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Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients. [ABSTRACT FROM AUTHOR]

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases. [ABSTRACT FROM AUTHOR]

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia. Here, the authors provide evidence that SARS-CoV-2 N protein leads to autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inducing DNA damage and proteotoxic stress, eventually causing pneumonia. The small-molecule drug PJ34 or anastrozole alleviates N protein-induced pneumonia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence. Methods: In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated. Results: The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p < 0.001). Conclusion: The presence of LLM use policies is suboptimal in radiological journals. A reporting guideline is encouraged to facilitate reporting quality and transparency. Critical relevance statement: It may facilitate the quality and transparency of the use of LLMs in scientific writing if a shared complete reporting guideline is developed by stakeholders and then endorsed by journals. Key Points: The policies on LLM use in radiological journals are unexplored. Some of the radiological journals presented policies on LLM use. A shared complete reporting guideline for LLM use is desired. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to determine the etiological characteristics of patients with dizziness/vertigo attending a neurological clinic according to the criteria of the International Classification of Vestibular Disorders (ICVD), hoping to provide a valuable reference for clinicians to diagnose and treat dizziness/vertigo. Method: A total of 638 consecutive patients with a chief complaint of dizziness/vertigo who attended the vertigo clinic of our neurology department from January 2019 to January 2020 were included. Clinical data of patients, including baseline data, medical history, neurological, neuro-otological, and auxiliary examination results were collected. The etiologic distribution of dizziness/vertigo was determined by analyzing the diagnoses of patients. Results: Of the 638 patients with dizziness/vertigo, 38.8% were males, 61.2% were females, with a male: female ratio of 1:1.58 and a mean age of 52.9 ± 16.9 years. Benign paroxysmal positional vertigo (BPPV) was the most common cause of dizziness/vertigo in both female (38.9%) and male patients (25.5%). Subgroup analysis based on sex showed that vestibular migraine (VM) and probable autoimmune inner ear disease (p-AIED) were more prevalent in female patients (10.7% and 3.8%, respectively), while vascular vertigo/dizziness was more common in male patients (10.1%). Subgroup analysis based on age showed that the most common diseases were VM in patients aged 0–30 years (27.4%), BPPV in patients aged 31–60 years (27.1%) and 61–100 years (46.0%). Episodic vestibular syndrome (EVS) was the most commonly observed, accounting for up to 60.6% (389/638) of all patients, and the most common diagnoses were BPPV (55.3%, 215/389), VM (15.2%, 59/389), primary unilateral peripheral vestibular dysfunction (p-UPVD) of unknown etiology (11.8%, 46/389), p-AIED (4.4%, 17/389), and vascular vertigo/dizziness (2.8%, 11/389) in these patients. Chronic vestibular syndrome (CVS) was found in 14.0% (90/638) of the patients, and the most common diagnoses were persistent postural-perceptual dizziness (PPPD, 35.6%, 32/90), psychogenic dizziness (18.9%, 17/90), p-UPVD of unknown etiology (15.6%, 14/90), vascular vertigo/dizziness (15.6%, 14/90), and bilateral vestibulopathy (7.8%, 7/90). Acute vestibular syndrome (AVS) was observed in 8.4% (54/638) of the patients, and the most common diagnoses were p-UPVD of unknown etiology (31.5%, 17/54), vestibular neuritis (24.1%, 13/54), probable labyrinthine apoplexy (16.7%, 9/54), stroke (13.0%, 7/54), and psychogenic dizziness (11.1%, 6/54). 16.4% (105/638) of the patients were found to have other disorders, including 15.2% (16/105) of patients with internal diseases, and 84.8% (89/105) of patients with unknown causes. In terms of localization diagnosis, 56.1%, 17.0%, 10.0%, and 16.4% of the patients were diagnosed with peripheral vestibular disorder, central vestibular disorder, psychiatric and functional vestibular disorders, and other disorders, respectively. Conclusion: (1) Dizziness/vertigo was more common in females, which was frequently caused by damage to the vestibular system. Non-vestibular or unknown etiologies were also seen in some patients; (2) VM was more prevalent in women than in men, vascular vertigo/dizziness was more commonly observed in men; (3) EVS was more common in patients with dizziness/vertigo. The most common causes of dizziness/vertigo were peripheral vestibular disorders in patients with AVS and EVS, PPPD and psychogenic dizziness in patients with CVS. The most common causes were BPPV and p-UPVD of unknown etiology in patients with a peripheral vestibular disorder, VM and vascular vertigo/dizziness in patients with central vestibular disorder, PPPD and psychogenic dizziness in patients with psychiatric and functional vestibular disorders. [ABSTRACT FROM AUTHOR]

Objective: To appraise the quality of guidelines on intravenous iodinated contrast media (ICM) use in patients with kidney disease, and to compare the recommendations among them. Methods: We searched four literature databases, eight guideline libraries, and ten homepages of radiological societies to identify English and Chinese guidelines on intravenous ICM use in patients with kidney disease published between January 2018 and June 2023. The quality of the guidelines was assessed with the Scientific, Transparent, and Applicable Rankings (STAR) tool. Results: Ten guidelines were included, with a median STAR score of 46.0 (range 28.5–61.5). The guidelines performed well in "Recommendations" domain (31/40, 78%), while poor in "Registry" (0/20, 0%) and "Protocol" domains (0/20, 0%). Nine guidelines recommended estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as the cutoff for referring patients to discuss the risk-benefit balance of ICM administration. Three guidelines further suggested that patients with an eGFR < 45 mL/min/1.73 m2 and high-risk factors also need referring. Variable recommendations were seen in the acceptable time interval between renal function test and ICM administration, and that between scan and repeated scan. Nine guidelines recommended to use iso-osmolar or low-osmolar ICM, while no consensus has been reached for the dosing of ICM. Nine guidelines supported hydration after ICM use, but their protocols varied. Drugs or blood purification therapy were not recommended as preventative means. Conclusion: Guidelines on intravenous ICM use in patients with kidney disease have heterogeneous quality. The scientific societies may consider joint statements on controversial recommendations for variable timing and protocols. Critical relevance statement: The heterogeneous quality of guidelines, and their controversial recommendations, leave gaps in workflow timing, dosing, and post-administration hydration protocols of contrast-enhanced CT scans for patients with kidney diseases, calling for more evidence to establish a safer and more practicable workflow. Key points: • Guidelines concerning iodinated contrast media use in kidney disease patients vary. • Controversy remains in workflow timing, contrast dosing, and post-administration hydration protocols. • Investigations are encouraged to establish a safer iodinated contrast media use workflow. [ABSTRACT FROM AUTHOR]

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies. Oncogenic KRAS mutations can dictate the formation of an immune-suppressive tumor microenvironment. Here the authors report that, in KRAS mutant colorectal cancer, the upregulation of circATXN7 in tumor-specific cytotoxic T lymphocytes is associated with increased sensitivity to activation-induced cell death and resistance to immunotherapy." [ABSTRACT FROM AUTHOR]

