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Yin-shan Jin,&ast; Yuan-qing Cui,&ast; Yan-ping Xu,&ast; Jie Chen, Xue-bao Zhang, Xiong Wang Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Wang, Department of Reproductive Medicine, Yantai Yuhuangding Hospital, No. 20, Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email wangxiong01903@163.comIntroduction: Varicocele is a dilatation of the internal spermatic vein and it is generally recognized as one cause of male infertility. This study aimed to analyze the roles of activating transcription factor 6 (ATF-6) in experimental varicocele-induced epididymal epithelial cells.Methods: Experimental left varicocele was established in rats through partial left renal vein ligation. At 8 weeks after surgery, the left epididymal damage was observed using H&E and TUNEL staining. The expressions of neutral α-glucosidase (NAG), ATF-6, tumor necrosis factor (TNF)-α, and phospho-nuclear factor (p-NF)-κB p65 (S536) in the left epididymis were measured by immunohistochemistry. ATF-6 silence in rat epididymal epithelial cells was established by ATF-6 siRNA transfection. The cells were treated with hypoxia for 24 h, and cell viability was measured by CCK-8, levels of NAG, TNF-α, and interleukin (IL)-8 in cells were measured by ELISA, levels of p-NF-κB p65 (S536)/NF-κB p65 protein in cells were measured by Western blotting.Results: The results showed that the experimental left varicocele induced hypertrophy and apoptosis of epididymal epithelial cells (p< 0.05), and decreased the expressions of NAG in the epididymal epithelial cells compared with the sham-operated control rats (p< 0.01). Meanwhile, the expressions of ATF-6, TNF-α, and p-NF-κB p65 (S536) were increased in the epididymal epithelial cells after the experimental left varicocele compared with the sham-operated control rats (p< 0.05). In the hypoxia-treated cells, ATF-6 silence increased the cell viability and decreased the levels of TNF-α, IL-8, and p-NF-κB p65 (S536) compared with the control cells (p< 0.05).Discussion: The ATF-6 pathway was activated in a rat’s left varicocele-induced epididymal damage. Inhibition of the ATF-6 pathway might be a possible novel therapeutic approach for left varicocele-induced epididymal damage.Keywords: epididymal neutral α-glucosidase, hypoxia, left varicocele, nuclear factor-kappa B p65, NF-κB p65

Cong-Cong He, Dong-Mei Lin, Hui-Zhen Liu, Fei-Fei Wang, Xiu-Fang Guo, Xiao-Bo Zhang, Yi-Qin Ai, Li-Min Meng School of Nursing, Gannan Medical University, Ganzhou City, Jiangxi Province, People’s Republic of ChinaCorrespondence: Li-Min Meng, School of Nursing, Gannan Medical University, No. 1 Medical Road, Ganzhou, People’s Republic of China, Tel +86 15970987999, Email 278646437@qq.comBackground: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster.Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients.Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate.Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.Keywords: breast cancer, pain-fatigue-sleep disturbance symptom cluster, nonpharmacological intervention, systematic review, network meta-analysis

