Rapid visual dual-mode detection of Zr(IV) based on L-histidine functionalized gold nanoparticles.

Heavy metal pollution has always been a great threat to human health and safety. Compared with other heavy metals, although zirconium ion (Zr(IV)) is equally harmful, due to the lack of research on Zr(IV) in the biological systems and environment, its detection does not seem to have received the attention it deserves. Herein, a rapid visual dual-mode detection (colorimetric and chrominance method) of Zr(IV) based on L-histidine functionalized gold nanoparticles (HIS-AuNPs) has been reported. AuNPs and HIS-AuNPs before and after adding Zr(IV) were characterized by UV-Vis, TEM, DLS, Zeta potential, EDS and FT-IR, etc. These results showed that L-histidine was successfully modified on the surface of AuNPs by forming a stable Au-N bond, and its modification had little effect on the dispersion degree of AuNPs. After the addition of Zr(IV), interaction of this metal ion with the imidazolyl group on L-histidine can obviously cause the aggregation of HIS-AuNPs within 12 min, and the dispersion state and particle size of HIS-AuNPs can be significantly changed. These two detection modes were established by means of absorbance and color change of solution, and being used in addition and recovery experiments of Zr(IV) in natural water. Under the optimal conditions, these two modes exhibited good linearity within 15-70 and 20-100 µmol L-1, and limit of detection of 2.62 and 6.25 µmol L-1. The proposed method was highly sensitive and selective, which provided a new convenient way to realize the detection of Zr(IV).

USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.

Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.

Construction of a three-mode sensor based on gold nanoparticles and carbon quantum dots as probes for the detection of thiosemicarbazone.

In this study, ginkgo leaves were used as a carbon source to synthesize carbon quantum dots (CQDs) with uniform particle size, high fluorescence (FL) intensity and strong stability, using a hydrothermal method. FL could be quenched by the FL resonance energy transfer effect between CQDs and gold nanoparticles (AuNPs), an important FL quenching agent. The electrostatic attraction between thiosemicarbazone (TSC) and citrate on the surface of AuNPs and the formation of a stable Au-S bond between TSC and AuNPs led to the aggregation of AuNPs and thus weakened the quenching effect on CQDs and partly recovered the FL. A sensor in FL mode for the detection of TSC was constructed based on the above-mentioned FL "off" and "on" phenomena. The results showed a good linear correlation in the concentration range 0-1.75 µM, and the limit of detection was as low as 0.05 µM. In addition, the aggregation of AuNPs caused by TSC also led to a change in the absorbance curve and color of the solution; colorimetric and chrominance detection modes were also constructed using these two types of changes, with sensitive responses ranging 0-2.25 µM and 0-1.60 µM and the limits of detection of 0.03 µM and 0.08 µM, respectively. More importantly, these three detection modes obtained satisfactory recovery rates in the detection of the TSC content in river water, liquor and wheat samples, and the detection results were mutually verified (95.18% to 104.96%).

Exploring the barriers and facilitators of palliative care in the adult intensive care unit from nurses' perspectives in China: A qualitative study.

BACKGROUND: Intensive care units (ICUs) in China primarily focus on active rescue efforts, and it is not common to provide palliative care services within the ICU. As nurses play a primary role as caregivers for end-of-life patients in the ICU, it is necessary to explore the factors that impede or facilitate palliative care from their perspective. AIM: To explore the barriers and facilitators associated with implementing palliative care in Chinese adult ICUs from nurses' perspectives. STUDY DESIGN: This study utilized a descriptive phenomenological research approach and purposive sampling to conduct face-to-face semi-structured interviews with nurses working in adult ICUs from three comprehensive hospitals in China during the period between February and May 2023. A total of 17 nurses were interviewed, and the collected data were transcribed, coded, and synthesized thematically. RESULTS: Two themes of barriers and facilitators of palliative care in the Chinese adult ICU were extracted. The three sub-themes of hindering factors are as follows: (1) The influence of Chinese traditional culture. (2) The specificity of the ICU context. (3) Lacking sufficient attention in the ICU. The three sub-themes of the promoting factors are as follows: (1) Government and society value palliative care. (2) Patients and their families have palliative care needs. (3) Nurses view palliative care positively. CONCLUSION: Currently, integrating palliative care into the ICU may face challenges such as cultural factors, the specificity of the ICU context, and insufficient attention. However, it is worth noting that as the government and society place more emphasis on palliative care, more and more people are gradually paying attention to the palliative care needs of critically ill patients and their families. RELEVANCE TO CLINICAL PRACTICE: This study serves as a reference for exploring an ICU palliative care service model that is suitable for China's national conditions, such as education and training, resource allocation, service processes, and the palliative care environment, among others.

Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1.

Intervertebral disc degeneration (IDD) is a prevalent degenerative disorder that closely linked to aging. Numerous studies have indicated the crucial involvement of autophagy in the development of IDD. However, the non-selective nature of autophagy substrates poses great limitations on the application of autophagy-related medications. This study aims to enhance our comprehension of autophagy in the development of IDD and investigate a novel therapeutic approach from the perspective of selective autophagy receptor NBR1. Proteomics and immunoprecipitation and mass spectrometry analysis, combined with in vivo and in vitro experimental verification were performed. NBR1 is found to be reduced in IDD, and NBR1 retards cellular senescence and senescence-associated secretory phenotype (SASP) of nucleus pulposus cells (NPCs), primarily through its autophagy-dependent function. Mechanistically, NBR1 knockdown leads to the accumulation of S1 RNA-binding domain-containing protein 1 (SRBD1), which triggers cellular senescence via AKT1/p53 and RB/p16 pathways, and promotes SASP via NF-κß pathway in NPCs. Our findings reveal the function and mechanism of selective autophagy receptor NBR1 in regulating NPCs senescence and degeneration. Targeting NBR1 to facilitate the clearance of detrimental substances holds the potential to provide novel insights for IDD treatment.

Promising adsorbent for dye detoxification: Exploring the potential of chitosan sodium carboxymethylcellulose silk fibroin aerogel.

The main goal of this study is to create a CS-CMC-SF aerogel consisting of chitosan sodium carboxymethylcellulose and silk fibroin. The aerogel is designed to remove types of dyes from water while also being environmentally friendly. This innovative adsorbent has been optimized for extracting both cationic and anionic dyes from solutions. It incorporates chitosan sodium carboxymethylcellulose and silk filament fibers to enhance its strength. Experimental data illustrates that the CS-CMC-SF aerogel possesses remarkable adsorption capabilities - 5461.77 mg/g for Congo Red (CR), 2392.83 mg/g for Malachite Green (MG), and 1262.20 mg/g for Crystal Violet (CV). A kinetic study aligns with the pseudo-second-order kinetic model suggesting predominant chemisorption phenomena occur during adsorption process. Isotherm analysis further identifies multilayered adsorption occurring on irregularly shaped surfaces of the aerogel while thermodynamic assessments validate exothermic and spontaneous characteristics inherent in its absorption mechanism. Several analytical methods such as SEM, FT-IR, XRD, and XPS were employed to examine physicochemical attributes tied to this unique material design conceptually; identifying mechanisms including pore filling, π-π interactions, ion exchange activity, electrostatic connections along with hydrogen bonding inducing overall superior performance output. Furthermore substantial soil biodegradability alongside compostable features associated with our proposed CS-CMC-SF aerogels established it's potential suitability within applications demanding sustainable options thereby validating its underlying ecological credibility.

Aortic calcification correlates with pseudoaneurysm or penetrating aortic ulcer of different etiologies.

