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Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

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Background: Over the past few decades, left ventricular (LV) dysfunction in ST-segment elevation myocardial infarction (STEMI) patients has been the focus of research. Recently, co-occurring right ventricular (RV) dysfunction has received more attention in clinical practice. We aimed to assess RV function using cardiac magnetic resonance (CMR) imaging and identify factors that may contribute to RV dysfunction in STEMI patients. Methods: We retrospectively studied 189 patients with STEMI who underwent CMR 1-7 days after successful percutaneous coronary intervention (PCI). The ejection fraction (EF), wall thickening rate (WTR), peak radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) of the LV, interventricular septum (IVS) and RV were measured with cine images. The location and extent of the infarct were determined using late gadolinium enhancement (LGE) imaging. The differences of function between STEMI patients with right ventricular ejection fraction (RVEF) <50% and those with RVEF ≥50% were compared using an independent-sample t-test. Linear regression analyses were used to determine independent predictors of RVEF. Results: RVEF <50% was observed in 32.28%% STEMI patients, who also demonstrated significantly lower left ventricular ejection fraction (LVEF), WTR, RS, CS, LS and larger infarct sizes than those with RVEF ≥50%. Patients with RVEF <50% also demonstrated a higher incidence of RV infarction, higher RV end-systolic volume (ESV) index, and lower RV RS and CS. Multivariable linear regression analysis revealed LV EF, IVS WTR and IVS RS as significant predictors for RVEF, while male gender, the culprit lesion in the right coronary artery (RCA), peak troponin were negative predictors for RVEF. Notably, peak troponin, LV EF, LV RS, LV CS, LV WTR, and IVS WTR demonstrated higher area under the curve (AUC) values for predicting RV dysfunction. Conclusions: RV dysfunction was detected in 32.28% of STEMI patients. Patients with acute STEMI and RVEF <50% had impaired LV and IVS functions. Systolic function of the LV and IVS, peak troponin, and culprit lesions in the RCA were independent predictors of RV dysfunction in STEMI patients.

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BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Asunto(s)

Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Progresión de la Enfermedad , Conducción Nerviosa , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/fisiología , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre

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The disposal of stone waste derived from the stone industry is a worldwide problem. The shortage of landfills, as well as transport costs and environmental pollution, pose a crucial problem. Additionally, as a substitute for cement that has high carbon emissions, energy consumption, and pollution, the disposal of stone wastes by utilizing solid waste-based binders as road base materials can achieve the goal of "waste for waste". However, the mechanical properties and deterioration mechanism of solid waste-based binder solidified stone waste as a road base material under complex environments remains incompletely understood. This paper reveals the durability performance of CGF all-solid waste binder (consisting of calcium carbide residue, ground granulated blast furnace slag, and fly ash) solidified stone waste through the macro and micro properties under dry-wet and freeze-thaw cycling conditions. The results showed that the dry-wet and freeze-thaw cycles have similar patterns of impacts on the CGF and cement stone waste road base materials, i.e., the stress-strain curves and damage forms were similar in exhibiting the strain-softening type, and the unconfined compressive strengths all decreased with the number of cycles and then tended to stabilize. However, the influence of dry-wet and freeze-thaw cycles on the deterioration degree was significantly different; CGF showed excellent resistance to dry-wet cycles, whereas cement was superior in freeze-thaw resistance. The deterioration grade of CGF and cement ranged from 36.15 to 47.72% and 39.38 to 47.64%, respectively, after 12 dry-wet cycles, whereas it ranged from 57.91 to 64.48% and 36.61 to 40.00% after 12 freeze-thaw cycles, respectively. The combined use of MIP and SEM confirmed that the deterioration was due to the increase in the porosity and cracks induced by dry-wet and freeze-thaw cycles, which in turn enhanced the deterioration phenomenon. This can be ascribed to the fact that small pores occupy the largest proportion and contribute to the deterioration process, and the deterioration caused by dry-wet cycles is associated with the formation of large pores through the connection of small pores, while the freeze-thaw damage is due to the increase in medium pores that are more susceptible to water intrusion. The findings provide theoretical instruction and technical support for utilizing solid waste-based binders for solidified stone waste in road base engineering.

