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1.
Sci Rep ; 14(1): 15411, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965337

ABSTRACT

Dielectric Elastomer Minimum Energy Structures (DEMES) have the ability of actively adjusting their shape to accommodate complex scenarios, understanding the actuation mechanism of DEMES is essential for their effective design and control, which has rendered them a focus of research in the field of soft robotics. The actuation ability of DEMES is usually influenced by external conditions, among which the electromechanical properties of DE materials are highly sensitive to temperature changes, and the pre-stretch ratio of DE materials has a significant impact on the dynamic performance of DEMES. Therefore, it is necessary to study the effects of temperature and pre-stretch ratio on the nonlinear dynamic behavior of DEMES. In this paper, in response to the lack of research on the influence of DE pre-stretch ratio on the actuation characteristics of DEMES, this paper proposes a systematic modeling and analysis framework that comprehensively considers pre-stretch factors, temperature factors, and viscoelastic factors, and establishes the motion control equation of DEMES affected by the coupling effect of DE pre-stretch ratio and temperature. The proposed analytical framework is used to analyze the evolution of the electromechanical response of DEMES under voltage excitation under the coupling of DE pre-stretch ratio and temperature. The results indicate that the bending angle, inelastic deformation, resonant frequency, and dynamic stability of DEMES can be jointly adjusted by the DE pre-stretch ratio and ambient temperature. A low pre-stretch ratio of DE can lead to dynamic instability of DEMES, while appropriate temperature conditions and higher pre-stretch ratios can significantly improve the actuation ability of DEMES. This can provide theoretical guidance for the design and deformation control of DEMES.

2.
World J Clin Cases ; 12(18): 3444-3452, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38983417

ABSTRACT

BACKGROUND: Lumbar disc herniation (LDH) commonly occurs during spinal surgery; LDH is on the increase in younger patients and is classified as "paralysis" and "back pain." Sanhanchushi Tongbi (SPST) is a customized prescription. It disperses cold, relieves pain, removes cold from the meridians and viscera, and treats neuropathic pain. However, few studies have investigated its mechanism of pain relief. AIM: To observe the clinical therapeutic effects on LDH treated with self-prescribed SPST. METHODS: A total of 211 patients with LDH syndrome were divided into two groups: 107 patients in the control group were treated with conventional massage combined with traction, and 104 patients in the observation group were treated with a combination of the control regimen and self-prescribed oral SPST. The patients were treated for 4 wk. Indices of traditional Chinese medicine (TCM) syndrome score and serum inflammatory factor levels were measured. RESULTS: After therapy, the TCM syndrome score in the observation group was significantly lower than that in the control group (P < 0.05). The main symptoms, clinical signs, daily activities, and Japanese Orthopedic Association scores in the observation group were significantly higher than those in the control group after therapy (P < 0.05). The levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein were lower in the observation group than in the control group (P < 0.05). In the observation group, superoxide dismutase levels were significantly higher, whereas malondialdehyde levels were significantly lower, compared with the control group (P < 0.05). The overall efficacy rate in the observation group was 96.15%, which was substantially higher than that in the control group (88.79%; P < 0.05). CONCLUSION: Self-prescribed SPST can reduce the levels of inflammatory and pain-causing factors as well as lumbar pain in patients with LDH.

3.
Blood ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976875

ABSTRACT

There is an urgent and unmet clinical need to develop non-pharmacological interventions for chronic pain management due to the critical side effects of opioids. Low-intensity transcranial focused ultrasound is an emerging non-invasive neuromodulation technology with high spatial specificity and deep brain penetration. Here, we developed a tightly-focused 128-element ultrasound transducer to specifically target small mouse brains, employing dynamic focus steering. We demonstrate that transcranial focused ultrasound stimulation at pain processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo. Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates heat pain sensitivity in wild-type mice and modulates heat and mechanical hyperalgesia in a humanized mouse model of chronic pain in sickle cell disease. Results further revealed a sustained behavioral change associated with heat hypersensitivity by targeting deeper cortical structures (e.g., insula) and multi-session focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitive- and chronic hyperalgesia-associated neural signals following focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting inter-experiment intervals, and investigating effects on age, gender, genotype, and in a head-fixed awake model. Importantly, transcranial focused ultrasound was found to be safe, causing no adverse effects on motor function and brain's neuropathology. In conclusion, the validated proof of principle experimental evidence demonstrates the translational potential of novel focused ultrasound neuromodulation for next-generation pain treatment without adverse effects.