Chronic risk factors for pseudoaneurysm (PSA) or penetrating aortic ulcer (PAU) have not been fully clarified. This study aims to evaluate the association of aortic calcification with PSA or PAU of different etiologies. Totally 77 pseudoaneurysms, 80 PAU, and 160 healthy controls (HCs) were retrospectively included, of which 30 were infected, 34 were immunological, and 93 were atherosclerotic etiologies. The aortic calcification status, position of aortic tears/ulcers, and risk factors for disease or acute aortic syndrome (AAS) were identified. Atherosclerotic patients aged more than 65 and infective patients aged more than 60 had significantly higher calcification scores. The immunological group had a lower level of calcification in the infrarenal aorta. For patients of infective or atherosclerotic etiology, 60% (18/30) and 60.22% (56/93) of the tears/ulcers occurred at the aortic parts with the highest level of calcification. Patients with longitudinal calcification exceeding 1/3 of the aortic arch had an increased risk of acquiring diseases (OR = 13.231). The presence of longitudinal calcification of the descending aorta or cross-sectional calcification of the infrarenal aorta increased the risks of acquiring diseases (OR = 8.484 and 8.804). After adjusting for age, longitudinal calcification of the descending aorta exceeding 1/3 length was found to be associated with AAS (OR = 4.662). Tears/ulcers of pseudoaneurysm and PAU were both generally found at the part of the aorta with most calcification. Distinct aorta calcification characteristics were observed for lesions of different etiologies. Longitudinal thoracic and cross-sectional infrarenal abdominal aortic calcification increased the risk of acquiring diseases, and descending aortic calcification was associated with symptomatic patients.

Identification and experimental validation of Stearoyl-CoA desaturase is a new drug therapeutic target for osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor. Fatty acid reprogramming plays an essential role in OS progression. However, new fatty acid related therapeutic targets of OS have not been completely elucidated. Therefore, we firstly identified 113 differentially expressed fatty acid metabolism genes using bioinformatic analysis, 19 of which were found to be associated with OS prognosis. Then, 7 hub genes were screened out and yielded a strong prediction accuracy (AUC value = 0.88, at 3 years) for predicting the survival status of OS patients. Furthermore, we confirmed that SCD was highly expressed in OS cells and patients. And Knock-down of SCD impaired proliferation and migration of OS cells. Moreover, SCD was transcriptionally activated by c-Myc to promote proliferation and migration of OS cells. Finally, SCD inhibitor could significantly induce OS ferroptosis in vitro and in vivo. In conclusion, we identified that SCD was a reliable risk factor for OS patients. And SCD was activated by c-Myc. The inhibitor of SCD could significantly impaired OS growth and induce OS ferroptosis, which indicated that SCD was a potential drug target for OS treatment.

Caffeic acid modulates activation of neutrophils and attenuates sepsis-induced organ injury by inhibiting 5-LOX/LTB4 pathway.

BACKGROUND: Sepsis is a critical systemic inflammatory syndrome which usually leads to multiple organ dysfunction. Caffeic acid (CA), a phenolic compound derived from various plants, has been proved to be essential in neuroprotection, but its role in septic organ damage is unclear. This research aimed to investigate whether CA protects against organ injury in a mouse model of cecal ligation and puncture (CLP). METHODS: CA (30 mg/kg) or vehicle was administered by intraperitoneal injection immediately after CLP. The samples of blood, lungs, and livers were collected 24 h later. Organ injury was assessed by histopathological examination (HE staining), neutrophil infiltration (myeloperoxidase fluorescence), oxidative stress levels (MDA, SOD, HO-1), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) release in lung and liver tissues. Neutrophil extracellular trap (NET) formation was analyzed by immunofluorescence. In vitro experiments were performed to investigate the potential mechanisms of CA using small interfering RNA (siRNA) techniques in neutrophils, and the effect of CA on neutrophil apoptosis was analyzed by flow cytometry. RESULTS: Results showed that CA treatment improved the 7-day survival rate and attenuated the histopathological injury in the lung and liver of CLP mice. CA significantly reduced neutrophil infiltration in the lungs and livers of CLP mice. TNF-α, IL-1ß, IL-6 and LTB4 were reduced in serum, lung, and liver of CA-treated CLP mice, and phosphorylation of MAPK (p38, ERK, JNK) and p65 NF-κB was inhibited in lungs and livers. CA treatment further increased HO-1 levels and enhanced superoxide dismutase (SOD) activity, but reduced malondialdehyde (MDA) levels and NET formation. Similarly, in vitro experiments showed that CA treatment and 5-LOX siRNA interference inhibited inflammatory activation and NET release in neutrophils, suppressed MAPK and NF-κB phosphorylation in LPS-treated neutrophils, and decreased LTB4 and cfDNA levels. Flow cytometric analysis revealed that CA treatment reversed LPS-mediated delayed apoptosis in human neutrophils, and Western blot also indicated that CA treatment inhibited Bcl-2 expression but increased Bax expression. CA treatment did not induce further changes in neutrophil apoptosis, inflammatory activation, and NET release when 5-LOX was knocked down by siRNA interference. CONCLUSIONS: CA has a protective effect on lung and liver injury in a murine model of sepsis, which may be related to inhibition of the 5-LOX/LTB4 pathway.

