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Dan-Dan Li,1,&ast; Xue Yang,1,&ast; Yang Yang,2,&ast; Li-Hua Zhao,1 Tian-Tian Zhang,3 Yi-Nan Wang,1 Jian-Bin Su,1 Li-Hua Wang,4 Hai-Yan Shi3 1Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 2Department of General Practice, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 4Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Hua Wang, Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email wlh512512@163.com Hai-Yan Shi, Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email 1198827119@qq.comBackground: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied.Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level.Results: One-way analysis of variance showed that β-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p< 0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p< 0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-β (p> 0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes.Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.Keywords: type 2 diabetes, physical activity, body composition, correlation

Hui Li,1,2,&ast; Xiao-Lei Fan,1,2,&ast; Yi-Nan Wang,1,2 Wei Lu,1,2 Haoyi Wang,1,2 Runzhi Liao,1,2 Min Zeng,1,2 Jun-Xiao Yang,1,2 Yihe Hu,1,2 Jie Xie1,2 1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Xie; Yihe HuDepartment of Orthopedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86– 731– 89753006; +86– 731– 89753706Email dr_xiejie@163.com; csuhuyihe@163.comPurpose: Wear debris particle-induced periprosthetic osteolysis is a severe complication of total joint replacement that results in aseptic loosening and subsequent arthroplasty failure. No effective therapeutic agents or drugs have been approved to prevent or treat osteolysis; thus, revision surgery is often needed. Extracellular vesicles (EVs) are vital nanosized regulators of intercellular communication that can be directly applied to promote tissue repair and regeneration. In this study, we assessed the therapeutic potential of EVs from human urine-derived stem cells (USCs) (USC-EVs) in preventing ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis.Methods: USCs were characterized by measuring induced multipotent differentiation and flow cytometry. USC-EVs were isolated and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and Western blotting. RAW264.7 cells and bone marrow mesenchymal stem cells (BMSCs) were cultured with USC-EVs to verify osteoclast differentiation and osteoblast formation, respectively, in vitro. The effects of USC-EVs were investigated on a UHMWPE particle-induced murine calvarial osteolysis model by assessing bone mass, the inflammatory reaction, and osteoblast and osteoclast formation.Results: USCs differentiated into osteogenic, adipogenic and chondrogenic cells in vitro and were positive for CD44, CD73, CD29 and CD90 but negative for CD34 and CD45. USC-EVs exhibited a cup-like morphology with a double-layered membrane structure and were positive for CD63 and TSG101 and negative for calnexin. In vitro, USC-EVs promoted the osteogenic differentiation of BMSCs and reduced proinflammatory factor production and osteoclastic activity in RAW264.7 cells. In vivo, local injection of USC-EVs around the central sites of the calvaria decreased inflammatory cytokine generation and osteolysis compared with the control groups and significantly increased bone formation.Conclusion: Based on our findings, USC-EVs prevent UHMWPE particle-induced osteolysis by decreasing inflammation, suppressing bone resorption and promoting bone formation.Keywords: extracellular vesicles, urine-derived stem cells, UHMWPE, wear particle-induced osteolysis, anti-inflammatory

Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2

Meng-Long Zhou,1,2,* Wang Yang,1,2,* Ya-Qi Wang,1,2,* Miao Mo,2,3 Ran Hu,1,2 Yan Wang,1,2 Jia-Ning Yang,1,2 Gui-Chao Li,1,2 Ya-Nong Wang,2,4 Zhen Zhang1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 4Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: N3 gastric cancer (GC) is characterized by a heavy burden of lymph node metastasis and a high postoperative recurrence rate. The role of radiotherapy in this group of patients remains undetermined. The purpose of this study was to compare the effectiveness of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) for N3 GC after D2/R0 resection.Patients and methods: From January 2004 to December 2015, patients with N3 GC in the database of Fudan University Shanghai Cancer Center were retrospectively reviewed. The eligible patients were enrolled in an adjuvant CRT group and an adjuvant ChT group. Four different methods based on a propensity score model were used to balance the baseline characteristics. Then, survival analyses between the two groups were performed in addition to patterns of recurrence and subgroup analyses.Results: In total, 175 and 365 eligible patients were enrolled into the CRT and ChT groups, respectively. After balancing, the disease-free survival (DFS) of patients in the CRT group was significantly better than that of patients in the ChT group (p=0.021). Subgroup analyses showed that patients with N3a GC benefitted from adjuvant CRT.Conclusion: Compared with adjuvant ChT, adjuvant CRT can further improve the DFS of patients with N3 GC after D2/R0 resection. Patients with lymph node metastases should be further stratified when selecting patients for adjuvant CRT.Keywords: stomach neoplasms, gastrectomy, chemoradiation, propensity score, survival analysis

