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Zheng-Dao Mao,1,* Zhi-Guang Liu,1,* Yan Qian,1 Yu-Jia Shi,1 Lian-Zheng Zhou,1 Qian Zhang,1 Chun-Jian Qi2 1Department of Respiratory and Critical Care Medicine, Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Central Laboratory, Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Jian Qi, Laboratory of Oncology, Changzhou Second People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213003, People’s Republic of China, Tel +86-519-81087391, Email qichunjian@njmu.edu.cn Qian Zhang, Department of Respiratory and Critical Care Medicine, Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, No. 29 Xinlong Road, Changzhou, 213003, People’s Republic of China, Tel +86-519-81087391, Email qianzhang@njmu.edu.cnIntroduction: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent clinical or subclinical allergic symptom of diseases of the upper and lower respiratory tract. This study is the first to explore the expression profiles of mRNA, lncRNA, and circRNA in CARAS using RNA sequencing, which may provide insight into the mechanisms underlying CARAS.Material and Methods: Whole blood samples from nine participants (three CARAS patients, three AR patients, and three normal control participants) were subjected to perform RNA sequencing, followed by identification of differentially expressed lncRNAs (DElncRNAs), circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Then, lncRNA/circRNA-mRNA regulatory pairs were constructed, followed by functional analysis, immune infiltration analysis, drug prediction, and expression validation with RT-qPCR and ELISA.Results: The results showed that 61 DEmRNAs, 23 DElncRNAs and 3 DEcircRNAs may be related to the occurrence and development of CARAS. KRT8 may be implicated in the development of AR into CARAS. Three immunity-related mRNAs (IDO1, CYSLTR2, and TEC) and two hypoxia-related mRNAs (TKTL1 and VLDLR) were associated with the occurrence and development of CARAS. TEC may be considered a drug target for Dasatinib in treating CARAS. Several lncRNA/circRNA-mRNA regulatory pairs were identified in CARAS, including LINC00452/MIR4280HG/hsa_circ_0007272/hsa_circ_0070934-CLC, HEATR6-DT/LINC00639/LINC01783/hsa_circ_0008903-TEC, RP11-71L14.3-IDO1/SMPD3, RP11-178F10.2-IDO1/HRH4, and hsa_circ_0008903-CYSLTR2, which may indicate potential regulatory effects of lncRNAs/circRNAs in CARAS. Dysregulated levels of immune cell infiltration may be closely related to CARAS.Conclusion: The regulating effect of lncRNA/circRNA-immunity/hypoxia-related mRNA regulatory pairs may be involved in the occurrence and development of CARAS.Keywords: combined allergic rhinitis and asthma syndrome, lncRNA, circRNA, immunity, hypoxia

Lian Zhen Zhou,1,* Xuan Li,2,* Li Min Zhou1 1Department of Anesthesiology, the Second Affiliated Hospital of Shandong First Medical University, Tai’ an, People’s Republic of China; 2Department of Anesthesiology and Pain Clinic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Min Zhou, Department of Anesthesiology, the Second Affiliated Hospital of Shandong First Medical University, No. 366 Taishan Street, Tai’ an, Shandong Province, 271000, People’s Republic of China, Tel +86-17661211078, Email zlm94523@sina.comBackground: The postoperative acute pain caused by surgery has been a major problem plaguing anesthesiologists, and even some acute pain progresses to chronic pain syndrome, terribly reducing the quality of life of patients. To this end, increasing attention has been paid to the management of perioperative analgesia. At present, with the increase of research on perioperative analgesia, the understanding and solution of this clinical problem have been further developed. Bibliometrics can estimate research hot-spots and trends of related fields in a certain period of time. However, a systematic bibliometric analysis has not been conducted to explore current research hotspots and future development trends, which is thus the purpose of this study.Methods: Articles and reviews published from 2012 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database, and the bibliometric analysis of the keywords and references of articles was performed using VOSviewer1.6.18. Besides, the number of articles related to perioperative analgesia in term of countries, affiliations, authors, and journals were analyzed.Results: Finally, 3157 articles meeting the screening requirements were retrieved, and it was hereby found that the research on perioperative analgesia had received more attention and interest in the past 10 years, with the United States making more contributions, where there were eight of the top ten affiliations by the number of publications. Kaye AD was the most active researcher in this field. Most related articles were published in Anesthesia and Analgesia, accounting for 2.76% of all literature. Enhanced recovery after surgery, different types of anesthesia and multi-mode analgesic drug intervention were the main trends and hotspots.Conclusion: Perioperative analgesia has attracted considerable academic interest. In the past decade, the effects of enhanced recovery after surgery, different types of anesthesia and multi-mode analgesic drug intervention on perioperative analgesia have become the research hotspots, which are also likely to be the focus of future study.Keywords: perioperative analgesia, pain, enhanced recovery after surgery, bibliometrics, VOSviewer

Juan Pan,1 Chao Ye,2 Ling-Zhi Zhou,1 Zu-Yi Li,1 Juan Wang,2 Xin He,2 Shen-Jue Chen,2 Guang-Qing Zhou2 1Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Ye, Department of Pharmacy, The Third Hospital of Changsha, No. 176 Laodong West Road, Tianxin District, Changsha, Hunan, 410015, People’s Republic of China, Email yechao1234256@163.com Ling-Zhi Zhou, Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, No. 67, Beizheng Middle Road, Changsha, Hunan, 410300, People’s Republic of China, Email 1024482174@qq.comIntroduction: Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP.Methods: Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis.Results: Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9– 87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5– 61) versus 57.5 years (range 9– 87) (P=0.03). The median time of symptom onset was 7 days (range 2– 29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1– 43), and the median time to relieve symptoms was 4 days (range 1– 12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia.Conclusion: Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.Keywords: tigecycline, pancreatitis, adverse drug reaction, solid organ transplantation

Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls. Injection of TEVs into mice impairs macrophage-mediated bacterial clearance, increases systemic bacterial dissemination, and enhances sepsis score in a PD-L1-dependent manner. Mechanistically, TEV-packaged PD-L1 inhibits Bruton's tyrosine kinase/PLCγ2 signaling-mediated cytoskeleton reorganization and reactive oxygen species generation, impacting bacterial phagocytosis and killing by macrophages. Neutralizing PD-L1 markedly normalizes macrophage-mediated bacterial clearance in tumor-bearing mice. Importantly, circulating sEV PD-L1 levels in patients with tumors can predict bacterial infection susceptibility, while patients with tumors treated with αPD-1 exhibit fewer postoperative infections. These findings identify a mechanism by which cancer cells dampen host innate immunity-mediated bacterial clearance and suggest targeting TEV-packaged PD-L1 to reduce bacterial infection susceptibility in tumor-bearing conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The ability to discriminate and categorize the meaning of environmental stimuli and respond accordingly is essential for survival. The ventral hippocampus (vHPC) controls emotional and motivated behaviors in response to environmental cues and is hypothesized to do so in part by deciphering the positive or negative quality of these cues. Yet, what features of the environment are represented in the activity patterns of vCA1 neurons, and whether the positive or negative meaning of a stimulus is present at this stage, remains unclear. Here, using 2-photon calcium imaging across six different experimental paradigms, we consistently found that vCA1 ensembles encode the identity, sensory features, and intensity of learned and innately salient stimuli, but not their overall valence. These results offer a reappraisal of vCA1 function, wherein information corresponding to individual stimulus features and their behavioral saliency predominates, while valence-related information is attached elsewhere., Competing Interests: Competing interests: The authors declare that they have no competing interests.

During sexual reproduction in flowering plants, tip-growing pollen tubes travel from the stigma inside the maternal tissues of the pistil towards ovules. In maize (Zea mays L.), the stigma is highly elongated, forming thread-like strands known as silks. Only compatible pollen tubes successfully penetrate and grow through the transmitting tract of the silk to reach the ovules. Like pollen, fungal spores germinate at the surface of silks and generate tube-like structures (hyphae) penetrating silk tissue. To elucidate commonalities and differences between silk responses to these distinctive invading cells, we compared growth behavior of the various invaders as well as the silk transcriptome after self-pollination, cross-pollination and infection using two different fungi. We report that self-pollination triggers mainly senescence genes, whereas incompatible pollen from Tripsacum dactyloides leads to downregulation of rehydration, microtubule, and cell wall-related genes, explaining the slower pollen tube growth and arrest. Invasion by the ascomycete Fusarium graminearum triggers numerous defense responses including the activation of monolignol biosynthesis and NAC as well as WRKY transcription factor genes, whereas responses to the basidiomycete Ustilago maydis are generally much weaker. We present evidence that incompatible pollination and fungal infection trigger transcriptional reprograming of maize silks cell wall. Pathogen invasion also activates the phytoalexin biosynthesis pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Objectives: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth., Materials and Methods: Immunohistochemical analysis was used to compare BRAF V600E, MMP2, MMP9, and Ki-67 expressions in AM (n = 49), normal oral mucosa (NOM) (n = 10), and odontogenic keratocyst (OKC) (n = 15) tissues. AM was further classified according to the presence or absence of BRAF V600E. The relationship between BRAF V600E and invasion as well as growth was evaluated. In addition, correlation analysis was performed using immunohistochemistry and confirmed via double-labeling immunofluorescence. Finally, comparative analyses using mass spectrometry, immunohistochemistry, and immunofluorescence were performed to explore and identify underlying mechanisms., Results: AM exhibited a higher incidence of BRAF V600E mutation than NOM and OKC. BRAF V600E expression was positively correlated with the invasion-associated proteins MMP2 and MMP9 and the growth-related protein Ki-67. Proteomic data revealed that BRAF V600E primarily activates the MAPK signaling pathway in AM, particularly driving the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)., Conclusions: In summary, the findings suggested that the BRAF V600E mutation enhances the invasion and growth abilities of AM via the MAPK/ERK signaling pathway. Thus, targeting BRAF V600E or the MAPK/ERK pathway may be a potential AM therapy., (© 2024 Wiley Periodicals LLC.)

Objectives: To summarize the clinical characteristics and investigate the efficacy of ethanol embolotherapy in the treatment of chest well arteriovenous malformation (AVM). Treatment-associated complications were also explored., Materials and Methods: Between March 2017 and August 2021, 32 consecutive patients (mean age, 23.7 years; age range, 5-54 years) who underwent ethanol embolotherapy for chest well AVMs under general anesthesia were included in this study. Embolization was performed through a direct puncture, transarterial catheterization, or a combination of the 2 procedures. The mean follow-up duration after the last treatment was 18.0 months (range, 3-42 months). The degree of devascularization on follow-up (assessed using angiography or computed tomography), and the clinical signs and symptoms of AVMs were evaluated as the therapeutic outcomes. The major and minor complications associated with the procedures were recorded., Results: A total of 103 embolization procedures (mean, 3.2; range, 2-7) comprising 101 ethanol embolization and 2 coil embolizations were performed on 32 patients with chest wall AVMs. The AVM nidus was accessed through the transarterial approach alone in 4 patients, by direct puncture in 11, and a combined procedure in 17 patients. Overall, more than 80% of the procedures were performed using the combined approach. Complete AVM devascularization was achieved in 12 (37.5%) patients. Moreover, 76% to 99% AVM was achieved in 18 patients (56.3%), and 50% to 75% in 2 patients (6.3%). Bleeding, pain, heart failure, and cosmetic deformities were the indications for treatment. For 3 patients (3/32, 9.4%) who had bleeding, the treatment stopped the hemorrhage. Complete pain relief was reported in 8 patients (8/32, 25.0%), whereas complete relief from congestive heart failure post-embolization was observed in 5 of the 6 patients with congestive heart failure (5/6, 83.3%). Complete correction of cosmesis deformities after embolization was achieved in 10 patients (10/32, 31.3%). Two patients who underwent surgery to correct persistent deformity after embolization only showed insignificant improvement. In addition, 6 (18.8%) patients developed 13 complications including blister, necrosis, hemothorax, transient hemoglobinuria, and transient pulmonary artery hypertension., Conclusions: Ethanol embolotherapy is a safe and effective procedure for chest well AVMs. Surgery is required for some patients with residual cosmesis deformity., Clinical Impact: Currently, there is no standard treatment for chest well AVMs due to their rarity and high heterogeneity. The present study shows that thanol embolotherapy is a safe and clinically effective treatment procedure for the chest well AVMs. Transarterial embolization in combination with direct puncture embolization can reach the AVM nidus. Ethanol embolotherapy can achieve complete obliteration of the AVM nidus in the majority of patients. Surgery may still be needed to correct cosmetic deformity after embolization. The present study provides valuable evidence to inform clinical decision-making., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

