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Ya-zhi Xi,1,2 Xue-lian Wei,1,2 Lei Xie,1,2 Xiao-yu Jia,2 Zhen-ping Li,2 Qing-he Zhou2 1Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, Jiaxing City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Qing-he Zhou, Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, No. 1882, South of the Second Ring Road, Jiaxing City, Zhejiang Province, 314000, People’s Republic of China, Tel +8613732573379, Fax +86057389997760, Email zqh10980@zjxu.edu.cnBackground: The effects of intraoperative permissive hypercapnia (PaCO2 of 45– 55 mmHg) on the central nervous system remain unclear. Neurofilament light chain (NfL, a protein found in the axons and nerve fibers of neurons) has been associated with central nervous system disorders. This study investigated the effect of intraoperative permissive hypercapnia on plasma NfL concentration 1 day postoperatively, and in turn on the central nervous system, during laparoscopic surgery.Methods: This investigation was a prospective, single-blind randomized controlled trial. Eighty-four individuals aged above 60 years were randomly allocated to either the normocapnia group with an PaCO2 of 35– 45 mmHg (n=42) or the hypercapnia group with a PaCO2 of 45– 55 mmHg (n=42). The primary outcome was the 1-day postoperative plasma NfL concentration. Secondary outcomes included the area under the curve (AUC) values for PaCO2 and regional cerebral oxygen saturation (rSO2). The Mann–Whitney U-test was mainly used to analyze the outcomes.Results: The final analysis included 38 and 40 patients in the normocapnia and hypercapnia groups, respectively. There was no statistically significant difference observed between the groups regarding the preoperative and 1-day postoperative plasma NfL concentration (14.0 [11.1, 19.9] vs 16.3 [9.06, 19.9] pg/mL, P> 0.05; 23.4 [16.8, 32.3] vs 21.5 [15.6, 29.9] pg/mL, P> 0.05, respectively). However, in both groups, the postoperative plasma concentration of NfL showed a significant increase when compared with the preoperative levels (both P < 0.001). The AUCs of PaCO2 and rSO2 from the beginning to the end of the pneumoperitoneum were significantly higher in the hypercapnia group compared with the normocapnia group (both P

Hong-Li Wu,1 Bater Hurile,1 Zhi-Peng Li,1 Hong-Wei Zhao2 1Department of Cardiology, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, People’s Republic of China; 2Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaCorrespondence: Hong-Wei Zhao, Email zhaohongwei@sysush.comBackground: As a nutritional indicator, a lower level of geriatric nutritional risk index (GNRI) has been suggested as a predictor for poor prognosis in acute coronary syndrome (ACS). However, whether GNRI could improve the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for the prognosis in elderly patients with non-ST segment elevation myocardial infarction (NSTEMI) after PCI remains unclear.Methods: A total of 446 elderly patients with NSTEMI after percutaneous coronary intervention (PCI) were consecutively enrolled. Patients were divided into major adverse cardiovascular and cerebrovascular events (MACCE) group and control group according to the occurrence of MACCE during one year follow up. The clinical parameters including GNRI were compared to investigate the predictors for MACCE. The performance after the addition of GNRI to the GRACE score for predicting MACCE was determined.Results: A total of 68 patients developed MACCE. In unadjusted analyses, the rate of MACCE was significantly higher in the 93.8

Yue-ru Hou,1,2 Cheng-yun Xu,1,2 Ming-zi An,1,2 Zhen-ping Li,2 Hua-dong Ni,2 Tao Chen,3 Qing-he Zhou2 1Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Tongxiang First People’s Hospital, Tongxiang, Zhejiang, People’s Republic of ChinaCorrespondence: Tao Chen, Department of Anesthesiology, Tongxiang First People’s Hospital, No. 1918, Xiaochang Road, Tongxiang, Zhejiang, 314599, People’s Republic of China, Tel +8613967327686, Fax +86 0573 8802 5098, Email goandjump@163.com Qing-he Zhou, Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, No. 1882, Ring 2nd South Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +8613732573379, Fax +86 0573 8999 7760, Email jxxmxy@163.comPurpose: Dexmedetomidine exerts a neuroprotective effect, however, the mechanism underlying this effect remains unclear. This study aimed to explore whether dexmedetomidine can reduce the increase in neurofilament light chain (NfL) protein concentration to play a neuroprotective role during thoracoscopic surgery.Patients and Methods: Patients aged ≥ 60 years undergoing general anesthesia for thoracoscopic surgery were randomly assigned to receive dexmedetomidine (group D) or not receive dexmedetomidine (group C). Patients in group D received a loading dose of dexmedetomidine 0.5 μg/kg before anesthesia induction and a continuous infusion at 0.5 μg·kg− 1·h− 1 until the end of the surgery. Dexmedetomidine was not administered in group C. The primary outcome was the NfL concentration on postoperative day 1. The concentrations of procalcitonin (PCT), serum amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) were detected preoperatively and on postoperative day 1. In addition, the numerical rating scale (NRS) and quality of recovery-40 (QoR-40) scores were evaluated.Results: A total of 38 patients in group D and 37 in group C were included in the analysis. No differences were observed between the groups in terms of the plasma concentration of NfL preoperatively and on postoperative day 1 (11.17 [8.86, 13.93] vs 13.15 [10.76, 15.56] pg/mL, P > 0.05; 16.70 [12.23, 21.15] vs 19.48 [15.25, 22.85] pg/mL, P > 0.05, respectively). However, the postoperative plasma NfL concentration was significantly higher than the preoperative value in both groups (both P < 0.001). The groups exhibited no differences in PCT, SAA, hs-CRP, NRS, and QoR-40 (all P > 0.05).Conclusion: Intraoperative administration of dexmedetomidine at a conventional dose does not appear to significantly reduce the increase in postoperative plasma NfL concentration in elderly patients undergoing thoracoscopic surgery. This finding suggests that the neuroprotective effect of dexmedetomidine at a conventional dose was not obvious during general anesthesia.Keywords: dexmedetomidine, thoracoscopic surgery, neurofilament light chain, general anesthesia

