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1.
Mater Horiz ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229702

ABSTRACT

Conductive hydrogel-based sensors are increasingly favored for flexible electronics due to their skin-like characteristics. However, conventional hydrogels suffer from significant swelling in humid environments and poor mechanical properties which largely restrict their applications in wearable electronic devices, especially for underwater sensing. Herein, drawing inspiration from the extracellular matrix (ECM) structure, a TPU-PVAc@AgNPs/MXene nanofibrous hydrogel composite (TPAMH) with excellent mechanical robustness and anti-swelling properties is developed. The TPAMH nanofibrous hydrogel composite is created by integrating the silver nanoparticles (AgNPs) and MXene nanosheets into an interwoven network comprising of stiff TPU nanofibers as the fibril scaffold and formic acid-crosslinked PVA hydrogel fibers as the elastic matrix (PVAc). Benefiting from the unique ECM structure, the obtained nanofibrous hydrogel composites exhibit exceptional tensile strength (4.47 MPa), remarkable elongation at break (621%), excellent anti-swelling properties, and high detection sensitivity (maximum gauge factor = 105.02), which are sufficient to monitor body motions in both air and water environments effectively. They can detect large strain movements of fingers, elbows, wrists, and knees, as well as small strain physiological signals such as frown, smile, and pulse beats, with high accuracy. Particularly noteworthy is their ability to accurately identify underwater multidirectional motions and facilitate underwater smart alarms using Morse code.

2.
EMBO Rep ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271775

ABSTRACT

Osteoclasts are bone resorbing cells that are essential to maintain skeletal integrity and function. While many of the growth factors and molecular signals that govern osteoclastogenesis are well studied, how the metabolome changes during osteoclastogenesis is unknown. Using a multifaceted approach, we identified a metabolomic signature of osteoclast differentiation consisting of increased amino acid and nucleotide metabolism. Maintenance of the osteoclast metabolic signature is governed by elevated glutaminolysis. Mechanistically, glutaminolysis provides amino acids and nucleotides which are essential for osteoclast differentiation and bone resorption in vitro. Genetic experiments in mice found that glutaminolysis is essential for osteoclastogenesis and bone resorption in vivo. Highlighting the therapeutic implications of these findings, inhibiting glutaminolysis using CB-839 prevented ovariectomy induced bone loss in mice. Collectively, our data provide strong genetic and pharmacological evidence that glutaminolysis is essential to regulate osteoclast metabolism, promote osteoclastogenesis and modulate bone resorption in mice.

3.
Ibrain ; 10(3): 378-384, 2024.
Article in English | MEDLINE | ID: mdl-39346796

ABSTRACT

Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-N-methyl-D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.

4.
Heliyon ; 10(18): e38003, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39328543

ABSTRACT

Regarding the issue of low granulation qualification rates during the granulation coating of red clover seeds, this study theoretically analyzed the force conditions of seeds and powder particles under the action of liquid to obtain the main factors affecting seed coating quality. During the seed granulation coating process, an intermittent powder supply method combined with continuous liquid supply was utilized to control the ratio of powder to liquid. Using the granulation qualification rate as the evaluation index, single-factor experiments were conducted to investigate the effects of coating pan fill ratio, single powder supply amount, powder supply interval, and liquid supply amount on the quality of red clover seed granulation coating. Based on the results of the single-factor experiments, orthogonal experiments were conducted, revealing that the interaction of factors would influence the experimental results. To further optimize the quality of seed granulation coating, the mechanisms of powder and liquid in the adhesion process on granulation coating were explored. Orthogonal experiments were conducted on the process parameters of the granulation coating machine, and the GA-BP model was employed for optimization and solution. The optimal process parameter combination obtained was a coating pan fill ratio of 33.78 %, a single powder supply amount of 5.17 g, a powder supply interval of 7.7 s, and a liquid supply amount of 0.42 mL/s. Under this optimal parameter combination, granulation coating experiments with red clover seeds were performed, and the seed granulation coating quality was relatively high, with a granulation qualification rate of 97.7 %. The research results can provide a reference for optimization experiments on coating irregular seeds.