With the increasing demand for food foaming, how to enhance the foaming properties of protein has gradually become the research focus. This work studied the effect of synephrine (SY) on foaming properties, structure properties, and physicochemical properties of soybean protein isolate (SPI). When the mass ratio of SY to SPI was 1:2, compared with SPI alone, the foam capacity and foam stability of the SY-SPI complex were significantly enhanced. Optical microscopy and confocal laser scanning microscope showed that the improvement in foaming performance was mainly due to the reduction of bubble size and uniform protein distribution. Circular dichroism spectrum and fluorescence spectra indicated that the hydrogen bond of SPI was destroyed and blue shifted with the addition of SY. What's more, the absolute value of Zeta potential, solubility, and hydrophobicity all increased, while the particle size decreased. As a result of molecular docking, surface hydrogen bonds, Van der Waals forces and hydrophobic interactions are the main driving forces. The addition of SY and SPI improved the specific volume and texture of angel cake. This study shows that SY has the potential to be developed into a new type of blowing agent., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Dietary nitrate intake is inversely related to numerous contributors towards frailty, including cardiovascular disease and poor physical function. Whether these findings extend to frailty remain unknown. We investigated if habitual nitrate intake, derived from plants or animal-based foods, was cross-sectionally associated with frailty in women., Methods: Community-dwelling older Australian women (n = 1390, mean age 75.1 ± 2.7 years) completed a validated semi-quantitative food frequency questionnaire (FFQ). Nitrate concentrations in food were obtained from international nitrate databases. We adopted the Rockwood frailty index (FI) of cumulative deficits comprising 33 variables across multiple health domains (scored 0 to 1), which predicts increased hospitalisation and mortality risk. A FI ≥ 0.25 indicated frailty. Cross-sectional associations between nitrate intake (total plant and animal nitrate, separately) and frailty were analysed using multivariable-adjusted logistic regression models (including lifestyle factors), as part of restricted cubic splines., Results: A non-linear inverse relationship was observed between total plant nitrate intake and frailty. Compared to women with the lowest plant nitrate intake (Quartile [Q]1), women with greater intakes in Q2 (OR 0.69 95%CI 0.56-0.84), Q3 (OR 0.67 95%CI 0.50-0.90) and Q4 (OR 0.66 95%CI 0.45-0.98) had lower odds for frailty. A nadir in the inverse association was observed once intakes reached ~ 64 mg/d (median Q2). No relationship was observed between total animal nitrate and frailty., Conclusion: Community-dwelling older women consuming low amounts of plant-derived nitrate were more likely to present with frailty. Consuming at least one daily serving (~ 75 g) of nitrate-rich green leafy vegetables may be beneficial in preventing frailty., (© 2024. The Author(s).)

Background: The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis and the formation of an optimized global width/length measure., Methods: Computed tomography scans and three-dimensional photographs were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid, creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion protrusion to control for head size, the vertex narrowing index is formed. By combining this index with the FBI and OBI, the scaphocephalic index (SCI) is created as a tailored width/length measure., Results: Using 221 controls and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head's height and 60% of the head's length. This point had an area under the curve of 0.97 and sensitivity and specificity of 91.2% and 92.2%, respectively. The SCI has an area under the curve of 0.9997, sensitivity and specificity greater than 99%, and interrater reliability of 0.995. The correlation coefficient between computed tomography imaging and three-dimensional photography was 0.96., Conclusions: The vertex narrowing index, FBI, and OBI evaluate regional severity, while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These measures allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p ( r =-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 ( r =0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p ( r =-0.394, P ＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G 0 /G 1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G 2 /M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased ( P ＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm 3 vs (857±114) mm 3 ] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P ＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

In Asian populations with non-small-cell lung cancer (NSCLC), EGFR mutations are highly prevalent, occurring in roughly half of these patients. Studies have revealed that individuals with EGFR mutation typically fare worse with immunotherapy. In patients who received EGFR tyrosine kinase inhibitor (TKI) treatment followed by anti-PD-1 therapy, poor results were observed. The underlying mechanism remains unclear. We used high-resolution flow cytometry and ELISA to detect the circulating level of small extracellular vesicle (sEV) PD-L1 in NSCLC individuals with EGFR mutations before and after receiving TKIs. The secretion amount of sEV PD-L1 of lung cancer cell lines with EGFR mutations under TKI treatment or not were detected using high-resolution flow cytometry and Western blotting. The results revealed that patients harboring EGFR mutations exhibit increased levels of sEV PD-L1 in circulation, which inversely correlated with the presence of CD8 + T cells in tumor tissues. Furthermore, tumor cells carrying EGFR mutations secrete a higher quantity of PD-L1-positive sEVs. TKI treatment appeared to amplify the levels of PD-L1-positive sEVs in the bloodstream. Mutation-induced and TKI-induced sEVs substantially impaired the functionality of CD8 + T cells. Importantly, our findings indicated that EGFR mutations and TKI therapies promote secretion of PD-L1-positive sEVs via distinct molecular mechanisms, namely the HRS and ALIX pathways, respectively. In conclusion, the increased secretion of PD-L1-positive sEVs, prompted by genetic alterations and TKI administration, may contribute to the limited efficacy of immunotherapy observed in EGFR -mutant patients and patients who have received TKI treatment.

Background: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue., Methods: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection., Results: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up., Conclusion: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs., Trial Registration: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023., (© 2024. The Author(s).)

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80 + I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity., (© 2024. The Author(s).)