Wang Tang1 &ast;, Zhen-Wei Li1 &ast;, Gui-Qiang Miao2 &ast;, Zhi-Peng Li,1 Tao Gui,1 Chong-Jie Wu,1 Zhen-Yan Li,1 Jie Yang,1 Xiao-Dong Zhao,2 Ning Liu,1 Zhen-Gang Zha,1 Lu-Tian Yao,3 Huan-Tian Zhang1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Orthopedics, Foshan Fosun Chancheng Hospital, Foshan, 528010, People’s Republic of China; 3Department of Orthopedics, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Tian Yao; Huan-Tian Zhang, Email ltyao@cmu.edu.cn; zhanghuantian@jnu.edu.cnPurpose: Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown.Methods: Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining.Results: We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification.Conclusion: This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.Keywords: SIFK, scRNA, TCF4, cartilage, hypoxia

Zhi Dong,1,&ast; Yingyu Lin,1,&ast; Fangzeng Lin,2,&ast; Xuyi Luo,3 Zhi Lin,1 Yinhong Zhang,1 Lujie Li,1 Zi-Ping Li,1 Shi-Ting Feng,1 Huasong Cai,1 Zhenpeng Peng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Emergency, Guangzhou First People’s Hospital, Guangzhou, Guangdong, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huasong Cai; Zhenpeng PengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766, extension 8471Fax +86 20-87615805Email caihuas@mail.sysu.edu.cn; pengzhp@mail.sysu.edu.cnPurpose: The treatment response to initial conventional transarterial chemoembolization (cTACE) is essential for the prognosis of patients with hepatocellular carcinoma (HCC). This study explored and verified the feasibility of machine-learning models based on clinical data and contrast-enhanced computed tomography (CT) image findings to predict early responses of HCC patients after initial cTACE treatment.Patients and Methods: Overall, 110 consecutive unresectable HCC patients who were treated with cTACE for the first time were retrospectively enrolled. Clinical data and imaging features based on contrast-enhanced CT were collected for the selection of characteristics. Treatment responses were evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) by postoperative CT examination within 2 months after the procedure. Python (version 3.70) was used to develop machine learning models. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select features with the impact on predicting treatment response after the first TACE procedure. Six machine learning algorithms were used to build predictive models, including XGBoost, decision tree, support vector machine, random forest, k-nearest neighbor, and fully convolutional networks, and their performances were compared using receiver operator characteristic (ROC) curves to determine the best performing model.Results: Following TACE, 31 patients (28.2%) were described as responsive to TACE, while 72 patients (71.8%) were nonresponsive to TACE. Portal vein tumor thrombosis type, albumin level, and distribution of tumors within the liver were selected for predictive model building. Among the models, the RF model showed the best performance, with area under the curve (AUC), accuracy, sensitivity, and specificity of 0.802, 0.784, 0.904, and 0.480, respectively.Conclusion: Machine learning models can provide an accurate prediction of the early response of initial TACE treatment for HCC, which can help in individualizing clinical decision-making and modification of further treatment strategies for patients with unresectable HCC.Keywords: hepatocellular carcinoma, transarterial chemoembolization, machine learning, prediction model, treatment response

