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Liu-Jun He,1 Dong-Lin Yang,1 He-Ying Chen,1– 3 Jiu-Hong Huang,1 Ya-Jun Zhang,1 Hong-Xia Qin,1 Juan-Li Wang,1 Dian-Yong Tang,1 Zhong-Zhu Chen1 1National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of China; 2Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3The Undergraduates Class of 2016 Entry the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaCorrespondence: Dong-Lin Yang; Zhong-Zhu ChenNational & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of ChinaTel/Fax +86-23-61162836Email dlyang@cqwu.edu.cn; 188831382372@163.comBackground: Breast cancer exhibits poor prognosis and high relapse rates following chemotherapy therapeutics. Thus, this study aims to develop effective novel agents regulating the core molecular pathway of breast cancer such as Wnt/β-catenin signaling.Methods: The present study screened a novel inhibitor, called “C188”, using MTT assay. The molecular formula of C188 is C21H15FN4O3 and the molecular weight is 390. Flow cytometry and Western blotting were employed to assess cell cycle arrest after treatment with C188. Wound-healing and transwell assays were applied to measure the cell migration and invasion viability. The regulatory effects of C188 on Wnt/β‑catenin signaling and localization of β‑catenin in the nucleus were investigated by Western blotting and immunofluorescence.Results: We found that C188 significantly suppressed proliferation and growth in a dose- and time-dependent manner in breast cancer cells, but not in normal breast cells. The inhibitory effect was caused by cell cycle arrest at the G1-phase which is induced by C188 treatment. Additionally, C188 dramatically inhibited cell migration of breast cancer cells in a dose-dependent manner. The migration inhibition was attributed to the suppression of Wnt/β‑catenin signaling and localization of β‑catenin in the nucleus mediated by regulating phosphorylation of β‑catenin and its subsequent stability. Furthermore, the target genes, including Axin 2, c-JUN, and c-Myc, were downregulated due to the decrease of β‑catenin in the nucleus after exposure to C188.Conclusion: C188 treatment resulted in the downregulation of cyclin D which led to cell cycle arrest at the G1 phase, and the inhibition of cell migration, indicating that C188 may be an effective novel therapeutic candidate as a potential treatment for human breast cancer.Keywords: C188, breast cancer, proliferation, cell cycle, cell migration, Wnt/β-catenin

Yanting Shen,1,2 Rui Li,1 Fei Tian,1 Zhenzhu Chen,1 Na Lu,2 Yunfei Bai,2 Qinyu Ge,2 Zuhong Lu1,2 1School of Biomedical Engineering, Southeast University, Nanjing 210096, Jiangsu Province, People’s Republic of China; 2State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, Jiangsu Province, People’s Republic of China Background: The reliability of RNA sequencing (RNA-seq) output is affected by the quality of RNAs, which is in turn dependent on the quality of samples. Therefore, the purposes of this study were to reconsider the threshold of the RNA integrity number (RIN) and propose a simple and efficient storage scheme of blood samples for RNA-seq.Patients and methods: The RNAs were extracted from blood samples that were stored at different conditions and used for sequencing. The bioinformatic analyses were performed to evaluate the impact of RNA integrity and blood sample storage conditions on the gene expression analysis.Results: Our outcomes showed that the samples with RIN values more than 5.3 scarcely affected the quantitative results of RNA-seq, and the influence of inherent cellular physiological processes on RNA-seq output could be negligible.Conclusion: The blood samples stored at 4°C within 7 days with RIN values more than 5.3 were available for RNA-seq. Keywords: RNA, NGS, blood, integrity, RIN, sequencing

Purpose: To evaluate the efficiency of an arthroscopic suturing technique for stabilizing anteriorly displaced discs in patients with internal derangement of the temporomandibular joint (TMJ) by magnetic resonance (MR) imaging. Patients and Methods: Six hundred thirty-nine patients (764 joints) diagnosed as having stages II to V of internal derangement were treated with arthroscopic disc repositioning and suturing from August 2004 to March 2007. Consecutive MR images were used to evaluate internal derangement before and approximately 1 to 7 days after the operation for all 639 patients. The disc position of the TMJ was judged according to the success criteria, which included 3 different sagittal planes (lateral, central, and medial). Operative efficiency in those patients, whose discs of the TMJ were affirmed to be in a normal position in all 3 planes, was evaluated to be excellent. Those patients whose discs were in a normal position in 2 planes were evaluated to be good. The others were evaluated to be poor. Cases evaluated as excellent and good were considered success cases (if the disc is displaced only in 1 or 2 planes before operation, the efficiency of the operation would be evaluated as a success only if the whole disc was in normal position). Results: Postoperative consecutive MR images for all 764 joints confirmed that 95.42% (729/764) of the joints were excellent, 3.14% (24/764) were good, and only 1.44% (11/764) were poor. Repeated arthroscopic surgery or open surgery was carried out for the joints that were evaluated as poor. Conclusion: This study indicates that the TMJ arthroscopic suturing technique is effective in repositioning the TMJ disc as confirmed by an MR imaging examination, but long-term follow-up is necessary. [ABSTRACT FROM AUTHOR]

