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Yin Li,1,* Manling Jiang,2,3,* Yongqi Wei,1,* Xiang He,2 Guoping Li,2,* Chunlai Lu,1 Di Ge1 1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science & Technology, Taipa, Macao Special Administrative Region of China*These authors contributed equally to this workCorrespondence: Chunlai Lu; Di Ge, Email lu.chunlai@zs-hospital.sh.cn; ge.di@zs-hospital.sh.cnBackground: The pyrimidine salvage pathway plays a critical role in tumor progression and patient outcomes. The roles of pyrimidine salvage pathway-related genes (PSPGs) in cancer, however, are not fully understood. This study aims to depict the characteristics of PSPGs across various cancers.Methods: An integrative pan-cancer analysis of six PSPGs (CDA, UCK1, UCK2, UCKL1, UPP1, and UPP2) was conducted using TCGA data, single-cell RNA sequencing datasets, and patient samples. Single-cell transcriptome analysis and RT-qPCR were used to validate the relation between UPP1 and cytokines. Flow cytometry was performed to validate the role of UPP1 in immune checkpoint regulation. The correlation between UPP1 and tumor associated neutrophils (TAN) were investigated and validated by single-cell transcriptome analysis and tissue microarrays (TMAs).Results: PSPGs showed low mutation rates but significant copy number variations, particularly amplifications in UCKL1, UPP1, and UCK2 across various cancers. DNA methylation patterns varied, with notable negative correlations between methylation and gene expression in UPP1. PSPGs were broadly up-regulated in multiple cancers, with correlations to clinical staging and prognosis. Proteomic data further confirmed these findings. Functional analysis revealed PSPGs’ associations with tumor proliferation, metastasis, and various signaling pathways. UPP1 showed strong correlations with the tumor microenvironment (TME), particularly with cytokines, immune checkpoints, and various immune cells. Single-cell transcriptome analysis confirmed these associations, highlighting UPP1’s influence on cytokine expression and immune checkpoint regulation. In esophageal squamous cell carcinoma (ESCC), UPP1-high tumor cells were significantly associated with immunosuppressive cells in the TME. Spatial analysis using TMAs revealed that UPP1+ tumor cells were predominantly located at the invasive margin and closely associated with neutrophils, correlating with poorer patient prognosis.Conclusion: Our study depicted the multi-dimensional view of PSPGs in cancer, with a particular focus on UPP1’s role in the TME. Targeting UPP1 holds promise as a potential strategy for cancer therapy.Keywords: pyrimidine salvage pathways, UPP1, microenvironment

Bili Liu, Dan Ge, Yue Shan, Yanping Li, Juan Lv, Shuzhi Gan Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of ChinaCorrespondence: Bili Liu, Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Xihu District, Hangzhou, Zhejiang Province, 310007, People’s Republic of China, Tel +86-057185827841, Email lbili_bl1@163.comObjective: Based on the analysis of the images of acromial slide, we explored the application of percutaneous ultrasound-guided subacromial bursography (PUSB) on rotator cuff tear (RCT) in diagnosing elderly patients with shoulder pain.Methods: Eighty-five patients who were clinically diagnosed with RCT and underwent PUSB examination in the department of ultrasound in our hospital were enrolled as the subjects. Independent samples t-test was used to analyze the general characteristics. Based on the gold standard of shoulder arthroscopy, the diagnostic efficacy of ultrasound, magnetic resonance imaging (MRI), and PUSB was evaluated. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated as well. The consistency of these techniques with shoulder arthroscopy in diagnosing the RCT stage was additionally compared using Kappa test.Results: In patients with large full-thickness RCT, the 100% detection rate was achieved by the techniques of ultrasound, MRI, and PUSB. For patients with small full-thickness RCT, the detection rate of PUSB (100%) was evidently higher than those of ultrasound and MRI. Similar results were shown in the detection rates of patients with bursal-side partial-thickness RCT (90.5%) and articular-side partial-thickness RCT (86.9%). More importantly, the sensitivity, specificity, and accuracy of PUSB in patients with both full-thickness RCT and partial-thickness RCT were significantly better than those of ultrasound and MRI.Conclusion: PUSB has a better efficacy in the detection of RCT than ultrasound and MRI, showing its feasibility as an important imaging method to evaluate the degree of RCT.Keywords: rotator cuff tear, percutaneous ultrasound-guided subacromial bursography, shoulder pain, acromial slide cystography, diagnosis