Haiyan Chen,1 An Lu,1 Xiaoyi Zhang,1 Lin Gui,1 Yaonan Wang,1 Jianhui Wu,1 Hua Feng,1 Shiqi Peng,1 Ming Zhao1,2 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Background: The impact of upregulation of platelet membrane glycoprotein (GP)IIb/IIIa and P-selectin on the onset of arterial thrombosis, venous thrombosis, and cancer encourages to hypothesize that dual inhibitor of GPIIb/IIIa and P-selectin receptors should simultaneously inhibit arterial thrombosis, block venous thrombosis, and slow tumor growth. Methods: For this reason, the structural characteristics and the CDOCKER interaction energies of 12 carbolines were analyzed. This led to the design of 1-(4-isopropyl-phenyl)-β-carboline-3-carboxylic acid (ICCA) as a promising inhibitor of GPIIb/IIIa and P-selectin receptors. Results: The synthetic route provided ICCA in 48% total yield and 99.6% high-performance liquid chromatography purity. In vivo 5 µmol/kg oral ICCA downregulated GPIIb/IIIa and P-selectin expression thereby inhibited arterial thrombosis, blocked venous thrombosis, and slowed down tumor growth, but did not damage the kidney and the liver. Conclusion: Therefore, ICCA could be a promising candidate capable of downregulating GPIIb/IIIa and P-selectin receptors, inhibiting arterial thrombosis, blocking venous thrombosis, and slowing down tumor growth. Keywords: thrombosis, cancer, GPIIb/IIIa, P-selectin

Xinyi Xu,1 Yuji Wang,1 Jianhui Wu,1 Xi Hu,1 Haimei Zhu,1 Xiaoyi Zhang,1 Yaonan Wang,1 Lin Gui,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Abstract: To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral (S)-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height

Jianhui Wu,1–4 Ming Zhao,1–5 Yuji Wang,1–4 Yaonan Wang,1–4 Haimei Zhu,1–4 Shurui Zhao,1–4 Lin Gui,1–4 Xiaoyi Zhang,1–4 Shiqi Peng1–4 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, 2Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China, 3Beijing Laboratory of Biomedical Materials, 4College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Abstract: It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin. N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug. Images of transmission electron micro­scopy, scanning electron microscopy and atomic force microscopy proved that HMCEF forms nanoparticles with a diameter of

PURPOSE: To evaluate the combination of surgical-grade calcium sulfate (SGCS) and platelet-rich plasma (PRP) for alveolar ridge preservation prior to implant placement. MATERIALS AND METHODS: Five mongrel dogs were used as subjects. Four enlarged mandibular extraction sockets, 2 on each side, were created in each dog. According to a split-mouth design, the 2 anterior sockets received either SGCS/PRP (SGCS/PRPant) or were left unfilled, while the 2 posterior sockets received either SGCS/PRP (SGCS/PRPpost) or SGCS. Computerized tomographic (CT) scans were conducted at 1 day and 8 weeks postextraction to detect the change in ridge height. Bone scintigraphy was performed at 2, 4, and 6 weeks to investigate new bone formation activity. At 8 weeks, 1 dog was sacrificed for histologic and histomorphometric study. Meanwhile, implants were placed in the remaining 4 dogs. These 4 dogs were sacrificed after 3 months. RESULTS: Less ridge resorption was observed in the anterior SGCS/PRP-filled sites compared to unfilled sites (P = .001), while no significant difference was found between the SGCS/PRPpost and SGCS groups (P = .544). Bone scintigraphy showed that sites filled with SGCS/PRP showed significantly higher count/pixel at 2 (P = .028), 4 (P = .009), and 6 weeks (P = .037) than the unfilled sites. Nevertheless, the SGCS/PRPpost group achieved significantly higher values than the SGSC group only at 2 weeks (P = .036). Histomorphometrically, the SGCS/PRPant group showed a significantly higher percentage of bone-implant contact than the unfilled group (P = .024), but no significant difference was detected between the SGCS/PRPpost and SGCS groups (P = .979). CONCLUSION: Grafting SGCS/PRP in fresh extraction sockets reduced alveolar ridge resorption and promoted the bone formation in this canine model. The addition of PRP to SGCS resulted in the enhancement of bone regeneration in the early phase of healing. [ABSTRACT FROM AUTHOR]