Macrophorins H ( 4 ) and L ( 5 ), two rare HMG-conjugate macrophorins along with three known macrophorins ( 1 - 3 ), three DMOA-derived meroterpenoids ( 6 - 8 ) and two ergosterol derivates ( 9 - 10 ) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC 50 values ranging from 17.6 to 32.8 µM.

Objective: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes., Research Design and Methods: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0-36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors., Results: Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function., Conclusions: Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes., (© 2024 by the American Diabetes Association.)

The discus fish, Symphysodon spp., a South American cichlid, has a unique parental care behavior where fry bite on parental skin mucus after hatching. In this study, we used LC-MS/MS technique to compare the skin mucus proteome composition of male or female discus fish during parental and non-parental care periods. By multivariate statistical analysis, we found clear separations between different periods and between different sexes of mucus proteome. Compared with non-parental female fish, parental female fish had 283 up-regulated and 235 down-regulated expressed proteins. Compared with non-parental male fish, parental male fish had 169 up-regulated and 120 down-regulated expressed proteins. The differentially expressed proteins for male fish were enriched in sulfur relay system, mucin type O-glycan biosynthesis and antigen processing and presentation pathways, while those for female fish were enriched in sulfur relay system, steroid biosynthesis and complement and coagulation cascades pathways. During the parental care, both male and female discus showed an enhanced lipid metabolism, producing more phospholipids and cholesterol. The difference is that male discus had increased tricarboxylic acid cycle producing more energy during the parental care, while females produced more nucleotides especially guanylic acid. Our study could provide new insights into the understanding of the unique mucus supply behavior of discus fish based on proteomic change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Wheatgrass is recognized for its nutritional and medicinal properties, partly attributed to its flavonoid content. The objective of this study was to assess the flavonoid content and antioxidant properties of wheatgrass obtained from a wide range of 145 wheat cultivars, which included Chinese landraces (CL), modern Chinese cultivars (MCC), and introduced modern cultivars (IMC). The flavonoids were extracted using a solution of 80% methanol, and their content was evaluated using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). The results revealed the assessed cultivars showed significant variation in their total flavonoid content (TFC), with MCCs generally having higher amounts compared to CLs. PCA analysis demonstrated clear variations in flavonoid profiles between different cultivar groups, emphasizing the evolutionary inconsistencies in wheat breeding. The antioxidant assays, ABTS, DPPH, and FRAP, exhibited robust abilities for eliminating radicals, which were found to be directly associated with the amounts of flavonoids. In addition, this study investigated the correlation between the content of flavonoids and the ability to resist powdery mildew in a collection of mutated wheat plants. Mutants exhibiting heightened flavonoid accumulation demonstrated a decreased severity of powdery mildew, suggesting that flavonoids play a protective role against fungal infections. The results highlight the potential of wheatgrass as a valuable source of flavonoids that have antioxidant and protective effects. This potential is influenced by the genetic diversity and breeding history of wheatgrass. Gaining insight into these connections can guide future wheat breeding endeavors aimed at improving nutritional value and in strengthening disease resistance. The current finding provides critical information for developing wheatgrass with high flavonoid content and antioxidant activity.

Genetic correlation refers to the correlation between genetic determinants of a pair of traits. When using individual-level data, it is typically estimated based on a bivariate model specification where the correlation between the two variables is identifiable and can be estimated from a covariance model that incorporates the genetic relationship between individuals, e.g., using a pre-specified kinship matrix. Inference relying on asymptotic normality of the genetic correlation parameter estimates may be inaccurate when the sample size is low, when the genetic correlation is close to the boundary of the parameter space, and when the heritability of at least one of the traits is low. We address this problem by developing a parametric bootstrap procedure to construct confidence intervals for genetic correlation estimates. The procedure simulates paired traits under a range of heritability and genetic correlation parameters, and it uses the population structure encapsulated by the kinship matrix. Heritabilities and genetic correlations are estimated using the close-form, method of moment, Haseman-Elston regression estimators. The proposed parametric bootstrap procedure is especially useful when genetic correlations are computed on pairs of thousands of traits measured on the same exact set of individuals. We demonstrate the parametric bootstrap approach on a proteomics dataset from the Jackson Heart Study., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16 demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3 and NSD2 inhibitor 15 . In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16 as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.