4.
bioRxiv ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38979298

ABSTRACT

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique able to target shallow and deep brain structures with high precision. Previous studies have demonstrated that tFUS stimulation responses are both cell-type specific and controllable through altering stimulation parameters. Specifically, tFUS can elicit time-locked neural activity in regular spiking units (RSUs) that is sensitive to increases in pulse repetition frequency (PRF), while time-locked responses are not seen in fast spiking units (FSUs). These findings suggest a unique capability of tFUS to alter circuit network dynamics with cell-type specificity; however, these results could be biased by the use of anesthesia, which significantly modulates neural activities. In this study, we develop an awake head-fixed rat model specifically designed for tFUS study, and address a key question if tFUS still has cell-type specificity under awake conditions. Using this novel animal model, we examined a series of PRFs and burst duty cycles (DCs) to determine their effects on neuronal subpopulations without anesthesia. We conclude that cell-type specific time-locked and delayed responses to tFUS as well as PRF and DC sensitivity are present in the awake animal model and that despite some differences in response, isoflurane anesthesia is not a major confound in studying the cell-type specificity of ultrasound neuromodulation. We further determine that, in an awake, head-fixed setting, the preferred PRF and DC for inducing time-locked excitation with our pulsed tFUS paradigm are 1500 Hz and 60%, respectively.

5.
bioRxiv ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38979359

ABSTRACT

Transcranial focused ultrasound stimulation (tFUS) has been proven capable of altering focal neuronal activities and neural circuits non-invasively in both animals and humans. The abilities of tFUS for cell-type selection within the targeted area like somatosensory cortex have been shown to be parameter related. However, how neuronal subpopulations across neural pathways are affected, for example how tFUS affected neuronal connections between brain areas remains unclear. In this study, multi-site intracranial recordings were used to quantify the neuronal responses to tFUS stimulation at somatosensory cortex (S1), motor cortex (M1) and posterior medial thalamic nucleus (POm) of cortico-thalamo-cortical (CTC) pathway. We found that when targeting at S1 or POm, only regular spiking units (RSUs, putative excitatory neurons) responded to specific tFUS parameters (duty cycle: 6%-60% and pulse repetition frequency: 1500 and 3000 Hz ) during sonication. RSUs from the directly connected area (POm or S1) showed a synchronized response, which changed the directional correlation between RSUs from POm and S1. The tFUS induced excitation of RSUs activated the feedforward and feedback loops between cortex and thalamus, eliciting delayed neuronal responses of RSUs and delayed activities of fast spiking units (FSUs) by affecting local network. Our findings indicated that tFUS can modulate the CTC pathway through both feedforward and feedback loops, which could influence larger cortical areas including motor cortex.

6.
Phytomedicine ; 132: 155827, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38955059

ABSTRACT

BACKGROUND: Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive. PURPOSE: This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism. MATERIALS AND METHODS: The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE-/- mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca2+ measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot. RESULTS: The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca2+ influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1. CONCLUSION: The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.

7.
J Biophotonics ; : e202400104, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955360

ABSTRACT

A number of hardware-based and software-based strategies have been suggested to eliminate motion artifacts for improvement of 3D-optical coherence tomography (OCT) image quality. However, the hardware-based strategies have to employ additional hardware to record motion compensation information. Many software-based strategies have to need additional scanning for motion correction at the expense of longer acquisition time. To address this issue, we propose a motion artifacts correction and motion estimation method for OCT volumetric imaging of anterior segment, without requirements of additional hardware and redundant scanning. The motion correction effect with subpixel accuracy for in vivo 3D-OCT has been demonstrated in experiments. Moreover, the physiological information of imaging object, including respiratory curve and respiratory rate, has been experimentally extracted using the proposed method. The proposed method offers a powerful tool for scientific research and clinical diagnosis in ophthalmology and may be further extended for other biomedical volumetric imaging applications.

8.
Neoplasma ; 71(3): 243-254, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38958714

ABSTRACT

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.


Subject(s)
Cell Proliferation , Disulfides , Ferroptosis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Reactive Oxygen Species , Sulfinic Acids , Humans , Ferroptosis/drug effects , Disulfides/pharmacology , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Cell Proliferation/drug effects , Sulfinic Acids/pharmacology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Cell Movement/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Glutathione/metabolism , Cell Survival/drug effects
9.
Article in English | MEDLINE | ID: mdl-38996753

