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1.
Biomol Biomed ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39388705

ABSTRACT

Myasthenia gravis (MG) is an acquired autoimmune disease characterized by impaired transmission at the neuromuscular junction, primarily manifesting as fluctuating muscle weakness, fatigability, and partial paralysis. Due to its long disease course, treatment resistance, and frequent relapses, it places a significant burden on patients and their families. In recent years, advances in molecular biology have provided growing evidence that mitochondrial dysfunction impairs muscle function and affects immune cell proliferation and differentiation in patients. Mitochondria, as the cell's energy source, play a critical role in various pathological processes in MG, including oxidative stress, dynamic abnormalities, mitophagy, and mitochondrial metabolism. The role of mitochondrial dysfunction in the pathogenesis of MG has garnered increasing attention. This manuscript primarily explores mitochondrial function and abnormal morphological changes in MG, as well as mitochondrial quality control, metabolic reprogramming, and their potential mechanisms in the pathological changes of the disease. It also reviews the current status of drug therapies aimed at improving mitochondrial function. The goal is to provide novel perspectives and strategies for future mitochondrial-targeted therapies in MG.

2.
J Orthop Surg Res ; 19(1): 654, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39402586

ABSTRACT

BACKGROUND: Traditional fixation methods for posterior wall acetabular fractures (PWAFs) typically require the utilization of multiple plates and intraoperative plate contouring, which are technically demanding and carry the risk of intra-articular screw penetration. A novel posterior anatomical integrated locking compression plate (PAILCP) has been designed to optimize these shortcomings. This study aims to evaluate the feasibility and effectiveness of the PAILCP fixation method for the surgical management of PWAFs. METHODS: A total of 48 patients with PWAFs who were treated surgically in our department between January 2018 and December 2022 were selected for retrospective analysis. The 48 patients were classified into groups A (PAILCP fixation, n = 25) and B (traditional fixation, n = 23) according to different fixation methods. Fracture reduction quality, number of utilized plates, blood loss, surgical time, instrumentation time, hip function, and complications were compared between the two groups. RESULTS: A total of 25 PAILCPs were used in group A, while 34 mini-T plates and 29 reconstruction plates were employed in group B. Compared to the patients in group B, those in group A had significantly shorter instrumentation time (- 16 min) and surgical time (- 23 min) as well as lower blood loss (- 123 ml). However, no significant differences were observed in fracture reduction quality and hip function between the two groups. Additionally, the complication rate was slightly lower in group A (3/25 patients) than in group B (6/23); however, this difference was not statistically significant. Finally, follow-up examination revealed no main plate breakage, miniplate displacement, screw loosening, or intra-articular screw penetration in all patients. CONCLUSION: The surgical treatment of PWAFs using the PAILCP fixation method results in shorter instrumentation and surgical time and lower blood loss than the traditional fixation method. Thus, the PAILCP fixation method is a promising alternative for PWAFs management, offering enhanced surgical ease and safety.


Subject(s)
Acetabulum , Bone Plates , Fracture Fixation, Internal , Fractures, Bone , Humans , Acetabulum/surgery , Acetabulum/injuries , Acetabulum/diagnostic imaging , Male , Female , Middle Aged , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentation , Retrospective Studies , Adult , Fractures, Bone/surgery , Fractures, Bone/diagnostic imaging , Feasibility Studies , Treatment Outcome , Operative Time , Aged
3.
Front Pharmacol ; 15: 1459655, 2024.
Article in English | MEDLINE | ID: mdl-39355779

ABSTRACT

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology. Methods: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD. Results: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including ß-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance. Conclusion: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.

4.
Gut ; 2024 Oct 14.
Article in English | MEDLINE | ID: mdl-39349007

ABSTRACT

BACKGROUND: The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment. OBJECTIVE: Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic strategy for remoulding the HCC microenvironment. DESIGN: The genome-wide in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted to identify the key genes associated with immune tolerance. Single-cell RNA-seq (scRNA-seq), flow cytometry, HCC mouse models, chromatin immunoprecipitation and coimmunoprecipitation were used to explore the function and mechanism of adenylate cyclase 7 (ADCY7) in HCC immune surveillance. RESULTS: Here, a genome-wide in vivo CRISPR screen identified a novel immune modulator-ADCY7. The transmembrane protein ADCY7 undergoes subcellular translocation via caveolae-mediated endocytosis and then translocates to the nucleus with the help of leucine-rich repeat-containing protein 59 (LRRC59) and karyopherin subunit beta 1 (KPNB1). In the nucleus, it functions as a transcription cofactor of CCAAT/enhancer binding protein alpha (CEBPA) to induce CCL5 transcription, thereby increasing CD8+ T cell infiltration to restrain HCC progression. Furthermore, ADCY7 can be secreted as exosomes and enter neighbouring tumour cells to promote CCL5 induction. Exosomes with high ADCY7 levels promote intratumoural infiltration of CD8+ T cells and suppress HCC tumour growth. CONCLUSION: We delineate the unconventional function and subcellular location of ADCY7, highlighting its pivotal role in T cell-mediated immunity in HCC and its potential as a promising treatment target.