Autocrine signaling pathways regulated by RAPID ALKALINIZATION FACTORs (RALFs) control cell wall integrity during pollen tube germination and growth in Arabidopsis (Arabidopsis thaliana). To investigate the role of pollen-specific RALFs in another plant species, we combined gene expression data with phylogenetic and biochemical studies to identify candidate orthologs in maize (Zea mays). We show that Clade IB ZmRALF2/3 mutations, but not Clade III ZmRALF1/5 mutations, cause cell wall instability in the sub-apical region of the growing pollen tube. ZmRALF2/3 are mainly located in the cell wall and are partially able to complement the pollen germination defect of their Arabidopsis orthologs AtRALF4/19. Mutations in ZmRALF2/3 compromise pectin distribution patterns leading to altered cell wall organization and thickness culminating in pollen tube burst. Clade IB, but not Clade III ZmRALFs, strongly interact as ligands with the pollen-specific Catharanthus roseus RLK1-like (CrRLK1L) receptor kinases Z. mays FERONIA-like (ZmFERL) 4/7/9, LORELEI-like glycosylphosphatidylinositol-anchor (LLG) proteins Z. mays LLG 1 and 2 (ZmLLG1/2), and Z. mays pollen extension-like (PEX) cell wall proteins ZmPEX2/4. Notably, ZmFERL4 outcompetes ZmLLG2 and ZmPEX2 outcompetes ZmFERL4 for ZmRALF2 binding. Based on these data, we suggest that Clade IB RALFs act in a dual role as cell wall components and extracellular sensors to regulate cell wall integrity and thickness during pollen tube growth in maize and probably other plants., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood., Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it., Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC., Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tie, Zhu, Yu, Dou, Wang, Wang and Ni.)

Background and Aim: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC., Methods: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a., Results: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription., Conclusion: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1 + sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1 + sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1 + sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1 + sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1 + sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1 + sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1 + sEVs, contributing to the clinical diagnosis and treatment of tumor.

The landlocked Atlantic salmon population "bleke" faces extinction due to environmental acidification (EA) and hydropower expansion in the Norwegian river Otra. Despite of restoration, unexpected mortality has been reported for this population, possibly due to gas bubble trauma (GBT) from gas supersaturation (GSS) downstream of hydroelectric plants, or EA induced aluminum toxicity. In this study, we applied the allostasis concept to investigate interactions between EA and GBT. This concept comprises additive effects of stressors, which can lead to allostatic overload. Stress coping mechanisms become maladaptive in such situations, which can be indicated by an inability to mount a proper cortisol response in fish. Fish were exposed to sublethal levels of simulated EA (SEA), GSS (a total gas pressure; TGP; of 110%) or a combination of these stressors for six days. Effects on allostatic load were subsequently investigated by assessing the cortisol response to an acute stress test. SEA increased cortisol responsiveness and GSS induced clinical signs of GBT, but no interacting effects between GSS and SEA were observed. This suggests that that 110% TGP did not have an additive effect on the allostatic load imposed by SEA., (© 2024. The Author(s).)

Objective: Many patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible for this therapeutic restriction., Methods: We obtained the transcriptional, clinical and single nucleotide polymorphism data for endometrial cancer (EC) from The Cancer Genome Atlas and the immunophenoscore data of EC from The Cancer Immunome Atlas, then analyzed in R to evaluate the relationship between MMR genes and clinicopathological features, prognosis, immune infiltration, immune checkpoint expression and responsiveness to ICIs in EC. We used differentially expressed genes in the MSH6 high and low expression groups to conduct GO and KEGG analyses to explore the impact of MSH6 on the biological functions of EC. Finally, we verified the bioinformatics results with in vitro experiments., Results: Our analyses showed that compared with the high MSH6 expression group, the low MSH6 expression group had better survival outcomes and less aggressive clinicopathological features. In the multivariate Cox analysis, MSH6 was the only independent risk factor that could predict the prognosis of EC. Besides, the low MSH6 expression group also had a higher immune score, more active immune infiltration and higher immune checkpoint expression, resulting in better responsiveness to ICIs treatment, consistent with the enrichment of GO terms and KEGG pathways related to immune response in this group. Meanwhile, the GO and KEGG enrichment results of the MSH6 high expression group were associated with cell cycle, DNA damage repair and tumorigenesis. To exclude the influence of MSH6 mutations, we performed the previous analyses on the MSH6 wild-type tumor samples and obtained consistent results. In vitro experiments also confirmed that after knocking down MSH6 in endometrial cancer cells, their proliferation, migration and invasion abilities were weakened, while the expression levels of PD-L1 and PD-L2 were elevated. In comparison, overexpression of MSH6 showed an opposite trend., Conclusion: Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Xiao and Chen.)

