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Xian-Wu Luo,1 Xue-Qing Du,2 Jie-Li Li,2 Xiao-Ping Liu,3,4 Xiang-Yu Meng3,4 1Department of Health Management, School of Health Sciences, Wuhan University, 2Department of Hematology, Zhongnan Hospital of Wuhan University, 3Department of Evidence-Based Medicine and Clinical Epidemiology, Second Clinical School, Wuhan University, 4Center for Evidence-based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China Background: The refractory/relapsed multiple myeloma (RRMM) remains a big clinical challenge, due to its biological and clinical complexity. Leading hematologists have performed many randomized controlled trials (RCTs) worldwide, and their findings were summarized in a recently published network meta-analysis (NMA) but with certain limitations. Materials and methods: We performed an updated NMA of RCTs related to RRMM treatment, focusing on efficacy measures including the nonresponse rate (NRR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS). The PubMed database was searched. We extended the literature search strategy of a previous NMA to June 30, 2017 and included additional primary RCTs. The surface under the cumulative ranking curve (SUCRA) was calculated to rank the regimens. A weighted-average method was used to rank the regimens by summarizing SUCRAs across different outcome measures. Results: Finally, a total of 24 RCTs were included in this updated NMA. According to the result, the combination of daratumumab, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of NRR, TTP, and PFS (NRR: odds ratio [OR] =0.046, 95% credible interval [CrI] =[0.024, 0.085]; TTP: hazard ratio [HR] =0.14, 95% CrI =[0.092, 0.2]; PFS: HR =0.12, 95% CrI =[0.077, 0.18], compared with dexamethasone singlet). The combination of ixazomib, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of OS (HR =0.30, 95% CrI =[0.17, 0.54], compared with dexamethasone). The combination of daratumumab, lenalidomide, and dexamethasone ranked first in terms of overall efficacy (weighted average of SUCRAs =0.920). Conclusion: The combination of daratumumab, lenalidomide, and dexamethasone may currently be the most effective regimen in the population of RRMM patients. Triplet regimens containing daratumumab, ixazomib, carfilzomib, or elotumumab plus lenalidomide and dexamethasone can be recommended as first-line therapies for RRMM patients. Keywords: multiple myeloma, refractory/relapsed, treatment regimens, efficacy, network meta-analysis

