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Rong Hong,1,2,* Xiaoxia Ping,2,3,* Yuanying Liu,2 Feiwen Feng,2 Su Hu,2,3 Chunhong Hu2,3 1Department of Radiology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215100, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhong Hu; Su Hu, Department of Radiology, The First Affiliated Hospital of Soochow University; Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, People’s Republic of China, Email sdhuchunhong@sina.com; husu@suda.edu.cnPurpose: The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model.Methods: In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models’ performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility.Results: Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664– 0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781– 0.906) and 0.836 (95% CI: 0.732– 0.940) in the training and testing cohorts, respectively.Conclusion: The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.Keywords: computed tomography, invasive mucinous adenocarcinoma, radiomics, machine learning

Linhua Wu,1 Jian Li,1 Xiaowei Ruan,2 Jialiang Ren,3 Xuejun Ping,4 Bing Chen1 1Department of Radiology, General Hosipital of Ningxia Medical University, YinChuan, Ningxia Hui Autonomous Region, People’s Republic of China; 2Department of Radiology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of China; 3Department of Pharmaceuticals Diagnosis, GE Healthcare, Beijing, People’s Republic of China; 4Department of Clinical Medical Faculty, Medical University of Ningxia, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of ChinaCorrespondence: Xuejun Ping, Department of Clinical Medical Faculty, Medical University of Ningxia, No. 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of China, Tel +8613709516402, Email 627898331@qq.comBackground: Energy spectrum CT is an effective method to evaluate the biological behavior of lung cancer. Radiomics is a non-invasive technology to obtain histological information related to lung cancer.Purpose: To investigate the value of the radiomics models on the bases of enhanced spectral CT images of peripheral lung cancer to predict the expression of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).Material and Methods: This study retrospectively analyzed 73 patients with peripheral lung cancer confirmed by postoperative pathology. All patients underwent dual-phase enhanced spectral CT scans before surgery. Regions of interest (ROI) were delineated in the arterial phase and venous phase. Key radiomics features were extracted and models were established to predict the expression of VEGF and EGFR, respectively. All models were established based on the expression levels of VEGF and EGFR in tissues detected by immunohistochemical staining as reference standards. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of each model, and decision curve analysis (DCA) was used to evaluate the clinical utility of the models.Results: In predicting the expression level of VEGF, the combined (COMB) model composed of one spectral feature and two radiomics features achieved the best performance with area under ROC (AUC) 0.867 (95% CI: 0.767– 0.966), accuracy of 0.812, sensitivity of 0.879, and specificity of 0.667. According to the expression level of EGFR, three importance radiomics features were retained in the arterial and venous phases to establish the multiphase phase model which has the best performance with AUC of 0.950 (95% confidence interval: 0.89– 1.00), accuracy of 0.896, sensitivity of 0.868, and specificity of 1.Conclusion: The radiomics model of enhanced spectral CT images of peripheral lung cancer can predict the expression of EGFR and VEGF.Keywords: peripheral lung cancer, radiomics, energy spectrum CT, VEGF, EGFR

The Cape hare (Lepus capensis) is among the most widely distributed hare species globally, inhabiting extensive regions across Africa, the Middle East, and Central Asia. However, evolutionary and genetic research on L. capensis was seriously impeded by the absence of a reference genome. Here, we assembled and constructed a chromosome-level genome of L. capensis (with scaffolds anchored to 25 chromosomes and a total assembled length of 2.9 Gb, achieving a contig N50 length of 124.44 Mb) using PacBio HiFi sequencing and Hi-C assembly technology. Evaluation using BUSCO indicated the genome assembly to be 98.2% complete. The de novo prediction revealed that repetitive sequences constitute 46.13% of the entire genome, and long interspersed nuclear elements (LINEs) constituted the largest portion. We annotated a total of 13, 868 protein-coding genes using transcriptomes from two tissues (muscle and skin). This high-quality reference genome serves as a valuable genomic resource for advancing genetic studies in this species., (© 2024. The Author(s).)

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53 , PCLO , and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

Maintaining protein homeostasis (proteostasis) requires precise control of protein folding and degradation. Failure to properly respond to stresses disrupts proteostasis, which is a hallmark of many diseases, including cataracts. Hibernators are natural cold-stress adaptors; however, little is known about how they keep a balanced proteome under conditions of drastic temperature shift. Intriguingly, we identified a reversible lens opacity phenotype in ground squirrels (GSs) associated with their hibernation-rewarming process. To understand this "cataract-reversing" phenomenon, we first established induced lens epithelial cells differentiated from GS-derived induced pluripotent stem cells, which helped us explore the molecular mechanism preventing the accumulation of protein aggregates in GS lenses. We discovered that the ubiquitin-proteasome system (UPS) played a vital role in minimizing the aggregation of the lens protein αA-crystallin (CRYAA) during rewarming. Such function was, for the first time to our knowledge, associated with an E3 ubiquitin ligase, RNF114, which appears to be one of the key mechanisms mediating the turnover and homeostasis of lens proteins. Leveraging this knowledge gained from hibernators, we engineered a deliverable RNF114 complex and successfully reduced lens opacity in rats with cold-induced cataracts and zebrafish with oxidative stress-related cataracts. These data provide new insights into the critical role of the UPS in maintaining proteostasis in cold and possibly other forms of stresses. The newly identified E3 ubiquitin ligase RNF114, related to CRYAA, offers a promising avenue for treating cataracts with protein aggregates.