5.
Food Chem ; 463(Pt 3): 141399, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39326316

ABSTRACT

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin with widespread contamination. Inspired by lactone hydrolases, a peptide-based enzyme mimetic material for degrading ZEN was developed by combining serine, histidine and glutamate (S/H/E) catalytic triad with pro-hydrophobic self-assembling sequences and oxyanion hole site. Chitosan hybrid membranes were prepared, followed by immobilizing enzyme mimic on the membrane surface to fabricate biocatalytic membrane reactor. The membrane reactor, with good thermal stability and high catalytic activity after repeated use, can be applied to the degradation of ZEN in food. Computer simulation studies of the degradation mechanism indicated that the carbon atom on the lactone bond within ZEN molecule was susceptible to catalytic triplex attack, leading to lactone bond broken, followed by spontaneous decarboxylation to produce dihydroxyphenyl derivatives with greatly reduced binding capacity to the estrogen receptors. This kind of peptide-based enzyme mimetic material would be very promising in degrading mycotoxins in food safety field.

6.
BMC Med ; 22(1): 407, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304842

ABSTRACT

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.


Subject(s)
Delayed Graft Function , Kidney Transplantation , Machine Learning , Tissue Donors , Humans , Kidney Transplantation/adverse effects , Female , Male , Child , Retrospective Studies , Adolescent , Child, Preschool , Infant
7.
Eur Spine J ; 33(10): 3933-3940, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39198288

ABSTRACT

PURPOSE: This study aimed to quantify and evaluate morphology of intervertebral space between neighboring cervical units using radiographic imaging indices, to help spine surgeons when performing anterior cervical discectomy and fusion (ACDF) surgery on the Chinese population. METHODS: The background and imaging parameters of the subjects were assessed. Cervical lateral radiographs were employed to measure the intervertebral height (IH), intervertebral height index (IHI), and segmental lordosis (SL). Endplate parameters measurements were conducted on sagittal T2-weighted magnetic resonance imaging (MRI), including endplate sagittal diameter (ESD), and endplate concavity depth (ECD). All individuals were divided into three age groups: individuals aged 20-35 were in group A, individuals aged 36-50 were in group B, and individuals aged over 50 were in group C. A comparison of the variables was conducted among the three groups. Additionally, these radiographic parameters were also compared between males and females. RESULTS: A total of 102 individuals were included in this study. IH was greater at C6/7 than those at other segmental levels (p < 0.001). The largest SL values were found at C6/7, while the least were found at C3/4. The superior ESD (ESDs) and ECD (ECDs) of the intervertebral space were significantly greater than those of the inferior endplates (p < 0.05). The ESD and ECD values were the largest at C6/7, while the least at C3/4. Additionally, age and gender had an influence on several parameters. IH was significantly lower in group A compared to group B (p < 0.05) and group C (p < 0.05) from C3/4 level to C6/7 level. ECDs were lower in group A compared to group B (p < 0.05) and group C (p < 0.05) at each level. IH and ESD in males were generally significantly greater than those in females at all levels (p < 0.05). CONCLUSION: The current study found that C6/7 had the greatest IH, SL, ESD, and ECD values in asymptomatic Chinese. SL gradually increased from C3/4 to C6/7 levels. IH and ECD were significantly associated with age. Males had greater IH and ESD values than females. These findings provide baseline information for planning for selection of anterior screws and intervertebral implants.


Subject(s)
Cervical Vertebrae , Humans , Male , Female , Adult , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/anatomy & histology , Middle Aged , Magnetic Resonance Imaging , Young Adult , Aged , Asian People , Lordosis/diagnostic imaging , Lordosis/surgery , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/surgery , Intervertebral Disc/anatomy & histology , China , Radiography , East Asian People
8.
BMC Med ; 22(1): 328, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39135035

ABSTRACT

BACKGROUND: Mothers play a crucial role in influencing their daughters' HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. METHODS: From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9-17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. RESULTS: Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02-1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. CONCLUSIONS: These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.