Drug-coated balloon for treatment of non-atherosclerotic renal artery stenosis-a multi-center study.

INTRODUCTION: Renal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment. METHODS AND ANALYSIS: This will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate. TRIAL REGISTRATION: ClinicalTrials.gov (number NCT05858190). Protocol version V.4 (3 May 2023).

Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications.

Carotid body tumors (CBTs) are a rare type of paraganglioma, and surgical resection is the only effective treatment. Because of the proximity of CBTs to the carotid artery, jugular vein, and cranial nerve, surgery is extremely difficult, with high risks of hemorrhage and neurovascular injury. The Shamblin classification is used for CBT clinical evaluation; however, molecular mechanisms underlying classification differences remain unclear. This study aimed to investigate pathogenic mechanisms and molecular differences between CBT types. In Shamblin I, II, and III tumors, differentially expressed proteins (DEPs) were identified using direct data-independent acquisition (DIA). DEPs were validated using immunohistochemistry. Proteomics profiling of three Shamblin subtypes differed significantly. Bioinformatics analysis showed that adrenomedullin signaling, protein kinase A signaling, vascular endothelial growth factor (VEGF) signaling, ephrin receptor signaling, gap junction signaling, interleukin (IL)-1 signaling, actin cytoskeleton signaling, endothelin-1 signaling, angiopoietin signaling, peroxisome proliferator-activated receptor (PPAR) signaling, bone morphogenetic protein (BMP) signaling, hypoxia-inducible factor 1-alpha (HIF-1α) signaling, and IL-6 signaling pathways were significantly enriched. Furthermore, 60 DEPs changed significantly with tumor progression. Immunohistochemistry validated several important DEPs, including aldehyde oxidase 1 (AOX1), mediator complex subunit 22 (MED22), carnitine palmitoyltransferase 1A (CPT1A), and heat shock transcription factor 1 (HSF1). To our knowledge, this is the first application of proteomics quantification in CBT. Our results will deepen the understanding of CBT-related pathogenesis and aid in identifying therapeutic targets for CBT treatment.

Semaphorin4A promotes lung cancer by activation of NF-κB pathway mediated by PlexinB1.

Background: Lung cancer (LC) is the most prevalent cancer with a poor prognosis. Semaphorin4A (Sema4A) is important in many physiological and pathological processes. This study aimed to explore the role and mechanism of Sema4A in LC. Methods: Firstly, Sema4A expression was analyzed by the available dataset and detected in human normal bronchial epithelial cell line (HBE) and LC cell line (NCI-H460). Then, LC cells were transfected with Sema4A siRNA, and the cells were stimulated by PlexinB1, PlexinB2, PlexinD1 blocking antibodies, IgG antibody, BAY 11-7082 (an inhibitor for NF-κB pathway) and Sema4A-Fc protein, alone or in combination. After transfection, PlexinB1 mRNA expression was analyzed. Next, the biological functions, including proliferative, migratory, invasive abilities and viability of the cells were detected by colony formation, scratch, Transwell and MTT assays, respectively. NF-κB, Stat3 and MAPK protein expressions were determined by western blot. Furthermore, the secretion of IL-6 in LC cells was tested by ELISA. Results: Sema4A was highly expressed in LC tissues and cells, could activate the NF-κB pathway and upregulate PlexinB1 mRNA expression. Furthermore, we observed that Sema4A knockdown suppressed the biological functions of NCI-H460 cells, while Sema4A-Fc protein reversed the situation. However, Sema4A-induced biological functions and activation in the NF-κB pathway were inhibited by PlexinB1 blocking antibody. Consistently, Sema4A promoted IL-6 production, which was down-regulated by PlexinB1 blocking antibody and BAY 11-7082. Conclusions: Sema4A may facilitate LC development via the activation of the NF-κB pathway mediated by PlexinB1, suggesting that Sema4A would be a novel therapeutic target for LC treatment.