Formaldehyde has long been the fixative of choice for histological examination of tissue. The use of alternatives to formaldehyde has grown, however, owing to the serious hazards associated with its use. Companies have striven to maintain the morphological characteristics of formaldehyde-fixed tissue when developing alternatives. Glyoxal-based fixatives now are among the most popular formaldehyde alternatives. Although there are many studies that compare staining quality and immunoreactivity, there have been no studies that quantify possible structural differences. Histomorphometric analysis commonly is used to evaluate diseased tissue. We compared fixation with formaldehyde and glyoxal with regard to the histomorphological properties of plantar foot tissue using a combination of stereological methods and quantitative morphology. We measured skin thickness, interdigitation index, elastic septa thickness, and adipocyte area and diameter. No significant differences were observed between formaldehyde and glyoxal fixation for any feature measured. The glyoxal-based fixative used therefore is a suitable fixative for structural evaluation of plantar soft tissue. Measurements obtained from the glyoxal-fixed tissue can be combined with data obtained from formalin-fixed for analysis. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate bone formation after marsupialization of odontogenic keratocysts (keratocystic odontogenic tumors) of the mandible. PATIENTS AND METHODS: A total of 53 patients with mandibular odontogenic keratocysts underwent marsupialization. Clinical and radiographic examinations were done at 1, 3, and 6 months postoperatively. The bone density of the cyst site was measured on the panoramic radiographs using the Digora. The volume of the cyst was measured by injection of saline solution into the cyst cavity. Student t test and Spearman's rank correlation were used for statistical analysis. RESULTS: Healing was uneventful in all patients. The diameter of the cysts was 4.1 to 11.0 cm (average 5.4). The panoramic radiographs showed a continuous increase in bone density of the cystic area, with a 22.42% increase at 1 month, 46.07% at 3 months, and 64.69% at 6 months postoperatively compared with the preoperative values. The decrease in cyst volume was 19.05% at 1 month, 55.62% at 3 months, and 79.67% at 6 months postoperatively. The increase in bone density and decrease in cyst volume were more significant in the first 3 months than in second 3 months (P < .01). The increase in bone density correlated inversely with the decrease in the cyst volume (P < .01). CONCLUSION: Bone regeneration can occur more rapidly in large mandibular odontogenic keratocysts after marsupialization with drainage by a cyst plug. After 3 months, secondary enucleation of the cyst can be performed. [ABSTRACT FROM AUTHOR]

Objectives: To examine the underlying structure of neuropsychological tests involving working memory components and those not involving working memory components that contribute to the performance of the Tower of Hanoi task in schizophrenic patients. Participants and Methods: A total of 90 patients with residual schizophrenia received a comprehensive cognitive assessment. Working memory was assessed with Letter-Number Span and Visual Patterns tests. Executive function was assessed by the Tower of Hanoi task. Stepwise multiple linear regressions were performed including age, education, duration of illness, and all cognitive functions. Results: Principal component analysis was conducted and yielded a 4-factor solution: auditory working memory, visual working memory, verbal working memory, and verbal fluency. Subsequent stepwise regression indicated that only visual working memory components and auditory working memory components were retained in the final model accounting, which explained 23.5% of the variance. Conclusions: These findings emphasise the importance of memory components, particularly those involving visual- and auditory-based working memory, when conceptualising the performance of the Tower of Hanoi task in residual schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract Background Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs) offer renewable cells for generating insulin-producing cells (IPCs). Methods We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation. Results Here, we report adding extracellular matrix proteins (ECM) such as fibronectin (FN) or laminin (LAM) enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor), PD98059 (MEK specific inhibitor) or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM. Conclusions These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.

