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Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
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Li-S batteries are considered as the next-generation batteries due to their exceptional theoretical capacity. However, their practical application is hampered by the shuttling effects of lithium polysulfides (LiPSs) and the sluggish Li2S decomposition, particularly the slow conversion from Li2S2 to Li2S. Addressing these challenges, the quest for effective catalysts that can accelerate the conversion of LiPSs and enhance the performance of Li-S batteries is crucial. In this study, we explored the electrocatalytic activity of two-dimensional phosphorus carbides (ß0-PC and ß1-PC) in Li-S batteries based on first-principles calculations. Our findings reveal that these materials demonstrate optimal binding strengths (ranging from 1.09 to 1.83 eV) with long-chain LiPSs, effectively preventing them from dissolving into the electrolyte. Additionally, they show remarkable catalytic activity during the sulfur redox reaction (SRR), with ΔG being only 0.37 eV for ß0-PC and 0.13 eV for ß1-PC. The low energy barrier induced by ß-PC enhances ion migration barrier and significantly expedites the charge/discharge cycles of Li-S batteries. Furthermore, we investigated the conversion dynamics of Li2S2 to Li2S, employing the computational lithium electrode (CLE) model. The excellent performance in these aspects underscores the potential of these materials as electrocatalysts for Li-S batteries, paving the way for advanced high-efficiency energy storage solutions.
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INTRODUCTION: Approximately, 50% of stroke survivors experience impaired walking ability 6 months after conventional rehabilitation and standard care. However, compared with upper limb motor function, research on lower limbs rehabilitation through non-invasive neuromodulation like repetitive transcranial magnetic stimulation (rTMS) has received less attention. Limited evidence exists regarding the effectiveness of intermittent theta-burst stimulation (iTBS), an optimised rTMS modality, on lower limbs rehabilitation after stroke. This study aims to evaluate the effects of iTBS on gait, balance and lower limbs motor function in stroke recovery while also exploring the underlying neural mechanisms using longitudinal analysis of multimodal neuroimaging data. METHODS AND ANALYSIS: In this double-blinded randomised controlled trial, a total of 46 patients who had a stroke will be randomly assigned in a 1:1 ratio to receive either 15 sessions of leg motor area iTBS consisting of 600 pulses or sham stimulation over the course of 3 weeks. Additionally, conventional rehabilitation therapy will be administered following the (sham) iTBS intervention. The primary outcome measure will be the 10 m walking test. Secondary outcomes include the Fugl-Meyer assessment of the lower extremity, Timed Up and Go Test, Functional Ambulation Category Scale, Berg Balance Scale, modified Barthel Index, Mini-Mental State Examination, montreal cognitive assessment, tecnobody balance assessment encompassing both static and dynamic stability evaluations, surface electromyography recording muscle activation of the lower limbs, three-dimensional gait analysis focusing on temporal and spatial parameters as well as ground reaction force measurements, corticomotor excitability tests including resting motor threshold, motor evoked potential and recruitment curves and multimodal functional MRI scanning. Outcome measures will be collected prior to and after the intervention period with follow-up at 3 weeks. ETHICS AND DISSEMINATION: The study has received approval from the Medical Research Ethics Committee of Wuxi Mental Health Center/Wuxi Central Rehabilitation Hospital (no. WXMHCCIRB2023LLky078). Results will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077431.
