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1.
Proc Natl Acad Sci U S A ; 120(21): e2209829120, 2023 May 23.
Article in English | MEDLINE | ID: mdl-37200363

ABSTRACT

Solids built out of active components have exhibited odd elastic stiffness tensors whose active moduli appear in the antisymmetric part and which give rise to non-Hermitian static and dynamic phenomena. Here, we present a class of active metamaterial featured with an odd mass density tensor whose asymmetric part arises from active and nonconservative forces. The odd mass density is realized using metamaterials with inner resonators connected by asymmetric and programmable feed-forward control on acceleration and active forces along the two perpendicular directions. The active forces produce unbalanced off-diagonal mass density coupling terms, leading to non-Hermiticity. The odd mass is then experimentally validated through a one-dimensional nonsymmetric wave coupling where propagating transverse waves are coupled with longitudinal ones whereas the reverse is forbidden. We reveal that the two-dimensional active metamaterials with the odd mass can perform in either energy-unbroken or energy-broken phases separated by exceptional points along principal directions of the mass density. The odd mass density contributes to the wave anisotropy in the energy-unbroken phase and directional wave energy gain in the energy-broken phase. We also numerically illustrate and experimentally demonstrate the two-dimensional wave propagation phenomena that arise from the odd mass in active solids. Finally, the existence of non-Hermitian skin effect is discussed in which boundaries host an extensive number of localized modes. It is our hope that the emergent concept of the odd mass can open up a new research platform for mechanical non-Hermitian system and pave the ways for developing next-generation wave steering devices.

2.
PLoS Comput Biol ; 20(6): e1012244, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38917196

ABSTRACT

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.


Subject(s)
Anti-Arrhythmia Agents , Computer Simulation , Models, Cardiovascular , Myocardial Infarction , Myocardial Ischemia , Anti-Arrhythmia Agents/pharmacology , Anti-Arrhythmia Agents/therapeutic use , Myocardial Ischemia/drug therapy , Myocardial Ischemia/physiopathology , Humans , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/physiopathology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Computational Biology
3.
Apoptosis ; 29(7-8): 1126-1144, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38824480

ABSTRACT

BACKGROUND: 5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy. METHODS: Using bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking. RESULTS: The 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity. CONCLUSION: We developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC.


Subject(s)
Colorectal Neoplasms , Drug Resistance, Neoplasm , Fluorouracil , Immunotherapy , Humans , Fluorouracil/therapeutic use , Fluorouracil/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Prognosis , Gene Expression Regulation, Neoplastic/drug effects , Female , Male , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/immunology , Molecular Docking Simulation
4.
Int J Obes (Lond) ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902386

ABSTRACT

BACKGROUND: As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear. METHODS: In this study, male wild-type (WT) and Pparα-null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues. RESULTS: The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells. CONCLUSION: Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis.

5.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38549133

ABSTRACT

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Subject(s)
Propofol , Sepsis , Mice , Humans , Animals , Propofol/pharmacology , Propofol/therapeutic use , Propofol/metabolism , Toll-Like Receptor 4/metabolism , Disease Models, Animal , Macrophages/metabolism , Sepsis/complications , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism
6.
Scand J Immunol ; 99(5): e13362, 2024 May.
Article in English | MEDLINE | ID: mdl-38605563

ABSTRACT

T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low-density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT-PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay. We found that GM-CSF+IFN-γ- ThGM cells existed in atherosclerotic aortas. Live ThGM cells were enriched in aortic CD4+CCR6-CCR8-CXCR3-CCR10+ T cells. Aortic ThGM cells triggered the expression of interleukin-1ß (IL-1ß), tumour necrosis factor (TNF), interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2) in macrophages. Besides, aortic ThGM cells expressed higher CD69 than other T cells and bound to oxLDL. oxLDL suppressed the cytokine expression in ThGM cells probably via inhibiting the signal transducer and activator of transcription 5 (STAT5) signalling. Furthermore, oxLDL alleviated the effect of ThGM cells on inducing macrophages to produce pro-inflammatory cytokines and generate foam cells. The nuclear receptor subfamily 4 group A (NR4A) members NR4A1 and NR4A2 were involved in the suppressive effect of oxLDL on ThGM cells. Collectively, oxLDL suppressed the supportive effect of ThGM cells on pro-atherosclerotic macrophages.