The serious problem of carbon monoxide (CO) poisoning on the surface of Pt-based catalysts has long constrained the commercialization of proton exchange membrane fuel cells (PEMFCs). Regeneration of Pt sites by maintaining CO scavenging ability through precise construction of the surface and interface structure of the catalyst is the key to obtaining high-performance CO-resistant catalysts. Here, we used molybdenum carbide (MoC x ) as the support for Pt and introduced Ru single atoms (SA-Ru) at the Pt-MoC x interface to jointly decrease the CO adsorption strength on Pt. More importantly, the MoC x and SA-Ru are immune to CO poisoning, which continuously assists in the oxidation of adsorbed CO by generating oxygen species from water dissociation. These two effects combine to confer this anode catalyst (SA-Ru@Pt/MoC x ) remarkable CO tolerance and the ability to operate stably in fuel cell with high CO concentration (power output 85.5 mW cm -2 @20,000 ppm CO + H 2 - O 2 ), making it possible to directly use the cheap reformed hydrogen as the fuel for PEMFCs., (© 2024. The Author(s).)

Purpose: To gain insight into patients' visual experiences and satisfaction when using different forms of myopia control lenses., Methods: PubMed, Cochrane Library, Embase, Scopus and Web of Science databases were searched for articles assessing subjective visual quality with myopia control lenses compared with single-vision lenses (SVLs) up to July 10, 2023. Eight-hundred-and-three articles were retrieved, reviewed and any questionnaire items on subjective impressions of lens wear were meta-analysed. Subgroup analyses were based on the magnitude of defocus (add power) of multifocal soft contact lenses (MFSCLs) and age groups. A random-effects model was employed for meta-analysis, and I 2 statistic used to assess the statistical heterogeneity., Results: Nineteen articles fit the criteria, but only six articles involving MFSCLs had relevant data. MFSCLs were associated with lower subjective ratings of vision at different distances compared to SVLs (p < 0.001), but the differences were less than one unit. MFSCLs also yielded lower ratings when moving or walking and/or climbing stairs at -0.38 (-0.69 to -0.07, p = 0.02; I 2  = 85 %, p < 0.001) and for subjective comfort (difference of -0.23, -0.41 to -0.05, p = 0.01; I 2  = 63 %, p < 0.001). Subjective ratings for playing sports were not different between groups. Experience with MFSCLs was rated lower by young adults compared to children for all variables. In both children and young adults, ratings were lower with higher add compared to lower add MFSCLs., Conclusion: Although subjective ratings for vision and comfort were lower with MFSCLs compared to SVLs, the difference was mostly less than one unit. Importantly, young adults rated their visual experience lower compared to children., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Metastasis worsens prostate cancer (PCa) prognosis, with the immunosuppressive microenvironment playing a key role in bone metastasis. This study aimed to investigate how an immunosuppressive environment promotes PCa metastasis and worsens prognosis of patients with PCa., Methods: Candidate oncogenes were identified through analysis of the Gene Expression Omnibus (GEO) database. A prognostic model was developed for the purpose of identifying target genes. A single-cell RNA sequencing data from GEO database was used to analyze the localization of target genes in the tumor microenvironment. A pan-cancer analysis was conducted to study the cancer-causing potential of target genes across different types of tumors., Results: Fifty-one genes were found to be differentially expressed in bone metastasis compared to non-metastatic PCa, with CKS2 identified as the most significant gene associated with poor prognosis. CKS2 was shown to be linked to an immunosuppressive microenvironment and osteoclastic bone metastases, as shown by its negative correlation with immune cell infiltration and osteoblast-related gene expression. Moreover, CKS2 was found in immunosuppressive cells and was linked to bone metastasis in PCa. It was also overexpressed in different types of tumors, making it as an oncogenic gene., Conclusions: This research offers a new perspective on the potential utility of CKS2 as a therapeutic target for the prevention of metastatic PCa., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2100/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: Cabbage Fusarium wilt (CFW) is a devastating disease caused by the soil-borne fungus Fusarium oxysporum f. sp. conglutinans (Foc). One of the optimal measures for managing CFW is the employment of tolerant/resistant cabbage varieties. However, the interplay between plant genotypes and the pathogen Foc in shaping the rhizosphere microbial community, and the consequent influence of these microbial assemblages on biological resistance, remains inadequately understood., Results: Based on amplicon metabarcoding data, we observed distinct differences in the fungal alpha diversity index (Shannon index) and beta diversity index (unweighted Bray-Curtis dissimilarity) within the rhizosphere of the YR (resistant to Foc) and ZG (susceptible to Foc) cabbage varieties, irrespective of Foc inoculation. Notably, the Shannon diversity shifts in the resistant YR variety were more pronounced following Foc inoculation. Disease-resistant plant variety demonstrate a higher propensity for harboring beneficial microorganisms, such as Pseudomonas, and exhibit superior capabilities in evading harmful microorganisms, in contrast to their disease-susceptible counterparts. Furthermore, the network analysis was performed on rhizosphere-associated microorganisms, including both bacteria and fungi. The networks of association recovered from YR exhibited greater complexity, robustness, and density, regardless of Foc inoculation. Following Foc infection in the YR rhizosphere, there was a notable increase in the dominant bacterium NA13, which is also a hub taxon in the microbial network. Reintroducing NA13 into the soil significantly improved disease resistance in the susceptible ZG variety, by directly inhibiting Foc and triggering defense mechanisms in the roots., Conclusions: The rhizosphere microbial communities of these two cabbage varieties are markedly distinct, with the introduction of the pathogen eliciting significant alterations in their microbial networks which is correlated with susceptibility or resistance to soil-borne pathogens. Furthermore, we identified a rhizobacteria species that significantly boosts disease resistance in susceptible cabbages. Our results indicated that the induction of resistance genes leading to varied responses in microbial communities to pathogens may partly explain the differing susceptibilities of the cabbage varieties tested to CFW. Video Abstract., (© 2024. The Author(s).)