Rationale: Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of hepatocellular carcinoma. Its imaging findings often resemble those of liver abscess, making preoperative diagnosis particularly challenging. To date, there have been no documented cases of SHC with subdiaphragmatic metastases. In this report, we present a case of SHC with subdiaphragmatic metastasis that was initially misdiagnosed as hepatic abscess. In addition, we conducted a retrospective analysis of the clinical and imaging findings to improve the clinical understanding of this disease., Patient Concerns: A 74-year-old woman was admitted to our hospital with recurrent right upper abdominal pain and discomfort, chills, and fever for >1 month., Diagnoses: The patient underwent abdominal computed tomography and magnetic resonance imaging, which revealed multiple nodules and masses in the left lobe of the liver. Furthermore, a thick-walled irregular cystic solid mass was identified in the anterior and subdiaphragmatic regions. Based on these findings, the patient was diagnosed with an abscess. The postoperative pathology confirmed SHC in both the left lobe of the liver and subdiaphragmatic mass., Interventions: The patient underwent a left external liver lobectomy., Outcomes: The patient's condition deteriorated after surgery, and hepatic encephalopathy developed 1.5 months postoperation, ultimately leading to death., Lessons: To the best of our knowledge, cases of SHC with subdiaphragmatic metastases are rare, and the preoperative diagnosis presents a significant challenge in clinical practice. More comprehensive case analyses of SHC are needed to enhance the accuracy of clinical and imaging diagnoses., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: OTUD7B, a member of the ovarian tumor (OTU) protein superfamily, functions as a deubiquitinating enzyme and is associated with various biological processes and disease conditions, including tumors. In this study, we aimed to explore the expression patterns, prognostic significance, and the functional roles and underlying mechanisms of OTUD7B in gastric cancer (GC)., Materials and Methods: Using a blend of bioinformatics, clinical case reviews, and molecular experiments, we evaluated the expression of OTUD7B in GC at both mRNA and protein levels. We examined the relationship between OTUD7B expression and clinicopathological characteristics of GC patients. Additionally, in vitro assays were utilized to assess the effects of OTUD7B on the migratory and invasive capabilities of GC cells. RNA sequencing analysis was conducted to identify critical genes and pathways linked to OTUD7B in GC., Results: OTUD7B was found to be significantly overexpressed in GC, both at mRNA and protein levels. Higher levels of OTUD7B were positively associated with advanced tumor TNM stage, higher histological grade, and presence of lymph/vein invasion. These correlations were indicative of poorer overall survival (OS) and disease-free survival (DFS) in GC patients. In vitro assays revealed that genetic knockout of OTUD7B markedly reduced the migration and invasion of GC cells, while overexpression of OTUD7B led to enhanced cellular migration and invasion. Furthermore, RNA sequencing and bioinformatic analyses indicated that the absence of OTUD7B suppressed signaling pathways related to cancer progression, metastasis, and metabolism. Mechanistically, OTUD7B likely promotes GC metastasis through the WNT signaling pathway, specifically targeting β-catenin., Conclusions: OTUD7B serves as a novel marker for poor prognosis in GC and actively promotes tumor metastasis. Our results shed light on the signaling pathways regulated by OTUD7B and highlight potential targets for therapeutic intervention., Competing Interests: Declaration of Competing Interest We declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Anthocyanin is an essential pigment in all major horticultural crops especially in ornamental trees. Magnolia wufengensis (new species of Magnolia) with red color flower was recently found as a popular species for ornamental use, but anthocyanin synthesis and regulation in M. wufengensis are poorly understood. Herein, transcriptome analysis was used to decipher the gene network associated with anthocyanin biosynthesis. An R2R3-like MwMYB-1 transcription factor was found. MwMYB-1 overexpression resulted in anthocyanin accumulation in tobacco and Arabidopsis. MwMYB-1 worked independently rather than forming a protein complex with bHLH or WD40 protein. According to MwMYB-1 DAP-seq analysis in Arabidopsis, the MwMYB-1 transcription factor preferred to bind the "AAGAGAG" motif (DREME-5) in the third exon of the AtMYB75 gene. The yeast one hybrid assay and transcription activity assay further confirmed this. Thus, MwMYB-1 activated AtMYB75 gene expression and conducted cascade amplification of anthocyanin biosynthesis. Taken together, our findings provide a novel understanding of anthocyanin biosynthesis regulation in M. wufengensis and can be used to promote agronomic trait improvement in tree species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Single nucleotide polymorphism (SNP), as one of the key components of the genetic factors, is important for disease detection and early screening of hereditary diseases. Current SNP genotyping methods require laboratory instruments or long operating times. To facilitate the diagnosis of hereditary diseases, we developed a new method referred to as the LwaCas13a-based SNP genotyping platform (Cas13a platform), which is useful for detecting disease-related SNPs. We report a CRISPR/Cas13a-based SNP genotyping platform that couples recombinase-aided amplification (RAA), T7 transcription, and Leptotrichia wadei Cas13a (LwaCas13a) detection for simple and fast genotyping of human disease-related SNPs. We used this Cas13a platform to identify 17 disease-related SNPs, demonstrating that position 2 in gRNA is suitable for the introduction of additional mismatches to achieve high discrimination in genotyping across a wide range of SNP targets. The discrimination specificity of 17 SNPs was improved 3.0-35.1-fold after introducing additional mismatches at position 2 from the 5'-end. We developed a method, which has a lower risk of cross-contamination and operational complexity, for genotyping SNPs using human saliva samples in an one-pot testing that delivers results within 60 min. Compared to TaqMan probe qPCR, RFLP, AS-PCR and other SNP genotyping methods, the Cas13a platform is simple, rapid and reliable, expanding the applications of the CRISPR/Cas system in nucleic acid detection and SNP genotyping., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes., Methods: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group ( n  = 10 mice in each group). Halfway through the 12 th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH., Results: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice ( p  < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA ( p  < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased ( p  < 0.05)., Conclusions: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

Myogenesis is essential for skeletal muscle formation and regeneration after injury, yet its regulators are largely unknown. Here we identified fibronectin type III domain containing 1 (FNDC1) as a previously uncharacterized myokine. In vitro studies showed that knockdown of Fndc1 in myoblasts reduces myotube formation, while overexpression of Fndc1 promotes myogenic differentiation. We further generated recombinant truncated mouse FNDC1 (mFNDC1), which retains reliable activity in promoting myoblast differentiation in vitro. Gain- and loss-of-function studies collectively showed that FNDC1 promotes cardiotoxin (CTX)-induced muscle regeneration in adult mice. Furthermore, recombinant FNDC1 treatment ameliorated pathological muscle phenotypes in the mdx mouse model of Duchenne muscular dystrophy. Mechanistically, FNDC1 bound to the integrin α5β1 and activated the downstream FAK/PI3K/AKT/mTOR pathway to promote myogenic differentiation. Pharmacological inhibition of integrin α5β1 or of the downstream FAK/PI3K/AKT/mTOR pathway abolished the pro-myogenic effect of FNDC1. Collectively, these results suggested that myokine FNDC1 might be used as a therapeutic agent to regulate myogenic differentiation and muscle regeneration for the treatment of acute and chronic muscle disease., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Bulk quantum Hall effect (QHE), the natural extension of the two-dimensional (2D) QHE, is one of the representative phenomena of coherent electron transport. However, bulk QHE has rarely been reported in real materials with macroscopic sizes. Here, we report a novel bulk QHE in macroscopic millimeter-sized and nanostructured TaP crystals consisting of nanometer-scale lamellae. Specifically, the simultaneous quantum plateaus were observed in both transverse resistivity ρ xy and vertical resistivity ρ zz . The bulk QHE is attributable to synergetic action between Landau cyclotron movement under magnetic field B and periodically modulated potential due to the nanometer-scaled lamellae. This mechanism would form the fixed number of edge states along B -perpendicular and B -parallel directions respectively, equivalent to stacked 2D-QHE layers, leading to quantized ρ xy and ρ zz . Our work verifies that microstructure engineering could result in the coherent transport of electrons and generate new quantum phenomena in bulk materials.

