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1.
Food Chem ; 459: 140315, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38986203

ABSTRACT

Casein, the major allergen in cow's milk, presents a significant challenge in providing nutritional support for children with allergies. To address this issue, we investigated a composite enzyme, comprising papain and chymotrypsin, to reduce the allergenicity of casein. Enzymatic hydrolysis induced substantial structural changes in casein, diminishing its affinity for specific IgE and IgG antibodies. Additionally, in a BALB/c mouse model, casein hydrolysate alleviated allergic symptoms, evidenced by lower serum IgE and IgG levels, reduced plasma histamine, and decreased Th2 cytokine release during cell co-culture. Peptidomic analysis revealed a 52.38% and 60% reduction in peptides containing IgE epitopes in casein hydrolyzed by the composite enzyme compared to papain and chymotrypsin, respectively, along with a notable absence of previously reported T cell epitopes. These results demonstrate the potential of enzyme combinations to enhance the efficiency of epitope destruction in allergenic proteins, providing valuable insights into the development of hypoallergenic dairy products.

2.
Sci Total Environ ; 948: 174655, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004375

ABSTRACT

Microplastics (MPs) are widely present in terrestrial ecosystems. However, how MPs impact carbon (C) and nitrogen (N) cycling within plant-soil system is still poorly understood. Here, we conducted a meta-analysis utilizing 3338 paired observations from 180 publications to estimate the effects of MPs on plant growth (biomass, nitrogen content, nitrogen uptake and nitrogen use efficiency), change in soil C content (total carbon (TC), soil organic carbon (SOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC)), C losses (carbon dioxide (CO2) and methane), soil N content (total nitrogen, dissolved organic nitrogen, microbial biomass nitrogen, total dissolve nitrogen, ammonium, nitrate (NO3--N) and nitrite) and nitrogen losses (nitrous oxide, ammonia (NH3) volatilization and N leaching) comprehensively. Results showed that although MPs significantly increased CO2 emissions by 25.7 %, they also increased TC, SOC, MBC, DOC and CO2 by 53.3 %, 25.4 %, 19.6 % and 24.7 %, respectively, and thus increased soil carbon sink capacity. However, MPs significantly decreased NO3--N and NH3 volatilization by 14.7 % and 43.3 %, respectively. Meanwhile, MPs significantly decreased plant aboveground biomass, whereas no significant changes were detected in plant belowground biomass and plant N content. The impacts of MPs on soil C, N and plant growth varied depending on MP types, sizes, concentrations, and experimental durations, in part influenced by initial soil properties. Overall, although MPs enhanced soil carbon sink capacity, they may pose a significant threat to future agricultural productivity.

3.
Int J Mol Sci ; 25(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39063131

ABSTRACT

The OSGEP gene encodes O-sialoglycoprotein endopeptidase, a catalytic unit of the highly conserved KEOPS complex (Kinase, Endopeptidase, and Other Proteins of small Size) that regulates the second biosynthetic step in the formation of N-6-threonylcarbamoyladenosine (t6A). Mutations in KEOPS cause Galloway-Mowat syndrome (GAMOS), whose cellular function in mammals and underlying molecular mechanisms are not well understood. In this study, we utilized lentivirus-mediated OSGEP knockdown to generate OSGEP-deficient human embryonic stem cells (hESCs). OSGEP-knockdown hESCs exhibited reduced stemness factor expression and G2/M phase arrest, indicating a potential role of OSGEP in the regulation of hESC fate. Additionally, OSGEP silencing led to enhanced protein synthesis and increased aggregation of proteins, which further induced inappropriate autophagy, as evidenced by the altered expression of P62 and the conversion of LC3-I to LC3-II. The above findings shed light on the potential involvement of OSGEP in regulating pluripotency and differentiation in hESCs while simultaneously highlighting its crucial role in maintaining proteostasis and autophagy, which may have implications for human disease.