Subject(s)
Gait , Lower Extremity , Postural Balance , Stroke Rehabilitation , Transcranial Magnetic Stimulation , Humans , Double-Blind Method , Transcranial Magnetic Stimulation/methods , Stroke Rehabilitation/methods , Lower Extremity/physiopathology , Lower Extremity/diagnostic imaging , Stroke/physiopathology , Stroke/diagnostic imaging , Randomized Controlled Trials as Topic , Male , Recovery of Function , Female , Neuroimaging/methods , Middle Aged , Adult , Aged , Magnetic Resonance Imaging/methods , Multimodal Imaging/methodsABSTRACT
Near-infrared (NIR) light, valuable for its biological penetration and invisibility to the human eye, is a crucial tool in biomedicine, environmental monitoring, anticounterfeiting, and information encryption, yet traditional NIR luminescent materials are often unstable in humid conditions. Here, a highly stable MgGeO3:Mn2+ glass ceramic (GC) with NIR luminescence was successfully synthesized. As-obtained GC700 boasts exceptional luminescent capabilities and possesses abundant trap structures, enabling data inscription with a 405 nm laser and retrieval via laser/thermal excitation. Moreover, the emission peak of Mn2+ can be manipulated from 630 to 691 nm by increasing the annealing treatment temperature. With the harnessing of the effective NIR emission, stable carrier characteristics, and numerous trap structures, there is potential for application in information encryption. Accordingly, we explored the application of MgGeO3:Mn2+ GC (GC700 and GC800) samples in precious three-dimensional (3D) information storage and NIR mechanoluminescence (ML) for biological tissue imaging. These applications demonstrate the potential and versatility of electron-capturing NIR luminescent materials in a range of cutting-edge fields.
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Quarantine plant bacteria (QPB) are significant component of invasive alien species that result in substantial economic losses and serious environmental damage. Herein, a colorimetric aptasensor has been proposed based on the sandwich structure and the cascaded catalytic strategy for on-site detecting Xanthomonas hyacinthi, a type of QPB, in natural environments. The self-screened aptamer obtained through SELEX can bind to specific sites on the surface of viable organism with high affinity and specificity, which guarantees the selectivity of aptasensor. As an important part of the aptasensor, MIL-88-NH2(Fe) not only acts as a multifunctional carrier for both aptamers and glucose oxidase, but also catalyzes enzyme-like reaction because of specific surface area, amino and peroxidase-like activity. The present of Xanthomonas hyacinthi can trigger the formation of a sandwich structure and the occurrence of cascade catalytic reaction, enabling the detection with UV-Vis spectra and naked eyes. The proposed aptasensor presents a low detection limit of 2 cfu/mL and a wide linear range of 10 -107 cfu/mL. Compared to traditional detection methods for QPB, the reasonable design, high selectivity and convenience significantly improve the detection efficiency and contribute to environmental protection.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Colorimetry , Xanthomonas , Aptamers, Nucleotide/chemistry , Colorimetry/methods , Xanthomonas/chemistry , Biosensing Techniques/methods , Catalysis , Limit of Detection , SELEX Aptamer Technique , Metal-Organic Frameworks/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolismABSTRACT
The miR-23a ~ 27a ~ 24-2 cluster, commonly upregulated in diverse cancers, including hepatocellular carcinoma (HCC), raises questions about the specific functions of its three mature miRNAs and their integrated function. Utilizing CRISPR knockout (KO), CRISPR interference (CRISPRi), and CRISPR activation (CRISPRa) technologies, we established controlled endogenous miR-23a ~ 27 ~ a24-2 cell models to unravel their roles and signaling pathways in HCC. Both miR-23a KO and miR-27a KO displayed reduced cell growth in vitro and in vivo, revealing an integrated oncogenic function. Functional analysis indicated cell cycle arrest, particularly at the G2/M phase, through the downregulation of CDK1/cyclin B activation. High-throughput RNA-seq, combined with miRNA target prediction, unveiled the miR-23a/miR-27a-regulated gene network, validated through diverse technologies. While miR-23a and miR-27a exhibited opposing roles in cell migration and mesenchymal-epithelial transition, an integrated CRISPRi/a analysis suggested an oncogenic role of the miR-23a ~ 27a ~ 24-2 cluster in cell migration. This involvement potentially encompasses two signaling axes: miR-23a-BMPR2 and miR-27a-TMEM170B in HCC cells. In conclusion, our CRISPRi/a study provides a valuable tool for comprehending the integrated roles and underlying mechanisms of endogenous miRNA clusters, paving the way for promising directions in miRNA-targeted therapy interventions.