5.
Nanomaterials (Basel) ; 14(18)2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39330667

ABSTRACT

Developing environmentally friendly bulk materials capable of easily and thoroughly removing trace amounts of dye pollutants from water to rapidly obtain clean water has always been a goal pursued by researchers. Herein, a green material with a 3D architecture and with strong underwater rebounding and fatigue resistance ability was prepared by means of the assembly of biopolymer chitosan (CS) and natural caraganate fibers (CKFs) under freezing conditions. The CKFs can randomly and uniformly distribute in the lamellar structure formed during the freezing process of CS and CKFs, playing a role similar to that of "steel bars" in concrete, thus providing longitudinal support for the 3D-architecture material. The 2D layers formed by CS and CKFs as the main basic units can provide the material with a higher strength. The 3D-architecture material can bear the compressive force of a weight underwater for multiple cycles, meeting the requirements for water purification. The underwater compression test shows that the 3D-architecture material can quickly rebound to its original shape after removing the stress. This 3D-architecture material can be used to purify dye-containing water. When its dosage is 3 g/L, the material can remove 99.65% of the Congo Red (CR) in a 50 mg/L dye solution. The adsorption performance of the 3D architecture adsorbent for CR removal in actual water samples (i.e., tap water, seawater) is superior than that of commercial activated carbon. Due to its porous block characteristics, this material can be used for the continuous and efficient treatment of wastewater containing trace amounts of CR dye to obtain pure clean water, meaning that it has great potential for the effective purification of dye wastewater.

6.
Adv Sci (Weinh) ; : e2403389, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264289

ABSTRACT

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.

7.
Ultrasonography ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39327718

ABSTRACT

PURPOSE: The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. METHODS: A total of 70 patients who underwent surgery for endometrial lesions at the authors' hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. RESULTS: Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). CONCLUSION: Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

8.
Cyborg Bionic Syst ; 5: 0135, 2024.
Article in English | MEDLINE | ID: mdl-39139629

ABSTRACT

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a kind of hydrocephalus that is easily to be misdiagnosed with brain atrophy due to the similarity of ventricular dilation and cognitive impairment. In this case, we present an old male patient who was diagnosed with iNPH by multimodality approaches. Outcomes: A 68-year-old male patient, with deteriorated gait, declined cognitive function for at least 3 years and urinary incontinence for 3 months. The doctors suspected him a patient with hydrocephalus or Alzheimer's disease based on his symptoms. We used multimodality diagnostic approaches including brain imaging, cerebrospinal fluid tap test, continuous intracranial pressure monitoring, and infusion study to make the final diagnosis of iNPH. He underwent ventriculoperitoneal shunt surgery and was well recovered. Conclusion: This case demonstrates the efficacy of using multimodality approaches for iNPH diagnosis, which saves patient time and clinical cost, worthy of further promotion.

9.
Sci Rep ; 14(1): 18867, 2024 08 14.
Article in English | MEDLINE | ID: mdl-39143187

ABSTRACT

Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.


Subject(s)
Ketamine , Machine Learning , Substance-Related Disorders , Animals , Rats , Male , Substance-Related Disorders/metabolism , Metabolomics/methods , Rats, Sprague-Dawley , Biomarkers/blood
10.
Anal Chem ; 96(37): 14800-14808, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39213642

ABSTRACT

Mitochondrial polarity is a critical indicator of numerous pathological and biological processes; thus, the development of fluorescent probes capable of targeting mitochondria and visually monitoring its polarity is of great significance. In this study, fluorescent probes were designed with a N, N-dialkylamino rhodol scaffold as the fluorophore sensitive to polarity environments, in which the alkyl chain length was adjusted rationally to obtain distinct polarity recognition modes. By integrating mitochondria targeting groups, three fluorogenic chemical probes ROML-1, ROML-2, and ROML-3 have been obtained, featuring the capability to target mitochondria and monitor its polarity precisely, dynamically and visually. The probes displayed a distinctive response to the alterations in polarity. ROML-1 and ROML-2 followed a turn-on pattern while ROML-3 was ratiometric. It has been demonstrated that the hypersensitivity to polarity and ratio fluorescence property of ROML-3 was attributed to methyl groups rather than ethyl or butyl groups. The introduction of short methyl chains made the dihedral angle between the dialkylamino substituent and fluorophore of ROML-3 (spirocyclic form) rotatable and enlarged the energy gap between the ground state and excited state, which has been validated by the results of density functional theory (DFT) calculations. Furthermore, ROML-3 was used to monitor mitochondrial polarity via confocal microscopy imaging, which revealed that compared to healthy cells the polarity of mitochondria in cancer cells was enhanced; meanwhile, the polarity of mitochondria in senescent cells was higher in contrast with young cells. The present probe ROML-3 has been proven to be an efficient tool to monitor mitochondrial polarity dynamics, which demonstrated potential significance in biomedical research and disease diagnosis.