Xian-Li Pan,1 Li Nie,1 Shu-Yi Zhao,1 Xiao-Bao Zhang,2 Shan Zhang,2 Zeng-Feng Su2 1Chaohu Hospital Affiliated with Anhui Medical University, Chaohu City, People’s Republic of China; 2Department of General Medicine, Chaohu Hospital Affiliated with Anhui Medical University, Chaohu City, People’s Republic of ChinaCorrespondence: Zeng-Feng Su, Tel +86 0551-82321572, Email suzengfeng@163.comAim: The objective of the study was to clarify the occurrence of atherosclerosis in patients with insomnia.Methods: A total of 60 patients with insomnia and 58 patients in a control group were selected to measure blood glucose, blood lipids and other biochemical and physiological indicators. Brachial-ankle pulse wave velocity (baPWV) was measured to assess arterial stiffness, and color Doppler ultrasound was used to examine carotid artery intima-media thickness (CIMT) and plaque incidence. These indicators were used to determine the occurrence and degree of carotid atherosclerosis, and to compare the differences between the two groups.Results: While there was no significant difference in biochemical or physiological indicators between the two groups (P > 0.05), the baPWV, CIMT, and incidence of carotid plaque in the insomnia group were higher than the control group. In addition, the baPWV, CIMT, and incidence of carotid plaque in the chronic insomnia group were higher than that in the short-term insomnia group. Multiple linear regression analysis was carried out to analyze the effects of insomnia, systolic blood pressure, blood glucose, triglycerides, cholesterol, BMI, age and low-density lipoprotein on atherosclerosis. The results showed that increased CIMT was significantly correlated with insomnia in atherosclerosis group (R2=0.27 on the left, R2=0.37 on the right, P < 0.001).Conclusion: Insomnia correlated with increased arterial stiffness and carotid atherosclerosis, and as the duration of insomnia prolongs, the correlation between them became more obvious.Keywords: insomnia, brachial-ankle pulse wave velocity, carotid intima-media thickness, carotid plaque

Xiang-Cheng Zhi,1–3,* Min Zhang,1–3,* Ting-Ting Meng,1–3,* Xiao-Bei Zhang,1–3 Zhen-Dong Shi,1–3 Yan Liu,1–3 Jing-Jing Liu,1–3 Sheng Zhang,1–3 Jin Zhang1–3 1Third Department of Breast Cancer, People’s Republic of China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, People’s Republic of China; 2Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Tianjin, People’s Republic of China; 3Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: A purpose of this study was to establish a novel molecular diagnostic model and provide new insight into the intraoperative evaluation of the sentinel lymph node (SLN) metastasis in breast cancer. A total of 124 breast cancer patients who met the criteria of sentinel lymph node biopsy (SLNB) and underwent intraoperative biopsy were consecutively enrolled in this study. After the SLNs obtained from each patient were labeled, MOC-31 monoclonal antibody-mediated immunomagnetic separation (IMS) and flow cytometry were used to determine the expressions of breast cancer metastasis-related markers, including Mucin 1 (MUC1), CD44v6, and HER2. Alternatively, conventional intraoperative hematoxylin and eosin (HE) staining and cytokeratin immunohistochemistry (CK-IHC) were performed to detect potential SLN metastasis. The sensitivity, specificity, and false-negative rate of the three intraoperative diagnostic methods were compared and analyzed. A total of 55 positive-SLNs were found in 38 breast cancer patients using IMS, yielding a sensitivity of 86.4% (38/44), specificity of 94.7% (36/38), accuracy of 93.5% (116/124), false-positive rate of 2.5% (2/80), false-negative rate of 13.6% (6/44), positive predictive value of 95.5% (42/44), and negative predictive value of 93.0% (80/86). Patients with high expressions of CD44v6, MUC1, and HER2 in SLNs tended to have higher number of positive lymph nodes, among which the MUC1 and HER2 showed significant differences (P

AbstractCd(OH)2nanobelts have been synthesized in high yield by a convenient polyol method for the first time. XRD, XPS, FESEM, and TEM were used to characterize the product, which revealed that the product consisted of belt-like crystals about 40 nm in thickness and length up to several hundreds of micrometers. Studies found that the viscosity of the solvent has important influence on the morphology of the final products. The optical absorption spectrum indicates that the Cd(OH)2nanobelts have a direct band gap of 4.45 eV.

