Artemether ameliorates acetaminophen-induced liver injury through Nrf2 pathway.

Acetaminophen (APAP) overdose is a prevalent cause of clinical pharmacological liver injury worldwide. Artemether (ART), a first-line antimalarial drug, has demonstrated hepatoprotective activity. However, its effect on APAP-induced acute liver injury (AILI) remains unclear. In this study, we investigated whether ART can protect against AILI and examined its underlying mechanisms. In vivo, ART mitigated APAP-induced liver histological changes, including mitochondrial damage, hepatocyte necrosis, hepatocyte apoptosis, and inflammatory infiltration. Additionally, ART reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in APAP-induced mice. ART also activated the Nrf2-HO-1/GPX4 signaling pathway, exerting antioxidant effects in both in vitro and in vivo models of AILI. To confirm Nrf2 as a target of ART in vivo, we pretreated C57BL/6 mice with the Nrf2 inhibitor, ML385. The results indicated that inhibiting Nrf2 diminishes the protective effect of ART against AILI. Overall, our findings suggest that ART's protective effect against AILI is mediated through the Nrf2-related antioxidant pathway.

Uterine tumors mimicking ovarian sex cord tumors with rhabdoid differentiation: a clinicopathologic study of 4 cases: A case series analysis.

RATIONALE: Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with rhabdoid features are uncommon mesenchymal neoplasms exhibiting diverse histological patterns, including significant rhabdoid morphology. A thorough comprehension of their clinicopathologic features is crucial for precise diagnosis and effective management. PATIENT CONCERNS: This study presents 4 cases of UTROSCT with rhabdoid features, diagnosed in patients aged 31 to 58. Varied recurrence patterns were observed, including similar recurrent lesions to the primary tumors with subsequent mortality, initial invasion and lymph node metastasis, and presence of only primary tumor. DIAGNOSES: Histopathological examination revealed diverse morphological patterns, prominently featuring rhabdoid differentiation. Immunohistochemical analysis showed expression of hormone receptors, sex cord, smooth muscle, and epithelial markers, notably WT1, CD56, and CD99. Molecular analysis identified ESR1-NCOA2 fusions and ESR1 and NCOA2/3 rearrangements, indicating a potential association between these genetic alterations and extensive rhabdoid differentiation. INTERVENTIONS: Various treatments were administered post-recurrence, including chemotherapy and targeted therapies. However, poor clinical outcomes were observed in all cases. OUTCOMES: Despite aggressive treatments, including chemotherapy and targeted therapies, poor clinical outcomes were observed, highlighting the aggressive nature of UTROSCT with significant rhabdoid differentiation. LESSONS: This case series emphasizes the importance of detailed pathological reporting, comprehensive molecular testing, and thorough tumor staging in UTROSCT cases with rhabdoid features. Enhanced understanding of the clinicopathologic characteristics of UTROSCT with rhabdoid differentiation is crucial for accurate diagnosis, prognostication, and management strategies.

Transcranial ultrasound with electrical stimulation of the cerebello-parietal nucleus on cerebral blood flow and limb function in patients with stroke.

OBJECTIVE: To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. METHODS: A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. RESULTS: The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). CONCLUSION: The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

VALD-2 mitigates cisplatin-induced acute kidney injury: Mechanistic insights into oxidative stress modulation and inflammation suppression.