Subject(s)
Fluorescent Dyes , Mitochondria , Fluorescent Dyes/chemistry , Mitochondria/metabolism , Mitochondria/chemistry , Humans , Density Functional Theory , Molecular Structure , Optical Imaging , HeLa Cells
11.
Mar Biotechnol (NY) ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39098943

ABSTRACT

Golden cuttlefish play a significant role in the food web of the East and Yellow Seas and are a valuable fishery resource in Chinese coastal waters. Samples of golden cuttlefish were obtained from the northern East China Sea between September 2021 and March 2022, and stable isotope methods were utilized in this study to examine the variations in the forage ecology of golden cuttlefish. Our findings reveal dynamic shifts in carbon and nitrogen stable isotopes (δ13C and δ15N), highlighting intricate foraging strategies tailored to growth and environmental changes. A notable trend emerges: an initial growth-linked rise in δ13C and δ15N enrichment, followed by seasonal fluctuations mirroring seasonal food availability. The ontogenetic niche evolution displays striking habitat shifts and trophic level escalation in small mantle length stages, transitioning to niche overlap and subtle trophic shifts later on. Sex-specific differences emerge, with females occupying higher trophic levels than males in most samples. This comprehensive study underscores the complexity and adaptability of golden cuttlefish feeding ecology, inviting further inquiry into their intricate relationships within the marine ecosystem.

12.
Mil Med Res ; 11(1): 54, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135208

ABSTRACT

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.


Subject(s)
Hydrocephalus , Humans , Hydrocephalus/genetics , Hydrocephalus/etiology , Animals , Genetic Predisposition to Disease
13.
J Formos Med Assoc ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39174395

ABSTRACT

BACKGROUND AND PURPOSE: To evaluate the effectiveness and safety of intravenous tirofiban before endovascular thrombectomy in subgroups of acute ischemic stroke patients with different degrees of leukoaraiosis (LA). METHODS: Patients of the RESCUE BT trial whose LA grade could be assessed were included. Eligible patients were dichotomized into two strata according to the van Swieten scale (VSS) score, absent-to-moderate LA (VSS score <3) and severe LA (VSS score ≥3). Furthermore, patients were divided into tirofiban and placebo groups in each stratum. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcome was radiological intracranial hemorrhage within 48 h. RESULTS: 861 patients were included, 439 patients with absent-to-moderate LA and 422 patients with severe LA. There were no significant differences in 90-day mRS score between the tirofiban and placebo groups in either stratum (absent-to-moderate LA: adjusted OR 0.92 (95%CI, 0.66-1.28), P = 0.62; severe LA: adjusted OR 0.99 (95% CI, 0.69-1.42), P = 0.96). In the severe LA stratum, the occurrence of radiologic intracranial hemorrhage was greater in the tirofiban group compared to the placebo group. (35.7% vs 26.4%; adjusted OR, 1.72 (95% CI, 1.12-2.66); P = 0.014). However, no difference was observed in the absent-to-moderate LA stratum (33.2% vs 29.3%; adjusted OR, 1.15 (95% CI, 0.76-1.75); P = 0.51). CONCLUSION: There was no significant difference in disability severity at 90 days when treating AIS patients using intravenous tirofiban before endovascular therapy, in either absent-to-moderate or severe LA strata. It should be noted that intravenous tirofiban before endovascular therapy increases the incidence of radiologic intracranial hemorrhage in patients with severe LA.

14.
Mil Med Res ; 11(1): 46, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992778

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.


Subject(s)
Global Burden of Disease , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/epidemiology , Male , Female , Incidence , Middle Aged , Aged , Adult , Global Burden of Disease/trends , Disability-Adjusted Life Years/trends , Global Health/statistics & numerical data , Aged, 80 and over
15.
J Pharm Biomed Anal ; 248: 116288, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38981330

ABSTRACT

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.


Subject(s)
Drugs, Chinese Herbal , Rats, Sprague-Dawley , Sesquiterpenes, Germacrane , Animals , Sesquiterpenes, Germacrane/metabolism , Rats , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/administration & dosage , Male , Chromatography, High Pressure Liquid/methods , Tissue Distribution , Administration, Oral , Feces/chemistry
16.
Basic Res Cardiol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992300

ABSTRACT

Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.