Yalan Li,1,* Na Li,1,* Jiajing Liu,1 Tieshan Wang,2 Ruijuan Dong,3 Dongyu Ge,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng, Email penggy@bucm.edu.cnObjective: Ulcerative colitis (UC) as one of the intractable diseases in gastroenterology seriously threatens human health. Respiratory pathology is a representative extraintestinal manifestation of UC affecting the quality of life of patients. Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine prescription for UC or acute lung injury. This study was aimed to reveal the therapeutic effect of GQD on UC and its pulmonary complications and uncover its molecular mechanism mediated by myeloid cells and microbiota.Methods: Mice with DSS-induced colitis were orally administrated with GQD. Overall vital signs were assessed by body weight loss and disease activity index (DAI). Pulmonary general signs were evaluated by pulmonary pathology and lung function. The mechanism of GQD relieving UC was characterized by detecting myeloid cells (neutrophils, macrophages, inflammatory monocytes, and resident monocytes) in colonic and lung tissues, related inflammatory cytokines, as well as the microbiota in bronchoalveolar lavage fluid (BALF) and feces.Results: GQD significantly reduced weight loss, DAI scores, and lung injury but improved the lung function of colitis mice. The DSS-induced colonic and concurrent pulmonary inflammation were also alleviated by GQD, as indicated by the down-regulated expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCR2, and CCL2) and the suppressed recruitment of neutrophils and inflammatory monocytes. Meanwhile, GQD greatly improved intestinal microbiota imbalance by enriching Ruminococcaceae UCG-013 while decreasing Parabacteroides, [Eubacterium]_fissicatena_group, and Akkermansia in the feces of colitis mice. Expectantly, GQD also restored lung microbiota imbalance by clearing excessive Coprococcus 2 and Ochrobactrum in the BALF of colitis mice. Finally, significant correlations appeared between GQD-mediated specific bacteria and inflammatory cytokines or immune cells.Conclusion: GQD could alleviate UC by decreasing excessive inflammatory myeloid cells and cytokines, and reshaping the microbiota between the colon and lung, which contributes to clarifying the mechanism by which GQD ameliorates colitis-associated pulmonary inflammation.Keywords: Gegen Qinlian Decoction, ulcerative colitis, lung and intestinal microbiota, pulmonary inflammation, myeloid cells

Yongan Wang,1,* Na Li,1,* Qiuyi Li,1 Zirui Liu,1 Yalan Li,1 Jingwei Kong,1 Ruijuan Dong,2 Dongyu Ge,2 Jie Li,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Jie Li Email penggy@bucm.edu.cn; lijie2007@126.comPurpose: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota.Methods: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD.Results: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1β, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury.Conclusion: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.Keywords: XBCQ, COPD, intestinal microbiota, Th17/Treg, pulmonary inflammation

Jie Tang,1 Liqun Zhu,1 Yuejiao Huang,2,3 Lixiang Yang,4 Dangen Ge,5 Zhengyu Hu,6 Chun Wang1 1Department of Oncology, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 2Medical School, Nantong University, Nantong, 226019, People’s Republic of China; 3Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226399, People’s Republic of China; 4Department of Neurosurgery, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Pharmacy, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 6Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Chun WangDepartment of Oncology, Liyang People’s Hospital, 70 Jianshe Road, Liyang, Jiangsu, 213300, People’s Republic of ChinaEmail zlkwangchun@163.comObjective: Anal canal cancer is a rare malignancy with increasing incidence in recent times. This study aimed to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with anal canal cancer.Methods: Information of patients with anal canal cancer from 2004 to 2015 was extracted from the surveillance, epidemiology, and end results (SEER) database. Cox analysis was used to select the risk factors for prognosis, and nomograms were constructed using the R software. The C-index, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) curves, calibration plot and decision curve analysis (DCA) were used to assess the clinical utility of the nomograms.Results: A total of 2458 patients with malignant tumours of the anal canal were screened out. Sex, age, marital status, histological type, grade, tumour size, AJCC stage, SEER stage and chemotherapy were independent prognostic factors for OS, whereas sex, age, race, histological type, grade, tumour size, AJCC stage, SEER stage and radiotherapy were independent prognostic factors for CSS. In the training cohort, the C-index value for OS nomogram was 0.73 (95% CI, 0.69– 0.77), and the AUC values that predicted the 1-, 3- and 5-year survival rates were 0.764, 0.758 and 0.760, respectively, whereas the C-index value for CSS nomogram model was 0.74 (95% CI, 0.69– 0.79), and the AUC values were 0.763, 0.769 and 0.763, respectively. The calibration plot and DCA curves demonstrated good prediction performance of the model in both the training and validation cohorts.Conclusion: The established nomogram is a visualisation tool that can effectively predict the OS and CSS of patients with anal canal cancer.Keywords: anal canal cancer, cancer specific survival, nomogram, overall survival, prognosis