Aim: Perineal wound complications after abdominoperineal resection (APR) have become a major clinical challenge. Myocutaneous flap closure has been proposed in place of primary closure to improve wound healing. We conducted this comprehensive meta‐analysis to evaluate the current scientific evidence of primary closure vs myocutaneous flap closure of perineal defects following APR for colorectal disease. Methods: We systematically searched the MEDLINE, Embase, PubMed, Web of Science and Cochrane Library databases to identify all relevant studies. After data extraction from the included studies, meta‐analysis was performed to compare perioperative outcomes of primary closure and myocutaneous flap closure. Results: Eighteen studies with a total of 17 913 patients (16 346 primary closure vs 1567 myocutaneous flap closure) were included. We found that primary closure was significantly associated with higher total perineal wound complications (P = 0.007), major perineal wound complications (P < 0.001) and perineal wound infection (P = 0.001). On the other hand, myocutaneous flap closure takes more operation time (P < 0.001) and increases the risk of perineal wound dehiscence (P = 0.01), deep surgical site infection (P < 0.001), enterocutaneous fistulas (P = 0.03) and return to the operating room (P = 0.0005). There were no significant differences between the two groups for other outcomes. Conclusions: This is the first systematic review with meta‐analysis comparing primary closure with myocutaneous flap closure of perineal defects after APR for colorectal disease. Although taking more operation time and an increased risk of specific complications, the pooled results have validated the use of myocutaneous flaps for reducing total/major perineal wound complications. More investigations are needed to draw definitive conclusions on this dilemma. [ABSTRACT FROM AUTHOR]

Organic luminophores have been widely utilized in cells and in vivo fluorescence imaging but face extreme challenges, including a low signal-to-noise ratio (SNR) and even false signals, due to non-negligible background signals derived from real-time excitation lasers. To overcome these challenges, in the last decade, functionalized organic long-persistent luminophores have gained much attention. Such luminophores could not only overcome the biological toxicity of inorganic long-persistent luminescent materials (metabolic toxicity and leakage risk of inorganic heavy metals), but also continue to emit long-persistent luminescence after removing the excitation source, thus effectively improving imaging quality. More importantly, organic long-persistent luminophores have good structure tailorability for the construction of activable probes, which is favorable for biosensing. Recently, the development of reactive oxygen species (ROS)-mediated long-persistent (ROSLP) luminophores (especially organic small-molecule ROSLP luminophores) is still in the rising stage. Notably, ROSLP luminophores for in vivo imaging have experienced from two-component separated nano-systems to integrated uni-luminophores, which obtained gradually better designability and biocompatibility. In this review, we summarize the progress and challenges of organic long-persistent luminophores, focusing on their development history, long-persistent luminescence working mechanisms, and biomedical applications. We hope that these insights will help scientists further develop functionalized organic long-persistent luminophores for the biomedical field.

Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O 2 ⋅ - /GSH, enabling real-time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide and dual oxidative stress-responsive catechol moieties, facilitates NE-mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685 nm (PA 685 ). Furthermore, oxidation and reduction of catechol groups by O 2 ⋅ - and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA 745 /PA 685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug-treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques., (© 2024 Wiley-VCH GmbH.)

CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors. Highlights Established a p21-mNeonGreen reporter iPSC line to track activation of the TP53-p21 pathway. Found a direct correlation between p21-mNeonGreen expression and indel frequencies, aiding in gRNA screening. Showed that LVs are preferable over AAVs for certain cells due to lower p21 activation, with viral promoter choice impacting p21 response., (© The Author(s) 2024. Published by Oxford University Press.)