Ethnopharmacological Relevance: In many famous formulas of traditional Chinese medicine (TCM), the rhizome of Ligusticum chuanxiong (L. chuanxiong) is commonly used as an ingredient for promoting blood circulation and resolving blood stasis to treat diabetic nephropathy. However, its material basis and mechanism of action are still needed to be explored., Aim of the Study: The aim of this work is to elucidate the potential effective parts (phthalides) of L. chuanxiong responsible for renal protection and to explore the possible mechanism of renal protection., Materials and Methods: A method based on column chromatography of macroporous resin was established to enrich an effective part (LCE70), and the composition of LCE70 was identified by HPLC-UV and UPLC-MS/MS methods. Mice model was induced by streptozotocin (STZ) to evaluate the protective effect of LCE70 on diabetic nephropathy (DN). In vitro, the suppressive effect of LCE70 on oxidative damage, inflammation and its mechanism were tested using immunoblot analysis, ELISA, etc. Cellular thermal shift assay (CETSA) was adopted to verify the interaction between the phthalides and the key targets involved in renal injury., Results: LCE70 displayed therapeutic potential against metabolic disorders, renal dysfunction, and fibrosis in a DN model induced by STZ in mice. Furthermore, it markedly reduced oxidative stress of the kidney in DN mice by activating Nrf2 pathway. Z-ligustilide, the main component of LCE70, reacted with Keap1, and thus promoted Nrf2 dissociating from Keap1 to activate Nrf2 pathway., Conclusions: LCE70 improved hyperglycemia-induced renal function by enhancing the Nrf2 activation, reducing collagen deposition, and alleviating inflammation and oxidative stress, which suggested its potential as a therapeutic agent for DN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The relationship between myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE MRI) and myocardial work (MW) indices assessed with MW echocardiography (MWE) has not been well characterized. This study aimed to determine an impaired MW using MIS in patients with acute myocardial infarction., Methods: Left ventricular (LV) two-dimensional speckle-tracking echocardiography, MWE, and LGE MRI were performed in 33 patients with ST-segment elevation myocardial infarction and in 30 age- and sex-comparable controls. LV global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) and MIS were acquired, respectively., Results: MIS was negatively correlated with GWI (r = -0.60, P  = 0.005), GCW (r =- 0.66, P  = 0.002) and GWE (r = -0.71, P  = 0.0004), but positively correlated with GLS (r = 0.68, P  = 0.001). With the receiver operating characteristic curve, the cutoff value of MIS for the prediction of an impaired GLS was 16.5% [area under the curve (AUC) = 0.867)], an impaired GWI was 19.2% (AUC = 0.727), an impaired GCW was 19.2% (AUC = 0.725), an increased GWW was 15.8% (AUC = 0.656), an impaired GWE was 15.8% (AUC = 0.880)., Conclusion: MIS is a strong predictor of impaired MW. Timely reduction of infarct size is essential to improve myocardial function., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In this paper, a green hydrophobic deep eutectic solvent (HDES) composed of menthol and hexanoic acid was employed to dissolve cosmetics containing Cd 2+ and Cd 2+ was extracted using an EDTA-2Na saturated solution, analyzed by FAAS. The study found that HDES-1 can be recycled and reused well; the stability constants of Cd 2+ EDTA chelates play an important role in the extracting process; the optimum conditions were: the solubility of HDES-1 was 20 mL/g for cosmetic sample at an indoor temperature of around 10 °C; the dissolver-extractant ratio was 2:1; the LOD was 0.037 mg/kg; the RSD was 3.5%; and the recovery was 85.5-118.3%. The developed method was successfully applied to actual cosmetic samples with satisfactory results, and it was also applied for the determination of Mg 2 + , Mn 2+ , and Cu 2+ in cosmetic samples., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Purpose: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC)., Methods: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC., Results: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells., Conclusion: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Based on the monitoring data of five pollutants in 168 key cities under air pollution prevention and control in China from 2015 to 2020, using the MAKESENS model and the aggregate risk index(ARI), this study quantitatively analyzed the spatial and temporal distribution characteristics of air pollution and health risks in China and the six urban agglomerations. The results showed that:① PM 2.5 pollution was the most serious pollution in Chinese key cities. Only 15% of the cities' six-year average concentrations of PM 2.5 reached the National Secondary Standard, followed by that of NO 2 ; 77% of the cities' six-year average concentrations of NO 2 reached the National Secondary Standard. The urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain had the most serious air pollution, and the six-year average concentrations of PM 2.5 , SO 2 , CO, and NO 2 were higher than those of other urban agglomerations. ② The concentrations of PM 2.5 , SO 2 , CO, and NO 2 in key cities of China showed a decreasing trend, whereas the concentration of O 3 in other urban agglomerations showed an increasing trend, except in the Chengdu-Chongqing urban agglomeration. The concentration of SO 2 in the urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain changed the most significantly. ③ The health risk of air pollution in the key cities of China generally showed a decreasing trend, with a sharp decline from 2017 to 2018, and the population exposed to extremely high risks dropped from 160 million to 32.54 million. The urban agglomeration in the middle reaches of the Yangtze River had the most significant decline in health risks, whereas the key cities in China faced higher health risks in spring and winter seasons. ④ The Beijing-Tianjin-Hebei and Fenwei plain urban agglomerations had the highest health risks, and the urban agglomeration in the middle reaches of the Yangtze River had the lowest; O 3 gradually replaced PM 2.5 as the main pollutant affecting the health risk. These results can provide a reference for evaluating the effectiveness of urban air pollution control in China during the 13th Five-Year Plan period.

Background: The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs., Methods: sEVs were isolated from different clinical samples of head and neck squamous cell carcinoma (HNSCC) patients, the level and cellular origins of PD-L1-positive sEVs were assessed. Co-expression of CD80 on PD-L1-positive sEVs was examined to evaluate the immunosuppressive and tumor-promotive effects., Results: PD-L1-positive sEVs in HNSCC patients had various cellular origins, including tumor cell, T cell, B cell, dendritic cell and monocyte/macrophage. However, PD-L1-positive sEVs derived from immune cells did not exert immunosuppressive functions due to the co-expression of CD80. It was verified that co-expression of CD80 disrupted the binding of sEV PD-L1 to its receptor PD-1 on T cells and attenuated the immunosuppression mediated by sEV PD-L1 both in vitro and in vivo., Conclusion: The study suggests that PD-L1-positive sEVs have the cellular origin and functional heterogeneity. Co-expression of CD80 could restrict the immunosuppressive effect of sEV PD-L1. A greater understanding of PD-L1-positive sEV subsets is required to further improve their clinical application., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression of RAB27A was assessed through immunohistochemical analysis utilizing tissue microarrays. In vitro experiments were conducted using RAB27A-knockdown cells to investigate its impact on OSCC tumor cells. Additionally, transcriptome sequencing was performed to elucidate potential underlying mechanisms. RAB27A was significantly overexpressed in OSCC, and particularly in metastatic lymph nodes. It was positively correlated with the clinical progression and poor survival prognosis. Silencing RAB27A notably decreased the proliferation, migration, and invasion abilities of OSCC cells in vitro. A Gene Ontology (GO) enrichment analysis indicated a strong association between RAB27A and the epidermal growth factor receptor (EGFR) signaling pathway. Further investigations revealed that RAB27A regulated the palmitoylation of EGFR via zinc finger DHHC-type containing 13 (ZDHHC13). These findings provide insights into OSCC progression and highlight RAB27A as a potential therapeutic target for combating this aggressive cancer.

Background: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens., Methods: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m 2 ) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life., Discussion: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia., Trial Registration: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Inspired by the synthetic method of benzoxazine derivatives and our previous research, a fluorescent probe (SWJT-6) was designed for formaldehyde (FA) detection based on the cyclization reaction. The synthetic SWJT-6 showed excellent colorimetric and ratiometric response to formaldehyde, and could be perfectly used as test strips to detect formaldehyde. It also showed a fast detection time (3 min), low detection limit (5.65 μM) and high selectivity for formaldehyde within various interfering analytes. In addition, SWJT-6 has been successfully applied in bioimaging of intracellular and lysosomal formaldehyde in both HeLa cells and zebrafish.