The article discusses several cancer studies. A study demonstrated the role of cyclin D1 which is independent from its role in cell-cycle regulation. Another study has revealed that sulfated hyaluronic acid (HA) is an effective inhibitor of prostate carcinoma cell proliferation, motility and invasion. It discusses studies that offer perspectives on the role of melanoma and exosomes in facilitating the metastatic process.

This paper presents an optical fiber hollow malposition structure (HMS) elaborated with cellular-like N-CQDs/Mg x Zn 1- x O for detecting ammonia (NH 3 ) at room temperature. The gas detection was realized by combining the HMS to excite the surface evanescent field on the outer surface of the hollow core fiber (HCF) and the surface-coated cellular-like N-CQDs/Mg x Zn 1- x O material for improving sensitivity. Experimental results demonstrate that the sensor coated with N-CQDs/Mg 0.2 Zn 0.8 O exhibits the highest sensitivity, reaching 8.9 pm/ppm, which is 11.6 times higher than that with Mg 0.2 Zn 0.8 O. Additionally, the NH 3 sensor can determine a minimum concentration of 1 ppm and has response and recovery times of 6.2 and 7.1 s, respectively. Density functional theory (DFT) calculations confirm that N-CQDs reduces the bandgap of the composite material and increase the carrier concentration on its surface, thereby enhancing gas adsorption capacity. The intrinsic characteristics of the proposed sensor including small size, high sensitivity, and good stability reveal its promising prospects in detecting low concentrations of NH 3 .

Objectives: This study aimed to investigate the prognostic significance of stress dynamic myocardial CT perfusion imaging (CTP) and determine whether it has incremental advantages over coronary computed tomography angiography (CTA)-derived parameters., Methods: This prospective multicenter study included patients with suspected coronary artery disease who had undergone coronary CTA and CTP and were followed for 6 years. The endpoint was time-to-first major adverse cardiovascular event (MACE). MACEs included all-cause mortality, cardiac death, nonfatal myocardial infarction, unstable angina, late revascularization, and heart failure or aggravated angina symptoms requiring hospitalization. The CTP-derived absolute myocardial blood flow (MBF), relative MBF ratio (r-MBF), and the CTA-derived fractional flow reserve (CT-FFR) and stenosis were analyzed. The independent predictors, time-to-event distributions and the incremental prognostic value of CTP over CTA-derived parameters were assessed., Results: A total of 226 patients (66.7 ± 11.3 years, 37.6% women) were enrolled with a median follow-up time of 1233 days. Twenty-one patients (9.29%) experienced MACEs and ten patients (4.4%) experienced hard MACEs. The r-MBF was the only independent predictor for MACEs in both all patients (hazard ratio [HR]: 0.82 (0.69-0.97), p = 0.01) and patients available for CTA stenosis (%) and CT-FFR calculation (HR: 0.72 (0.57-0.91), p = 0.006). The incremental prognostic significance of r-MBF over CT-FFR was confirmed after combining with CTA-derived parameters (concordance index: 0.919 vs. 0.811; p < 0.01). Patients with r-MBF < 0.77 were more likely to experience MACEs and have a lower average survival time (1565 vs. 1790 days; p < 0.01) after stent implantation., Conclusions: CTP-assessed r-MBF was independently correlated with MACEs and provided incremental prognostic significance., Key Points: Question The prognostic significance of CT perfusion (CTP) lacks sufficient support from clinical research. Findings In this Chinese population, CTP has the strongest prognostic significance, over CT-Fractional Flow Reserve (FFR) and CTA stenosis in predicting major adverse cardiovascular events (MACEs). Clinical relevance Relative myocardial blood flow ratio had the strongest prognostic value and incremental advantages in predicting MACEs beyond CT-FFR and coronary CTA stenosis quantification, as well as advantages in patients with stents, aiding in personalized diagnosis and treatment plans., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Y.-N.W. Conflict of interest: X.-B.Y. is an employee of Siemens Healthineers Ltd. The remaining authors state that there neither exists a conflict of interest nor that there is financial information to disclose. Statistics and biometry: Wei Han kindly provided statistical advice for this manuscript (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China). Informed consent: Written informed consent was obtained from all participants in this study. Ethical approval: Institutional Review Board approval was obtained. The Multicenter VALIDITY Trial protocol was approved by each of the institutional ethics committees (Peking Union Medical College Hospital, Fu Wai Hospital, Tianjin Medical University General Hospital, Guangdong Provincial People’s Hospital, and Shanghai General Hospital) and was conducted according to the Declaration of Helsinki. Study subjects or cohorts overlap: No study subjects or cohorts have been previously reported. Methodology: Prospective Diagnostic or prognostic study Multicenter study, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Ethnopharmacological Relevance: According to the theory of traditional Chinese medicine, Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient., Aim of the Study: To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial., Materials and Methods: A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT 3 ) and free thyroxine (FT 4 ) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint., Results: 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT 3 levels (group A, p=0.0027; group B, p < 0.0001; group C, p=0.0028) and FT 4 levels (group A, p < 0.0001; group B, p < 0.0001; group C, p < 0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p = 0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p < 0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p < 0.0001), eye (p=0.0490), tiredness (p < 0.0001), cognition (p < 0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety., Conclusions: Pingkang granules significantly reduced serum FT 3 , FT 4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism., Competing Interests: Declaration of competing interest This study was supported by the Project of Clinical Center (Traditional Chinese Medicine) of Endocrinology and Metabolism Disease of Shenyang (Grant Number SKF201875), the Traditional Chinese Medicine Clinical Discipline and Specialty Capacity Construction Project of Liaoning Province (Grant Number LNZYXZK201902). All the authors declare no conflicts of interest associated with this research and the study received no financial support that could have influenced its outcomes., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti-fibrotic and anti-inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine-induced chronic tubulointerstitial nephropathy (TIN) and in idole-3-acetic acid (IAA)-stimulated NRK-52E cells. Acetate and n-butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF-ƙB) and its target gene products as well as activated antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA-stimulated NRK-52E cells. The inhibitory effect of GPA on AHR, NF-Ƙb, and Nrf2 signaling were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191 compared with untreated IAA-stimulated NRK-52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling., (© 2024 John Wiley & Sons Ltd.)