Endophytes, prevalent in plants, mediate plant-insect interactions. Nevertheless, our understanding of the key members of endophyte communities involved in inhibiting or assisting EAB infestation remains limited. Employing ITS and 16S rRNA high-throughput sequencing, along with network analysis techniques, we conducted a comprehensive investigation into the reaction of endophytic fungi and bacteria within F. bungeana phloem by comparing EAB-infested and uninfected samples. Our findings reveal that EAB infestation significantly impacts the endophytic communities, altering both their diversity and overall structure. Interestingly, both endophytic fungi and bacteria exhibited distinct patterns in response to the infestation. For instance, in the EAB-infested phloem, the fungi abundance remained unchanged, but diversity decreased significantly. Conversely, bacterial abundance increased, without significant diversity changes. The fungi community structure altered significantly, which was not observed in bacteria. The bacterial composition in the infested phloem underwent significant changes, characterized by a substantial decrease in beneficial species abundance, whereas the fungal composition remained largely unaffected. In network analysis, the endophytes in infested phloem exhibited a modular topology, demonstrating greater complexity due to an augmented number of network nodes, elevated negative correlations, and a core genera shift compared to those observed in healthy phloem. Our findings increase understanding of plant-insect-microorganism relationships, crucial for pest control, considering endophytic roles in plant defense.

The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias ( P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [ DNAH8 ]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a ( Wnt5a ), Wnt5b , Smad family member 2 ( Smad2 ), and Smad3 ; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase ( AMPK ) and nuclear respiratory factor 1 ( Nrf-1 ); and vascular development-related genes such as myosin light chain ( MLC ), notch receptor 3 ( Notch3 ), and sphingosine kinase 1 ( Sphk1 ), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