ABSTRACT

Metalloproteins binding with trace elements play a crucial role in biological processes and on the contrary, those binding with exogenous heavy metals have adverse effects. However, the methods for rapid, high sensitivity and simultaneous analysis of these metalloproteins are still lacking. In this study, a fast method for simultaneously determination of both essential and toxic metal-containing proteins was developed by coupling size exclusion chromatography (SEC) with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). After optimization of the separation and detection conditions, seven metalloproteins with different molecular weight (from 16.0 to 443.0 kDa) were successfully separated within 10 min and the proteins containing iron (Fe), copper (Cu), zinc (Zn), iodine (I) and lead (Pb) elements could be simultaneously detected with the use of oxygen as the collision gas in ICP-MS/MS. Accordingly, the linear relationship between log molecular weight and retention time was established to estimate the molecular weight of unknown proteins. Thus, the trace metal and toxic metal containing proteins could be detected in a single run with high sensitivity (detection limits in the range of 0.0020-2.5 µg/mL) and good repeatability (relative standard deviations lower than 4.5 %). This method was then successfully used to analyze metal (e.g., Pb, Zn, Cu and Fe) binding proteins in the blood of Pb-intoxicated patients, and the results showed a negative correlation between the contents of zinc and lead binding proteins, which was identified to contain hemoglobin subunit. In summary, this work provided a rapid and sensitive tool for screening metal containing proteins in large number of biological samples.

10.
Nanoscale Adv ; 6(14): 3543-3552, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38989518

ABSTRACT

The integration of polymer self-assembly with non-solvent induced phase separation (SNIPS) represents a recent advancement in membrane fabrication. This breakthrough allows for the fabrication of membranes with uniformly sized pores, enabling precise and fast separation through a phase inversion process commonly used in industrial fabrication. Currently, block copolymers are used in implementing the SNIPS strategy. In order to facilitate an easier and more flexible fabrication procedure, we employed the widely used semi-crystalline polymer polyvinylidene fluoride (PVDF) as the base material for achieving SNIPS through self-seeding. This process involves filtering the PVDF casting solution to induce microphase separation and generate crystal seeds. Subsequently, NIPS is applied to enable the growth of crystal seeds into uniformly distributed nanoparticles with consistent size and shape, ultimately resulting in a membrane with a uniform pore size. The fabricated membrane exhibited improved flux (2924.67 ± 28.02 L m-2 h-1 at 0.5 bar) and rejection (91% for 500 nm polystyrene particles). Notably, the microphase separation in the casting solution is a distinguishing feature of the SNIPS compared to NIPS. In this study, we found that the microphase separation of semi-crystalline polymers is also crucial for achieving membranes with uniform pore sizes. This finding may extend the potential application of the SNIPS strategy to include semi-crystalline polymers.

11.
Materials (Basel) ; 17(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38998350

ABSTRACT

The current limitations of air-cooled proton exchange membrane fuel cells (AC-PEMFCs) in water and heat management remain a major obstacle to their commercialization. A 90 cm2 full-size AC-PEMFC multi-physical field-coupled numerical model was constructed; isothermal and non-isothermal calculations were performed to explore the effects of univariate and multivariate variables on cell performance, respectively. The isothermal results indicate that lower temperature is beneficial to increase the humidity of MEA, and distribution uniformity at lower stoichiometric ratios and lower temperatures is better. The correlation between current density distribution and temperature, water content, and concentration distribution shows that the performance of AC-PEMFCs is influenced by multiple factors. Notably, under high current operation, the large heat generation may lead to high local temperature and performance decline, especially in the under-channel region with drier MEA. The higher stoichiometric ratio can enhance heat dissipation, improve the uniformity of current density, and increase power density. Optimal fuel cell performance is achieved with a stoichiometric ratio of 300, balancing the mixed influence of multiple factors.

12.
J Food Drug Anal ; 32(2): 140-154, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38934689

ABSTRACT

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent. This article aims to explore the multifaceted effects of cinnamaldehyde on cancer cells and shed light on these existing issues. Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, anti-proliferation, anti-inflammatory and antioxidant. In addition, cinnamaldehyde also acts as a reactive oxygen species scavenger, reducing oxidative stress and preventing DNA damage and genomic instability. This article emphasizes the promising therapeutic potential of cinnamaldehyde in cancer treatment and underscores the need for future research to unlock novel mechanisms and strategies for combating cancer. By providing valuable insights into the role and mechanism of cinnamaldehyde in cancer, this comprehensive understanding paves the way for its potential as a novel therapeutic agent. Overall, cinnamaldehyde holds great promise as an anticancer agent, and its comprehensive exploration in this article highlights its potential as a valuable addition to cancer treatment options.