Chenyu Song,1,* Bingqi Shen,1,* Zhi Dong,1,* Zhenzhen Fan,2 Ling Xu,3 Zi-Ping Li,1 Yin Li,4 Shi-Ting Feng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China; 2Department of Radiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, People’s Republic of China; 3Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia; 4Department of Gastroenterology Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Ting FengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, the Second Zhongshan Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766 Extension 8471Fax +86 20-87615805Email fengsht@mail.sysu.edu.cnYin LiDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of ChinaEmail liyin2736@163.comBackground: The purpose of this study was to investigate the feasibility of CT parameters to predict the presence of KRAS mutations in rectal cancer patients. The relationship between the presence of a KRAS mutation and pathological findings was evaluated simultaneously.Methods: Eighty-nine patients (29 females, 60 males, age 27– 90, mean 59.7± 12 years) with pathologically proven rectal cancer were enrolled. A KRAS mutation test was completed following surgery. Parameters evaluated on CT included the tumor location, the diameter of the superior rectal vein (SRV) and inferior mesenteric vein (IMV), the presence of calcification, ulceration, lymph node enlargement (LNE), distant metastasis, tumor shape (intraluminal polypoid mass, infiltrative mass, or bulky), circumferential extent (C0–C1/4, C1/4–C1/2, C1/2–C3/4, or C3/4–C1), enhanced pattern (homogeneous or heterogeneous), CT ratio, and the length of the tumor (LOT). Pathological findings included lymphovascular emboli, signet ring cell, peripheral fat interval infiltration, focal ulcer, lymph node metastasis, tumor pathological type, and differentiation extent. The correlations between KRAS status and CT parameters, and KRAS status and pathological findings were investigated. The accuracy of CT characteristics for predicting KRAS mutation was evaluated.Results: A KRAS mutation was detected in 42 cases. On CT image, the diameter of the SRV was significantly increased in the KRAS mutation group compared to in the KRAS wild-type group (4.6± 0.9 mm vs 4.2± 0.9 mm, p=0.02), and LNE was more likely to occur in the KRAS mutation group (73.3% vs 26.7%, p=0.03). There was no significant difference between the KRAS mutation group and the KRAS wild-type group on the other CT parameters (location, IMV, calcification, ulcer, distant metastasis, tumor shape, enhanced pattern, circumferential extent, CT ratio, and LOT). In the pathological findings, a KRAS mutation was more likely to occur in the middle differentiation group (p=0.03). No significant difference was found between the KRAS mutation group and the KRAS wild-type group in the presence of lymphovascular emboli, signet ring cell, peripheral fat interval infiltration, focal ulcer, lymph node metastasis, and tumor pathological type. With the best cut-off value of 4.07 mm, the AUC of the SRV to predict a KRAS mutation was 0.63 with a sensitivity of 76.2% and a specificity of 48.9%.Conclusion: It was feasible to use the diameter of the SRV to predict a KRAS mutation in rectal cancer patients, and LNE also can be regarded as an important clue on preoperative CT images.Keywords: rectal neoplasms, mutation, computed tomography, superior rectal vein

Xiaoqi Zhou,1,* Meng Wang,1,* Shaoqiang Li,2 Huasong Cai,1 Lijian Liang,2 Zi-Ping Li,1 Shi-Ting Feng,1 Zhenpeng Peng,1 Xuehua Li1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, People’s Republic of China; 2Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenpeng Peng; Xuehua Li Email 37595198@qq.com; lixuehua803@163.comBackground: Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumour with poor prognosis. Surgical resection is the first line of treatment to achieve the best possible outcome. However, precise preoperative evaluation is essential to guide therapeutic decisions. Here, the preoperative evaluation potential of gadobutrol-enhanced magnetic resonance imaging (MRI) was assessed in the management of a 42-year-old patient with a large IVC mass.Methods: The patient first underwent enhanced computed tomography (CT), but the relationship between the left renal vein and the mass in the dilated IVC was ambiguous, and it remained unclear whether the right hepatic vein was invaded by the lesion. To make a precise assessment of the tumour, the patient subsequently underwent high-resolution MRI angiography examination combined with high-concentration contrast medium gadobutrol.Results: MRI demonstrated the integrity of the right hepatic vein and the left renal vein. Following a multidisciplinary consultation, a complicated surgery including complete resection of the mass, artificial vessel replacement of IVC, total hepatectomy, and bilateral nephrectomy with liver and kidney auto-transplantation was performed successfully. The surgical plan formulated after reviewing the MRI preoperatively was adhered to the course of the surgery. Postoperative CT re-examination showed that the blood flow of the artificial blood vessel and the right hepatic vein was unobstructed. Histopathological examination confirmed the tumour to be a leiomyosarcoma.Conclusion: Preoperative imaging diagnosis and assessment have important implications for the surgical planning of IVC leiomyosarcoma. High-resolution MRI angiography examination with high concentration contrast medium gadobutrol may be of particular benefit in IVC tumours.Keywords: leiomyosarcoma, inferior vena cava, preoperative care, magnetic resonance imaging, gadobutrol

Hong Jiang,1,* Zhi-Peng Li,1,* Gui-Xiang Tian,1,* Rui-Yan Pan,1 Chong-Mei Xu,2 Bo Zhang,2 Jing-liang Wu1 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, China *These authors contributed equally to this work Background: Recent efforts have been focused on combining two or more therapeutic approaches with different mechanisms to enhance antitumor therapy. Moreover, nanosize drug-delivery systems for codelivering two drugs with proapoptotic and antiangiogenic activities have exhibited great potential in efficient treatment of cancers. Methods: Glycyrrhetinic acid (GA)–modified liposomes (GA LPs) for liver-targeted codelivery of curcumin (Cur) and combretastatin A4 phosphate (CA4P) were prepared and characterized. In vitro cellular uptake, cytotoxicity, cell migration, in vivo biodistribution, antitumor activity, and histopathological studies were performed. Results: Compared with unmodified LPs (Cur-CA4P LPs), Cur-CA4P/GA LPs were taken up effectively by human hepatocellular carcinoma cells (BEL-7402) and showed higher cytotoxicity than free drugs. In vivo real-time near-infrared fluorescence–imaging results indicated that GA-targeted LPs increased accumulation in the tumor region. Moreover, Cur-CA4P/GA LPs showed stronger inhibition of tumor proliferation than Cur, Cur + CA4P, and Cur-CA4P LPs in vivo antitumor studies, which was also verified by H&E staining. Conclusion: GA-modified LPs can serve as a promising nanocarrier for liver-targeted co-delivery of antitumor drugs against hepatocellular carcinoma. Keywords: liver-targeted, LPs, curcumin, combretastatin A4 phosphate, combination therapy

Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P

Qiushi Wang,1 Jianghong Mou,1 Xin Yang,1 Yong He,2 Zengpeng Li,1 Qingya Luo,1 Yanqing Li,1 Li Lin,1 Yu Ma,1 Hualiang Xiao11Department of Pathology, 2Department of Respiration, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of ChinaBackground: The clinical characteristics of epidermal growth factor receptor (EGFR) hotspot mutations, such as deletions in exon 19, substitution of L858R in exon 21, and mutations in exon 20, have been widely reported in nonsmall cell lung cancer. However, the clinical features of other low frequency EGFR mutations in these four exons (especially the relationship with smoking history), eg, substitutions of G719S/A/C in exon 18 and L861Q in exon 21, remain unclear. This study investigated the relationship between G719S/A/C and L861Q mutations (in exon 18 and 21) and smoking history.Methods: Specimens from 194 patients with lung adenocarcinoma were analyzed for EGFR mutations in exons 18–21 by high-resolution melting curve analysis and amplification refractory mutation technology to establish the relationship between G719S/A/C and L861Q mutations and smoking history.Results: Ninety-six of 194 tumors (49.5%) were confirmed to be EGFR mutation-positive. Among these mutations, 71 of 104 (68.3%) were from never smokers, six of 17 (35.3%) were from former smokers, and 19 of 73 (26.0%) were from current smokers (P < 0.001). The mutation rate in heavy smokers (5/23, 21.7%) was significantly lower than in light smokers (20/67, 29.9%) and never smokers (71/104, 68.3%, P < 0.001). Seven low frequency EGFR mutations (four substitutions of G719S, and G719 A, respectively, and three of L861Q in exon 21) were identified. Five of these mutations were derived from smokers (one former light smoker, one current heavy smoker, and three current light smokers). Four of these patients had been treated with tyrosine kinase inhibitors and all had a partial response, with median overall survival (14.5 months) and median progression-free survival (6.8 months), being longer than in patients with similarly staged lung adenocarcinoma without EGFR mutation or treatment with tyrosine kinase inhibitors (6.8 and 3.1 months, respectively, according to data from an as yet unpublished study at our institution).Conclusion: This study provides further evidence that smoking status, include years of smoking and number of cigarettes smoked per day, plays an important role in EGFR mutation in patients with lung adenocarcinoma. Five of seven specimens with G719S/A or L861Q mutations coming from smokers indicates that there may be a relationship between G719S/A or L861Q mutation and smoking history. However, regardless of the influence of smoking, the effectiveness of tyrosine kinase inhibitors was satisfactory in four patients harboring G719S/A and L861Q EGFR mutation.Keywords: EGFR, lung adenocarcinoma, G719S/A, L861Q, smoking history

Background: The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes.Methods: HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR.Results: The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated.Conclusions: Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) has been reported to induce intestinal damage by several mechanisms, yet its role in modulating epithelial repair remains unclear. In this study, we find that chronic SD leads to colonic damage through continuous hypoxia. However, HIF1α, which generally responds to hypoxia to modulate barrier integrity, was paradoxically dysregulated in the colon. Further investigation revealed that a metabolic disruption during SD causes accumulation of α-ketoglutarate in the colon. The excessive α-ketoglutarate degrades HIF1α protein through PHD2 (prolyl hydroxylase 2) to abolish the intestinal repair functions of HIF1α. Collectively, these findings provide insights into how SD can exacerbate intestinal damage by fine-tuning metabolism to abolish HIF1α-mediated repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Non-line-of-sight (NLOS) imaging aims at recovering the shape and albedo of hidden objects. Despite recent advances, real-time video of complex and dynamic scenes remains a major challenge owing to the weak signal of multiply scattered light. Here we propose and demonstrate a framework of spectrum filtering and motion compensation to realize high-quality NLOS video for room-sized scenes. Spectrum filtering leverages a wave-based model for denoising and deblurring in the frequency domain, enabling computational image reconstruction with a small number of sampling points. Motion compensation tailored with an interleaved scanning scheme can compute high-resolution live video during the acquisition of low-quality image sequences. Together, we demonstrate live NLOS videos at 4 fps for a variety of dynamic real-life scenes. The results mark a substantial stride toward real-time, large-scale and low-power NLOS imaging and sensing applications., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Diverging from conventional cell division models, plant cells undergo incomplete division to generate plasmodesmata communication bridges between daughter cells. Although fundamental for plant multicellularity, the molecular events leading to bridge stabilization, as opposed to severing, remain unknown. Using electron tomography, we mapped the transition from cell plate fenestrae to plasmodesmata. We show that the endoplasmic reticulum (ER) connects daughter cells across fenestrae, and as the cell plate matures, fenestrae contract, causing the plasma membrane (PM) to mold around constricted ER tubes. The ER's presence prevents fenestrae fusion, forming plasmodesmata, whereas its absence results in closure. The ER-PM protein tethers MCTP3, MCTP4, and MCTP6 further stabilize nascent plasmodesmata during fenestrae contraction. Genetic deletion in Arabidopsis reduces plasmodesmata formation. Our findings reveal how plants undergo incomplete division to promote intercellular communication.