Vascular dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). While sodium is essential for maintaining vascular function, its role in AD pathology remains unclear. We included 353 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), assessing serum sodium levels, cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, magnetic resonance imaging (MRI), and cognitive function. An independent sample (N = 471) with available CSF sodium-related proteins and AD biomarkers was also included. Associations between serum sodium levels and AD pathology, neurodegeneration, and cognition were evaluated using linear regression models. Spearman's correlation analyses assessed the relationships between CSF sodium-related proteins and AD biomarkers. Higher serum sodium levels were associated with increased AD pathology, reduced hippocampal volume, and greater cognitive decline (all p < 0.05). The relationship between serum sodium and amyloid PET was evident in several AD-susceptible brain regions, including the neocortex and limbic system. Individuals with high serum sodium exhibited higher tau pathology, lower hippocampal volume, and more severe cognitive decline per unit increase in amyloid PET compared to those with low serum sodium (all p < 0.05). Among the 14 CSF sodium-related proteins, which were inter-correlated, six were significantly correlated with CSF AD pathology and amyloid PET, while two were correlated with hippocampal volume and cognitive function, with sodium channel subunit beta-2 (SCN2B) and sodium channel subunit beta-3 (SCN3B) showing the strongest correlations. These findings underscore the crucial role of serum sodium in AD progression, highlighting a potential network of sodium dysregulation involved in AD pathology. Targeting sodium may offer a novel therapeutic approach to slowing AD progression, particularly by impeding the progression of amyloid-related downstream events., (© 2024 International Society for Neurochemistry.)

Collaboration has an essential role in memory, and how to appropriately use it to affect individual memory positively is a matter of concern. The meta-analysis generally assessed the effect of collaboration on subsequent individual retrieval, registered on the PROSPERO platform and adhering to the PRISMA guidelines, using the Web of Science, Science Direct, CNKI and WanFang databases with post-collaborative memory as the main subject, screened studies published up to December 31, 2023, a total of 64 studies with 101 effect sizes, including 13,398 participants from 11 countries. Heterogeneity test, sensitivity analysis, subgroup analysis and meta-regression analysis were performed on the included studies, while publication bias was assessed. The results found that collaboration improves subsequent individual retrieval memory more than individuals, and collaboration has a moderate facilitating effect on subsequent individual retrieval. Group size, material category, category size, collaboration phase, collaboration approach, task process and test method were among the moderating variables. The study emphasizes the role of collaboration in cognition and demonstrates the post-collaborative benefits. The conclusions are of value for developing methods to improve individual memory., (© 2024 The British Psychological Society.)

Nucleases play pivotal roles in DNA repair and apoptosis. Moreover, they have various applications in biotechnology and industry. Among nucleases, TatD has been characterized as an exonuclease with various biological functions in different organisms. Here, we biochemically characterized the potential TatD nuclease from Thermus thermophilus. The tatD gene from T. thermophilus was cloned, then the recombinant TatD nuclease was expressed and purified. Our results revealed that the TthTatD nuclease could degrade both single-stranded and double-stranded DNA, and its activity is dependent on the divalent metal ions Mg 2+ and Mn 2+ . Remarkably, the activity of TthTatD nuclease is highest at 37 °C and decreases with increasing temperature. TthTatD is not a thermostable enzyme, even though it is from a thermophilic bacterium. Based on the sequence similarity and molecular docking of the DNA substrate into the modeled TthTatD structure, several key conserved residues were identified and their roles were confirmed by analyzing the enzymatic activities of the site-directed mutants. The residues E86 and H149 play key roles in binding metal ions, residues R124/K126 and K211/R212 had a critical role in binding DNA substrate. Our results confirm the enzymatic properties of TthTatD and provide a primary basis for its possible application in biotechnology., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest exist., (Copyright © 2024. Published by Elsevier Inc.)

The purpose of this experiment was to investigate the effects of Hot Water Extract of Juncao-substrate Ganoderma lucidum Residue (HWE-JGLR) on the immune function and intestinal health of yellow-feather broilers. In an animal feeding experiment, 288 male yellow-feather broilers (1 day old) were randomly allocated to four treatment groups with six replicates of 12 birds each. The control (CON) group was fed a basal diet. HJ-1, HJ-2, and HJ-3 were fed a basal diet supplemented with 0.25%, 0.50%, and 1.00% HWE-JGLR, respectively. The feeding trial lasted for 63 d. The results showed increased ADFI ( p = 0.033) and ADG ( p = 0.045) of broilers in HJ-3, compared with the CON group. Moreover, higher contents of serum IL-4 and IL-10 and gene expression of IL-4 and IL-10 in jejunum mucosa and lower contents of serum IL-1β and gene expression of IL-1β in jejunum mucosa in HJ-3 were observed ( p < 0.05). Additionally, the jejunal mucosal gene expression of Claudin-1 and ZO - 1 in HJ-2 and HJ-3 was higher than that in the CON group ( p < 0.05). As for the microbial community, compared with the CON group, the ACE index, Shannon index, and Shannoneven index of cecal microorganisms in HJ-2 and HJ-3 were elevated ( p < 0.05). PCoA analysis showed that the cecal microbial structure of broilers in HJ-2 and HJ-3 was different from the CON group ( p < 0.05). In contrast with the CON group, the broilers in HJ-2 and HJ-3 possessed more abundant Desulfobacterota at the phylum level and unclassified Lachnospiraceae , norank Clostridia vadinBB60 group and Blautia spp. at the genus level, while Turicibacter spp. and Romboutsia spp. were less ( p < 0.05). In conclusion, dietary supplementation with HWE-JGLR can improve growth performance, enhance body immunity and intestinal development, and maintain the cecum microflora balance of yellow-feather broilers.