This study explores the compelling antitumor properties of VALD-2, a synthetic Schiff base ligand known for its low toxicity. The focus is on investigating VALD-2's protective role against cisplatin-induced acute kidney injury (AKI) in mice, with a specific emphasis on mitigating oxidative stress and inflammation. The study involves daily intraperitoneal injections of amifostine or VALD-2 over 7 days to establish an AKI model. Subsequently, mice were assigned to normal control, cisplatin group, cisplatin + amifostine group, and cisplatin + VALD-2 10 mg/kg group, cisplatin + VALD-2 20 mg/kg, and cisplatin + VALD-2 40 mg/kg. Kidney injury is assessed through serum blood urea nitrogen (BUN) and creatinine (Cr) activity assays. Levels of inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in kidney tissue of mice were assessed through enzyme-linked immunosorbent assay (ELISA). The protective effect of VALD-2 is further examined through HE staining to observe pathological changes in kidney injury. The ultrastructural changes of renal cells and tubular epithelial cells were observed by electron microscopy under experimental conditions, indicating the effect of VALD-2 on reversing cisplatin-induced renal injury. The study delves into VALD-2's protective mechanisms against cisplatin-induced kidney injury by using western blot analysis to assess the expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in kidney tissues. VALD-2 demonstrates significant improvement in cisplatin-induced AKI, as evidenced by increased BUN and Cr levels. It effectively protects kidney tissue from oxidative damage, enhancing SOD and GSH-Px activities while reducing MDA levels. The study also reveals a decrease in TNF-α and IL-6 levels, supported by ELISA results, and histological findings confirm anti-nephrotoxic effects. Western blot analysis shows an upregulation of antioxidant enzymes (SOD, GSH-Px) and a reduction in MDA production. VALD-2 emerges as a promising mitigator of cisplatin-induced AKI, showcasing its ability to enhance oxidative stress-related protein expression. The findings suggest VALD-2 as a potential therapeutic agent for protecting against cisplatin-induced kidney injury.

Analysis of the efficacy of hyperbaric oxygen therapy for disorders of consciousness: A retrospective cohort study.

OBJECTIVE: To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment. METHODS: A retrospective study was carried out on patients with disorders of consciousness (DOC) receiving HBO treatment from January to January 2022 in the Second Department of Rehabilitation Medicine of the Second Hospital of Hebei Medical University, China. RESULTS: HBO therapy improved the Glasgow Coma Scale (GCS) and Chinese Nanjing Persistent Vegetative State Scale (CNPVSS), as well as the clinical efficacy in patients with DOC. The comparison of GCS and CNPVSS scores in patients with DOC before and after HBO treatment was all statistically significant, with 325 patients (67.1%) showing effective results and 159 patients (32.9%) having unchanged outcomes. Univariate analysis indicated that there were statistically significant differences in age, HBO intervention time, HBO treatment times, pre-treatment GCS score, and etiology and underlying diseases between the good and poor prognoses groups. Multivariate regression analysis showed that HBO intervention time ≤7 days, HBO treatment ＞ times, high GCS score before HBO treatment, and brain trauma were independent influencing factors in achieving a good prognosis for patients with DOC. Low pre-treatment GCS scores were an independent risk factor for a poor prognosis in patients with brain trauma while being male, late HBO intervention time, fewer HBO treatment times, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after a stroke. Being ≥50 years of age, late HBO intervention time, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after hypoxic-ischaemic encephalopathy. CONCLUSION: HBO therapy can improve the GCS, CNPVSS scores and clinical efficacy in patients with DOC, and the timing of HBO intervention ≤7 days, times of HBO treatment, high pre-treatment GCS score, and brain trauma were the independent influencing factors of good prognosis in patients with DOC.

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Cannabis sativa Leaves and Their Antioxidant Properties.

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity. A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity. A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors.

The H2Valdien derivatives regulate the epithelial-mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway.

This research delves into the influence of H2Valdien derivatives on the proliferation, migration, and apoptosis induction in hepatoma carcinoma cells (HepG2, Huh-7, and SMMC-7721), with a specific emphasis on inhibiting epithelial-mesenchymal transition (EMT) through modulation of the Hedgehog (Hh) signaling pathway. Utilizing the cell counting kit-8 method, flow cytometry, TUNEL assay, wound healing, and transwell assays, we observed a dose-dependent growth arrest and apoptosis induction in HepG2, Huh-7, and SMMC-7721 cells. Notably, H2Valdien derivatives exhibited a capacity to reduce migration and invasion, impacting the expression of EMT-associated proteins such as N-cadherin, vimentin, and E-cadherin. Mechanistically, these derivatives demonstrated the inhibition of the Hh signaling pathway by inactivating Sonic Hh (Shh) and smoothened proteins. This study underscores the robust antiproliferative and apoptosis-inducing effects of H2Valdien derivatives on hepatoma carcinoma cells and elucidates their regulatory role in EMT through modulation of the Hh signaling pathway, providing valuable insights for potential therapeutic interventions.