Subject(s)
Mothers , Papillomavirus Infections , Papillomavirus Vaccines , Social Media , Humans , Cross-Sectional Studies , Female , Adolescent , China , Papillomavirus Vaccines/administration & dosage , Papillomavirus Infections/prevention & control , Child , Mothers/psychology , Adult , Vaccination/psychology , Health Knowledge, Attitudes, Practice , Nuclear Family , Patient Acceptance of Health Care , Middle Aged , Surveys and Questionnaires
9.
Vaccine X ; 19: 100529, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39161948

ABSTRACT

Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers' decisional conflicts, satisfaction with governmental health promotion materials, and their daughters' HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9-17 years in Shenzhen, China. Participants were mothers having a daughter aged 9-17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9-17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government's health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers' decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.

10.
J Am Chem Soc ; 146(33): 22913-22917, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39110062

ABSTRACT

The magneto-optical response of chiral materials holds significant potential for applications in physics, chemistry, and biology. However, exploration of the near-infrared (NIR) magneto-optical response remains limited. Herein, we report the synthesis and strong NIR-II magneto-optical activity of three pairs of chiral 3d-4f clusters of R/S-Ln15Cu54 (Ln = Sm, Gd, and Dy). Structural analysis reveals that R/S-Ln15Cu54 features a triangular prism cage with C3 symmetry. Interestingly, magnetic circular dichroism (MCD) spectra exhibit remarkable magneto-optical response in the NIR-II region, driven by the f-f transition. The maximum g-factor of R/S-Sm15Cu54 reaches 5.5 × 10-3 T-1 around 1300-1450 nm, surpassing values associated with DyIII and CuII ions. This remarkable NIR-II magneto-optical activity may be attributed to strong magnetic-dipole-allowed f-f transitions and helix chirality of the structure. This work not only presents the largest Ln-Cu clusters to date but also demonstrate the key role of magnetic-dipole-allowed transitions on magneto-optical activity.

11.
Adv Sci (Weinh) ; 11(36): e2401085, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39056405

ABSTRACT

Cytotoxic neuronal swelling and glutamate excitotoxicity are two hallmarks of ischemic stroke. However, the underlying molecular mechanisms are not well understood. Here, it is reported that SWELL1, the essential subunit of the volume-regulated anion channel (VRAC), plays a dual role in ischemic injury by promoting neuronal swelling and glutamate excitotoxicity. SWELL1 expression is upregulated in neurons and astrocytes after experimental stroke in mice. The neuronal SWELL1 channel is activated by intracellular hypertonicity, leading to Cl- influx-dependent cytotoxic neuronal swelling and subsequent cell death. Additionally, the SWELL1 channel in astrocytes mediates pathological glutamate release, indicated by increases in neuronal slow inward current frequency and tonic NMDAR current. Pharmacologically, targeting VRAC with a new inhibitor, an FDA-approved drug Dicumarol, attenuated cytotoxic neuronal swelling and cell death, reduced astrocytic glutamate release, and provided significant neuroprotection in mice when administered either before or after ischemia. Therefore, these findings uncover the pleiotropic effects of the SWELL1 channel in neurons and astrocytes in the pathogenesis of ischemic stroke and provide proof of concept for therapeutically targeting it in this disease.


Subject(s)
Brain Ischemia , Disease Models, Animal , Glutamic Acid , Neurons , Animals , Mice , Glutamic Acid/metabolism , Glutamic Acid/toxicity , Neurons/metabolism , Neurons/drug effects , Neurons/pathology , Brain Ischemia/metabolism , Brain Ischemia/pathology , Male , Astrocytes/metabolism , Astrocytes/drug effects , Mice, Inbred C57BL , Membrane Proteins
12.
Bioengineering (Basel) ; 11(7)2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39061820

ABSTRACT

With the rapid advancement of computer vision, machine learning, and consumer electronics, eye tracking has emerged as a topic of increasing interest in recent years. It plays a key role across diverse domains including human-computer interaction, virtual reality, and clinical and healthcare applications. Near-eye tracking (NET) has recently been developed to possess encouraging features such as wearability, affordability, and interactivity. These features have drawn considerable attention in the health domain, as NET provides accessible solutions for long-term and continuous health monitoring and a comfortable and interactive user interface. Herein, this work offers an inaugural concise review of NET for health, encompassing approximately 70 related articles published over the past two decades and supplemented by an in-depth examination of 30 literatures from the preceding five years. This paper provides a concise analysis of health-related NET technologies from aspects of technical specifications, data processing workflows, and the practical advantages and limitations. In addition, the specific applications of NET are introduced and compared, revealing that NET is fairly influencing our lives and providing significant convenience in daily routines. Lastly, we summarize the current outcomes of NET and highlight the limitations.