Subject(s)
Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , MicroRNAs , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , MicroRNAs/genetics , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Animals , Mice , Cell Line, Tumor , Cell Proliferation/genetics , Multigene Family , Epithelial-Mesenchymal Transition/genetics , CRISPR-Cas Systems , Cell Movement/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/geneticsABSTRACT
Due to the sensitivity to water, the all-inorganic CsPbBr3 nanocrystals have been widely applied in information encryption with spatial dimensions. However, the absence of time-dimension information limits the information capacity for the application of CsPbBr3. In this work, the CsPbBr3 nanocrystal was combined with water-sensitive borophosphate glass, achieving decomposing/recrystallization of CsPbBr3 nanocrystal with multi-dimension. The addition of SiO2 confirms that the collapse of the borophosphate glass network structure causes the exposure of the CsPbBr3 nanocrystals. The decomposition and recrystallization mechanism of CsPbBr3 nanocrystals in glass-ceramics upon encountering water has been verified. Finally, an information encryption strategy, using the mixture of CsPbBr3 glass ceramic and sodium carboxymethylcellulose as ink, is designed via adopting screen-printing technology, which not only provides a new idea for the preparation of CsPbBr3 nanocrystals, but also establish a new avenue for the information encryption technology.
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Steel slag as an alkaline industrial solid waste, possesses the inherent capacity to engage in carbonation reactions with carbon dioxide (CO2). Capitalizing on this property, the current research undertakes a systematic investigation into the fabrication of high-carbonation precast concrete (HCPC). This is achieved by substituting a portion of the cementitious materials with steel slag during the carbonation curing process. The study examines the influence of varying water-binder ratios, silica fume dosages, steel slag dosages, and sand content on the compressive strength of HCPC. Findings indicate that adjusting the water-binder ratio to 0.18, adding 8% silica fume, and a sand volume ratio of 40% can significantly enhance the compressive strength of HCPC, which can reach up to 104.9 MPa. Additionally, the robust frost resistance of HCPC is substantiated by appearance damage analysis, mass loss rate, and compressive strength loss rate, after 50 freeze-thaw cycles the mass loss, and the compressive strength loss rate can meet the specification requirements. The study also corroborates the high-temperature stability of HCPC. This study optimized the preparation of HCPC and provided a feasibility for its application in precast concrete.
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Background: Esophageal cancer remains a significant burden of lethal cancers worldwide, particularly in China. This is an annual report of Shanghai Chest Hospital (SCH) on surgical treatment for esophageal cancer patients in 2017. Methods: All patients who received surgical treatment for esophageal cancer at SCH in 2017 were given a detailed summary of clinical information based on the database of SCH. Kaplan-Meier method was used to present their survival, subgroup analyses, and multivariate Cox regression analysis were used to estimate the potential risk factors for prognosis. Results: In 2017, a total of 663 patients received surgical treatment (628 esophagectomies and 35 endoscopic resections) for esophageal cancer at SCH. Of the patients who underwent esophagectomy, 292 patients received perioperative treatment, majority of which was postoperative treatment (47.9%). Only 69 (10.4%) patients received preoperative treatment. Minimally invasive techniques were used in 444 (70.7%) patients and robotic-assisted esophagectomies were used in 130 (20.7%) patients. Complete resection (R0) was achieved in 90.3% of esophagectomy patients. The 5-year overall survival (OS) rate after esophagectomy was 52.5%. Conclusions: The 5-year OS of patients with esophageal cancer can reach 52.5% after surgical treatment in 2017 at SCH. The exact beneficiaries of neoadjuvant therapy are still unclear in the 2017 cohort.
