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Introduction: The use rate of electronic cigarettes (e-cigarettes) among adolescents is continuously rising globally, posing new challenges to public health and negatively impacting adolescent health. This study employs bibliometric methods to systematically present the current state and evolving trends in global research on adolescent e-cigarette use., Methods: This study uses CiteSpace to conduct a bibliometric analysis of articles related to adolescent e-cigarette use from the Web of Science (WoS) Core Collection database. Firstly, performance analysis and collaboration network analysis were utilized to clarify the basic publication status, main knowledge producers, and knowledge collaboration networks in adolescent e-cigarette use research. Secondly, a co-citation network analysis was performed to visually analyze the disciplinary characteristics and 'hot topics' in this field. Finally, keyword burst detection and clustering techniques were employed to further explain the development trends and frontiers of research on adolescent e-cigarette use., Results: A total of 2063 research articles and review articles were included in this study. Research on adolescent e-cigarette use has significantly increased from 2002 to 2024. The United States, the United Kingdom and Canada are the main contributors, with their institutions and researchers playing key roles in the international collaborative network. Current research increasingly adopts interdisciplinary approaches. Keyword co-occurrence and burst identified current research 'hotspots' including vaping, substance use, public policy, prevention, advertising, and cessation. Co-citation cluster analysis revealed promising research areas such as attractiveness, environment and health, accessibility and smoking behavior, and mental health., Conclusions: Through data mining and visualization techniques, this study provides a comprehensive bibliometric analysis of published work on e-cigarettes and adolescence. The results of this work offer references for researchers in future investigations., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Chen W. et al.)

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas ( Ailurus fulgens ) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__norank_o__Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, the main functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity., 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, Chen, Zhang, Wu and Zhao.)

Adjusting decision-making under uncertain and dynamic situations is the hallmark of intelligence. It requires a system capable of converting feedback information to renew the internal value. The anterior cingulate cortex (ACC) involves in error and reward events that prompt switching or maintenance of current decision strategies. However, it is unclear whether and how the changes of stimulus-action mapping during behavioral adaptation are encoded, nor how such computation drives decision adaptation. Here, we tracked ACC activity in male mice performing go/no-go auditory discrimination tasks with manipulated stimulus-reward contingencies. Individual ACC neurons integrate the outcome information to the value representation in the next-run trials. Dynamic recruitment of them determines the learning rate of error-guided value iteration and decision adaptation, forming a non-linear feedback-driven updating system to secure the appropriate decision switch. Optogenetically suppressing ACC significantly slowed down feedback-driven decision switching without interfering with the execution of the established strategy., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) continues to be a major global health concern. Recent advances in molecular biology have highlighted the gut microbiota's role in CRC. This study investigates long-term (≥5 years) gut microbiota changes in patients postcholecystectomy, comparing them with CRC patients and healthy controls to assess their impact on CRC development., Methods: Sixty participants were divided into three groups: 20 healthy controls, 20 postcholecystectomy (PCE) patients, and 20 CRC patients. Demographic data and stool samples were collected. Gut microbiota composition, abundance, and diversity were analyzed using high-throughput 16S rDNA sequencing., Results: Significant differences in microbial community, α-diversity (P < 0.05) and β-diversity (P = 0.006), were observed among the three groups. At the phylum level, Firmicutes abundance was significantly reduced in PCE and CRC groups compared with the control group (P = 0.002), while changes in other phyla were not significant (P>0.05). At the genus level, Bacteroides, Dialister, and Parabacteroides increased progressively from control to PCE to CRC groups (P = 0.004, 0.001, and 0.002). Prevotella decreased across these groups (P = 0.041). Faecalibacterium and Roseburia abundances were reduced in PCE and CRC groups compared with controls (P = 0.001 and 0.003). The Random Forest algorithm identified Parabacteroides, Bacteroides, Roseburia, and Dialister as key distinguishing genera., Conclusion: The gut microbiota of long-term (≥5 years) PCE patients significantly differs from that of controls and resembles that of CRC patients, suggesting a potential link between cholecystectomy and CRC development through key microbial changes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Phenolic acids are natural compounds with potential therapeutic effects against various diseases. However, their incorporation into food and pharmaceutical products is limited by challenges such as instability, low solubility, and reduced bioavailability. This systematic review summarizes recent advances in phenolic acid encapsulation using food-grade carrier systems, focusing on proteins, lipids, and polysaccharides. Encapsulation efficiency, release behavior, and bioavailability are examined, as well as the potential health benefits of encapsulated phenolic acids in food products. Strategies to address limitations of current encapsulation systems are also proposed. Encapsulation has emerged as a promising method to enhance the stability and bioavailability of phenolic acids in food products, and various encapsulation technologies have been developed for this purpose. The use of proteins, lipids, and carbohydrates as carriers in food-grade encapsulation systems remains a common approach, but it is associated with certain limitations. Future research on phenolic acid encapsulation should focus on developing environmentally friendly, organic solvent-free, low-energy, scalable, and stable encapsulation systems, as well as co-encapsulation methods that combine multiple phenolic acids or phenolic acids with other bioactive substances to produce synergistic effects.

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu 2- x Se and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors., (© 2024 Wiley‐VCH GmbH.)

Introduction: Atopic dermatitis (AD) is a chronic, non-infectious inflammatory dermatosis. Chloroquine (CQ) has long been proven to possess anti-inflammatory properties., Objective: This paper aims to investigate the impact of CQ on type 2 inflammatory response in MC903-induced AD mice., Methods: An AD mouse model was established via MC903 induction. After CQ treatment, AD mice were intraperitoneally injected with polyinosinic: polycyclic acid [poly (I:C)] or Nigericin. Dermatitis severity was scored, and the thickness of the left ear was measured. The pathological changes in mouse skin tissues were observed by H&E staining. The number of mast cells was counted via TB staining. The content of peripheral blood T-helper 2 (Th2) cells and levels of immunoglobulin E (IgE), thymic stromal-derived lymphopoietin (TSLP), interleukin (IL)-4, IL-13, interferon (IFN)-γ, IL-1β, and IL-18 were assessed by flow cytometry and ELISA. The levels of toll-like receptor 3 (TLR3), NLRP3, ASC, and cleaved caspase-1 proteins in skin tissues were determined by Western blot., Results: CQ treatment abated dermatitis severity and left ear thickness in AD mice, alleviated skin damage, reduced mast cell number, diminished IgE, TSLP, IL-4, and IL-13 levels, and peripheral blood Th2 cell content, with no significant changes in IFN-γ level. CQ alleviated type 2 inflammatory response in AD mice by inhibiting the activation of TLR3. CQ suppressed NLRP3 inflammasome activation. Activating TLR3/NLRP3 annulled CQ-mediated alleviation on type 2 inflammatory response in AD mice., Conclusion: CQ alleviated type 2 inflammatory response in AD mice by inhibiting TLR3 activation and NLRP3 inflammasome activation., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 Wei et al.)

