influencing factors. The findings indicate that urban GEE in the Yellow River Basin exhibits complex and stable network characteristics. The spatial network analysis reveals that Jiayuguan City, Dongying City, Dingxi City, Zibo City, and Shizuishan City occupy central positions within the network. The results indicate that spatial adjacency, GDP per capita, industrial structure, and the level of science and technology expenditure are positively related to urban GEE, while environmental regulation and average temperature are negatively related. The findings of the study have led to policy recommendations aimed at enhancing urban GEE in the Yellow River Basin.

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