The naturally occurring peptides and digested proteins of fetal versus adult bovine serum were compared by LC-ESI-MS/MS after correction against noise from blank injections and random MS/MS spectra as statistical controls. Serum peptides were extracted by differential precipitation with mixtures of acetonitrile and water. Serum proteins were separated by partition chromatography over quaternary amine resin followed by tryptic digestion. The rigorous X!TANDEM goodness of fit algorithm that has a low error rate as demonstrated by low FDR q-values (q ≤ 0.01) showed qualitative and quantitative agreement with the SEQUEST cross correlation algorithm on 12,052 protein gene symbols. Tryptic digestion provided a quantitative identification of the serum proteins where observation frequency reflected known high abundance. In contrast, the naturally occurring peptides reflected the cleavage of common serum proteins such as C4A, C3, FGB, HPX, A2M but also proteins in lower concentration such as F13A1, IK, collagens and protocadherins. Proteins associated with cellular growth and development such as actins (ACT), ribosomal proteins like Ribosomal protein S6 (RPS6), synthetic enzymes and extracellular matrix factors were enriched in fetal calf serum. In contrast to the large literature from cord blood, IgG light chains were absent from fetal serum as observed by LC-ESI-MS/MS and confirmed by ELISA., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r =-0.64, P =0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r =0.46, P =0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P ＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P ＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P ＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r =-0.167, P =0.044), the level of serum CEA ( r =-0.061, P =0.032), and the level of serum ALT (r =-0.147, P =0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r =0.192, P =0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r =0.164, P =0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2 + cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the effects of metformin on food intake and body weight. Lastly, mediation analyses support a role for Lac-Phe as a downstream effector of metformin's effects on body mass index in participants of a large population-based observational cohort, the Multi-Ethnic Study of Atherosclerosis. Together, these data establish Lac-Phe as a critical mediator of the body weight-lowering effects of metformin., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD)., Method: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed., Results: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU., Conclusions: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Microplastics (MPs) could provide vector for microorganisms to form biofilm (plastisphere), but the shaping process of MPs biofilm and its effects on the structure and function of sedimentary microbial communities especially in aquaculture environments are not reported. For this, we incubated MPs biofilm in situ in an aquaculture pond and established a sediment microcosm with plastisphere. We found that the formation of MPs biofilm in surface water was basically stable after 30 d incubation, but the biofilm communities were reshaped after deposition for another 30 d, because they were more similar to plastisphere communities incubated directly within sediment but not surface water. Moreover, microbial communities of MPs-contaminated sediment were altered, which was mainly driven by the biofilm communities present on MPs, because they but not sediment communities in proximity to MPs had a more pronounced separation from the control sediment communities. In the presence of MPs, increased sediment nitrification, denitrification and N 2 O production rates were observed. The K00371 (NO 2 - ⇋NO 3 - ) pathway and elevated abundance of nxrB and narH genes were screened by metagenomic analysis. Based on structural equation model, two key bacteria (Alphaproteobacteria bacterium and Rhodobacteraceae bacterium) associated with N 2 O production were further identified. Overall, the settling of MPs could reshape the original biofilm and promote N 2 O production by selectively elevating sedimental microorganisms and functional genes in aquaculture pond., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Bin Wen reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Microplastic pollution has been frequently reported in natural water environments, but studies on the occurrence and characteristics of microplastic in aquaculture environments especially in pond production system are relatively scarce. Herein, we investigated the abundance and characteristics of microplastic pollution in aquaculture ponds that farm different species (fish, prawn and crab) near the Yangtze Estuary, China. The average abundance of microplastic in pond water and sediment was 36.25 ± 6.79 items/L and 271.65 ± 164.83 items/kg, respectively. Compared to fish ponds (208.43 ± 57.82 items/kg), microplastic abundance was significantly higher in sediment of crab and prawn ponds (312.02 ± 38.76 and 248.87 ± 36.51 items/kg respectively). Across all ponds, transparent, white and black microplastic were the common colors. Fiber was the most common type, accounting for 40.9% and 58.6% in pond water and sediment, respectively. The size of microplastic was mainly distributed between 300 and 1000 μm. For microplastic polymer composition, polyethylene (PE) was predominant in pond water, accounting for 55%, followed by polyamide with 15%. The predominant polymer in sediment was PE with 34%, followed by polypropylene with 18%. As for the ecological risk assessment of microplastic, the pollution load index was 7.6 (risk level I) and 8.9 (risk level I) for pond water and sediment, respectively. The polymer hazard index was 85.3 (risk level II) and 12.1 (risk level II) for pond water and sediment, respectively. Taken together, the pollution risk index was rated as high and very high for pond sediment and water, respectively. These results provide a basis for the comprehensive evaluation and developing practical approaches to deal with microplastic in aquaculture pond, which is of great significance to the healthy development of pond aquaculture., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsBin Wen reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Copper-catalyzed selective alkynylation with N-propargyl carboxamides as nucleophiles has been successfully developed for the synthesis of C2-functionalized chromanones. Under optimized reaction conditions, 21 examples were obtained in one-pot procedure through 1,4-conjugate addition. This protocol features readily available feedstocks, easy operations, and moderate to good yields, which provides viable access to pharmacologically active C2-functionalized chromanones., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Discus fish (Symphysodon aequifasciatus) exhibit a unique parental care behavior: adult discus produces secretion through their skin, on which the larvae live after birth. The immune components in the skin mucus of parental discus would change during different parental care. C-type lectins (CTLs) could identify and eliminate pathogenic microorganisms and play important roles in innate immunity. Studies on CTLs of discus fish especially during parental care, however, are scarce. Here, we identified 186 CTL genes that distributed in 27 linkage groups based on discus genome. Phylogenetic analysis showed that S. aequifasciatus CTL (SaCTL) members were grouped into 14 subfamilies. A total of 80 gene replication events occurred, of which 15 pairs were subjected to segmental duplication and 65 pairs underwent tandem duplication. Ka/Ks ranged from 0.11 (SaCTL25/SaCTL158) to 0.68 (SaCTL36/SaCTL69), all undergoing purifying selection. RNA-seq analysis revealed that SaCTL members, including duplicated genes, in the skin of parental discus show distinct expression patterns in different care stages and between male and female parents. The SaCTL11 was differentially expressed in most care stages and reached the maximum after eggs spawned, but the expression of its paired SaCTL14 was low in each stage. The SaCTL39 increased first and then decreased, reaching a peak in eggs spawned, while paired SaCTL48 first decreased and then increased, reaching a peak in hatched eggs. The SaCTL50 was differentially expressed only in female fish during care, but not in male fish. These results provide new insights into the evolution and potential functional differentiation of CTLs in discus fish during parental care., Competing Interests: Declaration of competing interest Authors declare no competing interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Recent developments in single-cell technology have enabled the exploration of cellular heterogeneity at an unprecedented level, providing invaluable insights into various fields, including medicine and disease research. Cell type annotation is an essential step in its omics research. The mainstream approach is to utilize well-annotated single-cell data to supervised learning for cell type annotation of new singlecell data. However, existing methods lack good generalization and robustness in cell annotation tasks, partially due to difficulties in dealing with technical differences between datasets, as well as not considering the heterogeneous associations of genes in regulatory mechanism levels. Here, we propose the scPML model, which utilizes various gene signaling pathway data to partition the genetic features of cells, thus characterizing different interaction maps between cells. Extensive experiments demonstrate that scPML performs better in cell type annotation and detection of unknown cell types from different species, platforms, and tissues., (© 2023. The Author(s).)