Introduction: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS)., Methods: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method., Results: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24)., Conclusions: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM., (S. Karger AG, Basel.)

As a simulant of hazardous 226 Ra 2+ , the simultaneously selective and rapid elimination of radioactive 133 Ba 2+ ions from geothermal water is necessary but still challenging. In this paper, we demonstrated the usability of a layered thiostannate with facile synthesis and inexpensive cost, namely, K 2 x Sn 4- x S 8- x (KTS-3, x = 0.65-1), for the remediation of radioactive 133 Ba 2+ in multiple conditions, including sorption isotherm, kinetics, and the influences of competitive inorganic/organic ions, pH values, and dosages. KTS-3 has a strong barium uptake ability (171.3 mg/g) and an ultrafast adsorption kinetics (about 2 min). Impressively, it can achieve a high preference for barium regardless of the excessive interference ions (Na + , K + , Mg 2+ , Ca 2+ , and humic acid) and acidic/alkaline environments, with the largest distribution coefficient K d value reaching 6.89 × 10 5 mL/g. Also, the Ba 2+ -laden products can be easily eluted by a concentrated KCl solution, and its adsorption performances for barium resist well even after five consecutive cycles. In addition, owing to the regular appearance and excellent mechanical strength, the prepared KTS-3/PAN (PAN = polyacrylonitrile) granule displays a good removal efficiency in the flowing ion-exchange column. These advantages mentioned above render it very promising for the effective and efficient cleanup of radioactive 133 Ba 2+ -contaminated wastewater.