Ganoderma lucidum polysaccharides (GLP) are the primary bioactive macromolecular compounds of Ganoderma lucidum, possessing antioxidant and immunomodulatory effects. Hot water extract of Juncao-substrate Ganoderma Lucidum residue (HWE-JGLR) is abundant in GLP. There are few research reports on the application of HWE-JGLR in animal husbandry. Therefore, this study aims to investigate the effects of HWE-JGLR supplementation on growth performance, serum biochemistry, the antioxidant function of serum and liver, and the intestinal microbiota of yellow-feathered broilers. The control group was fed a corn-soybean meal basal diet, while the HJ I, II, and III groups received diets supplemented with 0.25 %, 0.5 %, and 1 % of HWE-JGLR, respectively. Results showed that HWE-JGLR increased the serum HDL-C content and decreased the TG content in broilers. Moreover, HWE-JGLR enhanced the antioxidant function by the Keap1-Nrf2/ARE signaling pathway and the antioxidative enzyme in broilers. In addition, the cecum of the metagenomic analysis of 16S rRNA showed that the relative abundance of no-rank Ruminococcacea was increased in the HJ I group. Our findings indicate that HWE-JGLR has strong potential for development as a green feed additive based on its functions of lipid-lowering, antioxidation, and the modulation of gut microbiota composition., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu-Yun Gao reports financial support was provided by National Key Research and Development Program of China. Yu-Yun Gao reports financial support was provided by Agricultural Guiding (Key) Project of Fujian Provincial Science and Technology Department. Yu-Yun Gao reports financial support was provided by Fujian Specialist Funds of Chicken Industrial System in China. Yu-Yun Gao reports financial support was provided by Science and Technology Development Projects Funded by Chinese Central and Local Governments. Yu-Yun Gao reports equipment, drugs, or supplies was provided by National Engineering Research Centre of JUNCAO Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aggregation-induced electrochemiluminescence (AIECL) combines the merits of aggregation-induced emission (AIE) and electrochemiluminescence (ECL), which has become a research hot spot in recent years. Therefore, we synthesized a novel AIE compound ( Z )-3-(4-(2-butyl-1,3-dioxo-2,3-dihydro-1 H -benzo[de]isoquinolin-6-yl)phenyl)-2-(4-(1,2,2-triphenylvinyl)phenyl)acrylonitrile (TPENI) with a donor-acceptor (D-A) structure, that is, a simple peripheral modification of 4-(2-butyl-1,3-dioxo-2,3-dihydro-1 H -benzo[de]isoquinolin-6-yl) benzaldehyde (NI-CHO) with AIE-active tetraphenylethylene (TPE) to achieve the transition of NI-CHO from aggregation-caused quenching (ACQ) to an AIE molecule. When TPENI was in the aggregated state, the luminescence intensity was significantly enhanced due to the TPE structural unit restricting the free rotation of the intramolecular benzene ring, as well as the π-π stacking interactions of the molecules, which was conducive to the preparation of TPENI NPs as ECL materials. Satisfactorily, we found that the ECL intensity of TPENI NPs was increased by about 4.8-fold compared with that of the molecules dispersed in organic solution, and the stability reached about 1000 s. Based on the excellent ECL properties of TPENI NPs, an "on-off-on" ECL biosensor with a wider detection range (1 fg/mL to 100 ng/mL) and a lower detection limit of 0.20 fg/mL (S/N = 3) was proposed for sensitive analysis of a carcinoembryonic antigen (CEA). Overall, this work provided a new approach to the realization of AIECL and laid the foundation for the application of naphthalimide derivatives in ECL.

Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100 β , neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100 β ), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100 β , and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We aimed to construct an artificial intelligence-enabled electrocardiogram (ECG) algorithm that can accurately predict the presence of left atrial low-voltage areas (LVAs) in patients with persistent atrial fibrillation., Methods: The study included 587 patients with persistent atrial fibrillation who underwent catheter ablation procedures between March 2012 and December 2023 and 942 scanned images of 12-lead ECGs obtained before the ablation procedures were performed. Artificial intelligence-based algorithms were used to construct models for predicting the presence of LVAs. The DR-FLASH and APPLE clinical scores for LVA prediction were calculated. We used a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis to evaluate model performance., Results: The data obtained from the participants were split into training (n = 469), validation (n = 58), and test sets (n = 60). LVAs were detected in 53.7% of all participants. Using ECG alone, the deep learning algorithm achieved an area under the ROC curve (AUROC) of 0.752, outperforming both the DR-FLASH score (AUROC = 0.610) and the APPLE score (AUROC = 0.510). The random forest classification model, which integrated a probabilistic deep learning model and clinical features, showed a maximum AUROC of 0.759. Moreover, the ECG-based deep learning algorithm for predicting extensive LVAs achieved an AUROC of 0.775, with a sensitivity of 0.816 and a specificity of 0.896. The random forest classification model for predicting extensive LVAs achieved an AUROC of 0.897, with a sensitivity of 0.862, and a specificity of 0.935., Conclusion: The deep learning model based exclusively on ECG data and the machine learning model that combined a probabilistic deep learning model and clinical features both predicted the presence of LVAs with a higher degree of accuracy than the DR-FLASH and the APPLE risk scores., (© 2024 Wiley Periodicals LLC.)