YY1 is regulated by ALKBH5-mediated m6A modification and promotes autophagy and cancer progression through targeting ATG4B.

YY1 affects tumorigenesis and metastasis in multiple ways. However, the function of YY1 and the potential mechanisms through which it operates in gastric cancer (GC) progression by regulating autophagy remains poorly understood. This study aimed to assess the essential transcription factors (TFs) involved in autophagy regulation in GC. Western blot, RFP-GFP-LC3 double fluorescence and transmission electron microscopy (TEM) assays were used to probe autophagy activity in GC cells. Methylated RNA immunoprecipitation (MeRIP) was utilized to evaluate the ALKBH5-regulated m6A levels of YY1. Gain- and loss-of-function assays were employed in the scrutiny of the biological effects of the ALKBH5/YY1/ATG4B axis on cancer cell proliferation and invasion abilities in vitro. Per the findings, YY1 was identified as a crucial transcriptional activator of cancer autophagy-related genes and promoted the proliferation and aggressiveness of cancer cells associated with enhanced ATG4B-mediated autophagy. However, ectopic ALKBH5 expression abolished the YY1-induced effect via m6A modification. Importantly, YTHDF1 facilitated the mRNA stability of YY1 through m6A recognition. Collectively, this study found that YY1 was regulated by ALKBH5 and YTHDF1-mediated m6A modification and served as an autophagy-dependent tumor driver to accelerate cancer progression through ATG4B transactivation, providing an exploitable therapeutic target for GC.

Sparganosis of a thoracic vertebra misdiagnosed as bone metastasis from lung cancer.

Sparganosis is a rare parasitic infection caused by plerocercoid tapeworm larvae. We described a case of a 27-year-old man presenting with numbness in both legs and masses in the right lung and spine, initially thought to have spinal metastasis from lung cancer. However, after pathological and parasitological examinations, the patient was found to have spinal sparganosis, likely due to a history of consuming raw frogs. The patient was successfully treated with praziquantel, resulting in the recovery of muscle strength in his legs. This case highlights the importance of considering spinal sparganosis as a differential diagnosis in patients with spinal masses, especially those with a history of consuming raw or undercooked frogs. Accurate diagnosis and early treatment are crucial for managing this infection.

Spatial Distribution of Pinus koraiensis Trees and Community-Level Spatial Associations in Broad-Leaved Korean Pine Mixed Forests in Northeastern China.

Investigating the spatial distributions and associations of tree populations provides better insights into the dynamics and processes that shape the forest community. Korean pine (Pinus koraiensis) is one of the most important tree species in broad-leaved Korean pine mixed forests (BKMFs), and little is known about the spatial point patterns of and associations between Korean pine and community-level woody species groups such as coniferous and deciduous trees in different developmental stages. This study investigated the spatial patterns of Korean pine (KP) trees and then analyzed how the spatial associations between KP trees and other tree species at the community level vary in different BKMFs. Extensive data collected from five relatively large sample plots, covering a substantial area within the natural distribution range of KP in northeastern China, were utilized. Uni- and bivariate pair correlation functions and mark correlation functions were applied to analyze spatial distribution patterns and spatial associations. The DBH (diameter at breast height) histogram of KP trees in northeastern China revealed that the regeneration process was very poor in the Changbai Mountain (CBS) plot, while the other four plots exhibited moderate or expanding population structures. KP trees were significantly aggregated at scales up to 10 m under the HPP null model, and the aggregation scales decreased with the increase in size classes. Positive or negative spatial associations were observed among different life stages of KP trees in different plots. The life history stages of the coniferous tree group showed positive spatial associations with KP saplings and juvenile trees at small scales, and spatial independence or negative correlations with larger KP trees at greater scales. All broad-leaved tree groups (canopy, middle, and understory layers) exhibited only slightly positive associations with KP trees at small scales, and dominant negative associations were observed at most scales. Our results demonstrate that mature KP trees have strong importance in the spatial patterns of KP populations, and site heterogeneity, limited seed dispersal, and interspecific competition characterize the spatial patterns of KP trees and community-level spatial associations with respect to KP trees, which can serve as a theoretical basis for the management and restoration of BKMFs in northeastern China.

