Clinical Application Research Articles

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer (CRC) is a prevalent global malignancy with complex prognostic factors. Tumor-associated macrophages (TAMs) have shown paradoxical associations with CRC survival, particularly concerning the M2 subset. AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors. METHODS A cross-sectional study included histopathological assessment of paraffin-embedded tissue blocks obtained from 43 CRC patients. Using CD68 and CD163 immunohistochemistry, we quantified TAMs in tumor stroma and front, focusing on M2 proportion. Demographic, histopathological, and clinical parameters were collected. RESULTS TAM density was significantly higher at the tumor front, with the M2 proportion three times greater in both zones. The tumor front had a higher M2 proportion, which correlated significantly with advanced tumor stage (P = 0.04), pathological nodal involvement (P = 0.04), and lymphovascular invasion (LVI, P = 0.01). However, no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors. CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples. We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage, nodal involvement, and LVI. This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC, warranting further investigation and potential clinical application.

Biomechanical Integrity Score of the Female Pelvic Floor for Stress Urinary Incontinence.

This study is aimed at developing and validating a new integral parameter, the Biomechanical Integrity score (BI-score) of the female pelvic floor for stress urinary incontinence conditions. A total of 130 subjects were included in the observational cohort study; 70 subjects had normal pelvic floor conditions, and 60 subjects had stress urinary incontinence (SUI). A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t test, correlation) to identify the VTI parameters sensitive to the pelvic SUI conditions. Twenty-seven parameters were identified as statistically sensitive to SUI development. They were subdivided into five groups to characterize tissue elasticity (group 1), pelvic support (group 2), pelvic muscle contraction (group 3), involuntary muscle relaxation (group 4), and pelvic muscle mobility (group 5). Every parameter was transformed to its standard deviation units using the dataset for normal pelvic conditions, similar to the T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups 1-5 and to the BI-score in standard deviation units. The p value for the BI-score has p = 4.0 × 10-28 for SUI versus normal conditions. Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the SUI BI-score in future research and clinical applications.

Clinical applications and challenges of metagenomic next-generation sequencing in the diagnosis of pediatric infectious disease

Abstract Infectious diseases seriously threaten the lives of children. Timely and accurate detection of pathogenic microorganisms and targeted medication are the keys to the diagnosing and treatment of infectious diseases in children. The next-generation metagenomic sequencing technology has attracted great attention in infectious diseases because of its characteristics such as no culture, high throughput, short detection cycle, wide coverage, and a good application prospect. In this paper, we review the studies of metagenomic next-generation sequencing in pediatric infectious diseases and analyze the challenges of its application in pediatric diseases.

The influence of biological rhythms on the initial onset of status epilepticus in critically ill inpatients and the study of its predictive Model.

This study aims to explore the relationship between the circadian rhythms of critically ill patients and the incidence of Status Epilepticus (SE), and to develop a predictive model based on circadian rhythm indicators and clinical factors. We conducted a diurnal rhythm analysis of vital sign data from 4413 patients, discovering significant differences in the circadian rhythms of body temperature, blood oxygen saturation, and heart rate between the SE and non-SE groups, which were correlated with the incidence of SE. We also employed various machine learning algorithms to identify the ten most significant variables and developed a predictive model with strong performance and clinical applicability. Our research provides a new perspective and methodology for the study of biological rhythms in critically ill patients, offering new evidence and tools for the prevention and treatment of SE. Our findings are consistent or similar to some in the literature, while differing from or supplementing others. We observed significant differences in the vital signs of epileptic patients at different times of the day across various diagnostic time groups, reflecting the regulatory effects of circadian rhythms. We suggest heightened monitoring and intervention of vital signs in critically ill patients, especially during late night to early morning hours, to reduce the risk of SE and provide more personalized treatment plans.

Photodegradation of cannabidiol (CBD) and Δ9-THC in cannabis plant material.

Δ9-THC, the psychotropic cannabinoid in Cannabis sativa L., for many years has been the focus of all the pharmacological attention as the main promising principle of the plant. Recently, however, cannabidiol (CBD) has brought a sudden change in the scenario, exponentially increasing the interest in pharmacology as the main non-psychotropic cannabinoid with potential therapeutic, cosmetical and clinical applications. Although the reactivity of CBD and Δ9-THC has been considered, little attention has been paid to the possible photodegradation of these cannabinoids in the vegetal matrix and the data available in the literature are, in some cases, contradictory. The aim of the present work is to provide a characterization of the photochemical behaviour of CBD and Δ9-THC in three cannabis chemotypes, namely I (Δ9-THC 2.50%w/w), II (CBD:Δ9-THC 5.82%w/w:3.19%w/w) and III (CBD 3.02%w/w).