Background: In this study, we used computed tomography (CT)-based radiomics signatures to predict the mutation status of KRAS in patients with colorectal cancer (CRC) and to identify the phase of radiomics signature with the most robust and high performance from triphasic enhanced CT. Methods: This study involved 447 patients who underwent KRAS mutation testing and preoperative triphasic enhanced CT. They were categorized into training (n = 313) and validation cohorts (n = 134) in a 7:3 ratio. Radiomics features were extracted using triphasic enhanced CT imaging. The Boruta algorithm was used to retain the features closely associated with KRAS mutations. The Random Forest (RF) algorithm was used to develop radiomics, clinical, and combined clinical–radiomics models for KRAS mutations. The receiver operating characteristic curve, calibration curve, and decision curve were used to evaluate the predictive performance and clinical usefulness of each model. Results: Age, CEA level, and clinical T stage were independent predictors of KRAS mutation status. After rigorous feature screening, four arterial phase (AP), three venous phase (VP), and seven delayed phase (DP) radiomics features were retained as the final signatures for predicting KRAS mutations. The DP models showed superior predictive performance compared to AP or VP models. The clinical–radiomics fusion model showed excellent performance, with an AUC, sensitivity, and specificity of 0.772, 0.792, and 0.646 in the training cohort, and 0.755, 0.724, and 0.684 in the validation cohort, respectively. The decision curve showed that the clinical–radiomics fusion model had more clinical practicality than the single clinical or radiomics model in predicting KRAS mutation status. Conclusion: The clinical–radiomics fusion model, which combines the clinical and DP radiomics model, has the best predictive performance for predicting the mutation status of KRAS in CRC, and the constructed model has been effectively verified by an internal validation cohort. [ABSTRACT FROM AUTHOR]

Teaching–Learning-Based Optimization (TLBO) is a population-based intelligent optimization algorithm, which simulates the "teaching" process of teachers to students and the "learning" process of students in the class. In order to solve the problems of slow optimization speed, low optimization accuracy and easy to fall into local optimization, an improved TLBO algorithm based on Cauchy mutation and chaos operators are proposed. Firstly, the dynamic selection of teachers in the "teaching" stage leads to higher class average grades. Learning from the best students in the class during the "learning" phase makes class results more focused. Secondly, after a teaching is completed, Cauchy mutation is carried out to make the algorithm population more diverse so as to get rid of the local optimal solution. Finally, on the basis of Cauchy mutation, chaos theory is introduced into the optimization process of TLBO algorithm, and 10 chaos are embedded in the process of generating random numbers by Cauchy mutation, which enhances its ergo city and irreconcilability to further improve its convergence speed and accuracy. The performance of the proposed improved TLBO algorithm was tested by using 30 benchmark functions in CEC-BC-2017, and finally two engineering design problems (cantilever arm design and pressure vessel design) were optimized. The experimental results show that the proposed TLBO algorithm has significantly improved its convergence speed and optimization accuracy. [ABSTRACT FROM AUTHOR]

CLIC5 encoded protein associates with actin-based cytoskeletal and is increasingly thought to play significant roles in human cancers. We use TCGA and GEO to explore CLIC5 expression differences, mutation and DNA methylation, TMB, MSI, and immune cell infiltration. We verified the mRNA expression of CLIC5 in human ovarian cancer cells by real-time PCR and detected the expression of CLIC5 as well as immune marker genes in ovarian cancer by immunohistochemistry. The pan-cancer analysis showed that CLIC5 is highly expressed in several malignant tumors. In some cancers, CLIC5 expression in tumor samples is associated with poorer overall survival. For example, patients with ovarian cancer with high expression of CLIC5 have a poor prognosis. CLIC5 mutation frequency increased in all tumor types. The CLIC5 promoter is hypomethylated in most tumors. CLIC5 was associated with tumor immunity and different immune cells of different tumor types, such as CD8 + T cells, tumor-associated fibroblasts, macrophages, etc. CLIC5 was positively correlated with various immune checkpoints, and TMB and MSI were correlated with dysregulation of CLIC5 in tumors. The expression of CLIC5 in ovarian cancer was detected by qPCR and IHC, and the results were consistent with the bioinformatics results. There were a strong positive correlation between CLIC5 expression and M2 macrophage (CD163) infiltration and a negative correlation with CD8 + T-cell infiltration. In conclusions, our first pan-cancer analysis offered a detailed grasp of the cancerogenic functions of CLIC5 in a variety of malignancies. CLIC5 participated in immunomodulation and performed a crucial function in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

This study is aimed to evaluate effects of deep learning image reconstruction (DLIR) on image quality in single-energy CT (SECT) and dual-energy CT (DECT), in reference to adaptive statistical iterative reconstruction-V (ASIR-V). The Gammex 464 phantom was scanned in SECT and DECT modes at three dose levels (5, 10, and 20 mGy). Raw data were reconstructed using six algorithms: filtered back-projection (FBP), ASIR-V at 40% (AV-40) and 100% (AV-100) strength, and DLIR at low (DLIR-L), medium (DLIR-M), and high strength (DLIR-H), to generate SECT 120kVp images and DECT 120kVp-like images. Objective image quality metrics were computed, including noise power spectrum (NPS), task transfer function (TTF), and detectability index (d′). Subjective image quality evaluation, including image noise, texture, sharpness, overall quality, and low- and high-contrast detectability, was performed by six readers. DLIR-H reduced overall noise magnitudes from FBP by 55.2% in a more balanced way of low and high frequency ranges comparing to AV-40, and improved the TTF values at 50% for acrylic inserts by average percentages of 18.32%. Comparing to SECT 20 mGy AV-40 images, the DECT 10 mGy DLIR-H images showed 20.90% and 7.75% improvement in d′ for the small-object high-contrast and large-object low-contrast tasks, respectively. Subjective evaluation showed higher image quality and better detectability. At 50% of the radiation dose level, DECT with DLIR-H yields a gain in objective detectability index compared to full-dose AV-40 SECT images used in daily practice. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate image quality, diagnostic acceptability, and lesion conspicuity in abdominal dual-energy CT (DECT) using deep learning image reconstruction (DLIR) compared to those using adaptive statistical iterative reconstruction-V (Asir-V) at 50% blending (AV-50), and to identify potential factors impacting lesion conspicuity. Methods: The portal-venous phase scans in abdominal DECT of 47 participants with 84 lesions were prospectively included. The raw data were reconstructed to virtual monoenergetic image (VMI) at 50 keV using filtered back-projection (FBP), AV-50, and DLIR at low (DLIR-L), medium (DLIR-M), and high strength (DLIR-H). A noise power spectrum (NPS) was generated. CT number and standard deviation values of eight anatomical sites were measured. Signal-to-noise (SNR), and contrast-to-noise ratio (CNR) values were calculated. Five radiologists assessed image quality in terms of image contrast, image noise, image sharpness, artificial sensation, and diagnostic acceptability, and evaluated the lesion conspicuity. Results: DLIR further reduced image noise (p < 0.001) compared to AV-50 while better preserved the average NPS frequency (p < 0.001). DLIR maintained CT number values (p > 0.99) and improved SNR and CNR values compared to AV-50 (p < 0.001). DLIR-H and DLIR-M showed higher ratings in all image quality analyses than AV-50 (p < 0.001). DLIR-H provided significantly better lesion conspicuity than AV-50 and DLIR-M regardless of lesion size, relative CT attenuation to surrounding tissue, or clinical purpose (p < 0.05). Conclusions: DLIR-H could be safely recommended for routine low-keV VMI reconstruction in daily contrast-enhanced abdominal DECT to improve image quality, diagnostic acceptability, and lesion conspicuity. Key Points: • DLIR is superior to AV-50 in noise reduction, with less shifts of the average spatial frequency of NPS towards low frequency, and larger improvements of NPS noise, noise peak, SNR, and CNR values. • DLIR-M and DLIR-H generate better image quality in terms of image contrast, noise, sharpness, artificial sensation, and diagnostic acceptability than AV-50, while DLIR-H provides better lesion conspicuity than AV-50 and DLIR-M. • DLIR-H could be safely recommended as a new standard for routine low-keV VMI reconstruction in contrast-enhanced abdominal DECT to provide better lesion conspicuity and better image quality than the standard AV-50. [ABSTRACT FROM AUTHOR]