A key step of Canonical Nonhomologous End Joining (C-NHEJ) is synapsis of DNA double strand break (DSB) ends for ligation. The DNA-PKcs dimer mediates synapsis in a long-range complex with DSB ends remaining apart, whereas the XLF homodimer can mediate synapsis in both long-range and short-range complexes. Recent structural studies found the PAXX homodimer may also facilitate synapsis in long-range complexes with DNA-PKcs via its interactions with Ku70. Thus, we examined the influence of PAXX in C-NHEJ of chromosomal DSBs, which we compared to another Ku-binding factor, MRI. Using EJ of blunt DSBs with Cas9 reporters as a readout for C-NHEJ, we found that PAXX and/or MRI are dispensable. However, when combined with disruption of DNA-PKcs, particularly with DNA-PKcs kinase inhibition, PAXX becomes important for blunt DSB EJ. In contrast, while DNA-PKcs is also important to suppress short deletion mutations with microhomology, this effect is not magnified with PAXX loss. MRI loss had no effect combined with DNA-PKcs disruption, but becomes important for blunt DSB EJ when combined with disruption of XLF, as is PAXX. Finally, XLF loss causes an increase in larger deletions compared to DNA-PKcs inhibition, which is magnified with combined loss of MRI. Altogether, we suggest that PAXX promotes DSB end synapsis during C-NHEJ in a manner that is partially redundant with DNA-PKcs and XLF, whereas MRI appears to be mainly important in the context of XLF disruption., Competing Interests: COMPETING INTEREST DECLARATION The authors have no conflicts of interest to disclose.

Current biotechnology relies on a few well-studied model organisms, such as Escherichia coli and Saccharomyces cerevisiae, for which abundant information and efficient toolkits are available for genetic manipulation, but which lack industrially favorable characteristics. Non-model industrial microorganisms usually do not have effective and/or efficient genome-engineering toolkits, which hampers the development of microbial cell factories to meet the fast-growing bioeconomy. In this study, using the non-model ethanologenic bacterium Zymomonas mobilis as an example, we developed a workflow to mine and temper the elements of restriction-modification (R-M), CRISPR/Cas, toxin-antitoxin (T-A) systems, and native plasmids, which are hidden within industrial microorganisms themselves, as efficient genome-editing toolkits, and established a genome-wide iterative and continuous editing (GW-ICE) system for continuous genome editing with high efficiency. This research not only provides tools and pipelines for engineering the non-model polyploid industrial microorganism Z. mobilis efficiently, but also sets a paradigm to overcome biotechnological limitations in other genetically recalcitrant non-model industrial microorganisms., Competing Interests: Declaration of interests The authors declare that they have a patent application associated with this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ruthenium dioxide is presently the most active catalyst for the oxygen evolution reaction (OER) in acidic media but suffers from severe Ru dissolution resulting from the high covalency of Ru-O bonds triggering lattice oxygen oxidation. Here, we report an interstitial silicon-doping strategy to stabilize the highly active Ru sites of RuO 2 while suppressing lattice oxygen oxidation. The representative Si-RuO 2 -0.1 catalyst exhibits high activity and stability in acid with a negligible degradation rate of ~52 μV h -1 in an 800 h test and an overpotential of 226 mV at 10 mA cm -2 . Differential electrochemical mass spectrometry (DEMS) results demonstrate that the lattice oxygen oxidation pathway of the Si-RuO 2 -0.1 was suppressed by ∼95% compared to that of commercial RuO 2 , which is highly responsible for the extraordinary stability. This work supplied a unique mentality to guide future developments on Ru-based oxide catalysts' stability in an acidic environment., (© 2024. The Author(s).)

Objectives: Tenecteplase, a modified variant of alteplase with greater fibrin specificity and longer plasma half-life, may have better efficacy and safety than alteplase in patients with acute ischemic stroke (AIS). We aimed to compare the benefits and risks of tenecteplase versus alteplase in the treatment of AIS., Methods: Electronic databases were searched up to 10 February 2023 for randomized controlled trials evaluating the effect of tenecteplase versus alteplase in the treatment of AIS. The primary outcome was functional outcome at 90 days, and secondary outcomes including the symptomatic intracranial haemorrhage (SICH), and major neurological improvement. Subgroup analysis was performed based on the different dosage of tenecteplase., Results: Ten studies with a total of 5123 patients were analysed in this meta-analysis. Overall, no significant difference between tenecteplase and alteplase was observed for functional outcome at 90 days (excellent: OR 1.08, 95%CI 0.93-1.26, I 2  = 26%; good: OR 1.04, 95%CI 0.83-1.30, I 2  = 56%; poor: OR 0.95, 95%CI 0.75-1.21, I 2  = 31%), SICH (OR 1.12, 95%CI 0.79-1.59, I 2  = 0%), and early major neurological improvement (OR 1.26, 95%CI 0.80-1.96, I 2  = 65%). The subgroup analysis suggested that the 0.25 mg/kg dose of tenecteplase had potentially greater efficacy and lower symptomatic intracerebral haemorrhage risk compared with 0.25 mg/kg dose tenecteplase., Conclusions: Among AIS patients, there was no significant difference on clinical outcomes between tenecteplase and alteplase. Subgroup analysis demonstrated that 0.25 mg/kg doses of tenecteplase were more beneficial than 0.4 mg/kg doses of tenecteplase. Further studies are required to identify the optimal dosage of tenecteplase.

We have developed an integrated, project-oriented curriculum for undergraduate molecular biology and biochemistry laboratory courses spanning two semesters that is organized around the "ldhA" gene from the yogurt-fermenting bacterium "Lactobacillus bulgaricus," which encodes the enzyme d-lactate dehydrogenase. The molecular biology module, which consists of nine experiments carried out over eleven sessions, begins with the isolation of genomic DNA from "L. bulgaricus" in yogurt and guides students through the process of cloning the "ldhA" gene into a prokaryotic expression vector, followed by mRNA isolation and characterization of recombinant gene expression levels using RT-PCR. The biochemistry module, which consists of nine experiments carried out over eight sessions, begins with overexpression of the cloned ldhA gene and guides students through the process of affinity purification, biochemical characterization of the purified "LdhA" protein, and analysis of enzyme kinetics using various substrates and an inhibitor, concluding with a guided inquiry investigation of structure-function relationships in the three-dimensional structure of "LdhA" using molecular visualization software. Students conclude by writing a paper describing their work on the project, formatted as a manuscript to be submitted for publication in a scientific journal. Overall, this curriculum, with its emphasis on experiential learning, provides hands-on training with a variety of common laboratory techniques in molecular biology and biochemistry and builds experience with the process of scientific reasoning, along with reinforcement of essential transferrable skills such as critical thinking, information literacy, and written communication, all within the framework of an extended project having the look and feel of a research experience.

