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Objective: The purpose of this study was to evaluate the value of asymmetry values, gain, and pathological saccades of the video head impulse test (vHIT) in sudden sensorineural hearing loss (SSNHL)., Study Design: Retrospective study., Setting: Tertiary referral center., Patients: A total of 226 individuals diagnosed with unilateral definite SSNHL were hospitalized. The assessment included a comprehensive evaluation of medical history, pure-tone test, acoustic impedance, positional test, video nystagmography (VNG), vHIT, vestibular evoked myogenic potentials (VEMPs) and magnetic resonance., Interventions: vHIT, VNG, cVEMP, oVEMP. Statistical analysis was performed with SPSS version 22.0 for Windows., Main Outcome Measures: The asymmetry values, gain, and pathological saccades of the vHIT., Results: The abnormal gain of vHIT in anterior, horizontal, and posterior canal in SSNHL patients with vertigo were revealed in 20 of 112 (17.9%), 24 of 112 (21.4%), and 60 of 112 (53.6%), respectively. The vHIT pathological saccades (overt + covert) of anterior, horizontal, and posterior canal in SSNHL patients with vertigo were observed in 5 of 112 (4.6%), 52 of 112 (46.4%), and 58 of 112 (51.8%), respectively. Multivariate analysis indicated that the prognosis of patients with vertigo was correlated with vHIT gain of posterior canal, pathological saccade in horizontal canal, asymmetric ratio of horizontal canal gain, asymmetric ratio of posterior canal gain, Canal paresis (%) on caloric test and spontaneous nystagmus., Conclusion: In the vHIT of patients with SSNHL with vertigo, the posterior canal is most easily affected. Reduced gain of posterior canal, pathological saccade of horizontal canal, and larger asymmetric gain of posterior canal and horizontal canal may be negative prognostic factors., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Objective: To develop a model that integrates radiomics features and clinical factors to predict upper gastrointestinal bleeding (UGIB) in patients with decompensated cirrhosis., Methods: 104 decompensated cirrhosis patients with UGIB and 104 decompensated cirrhosis patients without UGIB were randomized according to a 7:3 ratio into a training cohort ( n  = 145) and a validation cohort ( n  = 63). Radiomics features of the abdominal skeletal muscle area (SMA) were extracted from the cross-sectional image at the largest level of the third lumbar vertebrae (L3) on the abdominal unenhanced multi-detector computer tomography (MDCT) images. Clinical-radiomics nomogram were constructed by combining a radiomics signature (Rad score) with clinical independent risk factors associated with UGIB. Nomogram performance was evaluated in calibration, discrimination, and clinical utility., Results: The radiomics signature was built using 11 features. Plasma prothrombin time (PT), sarcopenia, and Rad score were independent predictors of the risk of UGIB in patients with decompensated cirrhosis. The clinical-radiomics nomogram performed well in both the training cohort (AUC, 0.902; 95% CI, 0.850-0.954) and the validation cohort (AUC, 0.858; 95% CI, 0.762-0.953) compared with the clinical factor model and the radiomics model and displayed excellent calibration in the training cohort. Decision curve analysis (DCA) demonstrated that the predictive efficacy of the clinical-radiomics nomogram model was superior to that of the clinical and radiomics model., Conclusion: Clinical-radiomics nomogram that combines clinical factors and radiomics features has demonstrated favorable predictive effects in predicting the occurrence of UGIB in patients with decompensated cirrhosis. This helps in early diagnosis and treatment of the disease, warranting further exploration and research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, He, Yang, Zhu, Li, Lei, Tang and Peng.)

Precise and reliable monitoring of DNA adenine methyltransferase (Dam) activity is essential for disease diagnosis and biological analysis. However, existing techniques for detecting Dam activity often rely on specific DNA recognition probes that are susceptible to DNA degradation and exhibit limited target sensitivity and specificity. In this study, we designed and engineered a stable and dynamic DNA nanodevice called the d ouble-l o op interl o cked DNA ci r cuit (DOOR) that enables the sensitive and selective monitoring of Dam activity in complex biological environments. The DOOR incorporates two interlocked specialized sequences: a palindromic sequence for Dam identification and an initiator sequence for signal amplification. In the presence of Dam, the DOOR is cleaved by double-stranded DNA phosphodiesterase I endonuclease, generating massive double-stranded DNA (dsDNA) units. These units can self-assemble into a long dsDNA scaffold, thereby enhancing the subsequent reaction kinetics. The dsDNA scaffold further triggers a hyperbranched hybrid chain reaction to produce a fluorescent 3D DNA nanonet, enabling more precise monitoring of the Dam activity. The DOOR device exhibits excellent sensitivity, specificity, and stability, rendering it a powerful tool for studying DNA methylation in various biological processes and diseases.

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC 50 ) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy., 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 Inc. All rights reserved.)

Background: Anxiety and depression are common comorbidities in idiopathic pulmonary fibrosis (IPF) that impair health-related quality of life. However, there is a lack of studies focusing on the mental disorder of IPF after antifibrotic treatment and their related predictive factors., Methods: Patients with an initial diagnosis of IPF were enrolled. Data on demographics, lung function, Generalized Anxiety Disorder-7 (GAD-7) Scale, Patient Health Questionnaire 9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and St. George's Respiratory Questionnaire total score(SGRQ-T) were collected. Changes in anxiety, depression, somatic symptoms, and quality of life scores before and after nintedanib treatment were compared, and the related predictive factors were analyzed., Results: A total of 56 patients with a first diagnosis of IPF were enrolled, with 42 and 35 patients suffering from anxiety and depression, respectively. The GAD-7, PHQ-9, PHQ-15, and SGRQ scores were higher in the anxiety and depression groups. SGRQ total score (SGRQ-T) [OR = 1.075, 95%CI= (1.011, 1.142)] was an independent predictor of IPF combined with anxiety ( p  < 0.05); SGRQ-T [OR = 1.080, 95%CI= (1.001, 1.167)] was also an independent predictor of IPF combined with depression ( p  < 0.05). After treatment, GAD-7, PHQ-9, PHQ-15, and SGRQ scores decreased ( p  < 0.05). ΔSGRQ-T significantly affected ΔGAD-7 (β = 0.376, p  = 0.009) and ΔPHQ-9 (β = 0.329, p  = 0.022)., Conclusion: Anxiety and depression in IPF patients are closely related to somatic symptoms, pulmonary function, and quality of life. The SGRQ-T score is of great value for assessing anxiety and depression in patients with IPF. Short-term treatment with nintedanib antifibrotic therapy can alleviate anxiety and depression in IPF patients.

