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1.
J Nanobiotechnology ; 22(1): 299, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38812031

ABSTRACT

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.


Subject(s)
Diterpenes, Kaurane , Glutathione , Leukemia, Myeloid, Acute , Liposomes , Reactive Oxygen Species , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/pharmacology , Glutathione/metabolism , Glutathione/chemistry , Liposomes/chemistry , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Humans , Reactive Oxygen Species/metabolism , Animals , Mice , Cell Line, Tumor , Toll-Like Receptor 2/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects
2.
Exp Dermatol ; 33(5): e15101, 2024 May.
Article in English | MEDLINE | ID: mdl-38770555

ABSTRACT

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.


Subject(s)
Freezing , Hyperpigmentation , Melanins , Melanocytes , Monophenol Monooxygenase , Ultraviolet Rays , Wnt Signaling Pathway , beta Catenin , Animals , Melanins/biosynthesis , Melanins/metabolism , Melanocytes/metabolism , Mice , Hyperpigmentation/metabolism , beta Catenin/metabolism , Monophenol Monooxygenase/metabolism , Guinea Pigs , Microphthalmia-Associated Transcription Factor/metabolism , Cell Survival , Intramolecular Oxidoreductases/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Apoptosis , Oxidoreductases/metabolism , Interferon Type I , Pregnancy Proteins
3.
Nat Nanotechnol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649746

ABSTRACT

Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.

4.
Phys Rev E ; 109(3-1): 034125, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38632761

ABSTRACT

Besides its original spin representation, the Ising model is known to have the Fortuin-Kasteleyn (FK) bond and loop representations, of which the former was recently shown to exhibit two upper critical dimensions (d_{c}=4,d_{p}=6). Using a lifted worm algorithm, we determine the critical coupling as K_{c}=0.07770891(4) for d=7, which significantly improves over the previous results, and then study critical geometric properties of the loop Ising clusters on tori for spatial dimensions d=5 to 7. We show that as the spin representation, the loop Ising model has only one upper critical dimension at d_{c}=4. However, sophisticated finite-size scaling (FSS) behaviors, such as two length scales, two configuration sectors, and two scaling windows, still exist as the interplay effect of the Gaussian fixed point and complete-graph asymptotics. Moreover, using the loop-cluster algorithm, we provide an intuitive understanding of the emergence of the percolation-like upper critical dimension d_{p}=6 in the FK-Ising model. As a consequence, a unified physical picture is established for the FSS behaviors in all three representations of the Ising model above d_{c}=4.

5.
Nat Commun ; 15(1): 2834, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565846

ABSTRACT

The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.


Subject(s)
Circadian Clocks , Drosophila Proteins , Animals , Circadian Rhythm/physiology , Temperature , Sleep/physiology , Drosophila , Circadian Clocks/physiology , Drosophila Proteins/genetics , Drosophila melanogaster/physiology
6.
J Orthop Surg Res ; 19(1): 259, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38659060

ABSTRACT

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.


Subject(s)
Materials Testing , Polyethylenes , Scoliosis , Humans , Materials Testing/methods , Friction , Bone Screws , In Vitro Techniques
7.
Adv Mater ; : e2303311, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561020

ABSTRACT

The musculoskeletal system, constituting the largest human physiological system, plays a critical role in providing structural support to the body, facilitating intricate movements, and safeguarding internal organs. By virtue of advancements in revolutionized materials and devices, particularly in the realms of motion capture, health monitoring, and postoperative rehabilitation, "musculoskeletal electronics" has actually emerged as an infancy area, but has not yet been explicitly proposed. In this review, the concept of musculoskeletal electronics is elucidated, and the evolution history, representative progress, and key strategies of the involved materials and state-of-the-art devices are summarized. Therefore, the fundamentals of musculoskeletal electronics and key functionality categories are introduced. Subsequently, recent advances in musculoskeletal electronics are presented from the perspectives of "in vitro" to "in vivo" signal detection, interactive modulation, and therapeutic interventions for healing and recovery. Additionally, nine strategy avenues for the development of advanced musculoskeletal electronic materials and devices are proposed. Finally, concise summaries and perspectives are proposed to highlight the directions that deserve focused attention in this booming field.