Objective: To analyze from a pathological perspective the differences between intermittent and persistent hydronephrosis in children with uretero-pelvic junction obstruction., Methods: 23 children who underwent unilateral dismembered pyeloplasty (Anderson-Hynes operation) for intermittent hydronephrosis from September 2017 to March 2024 were included in the observation group. They were compared with a control group consisting of 23 children with persistent hydronephrosis matched for age, gender, and affected side. All children had the narrowed segment surgically excised during the operation, while other obstructive causes (such as polyps, crossing vessels, or tumor compression) were excluded. The specimens were analyzed for muscle and collagen content using Masson's trichrome staining, and the collagen-to-muscle ratio (CMR) was calculated. The number of Cajal-like cells was quantified with c-kit immunohistochemical staining. For all slides, 10 random fields of view were selected under a 400× optical microscope to record pathological data and calculate mean values. Pathological indicators between the two groups were compared using the T -test and the Chi-square test, with P  < 0.05 considered statistically significant., Results: The observation group showed a significant difference in the number of fields with low, medium, and high densities of Cajal-like cells compared to the control group [132 (57.4%) vs. 173 (75.2%); 70 (30.4%) vs. 38 (16.5%); 28(12.2%) vs. 19 (8.3%), P  < 0.001]. The uretero-pelvic junction in children with intermittent hydronephrosis had lower collagen content, higher muscle content, and a more regular arrangement. The collagen-muscle ratio was significantly lower than that in children with persistent hydronephrosis [(1.59 ± 0.65) vs. (3.98 ± 1.19), P  < 0.001]., Conclusion: Compared with persistent hydronephrosis, the narrowed segment at the uretero-pelvic junction in children with intermittent hydronephrosis has a higher density of Cajal-like cells; lower collagen content, and higher muscle content (lower collagen-muscle ratio)., 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., (© 2024 Yan, Jizhen, Ping, Cheng and Dongsheng.)

Soil is indispensable for agricultural production but has been seriously polluted by cadmium and salt in recent years. Many crops are suffering from this, including rapeseed, the third largest global oilseed crop. However, genes simultaneously related to both cadmium and salt stress have not been extensively reported yet. In this study, BnaA10.WRKY75 was screened from previous RNA-seq data related to cadmium and salt stress and further analyses including sequence comparison, GUS staining, transformation and qRT-PCR were conducted to confirm its function. GUS staining and qRT-PCR results indicated BnaA10.WRKY75 was induced by CdCl 2 and NaCl treatment. Sequence analysis suggested BnaA10.WRKY75 belongs to Group IIc of the WRKY gene family and transient expression assay showed it was a nuclear localized transcription factor. BnaA10.WRKY75 -overexpressing Arabidopsis and rapeseed plants accumulated more H 2 O 2 and O 2 - and were more sensitive to CdCl 2 and NaCl treatment compared with untransformed plants, which may be caused by the downregulation of BnaC03.CAT2 . Our study reported that BnaA10.WRKY75 increases sensitivity to cadmium and salt stress by disrupting the balance of reactive oxygen species both in Arabidopsis and rapeseed. The results support the further understanding of the mechanisms underlying cadmium and salt tolerance and provide BnaA10.WRKY75 as a valuable gene for rapeseed abiotic stress breeding.

To evaluate the efficacy of radiomics features extracted from preoperative high-resolution computed tomography (HRCT) scans in distinguishing benign and malignant pulmonary pure ground-glass nodules (pGGNs), a retrospective study of 395 patients from 2016 to 2020 was conducted. All nodules were randomly divided into the training and validation sets in the ratio of 7:3. Radiomics features were extracted using MaZda software (version 4.6), and the least absolute shrinkage and selection operator (LASSO) was employed for feature selection. Significant differences were observed in the training set between benign and malignant pGGNs in sex, mean CT value, margin, pleural retraction, tumor-lung interface, and internal vascular change, and then the mean CT value and the morphological features model were constructed. Fourteen radiomics features were selected by LASSO for the radiomics model. The combined model was developed by integrating all selected radiographic and radiomics features using logistic regression. The AUCs in the training set were 0.606 for the mean CT value, 0.718 for morphological features, 0.756 for radiomics features, and 0.808 for the combined model. In the validation set, AUCs were 0.601, 0.692, 0.696, and 0.738, respectively. The decision curves showed that the combined model demonstrated the highest net benefit.

Rationale: Cataract is the leading cause of blindness and low vision worldwide, yet its pathological mechanism is not fully understood. Although macroautophagy/autophagy is recognized as essential for lens homeostasis and has shown potential in alleviating cataracts, its precise mechanism remains unclear. Uncovering the molecular details of autophagy in the lens could provide targeted therapeutic interventions alongside surgery. Methods: We monitored autophagic activities in the lens and identified the key autophagy protein ATG16L1 by immunofluorescence staining, Western blotting, and transmission electron microscopy. The regulatory mechanism of ATG16L1 ubiquitination was analyzed by co-immunoprecipitation and Western blotting. We used the crystal structure of E3 ligase gigaxonin and conducted the docking screening of a chemical library. The effect of the identified compound riboflavin was tested in vitro in cells and in vivo animal models. Results: We used HLE cells and connexin 50 (cx50)-deficient cataract zebrafish model and confirmed that ATG16L1 was crucial for lens autophagy. Stabilizing ATG16L1 by attenuating its ubiquitination-dependent degradation could promote autophagy activity and relieve cataract phenotype in cx50 -deficient zebrafish. Mechanistically, the interaction between E3 ligase gigaxonin and ATG16L1 was weakened during this process. Leveraging these mechanisms, we identified riboflavin, an E3 ubiquitin ligase-targeting drug, which suppressed ATG16L1 ubiquitination, promoted autophagy, and ultimately alleviated the cataract phenotype in autophagy-related models. Conclusions: Our study identified an unrecognized mechanism of cataractogenesis involving ATG16L1 ubiquitination in autophagy regulation, offering new insights for treating cataracts., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