Identification of potential drug targets for varicose veins: a Mendelian randomization analysis.

Introduction: Varicose veins are a common chronic disease that creates a significant economic burden on the healthcare system. Current treatment options, including pharmacological treatments, are not always effective, and there is a need for more targeted therapies. A Mendelian randomization (MR) method uses genetic variants as instrumental variables to estimate the causal effect of an exposure on an outcome, and it has been successful in identifying therapeutic targets in other diseases. However, few studies have used MR to explore potential protein drug targets for varicose veins. Methods: To identify potential drug targets for varicose veins of lower extremities, we undertook a comprehensive screen of plasma protein with a two-sample MR method. We used recently reported cis-variants as genetic instruments of 2,004 plasma proteins, then applied MR to a recent meta-analysis of genome-wide association study on varicose veins (22,037 cases and 437,665 controls). Furthermore, pleiotropy detection, reverse causality testing, colocalization analysis, and external replication were utilized to strengthen the causal effects of prioritized proteins. Phenome-wide MR (PheW-MR) of the prioritized proteins for the risk of 525 diseases was conducted to screen potential side effects. Results: We identified eight plasma proteins that are significantly associated with the risk of varicose veins after Bonferroni correction (P < 2.495 × 10-5), with five being protective (LUM, POSTN, RPN1, RSPO3, and VAT1) and three harmful (COLEC11, IRF3, and SARS2). Most identified proteins showed no pleiotropic effects except for COLLEC11. Bidirectional MR and MR Steiger testing excluded reverse causal relationship between varicose veins and prioritized proteins. The colocalization analysis indicated that COLEC11, IRF3, LUM, POSTN, RSPO3, and SARS2 shared the same causal variant with varicose veins. Finally, seven identified proteins replicated with alternative instruments except for VAT1. Furthermore, PheW-MR revealed that only IRF3 had potential harmful adverse side effects. Conclusions: We identified eight potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that IRF3, LUM, POSTN, RSPO3, and SARS2 might be potential drug targets for varicose veins.

Asymmetric Catalytic Ring-Expansion of 3-Methyleneazetidines with α-Diazo Pyrazoamides towards Proline-Derivatives.

We realized a highly efficient formal [1,2]-sigmatropic rearrangement of ammonium ylides generated from 3-methylene-azetidines and α-diazo pyrazoamides. The employ of readily available chiral cobalt(II) complex of chiral N,N'-dioxide enabled the ring-expansion of azetidines, affording a variety of quaternary prolineamide derivatives with excellent yield (up to 99 %) and enantioselectivity (up to 99 % ee) under mild reaction condition. For the rearrangement of ammonium ylides, the installation of a pyrazoamide group as a masked brick to build chiral scaffolds proved successful. The enantioselective ring expansion process was elucidated by DFT calculations.

Risk Factors and Nomogram for Postoperative Pulmonary Infection in Patients with Cervical Spinal Cord Injury.