Analysis of factors associated with the development of delayed encephalopathy following acute carbon monoxide poisoning.

In this study, we analyzed the factors influencing the development of delayed encephalopathy in patients with acute carbon monoxide poisoning (ACOP) (DEACMP) following conventional treatment such as hyperbaric oxygen therapy (HBOT). Between January 2012 and January 2022, we retrospectively analyzed 775 patients with ACOP, who were admitted to the Second Department of Rehabilitation Medicine and received HBOT in the Second Hospital of Hebei Medical University. These patients were divided into the non-DEACMP and DEACMP groups based on their follow-up; we then compared the general data, clinical characteristics, admission examination, and treatment between the two groups to identify risk factors for the development of DEACMP. The DEACMP group comprised of 168 cases, while the non-DEACMP group consisted of 607 cases. Univariate analysis showed that there were 20 possible prognostic factors in the non-DEACMP and DEACMP groups. The results of multivariable regression analyses suggested that the occurrence of DEACMP was significantly correlated with advanced age, the combination of multiple medical histories, the duration of CO exposure, the duration of coma, poisoning degree, the Interval between ACOP and the first HBOT, the total number of HBOTs, and the combination with rehabilitation treatment. DEACMP patients who are older, have more comorbidities, prolonged CO exposure, prolonged coma, severe intoxication, long intervals between ACOP and the first HBOT, fewer HBOT treatments, and who are not treated with a combination of rehabilitative therapies have a poor prognosis.

Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury.

Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.

Quenching study of Cu2S-MPA/NGODs composites in electrochemiluminescence detection by modulating resonance energy transfer and adsorption process.

This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu2S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu2S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu2S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu+ ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples.

Research on improved YOLOv8n based potato seedling detection in UAV remote sensing images.

Introduction: Accurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model. Methods: We established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. Results: The VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%. Discussion: Comparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.

Anlotinib in Chinese patients aged ≥70 years with advanced non-squamous non-small cell lung cancer without prior chemotherapy: a multicenter, single-arm pilot trial.

Background: Based on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed. Methods: This multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS). Results: Forty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%). Conclusion: Anlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.

The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-ß/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells.

Background: EBV-miR-BARTs exhibit significant relevance in epithelial tumors, particularly in EBV-associated gastric and nasopharyngeal cancers. However, their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored. Material and Methods: Initially, EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines. Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45, and downregulation in EBV-positive cells (SUN-719). The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation, migration, and glycolytic processes, with the TGF-ß/SMAD4 signaling pathway value clarified using a TGF-ß inhibitor. Results: EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells, while its target gene SMAD4 demonstrates downregulated expression. Upregulation of it can promote the proliferation and migration of gastric cancer cells. Additionally, We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells. Inhibition of the TGF-ß/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells, concomitant with a diminished glycolytic capacity. Conclusion: In this study, we found that EBV-miRNA-BART6-5p can target SMAD4, effectively increasing glycolysis in gastric cancer cells by regulating the TGF-ß/SMAD4 signaling pathway, thereby enhancing the proliferation and metastasis of gastric cancer cells. Our findings may offer new insights into the metabolic aspects of gastric cancer.

Lactate Protects Intestinal Epithelial Barrier Function from Dextran Sulfate Sodium-Induced Damage by GPR81 Signaling.

The dysregulation of the intestinal epithelial barrier significantly contributes to the inflammatory progression of ulcerative colitis. Recent studies have indicated that lactate, produced by gut bacteria or derived from fermented foods, plays a key role in modulating inflammation via G-protein-coupled receptor 81 (GPR81). In this study, we aimed to investigate the potential role of GPR81 in the progression of colitis and to assess the impact of lactate/GPR81 signaling on intestinal epithelial barrier function. Our findings demonstrated a downregulation of GPR81 protein expression in patients with colitis. Functional verification experiments showed that Gpr81-deficient mice exhibited more severe damage to the intestinal epithelial barrier and increased susceptibility to DSS-induced colitis, characterized by exacerbated oxidative stress, elevated inflammatory cytokine secretion, and impaired expression of tight-junction proteins. Mechanistically, we found that lactate could suppress TNF-α-induced MMP-9 expression and prevent the disruption of tight-junction proteins by inhibiting NF-κB activation through GPR81 in vitro. Furthermore, our study showed that dietary lactate could preserve intestinal epithelial barrier function against DSS-induced damage in a GPR81-dependent manner in vivo. Collectively, these results underscore the crucial involvement of the lactate/GPR81 signaling pathway in maintaining intestinal epithelial barrier function, providing a potential therapeutic strategy for ulcerative colitis.