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The stone waste generated by stone industry occupy land resources, cause safety hazards and need to be efficiently resourcefully utilized. In this study, the CGF solid waste based binder (abbreviated as CGF) with calcium carbide residue (CCR), ground granulated blast furnace slag (GGBS), and fly ash (FA) as components was developed to solidify the stone waste. Through "treating waste with waste", the resource utilization of solid waste was realized. The mechanical properties and reaction mechanism of CGF solidified stone waste were investigated through unconfined compressive strength (UCS), XRD, and SEM-EDS tests. The results show that CGF has the better solidify effect on stone waste, and its strength meets the requirements of the road base material standards. Compared to cement, the CGF solidified stone waste existed higher UCS at both 7 and 28 d of curing. The UCS of CGF solidified stone waste reaches 2.93 and 4.42 MPa under curing of 7 and 28 d at 5% binder content, which is 1.61 and 1.37 times higher that of P.O. 42.5 cement. Furthermore, the primary mineral-based stone wastes will not react with the binder, and the CGF generates gelling products such as C-S-H C-A-H, and C-A-S-H through alkali-activated reactions between the components of CGF. These gelling products enhance the UCS of solidified stone wastes through cementing and filling effects. The findings provide a feasible approach with low-carbon emission and low-cost for resourceful utilization of stone wastes.

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Per- and polyfluoroalkyl substances (PFAS), known as "forever chemicals," are synthetic chemicals which have been used since the 1940s. Given their remarkable thermostability and chemical stability, PFAS have been widely utilized in commercial products, including textiles, surfactants, food packages, nonstick coatings, and fire-fighting foams. Thus, PFAS are widely distributed worldwide and have been detected in human urine, blood, breast milk, tissues and other substances. Growing concerns over the risks of PFAS, including their toxicity and carcinogenicity, have attracted people's attention. Recent reviews have predominantly emphasized advancements in the detection, adsorption, and degradation of PFAS through their chemical structures and toxic properties; however, further examination of the literature is needed to determine the link between PFAS exposure and cancer risk. Here, we introduced different PFAS detection methods based on sensors and liquid chromatography-mass spectrometry (LC-MS). Then, we discussed epidemiological investigations on PFAS levels and cancer risks in recent years, as well as the mechanisms underlying the carcinogenesis. Finally, we proposed the "4C principles" for ongoing exploration and refinement in this field. This review highlights PFAS-cancer associations to fill knowledge gaps and provide evidence-based strategies for future research.

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Polarons are quasiparticles formed as a result of lattice distortions induced by charge carriers. The single-electron Holstein model captures the fundamentals of single polaron physics. We examine the power of the exponential ansatz for the polaron ground-state wavefunction in its coupled cluster, canonical transformation, and (canonically transformed) perturbative variants across the parameter space of the Holstein model. Our benchmark serves to guide future developments of polaron wavefunctions beyond the single-electron Holstein model.

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To explore the regulatory mechanism of endogenous hormones in the synthesis of anthocyanins in Anoectochilus roxburghii (Wall.) Lindl (A. roxburghii) under different light intensities, this study used metabolomics and transcriptomics techniques to identify the key genes and transcription factors involved in anthocyanin biosynthesis. We also analyzed the changes in and correlations between plant endogenous hormones and anthocyanin metabolites under different light intensities. The results indicate that light intensity significantly affects the levels of anthocyanin glycosides and endogenous hormones in leaves. A total of 38 anthocyanin-related differential metabolites were identified. Under 75% light transmittance (T3 treatment), the leaves exhibited the highest anthocyanin content and differentially expressed genes such as chalcone synthase (CHS), flavonol synthase (FLS), and flavonoid 3'-monooxygenase (F3'H) exhibited the highest expression levels. Additionally, 13 transcription factors were found to have regulatory relationships with 7 enzyme genes, with 11 possessing cis-elements responsive to plant hormones. The expression of six genes and two transcription factors was validated using qRT-PCR, with the results agreeing with those obtained using RNA sequencing. This study revealed that by modulating endogenous hormones and transcription factors, light intensity plays a pivotal role in regulating anthocyanin glycoside synthesis in A. roxburghii leaves. These findings provide insights into the molecular mechanisms underlying light-induced changes in leaf coloration and contribute to our knowledge of plant secondary metabolite regulation caused by environmental factors.