Subject(s)
Autophagy , Cell Differentiation , Human Embryonic Stem Cells , Proteostasis , Humans , Autophagy/genetics , Human Embryonic Stem Cells/metabolism , Cell Differentiation/genetics , Endopeptidases/metabolism , Endopeptidases/genetics , Gene Knockdown Techniques
4.
Toxicon ; 248: 108040, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038664

ABSTRACT

As a traditional tonic Chinese medicine, Polygonum multiflorum is widely used in clinical practice. However, with the deepening of modern pharmacological research, its drug toxicity, especially hepatotoxicity, has become increasingly prominent. Based on a large number of clinical and experimental evidence, it has been confirmed that Polygonum multiflorum and its main active ingredients such as anthraquinones and diphenylethylene glucoside can cause different degrees of hepatotoxicity. Further studies have shown that the toxicological mechanisms involved in the hepatotoxicity of different extracts and components of Polygonum multiflorum may include oxidative phosphorylation, bile acid excretion, different metabolic pathways, genetic and metabolic factors, immune homeostasis, etc. By sorting out and summarizing the literature related to hepatotoxicity of Polygonum multiflorum in recent years, this paper discussed the hepatotoxicity mechanism of Polygonum multiflorum and its main components and some contradictions in related reports.

5.
Front Public Health ; 12: 1343550, 2024.
Article in English | MEDLINE | ID: mdl-38883192

ABSTRACT

Introduction: The precise associations between temperature-related indices and mental and behavioral disorders (MBDs) have yet to be fully elucidated. Our study aims to ascertain the most effective temperature-related index and assess its immediate impact on emergency ambulance dispatches (EADs) due to MBDs in Shenzhen, China. Methods: EADs data and meteorological data from January 1, 2013, to December 31, 2020, in Shenzhen were collected. Distributed lag non-linear models (DLNMs) were utilized to examine the non-linear and lagged effects of temperature-related indices on EADs due to MBDs. The Quasi Akaike Information criterion (QAIC) was used to determine the optimal index after standardizing temperature-related indices. After adjusting for confounding factors in the model, we estimated the immediate and cumulative effects of temperature on EADs due to MBDs. Results: The analysis of short-term temperature effects on EADs due to MBDs revealed Humidex as the most suitable index. Referring to the optimal Humidex (3.2th percentile, 12.00°C), we observed a significant effect of Humidex over the threshold (34.6th percentile, 26.80°C) on EADs due to MBDs at lag 0-5. The cumulative relative risks for high temperature (90th percentile, 41.90°C) and extreme high temperature (99th percentile, 44.20°C) at lag 0-5 were 1.318 (95% CI: 1.159-1.499) and 1.338 (95% CI: 1.153-1.553), respectively. No significant cold effect was observed on EADs due to MBDs. Conclusion: High Humidex was associated with more EADs due to MBDs in subtropical regions. Health authorities should implement effective measures to raise public awareness of risks related to high temperature and protect vulnerable populations.


Subject(s)
Ambulances , Mental Disorders , Temperature , Humans , China , Ambulances/statistics & numerical data , Mental Disorders/epidemiology , Male , Female , Adult , Middle Aged , Emergency Medical Dispatch/statistics & numerical data
6.
RSC Adv ; 14(27): 19550-19559, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38895524

ABSTRACT

Monoclonal antibodies (mAbs) are pivotal therapeutic agents for various diseases, and effective treatment hinges on attaining a specific threshold concentration of mAbs in patients. With the rising adoption of combination therapy involving multiple mAbs, there arises a clinical demand for multiplexing assays capable of measuring the concentrations of these mAbs. However, minimizing the complexity of serum samples while achieving rapid and accurate quantification is difficult. In this work, we introduced a novel method termed nano-surface and molecular orientation limited (nSMOL) proteolysis for the fragment of antigen binding (Fab) region-selective proteolysis of co-administered trastuzumab and pertuzumab based on the pore size difference between the protease nanoparticles (∼200 nm) and the resin-captured antibody (∼100 nm). The hydrolyzed peptide fragments were then quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this process, the digestion time is shortened, and the produced digestive peptides are greatly reduced, thereby minimizing sample complexity and increasing detection accuracy. Assay linearity was confirmed within the ranges of 0.200-200 µg mL-1 for trastuzumab and 0.300-200 µg mL-1 for pertuzumab. The intra- and inter-day precision was within 9.52% and 8.32%, except for 12.5% and 10.8% for the lower limit of quantitation, and the accuracy (bias%) was within 6.3%. Additionally, other validation parameters were evaluated, and all the results met the acceptance criteria of the guiding principles. Our method demonstrated accuracy and selectivity for the simultaneous determination of trastuzumab and pertuzumab in clinical samples, addressing the limitation of ligand binding assays incapable of simultaneously quantifying mAbs targeting the same receptor. This proposed assay provides a promising technical approach for realizing clinical individualized precise treatment, especially for co-administered mAbs.