Bioaerosols in healthcare facilities are closely related to the health of medical staff and patients. Inhalation of microbial aerosol particles can lead to both infectious and non-infectious diseases. However, a systematic summary of bioaerosol types, sources, impact factors and health risk analysis is lacking.This article condutcted a literature review to understand the distribution characteristics, sources, influencing factors and health risks of bioaerosols in healthcare facilities, both domestically and internationally. The goal is to increase awareness of the distribution characteristics of bioaerosols in healthcare facilities and health risk of bioaerosols in medical institutions. This article also provides a reference for prevention and control of bioaerosols.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification., (© 2023. The Author(s).)

The CO 2 absorption by Monoethanolamine (MEA) solutions as chemical absorption was conducted in the membrane gas absorption module with inserting 3D mini-channel turbulence promoters of the present work. A mathematical modeling of CO 2 absorption flux was analyzed by using the chemical absorption theory based on mass-transfer resistances in series. The membrane absorption module with embedding 3D mini-channel turbulence promoters in the current study indicated that the CO 2 absorption rate improvement is achieved due to the diminishing concentration polarization effect nearby the membrane surfaces. A simplified regression equation of the average Sherwood number was correlated to express the enhanced mass-transfer coefficient of the CO 2 absorption. The experimental results and theoretical predictions showed that the absorption flux improvement was significantly improved with implementing 3D mini-channel turbulence promoters. The experimental results of CO 2 absorption fluxes were performed in good agreement with the theoretical predictions in aqueous MEA solutions. A further absorption flux enhancement up to 30.56% was accomplished as compared to the results in the previous work, which the module was inserted the promoter without mini channels. The influences of the MEA absorbent flow rates and inlet CO 2 concentrations on the absorption flux and absorption flux improvement are also illustrated under both concurrent- and countercurrent-flow operations.

Most vertebrate species undergo tooth replacement throughout adult life. This process is marked by the shedding of existing teeth and the regeneration of tooth organs. However, little is known about the genetic circuitry regulating tooth replacement. Here, we tested whether fish orthologs of genes known to regulate mammalian hair regeneration have effects on tooth replacement. Using two fish species that demonstrate distinct modes of tooth regeneration, threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio), we found that transgenic overexpression of four different genes changed tooth replacement rates in the direction predicted by a hair regeneration model: Wnt10a and Grem2a increased tooth replacement rate, whereas Bmp6 and Dkk2 strongly inhibited tooth formation. Thus, similar to known roles in hair regeneration, Wnt and BMP signals promote and inhibit regeneration, respectively. Regulation of total tooth number was separable from regulation of replacement rates. RNA sequencing of stickleback dental tissue showed that Bmp6 overexpression resulted in an upregulation of Wnt inhibitors. Together, these data support a model in which different epithelial organs, such as teeth and hair, share genetic circuitry driving organ regeneration., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background: Limiting driving pressure and mechanical power is associated with reduced mortality risk in both patients with and without acute respiratory distress syndrome. However, it is still poorly understood how the intensity of mechanical ventilation and its corresponding duration impact the risk of mortality., Methods: Critically ill patients who received mechanical ventilation were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. A visualization method was developed by calculating the odds ratio of survival for all combinations of ventilation duration and intensity to assess the relationship between the intensity and duration of mechanical ventilation and the mortality risk., Results: A total of 6251 patients were included. The color-coded plot demonstrates the intuitive concept that episodes of higher dynamic mechanical power can only be tolerated for shorter durations. The three fitting contour lines represent 0%, 10%, and 20% increments in the mortality risk, respectively, and exhibit an exponential pattern: higher dynamic mechanical power is associated with an increased mortality risk with shorter exposure durations., Conclusions: Cumulative exposure to higher intensities and/or longer duration of mechanical ventilation is associated with worse outcomes. Considering both the intensity and duration of mechanical ventilation may help evaluate patient outcomes and guide adjustments in mechanical ventilation to minimize harmful exposure., (© 2023. The Author(s).)

Strobilomyces , one of the most noticeable genera of Boletaceae (Boletales), is both ecologically and economically important. Although many studies have focused on Strobilomyces in China, the diversity still remains incompletely understood. In the present study, several collections of Strobilomyces from Hainan Island, tropical China were studied based on morphology and molecular phylogenetic analyses. Four species are described as new, viz. S . baozhengii , S . conicus , S . hainanensis , and S . pachycystidiatus . Detailed descriptions, color photos of fresh basidiomata, and line drawings of microstructures of the four species are presented.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[ b ]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Background: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood., Aim: To explore the effect of DARPP-32 on CRC progression., Methods: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses., Results: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function., Conclusion: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

An efficient and direct approach to pyrroles was successfully developed by employing 3-formylchromones as decarboxylative coupling partners, and facilitated by microwave irradiation. The protocol utilizes easily accessible feedstocks, a catalytic amount of DBU without any metals, resulting in high efficiency and regioselectivity. Notably, all synthesized products were evaluated against five different cancer cell lines and compound 3l selectively inhibited the proliferation of HCT116 cells with an IC 50 value of 10.65 μM.