Dual modulation of blue-fluorescent carbon dots for simultaneous detection of topotecan and pantoprazole.

This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical applications. The significance of this study originates from the need to understand the pharmacokinetic changes of TOP after PNT administration, which can inform necessary dose adjustments of TOP. To achieve this, nitrogen blue emissive carbon dots (B@NCDs) were produced and employed due to their unique fluorescent properties. When TOP is added to B@NCDs, it exhibits strong native fluorescence at 545 nm without influencing the B@NCDs' fluorescence at 447 nm. Conversely, PNT causes quenching of B@NCDs fluorescence, a property that enables the distinct detection of both drugs. The B@NCDs were fully characterized using different techniques, including ultraviolet-visible spectrophotometry, fluorescence analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM), and FTIR spectroscopy. The proposed method demonstrated excellent linearity, selectivity, and sensitivity, with low detection limits (LOD, S/N = 3); 0.0016 μg mL-1 for TOP and 0.36 μg mL-1 for PNT. Applied to spiked rabbit plasma samples, this method offers a new approach for evaluating the pharmacokinetic interaction between TOP and PNT. It enables the determination of all pharmacokinetic parameters of TOP before and after coadministration with PNT, providing essential insights into whether dose adjustments are necessary. This research not only contributes to the field of drug monitoring and interaction studies but also exemplifies the potential of B@NCDs in complex biological matrices, paving the way for further pharmacological and therapeutic applications.

Application of 3D Printing in Cleft Lip and Palate Repair.

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.

Nanozymes for Treating Ocular Diseases.

Nanozymes, characterized by their nanoscale size and enzyme-like catalytic activities, exhibit diverse therapeutic potentials, including anti-oxidative, anti-inflammatory, anti-microbial, and anti-angiogenic effects. These properties make them highly valuable in nanomedicine, particularly ocular therapy, bypassing the need for systemic delivery. Nanozymes show significant promise in tackling multi-factored ocular diseases, particularly those influenced by oxidation and inflammation, like dry eye disease, and age-related macular degeneration. Their small size, coupled with their ease of modification and integration into soft materials, facilitates the effective penetration of ocular barriers, thereby enabling targeted or prolonged therapy within the eye. This review is dedicated to exploring ocular diseases that are intricately linked to oxidation and inflammation, shedding light on the role of nanozymes in managing these conditions. Additionally, recent studies elucidating advanced applications of nanozymes in ocular therapeutics, along with their integration with soft materials for disease management, are discussed. Finally, this review outlines directions for future investigations aimed at bridging the gap between nanozyme research and clinical applications. This article is protected by copyright. All rights reserved.

Research progress in the treatment of inflammatory bowel disease with natural polysaccharides and related structure-activity relationships.

Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.

Chinese expert consensus on the clinical application of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease.

Chinese expert consensus on the clinical application of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease.

Automatic planning of maxillary anterior dental implant based on prosthetically guided and pose evaluation indicator.

Preoperative planning of maxillary anterior dental implant is a prerequisite to ensuring that the implant achieves the proper three-dimensional (3D) pose, which is essential for its long-term stability. However, the current planning process is labor-intensive and subjective, relying heavily on the surgeon's experience. Consequently, this paper proposes an automatic method for computing the optimal pose of the dental implant. The method adopts the principle of prosthetically guided dental implant placement. Initially, the prosthesis coordinate system is established to determine the implant candidate orientations. Subsequently, virtual slices of the maxilla in the buccal-palatal direction are generated according to the prosthesis position. By extracting feature points from the virtual slices, the implant candidate starting points are acquired. Then, a candidate pose set is obtained by combining these candidate starting points and orientations. Finally, a pose evaluation indicator is introduced to determine the optimal implant pose from this set. Twenty-two cases were utilized to validate the method. The results show that the method could determine an ideal pose for the dental implant, with the average minimum distance between the implant and the left tooth root, the right tooth root, the palatal side, and the buccal side being mm, mm, mm, mm, respectively. The planning time was less than 9s. Unlike manual planning, the proposed method can efficiently and accurately complete maxillary anterior dental implant planning, providing a theoretical analysis of the success rate of the implant. Thus, it has great potential for future clinical application.