Background: The outcome of surgical treatment for colorectal cancer (CRC) remains unsatisfactory and warrants further exploration and optimization., Aim: To clarify the impact of chemotherapy plus cellular immunotherapy [dendritic cell-cytokine-induced killer (DC-CIK) cell immunotherapy] on patients after CRC surgery and to explore the mediating variables., Methods: A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected. The sample comprised a control group of 55 patients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX + DC-CIK immunotherapy. We performed comparative analyses of the clinical and pathological data of the two groups, including efficacy (2-year disease-free survival [DFS] rate), the incidence of adverse events (diarrhea, myelosuppression, gastrointestinal reactions, and peripheral neuritis), serum levels of tumor markers [carcinoembryonic antigens and carbohydrate antigens (CA)19-9 and CA242], and T-cell subsets [cluster of differentiation (CD)3 + , CD3 + CD4 + , CD3 + CD8 + , natural killer (NK), and NK T cells]. We also conducted preliminary univariate and multivariate analyses of the variables that affected the efficacy of the treatments., Results: We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group, with a statistically lower incidence of adverse events. Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference. After treatment, the various T-cell subgroup indicators in the control group were significantly lower than those in the research group. The indices of T-cell subsets in the research group showed no significant change from preoperative levels. Univariate analysis revealed a significant correlation between TNM staging, tumor differentiation, and the rates of nonresponse to treatment in CRC patients after surgery. Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment., Conclusion: We concluded that XELOX + DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events, extended 2-year DFS, enhanced immunity, and increased physiological antitumor responses., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s1}(2536)^{-} and e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s2}^{*}(2573)^{-} processes are studied using data samples collected with the BESIII detector at center-of-mass energies from 4.530 to 4.946 GeV. The absolute branching fractions of D&#95;{s1}(2536)^{-}→D[over ¯]^{*0}K^{-} and D&#95;{s2}^{*}(2573)^{-}→D[over ¯]^{0}K^{-} are measured for the first time to be (35.9±4.8±3.5)% and (37.4±3.1±4.6)%, respectively. The e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s1}(2536)^{-} and e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s2}^{*}(2573)^{-} cross sections are measured, and a resonant structure at around 4.6 GeV with a width of 50 MeV is observed in both processes with a statistical significance of 7.2σ and 15σ, respectively. The state is observed for the first time in e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s2}^{*}(2573)^{-} and could be the Y(4626) found by the Belle oration in the D&#95;{s}^{+}D&#95;{s1}(2536)^{-} final state, since they have similar masses and widths. There is also evidence for a structure at around 4.75 GeV in both processes.

Lithium metal batteries (LMBs) with high energy density are perceived as the most promising candidates to enable long-endurance electrified transportation. However, rapid capacity decay and safety hazards have impeded the practical application of LMBs, where the entangled complex degradation pattern remains a major challenge for efficient battery design and engineering. Here, we present an interpretable framework to learn the accelerated aging of LMBs with a comprehensive data space containing 79 cells varying considerably in battery chemistries and cell parameters. Leveraging only data from the first 10 cycles, this framework accurately predicts the knee points where aging starts to accelerate. Leaning on the framework's interpretability, we further elucidate the critical role of the last 10%-depth discharging on LMB aging rate and propose a universal descriptor based solely on early cycle electrochemical data for rapid evaluation of electrolytes. The machine learning insights also motivate the design of a dual-cutoff discharge protocol, which effectively extends the cycle life of LMBs by a factor of up to 2.8.

As a double-stranded RNA-editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically "cold" into "hot" tumors susceptible to immune checkpoint blockade.