This study investigated the effects of different types of short video addiction on social adaptation. The aim of this study was to identify the various types of short video addiction among freshmen and the correlations with career adaptability, insomnia, and depressive symptoms. We recruited 931 freshmen and used latent profile analysis to classify participants based on different characteristics of short video addiction. Based on the results of a short video addiction questionnaire, participants were found to exhibit distinct answer patterns, categorized into five types. Class 1 exhibited minimal signs of addiction. Class 2 displayed fluctuations with stronger tendencies towards withdrawal or escape. Class 3 demonstrated a moderate inability to control cravings for short videos. Class 4 showed fluctuations but with less anxiety and feelings of lost. Finally, Class 5 presented the most pronounced symptoms of short video addiction. Freshmen with varying degrees of short video addiction exhibited significant differences in career adaptability, sleep quality, and depressive symptoms. Class 1 students showed strong career adaptability and sound sleep, whereas Class 5 students had the highest depression rates. Overall, our findings suggest that the characteristics of short video addiction in first-year students also indicate poor social adaptation, which is mainly manifested as weak career adaptability, decreased sleep quality, and depressive symptoms. One way to guide first-year students to adapt to campus life is for educators to provide timely interventions for students with severe short video addiction., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLS B K) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLS B K in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLS B K antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLS B K antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance., (© 2024. The Author(s).)

Aflatoxin B 1 (AFB 1 ), classified as a class I carcinogen, is a widespread mycotoxin that poses a serious threat to public health and economic development, and the food safety problems caused by AFB 1 have aroused worldwide concern. The development of accurate and sensitive methods for the detection of AFB 1 is significant for food safety monitoring. In this work, a sandwich-type photoelectrochemical (PEC) biosensor for AFB 1 detection was constructed on the basis of an aptamer-antibody structure. A good photocurrent response was obtained due to the sensitization of In 2 S 3 by Ru(bpy) 3 2+ . In addition, this sandwich-type sensor constructed by modification with the antibody, target detector, and aptamer layer by layer attenuated the migration hindering effect of photogenerated carriers caused by the double antibody structure. The aptamer and antibody synergistically recognized and captured the target analyte, resulting in more reliable PEC response signals. CdSe@CdS QDs-Apt were modified as a signal-off probe onto the sensor platform to quantitatively detect AFB 1 with a "signal-off" response, which enhanced the sensitivity of the sensor. The PEC biosensor showed a linear response range from 10 -12 to 10 -6 g mL -1 with a detection limit of 0.023 pg mL -1 , providing a feasible approach for the quantitative detection of AFB 1 in food samples.

Electrochemiluminescence (ECL) biosensors provide a convenient and high sensitivity method for early disease diagnosis. However, creating luminophore arrays relying on powerful ECL signals remains a daunting task. Porphyrin-centered metal organic frameworks (MOFs) exhibit remarkable potential in ECL sensing applications. In this paper, based on a simple one-pot synthesis method, PCN-222@Ag NPs doped with CeO 2 was synthesized to enhance the ECL performance. Due to the strong catalytic ability of CeO 2 , the ECL signal strength of the new material PCN-222@CeO 2 @Ag NPs is much higher than that of the PCN-222@Ag NPs and PCN-222. The luminous properties of PCN-222@CeO 2 @Ag NPs become more intense and stable due to the excellent electronic conductivity of Ag NPs. Based on the fact that CuS@PDA composite can quench the ECL signal of PCN-222@CeO 2 @Ag NPs, we constructed a novel sandwich ECL immune sensor for the detection of phosphorylated Tau 181 (p-Tau-181) protein. The ECL sensor has a great linear relationship with p-Tau-181 protein concentration, ranging from 1 pg/mL to 100 ng/mL. The detection limit is as low as 0.147 pg/mL. This work provides new ideas for developing sensitive ECL sensors for the p-Tau-181 protein, the marker of Alzheimer's disease., 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. Published by Elsevier Inc.)

Background: Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study., Aim: To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes., Methods: A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections)., Results: The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035)., Conclusion: The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated., Competing Interests: Conflict-of-interest statement: Prof. Su has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs., 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 Chen, Wang, Liu, Xu and Mao.)

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-β1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-β1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-β/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two new mealybug species, Paracoccusgillianwatsonae Zhang, sp. nov. and P.wui Zhang, sp. nov. , collected from Jiangxi, South China, are described and illustrated based on the morphology of adult females. Paracoccusgillianwatsonae is similar to P.burnerae (Brain, 1915), but it differs in having fewer pairs of cerarii, and in lacking both ventral oral collar tubular ducts on the margins of the head and translucent pores on the hind femur. Paracoccuswui resembles P.keralae Williams, 2004 and P.neocarens (Lit, 1992), but it differs in lacking ventral oral collar tubular ducts on the margins of the head and in having multilocular disc-pores usually in double rows at the posterior edges of abdominal segments V and VI. A key to the Paracoccus species found in China is provided., Competing Interests: The authors have declared that no competing interests exist., (Jiang-Tao Zhang, Chao-Qun Li, Xing-Ping Liu, Yan Wang.)