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Introduction: Regulatory agencies generate a vast amount of textual data in the review process. For example, drug labeling serves as a valuable resource for regulatory agencies, such as U.S. Food and Drug Administration (FDA) and Europe Medical Agency (EMA), to communicate drug safety and effectiveness information to healthcare professionals and patients. Drug labeling also serves as a resource for pharmacovigilance and drug safety research. Automated text classification would significantly improve the analysis of drug labeling documents and conserve reviewer resources. Methods: We utilized artificial intelligence in this study to classify drug-induced liver injury (DILI)-related content from drug labeling documents based on FDA's DILIrank dataset. We employed text mining and XGBoost models and utilized the Preferred Terms of Medical queries for adverse event standards to simplify the elimination of common words and phrases while retaining medical standard terms for FDA and EMA drug label datasets. Then, we constructed a document term matrix using weights computed by Term Frequency-Inverse Document Frequency (TF-IDF) for each included word/term/token. Results: The automatic text classification model exhibited robust performance in predicting DILI, achieving cross-validation AUC scores exceeding 0.90 for both drug labels from FDA and EMA and literature abstracts from the Critical Assessment of Massive Data Analysis (CAMDA). Discussion: Moreover, the text mining and XGBoost functions demonstrated in this study can be applied to other text processing and classification tasks.
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Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.
Subject(s)
Acid Sensing Ion Channels , Calcitonin Gene-Related Peptide , Mice, Knockout , Psoriasis , Sensory Receptor Cells , Animals , Acid Sensing Ion Channels/metabolism , Acid Sensing Ion Channels/genetics , Female , Psoriasis/metabolism , Psoriasis/pathology , Psoriasis/genetics , Psoriasis/chemically induced , Mice , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/genetics , Sensory Receptor Cells/metabolism , Skin/metabolism , Skin/pathology , Imiquimod , Mice, Inbred C57BL , Disease Models, Animal , Inflammation/metabolism , Neurogenic Inflammation/metabolism , Humans , Nociceptors/metabolism , Interleukin-23/metabolism , Interleukin-23/geneticsABSTRACT
Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network's topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case-control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.
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BACKGROUND: This study aimed to observe the occurrence of recurrent laryngeal nerve injury after McKeown esophagectomy for esophageal squamous cell carcinoma, as well as its recovery and influencing factors within 7 months after surgery. METHODS: From July 2020 to July 2021, among all patients who underwent minimally invasive McKeown esophagectomy, 90 patients who developed vocal cord paralysis after surgery were included in the study. These patients underwent endoscopic vocal cord function assessment every 1 to 2 months and continued until 7 months postoperatively. RESULTS: Among all 388 patients undergoing esophagectomy, 23.2% (90/388) of patients suffered postoperative vocal cord paralysis. Left, right, and bilateral injuries were confirmed in 73 (81.1%), 12 (13.3%), and 5 patients (5.6%), respectively. With a median recovery time being 183 days, the cumulative overall recovery rate was 65.4% at 7 months, 68.6% for the left side, 55.6% for the right, and 20.0% for bilateral injuries. In multivariable analysis, cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be independent risk factors associated with non-recovery of vocal cord paralysis. CONCLUSIONS: After intensive endoscopic follow-up, a cumulative vocal cord paralysis recovery rate of 65.4% within 7 months was observed in patients after minimally invasive McKeown esophagectomy. Cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be risk factors hindering vocal cord paralysis recovery.