The diversity observed in canine breed phenotypes, together with their risk for heritabily disorders of relevance to dogs and humans, makes the species an ideal subject for studies aimed at understanding the genetic basis of complex traits and human biomedical models. Dog10K is an ongoing international collaboration that aims to uncover the genetic basis of phenotypic diversity, disease, behavior, and domestication history of dogs. To best present and make the extensive data accessible and user friendly, we have established the Dog10K (http://dog10k.kiz.ac.cn/) database, a comprehensive-omics resource summarizing multiple types of data. This database integrates single nucleotide variants (SNVs) from 1987 canine genomes, de-novo mutations (DNMs) from 43 dog breeds with >40× sequence, RNA-seq data of 105057 single nuclei from hippocampus, 74067 single cells from leukocytes and 30 blood samples from published canid studies. We provide clear visualization, statistics, browse, searching, and downloading functions for all data. We have integrated three analysis tools, Selscan, LiftOver and AgeConversion, to aid researchers in custom exploration of the comprehensive-omics data. The Dog10K database will serve as a foundational platform for analyzing, presenting and utilizing canine multi-omics data., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Multiple repetitive sequences of authentic genes commonly exist in fungal genomes. AT-biased genotypes of Ophiocordyceps sinensis have been hypothesized as repetitive pseudogenes in the genome of Hirsutella sinensis (GC-biased Genotype #1 of O. sinensis ) and are generated through repeat-induced point mutation (RIP), which is charactered by cytosine-to-thymine and guanine-to-adenine transitions, concurrent epigenetic methylation, and dysfunctionality. This multilocus study examined repetitive sequences in the H. sinensis genome and transcriptome using a bioinformatic approach and revealed that 8.2% of the authentic genes had repetitive copies, including various allelic insertions/deletions, transversions, and transitions. The transcripts for the repetitive sequences, regardless of the decreases, increases, or bidirectional changes in the AT content, were identified in the H. sinensis transcriptome, resulting in changes in the secondary protein structure and functional specification. Multiple repetitive internal transcribed spacer (ITS) copies containing multiple insertion/deletion and transversion alleles in the genome of H. sinensis were GC-biased and were theoretically not generated through RIP mutagenesis. The repetitive ITS copies were genetically and phylogenetically distinct from the AT-biased O. sinensis genotypes that possess multiple transition alleles. The sequences of Genotypes #2-17 of O. sinensis , both GC- and AT-biased, were absent from the H. sinensis genome, belong to the interindividual fungi, and differentially occur in different compartments of the natural Cordyceps sinensis insect-fungi complex, which contains >90 fungal species from >37 genera. Metatranscriptomic analyses of natural C. sinensis revealed the transcriptional silencing of 5.8S genes in all C. sinensis -colonizing fungi in natural settings, including H. sinensis and other genotypes of O. sinensis . Thus, AT-biased genotypes of O. sinensis might have evolved through advanced evolutionary mechanisms, not through RIP mutagenesis, in parallel with GC-biased Genotype #1 of H. sinensis from a common genetic ancestor over the long course of evolution.

Background: Cardiopulmonary bypass (CPB) is a common procedure in cardiac surgery. CPB is a high-risk factor for acute kidney injury (AKI), and diabetes is also such a factor. Diabetes can lead to copper overload. It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload., Aim: To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis., Methods: Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB. Levels of copper ion, lactate, glucose, heat shock protein-70 (HSP-70), and dihydrolipoamide dehydrogenase (DLAT) were determined. A diabetic rat model was established and CPB was performed. The rats were assessed for the development of CPB-AKI, and for the association of AKI with cuproptosis by detecting copper levels, iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy., Results: CPB resulted in elevations of copper, lactate, HSP-70 and DLAT in blood and urine in both diabetic and non-diabetic patients. CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats. Cuproptosis-related proteins also appeared to be significantly reduced., Conclusion: CPB-AKI is associated with cuproptosis. Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear., Aim: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC)., Methods: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing., Results: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria , AF12 , Adlercreutzia , Clostridium , Coriobacteriaceae , and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum , Odoribacter , RF32 , YS2 , and Rikenellaceae but increased the proportions of p&#95;Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora., Conclusion: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy., Competing Interests: Conflict-of-interest statement: The authors declare that there are no known competing financial interests or personal relationships among all authors of this article that could influence all studies reported in this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The landfill mining process is a main source of anthropogenic bioaerosol release, posing potential risks to the health of occupationally exposed personnel and nearby residents. In this study, microbial aerosolization behavior and potential pathogenicity during the landfill mining process were systematically investigated. The highest concentration of bacterial aerosols was measured in the refuse mining area, with a value of 5968 ± 1608 CFU/m 3 , while the highest concentration of fungal aerosols was 1196 ± 370 CFU/m 3 in the refuse screening area. The bacterial and fungal aerosols were distributed primarily in the particle size ranges of 4.7-7.0 µm and > 7.0 µm, respectively. The pathogenic microbes Arthrobacter, Bacillus, Arthrobotrys and Aspergillus had high bioaerosol aerosolization capacities, with aerosolization indices of 100-329, 31-62, 2-14 and 1-11, respectively, when released from mineralized refuse. There are more than 100 types of pathogenic bacteria in bioaerosols. The microorganisms Lysobacter, Luteimonas and Mycolicibacterium, which carry virulence factor genes (VFGs) (pilG, Rv0440, pilT, etc.), can spread VFGs, aggravate bioaerosol pollution, and threaten the health of workers and nearby residents. This research will help further the understanding of bioaerosol contamination behaviors and potential pathogenicity risks from landfill mining activities., 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.)