Objective: To compare the postoperative analgesic efficacy of ultrasound-guided infraspinatus-teres minor interfascial block and interscalene block in shoulder arthroscopic surgery. Methods: A total of 74 patients undergoing shoulder arthroscopic surgery at the Affiliated Hospital of Jiaxing University from December 2023 to February 2024 were prospectively included, whose age ranged from 18 to 80 years and the American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅲ. Patients were divided into two groups using block randomization: infraspinatus-teres minor interfascial block group (observation group) and interscalene block group (control group), with 37 cases in each group. In the anesthesia preparation room, all patients received nerve blocks under ultrasound guidance with 20 ml of 0.375% ropivacaine. Patient-controlled intravenous analgesia (PCIA) was administered to all patients following surgery. The primary outcome was the area under the curve (AUC) of the numeric rating scale (NRS) for pain within 24 hours postoperatively. Secondary outcome measures included the highest NRS score within 48 hours postoperatively, the amount of sufentanil used via PCIA within 48 hours postoperatively, the incidence of rescue analgesia and rebound pain, QoR-40 scores, and the rate of postoperative nausea and vomiting within 24 hours. The non-inferiority margin for the AUC of NRS scores between the two types of regional nerve blocks was set at "2.6". Results: A total of 35 patients were included in the observation group [17 males, 18 females, aged (58.1±9.1) years], and 36 patients were included in the control group [12 males, 24 females, aged (57.0±9.8) years]. The AUC of the NRS scores at rest within 24 hours post-operation was 51.7±10.9 in the observation group and 62.6±13.6 in the control group. The difference in AUC between the two groups was -10.9 (95% CI :-16.8--5.1), with the upper limit of the 95% CI falling below the predefined non-inferiority margin of "2.6" (non-inferiority P <0.001). The highest NRS score [ M ( Q 1 , Q 3 )] within 48 hours post-surgery was 3 (3, 4) in the control group, which was significantly higher than the observation group's score of 2 (2, 3) ( P <0.001). During the postoperative period of 0-12 hours, the observation group received a median dose of 12 (10, 14) μg of sufentanil, which was significantly higher than the control group's dose of 8 (6, 10) μg ( P <0.001). During the postoperative period of 12-24 hours, the observation group received a median dose of 8 (8, 10) μg of sufentanil, which was significantly lower than the control group's median dose of 12 (10, 14) μg ( P <0.001). During the postoperative period of 24-48 hours, there was no statistically significant difference in the dose of sufentanil between the two groups of patients ( P =0.548). In the observation group, the incidence of rescue analgesia within 48 hours postoperatively was 0 (0/35), which was lower than that of the control group at 22.2% (8/36) ( P =0.010). The occurrence of rebound pain in the observation group was 0 (0/35), and the control group was 11.1% (4/36), no statistically significant difference was found between two groups ( P =0.130). In the observation group, the QoR-40 score within 24 hours post-operation was 180.2±3.2, which was higher than the control group's score of 175.8±4.7 ( P <0.001). There was no statistically significant difference in the incidence of postoperative nausea and vomiting within 24 hours between the two groups ( P =0.372). Conclusion: Ultrasound-guided infraspinatus-teres minor interfascial block demonstrates a comparable analgesic effect to interscalene block in shoulder arthroscopic surgery within the first 24 hours postoperatively.

This review summarizes the latest progress in orthopedic nanotechnology, explores innovative applications of nanofibers in tendon repair, and evaluates the potential of selenium and cerium oxide nanoparticles in osteoarthritis and osteoblast differentiation. This review also describes the emerging applications of injectable hydrogels in cartilage engineering, emphasizing the critical role of interdisciplinary research and highlighting the challenges and future prospects of integrating nanotechnology into orthopedic clinical practice. This comprehensive approach provides a holistic perspective on the transformative impact of nanotechnology in orthopedics, offering valuable insights for future research and clinical applications., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO)., Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory., Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes bla KPC-2 and bla OXY-5 , as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred., Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality., 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 Jiang, Lyu, Liu, Li, Liu, Tai, Hu, Zhang, Chu, Zhao, Huang and Wu.)

Background: Acute Stanford Type A Aortic Dissection (ATAAD) is a critical medical emergency characterized by significant morbidity and mortality. This study aims to identify specific gene expression patterns and RNA modification associated with ATAAD., Methods: The GSE153434 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify differential expression genes (DEGs) associated with ATAAD. To validate the involvement of RNA modification in ATAAD, RNA modification-related genes (M6A, M1A, M5C, APA, A-to-I) were acquired from GeneCards, following by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. A gene prediction signature consisting of key genes was established, and Real-time PCR was used to validate the gene expression in clinical samples. The patients were then divided into high and low-risk groups, and subsequent enrichment analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and assessments of immune infiltration. A co-expression network analysis (WGCNA) was performed to explore gene-phenotype relationships and identify key genes., Results: A total of 45 RNA modification genes were acquired. Six gene signatures (YTHDC1, WTAP, CFI, ADARB1, ADARB2, TET3) were developed for ATAAD diagnosis and risk stratification. Enrichment analysis suggested the potential involvement of inflammation and extracellular matrix pathways in the progression of ATAAD. The incorporation of pertinent genes from the GSE147026 dataset into the six-gene signature further validated the model's effectiveness. A significant upregulation in WTAP, ADARB2, and TET3 expression, whereas YTHDC1 exhibited a noteworthy downregulation in the ATAAD group., Conclusion: Six-gene signature could serve as an efficient model for predicting the diagnosis of ATAAD., Competing Interests: None., (© 2024 JGC All rights reserved; www.jgc301.com.)