Glucose metabolism is known to orchestrate oncogenesis. Whether glucose serves as a signaling molecule directly regulating oncoprotein activity for tumorigenesis remains elusive. Here, we report that glucose is a cofactor binding to methyltransferase NSUN2 at amino acid 1-28 to promote NSUN2 oligomerization and activation. NSUN2 activation maintains global m 5 C RNA methylation, including TREX2, and stabilizes TREX2 to restrict cytosolic dsDNA accumulation and cGAS/STING activation for promoting tumorigenesis and anti-PD-L1 immunotherapy resistance. An NSUN2 mutant defective in glucose binding or disrupting glucose/NSUN2 interaction abolishes NSUN2 activity and TREX2 induction leading to cGAS/STING activation for oncogenic suppression. Strikingly, genetic deletion of the glucose/NSUN2/TREX2 axis suppresses tumorigenesis and overcomes anti-PD-L1 immunotherapy resistance in those cold tumors through cGAS/STING activation to facilitate apoptosis and CD8 + T cell infiltration. Our study identifies NSUN2 as a direct glucose sensor whose activation by glucose drives tumorigenesis and immunotherapy resistance by maintaining TREX2 expression for cGAS/STING inactivation., Competing Interests: Declaration of interests H.-K.L. is a consultant for Stablix, Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD., Methods: Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD ( n = 59), patients with MDD ( n = 14), and healthy controls ( n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t -tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways., Results: The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, β-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls., Conclusion: Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD., 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 Sun, Ma, Chen, Xiong, Jia, Wang and Ren.)

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease., Competing Interests: Declaration of interests M.D.B. reports investigator-initiated grants from Amgen and Boehringer-Ingelheim. P.N. reports investigator-initiated grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis and personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis, Roche/Genentech; is a co-founder of TenSixteen Bio; is a shareholder of geneXwell, TenSixteen Bio, and Vertex; is a scientific advisory board member of geneXwell and TenSixteen Bio; and reports spousal employment at Vertex, all unrelated to the present work., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: This study aimed to determine the diagnostic value of diffusion-weighted imaging (DWI) and to elucidate the clinical characteristics of medial group retropharyngeal lymph nodes (RLNs) based on multi-modal imaging. Also, we intended to explore the feasibility of optimizing the CTV60 boundary based on the characteristics of medial group RLNs., Methods: A total of 549 patients with nasopharyngeal carcinoma received magnetic resonance imaging (MRI), DWI, and contrast-enhanced computed tomography (CT) to detect and evaluate clinical characteristics of medial group RLNs. [18F] Fluorodeoxyglucose positron emission tomography/computed tomography was utilized to identify fluorodeoxyglucose uptaking and contrast-enhanced CT to ensure the reliability of CTV optimization during radiotherapy. The DESdC (Drinking, Eating, Swallowing Difficulties, and Coughing while Eating or Drinking) score was utilized to evaluate swallowing disability., Results: Fourteen of 549 patients had medial group RLNs with a transverse diameter of 2.0-19.0 mm, which distributed between the upper margin of 1st cervical vertebra (C1) and the upper one-third of C3. Lasso regression and Pearson chi-square test suggested that its occurrence was associated with stage N, bilateral cervical lymph node metastases, especially when the transverse diameter of cervical lymph nodes was > 3 cm. The sensitivity of DWI, T2 STIR, and contrast-enhanced CT was 100%, 57.1%, and 21.4%, respectively. We optimized CTV60 of medial group RLNs from the base of skull to the upper edge of C2 excluding specific cases. For patients with CTV60 optimization, radiation dose and volume of swallowing structures decreased obviously. Based on our radiotherapy strategy on CTV60, acute toxicities of enrolled patients were well tolerated. Ninety-six of 549 patients had scores with DESdC score. Eighty-three patients scored 1, seven patients scored 2, one patient scored 3, and three patients scored 4. The median interval from the onset of symptoms was 72 (4-114) months. The 5-year overall survival, progression-free survival, local recurrence-free survival, and distant metastasis-free survival were 87%, 80%, 93%, and 85%, respectively. None of the patients with regional recurrence happened in the optimized region., Conclusion: DWI possesses superiorities in displaying lymph nodes. Based on the low incidence of the medial RLNs, CTV60 of medial group RLNs from the base of skull to the upper edge of C2 is feasible and has dosimetric advantages for protecting swallowing structures., 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 Zong, Jiang, Kong, Wen, Wang, Guo, Zhang, He, Chen and Huang.)