Grape ripe rot is one of the most important diseases caused by Colletotrichum spp. Chinese wild grape (Vitis davidii) is highly resistant to Colletotrichum viniferum infection. But mechanisms underlying the resistance remain largely unclear. In this study, transcriptomic and metabolomic responses of V. davidii to C. viniferum were studied before and after 1, 2, 4, and 6 days of inoculation. C. viniferum infection induced the expression of a large number of defense-related genes. KEGG analysis indicated that the differentially expressed genes (DEGs) were largely those involved in alpha-linolenic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, stilbenoid biosynthesis, and other defense-related metabolic pathways. Based on transcriptome data and experimental analysis, we found that jasmonic acid (JA) biosynthesis was closely related to V. davidii resistance to C. viniferum. In addition, many genes related to the synthesis of lignin and phytoalexin resveratrol are upregulated by pathogen infection, and metabolomic analysis showed that there was an increasing accumulation of resveratrol on day 6 of C. viniferum inoculation. Further analysis indicated that transcription factors, such as VdWRKY75 regulated the biosynthesis of lignin and stilbenes. A working model for V. davidii against C. viniferum infection was proposed. The infection of C. viniferum induced JA production, JA along with transcription factors regulated the biosynthesis of secondary metabolites, such as lignin and resveratrol that enhanced plant resistance to C. viniferum. This study elucidated molecular mechanisms underlying the resistance of Chinese wild V. davidii to C. viniferum which can provide a theoretical basis for grape disease resistance breeding., 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 Masson SAS. All rights reserved.)

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8 -/- mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8 +/+ mice, Irf8 -/- mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Two new oxidovanadium(V) complexes, [VO2L1] (1) and [V2O2(μ-O)2L2)] (2), where L1 and L2 are the deprotonated form of 5-bromo-2-(((2-(pyrrolidin-1-yl)ethyl)imino)methyl)phenol (HL1) and 5-bromo-2-(((2-((2-hydroxyethyl)amino)ethyl)imino)methyl)phenol (HL2), respectively, have been synthesized and structurally characterized by physico-chemical methods and single crystal X-ray determination. X-ray analysis indicates that the V atom in complex 1 is in square pyramidal coordination, and those in complex 2 are in octahedral coordination. Crystal structures of the complexes are stabilized by hydrogen bonds. The catalytic property for epoxidation of styrene by the complexes was evaluated.

Background: To investigate factors associated with different reproductive outcomes in patients with Caesarean scar pregnancies (CSPs)., Methods: Between May 2017 and July 2022, 549 patients underwent ultrasound-guided uterine aspiration and laparoscopic scar repair at the Gynaecology Department of Hubei Maternal and Child Health Hospital. Ultrasound-guided uterine aspiration was performed in patients with type I and II CSPs, and laparoscopic scar repair was performed in patients with type III CSP. The reproductive outcomes of 100 patients with fertility needs were followed up and compared between the groups., Results: Of 100 patients, 43% had live births (43/100), 19% had abortions (19/100), 38% had secondary infertility (38/100), 15% had recurrent CSPs (RCSPs) (15/100). The reproductive outcomes of patients with CSPs after surgical treatment were not correlated with age, body mass index, time of gestation, yields, abortions, Caesarean sections, length of hospital stay, weeks of menopause during treatment, maximum diameter of the gestational sac, thickness of the remaining muscle layer of the uterine scar, type of CSP, surgical method, uterine artery embolisation during treatment, major bleeding, or presence of uterine adhesions after surgery. Abortion after treatment was the only risk factor affecting RCSPs (odds ratio 11.25, 95% confidence interval, 3.302-38.325; P < 0.01) and it had a certain predictive value for RCSP occurrence (area under the curve, 0.741)., Conclusions: The recurrence probability of CSPs was low, and women with childbearing intentions after CSPs should be encouraged to become pregnant again. Abortion after CSP is a risk factor for RCSP. No significant difference in reproductive outcomes was observed between the patients who underwent ultrasound-guided uterine aspiration and those who underwent laparoscopic scar repair for CSP., (© 2024. The Author(s).)