A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu–Cl and Cu–glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 μM with a detection limit of 0.024 μM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics. [ABSTRACT FROM AUTHOR]

Developing innovative, easy-to-manufacture, and non-Pt-group-metal (non-PGM) electrocatalysts is essential for the highly efficient oxygen reduction reaction (ORR). Herein, we report a self-sacrificing post-synthetic strategy to synthesize highly loaded Fe-isolated single atoms anchored on the hierarchical porous N,S co-doped carbon matrix (Fe-SAs/S,N-C/rGO). The optimized Fe-SAs/S,N-C/rGO exhibits excellent ORR activity in the pH-universal range with half-wave potentials of 0.89, 0.80, and 0.60 V in alkaline, acidic, and neutral media, comparable to the commercial Pt/C (0.85, 0.81, and 0.64 V, respectively). The homemade liquid Zn-air battery (ZAB) with Fe-SAs/S,N-C/rGO as the cathode catalyst displays an open-circuit voltage (OCV) of ∼ 1.61 V, discharging specific capacity of 817.23 mAh·g−1, and long-term durability of ∼ 1865 cycles, outperforming those of the device with commercial Pt/C+RuO2 (1.49 V, 657.32 mAh·g−1, and ∼ 120 cycles, respectively). Intriguingly, the corresponding flexible solid-state ZAB delivers satisfactory OCV, peak power density, foldability, and cycling stability at room temperature, as well as adaptability at a low temperature of −10 °C. Besides, density functional theory (DFT) calculation reveals that the atomic FeN3S moieties in Fe-SAs/S,N-C/rGO can cause charge redistribution and lower the binding strength of oxygen-containing intermediates, resulting in accelerated ORR kinetics and optimized catalytic activity. This work provides insights into experimental and theoretical guidance towards non-PGM electrocatalysts for efficient energy conversion. [ABSTRACT FROM AUTHOR]

Objective: To conduct an overview of meta-analyses of radiomics studies assessing their study quality and evidence level. Methods: A systematical search was updated via peer-reviewed electronic databases, preprint servers, and systematic review protocol registers until 15 November 2022. Systematic reviews with meta-analysis of primary radiomics studies were included. Their reporting transparency, methodological quality, and risk of bias were assessed by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 checklist, AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews, version 2) tool, and ROBIS (Risk Of Bias In Systematic reviews) tool, respectively. The evidence level supporting the radiomics for clinical use was rated. Results: We identified 44 systematic reviews with meta-analyses on radiomics research. The mean ± standard deviation of PRISMA adherence rate was 65 ± 9%. The AMSTAR-2 tool rated 5 and 39 systematic reviews as low and critically low confidence, respectively. The ROBIS assessment resulted low, unclear and high risk in 5, 11, and 28 systematic reviews, respectively. We reperformed 53 meta-analyses in 38 included systematic reviews. There were 3, 7, and 43 meta-analyses rated as convincing, highly suggestive, and weak levels of evidence, respectively. The convincing level of evidence was rated in (1) T2-FLAIR radiomics for IDH-mutant vs IDH-wide type differentiation in low-grade glioma, (2) CT radiomics for COVID-19 vs other viral pneumonia differentiation, and (3) MRI radiomics for high-grade glioma vs brain metastasis differentiation. Conclusions: The systematic reviews on radiomics were with suboptimal quality. A limited number of radiomics approaches were supported by convincing level of evidence. Clinical relevance statement: The evidence supporting the clinical application of radiomics are insufficient, calling for researches translating radiomics from an academic tool to a practicable adjunct towards clinical deployment. Key points: The systematic reviews on radiomics studies were insufficient in reporting, suboptimal in methodological quality, and with high risk of bias. The meta-analyses covered a wide range of clinical questions, while only three of them were rated as convincing level of evidence. More radiomics investigation is necessary to allow clinical translation of radiomics to a practicable adjunct toward clinical deployment. [ABSTRACT FROM AUTHOR]

In this paper, we focus on a general n-dimension system of k-Hessian equations. By introducing some new suitable growth conditions, the existence results of radial k-admissible solutions of the k-Hessian system are obtained. Our approach is largely based on the well-known fixed-point theorem. [ABSTRACT FROM AUTHOR]

We propose brane web configurations for D-type and E-type N =(1,0) little string theories based on a trivalent or quadrivalent gluing of 5-brane web diagrams. Tri-/quadri-valent gluing is a powerful way of computing 5d/6d partition functions for supersymmetric gauge theories based on the topological vertex. We generalize the gluing techniques to little string theories by introducing a new compact direction and compute their supersymmetric partition functions on Omega-deformed ℝ4×T2. As concrete examples, we consider little string theories arising from Type IIB NS5-branes probing D4 or D5 singularity. Their effective gauge theory descriptions as the affine D4 or D5 quiver gauge theory can be realized with quadrivalent or trivalent gluing, respectively. Based on these gluings of 5-brane webs, we compute their refined partition functions and compare them with the known results. We extend the computation of the partition function to little string theory engineered from IIB NS5-branes probing E6 singularity based on a trivalent gluing. We also discuss the generalization to higher rank cases and the symmetries of the partition functions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the study quality and clinical value of radiomics studies on chondrosarcoma. Methods: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data were searched for articles on radiomics for evaluating chondrosarcoma as of January 31, 2022. The study quality was assessed according to Radiomics Quality Score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, Image Biomarker Standardization Initiative (IBSI) guideline, and modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The level of evidence supporting clinical use of radiomics on chondrosarcoma differential diagnosis was determined based on meta-analyses. Results: Twelve articles were included. The median RQS was 10.5 (range, −3 to 15), with an adherence rate of 36%. The adherence rate was extremely low in domains of high-level evidence (0%), open science and data (17%), and imaging and segmentation (35%). The adherence rate of the TRIPOD checklist was 61%, and low for section of title and abstract (13%), introduction (42%), and results (56%). The reporting rate of pre-processing steps according to the IBSI guideline was 60%. The risk of bias and concern of application were mainly related to the index test. The meta-analysis on differential diagnosis of enchondromas vs. chondrosarcomas showed a diagnostic odds ratio of 43.90 (95% confidential interval, 25.33–76.10), which was rated as weak evidence. Conclusions: The current scientific and reporting quality of radiomics studies on chondrosarcoma was insufficient. Radiomics has potential in facilitating the optimization of operation decision-making in chondrosarcoma. Key Points: •Among radiomics studies on chondrosarcoma, although differential diagnostic models showed promising performance, only pieces of weak level of evidence were reached with insufficient study quality. •Since the RQS rating, the TRIPOD checklist, and the IBSI guideline have largely overlapped with each other, it is necessary to establish one widely acceptable methodological and reporting guideline for radiomics research. •The TRIPOD model typing, the phase classification of image mining studies, and the level of evidence category are useful tools to assess the gap between academic research and clinical application, although their modifications for radiomics studies are needed. [ABSTRACT FROM AUTHOR]