Subject(s)
Acrolein , Neoplasms , Acrolein/analogs & derivatives , Acrolein/pharmacology , Acrolein/chemistry , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Animals , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , DNA Damage/drug effects , Cell Proliferation/drug effects , Reactive Oxygen Species/metabolism
13.
Int J Biol Macromol ; 273(Pt 2): 132928, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38897510

ABSTRACT

Immobilized enzymes are one of the most common tools used in enzyme engineering, as they can substantially reduce the cost of enzyme isolation and use. However, efficient catalysis of solid substrates using immobilized enzymes is challenging, hydrolysis of insoluble cellulose by immobilized cellulases is a typical example of this problem. In this study, inspired by bees and honeycombs, we prepared gelatin-modified cellulase (BEE) and gelatin hydrogels (HONEYCOMB) to achieve reversible recycling versus release of cellulase through temperature-responsive changes in the triple-stranded helix-like interactions between BEE and HONEYCOMB. At elevated temperatures, BEE was released from HONEYCOMB and participated in hydrolytic saccharification. After 24 h, the glucose yields of both the free enzyme and BEE reached the same level. When the temperature was decreased, BEE recombined with HONEYCOMB to facilitate the effective separation and recycling of BEE from the system. The enzymatic system retained >70 % activity after four reuse cycles. In addition, this system showed good biocompatibility and environmental safety. This method increases the mass transfer capacity and enables easy recovery of immobilized cellulase, thereby serving as a valuable strategy for the immobilization of other enzymes.


Subject(s)
Cellulase , Cellulose , Enzymes, Immobilized , Gelatin , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Hydrolysis , Cellulase/chemistry , Cellulase/metabolism , Cellulose/chemistry , Gelatin/chemistry , Temperature , Hydrogels/chemistry , Solubility , Animals
14.
ACS Nano ; 18(26): 17251-17266, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38907727

ABSTRACT

Designing adaptive and smart hydrogel wound dressings to meet specific needs across different stages of wound healing is crucial. Here, we present a composite hydrogel, GSC/PBE@Lut, that offers self-regulating release of cupric ions and luteolin and modulates mechanical properties to promote chronic wound healing. The double network hydrogel, GSC, is fabricated through photo-cross-linking of gelatin methacrylate, followed by Cu2+-alginate coordination cross-linking. On one hand, GSC allows for rapid Cu2+ release to eliminate bacteria in the acidic pH environment during inflammation and reduces the hydrogel's mechanical strength to minimize tissue trauma during early dressing changes. On the other hand, GSC enables slow Cu2+ release during the proliferation stage, promoting angiogenesis and biocompatibility. Furthermore, the inclusion of pH- and reactive oxygen species (ROS)-responsive luteolin nanoparticles (PBE@Lut) in the hydrogel matrix allows for controlled release of luteolin, offering antioxidant and anti-inflammatory effects and promoting anti-inflammatory macrophage polarization. In a murine model of Staphylococcus aureus infected wounds, GSC/PBE@Lut demonstrates exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that smart hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic wounds.


Subject(s)
Anti-Bacterial Agents , Copper , Hydrogels , Luteolin , Staphylococcus aureus , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Copper/chemistry , Copper/pharmacology , Animals , Mice , Staphylococcus aureus/drug effects , Luteolin/pharmacology , Luteolin/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alginates/chemistry , Reactive Oxygen Species/metabolism , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Hydrogen-Ion Concentration , Gelatin/chemistry , Humans , Drug Liberation , Methacrylates/chemistry , Nanoparticles/chemistry , Microbial Sensitivity Tests
15.
Toxics ; 12(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38922076

ABSTRACT

Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.

16.
Eur J Med Chem ; 275: 116571, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38857566

ABSTRACT

Histone Deacetylase 6 (HDAC6) is an essential regulator of histone acetylation processes, exerting influence on a multitude of cellular functions such as cell motility, endocytosis, autophagy, apoptosis, and protein trafficking through its deacetylation activity. The significant implications of HDAC6 in diseases such as cancer, neurodegenerative disorders, and immune disorders have motivated extensive investigation into the development of specific inhibitors targeting this enzyme for therapeutic purposes. Single targeting drugs carry the risk of inducing drug resistance, thus prompting exploration of dual targeting therapy which offers the potential to impact multiple signaling pathways simultaneously, thereby lowering the likelihood of resistance development. While pharmacological studies have exhibited promise in combined therapy involving HDAC6, challenges related to potential drug interactions exist. In response to these challenges, researchers are investigating HDAC6 hybrid molecules which enable the concomitant targeting of HDAC6 and other key proteins, thus enhancing treatment efficacy while mitigating side effects and reducing the risk of resistance compared to traditional combination therapies. The published design strategies for dual targeting inhibitors of HDAC6 are summarized and discussed in this review. This will provide some valuable insights into more novel HDAC6 dual targeting inhibitors to meet the urgent need for innovative therapies in oncology and other related fields.