7.
Sci Total Environ ; 944: 173989, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-38879023

ABSTRACT

There is insufficient understanding of the spatio-temporal evolution of surface water-groundwater quality and hydraulic connection under both natural and human influences in urban river basins. To this end, this paper investigated the spatio-seasonal pattern of hydrochemical evolution and surface water-groundwater interaction in a typical urban river basin (Dahei River basin) based on isotopic and hydrochemical data of 132 water samples collected during three seasons (normal, wet and dry seasons). From the normal season to the wet season, surface water in the Dahei River basin was dominated by the impacts of evaporation and groundwater discharge processes. During this period, the precipitation and agricultural activities (canal irrigation) were frequent. Thus, groundwater was affected by irrigation infiltration of surface water and precipitation from high-altitude areas. From the wet season to the dry season, precipitation decreased and irrigation methods changed (canal irrigation → well irrigation). In this case, groundwater discharge had a stronger impact on surface water, and shallow groundwater was recharged by deep groundwater through the well irrigation. Under this hydrological pattern, the hydrochemical characteristics of surface water were mainly influenced by evaporation, human activities (agricultural irrigation and sewage treatment) and groundwater discharge. In contrast, the hydrochemical characteristics of groundwater were main influenced by water-rock interactions (dissolution of evaporites and silicates, and cation exchange) and human activities. This study contributed to a better understanding of the hydrochemical and hydrological processes in urban river basins and provided a theoretical basis for the sustainable management of water resources.

8.
Angew Chem Int Ed Engl ; : e202406043, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866704

ABSTRACT

Metal atom catalysts have been among the most important research objects due to their specific physical and chemical properties. However, precise control of the anchoring of metal atoms is still challenging to achieve. Cobalt and iridium atomic arrays formed sequentially ordered stable arrays in graphdiyne (GDY) triangular cavities depending on their intrinsic chemical properties and interactions. The success of this method was attributed to multifunctional integration of GDY, enabling selective growth from one to several atoms and various atomic densities. The bimetallic atom arrays show several advantages resulting from reducibility of acetylene bonds, space limiting effect, incomplete charge transfer between GDY and metal atoms, and sp-C hybridized triple bond skeleton. This well-designed system exhibits unprecedented oxygen evolution reaction (OER) performance with a mass activity of 2.6 A mgcat. -1 at a low overpotential of 300 mV, which is 216.6 times higher than the state-of-the-art IrO2 catalyst, and long-term stability.

9.
Biomater Sci ; 12(14): 3649-3658, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38857014

ABSTRACT

Despite cisplatin's pivotal role in clinically proven anticancer drugs, its application has been hampered by severe side effects and a grim prognosis. Herein, we devised a glutathione (GSH)-responsive nanoparticle (PFS-NP) that integrates a disulfide bond-based amphiphilic polyphenol (PP-SS-DA), a dopamine-modified cisplatin prodrug (Pt-OH) and iron ions (Fe3+) through coordination reactions between Fe3+ and phenols. After entering cells, the responsively released Pt-OH and disulfide bonds eliminate the intracellular GSH, in turn disrupting the redox homeostasis. Meanwhile, the activated cisplatin elevates the intracellular H2O2 level through cascade reactions. This is further utilized to produce highly toxic hydroxyl radicals (˙OH) catalyzed by the Fe3+-based Fenton reaction. Thus, the amplified oxidative stress leads to immunogenic cell death (ICD), promoting the maturation of dendritic cells (DCs) and ultimately activating the anti-tumor immune system. This innovative cisplatin prodrug nanoparticle approach offers a promising reference for minimizing side effects and optimizing the therapeutic effects of cisplatin-based drugs.


Subject(s)
Antineoplastic Agents , Cisplatin , Prodrugs , Cisplatin/pharmacology , Cisplatin/chemistry , Cisplatin/administration & dosage , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/administration & dosage , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Animals , Mice , Immunotherapy/methods , Nanoparticles/chemistry , Nanoparticles/administration & dosage , Dendritic Cells/drug effects , Glutathione/chemistry , Glutathione/metabolism , Cell Line, Tumor , Iron/chemistry , Drug Carriers/chemistry , Phenols/chemistry , Phenols/pharmacology , Phenols/administration & dosage
10.
Int J Biol Macromol ; 273(Pt 1): 132914, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38844290