13.
Eur J Radiol ; 178: 111621, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39018646

ABSTRACT

PURPOSE: Early diagnosis of benign and malignant vertebral compression fractures by analyzing imaging data is crucial to guide treatment and assess prognosis, and the development of radiomics made it an alternative option to biopsy examination. This systematic review and meta-analysis was conducted with the purpose of quantifying the diagnostic efficacy of radiomics models in distinguishing between benign and malignant vertebral compression fractures. METHODS: Searching on PubMed, Embase, Web of Science and Cochrane Library was conducted to identify eligible studies published before September 23, 2023. After evaluating for methodological quality and risk of bias using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we selected studies providing confusion matrix results to be included in random-effects meta-analysis. RESULTS: A total of sixteen articles, involving 1,519 vertebrae with pathological-diagnosed tumor infiltration, were included in our meta-analysis. The combined sensitivity and specificity of the top-performing models were 0.92 (95 % CI: 0.87-0.96) and 0.93 (95 % CI: 0.88-0.96), respectively. Their AUC was 0.97 (95 % CI: 0.96-0.99). By contrast, radiologists' combined sensitivity was 0.90 (95 %CI: 0.75-0.97) and specificity was 0.92 (95 %CI: 0.67-0.98). The AUC was 0.96 (95 %CI: 0.94-0.97). Subsequent subgroup analysis and sensitivity test suggested that part of the heterogeneity might be explained by differences in imaging modality, segmentation, deep learning and cross-validation. CONCLUSION: We found remarkable diagnosis potential in correctly distinguishing vertebral compression fractures in complex clinical contexts. However, the published radiomics models still have a great heterogeneity, and more large-scale clinical trials are essential to validate their generalizability.


Subject(s)
Fractures, Compression , Radiomics , Spinal Fractures , Spinal Neoplasms , Humans , Diagnosis, Differential , Fractures, Compression/diagnostic imaging , Fractures, Compression/etiology , Sensitivity and Specificity , Spinal Fractures/diagnostic imaging , Spinal Fractures/etiology , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/complications
14.
J Phys Chem B ; 128(30): 7322-7331, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39028892

ABSTRACT

Cyclic peptides (CPs) are emerging as promising drug candidates. Numerous natural CPs and their analogs are effective therapeutics against various diseases. Notably, many of them contain peptidyl cis-prolyl bonds. Due to the high rotational barrier of peptide bonds, conventional molecular dynamics simulations struggle to effectively sample the cis/trans-isomerization of peptide bonds. Previous studies have highlighted the high accuracy of the residue-specific force field (RSFF) and the high sampling efficiency of high-temperature molecular dynamics (high-T MD). Herein, we propose a protocol that combines high-T MD with RSFF2C and a recently developed reweighting method based on probability densities for accurate structure prediction of proline-containing CPs. Our method successfully predicted 19 out of 23 CPs with the backbone rmsd < 1.0 Å compared to X-ray structures. Furthermore, we performed high-T MD and density reweighting on the sunflower trypsin inhibitor (SFTI-1)/trypsin complex to demonstrate its applicability in studying CP-complexes containing cis-prolines. Our results show that the conformation of SFTI-1 in aqueous solution is consistent with its bound conformation, potentially facilitating its binding.