Subject(s)
Antineoplastic Agents , Histone Deacetylase 6 , Histone Deacetylase Inhibitors , Neoplasms , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase 6/metabolism , Humans , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/chemical synthesis , Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Molecular Structure , Animals
17.
Nat Commun ; 15(1): 4898, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851785

ABSTRACT

Developing artificial leaves to address the environmental burden of CO2 is pivotal for advancing our Net Zero Future. In this study, we introduce EcoLeaf, an artificial leaf that closely mimics the characteristics of natural leaves. It harnesses visible light as its sole energy source and orchestrates the controlled expansion and contraction of stomata and the exchange of petiole materials to govern the rate of CO2 sequestration from the atmosphere. Furthermore, EcoLeaf has a cellulose composition and mechanical strength similar to those of natural leaves, allowing it to seamlessly integrate into the ecosystem during use and participate in natural degradation and nutrient cycling processes at the end of its life. We propose that the carbon sequestration pathway within EcoLeaf is adaptable and can serve as a versatile biomimetic platform for diverse biogenic carbon sequestration pathways in the future.


Subject(s)
Carbon Dioxide , Carbon Sequestration , Cellulose , Plant Leaves , Carbon Dioxide/metabolism , Carbon Dioxide/chemistry , Plant Leaves/metabolism , Cellulose/metabolism , Cellulose/chemistry , Ecosystem , Plant Stomata/metabolism , Photosynthesis , Light
18.
MicroPubl Biol ; 20242024.
Article in English | MEDLINE | ID: mdl-38854633

ABSTRACT

Animals typically respond to their reflection as a conspecific and will respond as if the reflection were another animal that they could interact with, either fearfully or aggressively. We investigated how a modified reflective environment of a standard glass aquarium affects the aggressive and fearful behaviors of the crayfish Orconectes virilis , based on pre-determined behavior criteria. We found that the crayfish were both increasingly aggressive and slightly fearful in the reflective environment compared to minimal behavioral changes in the control non-reflective environment. Thus, our findings support that crayfish recognize their mirror image as a conspecific.

19.
Mol Biotechnol ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38858301

ABSTRACT

Late-onset hypogonadism (LOH) is an age-related syndrome characterized by deficiency of serum testosterone produced by Leydig cells. Previous evidence suggested that microRNA (miR)-361-3p can serve as a promising biomarker for LOH. Nonetheless, its detailed function and molecular mechanism in LOH remain unclarified. The 24-month-old male mice were selected as an animal LOH model, and mouse Leydig cell line TM3 was stimulated with H2O2. ELISA was employed for testosterone level evaluation. Hematoxylin-eosin staining was implemented for histologic analysis of mouse testicular tissues. Western blotting and RT-qPCR were utilized for evaluating molecular protein and RNA expression, respectively. Functional experiments were conducted to test miR-361-5p roles. Luciferase reporter assay was for verifying the interaction between miR-361-5p and protein inhibitor of activated STAT 1 (PIAS1). miR-361-5p displayed a decreased level in the testes of LOH mice. Overexpressing miR-361-5p attenuated Leydig cell loss in the testis and elevated serum and intratesticular testosterone levels in LOH mice. H2O2 stimulation impaired TM3 cell viability, proliferation and intracellular testosterone production and enhanced cell apoptosis. miR-361-5p targeted PIAS1 in TM3 cell. PIAS1 upregulation counteracted miR-361-5p overexpression-mediated alleviation of cell apoptosis and elevation of testosterone synthesis in H2O2-stimualetd TM3 cells. miR-361-5p ameliorates LOH progression by increasing testosterone production and alleviate Leydig cell apoptosis via downregulation of PIAS1.

20.
Nat Commun ; 15(1): 4382, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862476

ABSTRACT

A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting investigation into the potential reduction through concurrent targeted neuromodulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technology with high spatiotemporal precision. This study examines whether tFUS neuromodulation can improve BCI outcomes, and explores the underlying mechanism of action using high-density electroencephalography (EEG) source imaging (ESI). As a result, V5-targeted tFUS significantly reduced the error in a BCI speller task. Source analyses revealed a significantly increase in theta and alpha activities in the tFUS condition at both V5 and downstream in the dorsal visual processing pathway. Correlation analysis indicated that the connection within the dorsal processing pathway was preserved during tFUS stimulation, while the ventral connection was weakened. These findings suggest that V5-targeted tFUS enhances feature-based attention to visual motion.


Subject(s)
Attention , Brain-Computer Interfaces , Electroencephalography , Humans , Male , Attention/physiology , Adult , Female , Young Adult , Visual Cortex/physiology , Motion Perception/physiology , Photic Stimulation/methods
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