ABSTRACT

Pinus taeda L. is a fast-growing softwood with significant commercial value. Understanding structural changes in hemicellulose during growth is essential to understanding the biosynthesis processes occurring in the cell walls of this tree. In this study, alkaline extraction is applied to isolate hemicellulose from Pinus taeda L. stem segments of different ages (1, 2, 3, and 4 years old). The results show that the extracted hemicellulose is mainly comprised of O-acetylgalactoglucomannan (GGM) and 4-O-methylglucuronoarabinoxylan (GAX), with the molecular weights and ratios (i.e., GGM:GAX) of GGM and GAX increasing alongside Pinus taeda L. age. Mature Pinus taeda L. hemicellulose is mainly composed of GGM, and the ratio of (mannose:glucose) in the GGM main chain gradually increases from 2.45 to 3.60 with growth, while the galactose substitution of GGM decreases gradually from 21.36% to 14.65%. The acetylation of GGM gradually increases from 0.33 to 0.45 with the acetyl groups mainly substituting into the O-3 position in the mannan. Furthermore, the contents of arabinose and glucuronic acid in GAX gradually decrease with growth. This study can provide useful information to the research in genetic breeding and high-value utilization of Pinus taeda L.


Subject(s)
Pinus taeda , Polysaccharides , Polysaccharides/metabolism , Polysaccharides/chemistry , Pinus taeda/metabolism , Pinus taeda/growth & development , Xylans/metabolism , Xylans/chemistry , Mannans/metabolism , Mannans/chemistry , Molecular Weight , Cell Wall/metabolism , Cell Wall/chemistry , Acetylation
11.
China CDC Wkly ; 6(23): 553-557, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38933663

ABSTRACT

Introduction: Traditional methods for determining radiation dose in nuclear medicine include the Monte Carlo method, the discrete ordinate method, and the point kernel integration method. This study presents a new mathematical model for predicting the radiation dose rate in the vicinity of nuclear medicine patients. Methods: A new algorithm was created by combining the physical model of "cylinder superposition" of the human body with integral analysis to assess the radiation dose rate in the vicinity of nuclear medicine patients. Results: The model accurately predicted radiation dose rates within distances of 0.1-3.0 m, with a deviation of less than 11% compared to observed rates. The model demonstrated greater accuracy at shorter distances from the radiation source, with a deviation of only 1.55% from observed values at 0.1 m. Discussion: The model proposed in this study effectively represents the spatial and temporal distribution of the radiation field around nuclear medicine patients and demonstrates good agreement with actual measurements. This model has the potential to serve as a radiation dose rate alert system in hospital environments.

12.
Neuroimage ; 294: 120640, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38719154

ABSTRACT

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.


Subject(s)
Attention , Electroencephalography , Habituation, Psychophysiologic , Prefrontal Cortex , Humans , Prefrontal Cortex/physiology , Prefrontal Cortex/diagnostic imaging , Attention/physiology , Male , Female , Electroencephalography/methods , Habituation, Psychophysiologic/physiology , Adult , Young Adult , Stroop Test
13.
Foodborne Pathog Dis ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695190

ABSTRACT

Trans-cinnamaldehyde (TC), a typical plant-derived compound, has been widely used in the control of foodborne pathogen contamination. Nevertheless, the risk associated with the occurrence of viable but nonculturable (VBNC) bacteria induced by TC remains unclear. The results of this study showed that Salmonella Enteritidis (S. Enteritidis) entered the VBNC state after being induced by TC at a minimum inhibitory concentration of 312.5 µg/mL and survived for at least 22 days under TC treatment. Enhanced resistance was found against heat treatment (75°C, 30 s), antibiotics (i.e., ampicillin, ceftriaxone sodium, chloramphenicol), and hydrogen peroxide (3%) in VBNC S. Enteritidis. A synergistic effect against VBNC S. Enteritidis occurred when TC was combined with acid treatment, including lactic acid and acetic acid (pH = 3.5). VBNC and resuscitated S. Enteritidis by sodium pyruvate treatment (100 mM) were found to retain the infectious ability to Caco-2 cells. Relative expression levels of the stress-related genes relA, spoT, ppx, lon, katG, sodA, dnaK, and grpE were upregulated in VBNC S. Enteritidis. Accumulation of reactive oxygen species (ROS) and protein aggregates was observed in VBNC cells. Besides, the resuscitation of VBNC cells was accompanied with clearance of ROS and protein aggregates. In summary, this study presents a comprehensive characterization of stress tolerance and resuscitation of VBNC S. Enteritidis induced by cinnamaldehyde, and the results provide useful information for the development of effective control strategy against VBNC pathogenic bacteria in food production.