Purpose: To investigate the value of a multimodal deep learning (MDL) model based on computed tomography (CT) and magnetic resonance imaging (MRI) for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC)., Methods: A total of 287 patients with HCC from our institution and 58 patients from another individual institution were included. Among these, 119 patients with only CT data and 116 patients with only MRI data were selected for single-modality deep learning model development, after which select parameters were migrated for MDL model development with transfer learning (TL). In addition, 110 patients with simultaneous CT and MRI data were divided into a training cohort (n = 66) and a validation cohort (n = 44). We input the features extracted from DenseNet121 into an extreme learning machine (ELM) classifier to construct a classification model., Results: The area under the curve (AUC) of the MDL model was 0.844, which was superior to that of the single-phase CT (AUC = 0.706-0.776, P < 0.05), single-sequence MRI (AUC = 0.706-0.717, P < 0.05), single-modality DL model (AUC all-phase CT  = 0.722, AUC all-sequence MRI  = 0.731; P < 0.05), clinical (AUC = 0.648, P < 0.05), but not to that of the delay phase (DP) and in-phase (IP) MRI and portal venous phase (PVP) CT models. The MDL model achieved better performance than models described above (P < 0.05). When combined with clinical features, the AUC of the MDL model increased from 0.844 to 0.871. A nomogram, combining deep learning signatures (DLS) and clinical indicators for MDL models, demonstrated a greater overall net gain than the MDL models (P < 0.05)., Conclusion: The MDL model is a valuable noninvasive technique for preoperatively predicting MVI in HCC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI)., Aim of the Study: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method.", Materials and Methods: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1β, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1 H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis., Results: Eleven key anti-inflammatory targets of IL6, IL-1β, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism., Conclusions: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI., 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.)

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results., Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system., Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning., Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest., Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation., Competing Interests: Conflict of InterestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve (IAN)., Aim: To proposes a method for the partial grinding of an impacted mandibular third molar (IMM3) near the IAN to prevent IAN injury during IMM3 extraction., Methods: Between January 1996 and March 2022, 25 patients with IMM3 roots near the IAN were enrolled. The first stage of the operation consisted of grinding a major part of the IMM3 crown with a high-speed turbine dental drill to achieve sufficient space between the mandibular second molar and IMM3. After 6 months, when the root tips were observed to be away from the IAN on X-ray examination, the remaining part of the IMM3 was completely removed., Results: All IMM3s were extracted easily without symptoms of IAN injury after extraction., Conclusion: Partial IMM3 grinding may be a good alternative treatment option to avoid IAN injury in high-risk cases., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: As a traditional Chinese medicine, leech has obvious pharmacological activities in anticoagulantion and antithrombosis. Whitmania pigra Whitman (WP) is the most commonly used leech in the Chinese market. It is often used in clinical applications after high-temperature processing by talcum powder to remove the fishy taste and facilitate crushing. The anticoagulant and thrombolytic active ingredients are protein and polypeptide, which may denaturate and lose activity after high-temperature processing. The rationality of its processing has been questioned in recent years. This study aims to investigate the effect of talcum powder scalding on the antithrombotic activity of WP in vivo and to discuss its pharmacodynamic mechanism in vivo ., Methods: Raw and talcum-powdered processed WP were administered intragastrically for 14 days, and carrageenan was injected intraperitoneally to prepare a mouse model of tail vein thrombosis. The incidence rate of tail vein thrombosis and the thrombus area under pathological tissue sections were calculated to evaluate the antithrombotic effect between raw and processed WP. Non-targeted metabolomics was conducted using UPLC-Q-TOF/MS technology to analyze the changes of small molecule metabolites in the body after administration of WP., Results: After intragastric administration, both the raw product and the processed product of WP could inhibit the thrombosis induced by carrageenan, and the processed product had a more apparent antithrombotic effect than the raw product. The administration of WP could regulate the changes of some small molecular metabolites, such as amino acids, lipids, and steroids, in Sphingolipid metabolism and Glycerophospholipid metabolism., Conclusions: Based on the results of pharmacodynamics and metabolomics, processed WP will not reduce the antithrombotic activity of WP. This study provided a scientific basis for the rational use of leeches., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8 + T cells and accelerating apoptosis in CD8 + T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells., (© 2024. The Author(s).)

Vascular aging is an independent risk factor for age-related diseases and a specific type of organic aging. Endothelial progenitor cells (EPCs), a type of bone marrow stem cell, has been linked to vascular aging. The purpose of this study is to investigate if Ginseng-Sanqi-Chuanxiong (GSC) extract, a traditional Chinese medicine, can delay aortic aging in mice by enhancing the performance and aging of EPCs in vivo and to analyze the potential mechanisms through a d-Galactose (D-gal)-induced vascular aging model in mice. Our study revealed that GSC extracts not only enhanced the aortic structure, endothelial function, oxidative stress levels, and aging in mice, but also enhanced the proliferation, migration, adhesion, and secretion of EPCs in vivo, while reducing the expression of p53, p21, and p16. To conclude, GSC can delay vascular senescence by enhancing the function and aging of EPCs, which could be linked to a decrease in p16 and p53/p21 signaling. Consequently, utilizing GSC extracts to enhance the function and senescence of autologous EPCs may present a novel avenue for enhancing autologous stem cells in alleviating senescence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In recent years, remarkable advancements have been achieved in the field of halide perovskite solar cells (PSCs). However, the commercialization of PSCs has been impeded by challenges such as Pb leakage and the instability of hybrid organic-inorganic perovskites (HOIPs). Hence, the future lies in the development of environmentally friendly inorganic lead-free halide perovskites (LFHPs) based on elements like Sn, Ge, Bi, Sb, and Cu, which show great promise for photovoltaic applications. However, LFHP photovoltaic cells still face challenges such as low efficiency, poor film quality, and stability in comparison to HOIPs. These limitations significantly hinder their further development. To address these issues, element doping strategies, including cationic and anionic doping, as well as the use of additives, are frequently employed. These strategies aim to improve film quality, passivate defects, reduce the band gap, and enhance device performance and stability. In this paper, we aim to provide a comprehensive review of the recent research progress in doping strategies for LFHPs.