Background/aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet., Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation., Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL., Conclusion: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

Background and Aims: Contrasting patterns of host and microbiome biogeography can provide insight into the drivers of microbial community assembly. Distance-decay relationships are a classic biogeographical pattern shaped by interactions between selective and non-selective processes. Joint biogeography of microbiomes and their hosts is of increasing interest owing to the potential for microbiome-facilitated adaptation., Methods: In this study, we examine the coupled biogeography of the model macroalga Durvillaea and its microbiome using a combination of genotyping by sequencing (host) and 16S rRNA amplicon sequencing (microbiome). Alongside these approaches, we use environmental data to characterize the relationship between the microbiome, the host, and the environment., Key Results: We show that although the host and microbiome exhibit shared biogeographical structure, these arise from different processes, with host biogeography showing classic signs of geographical distance decay, but with the microbiome showing environmental distance decay. Examination of microbial subcommunities, defined by abundance, revealed that the abundance of microbes is linked to environmental selection. As microbes become less common, the dominant ecological processes shift away from selective processes and towards neutral processes. Contrary to expectations, we found that ecological drift does not promote structuring of the microbiome., Conclusions: Our results suggest that although host macroalgae exhibit a relatively 'typical' biogeographical pattern of declining similarity with increasing geographical distance, the microbiome is more variable and is shaped primarily by environmental conditions. Our findings suggest that the Baas Becking hypothesis of 'everything is everywhere, the environment selects' might be a useful hypothesis to understand the biogeography of macroalgal microbiomes. As environmental conditions change in response to anthropogenic influences, the processes structuring the microbiome of macroalgae might shift, whereas those governing the host biogeography are less likely to change. As a result, increasingly decoupled host-microbe biogeography might be observed in response to such human influences., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anaerobically digested swine wastewater (ASW) purification by microalgae provides a promising strategy for nutrients recovery, biomass production and CO 2 capture. However, the characteristics of ASW from different cleaning processes vary greatly. At present, the cultivation of microalgae in ASW from different manure cleaning processes is rarely investigated and compared. That may bring uncertainty for microalgae growth using different ASW in large-scale application. Thus, the ASW from three cleaning processes were tested for cultivating microalgae, including manure dry collection (I), water flushing (II) and water submerging processes (III). The characteristics of ASW from three manure cleaning processes varied greatly such as nutrient and heavy metals levels. High concentration of ammonia and copper in ASW significantly inhibited microalgae growth. Fortunately, the supply of high CO 2 (10%) effectively alleviated negative influences, ensuring microalgal growth at low dilution ratio. The characteristics of three ASW resulted in significant differences in microalgae growth and biomass components. The maximal biomass production in optimal diluted ASW-I, II and III reached 1.46 g L -1 , 2.19 g L -1 and 2.47 g L -1 , respectively. The removal of organic compounds, ammonia and phosphorus by optimal microalgae growth in diluted ASW-I, II and III was 50.6%/94.2%/64.7%, 63.7%/82.3%/57.6% and 83.2%/91.7%/59.7%, respectively. The culture in diluted ASW-I, II and III obtained the highest lipids production of 12.1 mg L -1 ·d -1 , 16.5 mg L -1 ·d -1 and 19.4 mg L -1 ·d -1 , respectively. The analysis of lipids compositions revealed that the proportion of saturated fatty acids accounted for 36.4%, 32.4% and 27.9 % in optimal diluted ASW-I, II and III, as ideal raw materials for biodiesel production., 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.)

Background and Aims: Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein-associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms., Methods: JCAD knockout (JCAD-KO), liver-specific JCAD-KO (Jcad △Hep ) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination-based cell cycle indicator (FUCCI) live-imaging system was used to visualise the phases of cell cycle., Results: Both global and liver-specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD-KO cell line was indicated by a FUCCI live-imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD-KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes-associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle-associated genes., Conclusion: JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo-YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation., Key Points: JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle-associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living-donor liver transplantation., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The gregarious ectoparasitic beetle Dastarcus helophoroides (Fairmaire) is considered a primary biocontrol agent for controlling several cerambycid pests in East Asian countries. A thorough study of reproductive behavior is a prerequisite for the mass production of natural insect predators. Nonetheless, little attention has been given to this ectoparasitic beetle. We performed a series of trials to assess whether the adult copulation duration, a key behavioral trait, is differentially influenced by physiological and ecological factors, including body size, mating history, kinship, sex ratio, mating sequence, feeding status, ambient temperature, photoperiod, and time of day. Additionally, the effect of the copulation duration on the reproductive output of this beetle was also investigated. The results indicated that the copulation duration varied considerably, ranging from 1.12 min to 16.40 min and lasting for an average of 9.11 ± 0.12 min. Females with longer copulations laid more eggs and had a greater proportion of eggs hatched. Medium-sized individuals copulated significantly longer than small- and large-sized individuals. The copulation durations were significantly longer when both sexes experienced an asymmetric mating history than when both sexes experienced a symmetric mating history. Inbred couples copulated significantly longer than outbred couples. In terms of the adult sex ratio, increasing the density of females (polygamous group) or males (polyandrous group) led to significantly longer copulation durations than those in the monogamous group. The copulation durations gradually decreased with increasing the mating sequence and temperature. Food-absence couples copulated significantly longer than food-presence couples. The mean copulation duration of the scotophase was significantly longer than that of the photophase. These results demonstrate that all of the analyzed factors emerge as important factors influencing the copulation duration, ultimately affecting the reproductive outputs in this ectoparasitic beetle.