Low sensitivity, photobleaching, high-power excitation and long acquisition times constrain the utility of afterglow luminescence. Here we report the design and imaging performance of nanoparticles made of electron-rich trianthracene derivatives that, on excitation by room light at ultralow power (58 μW cm -2 ), emit afterglow luminescence at ~500 times those of commonly used organic afterglow nanoparticles. The nanoparticles' ultrabright afterglow allowed for deep-tissue imaging (up to 6 cm), for ultrafast afterglow imaging (at short acquisition times down to 0.01 s) of naturally behaving mice with negligible photobleaching, even after re-excitation for over 15 cycles, and for the accurate visualization of subcutaneous and orthotopic tumours and of plaque in carotid arteries. We also show that an afterglow nanoparticle that is activated only in the presence of granzyme B allowed for the tracking of granzyme-B activity in the context of therapeutic monitoring. The high sensitivity and negligible photobleaching of the organic afterglow nanoparticles offer advantages for real-time in vivo monitoring of physiopathological processes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To evaluate the accuracy and parsing ability of GPT 4.0 for Japanese medical practitioner qualification examinations in a multidimensional way to investigate its response accuracy and comprehensiveness to medical knowledge., Methods: We evaluated the performance of the GPT 4.0 on Japanese Medical Licensing Examination (JMLE) questions (2021-2023). Questions are categorized by difficulty and type, with distinctions between general and clinical parts, as well as between single-choice (MCQ1) and multiple-choice (MCQ2) questions. Difficulty levels were determined on the basis of correct rates provided by the JMLE Preparatory School. The accuracy and quality of the GPT 4.0 responses were analyzed via an improved Global Qualily Scale (GQS) scores, considering both the chosen options and the accompanying analysis. Descriptive statistics and Pearson Chi-square tests were used to examine performance across exam years, question difficulty, type, and choice. GPT 4.0 ability was evaluated via the GQS, with comparisons made via the Mann-Whitney U or Kruskal-Wallis test., Results: The correct response rate and parsing ability of the GPT4.0 to the JMLE questions reached the qualification level (80.4%). In terms of the accuracy of the GPT4.0 response to the JMLE, we found significant differences in accuracy across both difficulty levels and option types. According to the GQS scores for the GPT 4.0 responses to all the JMLE questions, the performance of the questionnaire varied according to year and choice type., Conclusion: GTP4.0 performs well in providing basic support in medical education and medical research, but it also needs to input a large amount of medical-related data to train its model and improve the accuracy of its medical knowledge output. Further integration of ChatGPT with the medical field could open new opportunities for medicine., (© 2024. Huazhong University of Science and Technology.)

Mature microRNAs play crucial roles in tumorigenesis and progression. However, their potential as cancer biomarkers is limited by the sequence interference of precursor microRNAs and the occurrence of false positive signals mediated by single microRNAs. Herein, we reported a dual mature microRNA-responsive second-order (YES-AND) logic biosensing platform for accurate cancer diagnosis. Specifically, DNA nanocages were conceived as the first stage of "YES" gates, capable of signal transduction through strand displacement reactions, and realizing size-selective discrimination of mature microRNAs and pre-microRNAs. Subsequently, CRISPR/Cas12a system served as the second stage of "AND" gate, wherein dual activators cooperatively triggered trans-cleavage. As a proof-of-concept, this second-order logic biosensing platform was successfully applied to detect non-small cell lung cancer-related mature microRNA in clinical serum, and showed remarkable sensitivity (Lod = 100 pM) and trueness (recovery ≥90 %). Our study represents a significant step forward in the development of intelligent biosensors capable of performing complex computations within pathological networks, and opens up broader possibilities for applications in biological science study and clinic disease diagnosis., 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: Edaravone is utilized in intra-cerebral hemorrhage (ICH) patients for years, while personalized variances were observed in clinic. To explore the precision medicine strategy for Edaravone, this study investigated the association between genetic polymorphisms and Edaravone efficacy in ICH patients., Methods: We genotyped 7 SNPs in 4 potential genes, including COL4A2, TNF, WNK2 and IL6, from the peripheral blood of 217 ICH patients with or without Edaravone utilizations. PLINK and SPSS were utilized for association tests, Student's t tests, Mann-Whitney U tests and Chi-square tests., Results: Rs1800796 (C>G) in IL6 (OR: 0.41, 95 % CI: 0.18-0.94, p-value = 0.03) and rs16936752 (G>T) in WNK2 (OR: 0.28, 95 % CI: 0.09-0.88, p-value = 0.02) were found to be significantly associated with Edaravone efficacy. The association of rs1800796 and rs16936752 were found to be different in patients with or without smoking habit, alcohol drinking habit, hypertension history and hyperlipemia history were found to be different. Both of these two SNPs were found to be associated with the concentration of high-density lipoprotein cholesterol (HDL) in ICH patients., Conclusions: The IL6 rs1800796 and the WNK2 rs16936752 could be useful biomarkers for prognosis prediction during Edaravone treatment. These SNPs should be considered in the personalized medicine strategy for Edaravone in the future., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and β-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.