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ 2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs ( n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs ( n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors. Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora, epithelial barrier function, and intestinal immunology. Inflammatory bowel disease can be treated in new ways by using these potential molecules. This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications. In addition, we explore bile acid metabolism and the interaction of bile acids and the gut microbiota., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two new diterpenoids, 12,15-di- O -acetylhypargenin B ( 1 ) and taiwanin F-12- O -β-D-glucopyranoside ( 2 ), one new monoterpenoid, ( S )-7-methyl-3-methyleneoct-6-ene-1,2-diyl diacetate ( 3 ), together with eight known compounds ( 4 - 11 ), were obtained from the twigs and leaves of Nageia fleuryi Hickel. The structures of the new compounds were elucidated by extensive spectroscopic techniques including HR-ESI-MS and 1 D and 2 D NMR experiments. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 1 and 11 exhibited strong inhibitory activity on LPS-stimulated production of NO in RAW 264.7 murine macrophages, while compounds 1 , 3 , and 5 showed significant quinone reductase inducing activity in Hepa 1c1c7 murine hepatoma cells. Moreover, compounds 7 and 8 showed inhibitory activity against the proliferation of the human prostate carcinoma DU145 cells.

Background: Phosphonates are the main components in the global phosphorus redox cycle. Little is known about phosphonate metabolism in freshwater ecosystems, although rapid consumption of phosphonates has been observed frequently. Cyanobacteria are often the dominant primary producers in freshwaters; yet, only a few strains of cyanobacteria encode phosphonate-degrading (C-P lyase) gene clusters. The phycosphere is defined as the microenvironment in which extensive phytoplankton and heterotrophic bacteria interactions occur. It has been demonstrated that phytoplankton may recruit phycospheric bacteria based on their own needs. Therefore, the establishment of a phycospheric community rich in phosphonate-degrading-bacteria likely facilitates cyanobacterial proliferation, especially in waters with scarce phosphorus. We characterized the distribution of heterotrophic phosphonate-degrading bacteria in field Microcystis bloom samples and in laboratory cyanobacteria "phycospheres" by qPCR and metagenomic analyses. The role of phosphonate-degrading phycospheric bacteria in cyanobacterial proliferation was determined through coculturing of heterotrophic bacteria with an axenic Microcystis aeruginosa strain and by metatranscriptomic analysis using field Microcystis aggregate samples., Results: Abundant bacteria that carry C-P lyase clusters were identified in plankton samples from freshwater Lakes Dianchi and Taihu during Microcystis bloom periods. Metagenomic analysis of 162 non-axenic laboratory strains of cyanobacteria (consortia cultures containing heterotrophic bacteria) showed that 20% (128/647) of high-quality bins from eighty of these consortia encode intact C-P lyase clusters, with an abundance ranging up to nearly 13%. Phycospheric bacterial phosphonate catabolism genes were expressed continually across bloom seasons, as demonstrated through metatranscriptomic analysis using sixteen field Microcystis aggregate samples. Coculturing experiments revealed that although Microcystis cultures did not catabolize methylphosphonate when axenic, they demonstrated sustained growth when cocultured with phosphonate-utilizing phycospheric bacteria in medium containing methylphosphonate as the sole source of phosphorus., Conclusions: The recruitment of heterotrophic phosphonate-degrading phycospheric bacteria by cyanobacteria is a hedge against phosphorus scarcity by facilitating phosphonate availability. Cyanobacterial consortia are likely primary contributors to aquatic phosphonate mineralization, thereby facilitating sustained cyanobacterial growth, and even bloom maintenance, in phosphate-deficient waters. Video Abstract., (© 2023. The Author(s).)

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V + EGFR + EVs and Annexin V - EGFR + EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR + EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V + EGFR + EVs to Annexin V - EGFR + EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Animals associate cues with outcomes and update these associations as new information is presented. This requires the hippocampus, yet how hippocampal neurons track changes in cue-outcome associations remains unclear. Using two-photon calcium imaging, we tracked the same dCA1 and vCA1 neurons across days to determine how responses evolve across phases of odor-outcome learning. Initially, odors elicited robust responses in dCA1, whereas, in vCA1, odor responses primarily emerged after learning and embedded information about the paired outcome. Population activity in both regions rapidly reorganized with learning and then stabilized, storing learned odor representations for days, even after extinction or pairing with a different outcome. Additionally, we found stable, robust signals across CA1 when mice anticipated outcomes under behavioral control but not when mice anticipated an inescapable aversive outcome. These results show how the hippocampus encodes, stores and updates learned associations and illuminates the unique contributions of dorsal and ventral hippocampus., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Sarcopenia has attracted increasing attention with the study of nutrition in patients with liver disease. Sarcopenia is an independent risk factor for a poor prognosis of liver disease and is becoming increasingly common in patients with liver disease. Studies have shown that patients with liver disease and sarcopenic obesity have a worse prognosis than patients with liver disease and simple sarcopenia or obesity. In clinical practice, it is easy to recognize patients with malnutrition and decreased muscle mass, but we often ignore those patients with normal body weight or even obesity who will likewise experience muscle mass loss. Simply relying on the monitoring of body mass and body mass index to assess the nutritional and muscle status of patients with liver disease is not accurate. At present, our understanding of the relationship between chronic liver disease and sarcopenic obesity is still poorly understood. In this paper, the research progress on chronic liver disease, sarcopenia, and sarcopenic obesity in recent years is reviewed so as to provide a theoretical basis for improving the clinical prognosis of patients with liver disease.