Background: Incomplete species inventories for Antarctica represent a key challenge for comprehensive ecological research and conservation in the region. Additionally, data required to understand population dynamics, rates of evolution, spatial ranges, functional traits, physiological tolerances and species interactions, all of which are fundamental to disentangle the different functional elements of Antarctic biodiversity, are mostly missing. However, much of the fauna, flora and microbiota in the emerged ice-free land of the continent have an uncertain presence and/or unresolved status, with entire biodiversity compendia of prokaryotic groups (e.g. bacteria) being missing. All the available biodiversity information requires consolidation, cross-validation, re-assessment and steady systematic inclusion in order to create a robust catalogue of biodiversity for the continent., New Information: We compiled, completed and revised eukaryotic species inventories present in terrestrial and freshwater ecosystems in Antarctica in a new living database: terrANTALife (version 1.0). The database includes the first integration in a compendium for many groups of eukaryotic microorganisms. We also introduce a first catalogue of amplicon sequence variants (ASVs) of prokaryotic biodiversity. Available compendia and literature to date were searched for Antarctic terrestrial and freshwater species, integrated, taxonomically harmonised and curated by experts to create comprehensive checklists of Antarctic organisms. The final inventories comprises 470 animal species (including vertebrates, free-living invertebrates and parasites), 306 plants (including all Viridiplantae: embryophytes and green algae), 997 fungal species and 434 protists (sensu lato). We also provide a first account for many groups of microorganisms, including non-lichenised fungi and multiple groups of eukaryotic unicellular species (Stramenophila, Alveolata and Rhizaria (SAR), Chromists and Amoeba), jointly referred to as "protists". In addition, we identify 1753 bacterial (obtained from 348117 ASVs) and 34 archaeal genera (from 1848 ASVs), as well as, at least, 14 virus families. We formulate a basic tree of life in Antarctica with the main lineages listed in the region and their "known-accepted-species" numbers., (Luis R. Pertierra, Gilda Varliero, Andrés Barbosa, Elisabeth M. Biersma, Peter Convey, Steven L. Chown, Don Cowan, Asunción De Los Rios, Pablo Escribano-Alvarez, Diego Fontaneto, Ceridwen Fraser, Mathew Harris, Kevin Hughes, Huw Griffiths, Peter le Roux, Xiaoyue P. Liu, Heather Lynch, Roksana Majewska, Pablo A. Martinez, Marco Molina-Montenegro, Miguel A. Olalla-Tarraga, Lloyd Peck, Antonio Quesada, Cristina Ronquillo, Yan Ropert-Coudert, Leopoldo Sancho, Aleks Terauds, Juliana Vianna, Annick Wilmotte, Joaquín Hortal, Michelle Greve.)

In insects, vitellogenin (Vg) is generally viewed as a female-specific protein. Its primary function is to supply nutrition to developing embryos. Here, we reported Vg from the male adults of a natural predator, Chrysopa pallens. The male Vg was depleted by RNAi. Mating with Vg-deficient male downregulated female Vg expression, suppressed ovarian development and decreased reproductive output. Whole-organism transcriptome analysis after male Vg knockdown showed no differential expression of the known spermatogenesis-related regulators and seminal fluid protein genes, but a sharp downregulation of an unknown gene, which encodes a testis-enriched big protein (Vcsoo). Separate knockdown of male Vg and Vcsoo disturbed the assembly of spermatid cytoplasmic organelles in males and suppressed the expansion of ovary germarium in mated females. These results demonstrated that C. pallens male Vg signals through the downstream Vcsoo and regulates male and female reproduction., (© 2023 Royal Entomological Society.)

Objective: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US)., Methods: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set., Results: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884., Conclusion: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR., Advances in Knowledge: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling., Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology., Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages., Results: In the non-demented group, amyloid-β (Aβ)+ participants (e.g., as reflected by CSF Aβ42) exhibited significantly lower plasma insulin levels compared to non-demented Aβ-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aβ42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aβ42 levels (p < 0.001) across all participants. This association was particularly significant in the Aβ-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aβ42 (p = 0.006), whereas baseline CSF Aβ42 did not show a similar correlation with changes in plasma insulin over time., Conclusions: These findings suggest an association between plasma insulin and early Aβ pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aβ pathology.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

An ultrasensitive photoelectrochemical (PEC) aptasensor was originally designed by using ZnIn 2 S 4 /ReS 2 as a photoactive material and AgInS 2 as a signal amplifier. The signal amplifier AgInS 2 was incubated on the terminal of H-DNA (immobilized on the ZnIn 2 S 4 /ReS 2 /FTO surface), leading to an enhanced photocurrent response. Then, due to the introduction of DNA2, the formation of a double-stranded structure caused AgInS 2 to keep away from the electrode surface, and the photocurrent was reduced. In the presence of kanamycin, DNA2 was released from the system due to the competition relationship, and a restored photocurrent response was obtained. The combination of ZnIn 2 S 4 /ReS 2 and AgInS 2 accelerated the electron transfer and enhanced the separation efficiency of photogenerated electron-hole pairs, resulting in an improved performance of the PEC aptasensor, which was capable of accurate and sensitive detection of kanamycin in actual samples.