8.
J Hazard Mater ; 471: 134372, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38669933

ABSTRACT

Bioaerosol is one of the main ways to spread respiratory infectious diseases. In order to further improve the sterilization efficiency of copper-manganese-cerium oxide (CuMnCeOx), the post-treatment method based on acid etching was adopted. The results showed that sterilization efficiency of the treated CuMnCeOx could reach 99% in aerosol with space velocity of 1400 h-1. L(+)-ascorbic acid successfully promoted the formation of Cu+, oxygen vacancies and the generation of reactive oxygen species (ROS) on the surface of the treated CuMnCeOx. During sterilization in liquid system, the transcriptome identified 316 differentially expressed genes, including 270 up-regulated genes and 46 down-regulated genes. Differentially expressed genes were significantly enriched in cell wall (GO:0005618) and external encapsulating structure (GO:0030312). Up-regulated genes were shown in regulation of reactive oxygen species biosynthetic processes (GO:1903409, GO:1903426, GO:1903428) and positive regulation all of reactive oxygen species metabolic process (GO:2000379), indicating that ROS induced cell death by destroying cell wall.


Subject(s)
Aerosols , Copper , Manganese , Reactive Oxygen Species , Sterilization , Copper/chemistry , Reactive Oxygen Species/metabolism , Sterilization/methods , Manganese/chemistry , Oxides/chemistry , Transcriptome/drug effects
9.
Huan Jing Ke Xue ; 45(5): 2983-2994, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629559

ABSTRACT

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.


Subject(s)
Metals, Heavy , Soil Pollutants , Child , Adult , Humans , Environmental Monitoring , Soil , Cadmium/analysis , Soil Pollutants/analysis , Metals, Heavy/analysis , Risk Assessment , China
10.
J Funct Biomater ; 15(3)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38535248

ABSTRACT

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

11.
Huan Jing Ke Xue ; 45(2): 1015-1025, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471939

ABSTRACT

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons (PAHs) in soils of Guangzhou, 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method (ERL/ERM) and the (BaP) toxicity equivalent method, and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that: the content of surface soil (∑16PAHs) in Guangzhou was 38-11 115 µg·kg-1, with an average of 526 µg·kg-1, and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou, and there was already a significant ecological risk of PAHs pollution in individual sampling points, which were generally in a state of mild pollution. Based on the results of the health risk assessment, the contribution rates of total cancer risk in both adults and children were presented as follows: skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults, and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal (37.1%); diesel (32%); coking (17.3%); and mixed sources of traffic emissions, biomass combustion, and petrochemical product volatilization (13.6%). The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.


Subject(s)
Neoplasms , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Child , Adult , Humans , Soil/chemistry , Environmental Monitoring/methods , Polycyclic Aromatic Hydrocarbons/analysis , Soil Pollutants/analysis , Environmental Pollution/analysis , Risk Assessment , China
12.
Clin Orthop Relat Res ; 482(6): 1074-1086, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38427791

ABSTRACT

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm 2 versus 256 ± 43 /mm 2 , mean difference 188 /mm 2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m 2 versus 8 ± 4 kJ/m 2 , mean difference 8 kJ/m 2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.


Subject(s)
Achilles Tendon , Allografts , Ethanol , Peracetic Acid , Sterilization , Wound Healing , Animals , Rabbits , Male , Wound Healing/radiation effects , Wound Healing/drug effects , Peracetic Acid/pharmacology , Ethanol/pharmacology , Sterilization/methods , Achilles Tendon/surgery , Achilles Tendon/radiation effects , Achilles Tendon/pathology , Tensile Strength , Biomechanical Phenomena , Time Factors , Tendon Injuries/surgery
13.
Cell Res ; 34(5): 355-369, 2024 May.
Article in English | MEDLINE | ID: mdl-38448650

ABSTRACT

Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.


Subject(s)
Ras Homolog Enriched in Brain Protein , Humans , Ras Homolog Enriched in Brain Protein/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , HEK293 Cells , Guanine Nucleotide Exchange Factors/metabolism , Protein Binding , Signal Transduction , Cell Line, Tumor
14.
PLoS One ; 19(1): e0296709, 2024.
Article in English | MEDLINE | ID: mdl-38227590