Chromosome segregation is initiated by cohesin degradation, which is driven by anaphase-promoting complex/cyclosome (APC/C). Chromosome cohesin is removed by activated separase, with the degradation of securin and cyclinB1. Dynamin-related protein 1 (DRP1), a component of the mitochondrial fission machinery, is related to cyclin dynamics in mitosis progression. Here, we show that DRP1 is recruited to the kinetochore by centromeric Centromere protein F (CENP-F) after nuclear envelope breakdown in mouse oocytes. Loss of DRP1 during prometaphase leads to premature cohesin degradation and chromosome segregation. Importantly, acute DRP1 depletion activates separase by initiating cyclinB1 and securin degradation during the metaphase-to-anaphase transition. Finally, we demonstrate that DRP1 is bound to APC2 to restrain the E3 ligase activity of APC/C. In conclusion, DRP1 is a CENP-F-dependent atypical spindle assembly checkpoint (SAC) protein that modulates metaphase-to-anaphase transition by controlling APC/C activity during meiosis I in oocytes. Spindle assembly checkpoint controls anaphase onset and guarantees appropriate chromosome segregation. Here, the authors report that dynamin-related protein 1 is recruited to kinetochores by CENP-F to regulate metaphase-to-anaphase transition by controlling APC/C activity in mouse oocyte meiosis [ABSTRACT FROM AUTHOR]

The vessel heave motion caused by wave action increases the difficulty of installing offshore wind equipment. Onboard wave heave compensation devices have therefore become increasingly critical in ensuring the stability and safety of the gangway and working platform. This study accordingly improves the compensation effect of such devices by developing a wave heave compensation model and designing an optimized backstepping control method. First, a model of the compensation system including the servo motor and electric cylinder is established by using the mechanism method. Second, a backstepping control method is designed to track the vessel heave motion, and particle swarm optimization is applied to optimize the control parameters. Finally, MATLAB/Simulink is used to simulate the application of the optimized backstepping controller, then regular and irregular heave motions are applied as input to a Stewart platform to evaluate the effectiveness of the control method. The experimental results show that the compensation efficiency provided by the proposed optimized backstepping control method is larger than 75.0%. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Etiologic distribution of dizziness/vertigo in a neurological outpatient clinic according to the criteria of the international classification of vestibular disorders: a single-center study." The correction addresses an error in the affiliation details of the authors. The correct affiliation should be "Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, No. 15, Yuquan Road, Haidian District, Beijing 100049, China." The correction is made by authors Yue Xing, Lihong Si, Wanting Zhang, Yuru Wang, Kangzhi Li, and Xu Yang. [Extracted from the article]

Acute myocardial infarction (AMI) leads to anoxia and ischemia of cardiomyocytes, followed by apoptosis. This study investigated the protective effect of ginsenoside Rg1 (Rg1) on myocardial ischemia injury in rats with AMI. Rats were randomly divided into five groups: group A (blank control group), group B (hypoxia/reoxygenation group), group C (hypoxia/reoxygenation + 10 mg/L Rg1), group D (hypoxia/reoxygenation + 20 mg/L Rg1) and group E (hypoxia/reoxygenation + 40 mg/L Rg1). The survival rate, apoptosis rate, expression of cyclin-dependent kinase 4 (CDK4), fibroblast growth factor 9 (FGF9), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), microvessel density and myocardial infarction area of rats in each group were compared. The expressions of CDK4 and FGF9, the contents of SOD and GSH-Px in groups C, D and E injected with Rg1 were significantly promoted compared to group B without Rg1 injection (P < 0.05). The survival rate of myocardial cells was significantly increased while the apoptosis rate was significantly decreased in group C, D, E compared to group B (P < 0.05). On the 3rd, 7th and 10th day following Rg1 treatment, the infarct area of E group was significantly decreased in three groups C, D, E, and the microvessel density of infarct area was significantly increased compared with group B (P < 0.05). So, Rg1 can improve the survival rate of myocardial cells, reduce the apoptosis rate and the area of myocardial infarction, and increase the microvessel density of infarct area, thus playing a protective role in ischemic myocardial cells of AMI rats. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical outcomes of pediatric congenital blepharoptosis with poor Bell's phenomenon (BP) treated with modified levator muscle complex suspension. Methods: Forty-two pediatric congenital blepharoptosis patients with poor BP were treated with modified levator muscle complex suspension, and their major surgical outcomes such as marginal reflex distance1 (MRD1), palpebral fissure height (PFH), and postoperative lagophthalmos were retrospectively reviewed. Results: The mean follow-up was 10.28 ± 9.89 months (range 3–32 Months). Surgical success was achieved in 54 (87.1%) of 62 eyelids at the final visit, including excellent results in 46 (74.2%) eyelids, good results in 8 (12.9%) eyelids, and poor results in 8 (12.9%) eyelids, respectively. The postoperative PFH of affected eyes (7.97 ± 1.47 mm) was significantly improved compared with that before surgery (3.58 ± 1.31 mm). The mean MRD1 was improved from − 1.48 ± 1.36 mm before surgery to 2.94 ± 1.46 mm after surgery. The postoperative MRD1 was ≥ 3 mm in 46 eyelids and < 3 mm in 16 eyelids. The mean lagophthalmos was 1.42 ± 1.20 mm 3 months after surgery. All of the patients presented complete blink postoperatively. Postoperative complications were rarely observed during follow-up. No patient had exposure keratitis, but blepharoptosis recurred in 6 patients (8 eyelids). All patients had satisfactory eyelid symmetry and contour. No complications were observed until the last visit. Conclusions: The modified method results complete blink, mild, and quick recovery of lagophthalmos, flexible eyelid motility, stable ocular surface, and it is simple to perform with few complications and a low recurrence rate at 12.9%, which is worth to wide application on poor Bell's phenomenon blepharoptosis. [ABSTRACT FROM AUTHOR]

Developing innovative and efficient non-precious-metal-group (non-PMG) electrocatalysts is crucial for the wide use of zinc-air batteries (ZABs). Herein, a single-atom catalyst (termed as Fe-N-C/rGO SAC) with unique five N-coordinated Fe (Fe-N5) centers is prepared by pyrolyzing the composite of zeolitic-imidazolate-frameworks-8 (ZIF-8) and graphene oxide (GO). Specifically, the individual Fe site is stabilized by four equatorial and one axial N atoms donated by the N-doped carbon matrix and imidazole ring, respectively, thus forming an asymmetric electron depletion zone over the metal center, which can effectively promote the generation of reactive intermediates and accelerate the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) processes for ZABs. The rechargeable liquid ZAB with Fe-N-C/rGO catalyst exhibits an extremely high energy density (928.25 Wh·kg−1), a remarkable peak power density (107.12 mW·cm−2), and a long cycle life (400 h). Additionally, the corresponding flexible solid-state ZAB displays superior foldability and remarkable cycling stability. This work provides both experimental and theoretical guidance for rational design of non-PMG electrocatalyst-driven ZABs. [ABSTRACT FROM AUTHOR]

Objectives: To implement a pipeline to automatically segment the ROI and to use a nomogram integrating the MRI-based radiomics score and clinical variables to predict responses to neoadjuvant chemotherapy (NAC) in osteosarcoma patients. Methods: A total of 144 osteosarcoma patients treated with NAC were separated into training (n = 101) and test (n = 43) groups. After normalisation, ROIs for the preoperative MRI were segmented by a deep learning segmentation model trained with nnU-Net by using two independent manual segmentations as labels. Radiomics features were extracted using automatically segmented ROIs. Feature selection was performed in the training dataset by five-fold cross-validation. The clinical, radiomics, and clinical-radiomics models were built using multiple machine learning methods with the same training dataset and validated with the same test dataset. The segmentation model was evaluated by the Dice coefficient. AUC and decision curve analysis (DCA) were employed to illustrate the model performance and clinical utility. Results: 36/144 (25.0%) patients were pathological good responders (pGRs) to NAC, while 108/144 (75.0%) were non-pGRs. The segmentation model achieved a Dice coefficient of 0.869 on the test dataset. The clinical and radiomics models reached AUCs of 0.636 with a 95% confidence interval (CI) of 0.427–0.860 and 0.759 (95% CI, 0.589–0.937), respectively, in the test dataset. The clinical-radiomics nomogram demonstrated good discrimination, with an AUC of 0.793 (95% CI, 0.610–0.975), and accuracy of 79.1%. The DCA suggested the clinical utility of the nomogram. Conclusion: The automatic nomogram could be applied to aid radiologists in identifying pGRs to NAC. Key Points: • The nnU-Net trained by manual labels enables the use of an automatic segmentation tool for ROI delineation of osteosarcoma. • A pipeline using automatic lesion segmentation and followed by a radiomics classifier could aid the evaluation of NAC response of osteosarcoma. • A predictive nomogram composed of clinical variables and MRI-based radiomics score provides support for individualised treatment planning. [ABSTRACT FROM AUTHOR]

