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1.
J Med Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946306

ABSTRACT

GPR84 is a promising therapeutic target and biomarker for a range of diseases. In this study, we reported the discovery of BINOL phosphate (BINOP) derivatives as GPR84 antagonists. By investigating the structure-activity relationship, we identified 15S as a novel GPR84 antagonist. 15S exhibits low nanomolar potency and high selectivity for GPR84, while its enantiomer 15R is less active. Next, we rationally designed and synthesized a series of GPR84 fluorogenic probes by conjugating Nile red and compound 15S. The leading hybrid, probe F8, not only retained GPR84 activity but also exhibited low nonspecific binding and a turn-on fluorescent signal in an apolar environment. F8 enabled visualization and detection of GPR84 in GPR84-overexpressing HEK293 cells and lipopolysaccharide-stimulated neutrophils. Furthermore, we demonstrated that F8 can detect upregulated GPR84 protein levels in mice models of inflammatory bowel disease and acute lung injury. Thus, compound F8 represents a promising tool for studying GPR84 functions.

2.
Talanta ; 278: 126506, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38968659

ABSTRACT

Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.

3.
Front Neurol ; 15: 1419372, 2024.
Article in English | MEDLINE | ID: mdl-38948136

ABSTRACT

Background: Vestibular migraine (VM), an intricate subtype of migraine, amalgamates the dual attributes of migraine and vestibular disorders. In clinical settings, individuals with VM frequently articulate concerns regarding the manifestation of subjective cognitive impairment. This cognitive dysfunction is intricately linked with diminished mobility, heightened susceptibility to falls, and increased absenteeism in afflicted patients. Consequently, comprehending the features of cognitive impairment in VM patients holds potential clinical significance. The pursuit of rapid and objective methods for detection and assessment is foundational and prerequisite for efficacious cognitive management of VM patients. Methods: The study encompassed 50 patients diagnosed with vestibular migraine and recruited 50 age-sex matched healthy controls. All participants underwent anti-saccade tasks, and cognitive evaluation was performed using the MMSE and MoCA to assess overall cognitive function. Additionally, RBANS scales were employed to measure specific cognitive domains. Results: The VM patients and normal controls demonstrated statistical parity in terms of age, gender, education, weight, and BMI, with no significant differences observed. Analysis of cognitive scores divulged a marked increase in the incidence of Mild Cognitive Impairment (MCI) in VM patients compared to Healthy Controls (HCs). Both MMSE and MoCA scores were notably lower in VM patients compared to their healthy counterparts. The RBANS cognitive test indicated significant impairment in immediate memory, visuospatial construction, language, attention, and delayed memory among VM patients. Notably, the Trail Making Test and Stroop Color-Word Test revealed compromised processing speed and executive function cognitive domains. The anti-saccadic task highlighted significantly elevated anti-saccadic latency and frequency of direction errors in vestibular migraine patients. Symptom severity, illness duration, and episode frequency in VM patients positively correlated with counter-scanning errors and negatively correlated with cognitive performance across diverse cognitive domains. Conclusion: VM patients exhibit cognitive decline across multiple cognitive domains during the interictal period. This cognitive impairment may not be fully reversible, underscoring its potential clinical significance for cognitive management in VM patients. The sensitivity of anti-saccade tasks to the cognitive status of VM patients positions them as promising objective indicators for diagnosis, intervention, and evaluation of cognitive impairment effects in VM in future applications.

4.
Nat Mater ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867019

ABSTRACT

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic-electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm-2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.

5.
J Org Chem ; 89(13): 9381-9388, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38885147

ABSTRACT

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

6.
Mol Biotechnol ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825608

ABSTRACT

Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.