OBJECTIVE: To identify the risk factors for developing postoperative pulmonary infection in patients with acute cervical spinal cord injury (CSCI), and to develop a nomogram prediction model. METHODS: Patients with CSCI who were admitted to 3 different medical centers between July 2011 and July 2021 were included in this study. All patients underwent cervical spine surgery. Data for patients admitted to the first 2 centers were included in a training set to establish the nomogram prediction model, and data for patients admitted to the third center were included in a validation set to externally verify the efficacy of the prediction model. For the training set, patients were divided into an infected group and a noninfected group (control group). Independent risk factors for postoperative pulmonary infection in patients with CSCI were identified by univariate and multivariate logistic regression analyses. Additionally, a nomogram prediction model was developed and validated based on the risk factors. RESULTS: A total of 689 patients were enrolled, including 574 for the training set and 115 for the validation set. Of the patients included for the training set, 144 developed pulmonary infection, with an incidence of 25.09%; 40 patients included for the validation set developed pulmonary infection (34.78%). Multivariate logistic regression analysis showed that age, American Spinal Injury Association grade, steroid pulse, high-level injury, smoking, multistage surgery, and operation duration were risk factors for the development of postoperative pulmonary infection in patients with CSCI. The area under the curve of the receiver operating characteristic curve of the model built by the training set was 0.905, and that of the receiver operating characteristic curve of the verification set was 0.917. The decision curve indicated that the model was in the range 1%-100%, and the predicted net benefit value of the model was high. CONCLUSIONS: Age, American Spinal Injury Association grade, steroid pulse, CSCI site, smoking history, number of surgical levels, and surgical duration are correlated with the development of postoperative pulmonary infection in patients with CSCI. The risk prediction model of postoperative pulmonary infection has a good prediction efficiency and accuracy.

CircREOS suppresses lipid synthesis and osteosarcoma progression through inhibiting HuR-mediated MYC activation.

MYC proto-oncogene (MYC) is a transcription factor among the most commonly activated oncoproteins, playing vital roles in lipid metabolism and tumor aggressiveness with broad effects. However, it is still largely unknown about the regulating mechanisms of MYC in osteosarcoma (OS). In this study, we identify a circRNA with Reduced Expression in OS (termed as circREOS) generated from MYC gene, as a novel regulator of MYC and OS progression. CircREOS is down-regulated in OS cells and localized in the nucleus. CircREOS suppresses MYC expression, lipid metabolism and growth, invasion in OS cells. Mechanically, circREOS physically interacts with HuR (human antigen R) protein, and subsequently restrains its binding and activation on the 3'-UTR (untranslated region) of MYC mRNA, resulting in down-regulation of MYC and inhibition of OS. Moreover, circREOS serves as a tumor suppressor via targeting lipid metabolism. CircREOS reduces FASN expression and lipid accumulation through inhibiting MYC-facilitated FASN regulation. Taken together, these results indicate that circREOS suppress lipid synthesis and OS progression through inhibiting HuR-mediated MYC activation, providing a potential therapeutic target for OS.

Blood pressure and renal outcomes after renal artery aneurysm intervention: Single-center experience and review of literature.

Objective: To explore the results of hypertension improvement and renal function preservation after renal artery aneurysm (RAA) repair. Methods: This study retrospectively analyzed the change in blood pressure (BP) and renal outcomes of 59 RAA patients throughout either open or endovascular operations and follow-up at a large center. Patients were grouped according to the difference in their BP at the last follow-up vs. their baseline value. Logistic regression was conducted to explore risk factors for perioperative BP relief and long-term hypertension reonset. Previous studies of RAA with records of BP, blood creatinine level, or GFR/eGFR results are reviewed. Results: Hypertension was observed in 62.7% (37/59) of the patients included. Postoperative BP declined from 132.20 ± 16.46/79.92 ± 9.64 mmHg to 122.41 ± 11.17/71.10 ± 9.82 mmHg, while eGFR changed from 108.17 ± 24.73 to 98.92 ± 23.87 ml/min/1.73 m2. The median follow-up was 854 [IQR: 1,405] days. Both open and endovascular techniques significantly relieved hypertension and did not impair renal function much. Lower preoperative systolic BP (SBP) was significantly associated with hypertension relief (OR = 0.83, 95% CI: 0.70-0.99). Among patients with normal BP after the operation, higher postoperative SBP was significantly associated with new-onset hypertension (OR = 1.14, 95% CI: 1.01-1.29). Literature review indicated that renal function usually remained normal at follow-up, whereas relief of hypertension varied. Conclusion: Patients with lower preoperative SBP were likely to benefit more from the operation, while higher postoperative SBP indicated a higher chance of hypertension reonset. Creatinine level and eGFR generally remained stable regardless of operation type.