Background: Multiple tools have been applied to radiomics evaluation, while evidence rating tools for this field are still lacking. This study aims to assess the quality of pancreatitis radiomics research and test the feasibility of the evidence level rating tool. Results: Thirty studies were included after a systematic search of pancreatitis radiomics studies until February 28, 2022, via five databases. Twenty-four studies employed radiomics for diagnostic purposes. The mean ± standard deviation of the adherence rate was 38.3 ± 13.3%, 61.3 ± 11.9%, and 37.1 ± 27.2% for the Radiomics Quality Score (RQS), the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guideline for preprocessing steps, respectively. The median (range) of RQS was 7.0 (− 3.0 to 18.0). The risk of bias and application concerns were mainly related to the index test according to the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The meta-analysis on differential diagnosis of autoimmune pancreatitis versus pancreatic cancer by CT and mass-forming pancreatitis versus pancreatic cancer by MRI showed diagnostic odds ratios (95% confidence intervals) of, respectively, 189.63 (79.65–451.48) and 135.70 (36.17–509.13), both rated as weak evidence mainly due to the insufficient sample size. Conclusions: More research on prognosis of acute pancreatitis is encouraged. The current pancreatitis radiomics studies have insufficient quality and share common scientific disadvantages. The evidence level rating is feasible and necessary for bringing the field of radiomics from preclinical research area to clinical stage. [ABSTRACT FROM AUTHOR]

Objective: To update the systematic review of radiomics in osteosarcoma. Methods: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data were searched to identify articles on osteosarcoma radiomics until May 15, 2022. The studies were assessed by Radiomics Quality Score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), and modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The evidence supporting radiomics application for osteosarcoma was rated according to meta-analysis results. Results: Twenty-nine articles were included. The average of the ideal percentage of RQS, the TRIPOD adherence rate and the CLAIM adherence rate were 29.2%, 59.2%, and 63.7%, respectively. RQS identified a radiomics-specific issue of phantom study. TRIPOD addressed deficiency in blindness of assessment. CLAIM and TRIPOD both pointed out shortness in missing data handling and sample size or power calculation. CLAIM identified extra disadvantages in data de-identification and failure analysis. External validation and open science were emphasized by all the above three tools. The risk of bias and applicability concerns were mainly related to the index test. The meta-analysis of radiomics predicting neoadjuvant chemotherapy response by MRI presented a diagnostic odds ratio (95% confidence interval) of 28.83 (10.27–80.95) on testing datasets and was rated as weak evidence. Conclusions: The quality of osteosarcoma radiomics studies is insufficient. More investigation is needed before using radiomics to optimize osteosarcoma treatment. CLAIM is recommended to guide the design and reporting of radiomics research. [ABSTRACT FROM AUTHOR]

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Objective: We want to investigate the effect of aquaporin-4 (AQP4) on cerebral edema induced by ischemic stroke in rats and explore whether inhibiting the expression of AQP4 through acetazolamide (AZA) could attenuate brain edema and protect cerebral function. Methods: The Sprague Dawley (SD) rats were randomly divided into four groups: sham + saline group, sham + AZA group, AZA intervention group, and nonintervention group. Each group was divided into five subgroups according to the time of cerebral ischemia (6 h, 1 day, 3 days, 5 days, and 7 days). The model of cerebral infarction in rats was adopted by means of the bilateral carotid arteries ligation (2-VO) method. The rats in intervention group were given intraperitoneal injection of AZA (35 mg/kg/day). Hematoxylin–eosin staining was performed for pathological analysis of the infarcted area. The brain water content was calculated to evaluate the degree of brain edema. The messenger RNA (mRNA) and protein expressions of AQP4 in the brain were measured by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Results: Significant cerebral pathological damages were found in ischemic stroke rats. The brain water content, protein, and mRNA expression of AQP4 of the intervention and nonintervention groups were markedly higher than those of the sham groups. By contrast, AZA administration reduced the brain water content, whereas improved cerebral dysfunction was induced by ischemic stroke. Moreover, AZA obviously reduced the protein and mRNA expression of AQP4 after ischemic stroke in rats' brains. Conclusions: The expression of AQP4 was closely related to cerebral edema induced by ischemic stroke. Decreasing the expression of AQP4 mRNA by AZA administration can effectively relieve cerebral edema and decrease cerebral pathological damage. [ABSTRACT FROM AUTHOR]

Sesquiterpenes are one of the most diverse groups of secondary metabolites that have mainly been observed in terpenoids. It is a natural terpene containing 15 carbon atoms in the molecule and three isoprene units with chain, ring, and other skeleton structures. Sesquiterpenes have been shown to display multiple biological activities such as anti-inflammatory, anti-feedant, anti-microbial, anti-tumor, anti-malarial, and immunomodulatory properties; therefore, their therapeutic effects are essential. In order to overcome the problem of low-yielding sesquiterpene content in natural plants, regulating their biosynthetic pathways has become the focus of many researchers. In plant and microbial systems, many genetic engineering strategies have been used to elucidate biosynthetic pathways and high-level production of sesquiterpenes. Here, we will introduce the research progress and prospects of the biosynthesis of artemisinin, costunolide, parthenolide, and dendrobine. Furthermore, we explore the biosynthesis of dendrobine by evaluating whether the biosynthetic strategies of these sesquiterpene compounds can be applied to the formation of dendrobine and its intermediate compounds. Key points: • The development of synthetic biology has promoted the study of terpenoid metabolism and provided an engineering platform for the production of high-value terpenoid products. • Some possible intermediate compounds of dendrobine were screened out and the possible pathway of dendrobine biosynthesis was speculated. • The possible methods of dendrobine biosynthesis were explored and speculated. [ABSTRACT FROM AUTHOR]

Issues like morphology control and further multifunctional applications are of significant importance for rare earth nano-oxides, e.g., cerium dioxide (CeO2) nanostructures, however, relevant results in this respect are rather limited up to now. In the present work, ultrathin CeO2 nanosheets were synthesized through a facile low-temperature hydrothermal method. The structure, morphology and specific surface area of these CeO2 nanosheets were characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and N2 adsorption–desorption. Significantly, CeO2 nanosheets have the potential as bifunctional sensing materials to detect both humidity and formaldehyde vapor. The CeO2 nanosheet humidity sensor exhibited excellent sensing characteristics in the relative humidity range of 11%–97% with the response value as high as 3.1 × 104. Meanwhile, the CeO2 nanosheet gas sensor showed superior sensitivity and repeatability with fast response/recovery speed toward formaldehyde vapor at 300 °C. Finally, the humidity and formaldehyde sensing mechanism were discussed as well. [ABSTRACT FROM AUTHOR]