Differentiation syndrome (DS) is the second leading cause of death in acute promyelocytic leukaemia (APL) patients. Few studies have tested predictors of DS events. This study aimed to identify optimized predictors of DS events related to APL. The data of 298 consecutive patients who were newly diagnosed with APL between December 2012 and June 2023 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical data, including baseline characteristics, routine blood examination findings, biochemical indices and clinical manifestations of DS. Among the 298 patients, 158 were classified into the no-DS group, while 140 had DS. Compared with those of patients without DS, the peripheral blast count, age, and WBC count at each time point were significantly different in patients with DS (P < 0.05 for all time points). Generalized linear mixed models (GLMMs) revealed that WBC Double (Coeff. 0.442, P = 0.000) and WBC Peak (Coeff. 0.879, P = 0.000) were independent risk factors for DS. The frequencies of clinical manifestations of unexplained fever (P = 0.003), dyspnoea (P = 0.002), weight gain of more than 5 kg (P = 0.006), pleural effusion (P = 0.001), pulmonary infiltrates (P < 0.001), pericardial effusion (P = 0.002) and renal failure (P = 0.006) were considerably lower in moderate DS patients than in severe DS patients. The WBC Double occurs earlier than the WBC peak occurrence, so WBC  Double might be a new indicator of DS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intensive anthropogenic activities have led to drastic changes in land use/land cover (LULC) and impacted the carbon storage in high-groundwater coal basins. In this paper, we conduct a case study on the Yanzhou Coalfield in Shandong Province of China. We further classify waterbodies by using the Google Earth Engine (GEE) to better investigate the process of LULC transformation and the forces driving it in four periods from 1985 to 2020 (i.e., 1985-1995, 1995-2005, 2005-2015, and 2015-2020). We modeled the spatiotemporal dynamics of carbon storage by using InVEST based on the transformation in LULC and its drivers, including mining (M), reclamation (R), urbanization and village relocation (U), and ecological restoration (E). The results indicate that carbon storage had depleted by 19.69 % (321099.06 Mg) owing to intensive transformations in LULC. The area of cropland shrank with the expansion of built-up land and waterbodies, and 56.31 % of the study area underwent transitions in land use in the study period. U was the primary driver of carbon loss while E was the leading driver of carbon gain. While the direct impact of M on carbon loss accounted for only 5.23 % of the total, it affected urbanization and led to village relocation. R led to the recovery of cropland and the reclamation of water for aquaculture, which in turn improved the efficiency of land use. However, it contributed only 2.09 % to the total increase in carbon storage. Numerous complicated and intertwined processes (211) drove the changes in carbon storage in the study area. The work here provides valuable information for decision-makers as well as people involved in reclamation and ecological restoration to better understand the link between carbon storage and the forces influencing it. The results can be used to integrate the goals of carbon sequestration into measures for land management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yanhua Fu reports financial support was provided by National Natural Science Foundation of China. 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 Inc. All rights reserved.)

Fine particulate matter (PM 2.5 ) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM 2.5 , and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM 2.5 -triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM 2.5 . Results illustrated that PM 2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM 2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM 2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM 2.5 and that miR-421i and resveratrol exert protective effects against PM 2.5 -incurred cardiotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

During the physiological period, women have the problem of lateral and posterior leakage, and they expect to have period underwear that can reduce lateral and posterior leakage. This study is combined with menstrual needs, and in the crotch penetration layer, three types of yarns are used, seaweed viscose yarn, apocynum viscose yarn, and viscose yarn, as well as two fabric structures: honeycomb-shaped convex-concave stitching and grid-shaped convex point stitching. In the crotch absorption layer, three types of yarns are used, modal yarn, bamboo yarn, and viscose yarn, as well as two fabric structures: plush stitching and plain stitching. The above two parts establish a sample scheme according to full-factor experimental tests, and 12 knitted fabric samples were knitted. The experimental data were analyzed through SPSS one-way ANOVA. The results indicate that in terms of veil raw materials, the crotch penetration layer with seaweed viscose yarn has better penetration performance, while the crotch absorption layer with bamboo yarn has better absorption performance. In terms of fabric structure, the crotch penetration layer with grid-shaped convex point stitching has better penetration performance, while the crotch absorption layer with plush stitching has better absorption performance. This study provides a theoretical basis for the development of period underwear.

Human INO80 chromatin remodeling complex (INO80 complex) as a transcription cofactor is widely involved in gene transcription regulation and is frequently highly expressed in tumor cells. However, few reports exist on the mutual regulatory mechanism between INO80 complex and non-coding microRNAs. Herein, we showed evidence that the INO80 complex transcriptionally controls microRNA-372 (miR-372) expression through RNA-Seq analysis and a series of biological experiments. Knocking down multiple subunits in the INO80 complex, including the INO80 catalytic subunit, YY1 , Ies2 , and Arp8 , can significantly increase the expression level of miR-372. Interestingly, mimicking miR-372 expression in HCT116 cells, in turn, post-transcriptionally suppressed INO80 and Arp8 expression at both mRNA and protein levels, indicating the existence of a mutual regulatory mechanism between the INO80 complex and miR-372. The target relationship between miR-372 and INO80 complex was verified using luciferase assays in HCT116 colon cancer cells. As expected, miR-372 mimics significantly suppressed the luciferase activity of pMIR-luc/INO80 and pMIR-luc/Arp8 3'-UTR in cells. In contrast, the miR-372 target sites in the 3'-UTRs linked to the luciferase reporter were mutagenized, and both mutant sites lost their response to miR-372. Furthermore, the mutual modulation between the INO80 complex and miR-372 was involved in cell proliferation and the p53/p21 signaling pathway, suggesting the synergistic anti-tumor role of the INO80 complex and miR372. Our results will provide a solid theoretical basis for exploring miR-372 as a biological marker of tumorigenesis.

Pepper, as a vegetable crop with a wide cultivation area worldwide, besides being a significant condiment and food, also has a momentous use for chemistry, medicine, and other industries. Pepper fruits are rich in various pigments, such as chlorophyll, carotenoids, anthocyanins, and capsanthin, which have important healthcare and economic value. Since various pigments are continuously metabolized during the development of pepper fruits, peppers exhibit an abundant fruit-colored phenotype in both the mature and immature periods. In recent years, great progress has been made in the study of pepper fruit color development, but the developmental mechanisms are still unclear systematically dissected in terms of pigment, biosynthesis, and regulatory genes. The article outlines the biosynthetic pathways of three important pigments: chlorophyll, anthocyanin, and carotenoid in pepper and the various enzymes involved in these pathways. The genetics and molecular regulation mechanisms of different fruit colors in immature and mature peppers were also systematically described. The objective of this review is to provide insights into the molecular mechanisms of pigments biosynthesis in pepper. This information will provide theoretical basis for the breeding of high-quality colored pepper varieties in the future.