7.
Plast Reconstr Surg Glob Open ; 12(6): e5801, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38841523

ABSTRACT

Background: We aimed to track the global trend of cosmetic treatment outcomes for facial rejuvenation and the differences in modalities used in East Asian and Western populations. Methods: Articles reporting on facial rejuvenation procedures (invasive/noninvasive) were identified in PubMed from 2013 to March 2023 and bibliometrically analyzed for type of published document, citation frequency, authors with most articles, author's affiliation, and frequency distribution of keywords. Results: From 553 articles, most were published in 2021 (n = 86, 15.6%). Western countries (n = 323, 58.4%) contributed more than East Asian (n = 230, 41.6%), with more invasive interventions (n = 355, 64.2%) than noninvasive techniques (n = 198, 35.8%). Numbers of invasive techniques in West versus East Asian countries were 225 (40.7%) versus 135 (24.4%). Main indications were the reduction of facial wrinkles and antiageing treatments. Hyaluronic acid, fillers, and botulinum toxin were the main hotspots for invasive treatments, whereas laser, platelet-rich plasma, and radiofrequency were for noninvasive treatments. Nasolabial folds (13.4%) and glabellar lines (12.4%) were the top research hotspots in the East Asian and Western regions. Common adverse events were pain, erythema, swelling, and bruising. Approximately, 89.3% of publications were from single countries, whereas 10.7% of publications were from international collaborations. Most articles (n = 387; 69.95%) presented their findings using level II evidence. Dermatological surgery (IF = 2.914) had the greatest number of publications (n = 109; 19.71%). Conclusions: The main hotspots were antiaging and youthfulness. This study provides a trend and a new perspective on the future research directions in the field of facial rejuvenation.

8.
Sensors (Basel) ; 24(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38894322

ABSTRACT

In the development of meteorological detection technology and services, weather radar undoubtedly plays a pivotal role, especially in the monitoring and early warning of severe convective weather events, where it serves an irreplaceable function. This research delves into the landscape of weather radar research from 1945 to 2024, employing scientometric methods to investigate 13,981 publications from the Web of Science (WoS) core collection database. This study aims to unravel, for the first time, the foundational structures shaping the knowledge domain of weather radar over an 80-year period, exploring general features, collaboration, co-citation, and keyword co-occurrence. Key findings reveal a significant surge in both publications and citations post-1990, peaking in 2022 with 1083 publications and 13832 citations, signaling sustained growth and interest in the field after a period of stagnation. The United States, China, and European countries emerge as key drivers of weather radar research, with robust international collaboration playing a pivotal role in the field's rapid evolution. Analysis uncovers 30 distinct co-citation clusters, showcasing the progression of weather radar knowledge structures. Notably, deep learning emerges as a dynamic cluster, garnering attention and yielding substantial outcomes in contemporary research efforts. Over eight decades, the focus of weather radar investigations has transitioned from hardware and software enhancements to Artificial Intelligence (AI) technology integration and multifunctional applications across diverse scenarios. This study identifies four key areas for future research: leveraging AI technology, advancing all-weather observation techniques, enhancing system refinement, and fostering networked collaborative observation technologies. This research endeavors to support academics by offering an in-depth comprehension of the progression of weather radar research. The findings can be a valuable resource for scholars in efficiently locating pertinent publications and journals. Furthermore, policymakers can rely on the insights gleaned from this study as a well-organized reference point.

9.
Aging Cell ; : e14256, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898632

ABSTRACT

Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial ß-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis.

10.
Int J Mol Sci ; 25(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892125

ABSTRACT

A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose-response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals' behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied-the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)-responds significantly (p < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals' behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area's role in response to the drug.


Subject(s)
Behavior, Animal , Caudate Nucleus , Methylphenidate , Neurons , Nucleus Accumbens , Prefrontal Cortex , Ventral Tegmental Area , Animals , Methylphenidate/pharmacology , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiology , Rats , Neurons/drug effects , Neurons/physiology , Neurons/metabolism , Caudate Nucleus/drug effects , Caudate Nucleus/physiology , Caudate Nucleus/metabolism , Male , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/physiology , Nucleus Accumbens/drug effects , Nucleus Accumbens/physiology , Behavior, Animal/drug effects , Locus Coeruleus/drug effects , Locus Coeruleus/physiology , Rats, Sprague-Dawley , Dorsal Raphe Nucleus/drug effects , Dorsal Raphe Nucleus/physiology , Dorsal Raphe Nucleus/metabolism , Central Nervous System Stimulants/pharmacology
11.
Ecol Evol ; 14(6): e11469, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38826172