Subject(s)
Atherosclerosis , Granulocyte-Macrophage Colony-Stimulating Factor , Lipoproteins, LDL , Macrophages , T-Lymphocytes, Helper-Inducer , Animals , Mice , Atherosclerosis/genetics , Cytokines/metabolism , Foam Cells/pathology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Interleukin-6/metabolism , Lipoproteins, LDL/metabolism , Macrophages/metabolism , T-Lymphocytes, Helper-Inducer/metabolism
7.
Reproduction ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39042720

ABSTRACT

Oocyte activation failure, one of the main factors of total fertilization failure (TFF) after ICSI, could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCζ), a sperm factor, was associated with Ca2+ oscillations in oocytes of mammals. To date, only a limited number of mutations in PLCZ1 (the gene encodes PLCζ) have been linked to TFF demonstrated by the observed reduction in protein levels or activity. In this study, males with normozoospermic sperm suffering TFF after ICSI and their families were recruited. Firstly, mutations in the PLCZ1 sequence were identified by Whole exome sequencing and validated by Sanger sequencing. Then the transcript and protein levels and locations of PLCZ1/PLCζ in sperms of patients were studied followed by in vitro function analysis and in silico analysis to investigate the function-structure correlation of mutations identified in PLCZ1 through Western blotting, Immunofluorescence, RT-qPCR and Molecular Simulation. Ca2+ oscillations were detected after cRNA microinjection with MⅡ mouse oocyte to investigate the calcium oscillations of abnormal PLCζ. Five variants in compound heterozygosity were identified including five new mutations and three-reported mutations which were located across the main domains of PLCζ, except the EF hands domain. The transcript and protein levels were decreased among all the mutations identified in PLCZ1 at different degrees when transfected with HEK293T cells. Among these mutations, M138V and R391* of PLCζ could not trigger normal Ca2+ oscillations. In case 5, an abnormal location in the head of sperm and a higher expression of PLCζ in the sperm were found.

8.
Phys Rev Lett ; 132(20): 206502, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38829100

ABSTRACT

The disorder operator is often designed to reveal the conformal field theory (CFT) information in quantum many-body systems. By using large-scale quantum Monte Carlo simulation, we study the scaling behavior of disorder operators on the boundary in the two-dimensional Heisenberg model on the square-octagon lattice with gapless topological edge state. In the Affleck-Kennedy-Lieb-Tasaki phase, the disorder operator is shown to hold the perimeter scaling with a logarithmic term associated with the Luttinger liquid parameter K. This effective Luttinger liquid parameter K reflects the low-energy physics and CFT for (1+1)D boundary. At bulk critical point, the effective K is suppressed but it keeps finite value, indicating the coupling between the gapless edge state and bulk fluctuation. The logarithmic term numerically captures this coupling picture, which reveals the (1+1)D SU(2)_{1} CFT and (2+1)D O(3) CFT at boundary criticality. Our Letter paves a new way to study the exotic boundary state and boundary criticality.

9.
Phys Rev Lett ; 132(21): 215101, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38856257

ABSTRACT

Polarization of drift-Alfvén waves, defined as the ratio of electrostatic to electromagnetic fluctuations, has remained unmeasurable in fusion plasmas for decades, despite its pivotal role in understanding wave dynamics and their impact on plasmas. We report the first measurements of drift-Alfvén wave polarization in a hot, magnetically confined plasma. The breakthrough is enabled by a novel methodology developed from gyrokinetic theory, utilizing fluctuations of electron temperature and density. Analysis of data from the DIII-D tokamak reveals that the waves above the geodesic acoustic mode frequency exhibit dominant electromagnetic polarization, whereas lower-frequency waves show a mix of electromagnetic and electrostatic polarization, indicating a strong coupling between shear Alfvén waves and drift-acoustic waves.

10.
Langmuir ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39049428

ABSTRACT

In order to address the issue of protonation of functional groups and structural instability on the surface of aerogel due to strong acidic wastewater, a three-dimensional bis-pyridine N cellulose aerogel [PEIPD/carboxymethyl cellulose (CMC)] with protonation resistance was prepared in this paper by grafting pyridine onto polyethylenimine. The adsorption capacity for Cu2+ of the as-prepared aerogel is as high as 1.64 mmol/g (pH 5) and is maintained well in high-acidity solutions (1.15 mmol/g at pH = 2). It reveals high selectivity, splendid anti-interference ability, and also reliable on the recycle performance. Through the zeta potential tests, this adsorbent reveals a rather low zero charge point (pHpzc = 2.2). The adsorption of Cu2+ on the adsorbent is consistent with the pseudo-second-order kinetic model and the Langmuir model, suggesting that the adsorption process is dominated by chemisorption in a monolayer. The characterizations by Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy proved pyridine N as responsible binding sites, based on which two possible mechanisms are proposed, including chelation and cation-π interaction. Density functional theory calculations are further used to precisely investigate the pathway. By comparing the binding energies, molecular electrostatic potentials, electron densities, and differential charge densities, the bis-pyridine N functional group is finally determined to be of much higher affinity to Cu2+ following chelation reaction as designated. By integrating bis-pyridine N with the CMC and understanding their crucial roles, this will provide significant insights into the rational design of aerogel adsorbents to enhance the recovery of Cu from strongly acidic wastewaters.