Prussian blue analogs (PBAs) are promising insertion-type cathode materials for different types of aqueous batteries, capable of accommodating metal or non-metal ions. However, their practical application is hindered by their susceptibility to dissolution, which leads to a shortened lifespan. Herein, we have revealed that the dissolution of PBAs primarily originates from the locally elevated pH of electrolytes, which is caused by the proton co-insertion during discharge. To address this issue, the water-locking strategy has been implemented, which interrupts the generation and Grotthuss diffusion of protons by breaking the well-connected hydrogen bonding network in aqueous electrolytes. As a result, the hybrid electrolyte enables the iron hexacyanoferrate to endure over 1000 cycles at a 1 C rate and supports a high-voltage pH-decoupled cell with an average voltage of 1.95 V. These findings provide insights for mitigating the dissolution of electrode materials, thereby enhancing the viability and performance of aqueous batteries., (© 2024 Wiley-VCH GmbH.)

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury., (© 2024 Wiley-VCH GmbH.)

Purpose: To compare the clinical efficacy of 3D-printed artificial discs with that of ACDF for treating cervical spondylosis., Methods: This was a retrospective analysis of 73 patients with single-level cervical spondylosis who met the inclusion criteria between January 2020 and December 2022 at XX Hospital. The patients were divided: 38 patients in the ACDF group and 35 patients in the CADR group. Patient general information, including operation time and intraoperative blood loss, was collected. The clinical effect of the combination therapy was evaluated by the VAS, JOA, and NDI. The radiological effect was evaluated using the ROM test. Ethics No. 201,606,009., Results: The average follow-up times in the ACDF and CADR groups were 28.24 ± 4.65 and 29.11 ± 5.06 months, respectively (P = 0.443). Clinical symptoms (evaluated by VAS, NDI, and JOA) are significantly improved in both the ACDF and CADR groups with similar efficacy. The preoperative ROM of the ACDF group was 40.03 ± 8.79, while that of the CADR group was 42.11 ± 7.98 (P = 0.293). However, the postoperative ROM in the ACDF group was 35.29 ± 7.23, which was lower than that in the CADR group (40.43 ± 6.98) (P = 0.003). Furthermore, only one patient in the ACDF group experienced mild dysphagia after surgery, and the patient recovered within three days. ASD occurred in nine patients in the ACDF group and in two patients in the CADR group (Χ²=4.597, P = 0.032)., Conclusions: Compared with ACDF, 3D-printed artificial discs for treating single-level cervical spondylosis have proven to be clinically effective; it associated with less blood loss and a lower incidence of ASD, and maintain a better cervical ROM., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

In the pursuit of next-generation ultrahigh-energy-density Li-O 2 batteries, it is imperative to develop an electrolyte with stability against the strong oxidation environments. N,N-dimethylacetamide (DMA) is a recognized solvent known for its robust resistance to the highly reactive reduced oxygen species, yet its application in Li-O 2 batteries has been constrained due to its poor compatibility with the Li metal anode. In this study, a rationally selected hydrofluoroether diluent, methyl nonafluorobutyl ether (M3), has been introduced into the DMA-based electrolyte to construct a localized high concentration electrolyte. The stable -CH 3 and C-F bonds within the M3 structure could not only augment the fundamental properties of the electrolyte but also fortify its resilience against attacks from O 2 - and 1 O 2 . Additionally, the strong electron-withdrawing groups (-F) presented in the M3 diluent could facilitate coordination with the electron-donating groups (-CH 3 ) in the DMA solvent. This intermolecular interaction promotes more alignments of Li + -anions with a small amount of M3 addition, leading to the construction of an anion-derived inorganic-rich SEI that enhances the stability of the Li anode. As a result, the Li-O 2 batteries with the DMA/M3 electrolyte exhibit superior cycling performance at both 30 °C (359 th ) and -10 °C (120 th )., (© 2024 Wiley-VCH GmbH.)