Subject(s)
Esophageal Neoplasms , Esophagectomy , Postoperative Complications , Recovery of Function , Recurrent Laryngeal Nerve Injuries , Vocal Cord Paralysis , Humans , Esophagectomy/adverse effects , Esophagectomy/methods , Vocal Cord Paralysis/etiology , Vocal Cord Paralysis/epidemiology , Male , Female , Middle Aged , Esophageal Neoplasms/surgery , Risk Factors , Aged , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Recurrent Laryngeal Nerve Injuries/etiology , Recurrent Laryngeal Nerve Injuries/prevention & control , Recurrent Laryngeal Nerve Injuries/epidemiology , Esophageal Squamous Cell Carcinoma/surgery , Retrospective Studies , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Adult , Treatment Outcome , Lymph Node Excision/adverse effectsABSTRACT
Ferroptosis, a cell death pathway dependent on iron, has been shown in research to play a role in the development, advancement, and outlook of tumours through ferroptosis-related lncRNAs (FRLRs). However, the value of the FRLRs in bladder cancer (BLCA) has not been thoroughly investigated. This research project involved developing a predictive model using ten specific FRLRs (AC099850.4, AL731567.1, AL133415.1, AC021321.1, SPAG5-AS1, HMGA2-AS1, RBMS3-AS3, AC006160.1, AL583785.1, and AL662844.4) through univariate COX and LASSO regression techniques. The validation of this signature as a standalone predictor was confirmed in a group of 65 patients from the urology bladder tumour database at the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Patients were categorized based on their median risk score into either a low-risk group or a high-risk group. Enrichment analysis identified possible molecular mechanisms that could explain the variations in clinical outcomes observed in high-risk and low-risk groups. Moreover, we explored the correlation between FLPS and immunotherapy-related indicators. The ability of FLPS to forecast the effectiveness of immunotherapy was validated by the elevated levels of immune checkpoint genes (PD-L1, CTLA4, and PD-1) in the group at high risk. We also screened the crucial FRLR (HMGA2-AS1) through congruent expression and prognostic conditions and established a ceRNA network, indicating that HMGA2-AS1 may affect epithelial-mesenchymal transition by modulating the Wnt signalling pathway through the ceRNA mechanism. We identified the top five mRNAs (NFIB, NEGR1, JAZF1, JCAD, and ESM1) based on random forest algorithm and analysed the relationship between HMGA2-AS1, the top five mRNAs, and immunotherapy, and their interactions with drug sensitivities. Our results suggest that patients with BLCA have a greater sensitivity to four drugs (dasatinib, pazopanib, erismodegib and olaparib). Our study provides new insights into the TME, key signalling pathways, genome, and potential therapeutic targets of BLCA, with future guidance for immunotherapy and targeted precision drugs.
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Double-strand breaks (DSBs) are the most lethal form of DNA damage. Transcriptional activity at DSBs, as well as transcriptional repression around DSBs, are both required for efficient DNA repair. The chromatin landscape defines and coordinates these two opposing events. However, how the open and condensed chromatin architecture is regulated remains unclear. Here, we show that the GATAD2B-NuRD complex associates with DSBs in a transcription- and DNA:RNA hybrid-dependent manner, to promote histone deacetylation and chromatin condensation. This activity establishes a spatio-temporal boundary between open and closed chromatin, which is necessary for the correct termination of DNA end resection. The lack of the GATAD2B-NuRD complex leads to chromatin hyperrelaxation and extended DNA end resection, resulting in homologous recombination (HR) repair failure. Our results suggest that the GATAD2B-NuRD complex is a key coordinator of the dynamic interplay between transcription and the chromatin landscape, underscoring its biological significance in the RNA-dependent DNA damage response.
Subject(s)
Chromatin , DNA Breaks, Double-Stranded , Mi-2 Nucleosome Remodeling and Deacetylase Complex , Chromatin/metabolism , Chromatin/genetics , Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism , Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics , RNA/metabolism , RNA/genetics , DNA Damage , DNA/metabolism , DNA/genetics , Animals , Humans , Transcription, Genetic , DNA Repair , MiceABSTRACT
The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi0.96Co0.04O2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni2+ into Li sites and stabilizes lattice oxygen through strengthened AlâO and NbâO bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2âH3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni0.96Co0.04)0.985Al0.01Nb0.005O2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials.