Yin Yang 1 (YY1) is a well-known transcription factor that controls the expression of many genes and plays an important role in the occurrence and development of various cancers. We previously found that the human males absent on the first (MOF)-containing histone acetyltransferase (HAT) complex may be involved in regulating YY1 transcriptional activity; however, the precise interaction between MOF-HAT and YY1, as well as whether the acetylation activity of MOF impacts the function of YY1, has not been reported. Here, we present evidence that the MOF-containing male-specific lethal (MSL) HAT complex regulates YY1 stability and transcriptional activity in an acetylation-dependent manner. First, the MOF/MSL HAT complex was bound to and acetylated YY1, and this acetylation further promoted the ubiquitin-proteasome degradation pathway of YY1. The MOF-mediated degradation of YY1 was mainly related to the 146-270 amino acid residues of YY1. Further research clarified that acetylation-mediated ubiquitin degradation of YY1 mainly occurred through lysine 183. A mutation at the YY1K183 site was sufficient to alter the expression level of p53-mediated downstream target genes, such as CDKN1A (encoding p21), and it also suppressed the transactivation of YY1 on CDC6 . Furthermore, a YY1K183R mutant and MOF remarkably antagonized the clone-forming ability of HCT116 and SW480 cells facilitated by YY1, suggesting that the acetylation-ubiquitin mode of YY1 plays an important role in tumor cell proliferation. These data may provide new strategies for the development of therapeutic drugs for tumors with high expression of YY1.

Molecular toxicity prediction plays an important role in drug discovery, which is directly related to human health and drug fate. Accurately determining the toxicity of molecules can help weed out low-quality molecules in the early stage of drug discovery process and avoid depletion later in the drug development process. Nowadays, more and more researchers are starting to use machine learning methods to predict the toxicity of molecules, but these models do not fully exploit the 3D information of molecules. Quantum chemical information, which provides stereo structural information of molecules, can influence their toxicity. To this end, we propose QuantumTox, the first application of quantum chemistry in the field of drug molecule toxicity prediction compared to existing work. We extract the quantum chemical information of molecules as their 3D features. In the downstream prediction phase, we use Gradient Boosting Decision Tree and Bagging ensemble learning methods together to improve the accuracy and generalization of the model. A series of experiments on various tasks show that our model consistently outperforms the baseline model and that the model still performs well on small datasets of less than 300., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and aims: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) represents a type of severe fetal skeletal dysplasia (SD) characterized by shortened limbs, narrow thorax with or without polydactyly, which is caused by the homozygous or compound heterozygous mutations in the DYNC2H1 gene. SRTD3 is a recessive disorder, identification of the responsible genetic variation would be beneficial to an accurate prenatal diagnosis and well-grounded counseling for the affected families. Material and methods: Two families having experienced recurrent fetal SDs were recruited and submitted to a multiplatform genetic investigation. Whole-exome sequencing (WES) was performed with samples collected from the probands. Sanger sequencing and fluorescent quantitative PCR (qPCR) were conducted as validation assays for suspected variations. Results: WES identified two compound heterozygous variations in the DYNC 2H1(NM&#95;001080463.2) gene, namely c.2386C>T (p.Arg796Trp) and c.7289T>C (p.Ile2430Thr) for one; and exon (64-83)del and c.8190G>T (p.Leu2730Phe) for the other, respectively. One variant in them, exon (64-83)del, was novelly identified. Conclusion: The study detected two compound heterozygous variation in DYNC2H1 including one novel deletion: exon (64-83) del. Our findings clarified the cause of fetal skeletal dysplasia in the subject families, provided guidance for their future pregnancies, and highlighted the value of WES in diagnosis of skeletal dysplasia with unclear prenatal indications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Li, Zhang, Yuan, Sun, Yuan, Yang, Liang and Guo.)

In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-κB pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases., (© 2023. The Author(s).)

Background: The synergy between locoregional therapies and immune checkpoint inhibitors has not been investigated as conversion therapy for unresectable hepatocellular carcinoma. We aimed to investigate the activity of sequential transarterial chemoembolisation (TACE) and stereotactic body radiotherapy followed by avelumab (an anti-PD-L1 drug) for locally advanced, unresectable hepatocellular carcinoma., Methods: START-FIT was a single-arm, phase 2 trial in patients with locally advanced hepatocellular carcinoma who were not suitable for curative treatment, conducted in two hospitals in Hong Kong and one in Shenzhen, China. Eligible patients were those aged 18 years or older with an Eastern Cooperative Oncology Group performance status 0-1, Child-Pugh liver function score A5 to B7, tumour size of at least 5 cm, a maximum of three tumour lesions, and adequate hepatic, renal, and bone marrow function. Participants received TACE on day 1, followed by stereotactic body radiotherapy (27·5-40·0 Gy in five fractions) at day 28. Avelumab (10 mg/kg) was administered 14 days following stereotactic body radiotherapy and every 2 weeks thereafter. The primary endpoint was the proportion of patients deemed amenable to curative treatment, defined as those who had a sustained complete or partial treatment response for at least 2 months and if curative treatment could be performed (ie, resection, radiofrequency ablation, or transplantation), analysed by intention to treat. Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03817736) and has been completed., Findings: Between March 18, 2019, and Jan 27, 2021, 33 patients (32 [97%] men and one [3%] woman) were enrolled. The median sum of the largest diameters of lesions was 15·1 cm (IQR 8·3-14·9). 21 (64%) patients had macrovascular invasion (hepatic vein [n=13], branched portal vein [n=3], or both [n=5]). Median follow-up was 17·2 months (IQR 7·8-25·8). 18 (55%) patients were deemed amenable to curative treatment: four (12%) of 33 patients had curative treatment (resection [n=2] or radiofrequency ablation [n=2]), and 14 (42%) had a radiological complete response and opted for close surveillance. 11 (33%) of 33 patients had treatment-related adverse events that were grade 3 or worse. The most common treatment-related grade 3 or worse adverse event was transient increase in alanine aminotransferase or aspartate aminotransferase (five [15%]) after TACE. Five (15%) patients developed immune-related adverse events of grade 3 or worse (three had hepatitis, two had dermatitis)., Interpretation: To our knowledge, this is the first prospective trial using the combination of immunotherapy and locoregional treatment as conversion therapy for locally advanced unresectable hepatocellular carcinoma, with promising results. Future randomised trials with larger cohorts of patients are warranted., Funding: Merck., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Protein-protein interactions (PPIs) are a major component of the cellular biochemical reaction network. Rich sequence information and machine learning techniques reduce the dependence of exploring PPIs on wet experiments, which are costly and time-consuming. This paper proposes a PPI prediction model, multi-scale architecture residual network for PPIs (MARPPI), based on dual-channel and multi-feature. Multi-feature leverages Res2vec to obtain the association information between residues, and utilizes pseudo amino acid composition, autocorrelation descriptors and multivariate mutual information to achieve the amino acid composition and order information, physicochemical properties and information entropy, respectively. Dual channel utilizes multi-scale architecture improved ResNet network which extracts protein sequence features to reduce protein feature loss. Compared with other advanced methods, MARPPI achieves 96.03%, 99.01% and 91.80% accuracy in the intraspecific datasets of Saccharomyces cerevisiae, Human and Helicobacter pylori, respectively. The accuracy on the two interspecific datasets of Human-Bacillus anthracis and Human-Yersinia pestis is 97.29%, and 95.30%, respectively. In addition, results on specific datasets of disease (neurodegenerative and metabolic disorders) demonstrate the ability to detect hidden interactions. To better illustrate the performance of MARPPI, evaluations on independent datasets and PPIs network suggest that MARPPI can be used to predict cross-species interactions. The above shows that MARPPI can be regarded as a concise, efficient and accurate tool for PPI datasets., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Recent years have seen tremendous success in the design of novel drug molecules through deep generative models. Nevertheless, existing methods only generate drug-like molecules, which require additional structural optimization to be developed into actual drugs. In this study, a deep learning method for generating target-specific ligands was proposed. This method is useful when the dataset for target-specific ligands is limited. Deep learning methods can extract and learn features (representations) in a data-driven way with little or no human participation. Generative pretraining (GPT) was used to extract the contextual features of the molecule. Three different protein-encoding methods were used to extract the physicochemical properties and amino acid information of the target protein. Protein-encoding and molecular sequence information are combined to guide molecule generation. Transfer learning was used to fine-tune the pretrained model to generate molecules with better binding ability to the target protein. The model was validated using three different targets. The docking results show that our model is capable of generating new molecules with higher docking scores for the target proteins.

Hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous group of cells with expansion, differentiation, and repopulation capacities. How HSPCs orchestrate the stemness state with diverse lineage differentiation at steady condition or acute stress remains largely unknown. Here, we show that zebrafish mutants that are deficient in an epigenetic regulator Atf7ip or Setdb1 methyltransferase undergo excessive myeloid differentiation with impaired HSPC expansion, manifesting a decline in T cells and erythroid lineage. We find that Atf7ip regulates hematopoiesis through Setdb1-mediated H3K9me3 modification and chromatin remodeling. During hematopoiesis, the interaction of Atf7ip and Setdb1 triggers H3K9me3 depositions in hematopoietic regulatory genes including cebpβ and cdkn1a , preventing HSPCs from loss of expansion and premature differentiation into myeloid lineage. Concomitantly, loss of Atf7ip or Setdb1 derepresses retrotransposons that instigate the viral sensor Mda5/Rig-I like receptor (RLR) signaling, leading to stress-driven myelopoiesis and inflammation. We find that ATF7IP or SETDB1 depletion represses human leukemic cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation. These findings establish that Atf7ip/Setdb1-mediated H3K9me3 deposition constitutes a genome-wide checkpoint that impedes the myeloid potential and maintains HSPC stemness for diverse blood cell production, providing unique insights into potential intervention in hematological malignancy.

Aeromonas hydrophila is a Gram-negative pathogen that can infect various fish, including largemouth bass ( Micropterus salmoides ), which have caused huge economic losses. In present study, largemouth bass anti- A. hydrophila antibodies were produced, then a highly immunogenic outer membrane proteins, AHA&#95;3793, was identified by combined western blotting and mass spectrometry analysis. Moreover, AHA&#95;3793 was expressed, and its immunogenicity was further verified by western blotting. Subsequently, the protective efficacy of AHA&#95;3793 were evaluated in largemouth bass. The results showed that rAHA&#95;3793 could produce a relative percentage survival (RPS) of 61.76% for largemouth bass against A. hydrophila challenge. ELISA analysis showed the specific serum antibodies of largemouth bass against rAHA&#95;3793 and A. hydrophila in vaccinated group in weeks 4 and 5 after immunization were significantly higher than those in control group, which suggested that rAHA&#95;3793 induced production of specific serum antibodies against rAHA&#95;3793 and A. hydrophila . The qRT-PCR analysis showed that expressions of CD4-2 and MHC IIα were also significantly up-regulated after immunization. These results collectively demonstrated that rAHA&#95;3793 could induce a strong humoral immune response of largemouth bass, and then produce high immune protection effects against A. hydrophila infection., (© Chinese Society for Oceanology and Limnology, Science Press and Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Background: Biomedical named entity recognition is one of the important tasks of biomedical literature mining. With the development of natural language processing technology, many deep learning models are used to extract valuable information from the biomedical literature, which promotes the development of effective BioNER models. However, for specialized domains with diverse and complex contexts and a richer set of semantically related entity types (e.g., drug molecules, targets, pathways, etc., in the biomedical domain), whether the dependencies of these drugs, diseases, and targets can be helpful still needs to be explored. Method: Providing additional dependency information beyond context, a method based on the graph attention network and BERT pre-training model named MKGAT is proposed to improve BioNER performance in the biomedical domain. To enhance BioNER by using external dependency knowledge, we integrate BERT-processed text embeddings and entity dependencies to construct better entity embedding representations for biomedical named entity recognition. Results: The proposed method obtains competitive accuracy and higher efficiency than the state-of-the-art method on three datasets, namely, NCBI-disease corpus, BC2GM, and BC5CDR-chem, with a precision of 90.71%, 88.19%, and 95.71%, recall of 92.52%, 88.05%, and 95.62%, and F1-scores of 91.61%, 88.12%, and 95.66%, respectively, which performs better than existing methods. Conclusion: Drug, disease, and protein dependencies can allow entities to be better represented in neural networks, thereby improving the performance of BioNER., 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 © 2022 Han, Li, Wang, Wang, Gao and Chen.)

Identification of internal-rotation modes in the normal-mode analysis of complex molecules is important for accurately describing the thermodynamic properties and kinetics of complex molecules when it is necessary to treat the anharmonicity of torsions and the multiconformer anharmonicity caused by the internal rotations. However, identifying and distinguishing torsional modes are very challenging because they are coupled to one another. In this work, we present a new strategy to automatically identify torsional vibrations and separate them from the other vibrational modes. By combining a redundant-internal-coordinate auto-generation procedure with torsional projection techniques, we automate the procedure of identifying and separating the coupled torsions, and we show that we can obtain robust and consistent results with various reasonable definitions of redundant-internal-coordinate sets. This model has been implemented in a new development version of the MSTor program to reduce the user input needed for multistructural and torsional anharmonicity (MS-T) calculations. The new method is called multistructural and torsional anharmonicity with a coupled torsional potential and delocalized torsions ([MS-T(CD)]. As example applications, we consider MS-T(CD) calculations on three molecules (2-hexyl radical, n -propylbenzene, and 5-hydroperoxy-6-oxohexanoylperoxy radical) that have multiple rotors and that provide challenges to choosing good sets of nonredundant-internal coordinates, and we compare the performance of the new strategy to five other torsion identification methods. The new strategy is demonstrated to be efficient in separating the torsional and nontorsional elements in the Hessian matrix, as well as in providing reasonable projected nontorsional frequencies to be used for calculations of partition function and thermochemistry.