Subject(s)
Molecular Dynamics Simulation , Peptides, Cyclic , Proline , Peptides, Cyclic/chemistry , Proline/chemistry , Trypsin/chemistry , Trypsin/metabolism , Temperature , Protein Conformation
15.
IEEE J Biomed Health Inform ; 28(9): 5613-5623, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38869994

ABSTRACT

Sensor-based rehabilitation physical training assessment methods have attracted significant attention in refined evaluation scenarios. A refined rehabilitation evaluation method combines the expertise of clinicians with advanced sensor-based technology to capture and analyze subtle movement variations often unobserved by traditional subjective methods. Current approaches center on either body postures or muscle strength, which lack more sophisticated analysis features of muscle activation and coordination, thereby hindering analysis efficacy in deep rehabilitation feature exploration. To address this issue, we present a multimodal network algorithm that integrates surface electromyography (sEMG) and stress distribution signals. The algorithm considers the physical knowledge a priori to interpret the current rehabilitation stage and efficiently handles temporal dynamics arising from diverse user profiles in an online setting. Besides, we verified the performance of this model using a learned-nonuse phenomenon assessment task in 24 subjects, achieving an accuracy of 94.7%. Our results surpass those of conventional feature-based, distance-based, and ensemble baseline models, highlighting the advantages of incorporating multimodal information rather than relying solely on unimodal data. Moreover, the proposed model presents a network design solution for rehabilitation physical training that requires deep bioinformatic features and can potentially assist real-time and home-based physical training work.


Subject(s)
Algorithms , Electromyography , Humans , Electromyography/methods , Male , Adult , Female , Signal Processing, Computer-Assisted , Young Adult
16.
Spine J ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942298

ABSTRACT

BACKGROUND CONTEXT: Extreme Lateral Interbody Fusion (XLIF) has been established as an effective treatment for degenerative disorders of the lumbar spine. Nevertheless, there is a potential risk of lumbar plexus damage associated with XLIF, especially during surgeries at the L4-5 segment. Diffusion Tensor Imaging (DTI) evaluates the directional diffusion of water molecules in tissue, providing a more intricate depiction of internal tissue microstructure compared to conventional MRI techniques. The capability of DTI sequences to elucidate the 3-dimensional interplay between lumbar nerve pathways and adjacent musculoskeletal structures, potentially reducing the incidence of nerve injury complications related to XLIF, remains to be established. PURPOSE: This study evaluates the effectiveness of preoperative Diffusion Tensor Imaging (DTI) in reducing neurological complications after Extreme Lateral Interbody Fusion (XLIF) surgeries at the L4-5 level, focusing on the interaction between lumbar nerves and the psoas major muscle. STUDY DESIGN: Retrospective case-control study. PATIENT SAMPLE: The study included 128 patients undergoing XLIF surgery for degenerative disorders at the L4-5 segment: 68 in the traditional group and 62 in the DTI group. OUTCOME MEASURES: The study assessed Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores, along with complication rates. It also documented psoas major muscle morphology and its correlation with nerve pathways. METHODS: A retrospective analysis of 128 patients undergoing XLIF surgery for degenerative disorders at the L4-5 segment between February 2020 and August 2022 was conducted. The cohort was divided into a traditional group (68 patients) receiving presurgery MRI scans to identify surgical entry points at the intervertebral space midpoint (Zones II-III junction) and a DTI group (62 patients) who additionally underwent preoperative DTI to customize entry points. The study evaluated VAS and ODI scores, complication rates, psoas major muscle morphology, and its interaction with nerve pathways. RESULTS: The traditional group uniformly chose the Zone II-III junction for entry. In contrast, the DTI group's entry points varied. Postoperative follow-up revealed significant improvements in VAS and ODI scores in both groups. However, the DTI group experienced fewer immediate postoperative complications such as thigh pain, numbness, and motor disturbances. The study also noted a ventral shift in nerve positioning in patients with elevated psoas muscles. CONCLUSIONS: Preoperative DTI effectively maps the relationship between the psoas major muscle and lumbar nerves. Tailoring surgical entry points based on DTI results significantly reduces the risk of nerve damage in XLIF surgeries. The study underscores the importance of recognizing variability in lumbar nerve pathways due to differing psoas muscle morphologies, highlighting a higher risk of nerve injury in patients with elevated psoas muscles during XLIF procedures.