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Text summarization is crucial in scientific research, drug discovery and development, regulatory review, and more. This task demands domain expertise, language proficiency, semantic prowess, and conceptual skill. The recent advent of large language models (LLMs), such as ChatGPT, offers unprecedented opportunities to automate this process. We compared ChatGPT-generated summaries with those produced by human experts using FDA drug labeling documents. The labeling contains summaries of key labeling sections, making them an ideal human benchmark to evaluate ChatGPT's summarization capabilities. Analyzing >14000 summaries, we observed that ChatGPT-generated summaries closely resembled those generated by human experts. Importantly, ChatGPT exhibited even greater similarity when summarizing drug safety information. These findings highlight ChatGPT's potential to accelerate work in critical areas, including drug safety.
Subject(s)
Drug Labeling , United States Food and Drug Administration , Humans , United States , Natural Language Processing , Drug-Related Side Effects and Adverse ReactionsABSTRACT
Dexamethasone (DEX) is a hormone drug that is often detected in wastewater treatment plants, but its impact on activated sludge systems is unknown. This study explored the long-term effects of DEX on nutrient removal, microbial activities, microbial assembly, and microbial interactions in the activated sludge system. During the 90-day DEX exposure experiment, both chemical oxygen demand and total nitrogen removal efficiencies were initially inhibited and then recovered. Microbial activities, i.e., specific oxygen uptake rate and denitrification, did not differ significantly from that of the control reactor (p > 0.05), possibly due to the secretion of extracellular polymers that act as a protective barrier against excess reactive oxygen species induced by DEX. This barrier protects cell membrane integrity and ensures stable treatment performance. Analysis of microbial assembly identified the drift of stochastic processes (from 92.7 % to 51.8 %) and homogeneous selection of deterministic processes (from 1.6 % to 38.7 %) as the main driving forces of microbial community structure succession under long-term DEX stress. Although long-term exposure to 1000 µg/L DEX did not significantly increase the abundance levels of functional bacteria (Nitrosomonas and 996-1) and key genes (AmoCAB and Hao), the ammonia oxidation capacity of the activated sludge system was enhanced. Analysis of microbial interactions indicated that streamlining of functional subnetworks and increased cooperation were the primary reasons. This is the first study to explore the long-term effects of DEX on activated sludge and provide insights into microbial interaction and assembly. Moreover, the findings of this study broaden our knowledge and lay an experimental foundation for reducing risks associated with hormone drugs.
Subject(s)
Dexamethasone , Sewage , Waste Disposal, Fluid , Sewage/microbiology , Dexamethasone/pharmacology , Waste Disposal, Fluid/methods , Bioreactors/microbiology , Water Pollutants, Chemical , WastewaterABSTRACT
The canalis sinuosus, a canal containing the anterior superior alveolar nerve bundle, originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla. It was once regarded as an anatomical variation. However, with the widespread application of cone beam computed tomography (CBCT), the detection rate of canalis sinuosus in the population has increased. The canalis sinuosus exhibits diverse courses, branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region, with the majority traversing the palatal side of the central incisor. The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth, their corresponding soft tissues, and the maxillary sinus mucosa, but also relates to the nasal septum, lateral nasal wall, and parts of the palatal mucosa. To minimize surgical complications, implantologists need to investigate strategies for preventing and treating canalis sinuosus injuries. Preoperatively, implantologists should use CBCT to identify the canalis sinuosus and virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus. Intraoperatively, implantologists should assess bleeding and patient comfort, complemented by precision surgical techniques such as the use of implant surgical guide plates. Postoperatively, CBCT can be employed to examine the relationship between the implant and the canalis sinuosus, and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms. This review summarizes the detection of canalis sinuosus in the population, its anatomical characteristics, and its physiological functions in the anterior maxilla, and discusses strategies for effectively avoiding canalis sinuosus injuries during implant surgery, thereby enhancing implantologists' awareness and providing references for clinical decision-making.
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Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.