Recent progress of high-performance in-plane zinc ion hybrid micro-supercapacitors: design, achievements, and challenges.

With the increasing demand for wearable and miniature electronics, in-plane zinc (Zn) ion hybrid micro-supercapacitors (ZIHMSCs), as a promising and compatible energy power source, have attracted tremendous attention due to their unique merits. Despite enormous development and breakthroughs in this field, there is still a lack of a systematic and comprehensive review to update the recent progress of in-plane ZIHMSCs in the design and fabrication of both micro-anodes and micro-cathodes, the exploration and optimization of new electrolytes, and the investigation of related-energy storage mechanisms. This minireview summarizes the key breakthroughs and recent advances in the construction of high-performance in-plane ZIHMSCs. First, the background and fundamentals of in-plane ZIHMSCs are briefly introduced. Then, new concepts, strategies, and latest exciting developments in the preparation and interfacial engineering of Zn metal micro-anodes, the fabrication of advanced micro-cathodes, and the exploration of new electrolyte systems are discussed, respectively. Finally, the key challenges and future directions for the development of high-performance in-plane ZIHMSCs are presented as well. This review not only accounts for the recent research progress in the field of the in-plane ZIHMSCs, but also provides important new insights into the design of next-generation miniaturized energy storage devices.

Hypoxia-Mediated Upregulation of Xanthine Oxidoreductase Causes DNA Damage of Colonic Epithelial Cells in Colitis.

Xanthine oxidoreductase (XOR) serves as the primary source of hydrogen peroxide and superoxide anions in the intestinal mucosa. However, its specific contribution to the progression of colonic disease remains unclear. In this study, we investigated the role of XOR in ulcerative colitis (UC) and attempted to identify the underlying mechanisms. We used the dextran sulfate sodium (DSS)-induced mouse model to mimic UC and observed that XOR inhibitors, allopurinol and diphenyleneiodonium sulfate (DPI), significantly alleviated UC in mice. In addition, treatment with cobalt chloride (CoCl2) and 1% O2 increased the expression of XOR and induced DNA oxidative damage in colonic epithelial cells. Furthermore, we identified that XOR accumulation in the nucleus may directly cause DNA oxidative damage and regulates HIF1α protein levels. In addition, allopurinol effectively protected colon epithelial cells from CoCl2-induced DNA damage. Altogether, our data provided evidence that XOR could induce DNA damage under hypoxic conditions, indicating a significant role of XOR in the initiation and early development of colitis-associated colorectal cancer (CAC).

Pyrenecarboxaldehyde@Graphene Oxide Acted as a Highly Efficient ECL Emitter and Target-Triggered the Recyclable Cascade System as an Amplifier for Ultrasensitive APE1 Activity Detection.

Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10-9 U·mL-1 ranging from 10-8 to 10-2 U·mL-1. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.

Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman's disease: A case report.

Multicentric Castleman disease (MCD) is a heterogeneous, life-threatening disease. A subgroup of HIV-negative and HHV-8-negative MCD is defined as idiopathic MCD (iMCD) with a poor prognosis. Here we report an unusual case of a 47-year-old male patient with iMCD who experienced multiple treatment regimens such as chemotherapy, immunomodulatory therapy, and targeted therapy, all of which were considered ineffective. Subsequently, he was started on bortezomib in combination with dexamethasone for six cycles and he was in complete remission. The patient has survived nearly 13 years to date - the longest survival of any iMCD patient treated with bortezomib in combination with dexamethasone. Bortezomib combined with dexamethasone may be an effective salvage strategy for severe and refractory iMCD.