Objectives: To assess the methodological quality and risk of bias in radiomics studies investigating diagnosis, therapy response, and survival of patients with osteosarcoma. Methods: In this systematic review, literatures on radiomics in osteosarcoma were included and assessed for methodological quality through the radiomics quality score (RQS). The risk of bias and concern of application was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A meta-analysis of studies focusing on predicting osteosarcoma response to neoadjuvant chemotherapy was performed. Results: Twelve radiomics studies exploring osteosarcoma were identified, and five were included in meta-analysis. The RQS reached an average of 20.4% (6.92 of 36) with good inter-rater agreement (ICC 0.95, 95% CI 0.85-0.99). Four studies validated results with an internal dataset, none of which used external dataset; one study was prospectively designed, and another one shared part of the dataset. The risk of bias and concern of application were mainly related to index test aspect. The meta-analysis showed a diagnostic odds ratio of 43.68 (95%CI 13.5-141.31) for predicting response to neoadjuvant chemotherapy with high heterogeneity and low methodological quality. Conclusions: The overall scientific quality of included studies is insufficient; however, radiomics remains a promising technology for predicting treatment response, which might guide therapeutic decision-making and related to prognosis. Improvements in study design, validation, and open science needs to be made to demonstrate the generalizability of findings and to achieve clinical applications. Widespread application of RQS, pre-trained RQS scoring procedure, and modification of RQS in response to clinical needs are necessary. Key Points: • Limited radiomics studies were established in osteosarcoma with mean RQS of 20.4%, commonly due to unvalidated results, retrospective study design, and absence of open science. • Meta-analysis of radiomics studies predicting osteosarcoma response to neoadjuvant chemotherapy showed high diagnostic odds ratio 43.68, while high heterogeneity and low methodological quality were the main concerns. • A previously trained data extraction instrument allowed reaching moderate inter-rater agreement in RQS applications, while RQS still needs improvement to become a wide adaptive tool in reviews of radiomics studies, in routine self-check before manuscript submitting and in study design. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress is a common threat to photoreceptors during the pathogenesis of chronic retinopathies and often results in irreversible visual impairment. 2,3,5,6-Tetramethylpyrazine (TMP), which possesses many beneficial pharmacological activities, is a potential drug that could be used to protect photoreceptors. In the present study, we found that the cellular growth rate of 661 W cells cultured under low glucose conditions was lower than that of control cells, while the G2/M phase of the cell cycle was longer. We further found that the mitochondrial membrane potential (ΔΨm) was lower and that ER stress factor expression was increased in 661 W cells cultured under low glucose conditions. TMP reversed these trends. Visual function and cell counts in the outer nuclear layer (ONL) were low and the TUNEL-positive rate in the ONL was high in a C3H mouse model of spontaneous retinal degeneration. Similarly, visual function was decreased, and the TUNEL-positive rate in the ONL was increased in fasted C57/BL6j mice compared with control mice. On the other hand, ER stress factor expression was found to be increased in the retinas of both mouse models, as shown by reverse transcription real-time PCR (RT-qPCR) and western blotting. TMP reversed the physiological and molecular biological variations observed in both mouse models, and ATF4 expression was enhanced again. Further investigation by using western blotting illustrated that the proportion of insoluble prion protein (PRP) versus soluble PRP was reduced both in vitro and in vivo. Taken together, these results suggest that TMP increased the functions of photoreceptors by alleviating ER stress in vitro and in vivo, and the intrinsic mechanism was the ATF4-mediated inhibition of PRP aggregation. TMP may potentially be used clinically as a therapeutic agent to attenuate the functional loss of photoreceptors during the pathogenesis of chronic retinopathies. Key messages: • Already known: TMP is a beneficial drug mainly used in clinic to enhance organ functions, and the intrinsic mechanism is still worthy of exploring. • New in the study: We discovered that TMP ameliorated retinal photoreceptors function via ER stress alleviation, which was promoted by ATF4-mediated inhibition of PRP aggregation. • Application prospect: In prospective clinical practices, TMP may potentially be used in the clinic as a therapeutic agent to attenuate the photoreceptors functional reduction in chronic retinopathies. [ABSTRACT FROM AUTHOR]

Plant viruses can modify the performance and behavior of insect vectors to maximize their transmission rates. Whether viruses can evolve to mediate their insect vectors' interspecific competition is poorly understood. Here, we used two vectors of tomato zonate spot virus (TZSV), one native species (Thrips palmi) and one exotic species (Frankliniella occidentalis), to investigate this in laboratory and field experiments. TZSV infection increased the population growth of its insect vectors when the thrips species were isolated from one another. When both species coexisted, F. occidentalis displaced T. palmi on both TZSV-infected and uninfected plants. However, on TZSV-infected plant, F. occidentalis completely displaced T. palmi more rapidly (within 14 days) than on uninfected plants. Our results also revealed that reproductive interference occurred between the two thrips species, whereas TZSV-infected pepper significantly decreased the reproductive interference of T. palmi to F. occidentalis. When F. occidentalis and T. palmi co-occurred in Jinning County, Yunnan Province, we found a rising trend of natural proportions of F. occidentalis in the TZSV-infected pepper fields, suggesting that TZSV-infected pepper enhanced the competitive advantage of F. occidentalis over T. palmi in the field. Together, our findings demonstrate a plant virus that plays an important role in the competitive displacement of its insect vectors. [ABSTRACT FROM AUTHOR]

In2O3@Cu2MoS4 nanocomposite with superior photoelectrochemical (PEC) performance is used for the first time as a photoactivity material, and a signal-off PEC biosensing platform for miRNA detection has been successfully constructed. Firstly, the Cu2MoS4 nanosheets are synthesized by a hydrothermal method, and then, the homogeneous In2O3 nanoparticles (In2O3 NPs) are synthesized by calcination in the air. The In2O3@Cu2MoS4 nanocomposite is constructed with the Cu2MoS4 nanosheets as matrix and In2O3 NPs as sensitizer through a layer-by-layer assembly strategy. The nanocomposite with a tight interface and the matched band structure restrains the electron-hole pair recombination. Under visible light (400–700 nm), the nanocomposite exhibits a strong initial signal. With the catalyzed hairpin assembly, dozens of PbS quantum dots (QDs) are introduced on the surface of an electrode, significantly reducing the photocurrent of n-type In2O3@Cu2MoS4. Since PbS QDs can compete with the nanocomposite for light energy and electron donors, the signal decreased. Under optimal conditions, the biosensor manifests a broad linear range (1 fM–1 nM) and a low detection limit of about 0.57 fM, at a working potential of 0 V (vs. Ag/AgCl). The recovery of spiked human serum is between 94.0 and 102%, and the relative standard deviation (RSD) is between 1.3 and 2.7%. Therefore, the as-fabricated biosensor exhibits a potential for the determination of miRNA-21 in practical applications. Graphical abstract [ABSTRACT FROM AUTHOR]