Background: Differentiating adrenal adenomas from metastases poses a significant challenge, particularly in patients with a history of extra-adrenal malignancy. This study investigates the performance of three-phase computed tomography (CT) based robust federal learning algorithm and traditional deep learning for distinguishing metastases from benign adrenal lesions., Material and Methods: This retrospective analysis includes 1187 instances who underwent three-phase CT scans between January 2008 and March 2021, comprising 720 benign lesions and 467 metastases. Utilizing the three-phase CT images, both a Robust Federal Learning Signature (RFLS) and a traditional Deep Learning Signature (DLS) were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression. Their diagnostic capabilities were subsequently validated and compared using metrics such as the Areas Under the Receiver Operating Curve (AUCs), Net Reclassification Improvement (NRI), and Decision Curve Analysis (DCA)., Results: Compared with DLS, the RFLS showed better capability in distinguishing metastases from benign adrenal lesions (average AUC: 0.816 vs.0.798, NRI = 0.126, P < 0.072; 0.889 vs.0.838, NRI = 0.209, P < 0.001; 0.903 vs.0.825, NRI = 0.643, p < 0.001) in the four-testing cohort, respectively. DCA showed that the RFLS added more net benefit than DLS for clinical utility. Moreover, Comparison with state-of-the-art federal learning methods, the results once again confirmed that the RFLS significantly improved the diagnostic performance based on three-phase CT (AUC: AP, 0.727 vs. 0.757 vs. 0.739 vs. 0.796; PCP, 0.781 vs. 0.851 vs. 0.790 vs. 0.882; VP, 0.789 vs. 0.814 vs. 0.779 vs. 0.886)., Conclusion: RFLS was superior to DLS for preoperative distinguishing metastases from benign adrenal lesions with multi-phase CT Images., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To describe the impact of comorbidities on in-hospital mortality and overall survival in patients with acute mesenteric ischemia (AMI) due to superior mesentery artery (SMA) thromboembolism., Methods: A retrospective study was conducted for 40 patients with AMI due to SMA thromboembolism who were treated in our hospital between February 2013 and December 2019. The presence of comorbidities was described and their severities were classified into 1-4 levels by Geriatric Index of Comorbidity (GIC), the comorbidities were defined as any distinct additional clinical entity that has existed. Univariate and cox proportional-hazards analyses were performed to determine the effect of comorbidities on in-hospital mortality and overall survival., Results: During a mean follow-up of 15.05 ± 18.02 months (range from 0.3 to 58 months) for the 40 patients with AMI due to SMA thromboembolism, In-hospital mortality rate was 52.5% (21/40). One-year, 2-year, and 3-year overall estimated survival rates by the Kaplan-Meier method were 45%, 34%, and 26.5%, respectively, the average overall survival time was 20.84 ± 3.95 (95% CI: 13.10-28.58) months. In-hospital mortality was significantly related to the GIC classification ( χ 2 = 7.86, p = 0.049). The average overall survival was significantly related to the malignant tumor in pre-existing comorbidities and GIC classification (log-rank, p = 0.001). Cox proportional-hazards regressions analysis showed that the class 4 of comorbidities was an independent prognostic factor of mortality ( p = 0.031, HR = 10.45 [95% CI: 1.24-87.70])., Conclusion: Comorbidity is common and an important factor associated with all-cause mortality in AMI patients due to SMA thromboembolism. In managing AMI patients, we recommend a timely diagnosis of both AMI condition and its associated comorbidities., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Two isoreticular metal-organic frameworks (MOFs) constructed from M 8 (OH) 4 (H 2 O) 2 (pyz) 12 (M = Co, Ni; pyz = pyrazolate) secondary building units (SBUs) and Ni(salen)-derived metalloligands were synthesized. The two MOFs were found to be highly stable in a wide pH and temperature range. Together with the tetrabutylammonium bromide (TBAB) co-catalyst, they catalysed the cycloaddition of CO 2 to epoxides with near-quantitative yields and easy recyclability for at least 11 cycles.

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients., Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3)., Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05)., Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bu et al.)

Here we report for the first time the phenomenon of continuously color-tunable electrochemiluminescence (ECL) from individual gold nanoclusters (Au NCs) confined in a porous hydrogel matrix by adjusting the concentration of the co-reactant. Specifically, the hydrogel-confined Au NCs exhibit strong dual-color ECL in an aqueous solution with triethylamine (TEA) as a co-reactant, with a record-breaking quantum yield of 95%. Unlike previously reported Au NCs, the ECL origin of the hydrogel-confined Au NCs is related to both the Au(0) kernel and the Au(i)-S surface. Surprisingly, the surface-related ECL of Au NCs exhibits a wide color-tunable range of 625-829 nm, but the core-related ECL remains constant at 489 nm. Theoretical and experimental studies demonstrate that the color-tunable ECL is caused by the dynamic surface reconstruction of Au NCs and TEA radicals. This work opens up new avenues for dynamically manipulating the ECL spectra of core-shell emitters in biosensing and imaging research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Renal cell carcinoma is the most common and most lethal genitourinary tumor. The causes of renal clear cell carcinoma are complex and the heterogeneity of the tumor tissue is high, so patient outcomes are not very satisfactory. Exploring biomarkers in the progression of renal clear cell carcinoma is crucial to improve the diagnosis and guide the treatment of renal clear cell carcinoma. LRP6 is a co-receptor of the Wnt/β-catenin signaling pathway, which is involved in cell growth, inflammation and cell transformation through activation of the Wnt/β-catenin signaling pathway. Abnormal expression of LRP6 is associated with the malignant phenotype, metastatic potential and poor prognosis of various tumors. In this study, we found that LRP6 was abnormally highly expressed in a variety of tumors and significantly correlated with microsatellite instability, tumor mutation burden, and immune cell infiltration and immune checkpoint expression in a variety of tumors. Moreover, we found that LRP6 was significantly associated with the prognosis of renal clear cell carcinoma. Further we found a significant correlation between LRP6 and the expression of m6A-related genes and ferroptosis-related genes. Finally, we also found a significant correlation between the expression of LRP6 and the sensitivity to common drugs used in kidney clear cell carcinoma treatment. These results suggest that LRP6 is likely to be a potential target for kidney clear cell carcinoma treatment.