17.
Res Sq ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38947036

ABSTRACT

The Cystine-xCT transporter-Glutathione (GSH)-GPX4 axis is the canonical pathway to protect against ferroptosis. While not required for ferroptosis-inducing compounds (FINs) targeting GPX4, FINs targeting the xCT transporter require mitochondria and its lipid peroxidation to trigger ferroptosis. However, the mechanism underlying the difference between these FINs is still unknown. Given that cysteine is also required for coenzyme A (CoA) biosynthesis, here we show that CoA supplementation specifically prevents ferroptosis induced by xCT inhibitors but not GPX4 inhibitors. We find that, auranofin, a thioredoxin reductase inhibitor, abolishes the protective effect of CoA. We also find that CoA availability determines the enzymatic activity of thioredoxin reductase, but not thioredoxin. Importantly, the mitochondrial thioredoxin system, but not the cytosolic thioredoxin system, determines CoA-mediated ferroptosis inhibition. Our data show that the CoA regulates the in vitro enzymatic activity of mitochondrial thioredoxin reductase (TXNRD2) by covalently modifying the thiol group of cysteine (CoAlation) on Cys-483. Replacing Cys-483 with alanine on TXNRD2 abolishes its in vitro enzymatic activity and ability to protect cells from ferroptosis. Targeting xCT to limit cysteine import and, therefore, CoA biosynthesis reduced CoAlation on TXNRD2, an effect that was rescued by CoA supplementation. Furthermore, the fibroblasts from patients with disrupted CoA metabolism demonstrate increased mitochondrial lipid peroxidation. In organotypic brain slice cultures, inhibition of CoA biosynthesis leads to an oxidized thioredoxin system, mitochondrial lipid peroxidation, and loss in cell viability, which were all rescued by ferrostatin-1. These findings identify CoA-mediated post-translation modification to regulate the thioredoxin system as an alternative ferroptosis protection pathway with potential clinical relevance for patients with disrupted CoA metabolism.

18.
Biosens Bioelectron ; 263: 116597, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39059179

ABSTRACT

Traditional temporary cardiac pacemakers (TCPs), which employ transcutaneous leads and external wired power systems are battery-dependent and generally non-absorbable with rigidity, thereby necessitating surgical retrieval after therapy and resulting in potentially severe complications. Wireless and bioresorbable transient pacemakers have, hence, emerged recently, though hitting a bottleneck of unfavorable tissue-device bonding interface subject to mismatched mechanical modulus, low adhesive strength, inferior electrical performances, and infection risks. Here, to address such crux, we develop a multifunctional interface hydrogel (MIH) with superior electrical performance to facilitate efficient electrical exchange, comparable mechanical strength to natural heart tissue, robust adhesion property to enable stable device-tissue fixation (tensile strength: ∼30 kPa, shear strength of ∼30 kPa, and peel-off strength: ∼85 kPa), and good bactericidal effect to suppress bacterial growth. Through delicate integration of this versatile MIH with a leadless, battery-free, wireless, and transient pacemaker, the entire system exhibits stable and conformal adhesion to the beating heart while enabling precise and constant electrical stimulation to modulate the cardiac rhythm. It is envisioned that this versatile MIH and the proposed integration framework will have immense potential in overcoming key limitations of traditional TCPs, and may inspire the design of novel bioelectronic-tissue interfaces for next-generation implantable medical devices.


Subject(s)
Hydrogels , Pacemaker, Artificial , Wireless Technology , Hydrogels/chemistry , Animals , Humans , Biosensing Techniques/instrumentation , Equipment Design , Adhesives/chemistry
19.
J Affect Disord ; 363: 619-625, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39043307

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. METHODS: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. RESULTS: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). LIMITATIONS: The cross-sectional design of this study precludes establishing causal relationships. CONCLUSION: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD.


Subject(s)
Benzodiazepines , Depressive Disorder, Major , Humans , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/drug therapy , Male , Female , Adult , Benzodiazepines/therapeutic use , Benzodiazepines/adverse effects , Middle Aged , Cross-Sectional Studies , Adolescent , Prevalence , Young Adult , China/epidemiology , Risk Factors , Sleep Wake Disorders/epidemiology , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Anxiety Disorders/drug therapy
20.
Sci Rep ; 14(1): 12621, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38824201

ABSTRACT

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.


Subject(s)
Anaplasma , Anaplasmosis , Animals, Domestic , Ehrlichia , Genetic Variation , Goats , RNA, Ribosomal, 16S , Animals , Anaplasma/genetics , Anaplasma/isolation & purification , China/epidemiology , Ehrlichia/genetics , Ehrlichia/isolation & purification , Goats/microbiology , Dogs , Cattle , Anaplasmosis/epidemiology , Anaplasmosis/microbiology , Prevalence , Animals, Domestic/microbiology , RNA, Ribosomal, 16S/genetics , Ticks/microbiology , Ehrlichiosis/epidemiology , Ehrlichiosis/veterinary , Ehrlichiosis/microbiology , Phylogeny
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