With the development of municipal solid waste incineration technologies, the disposal of fly ash has become a difficult problem that many countries need to solve. High-temperature melting is a promising disposal technology. Based on this, a new process for collaborative treatment of fly ash in metallurgical blast furnaces had been proposed in this study. To explore the impact of disposal of fly ash on blast furnace production, by simulating the high-temperature reducing environment of blast furnaces, the melting changes of water-washed fly ash (W-FA), and the effects of W-FA injection on coal combustion and products (slag, iron) composition were studied. The results showed that W-FA, as a flux, could be sprayed into the blast furnace separately or mixed with coal. But when injected along with coal, W-FA would suppress the combustion of coal. After melting, the removal rates of S, P, Cl, and Pb in W-FA were 21%, 30%, 86%, and 89%, respectively. The removal rates of K, Na, and Zn were close to 100%, and Cr was basically not removed. When the proportion of W-FA to coal was less than 1%, in addition to controlling the alkalinity of the slag, the impact of W-FA on the composition of iron and slag was minimal. The successful execution of this work will not only achieve the reduction, harmless and resourceful utilization of fly ash, but also save investment and operating costs of disposal facilities, with both environmental and social benefits., 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 Ltd. All rights reserved.)

As the core sensing elements of ultra-long fiber interferometer, the distributed thermal strain difference of the fiber rings can cause extra noise of the flexural disk, resulting in a penalty of the deterioration accuracy. In this paper, the thermal strain distribution characteristics of the fiber ring are firstly analyzed by the finite element method (FEM), and the distribution result is consistent with that demonstrated by the Rayleigh optical frequency-domain reflectometry (R-OFDR) strain measurement. The interferometer phase noise caused by the distributed strain difference is further studied by constructing a fully symmetric polarization-maintaining fiber-ring Mach-Zehnder interferometer (MZI) with an arm length of over 100 meters. The results show that the distributed thermal strain difference of two fiber rings will cause additional phase fluctuation, which leads to higher low-frequency noise. Therefore, a dual-fiber-ring MZI with matched distributed thermal strains is proposed to suppress the phase noise caused by the thermal strain, and the best suppression is as high as 45.6 dB. This is very important for the research and design of low noise fiber seismometer.

The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na + reabsorption kinetics by SGLT1/2. For area under the plasma concentration-time curve, maximum plasma concentration, and cumulative EMP excretion in urine, the predicted values fell within a range of 0.5-2.0 when compared to observed data. Additionally, the simulated UGE data also matched well with the clinical data, further validating the accuracy of the model. According to the simulations, SGLT1 and SGLT2 contributed approximately 13% and 87%, respectively, to RGR in the absence of EMP. However, in the presence of EMP at doses of 2.5 and 10 mg, the contribution of SGLT1 to RGR significantly increased to approximately 76%-82% and 89%-93%, respectively, in patients with type 2 diabetes mellitus. Furthermore, the model supported the understanding that the compensatory effect of SGLT1 is the underlying mechanism behind the moderate inhibition observed in total RGR. The PBPK-UGE model has the capability to accurately predict the PK and UGE time profiles in humans. Furthermore, it provides a comprehensive analysis of the specific contributions of SGLT1 and SGLT2 to RGR in the presence or absence of EMP., (© 2024, The American College of Clinical Pharmacology.)

Background: Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting., Aims: The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model., Methods: Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1β (IL-1β) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding., Results: Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1β signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1β., Conclusion: This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The optimal range of protein dosage and effect of high-dose protein on critically ill patients remain controversial. We conducted a meta-analysis to compare higher and lower doses of protein supplementation for nutritional support in critically ill patients., Methods: We searched the PubMed, Embase, Scopus, and Cochrane Library databases for randomized controlled trials that compared higher (≥1.2 g/kg per day) versus lower (<1.2 g/kg per day) doses of protein supplementation among critically ill adult patients. This search spanned from the inception of relevant databases to November 20, 2023. Our primary endpoint of interest was overall mortality, while secondary endpoints included length of stay in the intensive care unit, length of hospital stay, duration of mechanical ventilation, and incidence of acute kidney injury., Results: Seventeen studies including 2,965 critically ill patients were included in our meta-analysis. The pooled analyses showed no significant difference in overall mortality (RR 1.03, 95%CI [0.92-1.15], P = 0.65, I 2 = 0%), length of intensive care unit stay (MD 0.19, 95%CI [-0.67 to 1.04], P = 0.66, I 2 = 25%), length of hospital stay (MD 0.73, 95%CI [-1.59 to 3.04], P = 0.54, I 2 = 27%), duration of mechanical ventilation (MD -0.14, 95%CI [-0.83 to 0.54], P = 0.68, I 2 = 8%), and incidence of acute kidney injury (RR 1.11, 95%CI [0.87-1.41], P = 0.38, I 2 = 0%) between critically ill patients receiving higher or lower doses of protein supplementation., Conclusions: For critically ill patients, the protein supplementation dose had no significant effect on clinical outcomes, including overall mortality, length of intensive care unit and hospital stay, duration of mechanical ventilation, and incidence of acute kidney injury., Competing Interests: The authors declare that they have no competing interests., (© 2024 Qin et al.)