The invasive whitefly (Bemisia tabaci) MED is one of the most economically damaging plant pests. The extensive use of insecticide over decades has led to that the invasive B. tabaci MED has developed resistance to a wide range of insecticide classes, but little is known about the genetic background associated with resistance. To this end, we conducted a comparative genome-wide analysis of single-base nucleotide polymorphisms between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line collected in 1976. First, low-coverage genome sequencings were conducted on DNA isolated from individual whiteflies. The sequencing results were evaluated using an available B. tabaci MED genome as a reference. Significant genetic differences were discovered between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line based on the principal component analyses. Top GO categories and KEGG pathways that might be involved in insecticide resistance development were identified, and several of them have not been previously associated with resistance. Additionally, we identified several genetic loci with novel variations including Cytochrome P450 monooxygenases (P450s), UDP-glucuronosyltransferases (UGTs), Glutathione S-transferases (GSTs), esterase, carboxyl-esterases (COE), ABC transporters, fatty acyl-CoA reductase, voltage-gated sodium channels, GABA receptor, and cuticle proteins (CPs) that were previously reported to have close associations with pesticide resistance in well-studied insect groups that provide an essential resource for the design of insecticide resistance-linked loci arrays insecticide. Our results was obtained solely on resequencing genome data sets, more pesticide bio-assays combined with omics datasets should be further used to verify the markers identified here., (© 2023 Wiley Periodicals LLC.)

Objectives: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture., Methods: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA 0 group (received one session of EA), EA 6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA 48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han 's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA 6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*)., Results: The amplitude of MEPs at T1 and T2 in the EA 0 group, at T0* in the EA 6h group and at T1, T2 and T3 in the EA 48h group was higher when compared with the value at T0 in each group separately ( P <0.001). At T1, the amplitude of MEPs in the EA 0 group and the EA 48h group was higher than that in the EA 6h group ( P <0.001, P <0.01); at T2, it was higher in the EA 0 group when compared with that in the EA 6h group ( P <0.01); at T3, the amplitude in the EA 0 group and the EA 6h group was lower than that of the EA 48h group ( P <0.001). The LAT at T1 was shorter than that at T0 in the three groups ( P <0.05), and the changes were not obvious at the rest time points compared with that at T0 ( P > 0.05). The GPT completion time of healthy subjects in the EA 0 group and the EA 48h group at T1, T2 and T3 was reduced in comparison with that at T0 ( P <0.001). The completion time at T3 was shorter than that at T0 in the EA 6h group ( P <0.05); at T2, it was reduced in the EA 48h group when compared with that of the EA 6h group ( P <0.05). There were no significant differences in rMT among the three groups and within each group ( P >0.05)., Conclusions: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Objective: To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer. Methods: This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2 . Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results: Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7-83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P =0.455); disease free survival was 90.0% and 83.3%, respectively ( P =0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P =0.625); and local recurrence rate both were 3.3% ( P =0.990), respectively. None of these differences was statistically significant. Conclusions: NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields. Based on the research, the silver-catalyzed decarboxylative acylation confirmed that an oxygen atom of the amide moiety was derived from the water and air as a sole oxidant for the whole process.

Throughout a vertebrate organism's lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy ( p < 0.000001, q = 0.000002; p = 0.000004, q = 0.000006; p = 0.000867, q = 0.000683, respectively). Moreover, these same measurements exhibited strong correlations with an established morphometric parameter of muscle atrophy (myofiber cross-sectional area), as determined by histological-based morphometric analysis (r = 0.831, p = 2 × 10 -12 ; r = 0.6959, p = 2 × 10 -8 ; and r = 0.7220; p = 4 × 10 -9 , respectively). Finally, the genetic deletion of gpr27 , an orphan G-protein coupled receptor (GPCR), exacerbated the atrophy of skeletal muscle in aged animals, as evidenced by both sEIM and histology. In conclusion, the data here show that surface EIM techniques can effectively discriminate between healthy young and sarcopenic aged muscle as well as the advanced atrophied muscle in the gpr27 KO animals. Moreover, these studies show how EIM values correlate with cell size across the animals, making it potentially possible to utilize sEIM as a "virtual biopsy" in zebrafish to noninvasively assess myofiber atrophy, a valuable measure for muscle and gerontology research.

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp 3 )-N bond and a C(sp 2 )-C(sp 2 ) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC 50 = 5.59 ± 0.78 μM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.

We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality β of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.