Background: Hypertrophic scar (HS) and keloid (KD) are common dermal fibroproliferative growth caused by pathological wound healing. HS's prevalence is currently undetermined in China. Though it primarily occurs in dark-skinned individuals, KD can develop in all races, and its prevalence among Chinese people is poorly documented., Objective: To explore the present epidemiological status of them in Chinese college students., Methods: We conducted a university-based cross-sectional study at one university in Fujian, China. A total of 1785 participants aged 16-34 years (mean age, 20.0 ± 2.0; 58.7% female) were enrolled and statistical analyses were performed., Results: HS and KD were observed in 5.2% (95% confidence interval [CI]: 4.2-6.2) and 0.6% (95% CI: 0.3-1.0) of the population respectively. There was a significant difference by sex in HS ( P  < 0.05), but not in KD. The prevalence of HS and KD both showed a significant difference by age ( P  < 0.05), but not in ethnic and native place distribution. The occurrence of HS and KD were both concentrated in individuals 9-20 years old (HS: 77.2%; KD: 81.8%). They were mainly distributed in the upper limbs (52.1%; 64.3%), and the main cause was trauma (51.0%; 35.7%). In addition, male sex was a risk factor for HS (adjusted P  < 0.001), and KD was associated with age ≥22 years and family history (adjusted P  < 0.050)., Conclusion: HS and KD are common in Chinese college students, and more attention and research is warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Several scoring systems are currently used to predict prognosis of hepatocellular carcinoma (HCC), but none of them integrates liver function, systemic inflammation, and tumor characteristics in a unified model. The current study aimed to develop and validate a novel prognostic score that integrates liver function, systemic inflammation, and tumor characteristics in a unified model to predict the prognosis of HCC after curative resection., Methods: Patients with HCC who underwent curative liver resection were included in a training set (n = 1027). Multivariate Cox regression was performed to determine the risk factors for a poor prognosis. A prognostic score was developed by assigning points for risk factors in proportion to beta coefficients in a Cox multivariable model. Predictive performance and distinction ability of the prognostic score were further evaluated in two independent validation cohorts treated with either curative resection (n = 281) or transarterial chemoembolization (TACE) (n = 404) and compared with 16 other models., Results: The prognostic predictive system, named the function-inflammation-burden-alpha-fetoprotein (FIBA) score, was derived by assigning points for six independent predictors including albumin, total bilirubin, lymphocyte count, diameter of the largest tumor, number of tumors, and alpha-fetoprotein (AFP). The FIBA score showed an outperformed predictive value compared with other systems in both training and validation cohorts by giving the highest C-index, likelihood ratio chi-square values, and Wald test values as well as the lowest Akaike information criterion., Conclusion: The FIBA score can be used to stratify HCC patients treated with curative resection. Meanwhile, the FIBA score performs well against other prognostic scoring systems and is potentially broadly applicable to a TACE-treated patient cohort., (© 2022. Society of Surgical Oncology.)

Background: Unlike the conventional spectral analyses of spectral computed tomography (CT) that cannot fully represent the whole lesion, the volumetric quantitative analysis reveals the information of the whole lesion and is of more accurate. So this study sought to evaluate the value of volumetric quantitative analysis in the differential diagnosis of pulmonary adenocarcinoma (ADC) and squamous cell carcinoma (SQCC)., Methods: Fifty-seven patients with lung cancer confirmed by pathology, including 35 ADC and 22 SQCC patients, were retrospectively analyzed. Calcium concentration and effective-Z (Eff-Z) in plain scan (PS), iodine concentration, and water concentration in the arterial phase (AP) were measured. The Student t -test or rank-sum test was used to determine the statistically significant parameters. Receiver operating characteristic (ROC) curve was used, and the corresponding area under the curve (AUC), sensitivity and specificity was calculated to evaluate the diagnostic efficacy in differential diagnosis of ADC and SQCC., Results: In the volumetric quantitative analysis of spectral CT, the concentration of calcium [(6.97±2.83) mg/cm 3 ], Eff-Z (7.90±0.14), and iodine [1.42 (0.84) mg/cm 3 ] was significantly higher in ADC than SQCC [(5.14±2.39) mg/cm 3 , (7.80±0.10), 1.16 (0.65) mg/cm 3 , t =2.513, 2.860, Z=-2.246, P=0.015, 0.006, 0.025], but the concentration of water was significantly lower in ADC [995.00 (38.70) mg/cm 3 ] than SQCC [1,007.00 (14.38) mg/cm 3 , Z=-2.082, P=0.037]. Moreover, whether it's ADC or SQCC, the concentrations of calcium [(8.51±4.28) mg/cm 3 , (5.96±2.50) mg/cm 3 ], Eff-Z (7.97±0.20, 7.86±0.13), and water [1,007.00 (14.38) mg/cm 3 , 1,029.28 (10.49) mg/cm 3 ] were lower in the volumetric spectral analysis than the conventional spectral analysis, while the concentration of iodine [1.33 (0.80) mg/cm 3 , 0.94 (0.63) mg/cm 3 ] was significantly higher in the volumetric spectral analysis than the conventional spectral analysis. The ROC curve analysis showed that the areas under the curves (AUC) (0.76, 0.76, 0.75, 0.71), sensitivity (66.7%, 66.7%, 66.7%, 85.2%), and specificity (92.3%, 84.6%, 86.9%, 69.2%) of the volumetric spectral analysis parameters for the differential diagnosis of ADC and SQCC were higher than those of the conventional spectral analysis [(0.65, 0.66, 0.73, 0.63), (44.4%, 48.1%, 59.3%, 66.7%), (69.2%, 69.2%, 84.6%, 53.8%)] parameters., Conclusions: The volumetric quantitative analysis has a promising advantage in the observation range of whole lesions, it may be invaluable in the differential diagnosis of ADC and SQCC, and is worthy of clinical recommendation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-115/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

This study describes a visible-light-induced cascade reaction for preparing cyanoalkyl-containing polyheterocycles initiated by the photoinduced radical cascade addition of N -arylacrylamide derivatives using cyclic oxime esters as radical sources followed by cyanoalkyl-mediated cyclization. This protocol features outstanding functional group compatibility, providing a variety of desired phenanthridine derivatives in moderate to good yields. Moreover, the application of a microflow technique enhanced these reactions compared with the equivalent batch reaction, significantly reducing reaction times to 10 min.

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune-checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining, and measurement of circulating sEV PD-L1, we found that the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cell carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC. The expression of HRS was also negatively correlated to the infiltration of CD8+ T cells. Knockdown of HRS markedly reduced PD-L1 expression in HNSCC cell-derived sEVs, and these sEVs from HRS knockdown cells showed decreased immunosuppressive effects on CD8+ T cells. Knockout of HRS inhibited tumor growth in immunocompetent mice together with PD-1 blockade. Moreover, a higher HRS expression was associated with a lower response rate to anti-PD-1 therapy in patients with HNSCC. In summary, our study reveals HRS, the core component of ESCRT-0, regulates sEV PD-L1 secretion, and is associated with the response to ICB therapy in patients with HNSCC, suggesting HRS is a promising target to improve cancer immunotherapy., (©2022 American Association for Cancer Research.)