Purpose: Depression is a psychiatric disorder and the treatment of depression is an urgent problem that need to be solved. Gastrodin (GAS) is a Traditional Chinese Medicine from an orchid and is used for neurological diseases, including depressive disorders., Methods: To assess the effect of GAS on gut microbiota of depressive mice, we established a chronic unpredictable mild stress (CUMS)-induced mouse model, and GAS was administered to one group of the mice. Animal behavior experiments were used to detect depressive-like behaviors, and 16 S rRNA gene analysis was applied to detect the gut microbiota of each group. All raw sequences were deposited in the NCBI Sequence Read Archive under accession number SRP491061., Results: GAS treatment significantly improved depressive-like behaviors as well as the diversity and abundance of the gut microbiota. The depressive-like behaviors of the CUMS-GAS group were improved in different degrees compared with the CUMS group. The linear discriminant analysis (LDA) of the gut microbiota showed that the makeup of the gut microbiota in mice changed dramatically in the CUMS-GAS group, compared with the CUMS group, Bacteroides (LDA = 3.94, P < 0.05) were enriched in the CUMS-GAS group at the genus level. In comparison to the CUMS group, the CUMS-GAS group had a greater concentration numbers of Lactobacillus, Corynebacterium, Staphylococcus, Bacteroides, Psychrobacter, and Alistipes., Conclusion: Our results suggested that GAS improved depressive-like behaviors in mice and impacted the microbial composition of the gut. Our research indicated that dysbiosis of the gut microbiota may be affected by GAS treatment, which improved depressive-like behaviors in the CUMS-induced mouse model of depression., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited iridescent color changes that corresponded to the birefringence phenomenon under polarized light, which was attributed to the formation of cholesteric structures. ZnO nanoparticles were proved to successfully adjust the helical pitches of the chiral arrangements of the CNCs, resulting in tunable optical light with shifted wavelength bands. Furthermore, the nanocomposite films showed fast humidity and ethanol stimuli response properties, exhibiting the potential of stimuli sensors of the CNC-based sustainable materials.

A series of imidazodiazepines has been developed that possess reduced sedative liabilities but retain efficacy in anticonvulsant screening models. The latest of these compounds, (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole known as KRM-II-81) is currently awaiting advancement into the clinic. A deuterated structural analog (D5-KRM-II-81) was made as a potential backup compound and studied here in comparison to KRM-II-81. In the present study, both compounds significantly prevented seizures in mice induced by 6 Hz (44 mA) electrical stimulation without significantly altering motoric function on a rotarod after intraperitoneal administration. Both compounds also significantly prevented clonic seizures, tonic seizures, and lethality induced by pentylenetetrazol in mice when given orally. D5-KRM-II-81 had a slightly longer duration of action against clonic and tonic seizures than KRM-II-81. Oral administration of 100 mg/kg of either KRM-II-81 or D5-KRM-II-81 was significantly less disruptive of sensorimotor function in mice than diazepam (5 mg/kg, p.o.). The present report documents that D5-KRM-II-81 represents another in this series of imidazodiazepines with anticonvulsant activity at doses that do not impair sensorimotor function., (© 2023 Wiley Periodicals LLC.)

Taq DNA polymerase, which was discovered from a thermophilic aquatic bacterium ( Thermus aquaticus ), is an enzyme that possesses both reverse transcriptase activity and DNA polymerase activity. Colicin E (CE) protein belongs to a class of Escherichia coli toxins that utilize the vitamin receptor BtuB as a transmembrane receptor. Among these toxins, CE2, CE7, CE8, and CE9 are classified as non-specific DNase-type colicins. Taq DNA polymerase consists of a 5'→3' exonuclease domain, a 3'→5' exonuclease domain, and a polymerase domain. Taq DNA polymerase lacking the 5'→3' exonuclease domain (Δ Taq ) exhibits higher yield but lower processivity, making it unable to amplify long fragments. In this study, we aimed to enhance the processivity of Δ Taq . To this end, we fused dCE with Δ Taq and observed a significant improvement in the processivity of the resulting dCE-Δ Taq compared to Taq DNA polymerase and dCE- Taq . Furthermore, its reverse transcriptase activity was also higher than that of Δ Taq . The most notable improvement was observed in dCE8-Δ Taq , which not only successfully amplified 8 kb DNA fragments within 1 minute, but also yielded higher results compared to other mutants. In summary, this study successfully enhanced the PCR efficiency and reverse transcription activity of Taq DNA polymerase by fusing Δ Taq DNA polymerase with dCE. This approach provides a novel approach for modifying Taq DNA polymerase and holds potential for the development of improved variants of Taq DNA polymerase.

Objective: This study aims to investigate the relationship between taste dysfunction and depression among patients with schizophrenia, to achieve early detection of depression in clinical practice., Methods: Following PRISMA guidance, a comprehensive literature search was conducted globally, covering papers published from 1961 to June 2023. A total of 17 manuscripts were selected through meta-analysis and sensitivity analysis after examining available materials from seven databases to determine the correlation between depression and taste dysfunction., Results: The comparison of the 17 selected manuscripts revealed that individuals with gustatory dysfunction may be more likely to experience depressive symptoms (SMD, 0.51, 95% CI, 0.08 to 0.93, p = 0.02). Depression is associated with taste dysfunction in certain aspects, as indicated by the pleasantness ratings of sucrose solutions (SMD, -0.53, 95% confidence interval [CI] -1.11 to 0.05, p = 0.08), gustatory identification ability (SMD, 0.96, 95% CI, 0.03 to 1.89, p = 0.04), and the perception threshold of sweet taste (MD, 0.80, 95% CI, 0.79 to 0.81, p < 0.00001)., Conclusions: Due to variations in the methods, designs, and selection criteria employed in the included studies, it is necessary to establish a feasible framework. Future research using detailed and targeted approaches can provide clearer and more unified conclusions on the relationship between taste dysfunction and depression. Moreover, further high-quality research is needed to obtain clearer conclusions and explore the potential of taste dysfunction as an effective tool for early screening of depression., Trial Registration: This review has been registered in the PROSPERO on April 2022 with the identifier CRD42023400172., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future., 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 Liu, Ping, Sun, Yang, Lu and Pei.)

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep., (© 2024 Federation of American Societies for Experimental Biology.)