The prediction of a protein-protein interaction site (PPI site) plays a very important role in the biochemical process, and lots of computational methods have been proposed in the past. However, the majority of the past methods are time consuming and lack accuracy. Hence, coming up with an effective computational method is necessary. In this article, we present a novel computational model called RGN (residue-based graph attention and convolutional network) to predict PPI sites. In our paper, the protein is treated as a graph. The amino acid can be seen as the node in the graph structure. The position-specific scoring matrix, hidden Markov model, hydrogen bond estimation algorithm, and ProtBert are applied as node features. The edges are decided by the spatial distance between the amino acids. Then, we utilize a residue-based graph convolutional network and graph attention network to further extract the deeper feature. Finally, the processed node feature is fed into the prediction layer. We show the superiority of our model by comparing it with the other four protein structure-based methods and five protein sequence-based methods. Our model obtains the best performance on all the evaluation metrics (accuracy, precision, recall, F 1 score, Matthews correlation coefficient, area under the receiver operating characteristic curve, and area under the precision recall curve). We also conduct a case study to demonstrate that extracting the protein information from the protein structure perspective is effective and points out the difficult aspect of PPI site prediction.

Objectives: To explore the value of an ultrasound contrast agent (Sonovue) as an interventional treatment for periappendiceal abscesses., Methods: From January 2019 to December 2020, 30 patients were recruited who were admitted to Jinan Central Hospital due to periappendiceal abscesses. Before the operation, 2.5 ml of SonoVue ® contrast agent was injected intravenously to determine the non-enhanced area of liquefaction and necrosis in the abscess cavity. The puncture sites were selected. Percutaneous catheterization and drainage (PCD) were performed under contrast-enhanced ultrasound guidance. After the operation, 1 ml of diluted SonoVue ® suspension was injected through the drainage tube to observe the position of the drainage tube, the degree of drainage and the development of the abscess., Results: An ultrasound contrast agent was used preoperatively to assess the extent of the abscess. Liquefaction and necrosis were observed in the abscess cavity. CEUS showed hyperenhancement in the wall of the abscess in the arterial phase and the liquefied necrotic area in the abscess cavity was not enhanced before PCD. CEUS allowed operators to confidently identify the puncture site. Amongst the 30 cases of PCD, 27 cases showed the clear positioning of the drainage tube. The head of the drainage tube was placed in the ideal position and development could be seen in the abscess cavity. The diffusion effect of the contrast agent was good with no spillover and the drainage was unobstructed. Abscess development was observed in 3 patients after puncture injection of the contrast agent but the head of the drainage tube was not in the predetermined position. After adjusting the position of the drainage tube, CEUS was repeated and showed a strong diffusion effect of the contrast agent., Conclusions: Intravenous injection of Sonovue before PCD of periappendiceal abscesses can evaluate the extent of the abscess, liquefaction and necrosis in the abscess cavity. The approach can also provide guidance for the placement of the drainage tube. After the operation, a diluted contrast agent was injected through the drainage tube. The position of the drainage tube and the flow direction of the contrast agent could be seen. This approach has good value for clinical applications to accurately judge the position of the drainage tube., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

The abstraction reaction of hydrogen from formaldehyde by OH radical plays an important role in formaldehyde oxidation. The reaction involves a bimolecular association to form a chemically activated hydrogen-bonded reaction complex followed by a unimolecular reaction of the complex to generate the products. The reaction rate is usually considered to be pressure-independent by assuming equilibrium between the reactants and the complex. However, our nonequilibrium calculations based on the chemically significant eigenmode of the master equation, carried out with our recently developed TUMME program, indicate that the reaction complex makes the rate constant dependent on pressure at low temperatures ( T < 200 K). The calculations include anharmonicity, variational effects, and multi-dimensional tunneling. We find that the reaction rate constant reaches a low-pressure limit at pressures below 10 Torr over the whole investigated temperature range (20-1800 K), which explains why the available low-temperature experiments, which are for pressures below 2 Torr, did not observe the pressure dependence. A new extension of the TUMME master-equation program is used to explore the time evolutions of the concentrations of the OH radical and the complex under pseudo-first-order conditions. The time-dependent evolution of the concentrations of the complex at a low temperature provide direct evidence for the stabilization of the reaction complex at high pressures, and it shows the negligible role of the stabilized reaction complex at low pressures. The picture that emerges is qualitatively consistent with our previous study of the reaction of methanol with OH in that the tunneling in the unimolecular step from the complex to the products affects the phenomenological reaction rate constants differently at high and low pressures and leads to a significant pressure effect.

Urban waterbodies are one of the most pertinent issues involved in multiple aspects of Sustainable Development Goals (SDGs). However, waterbodies in large Chinese cities are highly vulnerable to urban-land expansion, which is mostly due to economic development, population growth, and rural-urban migration. In this work, we selected 159 Chinese cities of over one million in population to investigate the encroachment on waterbodies due to rapid urbanization from 1990 to 2018. Overall, 20.6% of natural waterbody area was lost during this period to urban expansion, and this fraction varied from city to city which was related to waterbody abundance. With the acceleration of urbanization, waterbody occupation is becoming more serious (P < 0.01). However, in all cities, this encroachment has eased since 2010, which justifies the effective implementation of national-scale policies to conserve urban waterbodies. Meanwhile, gains have occurred during urbanization, in addition to the loss of waterbodies. Especially, cities lacking waterbody placed a greater emphasis on ecological factors, whose urban waterbody areas showed an increasing trend. In the future, ecological resources, including waterbody, should be considered in urban planning to provide reasonable protection to waterbodies in the quest for urban sustainability., (© 2022. The Author(s).)