Large abscesses are walled-off collections of pus and bacteria that often do not respond to antibiotic therapy. Standard of care involves percutaneous placement of indwelling catheter(s) for drainage, a long and uncomfortable process with high rehospitalization rates. The long-term goal of this work is to develop therapeutic ultrasound approaches to eradicate bacteria within abscesses as a noninvasive therapeutic alternative. Inertial cavitation induced by short pulses of focused ultrasound (histotripsy) is known to generate lethal mechanical damage in bacteria. Prior studies with Escherichia coli (E. coli) in suspension demonstrated that bactericidal effects increase with increasing peak negative amplitude, treatment time and duty cycle. The current study investigated correlates of bactericidal activity with histotripsy cavitation cloud size. Histotripsy was applied to E. coli suspensions in 10-mL sample vials at 810 kHz, 1.2 MHz, or 3.25 MHz for 40 minutes. The cavitation activity in the sample vials was separately observed with high-speed photography. The cavitation cloud area was quantified from those images. A linear relationship was observed between bacterial inactivation and cavitation cloud size (R 2 = 0.96), regardless of the acoustic parameters (specifically frequency, pulse duration and power) used to produce the cloud.

Background: Self-directed, lifelong learning is essential for nurses' competence in complex healthcare environments, which are characterised by rapid advancements in medicine and technology and nursing shortages. Previous studies have demonstrated that ChatGPT technology fosters self-directed learning by motivating users to engage with it., Objectives: To explore the relationships amongst socio-demographic data, attitudes towards ChatGPT use, and self-directed learning amongst registered nurses in Taiwan., Methods: A cross-sectional study design with an online survey was adopted. Registered nurses from various healthcare settings were recruited through Facebook and LINE, a widely used messaging application in East Asia, reaching over 1000 nurses across five distinct online groups. An online survey was used to collect data, including socio-demographic characteristics, attitudes towards ChatGPT use, and a self-directed learning scale. Data were analysed using descriptive statistical methods, t-tests, Pearson's correlation, one-way analysis of variance, and multiple linear regression analysis., Results: Amongst the 330 participants, 50.6% worked in hospitals, 51.8% had more than 15 years of work experience, and 78.2% did not hold supervisory positions. Of the participants, 46.7% had used ChatGPT. For all nurses, work experience and awareness of ChatGPT statistically significantly predicted self-directed learning, explaining 32.0% of the variance. For those familiar with ChatGPT, work experience in nursing and the technological/social influence of ChatGPT statistically significantly predicted self-directed learning, explaining 35.3% of the variance., Conclusions: Work experience in nursing provides critical opportunities for professional development and training. Therefore, ChatGPT-supported self-directed learning should be customised for degrees of experience to optimise continuous education., Implications for Nursing Management and Health Policy: This study explores nurses' diverse use of and attitudes towards ChatGPT for self-directed learning. It suggests that administrators customise support and training when incorporating ChatGPT into professional development, accounting for nurses' varied experiences to enhance learning outcomes., Patient or Public Contribution: No patient or public contribution., Reporting Method: This study adhered to the relevant cross-sectional STROBE guidelines., (© 2024 John Wiley & Sons Ltd.)

The growth in municipal solid waste incineration (MSWI) has resulted in a substantial rise in the production of fly ash in China. It is anticipated that during the "14th Five-Year Plan", the accumulated amount of fly ash stocked and disposed of at landfills will surpass 100 million tons. With the development of the economy and the implementation of garbage classification relevant policies, the pollution characteristics of heavy metal change in spatiotemporal distribution. Solidification/stabilization (S/S) pre-treatment coupled with landfill disposal is the mainstream method for fly ash. This study provides a systematic overview and comparison of the current application status and research on the mechanism of S/S technology, and the long-term stability of solidified/stabilized fly ash is a crucial factor in controlling the risks of landfills. Subsequently, it examines the influencing factors and mechanisms associated with heavy metals leaching under different environmental scenarios (meteorological factors, leachate and acid rain erosion, and carbonation, etc.), and concludes that single stabilization technology is difficult to meet long-term landfill requirements. Finally, the limits of heavy metal leaching toxicity evaluation methods and landfilled fly ash supervision were discussed, and relevant suggestions for future development were proposed. This study can provide theoretical instruction and technical support for the risk control of potential environmental risks of heavy metals in solidified/stabilized fly ash from landfills in China., 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.)