14.
Protein Cell ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721690

ABSTRACT

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

15.
Cell Res ; 34(7): 504-521, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811766

ABSTRACT

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.


Subject(s)
Adenine Nucleotide Translocator 2 , Mitochondria , Mitochondrial Membranes , RNA, Double-Stranded , Animals , Adenine Nucleotide Translocator 2/metabolism , Adenine Nucleotide Translocator 2/genetics , Humans , RNA, Double-Stranded/metabolism , Mitochondria/metabolism , Mitochondrial Membranes/metabolism , Mice , Immunity, Innate , RNA Transport , HEK293 Cells , Mice, Inbred C57BL
16.
Materials (Basel) ; 17(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38730859

ABSTRACT

The wide size range and high tendency to agglomerate of in-situ TiB2 particles in reinforced Al matrix composites introduce great difficulties in their size characterization. In order to use a nanoparticle size analyzer (NSA) to obtain the precise size distribution of TiB2 particles, a controlled size characterization process has been explored. First, the extraction and drying processes for TiB2 particles were optimized. In the extraction process, alternated applications of magnetic stirring and normal ultrasound treatments were proven to accelerate the dissolution of the Al matrix in HCl solution. Furthermore, freeze-drying was found to minimize the agglomeration tendency among TiB2 particles, facilitating the acquisition of pure powders. Such powders were quantitatively made into an initial TiB2 suspension. Second, the chemical and physical dispersion technologies involved in initial TiB2 suspension were put into focus. Chemically, adding PEI (M.W. 10000) at a ratio of mPEI/mTiB2 = 1/30 into the initial suspension can greatly improve the degree of TiB2 dispersion. Physically, the optimum duration for high-energy ultrasound application to achieve TiB2 dispersion was 10 min. Overall, the corresponding underlying dispersion mechanisms were discussed in detail. With the combination of these chemical and physical dispersion specifications for TiB2 suspension, the bimodal size distribution of TiB2 was able to be characterized by NSA for the first time, and its number-average diameter was 111 ± 6 nm, which was reduced by 59.8% over the initial suspension. Indeed, the small-sized and large-sized peaks of the TiB2 particles characterized by NSA mostly match the results obtained from transmission electron microscopy and scanning electron microscopy, respectively.

17.
Psychon Bull Rev ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689187

ABSTRACT

Visual search is facilitated when targets are repeatedly encountered at a fixed position relative to an invariant distractor layout, compared to random distractor arrangements. However, standard investigations of this contextual-facilitation effect employ fixed distractor layouts that predict a constant target location, which does not always reflect real-world situations where the target location may vary relative to an invariant distractor arrangement. To explore the mechanisms involved in contextual learning, we employed a training-test procedure, introducing not only the standard full-repeated displays with fixed target-distractor locations but also distractor-repeated displays in which the distractor arrangement remained unchanged but the target locations varied. During the training phase, participants encountered three types of display: full-repeated, distractor-repeated, and random arrangements. The results revealed full-repeated displays to engender larger performance gains than distractor-repeated displays, relative to the random-display baseline. In the test phase, the gains were substantially reduced when full-repeated displays changed into distractor-repeated displays, while the transition from distractor-repeated to full-repeated displays failed to yield additional gains. We take this pattern to indicate that contextual learning can improve performance with both predictive and non-predictive (repeated) contexts, employing distinct mechanisms: contextual guidance and context suppression, respectively. We consider how these mechanisms might be implemented (neuro-)computationally.