Asunto(s)

Antocianinas , Regulación de la Expresión Génica de las Plantas , Luz , Metaboloma , Orchidaceae , Hojas de la Planta , Proteínas de Plantas , Transcriptoma , Antocianinas/biosíntesis , Antocianinas/genética , Antocianinas/metabolismo , Orchidaceae/genética , Orchidaceae/metabolismo , Orchidaceae/efectos de la radiación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metaboloma/efectos de la radiación , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/genética , Perfilación de la Expresión Génica/métodos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo

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OBJECTIVES: Malnutrition and nutritional risk are risk factors for many adverse health outcomes in older adults, but they have rarely been assessed in China. The aim of this study was to evaluate the availability of Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA), a nutritional scale originally developed to predict mortality, in assessing nutritional risks and predicting adverse health outcomes in Chinese community-dwelling older adults. METHODS: This was a population-based longitudinal cohort study (Chinese Longitudinal Healthy Longevity Survey), with a 4-y follow-up of 2063 community-dwelling adults aged 65 y or older. Nutritional risks were assessed via the use of ENIGMA and Geriatric Nutritional Risk Index (GNRI) at baseline (the 2014 wave). Cognitive impairment, functional limitation, and frailty were evaluated using the Chinese version of the Mini-Mental State Examination, Instrumental Activities of Daily Living/Instrumental Activities of Daily Living scale, and Frailty Index, respectively, at baseline and 4-y follow-up (the 2018 wave). Mortality was measured by survival status and duration of exposure to death from baseline to follow-up. The associations of nutritional risks with prevalent/incident cognitive impairment, functional limitation and frailty, and 4-y mortality were estimated using logistic regression and Cox proportional hazards regression models, adjusting for confounders. The discriminatory accuracy of ENIGMA and GNRI for these adverse health outcomes were compared by receiver operating characteristic analyses. RESULTS: According to ENIGMA, 48.6% of the Chinese community-dwelling older adults (age: 86.5±11.3 y) showed moderate and high nutritional risk. Nutritional risks defined by the ENIGMA were significantly associated with increased prevalence and incidence of cognitive impairment, functional limitation, and frailty (odds ratio ranging from 1.79 to 89.6, values ranging from P < 0.001 to 0.048) but were mostly insignificant for that defined by GNRI. With respect to 4-y mortality, nutritional risks as defined by GNRI showed better prediction effects than those defined by ENIGMA. Receiver operating characteristic analyses indicated that nutritional risks defined by ENIGMA had better discriminatory accuracy than those defined by GNRI for prevalent and incident cognitive impairment (C = 0.73 vs 0.64, P < 0.001; C = 0.65 vs 0.59, P = 0.015, respectively), functional limitation (C = 0.74 vs 0.63, P < 0.001 at baseline; C = 0.61 vs 0.56, P = 0.016 at follow-up), frailty (C = 0.85 vs 0.67, P < 0.001 at baseline; C = 0.64 vs 0.55, P < 0.001 at follow-up), and even 4-y mortality (C = 0.68 vs 0.64, P = 0.020). CONCLUSIONS: ENIGMA could serve as a nutritional risk screening tool that has a robust role in predicting cognitive impairment, functional limitation, and frailty in Chinese community-dwelling older adults. It may be recommended for early nutritional risk screening and has the potential to guide early nutritional intervention in communities and primary care settings in China.