A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating growth differentiation factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cyclic di-adenosine monophosphate (c-di-AMP) is a newly identified prokaryotic cyclic dinucleotide second messenger well elucidated in bacteria, while less studied in archaea. Here, we describe the enzymes involved in c-di-AMP metabolism in the hyperthermophilic archaeon Pyrococcus yayanosii. Our results demonstrate that c-di-AMP is synthesized from two molecules of ATP by diadenylate cyclase (DAC) and degraded into pApA and then to AMP by a DHH family phosphodiesterase (PDE). DAC can be activated by a wider variety of ions, using two conserved residues, D188 and E244, to coordinate divalent metal ions, which is different from bacterial CdaA and DisA. PDE possesses a broad substrate spectrum like bacterial DHH family PDEs but shows a stricter base selection between A and G in cyclic dinucleotides hydrolysis. PDE shows differences in substrate binding patches from bacterial counterparts. C-di-AMP was confirmed to exist in Thermococcus kodakarensis cells, and the deletion of the dac or pde gene supports that the synthesis and degradation of c-di-AMP are catalyzed by DAC and PDE, respectively. Our results provide a further understanding of the metabolism of c-di-AMP in archaea., (© 2023 The Protein Society.)

Introduction: To determine the risk factors of hyperlactatemia in pulmonary endarterectomy (PEA) surgery and assess whether elevated blood lactate levels are associated with adverse outcomes., Methods: In this retrospective observational study, a total of 111 consecutive patients who underwent PEA for chronic thromboembolic pulmonary hypertension at the XXX Hospital between December 2016 and January 2022 were included. We retrospectively evaluated arterial blood samples analyzed intraoperatively. The pre- and intraoperative risk factors for hyperlactatemia and the postoperative outcomes were recorded., Results: Lactate levels gradually increased during surgery. The optimal cut-off lactate level for major postoperative complications, calculated using receiver operating characteristic analysis, was 7.0 mmol/L. Deep hypothermic circulatory arrest (DHCA) duration, nadir hematocrit, and preoperative pulmonary vascular resistance were risk factors for lactate levels >7 mmol/L. Moreover, the intraoperative peak lactate level during PEA under DHCA was found to be a statistically significant predictor of major complications being associated with longer mechanical ventilation time ( r = 0.294; p = .003) and intensive care unit length of stay ( r = 0.327; p = .001)., Conclusions: Deep hypothermic circulatory arrest duration, nadir hematocrit, and preoperative pulmonary vascular resistance were associated with hyperlactatemia. Increased lactate levels were independent predictors of longer mechanical ventilation time, intensive care unit length of stay, and major complications.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5 , 8 , and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

The relationships of KRAS, NRAS, BRAF and PIK3CA gene mutations with the clinicopathological features and prognosis of colorectal cancer (CRC) in patient are lacking. Furthermore, the role of ring finger protein 215 (RNF215) in CRC patients with KRAS, NRAS, BRAF and PIK3CA mutations remains unclear. In the present study, 182 surgical resection specimens from patients with primary CRC for retrospective analysis, were collected. KRAS/NRAS/BRAF/PIK3CA gene mutations were confirmed by an amplification-refractory mutation system. Immunohistochemistry (IHC) was conducted to confirm KRAS, NRAS, BRAF and PIK3CA protein expression. RNF215 expression in patients with CRC was evaluated using TIMER 2.0 database and IHC. The individual mutation rates of KRAS, NRAS, BRAF and PIK3CA were 40.7% (74/182), 4.4% (8/182), 4.4% (8/182) and 3.3% (6/182), respectively. The KRAS exon 2 mutation rate was the highest (61.5%, 64/104), and these mutations mainly occurred at codons 12 and 13. KRAS/NRAS/BRAF/PIK3CA wild-type CRC patients had significantly longer overall survival and disease-free survival than mutated KRAS/NRAS/BRAF/PIK3CA CRC patients (P<0.05). Overall, 45.4% (5/11) of patients with PIK3CA mutations had concomitant KRAS mutations. The KRAS/NRAS/BRAF/PIK3CA gene mutation rate in patients with lymph node metastasis (76.1%, 35/46) was significantly higher than that in patients without lymph node metastasis (50.8%, 69/136) (P=0.0027). There were no significant differences in IHC expression between patients with and without KRAS, NRAS, BRAF and PIK3CA mutations (P>0.05). The TIMER 2.0 analysis showed that RNF215 expression was significantly higher in the mutated BRAF group than in the wild-type BRAF group in CRC (P<0.05). In conclusion, KRAS is the most commonly mutated gene, and KRAS mutations may be a poor prognostic factor for patients with CRC. KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Wu et al.)