18.
Front Oncol ; 14: 1323366, 2024.
Article in English | MEDLINE | ID: mdl-38665947

ABSTRACT

In 2020, bladder cancer, which commonly presents as urothelial carcinoma, became the 10th most common malignancy. For patients with metastatic urothelial carcinoma, the standard first-line treatment remains platinum-based chemotherapy, with immunotherapy serving as an alternative in cases of programmed death ligand 1 expression. However, treatment options become limited upon resistance to platinum and programmed death 1 or programmed death ligand 1 agents. Since the FDA's approval of Enfortumab Vedotin and Sacituzumab Govitecan, the therapeutic landscape has expanded, heralding a shift towards antibody-drug conjugates as potential first-line therapies. Our review employed a robust scientometric approach to assess 475 publications on antibody-drug conjugates in urothelial carcinoma, revealing a surge in related studies since 2018, predominantly led by U.S. institutions. Moreover, 89 clinical trials were examined, with 36 in Phase II and 13 in Phase III, exploring antibody-drug conjugates as both monotherapies and in combination with other agents. Promisingly, novel targets like HER-2 and EpCAM exhibit substantial therapeutic potential. These findings affirm the increasing significance of antibody-drug conjugates in urothelial carcinoma treatment, transitioning them from posterior-line to frontline therapies. Future research is poised to focus on new therapeutic targets, combination therapy optimization, treatment personalization, exploration of double antibody-coupled drugs, and strategies to overcome drug resistance.

19.
Psychophysiology ; 61(7): e14557, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38459638

ABSTRACT

When memorizing an integrated object such as a Kanizsa figure, the completion of parts into a coherent whole is attained by grouping processes which render a whole-object representation in visual working memory (VWM). The present study measured event-related potentials (ERPs) and oscillatory amplitudes to track these processes of encoding and representing multiple features of an object in VWM. To this end, a change detection task was performed, which required observers to memorize both the orientations and colors of six "pacman" items while inducing configurations of the pacmen that systematically varied in terms of their grouping strength. The results revealed an effect of object configuration in VWM despite physically constant visual input: change detection for both orientation and color features was more accurate with increased grouping strength. At the electrophysiological level, the lateralized ERPs and alpha activity mirrored this behavioral pattern. Perception of the orientation features gave rise to the encoding of a grouped object as reflected by the amplitudes of the Ppc. The grouped object structure, in turn, modulated attention to both orientation and color features as indicated by the enhanced N1pc and N2pc. Finally, during item retention, the representation of individual objects and the concurrent allocation of attention to these memorized objects were modulated by grouping, as reflected by variations in the CDA amplitude and a concurrent lateralized alpha suppression, respectively. These results indicate that memorizing multiple features of grouped, to-be-integrated objects involves multiple, sequential stages of processing, providing support for a hierarchical model of object representations in VWM.


Subject(s)
Alpha Rhythm , Electroencephalography , Evoked Potentials , Memory, Short-Term , Humans , Memory, Short-Term/physiology , Male , Female , Young Adult , Alpha Rhythm/physiology , Evoked Potentials/physiology , Adult , Visual Perception/physiology , Attention/physiology , Photic Stimulation , Pattern Recognition, Visual/physiology
20.
Plant J ; 118(6): 1955-1971, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38491864

ABSTRACT

Photoperiod employs complicated networks to regulate various developmental processes in plants, including flowering transition. However, the specific mechanisms by which photoperiod affects epigenetic modifications and gene expression variations in plants remain elusive. In this study, we conducted a comprehensive analysis of DNA methylation, small RNA (sRNA) accumulation, and gene expressions under different daylengths in facultative long-day (LD) grass Brachypodium distachyon and short-day (SD) grass rice. Our results showed that while overall DNA methylation levels were minimally affected by different photoperiods, CHH methylation levels were repressed under their favorable light conditions, particularly in rice. We identified numerous differentially methylated regions (DMRs) that were influenced by photoperiod in both plant species. Apart from differential sRNA clusters, we observed alterations in the expression of key components of the RNA-directed DNA methylation pathway, DNA methyltransferases, and demethylases, which may contribute to the identified photoperiod-influenced CHH DMRs. Furthermore, we identified many differentially expressed genes in response to different daylengths, some of which were associated with the DMRs. Notably, we discovered a photoperiod-responsive gene MYB11 in the transcriptome of B. distachyon, and further demonstrated its role as a flowering inhibitor by repressing FT1 transcription. Together, our comparative and functional analysis sheds light on the effects of daylength on DNA methylation, sRNA accumulation, and gene expression variations in LD and SD plants, thereby facilitating better designing breeding programs aimed at developing high-yield crops that can adapt to local growing seasons.


Subject(s)
DNA Methylation , Gene Expression Regulation, Plant , Oryza , Photoperiod , RNA, Plant , Oryza/genetics , Oryza/metabolism , Oryza/physiology , RNA, Plant/genetics , RNA, Plant/metabolism , Brachypodium/genetics , Brachypodium/metabolism , Brachypodium/physiology , Epigenesis, Genetic , Flowers/genetics , Flowers/physiology , Plant Proteins/genetics , Plant Proteins/metabolism
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