Background: Liver resection (LRE) and microwave ablation (MWA) for hepatocellular carcinoma (HCC) have been widely compared., Aims: To compare the therapeutic outcomes of percutaneous MWA and LRE for HCC in ideal candidates for ablation according to Barcelona Clinic Liver Cancer (BCLC) staging METHODS: Between August 2013 and November 2020, 483 consecutive patients meeting criteria for "ideal candidates for ablation" per the BCLC staging initially treated with MWA (n = 168) or LRE (n = 315) were included. Patients were further divided into BCLC-0 (n = 116) and BCLC-A (n = 367) groups. Overall survival (OS), recurrence-free survival (RFS) and post-procedure-related complication rates were compared before and after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) in the overall population and subgroups. Multivariate Cox regression analysis was performed to determine whether the treatment modality was an independent prognostic factor., Results: LRE had a better RFS and similar OS and post-procedure-related complication rates compared to MWA in the overall population and in the BCLC-A subgroup both before and after PSM and IPTW. However, the OS, RFS and post-procedure-related complication rates were equivalent between the two groups before and after PSM and IPTW in patients with BCLC-0 disease. The multivariate Cox regression analysis showed that LRE was associated with better RFS over MWA in overall population (p = 0.003; HR = 0.67; 95% CI: 0.51-0.87) and BCLC-A disease (p = 0.046; HR = 0.74; 95% CI: 0.56-0.99), while it did not differ in OS., Conclusion: An 'ideal candidate for ablation' according to the BCLC staging system may not be an ideal candidate for MWA. However, patients with BCLC-0 may be the optimal population for MWA., (© 2022 John Wiley & Sons Ltd.)

Purpose: The aim of this study was to describe the treatment technique, outcomes, and complications of Schobinger stage IV head and neck arteriovenous malformations (HNAVMs) with associated high-output cardiac failure (HOCF) using ethanol and coils with the percutaneous suture technique., Methods: From January 2015 to December 2019, 19 patients who had HNAVMs with associated HOCF were treated first with a percutaneous suture of the remarkably dilated dominant drainage vein (RDDOV) and subsequent embolization with coils and ethanol. The percutaneous suture of RDDOV was preferred to be performed, followed by the deployment of coils and the injection of absolute ethanol via transarterial approach, direct puncture approach, or both of them. Treatment outcomes and complication rates were evaluated at follow-up., Results: A total of 19 patients who experienced HNAVMs with HOCF received 19 percutaneous suture procedures and 84 embolization procedures with ethanol and coils. Complete or >90% shunt reduction of the AVM was achieved in 16 patients. Notably, 19 patients with New York Heart Association (NYHA) stage II improved to stage I, and the symptom of dyspnea disappeared after embolization. The symptoms of five patients with bleeding disappeared. All patients presented with cosmetic concerns; Four were cured, and eight had a clearly recognizable improvement. Of note, 19 (100%) patients presented with impairment of daily life, which was resolved. The minor complications were encountered and recovered by the self. No major complications occurred., Conclusion: This study provides evidence that ethanol and coil embolotherapy is effective and safe in treating HOCF caused by HNAVMs with acceptable complications in these cases. The percutaneous suture technique for RDDOV management can act as an adjunct for embolotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Li, Shen, Wang, Zheng, Wang, Fan, Su and Yang.)

Objective: To establish a graphite furnace atomic absorption spectrometry method for the determination of trace gallium in whole blood. Methods: From January to May 2021, the five factors of ashing temperature, ashing time, atomization temperature, atomization time and matrix modifier concentration in the determination of gallium in whole blood by graphite furnace atomic absorption spectrometry were optimized by using L(16) (4(5)) orthogonal test design. At the same time, within-run, between-run, spiking recovery test and other methodological indicators were tested. Results: Under the optimized detection conditions, the linear range of determination of gallium in whole blood by graphite furnace atomic absorption spectrometry was 0.29-100.00 μg/L ( r =0.9991) . The within-run and between-run relative standard deviations ( RSD ) of repetitive measurement at 10.0, 50.0, 80.0 μg/L concentration levels were 2.3%-4.4% and 1.5%-3.6%, the recovery rate of spiking was 98.1%-103.8%, and the detection limit of the method was 0.13 μg/L. Conclusion: Graphite furnace atomic absorption spectrometry for the determination of trace gallium in whole blood is easy to operate, has a wide linear range, low detection limit, accurate and reliable results, which is suitable for occupational health examinations and the determination of acute gallium poisoning.

Venous malformations (VMs), featuring localized dilated veins, are the most common developmental vascular anomalies. Aberrantly organized perivascular extracellular matrix (ECM) is one of the prominent pathological hallmarks of VMs, accounting for vascular dysfunction. Although previous studies have revealed various proteins involved in ECM remodeling, the detailed pattern and molecular mechanisms underlying the endothelium-ECM interplay have not been fully elucidated. Our previous studies revealed drastically elevated extracellular vesicle (EV) secretion in VM lesions. Here, we identified increased EV-carried MMP14 in lesion fluids of VMs and culture medium of TIE2-L914F mutant endothelial cells (ECs), along with stronger ECM degradation. Knockdown of RAB27A, a required regulator for vesicle docking and fusion, led to decreased secretion of EV-carried MMP14 in vitro. Histochemical analysis further demonstrated a highly positive correlation between RAB27A in the endothelium and MMP14 in the perivascular environment. Therefore, our results proved that RAB27A-regulated secretion of EV-MMP14, as a new pattern of endothelium-ECM interplay, contributed to the development of VMs by promoting ECM degradation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteosarcoma is a bone cancer formed by the cells of the bone. Children, young adults, and teens are highly affected by osteosarcoma. Early identification of osteosarcoma is mandatory to improve the treatment and increase the lifespan of the patients. MicroRNA-195 (miR-195) was shown to be a suitable biomarker for osteosarcoma, and the present study describes a sensitive method of miR-195 identification by nuclease digestion in ELISA to detect and quantify the level of miR-195. S1 nuclease catalyzed endo- and exonucleolytic digestion of single-stranded (ss) RNA and DNA on ELISA polystyrene substrate, which helped to identify duplexed miR-195. This method selectively and specifically identified miR-195 without any biofouling interactions and reached the limit of detection at 10 fM within the range from 10 fM to 10 nM. Due to complete digestion of ssDNA, single- and triple-mismatched sequences failed to increase the ELISA signal, indicating specific miRNA detection. Furthermore, human serum spiked with miR-195 did not interfere with the detection, confirming selective identification. This method identified miR-195 at a lower level and will help to diagnose earlier stages of osteosarcoma., (© 2021 International Union of Biochemistry and Molecular Biology, Inc.)