11.
J Gastroenterol Hepatol ; 39(1): 81-106, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37855067

ABSTRACT

BACKGROUND AND AIM: Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS: Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS: The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS: A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.


Subject(s)
Colonoscopy , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/epidemiology , Risk Factors , Early Detection of Cancer , Hallucinations
12.
J Chem Phys ; 160(20)2024 May 28.
Article in English | MEDLINE | ID: mdl-38804489

ABSTRACT

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

13.
J Sep Sci ; 47(1): e2300677, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37994256

ABSTRACT

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.


Subject(s)
Drugs, Chinese Herbal , Glucosides , Monoterpenes , Tandem Mass Spectrometry , Animals , Rats , Administration, Oral , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , Prescriptions , Rats, Sprague-Dawley , Tandem Mass Spectrometry/methods
14.
BMC Musculoskelet Disord ; 25(1): 521, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970016

ABSTRACT

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.


Subject(s)
Arthritis, Rheumatoid , Bone Density , Fractures, Bone , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Bone Density/genetics , Fractures, Bone/genetics , Fractures, Bone/epidemiology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/epidemiology , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Rheumatic Diseases/genetics , Rheumatic Diseases/epidemiology , Rheumatic Diseases/complications , Risk Factors , Spondylitis, Ankylosing/genetics , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/epidemiology , Genetic Predisposition to Disease
15.
Article in English | MEDLINE | ID: mdl-38836736

ABSTRACT

Objective: This study aimed to investigate the efficacy of electroacupuncture (EA) combined with growth hormone in alleviating quadriceps atrophy and enhancing knee function following anterior cruciate ligament reconstruction. Methods: A prospective study was conducted, and a total of 90 patients exhibiting quadriceps atrophy after anterior cruciate ligament reconstruction were recruited between July 2020 and July 2022 from Shenzhen Pingle Orthopedic Hospital. They were randomly assigned to either the control group or the observation group , with 45 patients in each. The control group received routine rehabilitation training along with growth hormone treatment, while the observation group received routine rehabilitation training in addition to EA and growth hormone treatment. The study assessed the visual analogue score (VAS) for postoperative pain, knee function, and clinical outcomes in both groups. Results: The total effective rate in the observation group was significantly higher compared to the control group, with a statistically significant difference (P < .05). Initially, there were no significant differences between the two groups in peri-thigh atrophy index, VAS score, Lysholm score, knee swelling, knee stability, and range of motion (ROM) score (P > .05). However, after 3 and 6 months of treatment, significant reductions were observed in peri-thigh atrophy index, VAS score, knee swelling, and ROM score in the observation group compared to the control group (P < .05). Moreover, Lysholm score and knee stability significantly increased in the observation group (P < .05), with changes significantly higher than those in the control group (P < .05). Conclusions: EA combined with growth hormone treatment significantly reduces quadriceps atrophy and knee joint function in patients undergoing anterior cruciate ligament reconstruction. This combination therapy holds promise for enhancing rehabilitation outcomes in this patient population.

16.
J Med Internet Res ; 26: e57721, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39047282

ABSTRACT

BACKGROUND: Discharge letters are a critical component in the continuity of care between specialists and primary care providers. However, these letters are time-consuming to write, underprioritized in comparison to direct clinical care, and are often tasked to junior doctors. Prior studies assessing the quality of discharge summaries written for inpatient hospital admissions show inadequacies in many domains. Large language models such as GPT have the ability to summarize large volumes of unstructured free text such as electronic medical records and have the potential to automate such tasks, providing time savings and consistency in quality. OBJECTIVE: The aim of this study was to assess the performance of GPT-4 in generating discharge letters written from urology specialist outpatient clinics to primary care providers and to compare their quality against letters written by junior clinicians. METHODS: Fictional electronic records were written by physicians simulating 5 common urology outpatient cases with long-term follow-up. Records comprised simulated consultation notes, referral letters and replies, and relevant discharge summaries from inpatient admissions. GPT-4 was tasked to write discharge letters for these cases with a specified target audience of primary care providers who would be continuing the patient's care. Prompts were written for safety, content, and style. Concurrently, junior clinicians were provided with the same case records and instructional prompts. GPT-4 output was assessed for instances of hallucination. A blinded panel of primary care physicians then evaluated the letters using a standardized questionnaire tool. RESULTS: GPT-4 outperformed human counterparts in information provision (mean 4.32, SD 0.95 vs 3.70, SD 1.27; P=.03) and had no instances of hallucination. There were no statistically significant differences in the mean clarity (4.16, SD 0.95 vs 3.68, SD 1.24; P=.12), collegiality (4.36, SD 1.00 vs 3.84, SD 1.22; P=.05), conciseness (3.60, SD 1.12 vs 3.64, SD 1.27; P=.71), follow-up recommendations (4.16, SD 1.03 vs 3.72, SD 1.13; P=.08), and overall satisfaction (3.96, SD 1.14 vs 3.62, SD 1.34; P=.36) between the letters generated by GPT-4 and humans, respectively. CONCLUSIONS: Discharge letters written by GPT-4 had equivalent quality to those written by junior clinicians, without any hallucinations. This study provides a proof of concept that large language models can be useful and safe tools in clinical documentation.