Background: Protein-protein interaction (PPI) is very important for many biochemical processes. Therefore, accurate prediction of PPI can help us better understand the role of proteins in biochemical processes. Although there are many methods to predict PPI in biology, they are time-consuming and lack accuracy, so it is necessary to build an efficiently and accurately computational model in the field of PPI prediction., Results: We present a novel sequence-based computational approach called DCSE (Double-Channel-Siamese-Ensemble) to predict potential PPI. In the encoding layer, we treat each amino acid as a word, and map it into an N-dimensional vector. In the feature extraction layer, we extract features from local and global perspectives by Multilayer Convolutional Neural Network (MCN) and Multilayer Bidirectional Gated Recurrent Unit with Convolutional Neural Networks (MBC). Finally, the output of the feature extraction layer is then fed into the prediction layer to output whether the input protein pair will interact each other. The MCN and MBC are siamese and ensemble based network, which can effectively improve the performance of the model. In order to demonstrate our model's performance, we compare it with four machine learning based and three deep learning based models. The results show that our method outperforms other models in all evaluation criteria. The Accuracy, Precision, [Formula: see text], Recall and MCC of our model are 0.9303, 0.9091, 0.9268, 0.9452, 0.8609. For the other seven models, the highest Accuracy, Precision, [Formula: see text], Recall and MCC are 0.9288, 0.9243, 0.9246, 0.9250, 0.8572. We also test our model in the imbalanced dataset and transfer our model to another species. The results show our model is excellent., Conclusion: Our model achieves the best performance by comparing it with seven other models. NLP-based coding method has a good effect on PPI prediction task. MCN and MBC extract protein sequence features from local and global perspectives and these two feature extraction layers are based on siamese and ensemble network structures. Siamese-based network structure can keep the features consistent and ensemble based network structure can effectively improve the accuracy of the model., (© 2022. The Author(s).)

Objectives: Joubert syndrome is a spectrum of rare genetic disorders, mainly characterized by a distinctive cerebellar and brain stem malformation called the "molar tooth sign" (MTS), hypotonia, and intellectual disability/developmental delay., Methods: In this study, 4 pediatric cases with developmental delay and oculomotor abnormities were recruited, and submitted to a clinical evaluation and magnetic resonance imaging (MRI) examination. Afterwards, genetic detection with whole exome sequencing (WES) was conducted on the 4 patients., Results: Imaging results demonstrated cerebellar dysplasia in all probands, yet the MTS findings varied in severity. WES detected diagnostic variations in all four probands, which were distributed in four genes, namely CC2D2A, NPHP1, AHI1 , and C5orf42 . Two variants were novelly identified, which were the CC2D2A : c.2444delC (p.P815fs*2) and the AIH1 : exon (15-17) del. In silico analysis supported the pathogenicity of the variations in this study., Conclusions: Our findings expanded the mutation spectrum of Joubert syndrome related disorders, and provided solid evidence to the affected families for further genetic counseling and pregnancy guidance., Competing Interests: None., (AJTR Copyright © 2022.)

Background: Protein-protein interactions (PPIs) dominate intracellular molecules to perform a series of tasks such as transcriptional regulation, information transduction, and drug signalling. The traditional wet experiment method to obtain PPIs information is costly and time-consuming., Result: In this paper, SDNN-PPI, a PPI prediction method based on self-attention and deep learning is proposed. The method adopts amino acid composition (AAC), conjoint triad (CT), and auto covariance (AC) to extract global and local features of protein sequences, and leverages self-attention to enhance DNN feature extraction to more effectively accomplish the prediction of PPIs. In order to verify the generalization ability of SDNN-PPI, a 5-fold cross-validation on the intraspecific interactions dataset of Saccharomyces cerevisiae (core subset) and human is used to measure our model in which the accuracy reaches 95.48% and 98.94% respectively. The accuracy of 93.15% and 88.33% are obtained in the interspecific interactions dataset of human-Bacillus Anthracis and Human-Yersinia pestis, respectively. In the independent data set Caenorhabditis elegans, Escherichia coli, Homo sapiens, and Mus musculus, all prediction accuracy is 100%, which is higher than the previous PPIs prediction methods. To further evaluate the advantages and disadvantages of the model, the one-core and crossover network are conducted to predict PPIs, and the data show that the model correctly predicts the interaction pairs in the network., Conclusion: In this paper, AAC, CT and AC methods are used to encode the sequence, and SDNN-PPI method is proposed to predict PPIs based on self-attention deep learning neural network. Satisfactory results are obtained on interspecific and intraspecific data sets, and good performance is also achieved in cross-species prediction. It can also correctly predict the protein interaction of cell and tumor information contained in one-core network and crossover network.The SDNN-PPI proposed in this paper not only explores the mechanism of protein-protein interaction, but also provides new ideas for drug design and disease prevention., (© 2022. The Author(s).)

Hepatocellular carcinoma (HCC) is a common malignancy with high mortality rates. While surgery can be curative in early-stage disease, 80% of patients cannot undergo surgical resection. Stereotactic body radiotherapy (SBRT), an emerging, non-invasive, precision treatment, has shown promising results across various stages of HCC and has thus been adopted in practice to varying degrees around the world. This article aims to review current guideline recommendations on SBRT, clinical evidence, and outcome comparisons with other local treatment modalities. Attempts are also made to compare the differences in clinical trials between Asian and Western countries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Feng-Ming (Spring) Kong reported that the equipment, drugs, or supplies were provided by Shenzhen Science and Technology program and a Varian Medical Systems. Other authors declare that they have no conflict of interests., (© 2022 Chinese National Cancer Center. Published by Elsevier B.V.)

Sucrose, an essential carbohydrate, is transported from source to sink organs in the phloem and is involved in a variety of physiological and metabolic processes in plants. Sucrose transporter proteins (SUTs) may play significant parts in the phloem loading and unloading of sucrose. In our study, the SUT gene family was identified in four Solanaceae species ( Capsicum annuum, Solanum lycopersicum, S. melongena , and S. tuberosum ) and other 14 plant species ranged from lower and high plants. The comprehensive analysis was performed by integration of chromosomal distribution, gene structure, conserved motifs, evolutionary relationship and expression profiles during pepper growth under stresses. Chromosome mapping revealed that SUT genes in Solanaceae were distributed on chromosomes 4, 10 and 11. Gene structure analysis showed that the subgroup 1 members have the same number of introns and exons. All the SUTs had 12 transmembrane structural domains exception from CaSUT2 and SmSUT2 , indicating that a structure variation might occurred among the Solanaceae SUT proteins. We also found a total of 20 conserved motifs, with over half of them shared by all SUT proteins, and the SUT proteins from the same subgroup shared common motifs. Phylogenetic analysis divided a total of 72 SUT genes in the plant species tested into three groups, and subgroup 1 might have diverged from a single common ancestor prior to the mono-dicot split. Finally, expression levels of CaSUTs were induced significantly under heat, cold, and salt treatments, indicating diverse functions of the CaSUTs to adapt to adverse environments.