Panghua Ding,1,* Jiajing Liu,2,* Qiuyi Li,2 Qiongqiong Lu,3 Junxiang Li,3 Rui Shi,3 Lei Shi,2 Tangyou Mao,3 Dongyu Ge,4 HaiJun Niu,5 Guiying Peng,2 Zhibin Wang3 1Department of Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Anhui Joyfar Pharmaceutical Research Institute Co. Ltd, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Zhibin Wang Email penggy@bucm.edu.cn; wangsanger@126.comBackground: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by high-performance liquid chromatography. The relative expressions of HDC’s core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins.Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β. Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/STAT3 signaling pathway.Conclusion: The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.Keywords: Hudi enteric-coated capsule, ulcerative colitis, network pharmacology, IL-17/JAK2/STAT3 pathway

Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with regulatory roles in disease pathogenesis. Computational models aimed at predicting circRNA-disease associations offer valuable insights into disease mechanisms, thereby enabling the development of innovative diagnostic and therapeutic approaches while reducing the reliance on costly wet experiments. In this study, SGFCCDA is proposed for predicting potential circRNA-disease associations based on scale graph convolutional networks and feature convolution. Specifically, SGFCCDA integrates multiple measures of circRNA and disease similarity and combines known association information to construct a heterogeneous network. This network is then explored by scale graph convolutional networks to capture both topological and attribute information. Additionally, convolutional neural networks are employed to further learn the features and obtain higher-order feature representations containing richer information about nodes. The Hadamard product is utilized to effectively combine circRNA features with disease features, and a multilayer perceptron is applied to predict the association between each pair of circRNA and disease. Five- fold cross validation experiments conducted on the CircR2Disease dataset demonstrate the accurate prediction capabilities of SGFCCDA in identifying potential circRNA-disease associations. Furthermore, case studies provide further confirmation of SGFCCDA's ability to identify disease-associated circRNAs.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The understanding of nonlinear propagation effects in low-crosstalk few-mode fiber is crucial for a weakly coupled mode-division multiplexed system. In this Letter, we report the first, to the best of our knowledge, experimental verification of the advantage of intramodal dispersion on mitigating intramodal cross-phase modulation in a weakly coupled few-mode fiber transmission. The experimental system is established over a 70-km multiple-ring-core few-mode fiber accommodating 6 linearly polarized modes, based on which the influences of intramodal cross-phase modulation on transmission performances of each linearly polarized mode are evaluated. Experimental results show that the intramodal cross-phase modulation of degenerate linearly polarized modes with much larger intramodal dispersion values are significantly weaker than those of non-degenerate linearly polarized modes, in which the maximum suppression of intramodal cross-phase modulation noise is up to 9.7 dB. We believe that this work would be beneficial to practical applications of weakly coupled mode-division multiplexing technologies.

The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC., 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.)

Background: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood., Method: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways., Results: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis., Conclusion: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies., (© 2024. The Author(s).)

Multicomponent reactions hold the potential to maximize the synthetic efficiency in the preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for the one-step synthesis of fluoroalkylated 2- H -pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, and ammonium carbonate is described. By harnessing readily accessible (CH 2 O) n and cheap (NH 4 ) 2 CO 3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with a pyrimidine assembly. The multicomponent reaction proceeds in a step-economical, operationally simple, metal-free, and additive-free manner, featuring a broad substrate scope, excellent functional group compatibility, and scalability. The potential for the synthetic elaboration of the obtained 2- H -pyrimidine is further demonstrated in the alkylation and vinylation of its C2 position.