Waldenström macroglobulinemia (WM) is a type of B-cell lymphoma that produces IgM. Our study aimed to investigate the role of CXCL13, a chemokine essential for B lymphocytes, in the evaluation of treatment response and prognosis in WM. We collected serum samples and clinical data from 72 WM patients, with 69 patients receiving systemic therapy and 3 patients opting not to receive treatment. Serum CXCL13 levels at baseline and after six months of treatments were measured by enzyme-linked immunosorbent assay. The median serum level of CXCL13 was 1 539.2 pg/ml (range 10.0-21 389.9) at baseline and significantly decreased to 123.1 pg/ml (range 0.0-6 741.5) after 6 months of treatments. At baseline, higher CXCL13 levels were associated with lower hemoglobin levels (p = 0.001), higher β2-microglobulin levels (p = 0.001), lower albumin levels (p = 0.046), and higher IPSS-WM scores (p = 0.013). After 6 months of treatment, patients who achieved PR/VGPR had significantly lower CXCL13 levels compared to those with SD (70.2 pg/ml vs 798.6 pg/ml, p = 0.002). The median follow-up period was 40 months (range 4.2-188). Eight patients died during the follow-up period. Overall survival differed based on CXCL13 levels. When grouped by baseline CXCL13 levels, the median OS was 60.0 months in patients with serum CXCL13 > 2 000 pg/ml, while it was not reached in patients with low CXCL13 levels (p < 0.001). Based on CXCL13 levels after the treatments, the median OS was 74.0 months in patients with serum CXCL13 > 200 pg/ml, while it was not reached in patients with CXCL13 ≤ 200 pg/ml. In a subgroup of 28 patients with a series of serum samples, the increase of serum CXCL13 level was associated with disease progression or the start of next-line therapy (p < 0.001). Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In this study, the chemical properties of Ganoderma applanatum polysaccharides (GAP) were systematically investigated, followed by a comprehensive analysis of their antitumor and antioxidant capabilities., Methods: Ultrasonic circulation technology was employed for the extraction of GAP, facilitating the procurement of crude polysaccharides through the Sevag method, dialysis, and sequential alcohol precipitation. The chemical constituents of these polysaccharides were subsequently analyzed utilizing Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry. The antitumor and antioxidant properties of the polysaccharide components were assessed utilizing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and free radical scavenging methods, respectively., Results: Gradient ethanol precipitation yielded three principal polysaccharide fractions: GAP-40, GAP-60 and GAP-80. Analysis revealed glucose as the predominant component in these fractions, with average molecular weights determined to be 77.75, 9.25 and 1.03 kDa, respectively. The antitumor activity of GAP-40, GAP-60 and GAP-80 against MCF-7 cells demonstrated both time and concentration dependence. Significantly, GAP-40, at a concentration of 1000 μg/mL over 48 h, presented a notable inhibition rate of 56.77%, outperforming GAP-60 and GAP-80. Furthermore, the antioxidant capacities of GAP-40, GAP-60 and GAP-80 were comparably significant to that of vitamin C, with detailed analysis revealing marked differences in antioxidant activity among the GAP variants. Specifically, GAP-40 exhibited superior efficacy in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals relative to GAP-60 and GAP-80. In contrast, GAP-80 was distinguished by its exceptional hydroxyl radical scavenging capacity, surpassing that of both GAP-40 and GAP-60., Conclusion: These results substantiate the potential of GAPs as viable and effective antitumor agents, additionally suggesting their utility as functional foods endowed with antioxidant attributes.