Asunto(s)

Evaluación Geriátrica , Vida Independiente , Desnutrición , Evaluación Nutricional , Estado Nutricional , Humanos , Anciano , Masculino , Femenino , Evaluación Geriátrica/métodos , Vida Independiente/estadística & datos numéricos , China/epidemiología , Desnutrición/diagnóstico , Desnutrición/epidemiología , Desnutrición/mortalidad , Estudios Longitudinales , Anciano de 80 o más Años , Factores de Riesgo , Fragilidad/mortalidad , Fragilidad/diagnóstico , Fragilidad/epidemiología , Actividades Cotidianas , Disfunción Cognitiva/epidemiología , Anciano Frágil/estadística & datos numéricos , Medición de Riesgo/métodos , Prevalencia , Estudios de Cohortes

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BACKGROUND: Diaphragmatic myoclonus is a rare motor disorder that affects muscle tone. It is characterized by involuntary movements of the abdominal wall and rhythmic, repetitive contractions of the accessory or respiratory muscles, all of which are innervated by the cervical nerve roots. CASE DESCRIPTION: We reviewed the case of a 57-year-old male patient who underwent surgery for a left cerebellar hemorrhage. He exhibited persistent myoclonus in the palate, jaw, and thoracoabdominal region. Following treatment, there was a significant reduction in flutter amplitude in these areas. CONCLUSION: The clinical rarity and variability of presentations often make diagnosis challenging and delayed. It is believed that this condition stems from abnormal excitation within the central nervous system or neural pathways that involve the phrenic nerve. Another potential mechanism is the direct irritation of the diaphragm. Ultrasound, chest fluoroscopy, and electromyography (EMG) can support the diagnosis. Various pharmacological and surgical treatments have been tried, yet specific treatment guidelines are still lacking.

Asunto(s)

Diafragma , Mioclonía , Humanos , Masculino , Persona de Mediana Edad , Mioclonía/etiología , Mioclonía/diagnóstico , Mioclonía/fisiopatología , Diafragma/fisiopatología , Diafragma/diagnóstico por imagen , Diafragma/inervación , Electromiografía/métodos , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/complicaciones

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Combined large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) is extremely rare, with only a few reports available in the literature. An accurate diagnosis is difficult to make due to the overlapping clinical features between LCNEC and SCLC, and a standardized treatment option is lacking. A 53-year-old female patient was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) due to symptoms of dyspnea and phlegm, with blood in the sputum. Computed tomography revealed a 52×32×26-mm irregular soft-tissue mass in the left upper lung. Pathological examination of the biopsy specimen showed a poorly differentiated neuroendocrine carcinoma with compression injury, consistent with a mixed type of large and small cell carcinoma. The patient was administered chemotherapy, radiotherapy and targeted therapy, and as of October 2023, the patient had a survival period of 29 months. LCNEC combined with SCLC is a sporadic tumor with a high potential for malignancy. Multidisciplinary treatment and close follow-up are recommended. The multidisciplinary treatment strategy used in the present study is expected to help inform future therapeutic decisions.

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Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform.  Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.

Asunto(s)

Glioblastoma , Ribonucleoproteínas Nucleares Heterogéneas , Proteína de Unión al Tracto de Polipirimidina , Proteína de Unión al GTP cdc42 , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Humanos , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP cdc42/metabolismo , Línea Celular Tumoral , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , Empalme del ARN , Neuronas/metabolismo , Neuronas/patología

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This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man. A literature review was conducted to explore recent advances in detecting, diagnosing, and treating intraocular metastatic malignancies. Positron emission tomography-computed tomography played a crucial role in identifying primary sites and systemic metastases. Local treatment combined with systemic therapy effectively reduced tumor size, preserved useful vision, and improved the patient's survival rate. A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer, including age, gender, tumor characteristics, and treatment. The challenges associated with diagnosis and treatment are discussed, highlighting the implications for clinical practice.

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Herein, we report a facile and efficient deuteration degree controllable method for the preparation of aryl deuteromethyl ethers through dual photoredox and thiol catalysis using phenols as the starting materials and inexpensive D2O and CDCl3 as the deuterium sources. All aryl d1, d2, and d3 deuteromethyl ethers can be precisely prepared with good to excellent yields and deuteration ratios. The reaction operates under mild conditions without the need for high temperatures or high loading of transition metal catalysts, and a wide range of functional groups are well tolerated.

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An 11-year nitrogen addition experiment reveals that for both plants and soil microorganisms, the ruderal strategists had higher productivity but lower stability, while the tolerant strategists had higher stability and lower productivity, leading to the tradeoff between productivity and stability within and across above- and below-ground communities.