Copy number variations (CNVs) at the chromosomal 1q21.1 region represent a group of hot-spot recurrent rearrangements in human genome, which have been detected in hundreds of patients with variable clinical manifestations. Yet, report of such CNVs in prenatal scenario was relatively scattered. In this study, 17 prenatal cases involving the 1q21.1 microdeletion or duplication were recruited. The clinical survey and imaging examination were performed; and genetic detection with karyotyping and CNV analysis using chromosomal microarray (CMA) or CNVseq were subsequently carried out. These cases were all positive with 1q21.1 CNV, yet presented with exceedingly various clinical and utrasonographic indications. Among them, 12 pregnancies carried 1q21.1 deletions, while the other 5 carried 1q21.1 duplications, all of which were within the previously defined breaking point (BP) regions. According to the verification results, 9 CNVs were de novo , 7 were familial, and the other 1 was not certain. We summarized the clinical information of these cases, and the size and distribution of CNVs, and attempted to analyze the association between these two aspects. The findings in our study may provide important basis for the prenatal diagnosis and genetic counseling on such conditions in the future., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Xiaohui Wen et al.)

Human males absent on the first (MOF), a histone acetyltransferase (HAT), forms male-specific lethal (MSL) and non-specific lethal (NSL), two multiprotein HATs, in cells. MSL was originally discovered in dosage compensation study in Drosophila that can specifically acetylate H4K16, while NSL can simultaneously catalyze the H4 at K5, K8, and K16 sites. However, comparative studies of the two HATs in regulating specific biological functions are rarely reported. Here, we present evidence to argue that MSL and NSL function in different ways in the epithelial-to-mesenchymal transition (EMT) process. At first, CRISPR/Cas9-mediated MSL1 (a key subunit of the MSL)-knockout (KO) and NSL3 (a key subunit of the NSL)-KO cells seem to prefer to grow in clusters. Interestingly, the former promotes cell survival and clonal formation, while the latter has the opposite effect on it. Cell staining revealed that MSL1-KO leads to multipolarized spindles, while NSL3-KO causes more lumen-like cells. Furthermore, in Transwell experiments, silencing of MSL1 promotes cell invasion in 293 T, MCF-7, and MDA-MB-231 cells. In contrast, the inhibitory effects on cell invasion are observed in the same NSL3-silenced cells. Consistent with this, mesenchymal biomarkers, like N-cadherin, vimentin, and snail, are negatively correlated with the expression level of MSL1; however, a positive relationship between these proteins and NSL3 in cells has been found. Further studies have clarified that MSL1, but not NSL3, can specifically bind to the E-box-containing Snail promoter region and thereby negatively regulate Snail transactivation. Also, silencing of MSL1 promotes the lung metastasis of B16F10 melanoma cells in mice. Finally, ChIP-Seq analysis indicated that the NSL may be mainly involved in phosphoinositide-mediated signaling pathways. Taken together, the MOF-containing MSL and NSL HATs may regulate the EMT process in different ways in order to respond to different stimuli., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Different physicochemical properties between Cr(VI) and phenolic compounds pose serious challenges for the effective treatment of co-contamination. This study developed an electrodeless high-flow microwave atmospheric plasma jet for the single-step simultaneous degradation of p-nitrophenol (PNP) and reduction of Cr(VI). Following a 15 min treatment with microwave atmospheric pressure plasma, the removal efficiency of Cr(VI) and PNP reached 97.5% and 93.6%, respectively, whereas that of total organic carbon reached 30.2%. Adding PNP to the solution significantly improved Cr(VI) reduction, whereas PNP degradation increased slightly with Cr(VI). The results indicate that the PNP intermediates significantly affected Cr(VI) reduction. Additionally, long-lived H 2 O 2 and short-lived · H aided the reduction of Cr(VI) during plasma treatment. The addition of hydroxyl scavengers during treatment implied that · OH was largely responsible for PNP oxidation. High-performance liquid chromatography-mass spectroscopy (HPLC-MS) revealed that PNP intermediates, including p-nitrocatechol and 5-nitrobenzene-1,2,3-triol, function as Cr(VI) reductants. On the basis of the examined intermediate products, the potential PNP degradation pathway was investigated. The factors that could influence simultaneous dehgradation and reduction, including solution pH, gas velocity, and distance between the plasma outlet and the water surface were researched. Low pH supports Cr(VI) reduction, and the promotion of PNP for Cr(VI) reduction applies to all pH values. The degradation of PNP is insensitive to pH values with or without Cr(VI). The optimal gas velocity for PNP degradation and Cr(VI) reduction was revealed to be 6 L/min. The simultaneous removal of PNP and Cr(VI) benefits from a shorter distance between the plasma outlet and the water's surface., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic viral double-stranded RNA analog that can activate Toll-like receptor 3 (TLR3) and induce the release of thymic stromal lymphopoietin (TSLP). TSLP has been shown to contribute to atopic dermatitis (AD). This study explored the effects of poly (I:C) in a calcipotriol-induced model of murine AD., Methods: Calcipotriol (MC903) was used to establish AD-like mice model. Mice in the MC903 + poly (I:C) group were then treated with poly (I:C) in a concentration of 5 µg/g bodyweight. The impact of poly (I:C) treatment on these animals was assessed based upon changes in lesions, bodyweight, ear thickness, and histopathological findings. In addition, serum interleukin 4 (IL-4), interferon-γ (IFN-γ), immunoglobulin E (IgE), IL-13, and TSLP levels were measured using enzyme-linked immunosorbent assay (ELISA), while tissue IL-13 and TSLP levels were assessed using ELISA, Western blotting, and immunohistochemical staining, and mast cell infiltration was assessed through toluidine blue (TBO) staining., Results: Relative to vehicle control treatment, poly (I:C) administration was associated with a significant exacerbation of calcipotriol-induced AD-like murine skin lesions. In animals treated with poly (I:C), the levels of serum IL-4, IL-13 and TSLP increased significantly, while the level of IFN-γ did not change. It also increased IL-13 and TSLP levels in skin lesions relative to the control-group mice and increased dermal mast cell infiltration and IgE production., Conclusions: These data indicate that poly (I:C) treatment and exogenous activation of TLR3 exacerbate murine calcipotriol-induced AD-like skin lesions in part by increasing the production of TSLP and other T-helper 2 (Th2)-related cytokines., Keywords: Atopic dermatitis (AD); polyinosinic:polycytidylic acid [poly (I:C)]; thymic stromal lymphopoietin (TSLP); Toll-like receptor 3 (TLR3)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-282/coif). All authors report funding from Nanjing Medical Science and Technology Development Project (Grant No. YKK16134). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Abstract: Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for unresectable hepatocellular carcinoma (HCC). Whether its efficacy is comparable to radiofrequency ablation (RFA), a recommended therapy for unresectable HCC, is unknown. The present study aims to compare the clinical outcome between SBRT and RFA for patients with unresectable HCC.The clinical data of 60 patients with unresectable HCC from January 2018 to January 2021 were retrospectively reviewed. There were 22 cases treated by SBRT and 38 cases by RFA. The short-term and long-term clinical outcomes were compared.There was no significant difference in the baseline demographic characteristics between two groups. The complete remission rate at 3 months was comparable between SBRT group (81.8%) and RFA group (89.4%). Local tumor control rate was also similar between two groups (90.9% vs. 94.7%). There was no severe complication (grade IIIa or above) in both groups. The 1-year and 2-year overall survival rates were 88.2% and 85.7% in SBRT group and 100% and 75% in RFA group, respectively. There was no statistical significant difference between groups (P = .576).SBRT can achieve similar short and long-term clinical outcome as RFA for unresectable HCC. Future prospective clinical study is needed to justify its role in patients with HCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The toxicological effects of fine particulate matter (PM 2.5 ) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM 2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM 2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM 2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM 2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM 2.5 plus LPS for 23 weeks in Linfen, a city with a high PM 2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM 2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM 2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM 2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM 2.5 plus LPS.