Acute kidney injury (AKI) poses a significant global public health challenge. Current methods for detecting AKI rely on monitoring changes in serum creatinine (Scr), blood urea nitrogen (BUN), urinary output and some commonly employed biomarkers. However, these indicators are usually neither specific nor sensitive to AKI, especially in cases of mild kidney injury. AKI is accompanied by severe inflammatory reactions, resulting in the upregulation of numerous inflammation-associated proteins in the plasma. Plasma biomarkers are a noninvasive method for detecting kidney injury, and to date, plasma inflammation-associated cytokines have not been adequately studied in AKI patients. The objective of our research was to identify novel inflammatory biomarkers for AKI. We utilized Olink proteomics to analyze the alterations in plasma inflammation-related proteins in the serum of healthy mice (n = 2) or mice treated with cisplatin (n = 6). Additionally, transcriptome datasets for the lipopolysaccharide (LPS), cisplatin, and ischemia‒reperfusion injury (IRI) groups were obtained from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We calculated the intersection of differentially expressed proteins (DEPs) and genes (DEGs) from both datasets. In the Olink proteomics analysis, the AKI group had significantly greater levels of 11 DEPs than did the control group. In addition, 56 common upregulated DEGs were obtained from the transcriptome dataset. The expression of CXCL1 and TNFRSF12A overlapped across all the datasets. The transcription and protein expression levels of CXCL1 and TNFRSF12A were detected in vivo. The gene and protein levels of CXCL1 and TNFRSF12A were significantly increased in different AKI mouse models and clinical patients, suggesting that these genes and proteins could be potential specific biomarkers for the identification of AKI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

KRM-II-81 (1) is an imidazodiazepine GABA A receptor (GABAAR) potentiator with broad antiseizure efficacy and a low sedative burden. A brominated analogue, DS-II-73 (5), was synthesized and pharmacologically characterized as a potential backup compound as KRM-II-81 moves forward into development. The synthesis from 2-amino-5-bromophenyl)(pyridin-2yl)methanone (6) was processed in five steps with an overall yield of 38% and without the need for a palladium catalyst. GABAAR binding occurred with a K i of 150 nM, and only 3 of 41 screened binding sites produced inhibition ≥50% at 10 μM, and the potency to induce cytotoxicity was ≥240 mM. DS-II-73 was selective for α2/3/5- over that of α1-containing GABAARs. Oral exposure of plasma and brain of rats was more than sufficient to functionally impact GABAARs. Tonic convulsions in mice and lethality induced by pentylenetetrazol were suppressed by DS-II-73 after oral administration and latencies to clonic and tonic seizures were prolonged. Cortical slice preparations from a patient with pharmacoresistant epilepsy (mesial temporal lobe) showed decreases in the frequency of local field potentials by DS-II-73. As with KRM-II-81, the motor-impairing effects of DS-II-73 were low compared to diazepam. Molecular docking studies of DS-II-73 with the α1β3γ2L-configured GABAAR showed low interaction with α1His102 that is suggested as a potential molecular mechanism for its low sedative side effects. These findings support the viability of DS-II-73 as a backup molecule for its ethynyl analogue, KRM-II-81, with the human tissue data providing translational credibility.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

We report a general molecular design strategy of spatial proximity, which allows intramolecular [2+2] photocycloaddition reaction to take place in both single molecules and molecular aggregates. Sharply contrasting photoinduced fluorescence changes in solution and in the solid state were found and attributed to the aggregation-induced quenching property of the monomers and the aggregation-induced emission nature of the photodimers.

Objective: In this study, a radiomics model was created based on High-Resolution Computed Tomography (HRCT) images to noninvasively predict whether the sub-centimeter pure Ground Glass Nodule (pGGN) is benign or malignant., Methods: A total of 235 patients (251 sub-centimeter pGGNs) who underwent preoperative HRCT scans and had postoperative pathology results were retrospectively evaluated. The nodules were randomized in a 7:3 ratio to the training (n=175) and the validation cohort (n=76). The volume of interest was delineated in the thin-slice lung window, from which 1316 radiomics features were extracted. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to select the radiomics features. Univariate and multivariable logistic regression were used to evaluate the independent risk variables. The performance was assessed by obtaining Receiver Operating Characteristic (ROC) curves for the clinical, radiomics, and combined models, and then the Decision Curve Analysis (DCA) assessed the clinical applicability of each model., Results: Sex, volume, shape, and intensity mean were chosen by univariate analysis to establish the clinical model. Two radiomics features were retained by LASSO regression to build the radiomics model. In the training cohort, the Area Under the Curve (AUC) of the radiomics (AUC=0.844) and combined model (AUC=0.871) was higher than the clinical model (AUC=0.773). In evaluating whether or not the sub-centimeter pGGN is benign, the DCA demonstrated that the radiomics and combined model had a greater overall net benefit than the clinical model., Conclusion: The radiomics model may be useful in predicting the benign and malignant sub-centimeter pGGN before surgery.