17.
Analyst ; 149(15): 3951-3960, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38940008

ABSTRACT

Safety problems caused by organophosphorus pesticide (OP) residues are constantly occurring, so the development of new methods for the degradation and detection of OPs is of great scientific significance. In the present study, ß-sheet peptides and ß-hairpin peptides for catalyzing the hydrolysis of OPs were designed and synthesized. The peptide sequences with the highest hydrolytic activity (EHSGGVTVDPPLTVEHSAG) were screened by investigating the effect of the location of the active sites of the peptide and the peptide's structure on the degradation of OPs. In addition, the relationship between the peptides' conformation and hydrolytic activity was further analyzed based on density functional theory calculations. The noncovalent interactions of the peptides with the OPs and the electrostatic potential on the molecular surface and molecular docking properties were also investigated. It was found that peptides with approximate active amino acids consisting of the catalytic triad and with the hairpin structure had enhanced hydrolytic activity toward the hydrolysis of OPs. To develop an electrochemical sensor technique to detect OPs, the conductive MXene (Ti3C2) material was first immobilized with a caffeic acid monolayer via enediol-metal complex chemistry and then bound with the ß-hairpin peptide (EHSGGVTVDPPLTVEHSAG) via carboxy-amine condensation chemistry between the -COOH of caffeic acid and the -NH2 of the peptide to prepare a MXene-peptide composite. Then, the prepared composite was modified on the surface of a glassy carbon electrode to construct an electrochemical sensor for the detection of OPs. The developed technique could be used to monitor OPs within 15 min with a two orders of linear working range and with a detection limit of 0.15 µM. Meanwhile, the sensor showed good reliability for the detection of OPs in real vegetables.


Subject(s)
Organophosphorus Compounds , Pesticides , Pesticides/analysis , Pesticides/chemistry , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/analysis , Hydrolysis , Molecular Docking Simulation , Peptides/chemistry , Limit of Detection , Electrochemical Techniques/methods , Amino Acid Sequence , Caffeic Acids
18.
Chem Commun (Camb) ; 60(56): 7228-7231, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38912666

ABSTRACT

A visible-light-induced K2S2O8-promoted cascade sulfonation/cyclization reaction was established using 3-(2-(ethynyl)phenyl)quinazolinones as efficient substrates under mild conditions. A series of sulfonated quinolino[2,1-b]quinazolinones were successfully synthesized under transition-metal- and photocatalyst-free conditions. Notably, this strategy has the advantages of room temperature and simple operation, easy scale-up, and good functional group tolerance.

19.
Water Res ; 260: 121943, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38909423

ABSTRACT

Krypton chloride (KrCl*) excimer lamps (222 nm) are used as a promising irradiation source to drive ultraviolet-based advanced oxidation processes (UV-AOPs) in water treatment. In this study, the UV222/peracetic acid (PAA) process is implemented as a novel UV-AOPs for the degradation of emerging contaminants (ECs) in water. The results demonstrate that UV222/PAA process exhibits excellent degradation performance for carbamazepine (CBZ), with a removal rate of 90.8 % within 45 min. Notably, the degradation of CBZ in the UV222/PAA process (90.8 %) was significantly higher than that in the UV254/PAA process (15.1 %) at the same UV dose. The UV222/PAA process exhibits superior electrical energy per order (EE/O) performance while reducing resource consumption associated with the high-energy UV254/PAA process. Quenching experiments and electron paramagnetic resonance (EPR) detection confirm that HO• play a dominant role in the reaction. The contributions of direct photolysis, HO•, and other active species (RO• and 1O2) are estimated to be 5 %, 88 %, and 7 %, respectively. In addition, the effects of Cl-, HCO3-, and humic acid (HA) on the degradation of CBZ are evaluated. The presence of relatively low concentrations of Cl-, HCO3-, and HA can inhibit CBZ degradation. The UV222/PAA oxidation process could also effectively degrade several other ECs (i.e., iohexol, sulfamethoxazole, acetochlor, ibuprofen), indicating the potential application of this process in pollutant removal. These findings will propel the development of the UV222/PAA process and provide valuable insights for its application in water treatment.


Subject(s)
Peracetic Acid , Photolysis , Ultraviolet Rays , Water Pollutants, Chemical , Water Purification , Water Pollutants, Chemical/chemistry , Peracetic Acid/chemistry , Water Purification/methods , Carbamazepine/chemistry , Oxidation-Reduction
20.
World J Surg Oncol ; 22(1): 153, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38863003

ABSTRACT

In rectal cancer treatment, the diagnosis and management of lateral pelvic lymph nodes (LLN) are critical for preventing local recurrence. Over time, scholars have reached a consensus: when imaging suggests LLN metastasis, combining neoadjuvant chemoradiotherapy (nCRT) with selective LLN dissection (LLND) can mitigate the risk of recurrence. Selective LLND typically encompasses lymph nodes in the internal iliac and obturator regions. Recent studies emphasize distinctions between internal iliac and obturator lymph nodes regarding prognosis and treatment outcomes, prompting the need for differentiated diagnostic and treatment approaches.


Subject(s)
Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymph Node Excision/methods , Prognosis , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Pelvis/pathology
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