ABSTRACT

This study examined 70 Klebsiella pneumoniae isolates derived from companion animals with urinary tract infections in Taiwan. Overall, 81% (57/70) of the isolates carried extended-spectrum ß-lactamase (ESBL) and/or plasmid-encoded AmpC (pAmpC) genes. ESBL genes were detected in 19 samples, with blaCTX-M-1, blaCTX-M-9, and blaSHV being the predominant groups. pAmpC genes were detected in 56 isolates, with blaCIT and blaDHA being the predominant groups. Multilocus sequence typing revealed that sequence types (ST)11, ST15, and ST655 were prevalent. wabG, uge, entB, mrkD, and fimH were identified as primary virulence genes. Two isolates demonstrated a hypermucoviscosity phenotype in the string test. Antimicrobial susceptibility testing exhibited high resistance to ß-lactams and fluoroquinolones in ESBL-positive isolates but low resistance to aminoglycosides, sulfonamides, and carbapenems. Isolates carrying pAmpC genes exhibited resistance to penicillin-class ß-lactams. These findings provide valuable insights into the role of K. pneumoniae in the context of the concept of One Health.


Subject(s)
Klebsiella Infections , Urinary Tract Infections , Animals , Klebsiella pneumoniae/genetics , Enterobacteriaceae/genetics , beta-Lactamases/genetics , Bacterial Proteins/genetics , Pets , Anti-Bacterial Agents/pharmacology , beta-Lactams , Urinary Tract Infections/drug therapy , Urinary Tract Infections/veterinary , Urinary Tract Infections/epidemiology , Klebsiella Infections/drug therapy , Klebsiella Infections/veterinary , Microbial Sensitivity Tests
15.
PLoS One ; 19(1): e0291538, 2024.
Article in English | MEDLINE | ID: mdl-38295135

ABSTRACT

Frequent occlusion of tracking targets leads to poor performance of tracking algorithms. A common practice in multi-target tracking algorithms is to re-identify the occluded tracking targets, which increases the number of identity switching occurrences. This paper focuses on online multi-object tracking and designs an anti-occlusion, robust association strategy, and feature extraction model. Specifically, the least squares algorithm and the Kalman filter are used to predict the trajectory of the tracking target, while the two-way self-attention mechanism is employed to extract the features of the tracking target, as well as positive and negative samples. After the tracking target is occluded, the association strategy is used to assign the identity information from before the occlusion. The experimental results demonstrate that the algorithm proposed in this paper has achieved excellent tracking performance on the MOT dataset.


Subject(s)
Pedestrians , Humans , Algorithms , Least-Squares Analysis
16.
J Fluoresc ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38252215

ABSTRACT

Three rhodamine 6G derivatives (REHA, RETA and REDA) were designed and synthesized by connecting rhodamine 6G and 3-methyl-2-thiophenal with hydrazine hydrate, ethylenediamine and diethylenetriamine, respectively. In CH3CN/H2O (50/50, v/v), the absorbance of REHA, RETA and REDA at 528 nm was suddenly enhanced by 3.2, 3.8 and 7.2 times within the pH range of 3.03-2.31, 3.05-2.32 and 3.06-2.34, respectively, and the solution changed from colorless to pink. Meanwhile, the maximal fluorescence intensity sharply increased by 53.9, 26.6 and 24.9 times in the pH range of 3.86-3.46, 3.88-3.47 and 3.89-3.48, respectively, and the solution changed from dark to bright yellow-green fluorescence. REHA, RETA and REDA can act as highly selective and sensitive colorimetric and fluorescent pH switches with good recyclability and anti-interference ability. The response mechanism of REHA, RETA and REDA to pH was studied by 1H NMR spectroscopy, and their application in indicating small pH changes in dyeing wastewater was investigated.

17.
Opt Express ; 31(25): 41518-41532, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38087548

ABSTRACT

Turbulence generated by random ups and downs in the refractive index of the atmosphere produces varying degrees of distortion and blurring of images in the camera. Traditional methods ignore the effect of strong turbulence on the image. This paper proposes a deep neural network to enhance image clarity under strong turbulence to handle this problem. This network is divided into two sub-networks, the generator and the discriminator, whose functions are to mitigate the effects of turbulence on the image and to determine the authenticity of the recovered image. After extensive experiments, it is proven that the present network plays a role in mitigating the image degradation problem caused by atmospheric turbulence.