Aging of the brain usually leads to the decline of neurological processes and is a major risk factor for various neurodegenerative diseases, including sleep disturbances and cognitive decline. Adipose tissue exosomes, as adipocyte-derived vesicles, may mediate the regulatory processes of adipose tissue on other organs, including the brain; however, the regulatory mechanisms remain unclear. We analyzed the sleep-wake behavior of young (10 days) and old (40 days) Drosophila and found that older Drosophila showed increased sleep fragmentation, which is similar to mammalian aging characteristics. To investigate the cross-tissue regulatory mechanisms of adiposity on brain aging, we extracted 10-day and 40-day Drosophila adipose tissue exosomes and identified circRNAs with age-dependent expression differences by RNA-seq and differential analysis. Furthermore, by combining data from 3 datasets of the GEO database (GSE130158, GSE24992, and GSE184559), circ&#95;sxc that was significantly downregulated with age was finally screened out. Moreover, dme-miR-87-3p, a conserved target of circ&#95;sxc, accumulates in the brain with age and exhibits inhibitory effects in predicted binding relationships with neuroreceptor ligand genes. In summary, the current study showed that the Drosophila brain could obtain circ&#95;sxc by uptake of adipose tissue exosomes which crossed the blood-brain barrier. And circ&#95;sxc suppressed brain miR-87-3p expression through sponge adsorption, which in turn regulated the expression of neurological receptor ligand proteins (5-HT1B, GABA-B-R1, Rdl, Rh7, qvr, NaCP60E) and ensured brain neuronal synaptic signaling normal function of synaptic signaling. However, with aging, this regulatory mechanism is dysregulated by the downregulation of the adipose exosome circ&#95;sxc, which contributes to the brain exhibiting sleep disturbances and other "aging" features., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A clinical case of a 19-year-old male patient with pharmacoresistant seizures occurring following parieto-occipital tumor-resection at age 6 is described. Seizure surgery work-up included prolonged video EEG monitoring and head CT without contrast. Seizure focus was localized to the left temporal lobe, and we felt that the patient was an excellent candidate for seizure surgery. The patient underwent a left frontotemporal craniotomy for removal of the seizure focus with intraoperative electrocorticography (ECoG) conducted pre and post resection. ECoG recordings pre- and post-resection confirmed resolution of seizure generation. Imaging obtained immediately postoperatively showed complete resection of the residual tumor with no evidence of recurrence in follow-ups. A year after the surgery the patient is seizure-free but remains on seizure medication. With the patient's consent the excised epileptogenic tissue was used for ex-vivo research studies. The microelectrode recordings confirmed epileptiform activity in the excised tissue incubated in excitatory artificial cerebrospinal fluid. The epileptiform activity in the epileptogenic tissue was suppressed by addition of KRM-II-81, a novel α2/3 subtype preferring GABA A receptor (GABAAR) potentiator with previously demonstrated antiepileptic efficacy in multiple animal models of epilepsy and with reduced potential for CNS side-effects compared to classical benzodiazepine GABAAR potentiators. These findings support the proposition that KRM-II-81 might reduce seizure burden in pharmacoresistant patients., Competing Interests: James Cook is a patent holder for KRM–II–81. Arnold Lippa, Rok Cerne, and Jeffrey Witkin are associated with RespireRx Pharmaceuticals Inc that holds the license agreement for KRM–II–81., (© 2023 The Authors.)

The interconnection between cardiac function and circadian rhythms is of great importance. While the role of the biological clock gene Timeless (Tim) in circadian rhythm has been extensively studied, its impact on cardiac function remains largely been unexplored. Previous research has provided experimental evidence for the regulation of the heart by adipose tissue and the targeting of miR-276a/b on Timeless. However, the extent to which adipose tissue regulates cardiac Timeless genes trans-organically through miR-276a/b, and subsequently affects cardiac function, remains uncertain. Therefore, the objective of this study was to investigate the potential trans-organ modulation of the Timeless gene in the heart by adipose tissue through miR-276a/b. We found that cardiac-specific Timeless knockdown and overexpression resulted in a significant increase in heart rate (HR) and a significant decrease in Heart period (HP), diastolic intervals (DI), systolic intervals (SI), diastolic diameter (DD), and systolic diameter (SD). miR-276b systemic knockdown resulted in a significant increase in DI, arrhythmia index (AI), and fractional shortening (FS) significantly increased and SI, DD and SD significantly decreased. Adipose tissue-specific miR-276a/b knockdown and miR-276a overexpression resulted in a significant increase in HR and a significant decrease in DI and SI, which were improved by exercise intervention. This study presents a novel finding that highlights the significance of the heart circadian clock gene Timeless in heart function. Additionally, it demonstrates that adipose tissue exerts trans-organ modulation on the expression of the heart Timeless gene via miR-276a/b., 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. Graphical abstract created with “BioRender.com.”, (© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society.)

Here, the modulation of the Pt electronic structure by the formation of an amorphous WO x overlayer on Pt nanoparticles is proposed. The resulting Pt/WO x @NC electrode shows exceptional CO oxidation potential (0.24 V vs . RHE) in aqueous test, and the corresponding membrane electrode assembly (MEA) steadily generates power in fuel cells fed with H 2 gas containing 1000 ppm CO.

According to the characteristic of T-functions,along with the definition of narrow T-functions,the linear prop-erty and differential property were studied.Markov chain and transition matrices were constructed to propose fast algo-rithm for computing Walsh spectrum and differential probability,of which the time complexity is O(n).In addition,the algorithm is applied in the T-functions in TSC-family and finally the result expression is given.

The imidazodiazepine, (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo [f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81) is a new α2/3-selective GABAkine (gamma aminobutyric acid A receptor potentiator) with anticonvulsant, anxiolytic, and antinociceptive activity in preclinical models. Reducing metabolism was utilized as a means of potentially extending the half-life of KRM-II-81. In vitro and in vivo studies were conducted to evaluate metabolic liabilities. Incubation of KRM-II-81 in hepatocytes revealed sites of potential metabolism on the oxazole and the diazepine rings. These sites were targeted in the design of a deuterated analog (D5-KRM-II-81) that could be evaluated as a potentially longer-acting analog. In contrast to computer predictions, peak plasma concentrations of D5-KRM-II-81 in rats were not significantly greater than those produced by KRM-II-81 after oral administration. Furthermore, brain disposition of KRM-II-81 was higher than that of D5-KRM-II-81. The half-life of the two compounds in either plasma or brain did not statistically differ from one another but the t max for D5-KRM-II-81 occurred slightly earlier than for KRM-II-81. Non-metabolic considerations might be relevant to the lack of increases in exposure by D5-KRM-II-81. Alternative sites of metabolism on KRM-II-81, not targeted by the current deuteration process, are also possible. Despite its lack of augmented exposure, D5-KRM-II-81, like KRM-II-81, significantly prevented seizures induced by pentylenetetrazol when given orally. The present findings introduce a new orally active anticonvulsant GABAkine, D5-KRM-II-81., (© 2022 John Wiley & Sons Ltd.)