Improving Targeted Mass Spectrometry Data Analysis with Nested Active Machine Learning

Targeted mass spectrometry (MS) holds promise for precise protein and protein‐representative peptide identification and quantification, enhancing disease diagnosis. However, its clinical application is hindered by complex data analysis and expert review requirements. It is hypothesized that machine learning (ML) models can automate data analysis to accelerate the clinical application of MS. The approach involves an ML‐driven pipeline that extracts statistical and morphological features from an MS target region and feeds these features into ML algorithms to generate and assess predictive models. The findings demonstrate ML prediction models exhibit superior performance when trained on extracted features versus raw spectra intensity data and that random forest models exhibit robust classification performance in both internal and external validation datasets. These models remain effective across varying training dataset sizes and positive sample rates and are enhanced by a nested active learning approach. This approach can thus revolutionize clinical MS applications.

[Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension, characterized by thrombotic occlusion of the pulmonary arteries leading to vascular stenosis or obstruction, progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and eventual right heart failure. Unlike other types of pulmonary hypertension, the prognosis of CTEPH can be significantly improved by surgery, vascular intervention, and/or targeted drug therapy. Pulmonary endarterectomy (PEA) is the preferred treatment of choice for CTEPH. However, PEA is an invasive procedure with high operative risks, and is currently only performed in a few centers in China. Balloon pulmonary angioplasty (BPA) is an emerging interventional technique for CTEPH, serving as an alternative for patients who are ineligible for PEA or with residual pulmonary hypertension after PEA. BPA is gaining traction in China, but its widespread adoption is limited due to its complexity, operator skills, and equipment requirements, a lack of standard operating procedures and technical guidance, which limit the further improvement and development of BPA in China. To address this, a multidisciplinary panel of experts was convened to develop the Consensus on the Procedure of Balloon Pulmonary Angioplasty for the Chronic Thromboembolic Pulmonary Hypertension, which fomulates guidelines on BPA procedural qualification, perioperative management, procedural planning, technical approach, and complication prevention, with the aim of providing recommendations and clinical guidance for BPA treatment in CTEPH and standardizing its clinical application in this setting. Summary of recommendations: Recommendation 1: It is recommended that physicians who specialize in pulmonary vascular diseases take the lead in formulating the diagnostic and treatment plans for CTEPH, using a multidisciplinary approach.Recommendation 2: Training in BPA technique is critical; novice operators should undergo standardized operative training with at least 50 procedures under the guidance of experienced physicians before embarking on independent BPA procedures.Recommendation 3: BPA requires catheterization labs, angiography systems, standard vascular interventional devices and consumables, drugs, and emergency equipment.Recommendation 4: Patient selection for BPA should consider cardiac and pulmonary function, coagulation status, and comorbid conditions to determine indications and contraindications, thereby optimizing the timing of the procedure and improving safety.Recommendation 5: In experienced centers, patients deemed likely to benefit from early BPA, based on clinical and imaging features of CTEPH and without elevated D-dimer levels, could bypass standard 3-month anticoagulation therapy.Recommendation 6: BPA is a complex interventional treatment that requires thorough pre-operative assessment and preparation.Recommendation 7: The use of perioperative anticoagulants in BPA requires a comprehensive risk assessment of intraoperative bleeding by the operator for individualized decision making.Recommendation 8: A variety of venous access routes are available for BPA; unless contraindicated, the right femoral vein is usually preferred because of its procedural convenience and reduced radiation exposure.Recommendation 9: For the different types of vascular lesion in CTEPH, treatment of ring-like stenoses, web-like lesions, and subtotal occlusions should be prioritized before addressing complete occlusions and tortuous lesions, in order to reduce complications and improve procedural safety.Recommendation 10: A targeted, incremental balloon dilatation strategy based on vascular lesions is recommended for BPA.Recommendation 11: Intravascular pulmonary artery imaging technologies, such as OCT and IVUS can assist in accurate vessel sizing and confirmation of wire placement in the true vascular lumen. Pressure wires can be used to objectively assess the efficacy of dilatation during BPA.Recommendation 12: Endpoints for BPA treatment should be individually assessed, taking into account improvements in clinical symptoms, hemodynamics, exercise tolerance, and quality of life.Recommendation 13: Post-BPA routine monitoring of vital signs is essential; anticoagulation therapy should be initiated promptly post-procedure in the absence of complications. In cases of intraoperative hemoptysis, postoperative anticoagulation regimen adjustments should be adjusted according to the bleeding severity.Recommendation 14: If reperfusion pulmonary edema occurs during or after BPA, ensure adequate oxygenation, diuresis, and consider non-invasive positive-pressure ventilation if necessary, while severe cases may require early mechanical ventilation assistance or ECMO.Recommendation 15: In cases of intraoperative hemoptysis, temporary balloon occlusion to stop bleeding is recommended, along with protamine to neutralize heparin. Persistent bleeding may warrant the use of gelatin sponges, coil embolization, or covered stent implantation.Recommendation 16: For contrast imaging during BPA, non-ionic, low or iso-osmolar contrast agents are recommended, with hydration status determined by the patient's clinical condition, cardiac and renal function, and intraoperative contrast volume used.