Objective: To investigate factors affecting the pattern of motor brain activation reported in people with Parkinson's (PwP), aiming to differentiate disease-specific features from treatment effects. Methods: A co-ordinate-based-meta-analysis (CBMA) of functional motor neuroimaging studies involving patients with Parkinson's (PwP), and healthy controls (HC) identified 126 suitable articles. The experiments were grouped based on subject feature, medication status (onMed/offMed), deep brain stimulation (DBS) status (DBSon/DBSoff) and type of motor initiation. Results: HC and PwP shared similar neural networks during upper extremity motor tasks but with differences of reported frequency in mainly bilateral putamen, insula and ipsilateral inferior parietal and precentral gyri. The activation height was significantly reduced in the bilateral putamen, left SMA, left subthalamus nucleus, right thalamus and right midial global pallidum in PwPoffMed (vs. HC), and pre-SMA hypoactivation correlated with disease severity. These changes were not found in patients on dopamine replacement therapy (PwPonMed vs. HC) in line with a restorative function. By contrast, left SMA and primary motor cortex showed hyperactivation in the medicated state (vs. HC) suggesting dopaminergic overcompensation. Deep-brain stimulation (PwP during the high frequency subthalamus nucleus (STN) DBS vs. no stimulation) induced a decrease in left SMA activity and the expected increase in the left subthalamic/thalamic region regardless of hand movement. We further demonstrated a disease related effect of motor intention with only PwPoffMed showing increased activation in the medial frontal lobe in self-initiated studies. Conclusion: We describe a consistent disease-specific pattern of putaminal hypoactivation during motor tasks that appears reversed by dopamine replacement. Inconsistent reports of altered SMA/pre-SMA activation can be explained by task- and medication-specific variation in intention. Moreover, SMA activity was reduced during STN-DBS, while dopamine-induced hyperactivation of SMA which might underpin hyperdynamic L-dopa related overcompensation. [ABSTRACT FROM AUTHOR]

Ratiometric assays, which can effectively surmount external interference, have attracted extensive research interests. Herein, a novel ratiometric sensing platform for Hg2+ is designed based on nitrogen-doped carbon dots (N-CDs) with two different optical signals. Under a single excitation, N-CDs have two emission peaks around 668 nm and 412 nm, which are second-order scattering and fluorescence, respectively. Upon the addition of Hg2+, the weak scattering emission at 668 nm can be increased apparently, while the strong fluorescence intensity at 412 nm is weakened. Moreover, the ratio of scattering intensity to fluorescence intensity is linearly dependent on Hg2+ concentration (0.1–10 μM and 10–30 μM, respectively), and the detection limit is 66 nM. In addition, the ratiometric sensing mechanism is investigated in detail, which is due to the combined effect of aggregation-induced fluorescence quenching and scattering enhancement. Furthermore, the developed sensing approach holds a promising application for Hg2+ detection in actual samples. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1–3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4–6. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear. Here we show that NETs are abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs can predict the occurrence of liver metastases in patients with early-stage breast cancer. NET-DNA acts as a chemotactic factor to attract cancer cells, rather than merely acting as a 'trap' for them; in several mouse models, NETs in the liver or lungs were found to attract cancer cells to form distant metastases. We identify the transmembrane protein CCDC25 as a NET-DNA receptor on cancer cells that senses extracellular DNA and subsequently activates the ILK–β-parvin pathway to enhance cell motility. NET-mediated metastasis is abrogated in CCDC25-knockout cells. Clinically, we show that the expression of CCDC25 on primary cancer cells is closely associated with a poor prognosis for patients. Overall, we describe a transmembrane DNA receptor that mediates NET-dependent metastasis, and suggest that targeting CCDC25 could be an appealing therapeutic strategy for the prevention of cancer metastasis. DNA from neutrophil extracellular traps interacts with the transmembrane receptor CCDC25 on cancer cells, activating the ILK-β-parvin pathway to enhance cell motility and promote distant metastases. [ABSTRACT FROM AUTHOR]

Background: The advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3–5 patients are still a controversial issue. Methods: Two investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3–5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value < 0.05 was considered statistically significant, and all statistical analyses were performed using STATA, version 15.0. This network meta-analysis was undertaken by the frequency model. Results: Forty-four randomised clinical trials with 42,319 patients were included in our network meta-analysis. ACEIs monotherapy significantly decreased the odds of kidney events (OR 0.54, 95% CI 0.41–0.73), cardiovascular events (OR 0.73, 95% CI 0.64–0.84), cardiovascular death (OR 0.73, 95% CI 0.63–0.86) and all-cause death (OR 0.77, 95% CI 0.66–0.91) when compared to placebo. According to the cumulative ranking area (SUCRA), ACEI monotherapy had the highest probabilities of their protective effects on outcomes of kidney events (SUCRA 93.3%), cardiovascular events (SUCRA 77.2%), cardiovascular death (SUCRA 86%), and all-cause death (SUCRA 94.1%), even if there were no significant differences between ACEIs and other antihypertensive drugs, including calcium channel blockers (CCBs), β-blockers and diuretics on above outcomes except for kidney events. ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than CCBs, β-blockers and diuretics in all primary outcomes. In the subgroup of non-dialysis diabetic kidney disease patients, no drugs, including ACEIs or ARBs, significantly lowered the odds of cardiovascular events and all-cause death. However, ACEIs were still better than other antihypertensive drugs including ARBs in all-cause death but not ARBs in cardiovascular events according to the SUCRA. Only ARBs had significant differences in preventing the occurrence of kidney events compared with placebo (OR 0.82, 95% CI 0.72–0.95). Both ACEI/ARB monotherapy and combination therapy had higher odds of hyperkalaemia. ACEIs had 3.81 times higher odds than CCBs (95% CI 1.58–9.20), ARBs had 2.08–5.10 times higher odds than placebo and CCBs and combination therapy of an ACEI and an ARB had 4.80–24.5 times higher odds than all other treatments. Compared with placebo, CCBs and β blockers, ACEI therapy significantly increased the odds of cough (OR 2.90, 95% CI 1.76–4.77; OR 8.21, 95% CI 3.13–21.54 and OR 1.80, 95% CI 1.08–3.00). There were no statistical differences in hypotension among all comparisons except ACEIs versus placebo. Conclusions: Although ACEIs increased the odds of hyperkalaemia, cough and hypotension, they were still superior to ARBs and other antihypertensive drugs and had the highest benefits for the prevention of kidney events, cardiovascular outcomes, cardiovascular death and all-cause mortality in non-dialysis CKD3–5 patients. In patients with advanced diabetic kidney disease, ACEIs were superior to ARBs in lowering risk of all-cause death but not in kidney events and cardiovascular events. [ABSTRACT FROM AUTHOR]

An electrochemical aptasensor for thrombin is introduced that makes use of a nanohybrid composed of silver nanoparticles and graphite-like carbon nitride (Ag-g-C3N4). The material has a large surface and good biocompatibility. AgNPs are modified directly on the surface of g-C3N4 via chemical reduction. A glass carbon electrode (GCE) modified with Ag-g-C3N4 can immobilize a large number of amino-terminated thrombin binding aptamers (NH2-TBA) through strong Ag-N bonds. The electrochemical impedance signal of the aptasensor increases in the presence of thrombin. Under the optimal conditions and by using [Fe(CN)6]3−/4- as an electrochemical probe, the aptasensor shows a wide linear range of 100 fM – 20 nM with a lower detection limit of 38 fM. The method was applied to the determination of thrombin in spiked human plasma and the recoveries fluctuated from 97.2% to 103%. [ABSTRACT FROM AUTHOR]