The effective method for trypsin purification should be established because trypsin has important economic value. In this work, a novel and simple strategy was proposed for fabricating micron-sized magnetic Fe 3 O 4 @agarose-benzamidine beads (MABB) with benzamidine as a ligand, which can efficiently and selectively capture trypsin. The micro-sized MABB, with clear spherical core-shell structure and average particle size of 6.6 μm, showed excellent suspension ability and magnetic responsiveness in aqueous solution. The adsorption capacity and selectivity of MABB towards target trypsin were significantly better than those of non-target lysozyme. According to the Langmuir equation, the maximum adsorption capacity of MABB for trypsin was 1946 mg g -1  at 25 °C, and the adsorption should be a physical sorption process. Furthermore, the initial adsorption rate and half equilibrium time of MABB toward trypsin were 787.4 mg g -1  min -1 and 0.71 min, respectively. To prove the practicability, MABB-based magnetic solid-phase extraction (MSPE) was proposed, and the related parameters were optimized in detail to improve the purification efficiency. With Tris-HCl buffer (50 mM, 10 mM CaCl 2 , pH 8.0) as extraction buffer, Tris-HCl buffer (50 mM, 100 mM CaCl 2 , pH 8.0) as rinsing buffer, acidic eluent (0.01 M HCl, 0.5 M NaCl, pH 2.0) as eluent buffer and alkaline buffer (1 M Tris-HCl buffer, pH 10.0) as neutralization solution, the MABB-based MSPE was successfully used for trypsin purification from the viscera of grass carp (Ctenopharyngodon idella). The molecular weight of purified trypsin was determined as approximate 23 kDa through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified trypsin was highly active from 30 °C to 60 °C, with an optimum temperature of 50 °C, and was tolerant to pH variation, exhibiting 85 % of maximum enzyme activity from pH 7.0 to 10.0. The results demonstrated that the proposed MABB-based MSPE could effectively purify trypsin and ensure the biological activity of purified trypsin. Therefore, we believe that the novel MABB could be applicable for efficient purification of trypsin from complex biological systems., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: To analyze the changes in cardiac structure and function in women with different types of hypertensive disorders in pregnancy (HDP) and explore their influencing factors. Methods: A total of 1 967 pregnant women diagnosed with HDP who delivered at Peking University Third Hospital from January 1, 2014 to April 15, 2022 were included in the study. They were categorized into four groups based on specific HDP diagnoses: gestational hypertension (506 cases, 25.7%), pre-eclampsia (589 cases, 29.9%), pregnancy complicated with chronic hypertension (332 cases, 16.9%) and chronic hypertension with pre-eclampsia (540 cases, 27.5%). Differences in cardiac structure and function among four groups were retrospectively analyzed. Cardiac structure indicators included left atrial diameter (LAD), left atrial area (LAA), right atrial area (RAA), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), systolic function indicators included left ventricular ejection fraction (LVEF), lateral systolic mitral annular velocity (Sm), diastolic function indicators included peak early diastolic mitral in flow velocity (E)/peak late diastolic mitral in flow velocity (A), and E/peak early diastolic myocardial velocity of the lateral mitral annulus early diastolic velocity (Em). Influencing factors on cardiac structure and function were analyzed using generalized linear regression. Influencing factors were assessed by generalized linear regression. Results: (1) General clinical data: the differences in age, gestational week at delivery, blood pressure, proportion of diabetes, and length of hospital stay were statistically significant among four different HDP types (all P <0.05). (2) Compared with pregnant women with pregnancy complicated with chronic hypertension, pre-eclampsia, and gestational hypertension, those with chronic hypertension with pre-eclampsia had larger LAD, LAA, RAA and LVEDD (all P <0.001), thicker IVST and LVPWT (all P <0.001), and reduced left ventricular diastolic function (E/A, lateral Em, E/Em) and systolic function (lateral Sm; all P <0.001). Pregnant women with gestational hypertension had the least changes in cardiac structure and function. Compared with pregnant women with pre-eclampsia, those with pregnancy complicated with chronic hypertension had smaller RAA ( P <0.001) and lower E/A ( P <0.001), with no significant difference in other indicators (all P >0.05). (3) Chronic hypertension with pre-eclampsia, pregnancy complicated with chronic hypertension, and pre-eclampsia were associated with larger LAD, LAA, and LVEDD, and lower lateral Em (all P <0.05). Conclusions: Different types of HDP are associated with distinct changes in cardiac structure and function. Chronic hypertension with pre-eclampsia demonstrates the most pronounced alterations, followed by pre-eclampsia and pregnancy complicated with chronic hypertension, and gestational hypertension showed the least changes.

The genus Amomum includes over 111 species, 6 of which are widely utilized as medicinal plants and have already undergone taxonomic revision. Due to their morphological similarities, the presence of counterfeit and substandard products remains a challenge. Accurate plant identification is, therefore, essential to address these issues. This study utilized 11 newly sequenced samples and extensive NCBI data to perform molecular identification of the six medicinal "Doukou" species. The plastomes of these species exhibited a typical quadripartite structure with a conserved gene content. However, independent variation shifts of the SC/IR boundaries existed between and within species. The comprehensive set of genetic sequences, including ITS, ITS1, ITS2, complete plastomes, mat K, rbc L, psb A- trn H, and ycf 1, showed varying discrimination of the six "Doukou" species based on both distance and phylogenetic tree methods. Among these, the ITS, ITS1, and complete plastome sequences demonstrated the highest identification success rate (3/6), followed by ycf 1 (2/6), and then ITS2, mat K, and psb A- trn H (1/6). In contrast, rbc L failed to identify any species. This research established a basis for a reliable molecular identification method for medicinal "Doukou" plants to protect wild plant resources, promote the sustainable use of medicinal plants, and restrict the exploitation of these resources.

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and feralization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, we gathered 915 accessions from 23 countries, comprising cultivars, major landraces, feral populations, and the wild progenitor. Based on whole-genome resequencing of these accessions, we constructed the most comprehensive ramie genomic variation map to date. Phylogenetic, demographic, and admixture signal detection analyses indicated that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and the wild progenitor or ancient landraces. Feral ramie has higher genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization differ from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches that differ substantially from the niche of the wild progenitor, and three environmental variables are associated with habitat-specific adaptation in feral ramie. These findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro , but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU 0.89 @LA, WPU 0.99 @LA, WPU 1.09 @LA, and WPU 1.19 @LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU 0.99 @LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU 0.99 @LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1 ) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU 0.99 @LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU 0.99 @LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine., 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., (© 2024 The Authors.)

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis., Methods: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH 2 O) or exposed to HHP (50 cmH 2 O or 100 cmH 2 O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism., Results: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors., Conclusion: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1., (© 2024. Huazhong University of Science and Technology.)