Subject(s)
Patient Discharge , Humans , Patient Discharge/standards , Electronic Health Records/standards , Single-Blind Method , Language
17.
Nano Lett ; 23(2): 597-605, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36622320

ABSTRACT

The development of high-performance miniaturized and flexible airflow sensors is essential to meet the need of emerging applications. Graphene-based airflow sensors are hampered by the sluggish response and recovery speed and low sensitivity. Here we employ laser-induced graphene (LIG) with poststructural biomimicry for fabricating high-performance, flexible airflow sensors, including cotton-like porous LIG, caterpillar fluff-like vertical LIG fiber, and Lepidoptera scale-like suspended LIG fiber (SLIGF) structures. The structural engineering changes the deformation behavior of LIGs under stress, among which the synchronous propagation of the scale-like structure of SLIGF is the most conducive to airflow sensing. The SLIGF achieves the shortest average response time of 0.5 s, the highest sensitivity of 0.11 s/m, and a record-low detection threshold of 0.0023 m/s, benchmarked against the state-of-the-art airflow sensors. Furthermore, we showcase the SLIGF airflow sensors in weather forecasting, health, and communications applications. Our study will help develop next-generation waterflow, sound, and motion sensors.

18.
J Environ Manage ; 361: 121258, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38815428

ABSTRACT

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.


Subject(s)
Biodegradation, Environmental , Polyesters , Polyethylene Terephthalates , Polyethylene Terephthalates/chemistry , Polyethylene Terephthalates/metabolism , Polyesters/metabolism , Polyesters/chemistry , Carboxylic Ester Hydrolases
19.
J Sci Food Agric ; 104(5): 2561-2573, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-37935642

ABSTRACT

Plant protein is rapidly becoming more of a prime interest to consumers for its nutritional and functional properties, as well as the potential to replace animal protein. In the frame of alternative protein new sources, mung bean is becoming another legume crop that could provide high quality plant protein after soybean and pea. In particular, the 8S globulins in mung bean protein have high structural similarity and homology with soybean ß-conglycinin (7S globulin), with 68% sequence identity. Currently, mung bean protein has gained popularity in food industry because of its high nutritional value and peculiar functional properties. In that regard, various modification technologies have been applied to further broaden its application. Here, we provide a review of the composition, nutritional value, production methods, functional properties and modification technologies of mung bean protein. Furthermore, its potential applications in the new plant-based products, meat products, noodles, edible packaging films and bioactive compound carriers are highlighted to facilitate its utilization as an alternative plant protein, thus meeting consumer demands for high quality plant protein resources. © 2023 Society of Chemical Industry.


Subject(s)
Fabaceae , Vigna , Animals , Vigna/chemistry , Plant Proteins/metabolism , Fabaceae/chemistry , Glycine max
20.
Hum Genet ; 142(6): 735-748, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36995441

ABSTRACT

Asthenozoospermia is one of the main factors leading to male infertility, but the genetic mechanisms have not been fully elucidated. Variants in the androglobin (ADGB) gene were identified in an infertile male characterized by asthenozoospermia. The variants disrupted the binding of ADGB to calmodulin. Adgb-/- male mice were infertile due to reduced sperm concentration (< 1 × 106 /mL) and motility. Spermatogenesis was also abnormal, with malformation of both elongating and elongated spermatids, and there was an approximately twofold increase in apoptotic cells in the cauda epididymis. These exacerbated the decline in sperm motility. It is surprising that ICSI with testicular spermatids allows fertilization and eventually develops into blastocyst. Through mass spectrometry, we identified 42 candidate proteins that are involved in sperm assembly, flagella formation, and sperm motility interacting with ADGB. In particular, CFAP69 and SPEF2 were confirmed to bind to ADGB. Collectively, our study suggests the potential important role of ADGB in human fertility, revealing its relevance to spermatogenesis and infertility. This expands our knowledge of the genetic causes of asthenozoospermia and provides a theoretical basis for using ADGB as an underlying genetic marker for infertile males.


Subject(s)
Asthenozoospermia , Infertility, Male , Animals , Humans , Male , Mice , Asthenozoospermia/genetics , Infertility, Male/genetics , Infertility, Male/metabolism , Semen/metabolism , Sperm Motility/genetics , Spermatozoa/metabolism
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