18.
Front Genet ; 14: 1320185, 2023.
Article in English | MEDLINE | ID: mdl-38152652

ABSTRACT

Ovarian cancer is one of the female reproductive system tumors. Chemotherapy is used for advanced ovarian cancer patients; however, drug resistance is a pivotal cause of chemotherapeutic failure. Hence, it is critical to explore the molecular mechanisms of drug resistance of ovarian cancer cells and to ameliorate chemoresistance. Noncoding RNAs (ncRNAs) have been identified to critically participate in drug sensitivity in a variety of human cancers, including ovarian cancer. Among ncRNAs, circRNAs sponge miRNAs and prevent miRNAs from regulation of their target mRNAs. CircRNAs can interact with DNA or proteins to modulate gene expression. In this review, we briefly describe the biological functions of circRNAs in the development and progression of ovarian cancer. Moreover, we discuss the underneath regulatory molecular mechanisms of circRNAs on governing drug resistance in ovarian cancer. Furthermore, we mention the novel strategies to overcome drug resistance via targeting circRNAs in ovarian cancer. Due to that circRNAs play a key role in modulation of drug resistance in ovarian cancer, targeting circRNAs could be a novel approach for attenuation of chemoresistance in ovarian cancer.

19.
Chronobiol Int ; 40(12): 1574-1581, 2023 12 02.
Article in English | MEDLINE | ID: mdl-37990547

ABSTRACT

The goal of the current study was to demonstrate if the rest-activity rhythm (RAR) was altered in apathetic older adults with cerebral small vessel disease (CSVD) and find out the relationship between apathy/depression severity and RAR features in CSVD patients. This is a cross-sectional observational investigation including 53 CSVD cases (54.74% men), aged 70.70 ± 6.18 years old. The participants were assessed by neuropsychiatric inventory (NPI) subscale of apathy (NPI-apathy) and depression (NPI-depression) in succession, according to updated diagnostic criteria for apathy (DCA). Each subject wore an actigraph device (ActiGraph GT3X) in their nondominant hand for 7 days to collect raw data. Using a non-parametric methodological analysis, this study determined RAR variables such as interdaily stability (IS), intraday variability (IV) and relative amplitude (RA). Patients in the apathy-positive group had a higher Fazekas score than those in the apathy-negative group. IS, but not IV, RA, or objective sleep variables, differed between elderly patients with varying degrees of CSVD burden. Furthermore, apathy severity was statistically correlated with RA after adjusting for age, gender and education level, whereas depression severity was not associated with RAR variables. Finally, we discovered that the severity of apathy had no significant relationship with the severity of depression. All these findings indicated that the RAR altered in apathetic older adults with CSVD, and apathy was associated with decreased RAR amplitude.


Subject(s)
Apathy , Cerebral Small Vessel Diseases , Aged , Female , Humans , Male , Middle Aged , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/psychology , Circadian Rhythm , Cross-Sectional Studies , Rest
20.
J Neural Eng ; 20(6)2023 11 16.
Article in English | MEDLINE | ID: mdl-37931297

ABSTRACT

Objective.Real-time brain monitoring is of importance for intraoperative surgeries and intensive care unit, in order to take timely clinical interventions. Electroencephalogram (EEG) is a conventional technique for recording neural excitations (e.g. brain waves) in the cerebral cortex, and near infrared diffuse correlation spectroscopy (DCS) is an emerging technique that can directly measure the cerebral blood flow (CBF) in microvasculature system. Currently, the relationship between the neural activities and cerebral hemodynamics that reflects the vasoconstriction features of cerebral vessels, especially under both active and passive situation, has not been elucidated thus far, which triggers the motivation of this study.Approach.We used the verbal fluency test as an active cognitive stimulus to the brain, and we manipulated blood pressure changes as a passive challenge to the brain. Under both protocols, the CBF and EEG responses were longitudinally monitored throughout the cerebral stimulus. Power spectrum approaches were applied the EEG signals and compared with CBF responses.Main results.The results show that the EEG response was significantly faster and larger in amplitude during the active cognitive task, when compared to the CBF, but with larger individual variability. By contrast, CBF is more sensitive when response to the passive task, and with better signal stability. We also found that there was a correlation (p< 0.01,r= 0.866,R2= 0.751) between CBF and EEG in initial response during the active task, but no significant correlation (p> 0.05) was found during the passive task. The similar relations were also found between regional brain waves and blood flow.Significance.The asynchronization and correlation between the two measurements indicates the necessity of monitoring both variables for comprehensive understanding of cerebral physiology. Deep exploration of their relationships provides promising implications for DCS/EEG integration in the diagnosis of various neurovascular and psychiatric diseases.


Subject(s)
Brain , Cerebrovascular Circulation , Cerebrovascular Circulation/physiology , Electroencephalography , Spectroscopy, Near-Infrared/methods , Hemodynamics
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