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Effect of fence tray matching care on excess adhesive and bracket placement accuracy for orthodontic bonding: an in vitro study

ObjectiveThis study aimed to evaluate the effect of fence tray matching care (FTMC) in bracket bonding by measuring excess adhesive, as well as linear and angular deviations, and by comparing it with the half-wrapped tray (HWT).Materials and methodsAn intraoral scanner was used to acquire data on the maxillary dental arch of a patient with periodontitis.Furthermore, 20 maxillary dental arch models were 3D printed. Using 3Shape, PlastyCAD software, and 3D printing technology, 10 FTMC (method I) and HWT (method II) were obtained. By preoperative preparation, intraoperative coordination, and postoperative measurement, the brackets were transferred from the trays to the 3D-printed maxillary dental arch models. Additionally, the bracket’s excess adhesive as well as linear and angular deviations were measured, and the differences between the two methods were analyzed.ResultsExcess adhesive was observed in both methods, with FTMC showing less adhesive (P< 0.001), with a statistical difference. Furthermore, HWT’s vertical, tip and torque, which was significantly greater than FTMC (P< 0.05), with no statistical difference among other respects. The study data of incisors, canines, and premolars, showed that the premolars had more adhesive residue and were more likely to have linear and angular deviations.ConclusionsThe FTMC had higher bracket bonding effect in comparison to HWT, and the adhesive residue, linear and angular deviations are smaller. The fence tray offers an intuitive view of the precise bonding of the bracket, and can remove excess adhesive to prevent white spot lesions via care, providing a different bonding method for clinical applications.

A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma.

Chemoresistance is a key obstacle in the long-term survival of patients with locally and advanced lung adenocarcinoma (LUAD). This study used bioinformatic analysis to reveal the chemoresistance of gene-neutrophil extracellular traps (NETs) associated with LUAD. RNA sequencing data and LUAD expression patterns were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The GeneCards database was used to identify NETosis-related genes (NRGs). To identify hub genes with significant and consistent expression, differential analysis was performed using the TCGA-LUAD and GEO datasets. LUAD subtypes were determined based on these hub genes, followed by prognostic analysis. Immunological scoring and infiltration analysis were conducted using NETosis scores (N-scores) derived from the TCGA-LUAD dataset. A clinical prognostic model was established and analyzed, and its clinical applications explored. Twenty-two hub genes were identified, and consensus clustering was used to identify two subgroups based on their expression levels. The Kaplan-Meier (KM) curves demonstrated statistically significant differences in prognosis between the two LUAD subtypes. Based on the median score, patients were further divided into high and low N-score groups, and KM curves showed that the N-scores were more precise at predicting the prognosis of patients with LUAD for overall survival (OS). Immunological infiltration analysis revealed significant differences in the abundances of 10 immune cell infiltrates between the high and low N-score groups. Risk scores indicated significant differences in prognosis between the two extreme score groups. The risk scores for the prognostic model also indicated significant differences between the two groups. The results provide new insights into NETosis-related differentially expressed genes (NRDEGs) associated with chemotherapy resistance in patients with LUAD. The established prognostic model is promising and could help with clinical applications to evaluate patient survival and therapeutic efficiency.

A non-invasive method to monitor respiratory muscle effort during mechanical ventilation.

This study introduces a method to non-invasively and automatically quantify respiratory muscle effort (Pmus) during mechanical ventilation (MV). The methodology hinges on numerically solving the respiratory system's equation of motion, utilizing measurements of airway pressure (Paw) and airflow (Faw). To evaluate the technique's effectiveness, Pmus was correlated with expected physiological responses. In volume-control (VC) mode, where tidal volume (VT) is pre-determined, Pmus is expected to be linked to Paw fluctuations. In contrast, during pressure-control (PC) mode, where Paw is held constant, Pmus should correlate with VT variations. The study utilized data from 250 patients on invasive MV. The data included detailed recordings of Paw and Faw, sampled at 31.25Hz and saved in 131.1-second epochs, each covering 34 to 41 breaths. The algorithm identified 51,268 epochs containing breaths on either VC or PC mode exclusively. In these epochs, Pmus and its pressure-time product (PmusPTP) were computed and correlated with Paw's pressure-time product (PawPTP) and VT, respectively. There was a strong correlation of PmusPTP with PawPTP in VC mode (R² = 0.91 [0.76, 0.96]; n = 17,648 epochs) and with VT in PC mode (R² = 0.88 [0.74, 0.94]; n = 33,620 epochs), confirming the hypothesis. As expected, negligible correlations were observed between PmusPTP and VT in VC mode (R² = 0.03) and between PmusPTP and PawPTP in PC mode (R² = 0.06). The study supports the feasibility of assessing respiratory effort during MV non-invasively through airway signal analysis. Further research is warranted to validate this method and investigate its clinical applications.