Keloids are benign skin tumors characterized by excessive fibroblast proliferation and collagen deposition. The current treatment of keloids with hormone drug injection, surgical excision, radiotherapy, physical compression, laser therapy, cryotherapy often have unsatisfactory outcomes. The phytochemical compounds have shown great potential in treating keloids. Tripterine, a natural triterpene derived from the traditional Chinese medicine Thunder God Vine (Tripterygium wilfordii), was previously reported to exhibit an anti-scarring bioactivity in mouse embryonic fibroblast NIH/3T3 cells. Accordingly, our study was dedicated to explore its role in regulating the pathological phenotypes of keloid fibroblasts. Human keloid fibroblasts were treated with tripterine (0-10 μM) for 24 hours. Cell viability, proliferation, migration, apoptosis, and extracellular matrix (ECM) deposition were determined by CCK-8, EdU, wound healing, Transwell, flow cytometry, western blotting, and RT-qPCR assays. The effects of tripterine treatment on reactive oxygen species (ROS) generation and JNK activation in keloid fibroblasts were assessed by DCFH-DA staining and western blotting analysis. Tripterine at the concentrations higher than 4 μM attenuated the viability of human keloid fibroblasts in a dose-dependent manner. Treatment with tripterine (4, 6, and 8 μM) dose-dependently inhibited cell proliferation and migration, promoted cell apoptosis, reduced α-SMA, Col1, and Fn expression, induced ROS production, and enhanced JNK phosphorylation in keloid fibroblasts. Collectively, tripterine ameliorates the pathological characteristics of keloid fibroblasts that are associated with keloidformation and growth by inducing ROS generation and activating JNK signalingpathway., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This research aimed to assess the levels of cognitive function and its contributing factors among individuals experiencing cancer pain (CP) in mainland China., Design: A descriptive, cross-sectional study., Setting: The investigation was undertaken within three tertiary oncology hospitals., Participants: We included 220 hospitalised individuals who reported experiencing cancer-related pain and consented to complete the research questionnaires., Outcome Measures: The collected data encompassed sociodemographic and clinical variables, augmented by results from validated questionnaires. Cognitive impairment (CI) was evaluated using the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) scale, with scores ranging from 0 to 148. Sleep quality, depression and anxiety were assessed through the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder-7, respectively. A binary logistic regression model was used to identify factors associated with CI in individuals with CP., Results: Of the 225 individuals approached, 220 (97.8%) participated in the study. The mean FACT-Cog score for those with CP was 101.29 (SD=25.24; range=25-148). The prevalence of CI among these individuals was 35.90%. Sleep quality was rated below medium in 45% of participants with CP. More than moderate pain was reported by 28.2%, with 64.6% experiencing depression and 38.6% experiencing anxiety. Increased odds of developing CI were observed in those with CP (OR 1.422, 95% CI 1.129 to 1.841), depression (OR 1.119, 95% CI 1.029 to 1.2117), anxiety (OR 1.107, 95% CI 1.005 to 1.220), advancing age (OR 1.042, 95% CI 1.013 to 1.073), poor sleep quality (OR 1.126, 95% CI 1.013 to 1.252) and a history of smoking (OR 3.811, 95% CI 1.668 to 8.707)., Conclusions: CI associated with CP is notably prevalent in China. Those older, with a smoking history, inadequate sleep, more severe pain, depression and anxiety, have a heightened risk of CI. Consequently, interventions need to be personalised, addressing these key determinants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it's essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H 2 O 2 -induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI., (© 2023. The Author(s).)

Objectives: To develop and externally validate multiphase CT-based deep learning (DL) models for differentiating adrenal metastases from benign lesions., Materials and Methods: This retrospective two-center study included 1146 adrenal lesions from 1059 patients who underwent multiphase CT scanning between January 2008 and March 2021. The study encompassed 564 surgically confirmed adenomas, along with 135 benign lesions and 447 metastases confirmed by observation. DL models based on multiphase CT images were developed, validated and tested. The diagnostic performance of the classification models, imaging phases and radiologists with or without DL were compared using accuracy (ACC) and receiver operating characteristic (ROC) curves. Integrated discrimination improvement (IDI) analysis and the DeLong test were used to compare the area under the curve (AUC) among models. Decision curve analysis (DCA) was used to assess the clinical usefulness of the predictive models., Results: The DL signature based on LASSO (DLSL) had a higher AUC than that of the other classification models (IDI > 0, P < 0.05). Furthermore, the precontrast phase (PCP)-based DLSL performed best in the independent external validation (AUC = 0.881, ACC = 82.9 %) and clinical test cohorts (AUC = 0.790, ACC = 70.4 %), outperforming DLSL based on the other single-phase or three-phase images (IDI > 0, P < 0.05). DCA demonstrated that PCP-based DLSL provided a higher net benefit (0.01-0.95). The diagnostic performance led to statistically significant improvements when radiologists incorporated the DL model, with the AUC improving by 0.056-0.159 and the ACC improving by 0.069-0.178 (P < 0.05)., Conclusion: The DL model based on PCP CT images performed acceptably in differentiating adrenal metastases from benign lesions, and it may assist radiologists in accurate tumor staging for patients with a history of extra-adrenal malignancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: This review aimed to synthesize the available evidence on the effectiveness of nurse-led multidisciplinary interventions in primary health care., Methods: The following Chinese and English databases were searched for relevant articles: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM), from the establishment of the databases until the last updating search 1 April 2022. Two researchers screened the studies independently and extracted the data. Meta-analysis was performed using the RevMan 5.3 software., Results: A total of 12 studies were included in this review. It was found that nurse-led multidisciplinary interventions significantly shortened patients' length of stay in hospital (standardized mean differences [SMD] = -1.28, 95%CI: -2.03 to -0.54; P<0.001) and decreased incidences of complications (RR = 0.24, 95%CI:0.10 to 0.54; P = 0.0006) compared to the control group, and lowered patients' anxiety levels (SMD = -1.21, 95%CI: -1.99 to -0.44; P<0.01) and depression levels (SMD = -1.85, 95%CI: -3.42 to -0.28; P<0.0001). Furthermore, the results of subgroup analysis indicated that nurse-led multidisciplinary interventions had significant effects on patients' self-management ability (SMD = 4.45, 95%CI:2.45 to 6.44; P<0.0001) and quality of life (SMD = 1.01, 95%CI: 0.63 to 1.40; P<0.0001) compared to the control group., Conclusions: Nurse-led multidisciplinary interventions had strong effects in primary health care, contributing to shorten patients' length of stay in hospital, decrease incidences of complications and reduce the levels of anxiety and depression. Moreover, nurse-led multidisciplinary interventions also improved patients' self-management ability and quality of life., (© 2023 John Wiley & Sons Australia, Ltd.)

Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied., Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed., Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis., Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Liu et al.)

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen ( Pueraria lobata Ohwi), Di huang ( Rehmannia glutinosa Libosch.), Tian Huafen ( Trichosanthes kirilowii Maxim.), Mai Dong ( Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi ( Schisandra chinensis (Turcz.) Baill.) and Gan Cao ( Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetes-related glucose and lipid metabolism disorders. But what's the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear. Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW's intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics. Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques. Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels ( p < 0.05) while increasing HDL-C levels ( p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3'-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using high-throughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study. Conclusion: The mechanism of YQW's intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lei, Huang, Xie, Wang, Li, Hua, Liu and Yuan.)

Selective laser melting (SLM) can effectively replace traditional processing methods to prepare parts with arbitrary complex shapes through layer-by-layer accumulation. However, SLM Ti-6Al-4V alloy typically exhibits low ductility and significant mechanical properties anisotropy due to the presence of acicular α' martensite and columnar prior β grains. Post-heat treatment is frequently used to obtain superior mechanical properties by decomposing acicular α' martensite into an equilibrium α + β phase. In this study, the microstructure and tensile properties of SLM Ti-6Al-4V alloy before and after various heat treatments were systematically investigated. The microstructure of the as-fabricated Ti-6Al-4V sample was composed of columnar prior β grains and acicular α' martensite, which led to high strength (~1400 MPa) but low ductility (~5%) as well as significantly tensile anisotropy. The single heat treatment samples with lamellar α + β microstructure exhibited improved elongation to 6.8-13.1% with a sacrifice of strength of 100-200 MPa, while the tensile anisotropy was weakened. A trimodal microstructure was achieved through multi-step high-to-low-temperature (HLT) heat treatment, resulting in an excellent combination of strength (~1090 MPa) and ductility (~17%), while the tensile anisotropy was almost eliminated. The comprehensive mechanical properties of the HLT samples were superior to that of the conventional manufactured Ti-6Al-4V alloy.

Endometriosis (EM) is a prevalent estrogen-dependent disorder that adversely affects the life quality of many reproductive-age women. Previous evidence has suggested the significant role of miR-429 in EM; however, its molecular mechanisms underlying EM pathogenesis are unclarified. Human endometrial stromal cells (HESCs) were identified using immunofluorescence staining and flow cytometry. A mouse EM model was established by endometrial auto-transplantation. RNA and protein expression of molecules was examined using real-time quantitative polymerase chain reaction and western blotting, respectively. In vitro functional experiments showed that inhibiting miR-429 restrained HESC proliferation, migration, and invasiveness. Luciferase reporter assay confirmed that miR-429 targeted hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) in HESCs. HIF1AN silencing offset the negative regulation of miR-429 inhibition on the HIF1A/vascular endothelial growth factor (VEGF) signaling pathway. In vivo experiments showed that depletion of miR-429 attenuated ectopic lesion development in the mouse EM model. Collectively, suppressing miR-429 hinders the invasive behaviors of HESCs and EM progression in mice by targeting HIF1AN and regulating the HIF1A/VEGF signaling pathway., Competing Interests: Conflict of interest: The authors have no competing interests., (© 2023 the author(s), published by De Gruyter.)

Recently, growing interest in self-powered devices has led to the invention of new energy conversion devices. Photo-thermoelectric generators (PTEGs) have rapidly developed for their ability to harvest both light and thermal energy, but these devices are overly dependent on the continuity of energy input and cannot sustain output in an emergency situation. In the current study, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/graphene oxide (GO)/graphene nanosheets (GNPs)/polyethylene glycol (PEG) phase-change composites (PCCs) were prepared with freeze-drying and vacuum-filling processes to acquire materials suitable for imparting energy storage characteristics to PTEGs. The melting and crystallization enthalpies of the PCCs fabricated based on the PEDOT:PSS/GO/GNP aerogels can reach 211.5 and 207.6 J g -1 , respectively, which increase by nearly 5% compared with pure PEG, and the growth rate of thermal conductivity of the composites is as high as 262.7% (1.12 W m -1 K -1 ). Meanwhile, the excellent photothermal properties and high-temperature shape stability that pure PEG does not possess can also be imparted to PCCs by the aerogels. The PTEG assembled with PCCs and thermoelectric components can achieve a continuous output of over 1500 s after 300 s of light irradiation. After integrating the output of the device during the lamp on/off period, it is found that the total output of the device during the light-off period (8.4 V and 9.6 mW) can far exceed its total output during the light-on period (2.7 V and 4.4 mW). This work provides guidance for modulating the performance of PCCs and giving PTEGs the ability to operate under emergency or extremely harsh conditions and the prepared PTEGs are highly promising for practical use.