ABSTRACT

In recent years, the continuous expansion of Spartina alterniflora (S. alterniflora) has caused serious damage to coastal wetland ecosystem. Mapping the coverage of S. alterniflora by remote sensing and analyzing its growth pattern pose great importance in controlling the expansion and maintaining the biodiversity of coastal wetlands in Guangxi. This study aimed to use harmonic regression to fit time series data of vegetation indices based on Landsat images, and the phenological features were extracted as the input of random forest model to distinguish S. alterniflora in coastal zone of Guangxi from 2009 to 2020. The influence of natural environmental factors on the distribution of S. alterniflora was evaluated by Maxent model, and the potential distribution was analyzed. The results showed that: (1) Based on the time series data of characteristic indices fitted by harmonic regression, the extraction of phenological features of S. alterniflora identification effect exhibited high accuracy (in the result of 2009, Overall Accuracy [OA] = 97.33%, Kappa = 0.95). (2) During 2009-2020, the S. alterniflora in coastal zone of Guangxi kept proliferating and expanding from east to west. The total area of S. alterniflora continued to increase while the growth rate showed a trend that increased first and then decreased. (3) The Maxent model shows good accuracy in simulating the habitat of S. alterniflora, with a potential distribution area of 14,303.39 hm2. The findings will be beneficial to the understanding of dynamic changes of S. alterniflora in coastal zone of Guangxi and provide a scientific reference for other coastal wetland studies on S. alterniflora expansion.

12.
Nat Commun ; 15(1): 4743, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834672

ABSTRACT

Recent theoretical studies have suggested that transition metal perovskite oxide membranes can enable surface phonon polaritons in the infrared range with low loss and much stronger subwavelength confinement than bulk crystals. Such modes, however, have not been experimentally observed so far. Here, using a combination of far-field Fourier-transform infrared (FTIR) spectroscopy and near-field synchrotron infrared nanospectroscopy (SINS) imaging, we study the phonon polaritons in a 100 nm thick freestanding crystalline membrane of SrTiO3 transferred on metallic and dielectric substrates. We observe a symmetric-antisymmetric mode splitting giving rise to epsilon-near-zero and Berreman modes as well as highly confined (by a factor of 10) propagating phonon polaritons, both of which result from the deep-subwavelength thickness of the membranes. Theoretical modeling based on the analytical finite-dipole model and numerical finite-difference methods fully corroborate the experimental results. Our work reveals the potential of oxide membranes as a promising platform for infrared photonics and polaritonics.

13.
Therap Adv Gastroenterol ; 17: 17562848241251567, 2024.
Article in English | MEDLINE | ID: mdl-38903448

ABSTRACT

Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053).


A review and network meta-analysis of different medications for treating erosive esophagitis: potassium-competitive acid blockers and proton-pump inhibitors Why was the study done? Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are commonly used to treat Erosive esophagitis (EE) due to their good safety and tolerance. This study aimed to compare the effectiveness of P-CABs and PPIs in healing EE patients. We wanted to determine the best treatment choice in terms of the duration of treatment (4 or 8 weeks) and the dosage (standard or double-dose). What did the researchers do? The researchers searched relevant databases for randomized controlled trials that studied the use of PPIs and P-CABs in treating EE up until May 31, 2023. They included studies that evaluated the healing effects of standard or double-dose PPIs or P-CABs over a period of 4 or 8 weeks. A network meta-analysis was performed to compare the effectiveness of these treatments. They also conducted sensitivity analysis and subgroup analysis to examine the effects on patients with different levels of EE. What did the researchers find? The results showed that the healing rate after 4 weeks of treatment was significantly lower than the healing rate after 8 weeks for most treatments. Additionally, the higher healing rate observed with double-dose treatment compared to standard-dose treatment was not seen in the initial treatment of most drugs. In the main analysis, which included studies with patients both with and without severe EE at the beginning, Keverprazan 20mg qd was ranked as the most effective treatment with a healing rate of 84.7, followed by Ilaprazole 10mg qd with a healing rate of 82.0 at 8 weeks. The results were robust in sensitivity analysis. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, especially for patients with severe EE. What do the findings mean? Treating EE patients for 8 weeks was more effective than treating them for 4 weeks. Keverprazan (20mg once a day) with the 8-week treatment is the optimal method.