Numerous human circular RNAs (circRNAs/circ) have been functionally characterized. However, the potential role of circ-protein kinase C iota (PRKCI) in hepatocellular carcinoma (HCC) remains unknown. The effects of each transfection and expression levels of circ-PRKCI, microRNA (miR)-1294, miR-186-5p and forkhead box K1 (FOXK1) in HCC cells were analyzed using reverse transcription-quantitative PCR analysis. The interactions between circ-PRKCI and miR-1294 or miR-186-5p, and miR-1294 or miR-186-5p and FOXK1 were validated using dual luciferase reporter assays. The viability, invasion and migration of HCC cells were determined using Cell Counting Kit-8, Transwell and wound healing assays, respectively. The expression levels of FOXK1, hexokinase-2 (HK2), glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA) in HCC cells were analyzed using western blotting. The levels of glucose and lactic acid in the cultured supernatant were detected using commercially available kits. The results of the present study revealed that miR-1294 and miR-186-5p expression levels were downregulated in the HCC cell line, HCCLM3, and were subsequently downregulated by circ-PRKCI overexpression and upregulated by the knockdown of circ-PRKCI. circ-PRKCI overexpression promoted the viability, invasion and migration of HCCLM3 cells, which was also reversed by the overexpression of miR-1294 and miR-186-5p. In addition, the overexpression of circ-PRKCI upregulated FOXK1 expression levels, while the overexpression of miR-1294 and miR-186-5p downregulated FOXK1 expression levels. Conversely, the knockdown of circ-PRKCI expression downregulated FOXK1 expression levels, while the knockdown of miR-1294 and miR-186-5p upregulated FOXK1 expression levels. Furthermore, circ-PRKCI was identified to target miR-1294 and miR-186-5p, and miR-1294 and miR-186-5p were subsequently found to target FOXK1. The overexpression of circ-PRKCI also increased glucose and lactic acid levels, while the knockdown of FOXK1 decreased glucose and lactic acid levels. The knockdown of circ-PRKCI decreased glucose and lactic acid levels, which were reversed by FOXK1 overexpression. In conclusion, the findings of the present study suggested that circ-PRKCI may promote the viability, invasion and migration of HCC cells by sponging miR-1294 and miR-186-5p to upregulate FOXK1 expression levels.

The polymeric immunoglobulin receptor (pIgR) is an important molecule in the mucosal immunity of teleosts. Previous studies have shown that pIgR can bind and transport polymeric immunoglobulins (pIgs), but few studies have focused on the binding of teleost pIgR to bacteria. In this study, we identified a gene encoding pIgR in largemouth bass (Micropterus salmoides). The pIgR gene contained two Ig-like domains (ILDs), which were homologous to ILD1 and ILD5 of mammalian pIgR. Our results showed that largemouth bass pIgR-ILD could combine with IgM. Moreover, we also found that largemouth bass pIgR-ILD could bind to Aeromonas hydrophila and Micrococcus luteus. Further analysis showed that largemouth bass pIgR-ILD could also combine with lipopolysaccharide (LPS), peptidoglycan (PGN) and various saccharides, and reduced binding to bacteria was observed with LPS and PGN treatment, indicating that largemouth bass pIgR could bind to bacteria to prevent infection and that saccharide binding is an important interaction mechanism between pIgR and bacteria. These results collectively demonstrated that largemouth bass pIgR not only combines with IgM but also binds to bacteria by various saccharides., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hydrogen abstraction reactions of (cyclo)alkanes by radicals play a fundamental role in both combustion and atmospheric chemistry. In this work, we select three common radicals in the pyrolysis of hydrocarbon fuels: hydrogen radical (H[combining dot above]), methyl radical (ĊH 3 ), and ethyl radical (ĊH 2 CH 3 ) to investigate the kinetics of their hydrogen abstraction reactions with cyclopentane. The rate constants over a broad temperature range of 150-3000 K are calculated by using the multi-structural variational transition state theory in the small-curvature tunneling approximation (MS-CVT/SCT), by which the multi-structural torsional (MS-T) anharmonicity of partition functions, variational effects, and corner-cutting tunneling are all included in dynamics calculations. We stress the particular importance of considering the MS-T anharmonicity in the rate constant calculation for the reaction with the ethyl radical compared to those with hydrogen and methyl radicals. The MS-T anharmonicity significantly accelerates the reaction with the ethyl radical in the whole temperature range, and in particular, it increases the rate constant by a factor of >-9 at 1000 K. We also found that the tunneling effect drastically increases the rate constants at low-temperatures by up to 3-5 orders of magnitudes. The calculated reaction rate constants have an order of .

Primary liver cancer includes hepatocellular carcinoma (HCC, 75-85%) and intrahepatic cholangiocarcinoma (10-15%). The vast majority of patients with primary HCC are not candidates for surgical treatment. Surgical resection, liver transplantation and percutaneous puncture are effective potentially curable treatments for patients with early stage liver cancer. Radiation therapy is a non-surgical alternative treatment that has generally been used to treat patients with advanced liver cancer, although it's use in the potentially curative setting is increasing. Radiotherapy is a non-invasive local treatment which works through ionizing radiation. This review summarizes the efficacy and safety of commonly used radiotherapy methods, and reviews three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiation therapy (IMRT), stereotactic body radiotherapy (SBRT), volume-modulated arc therapy (VMAT), and internal radiation therapies, for primary liver cancer (in particular for HCC).

This study investigated the effects of both force level and gender on pinch force reproduction errors in normal participants during an ipsilateral force reproduction task. In total, 20 healthy participants were asked to generate a range of levels of reference forces ranging from 5% to 60% maximal voluntary isometric contraction (MVIC) in increments of 5% MVIC using the tip pinch and to reproduce these forces using the same hand. The results showed that the males more accurately and consistently reproduced the forces than did the females, and the most accurate estimation occurred at approximately 20% to 35% MVIC. This finding can help us better understand the reasons for the higher rate of musculoskeletal disorders in females than in males and to develop tools and preventive strategies to decrease the rate of hand injuries in both genders., (© The Author(s) 2020.)