Hatching out from the zona pellucida (ZP) is a crucial step for blastocyst implantation and development. However, it is still unknown whether the location of the hatching site relative to the inner cell mass (ICM) affects embryo implantation and foetal development. Here, we classified hatching blastocysts into three categories, 0° ≤ θ ≤ 30°, 30° < θ ≤ 60°, and 60° < θ ≤ 90°, in which θ is determined based on the relative position of the hatching site to the arc midpoint of the ICM. Non-surgical embryo transfer (NSET) devices were employed to evaluate blastocyst implantation and embryo development. Of 1,827 hatching blastocysts, 43.84%, 30.60%, and 21.67% were categorized as 30° < θ ≤ 60°, 0° ≤ θ ≤ 30°, and 60° < θ ≤ 90°, respectively. Embryos with different hatching sites showed no distinct differences in blastocyst implantation; surrogate female pregnancy; embryo development to term; litter size, or offspring survival, gender, or body weight. Our results indicate that mouse blastocyst hatching site is not randomly distributed. Embryo implantation and development are not correlated with the blastocyst hatching site in mice. Thus, assessment of the blastocyst hatching site should not be recommended to evaluate mouse blastocyst implantation and developmental potential. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effectiveness and safety of Xingnaojing Injection (XNJ, 醒脑静注射 液) compared with naloxone for the treatment of acute alcohol intoxication (AAI), and provide the latest evidence through evidence-based approach. Methods: Seven electro-databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure Databases, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database (VIP) and Wanfang Database were searched from the inception to January 2018. Randomized controlled trials (RCTs) comparing XNJ with naloxone for patients with AAI and reporting at least one of the below outcomes were included: patients' conscious recovery time, stay length in emergency department, disappearance time of the ataxia symptom, the severity of the symptoms, the blood alcohol content as well as the adverse events. Methodological quality of included trials was assessed using the risk of bias tool which recommended by the Cochrane Collaboration. Meta-analysis was conducted by Review Manager 5.3 software. Results: Totally 141 trials with 13,901 patients were included in this review, all of them were assessed as unclear or high risk of bias. Results showed that on the basis of routine therapy, standard dose XNJ (10–20 mL) may have similar results with naloxone on the recovery time of consciousness (MD 12 min, 95% CI 7.2–17.4 min) and disappearance time of symptoms (MD 6 min, 95% CI–13.8–25.8 min) for patients with AAI. Larger dose of XNJ Injection (21–40 mL) may speed up the time (almost 1 h earlier). Combination of XNJ and naloxone seemed superior to the naloxone alone for all the relevant outcomes. The average difference of time in consciousness recovery was 2 h and the number of AAI patients whose consciousness recovery within 1 h was above 50% the combination group than in the control group (RR 1.42, 95% CI 1.29 to 1.56). No severe adverse events or adverse reactions of XNJ were reported in the included trials. Conclusions: Low quality of evidence showed XNJ may have equal effect as naloxone and may achieve better effect as add-on intervention with naloxone for patients with AAI. We failed to evaluate the safety of XNJ Injection due to the insufficient evidence in this review. Registration number. in PROSPERO (No. CRD42018087804) [ABSTRACT FROM AUTHOR]

Objectives: To explore if there is a correlation between T2WI histogram features of the primary tumor and the existence of regional lymph node (LN) metastasis in rectal cancer.Methods: Eighty-eight patients with pathologically proven rectal adenocarcinoma, who received direct surgical resection and underwent preoperative rectal MRIs, were enrolled retrospectively. Based on pathological analysis of surgical specimen, patients were classified into negative LN (LN-) and positive LN (LN+) groups. The degree of differentiation and pathological T stage were recorded. Clinical T stage, tumor location, and maximum diameter of tumor were evaluated of each patient. Whole-tumor texture analysis was independently performed by two radiologists on axial T2WI, including skewness, kurtosis, energy, and entropy.Results: The interobserver agreement was overall good for texture analysis between two radiologists, with intraclass correlation coefficients (ICCs) ranging from 0.626 to 0.826. The LN- group had a significantly higher skewness (p < 0.001), kurtosis (p < 0.001), and energy (p = 0.004) than the LN+ group, and a lower entropy (p = 0.028). These four parameters showed moderate to good diagnostic power in predicting LN metastasis with respective AUC of 0.750, 0.733, 0.669, and 0.648. In addition, they were both correlated with LN metastasis (rs = - 0.413, - 0.385, - 0.28, and 0.245, respectively). The multivariate analysis showed that lower skewness was an independent risk factor of LN metastasis (odds ratio, OR = 9.832; 95%CI, 1.171-56.295; p = 0.01).Conclusions: Signal intensity histogram parameters of primary tumor on T2WI were associated with regional LN status in rectal cancer, which may help improve the prediction of nodal stage.Key Points: • Histogram parameters of tumor on T2WI may help to reduce uncertainty when assessing LN status in rectal cancer. • Histogram parameters of tumor on T2WI showed a significant difference between different regional LN status groups in rectal cancer. • Skewness was an independent risk factor of regional LN metastasis in rectal cancer. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing using cyclic pumping is a potential method for effective stimulation of unconventional oil and gas reservoirs. In our study, the laboratory-scale hydraulic fracturing experiments using cyclic pumping were conducted using cuboid concrete specimens with multiple perforation clusters. The results showed that by cyclic pumping more fractures were created from perforation clusters when compared to non-cyclic monotonic pumping. This trend was shown to increase when using high-viscosity fracturing fluids. In our cyclic pumping experiments, the maximum pressure in the first pumping cycle reached the breakdown pressure and at each subsequent cycle the maximum pressure increased. The increased maximum pressure likely acted to generate more fractures initiating from the given perforation clusters even under greater fracture height to spacing ratios and more acoustic emission (AE) events were generated by cyclic pumping compared with those by monotonic pumping. Well compliance was examined and showed a negligible change in the system compressibility among cycles. This suggests that the fractures formed by previous injection cycles were isolated from the wellbore at the start of this cycle and at least their near-well portions are closed. There are a few possibilities contributing to the difficulty in reopening the existing hydraulic fractures in subsequent injection cycles. Detailed discussion is provided based on the varying features of injection pressure. This cyclic injection method could deliver an alternative for multi-stage fracturing treatments in field applications. [ABSTRACT FROM AUTHOR]

Intercropping Persian walnut (Juglans regia L.) and wheat (Triticum aestivum L.) have been widely applied in the Xinjiang Uygur Autonomous Region in Northwest China as a means of reducing soil and water losses and improving both land-use efficiency and economic returns. To understand how changes in soil conditions and nematode community structure can contribute to the evaluation of wheat-walnut intercropping systems from the view of soil fauna, we studied the soil nematode community in wheat rhizosphere soil under both monoculture and intercropping systems for 2 years. The results showed that the pH and total nitrogen and organic matter contents in intercropping systems with walnut trees were decreased compared with those of system with wheat alone. The nematode communities differed significantly between intercropping and monoculture plots, e.g., Rhabditis and Dorylaimus were dominant only in monocultures, whereas Tylenchus was dominant only in intercropping systems. Moreover, intercropping systems resulted in decreased nematode abundance, increased proportions of plant-feeding nematodes, and decreased omnivores/predators, particularly in the second year (2012). The decrease in diversity indices (H′) and ecological indices (WI, EI, and SI) of the nematode communities indicated high disturbance and low soil fertility in intercropping systems. Overall, wheat intercropping with walnut had a significant negative effect on wheat rhizosphere soil conditions. [ABSTRACT FROM AUTHOR]

Background: With the worldwide use and modern development of acupuncture-moxibustion, there is disagreement on its basic definition. There has been an obstacle for clinical practice, research, and legislation. Considering this challenge, the World Federation of Acupuncture-Moxibustion Societies proposes to develop the definition and basic scope of acupuncture-moxibustion with a Delphi study.Methods: A reactive Delphi method will be used to ask a group of experts to rate the relevance and clarity of a predesigned initial item list. This list was generated by the steering committee through a literature review and group discussion. Forty experts will be selected from many disciplines and continents to ensure appropriate representation. Predefined rules will be applied to modify the items until a consensus is achieved. After achieving the consensus on all items through the survey round, the steering committee will form the definition and basic scope of acupuncture-moxibustion by organizing a literal statement with a detailed explanation. [ABSTRACT FROM AUTHOR]

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