Background: Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery., Aim: To explore the effect of the operative position during bariatric surgery on PONV., Methods: Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors' hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t -test were used to study the influence of operative position on PONV., Results: There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) ( P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group ( P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766)., Conclusion: Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

CRISPR-Cas9 technology has become an essential tool for plant genome editing. Recent advancements have significantly improved the ability to target multiple genes simultaneously within the same genetic background through various strategies. Additionally, there has been significant progress in developing methods for inducible or tissue-specific editing. These advancements offer numerous possibilities for tailored genome modifications. Building upon existing research, we have developed an optimized and modular strategy allowing the targeting of several genes simultaneously in combination with the synchronized expression of the Cas9 endonuclease in the egg cell. This system allows significant editing efficiency while avoiding mosaicism. In addition, the versatile system we propose allows adaptation to inducible and/or tissue-specific edition according to the promoter chosen to drive the expression of the Cas9 gene. Here, we describe a step-by-step protocol for generating the binary vector necessary for establishing Arabidopsis edited lines using a versatile cloning strategy that combines Gateway ® and Golden Gate technologies. We describe a versatile system that allows the cloning of as many guides as needed to target DNA, which can be multiplexed into a polycistronic gene and combined in the same construct with sequences for the expression of the Cas9 endonuclease. The expression of Cas9 is controlled by selecting from among a collection of promoters, including constitutive, inducible, ubiquitous, or tissue-specific promoters. Only one vector containing the polycistronic gene (tRNA-sgRNA) needs to be constructed. For that, sgRNA (composed of protospacers chosen to target the gene of interest and sgRNA scaffold) is cloned in tandem with the pre-tRNA sequence. Then, a single recombination reaction is required to assemble the promoter, the zCas9 coding sequence, and the tRNA-gRNA polycistronic gene. Each element is cloned in an entry vector and finally assembled according to the Multisite Gateway ® Technology. Here, we detail the process to express zCas9 under the control of egg cell promoter fused to enhancer sequence (EC1.2en-EC1.1p) and to simultaneously target two multiple C2 domains and transmembrane region protein genes ( MCTP3 and MCTP4 , respectively at3g57880 and at1g51570), using one or two sgRNA per gene. Key features • A simple method for Arabidopsis edited lines establishment using CRISPR-Cas9 technology • Versatile cloning strategy combining various technologies for convenient cloning (Gateway ® , Golden Gate) • Multigene targeting with high efficiency., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY license.)

We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis., 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., (© 2024 The Authors.)

Humans have substantially transformed the global land surface, resulting in the decline in variation in biotic communities across scales, a phenomenon known as "biological homogenization." However, different biota are affected by biological homogenization to varying degrees, but this variation and the underlying mechanisms remain little studied, particularly in soil systems. To address this topic, we used metabarcoding to investigate the biogeography of soil protists and their prey/hosts (prokaryotes, fungi, and meso- and macrofauna) in three human land-use ecosystem types (farmlands, residential areas, and parks) and natural forest ecosystems across subtropical and temperate regions in China. Our results showed that the degree of community homogenization largely differed between taxa and functional groups of soil protists, and was strongly and positively linked to their colonization ability of human land-use systems. Removal analysis showed that the introduction of widespread, generalist taxa (OTUs, operational taxonomic units) rather than the loss of narrow-ranged, specialist OTUs was the major cause of biological homogenization. This increase in generalist OTUs seemingly alleviated the negative impact of land use on specialist taxa, but carried the risk of losing functional diversity. Finally, homogenization of prey/host biota and environmental conditions were also important drivers of biological homogenization in human land-use systems, with their importance being more pronounced in phagotrophic than parasitic and phototrophic protists. Overall, our study showed that the variation in biological homogenization strongly depends on the colonization ability of taxa in human land-use systems, but is also affected by the homogenization of resources and environmental conditions. Importantly, biological homogenization is not the major cause of the decline in the diversity of soil protists, and conservation and study efforts should target at taxa highly sensitive to local extinction, such as parasites., (© 2024 John Wiley & Sons Ltd.)

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf&#95;IL-12p35a/b, Pf&#95;IL-23p19 and Pf&#95;IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf&#95;IL-12p35a/b and Pf&#95;IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf&#95;IL-12p35a/b and Pf&#95;IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf&#95;IL-12p40a mRNA was induced in gill, and Pf&#95;IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf&#95;IL-12p35a and Pf&#95;IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf&#95;IL-12 and rPf&#95;IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf&#95;IL-12 and Pf&#95;IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI., Methods: The rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction (HAMI) group were established. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites., Results: A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95., Conclusions: N8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.

Objective: To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation. Methods: From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared. Results: The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values. Conclusion: The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

Background: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear., Aim: To determine whether smoking is linked to the recurrence and progression of bladder cancer., Methods: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted., Results: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61)., Conclusion: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest related to this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.

The screening of colorectal cancer (CRC) is pivotal for both the prevention and treatment of this disease, significantly improving early-stage tumor detection rates. This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment. However, the adoption of CRC screening methods faces numerous challenges, including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity. Moreover, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness affect screening uptake. The coronavirus disease 2019 pandemic further intensified these cha-llenges, leading to reduced screening participation and increased waiting periods. Additionally, the growing prevalence of early-onset CRC necessitates innovative screening approaches. In response, research into new methodologies, including artificial intelligence-based systems, aims to improve the precision and accessibility of screening. Proactive measures by governments and health organizations to enhance CRC screening efforts are underway, including increased advocacy, improved service delivery, and international cooperation. The role of technological innovation and global health collaboration in advancing CRC screening is undeniable. Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening, making a significant impact on the fight against this disease. Given the rise in early-onset CRC, it is crucial for screening strategies to continually evolve, ensuring their effectiveness and applicability., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)