Clinical research on neurological and psychiatric diagnosis and monitoring using wearable devices: A literature review

AbstractWearable devices have opened up exciting possibilities for monitoring and managing home health, particularly in the realm of neurological and psychiatric diseases. These devices capture signals related to physiological and behavioral changes, including heart rate, sleep patterns, and motor functions. Their emergence has resulted in significant advancements in the management of such conditions. Traditional clinical diagnosis and assessment methods heavily rely on patient reports and evaluations conducted by healthcare professionals, often leading to a detachment of patients from their home environment and creating additional burdens for both patients and healthcare providers. The increasing popularity of wearable devices offers a potential solution to these challenges. This review focuses on the clinical utility of wearable devices in diagnosing and monitoring neurological and psychiatric diseases. Through research findings and practical examples, we highlight the potential role of wearable devices in diagnosing and monitoring conditions such as autism spectrum disorder, depression, epilepsy, stroke prognosis, Parkinson's disease, dementia, and other diseases. Additionally, the review discusses the benefits and limitations of wearable devices in clinical applications, while highlighting the challenges they face. Finally, it provides prospects for enhancing the value of wearable devices in the monitoring and diagnosis of neurological and psychiatric diseases.

Human Serum Albumin Mediated Controllable Synthesis of Defect-Rich Copper Hydroxide Nanowire for Cuproptosis-Based Anti-Tumor Therapy.

Cuproptosis, as a newly identified form of programmed cell death, shows great promise in cancer treatment. Efficient Cu+ delivery while avoiding systemic toxicity and elimination of the resistance from over-expressed intracellular copper chelator glutathione (GSH) are critical for cuproptosis. Herein, this work innovatively constructs a biocompatible and defect-rich copper hydroxide nanowire (HCu nanowire) through a human serum albumin (HSA) mediated biomineralization method. This work finds that the morphology and size of HCu nanowires can be controlled adjusted by the feed ratio of HSA and Cu2+. Remarkably, except for outstanding biocompatibility, HSA coordination endows HCu nanowires abundant oxygen vacancies (OVs), and the defect-rich HCu nanowire possesses excellent GSH consumption efficiency. Density functional theory studies indicate that OVs change GSH absorption energy on defective HCu nanowires. In cancer cells, HCu nanowires deplete GSH and simultaneously produce sufficient free Cu+ for enhanced cuproptosis. Meanwhile, Cu+ can catalyze endogenous H2O2 into hydroxyl radicals (·OH) via a Fenton-like reaction. Thus, synergetic cuproptosis and ROS mediated apoptosis against tumor are achieved. The experimental results show that HCu nanowires have a better performance in both antitumor efficiency and safety compared with chemotherapeutic drug Dox at the same dose, demonstrating its great potential in clinical applications.

Evaluating the strengths and weaknesses of large language models in answering neurophysiology questions

Large language models (LLMs), like ChatGPT, Google’s Bard, and Anthropic’s Claude, showcase remarkable natural language processing capabilities. Evaluating their proficiency in specialized domains such as neurophysiology is crucial in understanding their utility in research, education, and clinical applications. This study aims to assess and compare the effectiveness of Large Language Models (LLMs) in answering neurophysiology questions in both English and Persian (Farsi) covering a range of topics and cognitive levels. Twenty questions covering four topics (general, sensory system, motor system, and integrative) and two cognitive levels (lower-order and higher-order) were posed to the LLMs. Physiologists scored the essay-style answers on a scale of 0–5 points. Statistical analysis compared the scores across different levels such as model, language, topic, and cognitive levels. Performing qualitative analysis identified reasoning gaps. In general, the models demonstrated good performance (mean score = 3.87/5), with no significant difference between language or cognitive levels. The performance was the strongest in the motor system (mean = 4.41) while the weakest was observed in integrative topics (mean = 3.35). Detailed qualitative analysis uncovered deficiencies in reasoning, discerning priorities, and knowledge integrating. This study offers valuable insights into LLMs’ capabilities and limitations in the field of neurophysiology. The models demonstrate proficiency in general questions but face challenges in advanced reasoning and knowledge integration. Targeted training could address gaps in knowledge and causal reasoning. As LLMs evolve, rigorous domain-specific assessments will be crucial for evaluating advancements in their performance.