Because of the potential environmental harm caused by the extensive application of tetracycline (TC), this study used jasmine waste rich in organic matter as a precursor and one-step carbonization into metal-free carbon-based materials to efficiently activate peroxymonosulfate (PMS) toward degrading TC. The jasmine waste biochar (JWB) with a heating rate of 10 °C min -1 and a heating temperature of 700 °C was selected as the most suitable material based on its catalytic performance. The effects of catalyst dose, PMS dose, initial pH value, coexisting inorganic anions and TC concentration on the JWB/PMS/TC system were thoroughly optimized. The results showed that the degradation efficiency of TC by JWB/PMS system was 90%. Meanwhile, the combination of electron paramagnetic resonance, masking experiments and X-ray photoelectron spectrometry confirmed that JWB degraded TC mainly through the non-radical radical pathway of 1 O 2 oxidation and mediated the electron transfer to PMS. In addition, some degradation products were analyzed by LC-MS and possible degradation pathways of the system were proposed. Therefore, this paper proposes a novel method for recycling jasmine waste and providing a low-cost catalyst for the oxidation treatment of refractory organic matter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Aim: To investigate the predictive value of human epididymis protein 4 (HE4) for heart failure in patients with chronic kidney disease (CKD)., Methods: This study retrospectively analyzed the data of 241 patients with CKD admitted to Zhangjiakou First Hospital from January 2019 to January 2021. The subjects were divided into a heart failure (HF) group (n=117) and a non-HF group (n=124) according to whether heart failure occurred. The baseline data and laboratory hematologic indicators (complete set of HE4, blood routine and biochemistry) were collected and analyzed by univariate analysis. Subsequently, the variables that were significant in the correlation analysis were included in a multi-factor logistic regression analysis., Results: The HF group exhibited higher serum creatinine, HE4, hemoglobin, total cholesterol, triglycerides (TG), high-density lipoprotein (P<0.05), as well as higher B-type natriuretic peptide (BNP), creatine kinase, and creatine kinase-MB than the non-HF group, with significant differences (P<0.05). Spearman's rank correlation analysis revealed that age, HE4, calcium, TG, BNP and left ventricle ejection fraction were associated with the occurrence of heart failure (P<0.05). Multivariate analysis demonstrated that HE4 was a significant factor that could predict the development of heart failure in CKD patients (P<0.01), and the risk of heart failure was higher when HE4>27.2368 pmol/L., Conclusions: HE4 is an important factor for predicting the occurrence of heart failure in CKD patients. A higher HE4 level predicts greater possibility of heart failure., Competing Interests: None., (AJTR Copyright © 2023.)

Wide-bandgap perovskite solar cells (PSCs) are attracting increasing attention because they play an irreplaceable role in tandem solar cells. Nevertheless, wide-bandgap PSCs suffer large open-circuit voltage (V OC ) loss and instability due to photoinduced halide segregation, significantly limiting their application. Herein, a bile salt (sodium glycochenodeoxycholate, GCDC, a natural product), is used to construct an ultrathin self-assembled ionic insulating layer firmly coating the perovskite film, which suppresses halide phase separation, reduces V OC loss, and improves device stability. As a result, 1.68 eV wide-bandgap devices with an inverted structure deliver a V OC of 1.20 V with an efficiency of 20.38%. The unencapsulated GCDC-treated devices are considerably more stable than the control devices, retaining 92% of their initial efficiency after 1392 h storage under ambient conditions and retaining 93% after heating at 65 °C for 1128 h in an N 2 atmosphere. This strategy of mitigating ion migration via anchoring a nonconductive layer provides a simple approach to achieving efficient and stable wide-bandgap PSCs., (© 2023 Wiley-VCH GmbH.)

Background: Kinesin is a molecular motor for transporting "goods" within cells and plays a key role in many types of tumors. The multi-angle study of kinesin at the pan-cancer level is conducive to understanding its role in tumorigenesis and development and clinical treatment potential., Methods: We evaluated the expression of KIF genes, performed differential analysis by using the R package limma, and explored the pan-cancer prognosis of KIF genes by univariate Cox regression analysis. To evaluate the pan-cancer role of KIF genes as a whole, we defined the KIFscore with the help of gene set variation analysis (GSVA) and explored the KIFscores across normal tissues, tumor cell lines, and 33 tumor types in TCGA. Next, we used spearman correlation analysis to extensively study the correlation between the KIFscore and tumor prognosis and be-tween the KIFscore and clinical indicators. We also identified the relationship between the KIFscore and genomic variation and immune molecular signatures by multiplatform analysis. Finally, we identified the key genes in clear cell renal cell carcinoma (ccRCC) through machine learning algorithms and verified the candidate genes by CCK8, wound healing assay, Transwell assay, and flow cytometry., Results: In most cancers, KIFscores are high and they act as a risk factor for cancer. The KIFscore was significantly associated with copy number variation (CNV), tumor mutation burden (TMB), immune subtypes, DNA repair deficiency, and tumor stemness indexes. Moreover, in almost all cancer species, the KIFscore was positively correlated with T cell CD4+ TH2, the common lymphoid pro-genitor, and the T cell follicular helper. In addition, it was negatively correlated with CXCL16, CCL14, TNFSF13, and TNFRSF14 and positively correlated with ULBP1, MICB, and CD276. Machine learning helped us to identify four hub-genes in ccRCC. The suitable gene, KIF14, is highly expressed in ccRCC and promotes tumor cell proliferation, migration, and invasion., Conclusion: Our study shows that the KIF genes play an important pan-cancer role and may become a potential new target for a variety of tumor treatments in the future. Furthermore, KIF14, a key molecule in the KIF genes, can provide a new idea for the ccRCC treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Gong, Li, Guan, Gong, Zhong, Zhu, Wang, Jiang, Li, Lei, Liu, Chen and Zheng.)