The adsorption performances of ammonia nitrogen (NH + 4 -N) in water by unmodified biochar are ineffective. In this study, nano zero-valent iron-modified biochar (nZVI@BC) was prepared to remove NH + 4 -N from water. The NH + 4 -N adsorption characteristics of nZVI@BC were investigated through adsorption batch experiments. The composition and structure characteristics of nZVI@BC were analyzed using scanning electron microscopy, energy spectrum analysis, BET-N 2 surface area (SSA), X-ray diffraction, and FTIR spectra to explore the main adsorption mechanism of NH + 4 -N by nZVI@BC. The results showed that the composite synthesized at the iron to biochar mass ratio of 1:30 (nZVI@BC1/30) performed well in NH + 4 -N adsorption at 298 K. The maximum adsorption amount of nZVI@BC1/30 at 298 K was remarkably increased by 45.96% and reached 16.60 mg·g -1 . The pseudo-second-order model and Langmuir model fitted well with the adsorption process of NH + 4 -N by nZVI@BC1/30. There was competitive adsorption between coexisting cations and NH + 4 -N, and the sequence of coexisting cations to the adsorption of NH + 4 -N by nZVI@BC1/30 was Ca 2+ > Mg 2+ > K + > Na + . The adsorption mechanism of NH + 4 -N by nZVI@BC1/30 could be mainly attributed to ion exchange and hydrogen bonding. In conclusion, nano zero-valent iron-modified biochar can improve the adsorption performance of NH + 4 -N and enhance the application potential of biochar in the field of nitrogen removal from water.

Objective: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level., Methods: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied., Results: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD., Conclusions: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

N-acyl amino acids are a large family of circulating lipid metabolites that modulate energy expenditure and fat mass in rodents. However, little is known about the regulation and potential cardiometabolic functions of N-acyl amino acids in humans. Here, we analyze the cardiometabolic phenotype associations and genomic associations of four plasma N-acyl amino acids (N-oleoyl-leucine, N-oleoyl-phenylalanine, N-oleoyl-serine, and N-oleoyl-glycine) in 2351 individuals from the Jackson Heart Study. We find that plasma levels of specific N-acyl amino acids are associated with cardiometabolic disease endpoints independent of free amino acid plasma levels and in patterns according to the amino acid head group. By integrating whole genome sequencing data with N-acyl amino acid levels, we identify that the genetic determinants of N-acyl amino acid levels also cluster according to the amino acid head group. Furthermore, we identify the CYP4F2 locus as a genetic determinant of plasma N-oleoyl-leucine and N-oleoyl-phenylalanine levels in human plasma. In experimental studies, we demonstrate that CYP4F2-mediated hydroxylation of N-oleoyl-leucine and N-oleoyl-phenylalanine results in metabolic diversification and production of many previously unknown lipid metabolites with varying characteristics of the fatty acid tail group, including several that structurally resemble fatty acid hydroxy fatty acids. These studies provide a structural framework for understanding the regulation and disease associations of N-acyl amino acids in humans and identify that the diversity of this lipid signaling family can be significantly expanded through CYP4F-mediated ω-hydroxylation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the clinical effect and advantages of dynamic and static acupuncture method combined with manual reduction on posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV)., Methods: Ninety patients with PC-BPPV who met the inclusion criteria were randomly divided into manual reduction control group, acupuncture control group and experimental group, with 30 cases in each group. Epley reduction method was used for manual reduction control treatment of patients in the manual reduction control group, until there was no obvious vertigo of patients. Patients in the acupuncture control group received ordinary acupuncture treatment, while patients in the experiment group received dynamic and static acupuncture treatment, both on the basis of manual reduction control treatment. Baihui(GV20) and Yintang(GV24 + ), Sanyinjiao(SP6), Zhongzhu(TE3), Houxi(SI3) and Waiguan(TE5) on the healthy side, and the vertigo-auditory area and Fengchi(GB20) on the affected side were selected for acupuncture intervention, which was performed once a day, with needles retained for 30 minutes in two acupuncture groups. Every six times was taken as a session and two sessions were required. Dizziness handicap inventory (DHI) scale and visual analogue score (VAS) were used to evaluate the degree of vertigo before, after 1 and 2 sessions of treatment respectively., Results: Compared with those before treatment, the DHI score and VAS score of each group after 1 and 2 sessions of treatment were both significantly decreased ( P <0.05). Compared with the acupuncture control group and the manual reduction control group, the DHI score of the experiment group was significantly decreased ( P <0.05) after 1 and 2 sessions of treatment. VAS score of the experiment group was significantly decreased compared with that of the manual reduction control group( P <0.05) after 1 and 2 sessions of treatment. The total effective rate of the experiment group was 86.67%, better than those of the acupuncture control group (83.33%, P <0.05) and the manual reduction control group(66.67%, P <0.05)., Conclusion: The dynamic and static acupuncture method combined with manual reduction effectively improved vertigo symptoms in PC-BPPV with rapid and lasting effects, which is worthy of further clinical promotion and application.