14.
Acta Pharmacol Sin ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871922

ABSTRACT

Oligodendrocytes (OLs) are differentiated from oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). Demyelination is a common feature of many neurological diseases such as multiple sclerosis (MS) and leukodystrophies. Although spontaneous remyelination can happen after myelin injury, nevertheless, it is often insufficient and may lead to aggravated neurodegeneration and neurological disabilities. Our previous study has discovered that MEK/ERK pathway negatively regulates OPC-to-OL differentiation and remyelination in mouse models. To facilitate possible clinical evaluation, here we investigate several MEK inhibitors which have been approved by FDA for cancer therapies in both mouse and human OPC-to-OL differentiation systems. Trametinib, the first FDA approved MEK inhibitor, displays the best effect in stimulating OL generation in vitro among the four MEK inhibitors examined. Trametinib also significantly enhances remyelination in both MOG-induced EAE model and LPC-induced focal demyelination model. More exciting, trametinib facilitates the generation of MBP+ OLs from human embryonic stem cells (ESCs)-derived OPCs. Mechanism study indicates that trametinib promotes OL generation by reducing E2F1 nuclear translocation and subsequent transcriptional activity. In summary, our studies indicate a similar inhibitory role of MEK/ERK in human and mouse OL generation. Targeting the MEK/ERK pathway might help to develop new therapies or repurpose existing drugs for demyelinating diseases.

15.
Nat Commun ; 15(1): 5014, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866774

ABSTRACT

Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.


Subject(s)
CRISPR-Cas Systems , INDEL Mutation , Leukemia, Myeloid, Acute , Nucleophosmin , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/diagnosis , Neoplasm, Residual/genetics , Neoplasm, Residual/diagnosis , Nuclear Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Genetic Testing/methods , ErbB Receptors/genetics , Bacterial Proteins , Endodeoxyribonucleases , CRISPR-Associated Proteins
16.
Chemosphere ; : 142674, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908443

ABSTRACT

Triclocarban (TCC), an emerging contaminant in water environments, its effects on freshwater biofilms remain insufficiently understood. This study investigates the effects of TCC exposure (at concentrations of 10 µg L-1 and 10 mg L-1) on mature freshwater biofilms. TCC was found to inhibit biofilm activity as evidenced by changes in surface morphology and the ratio of live/dead cells. Moreover, both concentrations of TCC were observed to modify the structure of the biofilm community. Metabolomics analysis revealed an overlap in the toxicity mechanisms and detoxification strategies triggered by various concentrations of TCC in biofilms. However, the higher toxicity induced by 10 mg L-1 TCC resulted from the downregulation of proline betaine, disrupting the homeostasis of cellular osmotic pressure regulation in biofilms. Notably, lipid and lipid-like molecules showed high sensitivity to different concentrations of TCC, indicating their potential as biomarkers for TCC exposure. Annotation of the differential metabolites by KEGG revealed that alterations in amino acid and carbon metabolism constituted the primary response mechanisms of biofilms to TCC. Moreover, the biofilm demonstrated enhanced nucleic acid metabolism, which bolstered resistance against TCC stress and heightened tolerance. Furthermore, elevated TCC concentrations prompted more robust detoxification processes for self-defense. Overall, short-term exposure to TCC induced acute toxicity in biofilms, yet they managed to regulate their community structure and metabolic levels to uphold oxidative homeostasis and activity. This research contributes to a deeper comprehension of TCC risk assessment and policy control in aquatic environments.