Background: Pulmonary nocardiosis (PN) is a rare and opportunistic infection. This study aimed to analyze clinical, radiological, and microbiological features, treatment and outcome of PN in southern china., Methods: Clinical, laboratory, imaging, treatment and outcome data of PN patients at two tertiary hospitals from January 1, 2018, to January 1, 2024 were collected. Factors associated with clinical outcomes were determined by multivariate logistic regression analysis., Results: 67 PN patients including 53 with clinical improvement and 14 with treatment failure were enrolled. Bronchiectasis was the most common respiratory disease in patients with PN (31.3%). The major symptoms of PN were cough (89.6%) and sputum (79.1%). Lung nodules, bronchiectasis, consolidation, pleural involvement, mass, cavity, and lymph node enlargement were the frequent computed tomography findings of PN. Among the Nocardia species detected, N. farcinica was the most common pathogen. Neutrophil-to-lymphocyte ratio (OR = 1.052, p = 0.010), concurrent bacterial infection (OR = 7.706, p = 0.016), and the use of carbapenems (OR = 9.345, p = 0.023) were independently associated with poor prognosis in patients with PN., Conclusions: This study provides important insights into the clinical features of PN in southern china. neutrophil-to-lymphocyte ratio, concurrent bacterial infection, and the use of carbapenems were independently associated with poor prognosis in patients with PN., (© 2024. The Author(s).)

Immune checkpoints blockade (ICB) therapies have demonstrated remarkable clinical success in treating cancer. However, its objective response rate remains suboptimal because current therapies rely on limited immune checkpoints that failed to cover the multiple immune evasion pathways of cancer. To explore potential ICB strategies, herein, we propose a glycoimmune checkpoint elimination (glycoICE) therapy depending on targeted edition of sialoglycans on tumor cell surface using aptamer-enzyme chimera (ApEC). The ApEC is readily generated via a one-step bioorthogonal procedure, allowing for large-scale and uniform production. The ApEC is able to target and desialylate cancer cells, leading to the elimination of sialoglycan-Siglec axis, which in turn activates immune cells and enhances immunotherapy efficiency. In addition to its remarkable therapeutic efficiency, the ApEC exhibits high tumor selectivity, which helps to avoid side effects caused by indiscriminate desialylation of normal tissues. Furthermore, the ApEC has the potential to be a versatile platform for specifical editing of sialoglycans in different tumor models by adjusting the aptamer sequences targeting associated with specific protein markers. This research not only introduces a novel molecular tool for the effective editing of sialoglycans in complex environments, but also provides valuable insights for advancing DNA-based drugs towards in vivo and clinical applications., (© 2024 Wiley‐VCH GmbH.)

Inspired by efficient natural biomolecule assembly with precise control on key parameters such as distance, number, orientation, and pattern, the constructions and applications of artificial precise molecule assembly are highly important in many research areas including chemistry, biology, and medicine. DNA origami, a sophisticated DNA nanotechnology with rational design, can offer a predictable, programmable, and addressable nanoscale scaffold for the precise assembly of various kinds of molecules. Herein, we summarize recent progress, particularly in the last three years, in DNA-origami-based precise molecule assembly and their emerging biological applications. We first introduce DNA origami and the progress on DNA-origami-based precise molecule assembly, including assembly of various kinds of molecules (e.g., nucleic acids, proteins, organic molecules, nanoparticles), and precise control of important parameters (e.g., distance, number, orientation, pattern). Their biological applications in sensing, imaging, therapy, bionics, biophysics, and chemical biology are then summarized, and current challenges and opportunities are finally discussed.

Objective: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms., Methods: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-β 1 (TGF-β 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-β 1, TGF-β 1+10% DMS, TGF-β 1+10% DMS+miR-29b-2-5p inhibitor, TGF-β 1+10% DMS+inhibitor negative control, TGF-β 1+10% DMS+miR-29b-2-5p mimic and TGF-β 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA., Results: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01)., Conclusions: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.