Background: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers., Case Presentation: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1β isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months., Conclusions: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification., (© 2023. BioMed Central Ltd., part of Springer Nature.)

To explore the association between serum lipids and the occurrence and development of endometriosis using a retrospective review of clinical data. A total of 177 patients who underwent laparoscopic or open surgery due to benign ovarian masses, 117 patients with endometriosis (53 stage III and 64 stage IV), and 60 patients with benign ovarian masses without endometriosis were selected from the gynecology department of Maternal and Child Health Hospital of Hubei Province, between January 1, 2020, and October 30, 2022, to search for endometriosis occurrence by retrospectively analyzed the patients clinical data Risk factors for development and to explore the relationship between blood lipids and endometriosis. The scores of estradiol (E2), carbohydrate antigen 125 (CA125), and pain in the endo - and non-endometriosis groups were significantly different (P < .05), but there was no significant correlation between these 3. There were significant differences (P < .05) in E2, triglyceride (TG), CA125, and the size of the masses between patients with stage III and IV endometriosis. TG, E2, and CA125 were found to be valuable as separate indicators for the prediction of endometriosis, and the 3 indicators could improve the accuracy of the diagnosis of endometriosis when combined. Triglycerides may be positively correlated with the severity of endometriosis. The combination of TG, E2 and CA125 can improve the accuracy of the diagnosis of endometriosis staging., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy via sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA. Impressively, a novel FLRNA with sequence and structure bispecific RNA named as a structure-switching aptamer (SSA) was introduced to monitor the real-time concentration and spatiotemporal localization of biomolecules, contributing to a deeper insight of the dynamic monitoring and visualization of biomolecules in live systems.

Triple-negative breast cancers (TNBC) represent a pathological subtype of breast cancer, which are characterized by strong invasiveness, high metastasis rate, low survival rate, and poor prognosis, especially in patients who have developed resistance to multiline treatments. Here, we present a female patient with advanced TNBC who progressed despite multiple lines of treatments; next-generation sequencing (NGS) was used to find drug mutation targets, which revealed a coiled-coil domain-containing protein 6 (CCDC6)-rearranged during transfection (RET) gene fusion mutation. The patient was then given pralsetinib, and after one treatment cycle, a CT scan revealed partial remission and adequate tolerance to therapy. Pralsetinib (BLU-667) is a RET-selective protein tyrosine kinase inhibitor that can inhibit the phosphorylation of RET and downstream molecules as well as the proliferation of cells expressing RET gene mutations. This is the first case in the literature of metastatic TNBC with CCDC6-RET fusion treated with pralsetinib, an RET-specific antagonist. This case demonstrates the potential efficacy of pralsetinib in cases of TNBC with RET fusion mutations and suggests that NGS may reveal new opportunities and bring new therapeutic interventions to patients with refractory TNBC., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism., Methods: We analyzed whole-exome sequencing (WES) data for 38 osteosarcoma with paired samples in different relapse patterns. We also sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms., Results: We investigated WES of 12/38 patients with high-grade osteosarcoma (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions. We found that osteosarcoma in group A mainly carries single-nucleotide variations displaying higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures, while those in group B mainly exhibits structural variants. High conservation of reported genetic sequencing over time in their evolving cladograms., Conclusions: Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases as well as better immunogenicity in tumor microenvironment., (© 2023 The Authors.)

Background: Aging is a major factor for cardiovascular disease, and cardiac aging is closely related to the incidence of cardiovascular disease. Clarifying the mechanism of cardiac aging and finding reliable intervention is critical for preventing cardiovascular diseases and achieving healthy longevity. Traditional Chinese medicine Yiqi Huoxue Yangyin (YHY) decoction has unique advantage in the treatment of cardiovascular disease and aging. However, the associated molecular mechanisms remain unknown., Purpose: The present study aimed to verify the efficacy of YHY decoction against cardiac aging in D-gal-induced mouse model, and explore the potential mechanism of YHY decoction treatment through whole-transcriptome sequencing technique, providing novel insights into the molecular basis of YHY decoction in treating cardiac aging., Methods: The component of YHY decoction was identified by High Performance Liquid Chromatography (HPLC). D-gal-induced aging mouse model was established for this study. HE and Masson staining were applied to determine pathological changes of heart; telomere length, telomerase activity, AGEs and p53 were used to evaluate the degree of heart aging. Transcriptome sequencing, GO, KEGG, GSEA and ceRNA network were applied to analyze the potential mechanism of YHY decoction treatment of cardiac aging., Results: In this study, we found that YHY decoction not only improved the pathological structure of aging heart, but also regulated the expression of aging-related markers, telomere length, telomerase activity, AGEs and p53, the myocardial tissue, suggesting that it has a specific effect in delaying cardiac aging. Whole-transcriptome sequencing showed that the total of 433 mRNAs, 284 lncRNAs, 62 miRNAs, and 39 circRNAs were significantly differentially expressed after YHY decoction treatment. According to the analysis results of KEGG and GSEA, the differentially expressed mRNAs were found significantly involved in immune system, cytokine-cytokine receptor interaction and cell adhesion molecules. The ceRNA network showed that miR-770, miR-324, and miR-365 are localized in center, mainly affecting the immune system, PI3K-Akt signaling pathway, and MAPK signaling pathway., Conclusion: In conclusion, our results evaluated the ceRNA network of YHY decoction in treating cardiac aging for the first time, which could provide better understanding of the potential mechanism of YHY decoction treatment of cardiac aging.