17.
Funct Plant Biol ; 512024 Jun.
Article in English | MEDLINE | ID: mdl-38902904

ABSTRACT

Potassium (K) is essential for the development of grapevines (Vitis vinifera ), accumulating into berries during maturation. Elevated K has been associated with high sugar and low acidity in juice. Characterising the accumulation patterns of K and other components in pericarps treated with various experimental factors may indicate potential regulators of berry K levels. A soil fertiliser trial using nutrient solutions with two K supply rates was conducted on potted Shiraz vines during berry ripening. Doubled-K supply increased L-malic acid content in the early-ripening phase, and increased K and magnesium concentrations in the late-ripening phase. Doubled-K supply reduced the ratio of K to sodium in later ripening phases, suggesting that the accumulation of K relative to sodium was limited in more mature berries supplied with extra K. Pericarp water percentage, sugar, K and ATP were correlated in both treatments, indicating links between hydration, solute transport and energy in maturing berries. In a separate rootstock trial over the two growing seasons, Shiraz scions grafted onto 420-A rootstock produced berries with lower K concentration and content than those grafted onto Ramsey or Ruggeri-140 rootstocks and own-rooted vines. This study demonstrated that the K supply and berry ripening phase impacted the berry K level.


Subject(s)
Fruit , Plant Roots , Potassium , Vitis , Water , Potassium/metabolism , Fruit/metabolism , Fruit/growth & development , Vitis/growth & development , Vitis/metabolism , Water/metabolism , Plant Roots/metabolism , Plant Roots/growth & development , Sodium/metabolism
19.
Environ Sci Technol ; 58(26): 11637-11648, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38822815

ABSTRACT

Lithium (Li) is an important resource that drives sustainable mobility and renewable energy. Its demand is projected to continue to increase in the coming decades. However, the risk of Li pollution has also emerged as a global concern. Here, we investigated the pollution characteristics, sources, exposure levels, and associated health risks of Li in the Jinjiang River basin, the largest area for Li2CO3 production in China. Our results revealed the dominant role of Li extraction activities in the pollution of the river, with over 95% of dissolved Li in downstream river water being emitted from this source. Moreover, the Li concentration in aquatic plants (i.e., water hyacinth) and animals (i.e., fish) significantly increased from upstream to downstream areas, indicating a significant risk to local aquatic ecosystems. More importantly, our study found that local residents were suffering potential chronic noncarcinogenic health risks primarily from consuming contaminated water and vegetables. We also investigated the pollution characteristics of associated elements present in Li ores (e.g., Rb, Cs, Ni, and F-). By uncovering the remarkable impact of Li extraction activities on the Li content in ecosystems for the first time, our study emphasizes the importance of evaluating Li pollution from Li-related industrial activities, including mining, extraction, and recovery.


Subject(s)
Lithium , Lithium/analysis , China , Water Pollutants, Chemical/analysis , Humans , Rivers/chemistry , Risk Assessment , Environmental Monitoring , Animals
20.
Res Sq ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38798600

ABSTRACT

Glioblastoma is a highly aggressive brain tumor with poor prognosis despite surgery and chemoradiation. The visual sequelae of glioblastoma have not been well characterized. This study assessed visual outcomes in glioblastoma patients through neuro-ophthalmic exams, imaging of the retinal microstructures/microvasculature, and perimetry. A total of 19 patients (9 male, 10 female, average age at diagnosis 69 years) were enrolled. Best-corrected visual acuity ranged from 20/20-20/50. Occipital tumors showed worse visual fields than frontal tumors (mean deviation - 14.9 and - 0.23, respectively, p < 0.0001). Those with overall survival (OS) < 15 months demonstrated thinner retinal nerve fiber layer and ganglion cell complex (p < 0.0001) and enlarged foveal avascular zone starting from 4 months post-diagnosis (p = 0.006). There was no significant difference between eyes ipsilateral and contralateral to radiation fields (average doses were 1370 cGy and 1180 cGy, respectively, p = 0.42). A machine learning algorithm using retinal microstructure and visual fields predicted patients with long (≥ 15 months) progression free and overall survival with 78% accuracy. Glioblastoma patients frequently present with visual field defects despite normal visual acuity. Patients with poor survival duration demonstrated significant retinal thinning and decreased microvascular density. A machine learning algorithm predicted survival; further validation is warranted.

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