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BACKGROUND: Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target for SCLC. However, none of the DLL3-targeting antibody-drug conjugates (ADCs) have been approved for SCLC therapy yet. We developed DB-1314, the new anti-DLL3 ADC composed of a novel humanized anti-DLL3 monoclonal antibody (DB131401) conjugated with eight molecules of P1021 (topoisomerase I inhibitor), and described its preclinical profiles. METHODS: The binding epitope for DB131401 and Rovalpituzumab was tested by biolayer interferometry. The binding affinity and specificity of DB-1314 to DLL3 and other homologous proteins were respectively measured by surface plasmon resonance and enzyme-linked immunosorbent assay. Internalization, bystander effects, and antibody-dependent cell-mediated cytotoxicity (ADCC) were assessed by respective assay. DLL3 was quantified by antibodies bound per cell assay and immunohistochemistry. In vitro and in vivo growth inhibition studies were evaluated in SCLC cell lines, and cell line/patient-derived xenograft models. The safety profile was measured in cynomolgus monkeys. RESULTS: DB-1314 induces potent, durable, and dose-dependent antitumor effects in cells in vitro and in cell/patient-derived xenograft models in vivo. The killing activity of DB-1314 mechanically arises from P1021-induced DNA damage, whereby P1021 is delivered and released within tumor cells through DLL3-specific binding and efficient internalization. Bystander effects and ADCC also contribute to the antitumor activity of DB-1314. DB-1314 displays favorable pharmacokinetic and toxicokinetic profiles in rats and cynomolgus monkeys; besides, DB-1314 is well-tolerated at a dose of up to 60 mg/kg in monkeys. CONCLUSIONS: These results suggest that DB-1314 may be a candidate ADC targeting DLL3 for the treatment of DLL3-positive SCLC, supporting further evaluation in the clinical setting.

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Inmunoconjugados , Neoplasias Pulmonares , Proteínas de la Membrana , Carcinoma Pulmonar de Células Pequeñas , Inhibidores de Topoisomerasa I , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Línea Celular Tumoral , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Macaca fascicularis , Ensayos Antitumor por Modelo de Xenoinjerto , Ratas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Ratones , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Benzodiazepinonas

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Ferro-rotational (FR) materials, renowned for their distinctive material functionalities, present challenges in the growth of homo-FR crystals (i.e., single FR domain). This study explores a cost-effective approach to growing homo-FR helimagnetic RbFe(SO4)2 (RFSO) crystals by lowering the crystal growth temperature below the TFR threshold using the high-pressure hydrothermal method. Through polarized neutron diffraction experiments, it is observed that nearly 86% of RFSO crystals consist of a homo-FR domain. Notably, RFSO displays remarkable stability in the FR phase, with an exceptionally high TFR of ≈573 K. Furthermore, RFSO exhibits a chiral helical magnetic structure with switchable ferroelectric polarization below 4 K. Importantly, external electric fields can induce a single magnetic domain state and manipulate its magnetic chirality. The findings suggest that the search for new FR magnets with outstanding material properties should consider magnetic sulfates as promising candidates.

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Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

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Magnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.

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Band structure of a semiconducting film critically determines the charge separation and transport efficiency. In antimony selenosulfide (Sb2(S,Se)3) solar cells, the hydrothermal method has achieved control of band gap width of Sb2(S,Se)3 thin film through tuning the atomic ratio of S/Se, resulting in an efficiency breakthrough towards 10 %. However, the obtained band structure exhibits an unfavorable gradient distribution in terms of carrier transport, which seriously impedes the device efficiency improvement. To solve this problem, here we develop a strategy by intentionally regulating hydrothermal temperature to control the chemical reaction kinetics between S and Se sources with Sb source. This approach enables the control over vertical distribution of S/Se atomic ratio in Sb2(S,Se)3 films, forming a favorable band structure which is conducive to carrier transport. Meanwhile, the adjusted element distribution not only ensures the uniformity of grain structure, but also increases the Se content of the films and suppress sulfur vacancy defects. Ultimately, the device delivers a high efficiency of 10.55 %, which is among the highest reported efficiency of Sb2(S,Se)3 solar cells. This study provides an effective strategy towards manipulating the element distribution in mixed-anion compound films prepared by solution-based method to optimize their optical and electrical properties.