Objective: This study aimed to investigate the relationship between social isolation, perceived ageism and subjective well-being among rural Chinese older adults and its mechanisms of action., Methods: A total of 403 rural resident older adults were surveyed from March to April 2024. Data were collected using the General Information Questionnaire, the General Alienation Scale (GAS), the Perceived Ageism Questionnaire (PAQ), and the Memorial University of Newfoundland Scale of Happiness (MUNSH). SPSS 27.0 and PROCESS macro were used to analyze the data., Results: Pearson correlation analysis revealed a significant negative correlation (p<0.01) between subjective well-being and social isolation (r = -0.720) and perceived ageism (r = -0.661) among rural older adults. Perceived ageism partially mediated the effect between social isolation and subjective well-being in rural older adults, and the mediating effect accounted for 29.9 % of the total effect (p<0.001)., Conclusion: Social isolation can reduce the subjective well-being of rural older adults through perceived ageism., 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Leafhoppers are economically important pests and may serve as vectors for pathogenic viruses that cause substantial crop damage. In this study, using deep transcriptome sequencing, we identified three novel viruses within the order Mononegavirales , including two viruses belonging to the family Rhabdoviridae and one to the family Lispiviridae . The complete genome sequences were obtained via the rapid amplification of cDNA ends and tentatively named Recilia dorsalis rhabdovirus 1 (RdRV1, 14,251 nucleotides, nt), Nephotettix virescens rhabdovirus 1 (NvRV1, 13,726 nt), and Nephotettix virescens lispivirus 1 (NvLV1, 14,055 nt). The results of a phylogenetic analysis and sequence identity comparison suggest that RdRV1 and NvRV1 represent novel species within the family Rhabdoviridae , while NvLV1 is a new virus belonging to the family Lispiviridae . As negative-sense single-strand RNA viruses, RdRV1 and NvRV1 contain the conserved transcription termination signal and intergenic trinucleotides in the non-transcribed region. Intergenomic sequence and transcriptome profile analyses suggested that all these genes were co-transcriptionally expressed in these viral genomes, facilitated by specific intergenic trinucleotides and putative transcription initiation sequences.

Herein, an improved subtraction model was proposed to characterise the polar stationary phases in supercritical fluid chromatography (SFC). Fifteen stationary phases were selected, including two types of aromatic columns, Waters Torus and Viridis series columns, as well as silica and amino columns. Ethylbenzene and Torus 1-AA were defined as the reference solute and column, respectively. Identifying the interaction with the maximum contribution to retention in SFC separation and using it as the initial term is a key step in modelling. The dipole, or induced dipole interaction (θ ' P), replaced the hydrophobic interaction (η ' H) as the starting term. The improved model was expressed as logα=η ' H+β ' A+α ' B+κ ' C+θ ' P+ε ' E+σ ' S, where the term ε ' E indicated that anion exchange interaction was intentionally supplemented. A 7-step modelling process, including bidirectional fitting and residual analysis, was proposed. The obtained column parameters had reasonable physical significance, with the adjusted determination coefficient (R 2 adj ) greater than 0.999 and the standard error (SE) less than 0.029. Methodological validation was further performed using the other four columns and 12 solutes that were not involved in the modelling. The result revealed good predictions of solutes' retention, as demonstrated by R 2 adj from 0.9923 to 0.9979 and SE from 0.0636 to 0.1088. This study indicated the feasibility of using the improved subtraction model to characterise polar stationary phases in SFC, with the most crucial being the determination of an initial term, followed by the addition of a new descriptor and the selection of an appropriate reference column. The study expanded the application scope of the subtraction model in SFC, which will help gain an in-depth understanding of the SFC separation mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier B.V.)

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Mitochondria are essential organelles because they generate the energy required for cellular functions. Kidney stones, as one of the most common urological diseases, have garnered significant attention. In this study, we first collected peripheral venous blood from patients with kidney stones and used qRT-PCR to detect mitochondrial DNA (mtDNA) copy number as a means of assessing mitochondrial function in these patients. Subsequently, through Western blotting, qPCR, immunofluorescence, immunohistochemistry, and transmission electron microscopy, we examined whether calcium oxalate crystals could cause mitochondrial dysfunction in the kidney in both in vitro and in vivo. We then examined the intersection of the DEGs obtained by transcriptome sequencing of the mouse kidney stone model with mitochondria-related genes, and performed KEGG and GO analyses on the intersecting genes. Finally, we administered the mitochondrial ROS scavenger Mito-Tempo in vivo and observed its effects. Our findings revealed that patients with kidney stones had a reduced mtDNA copy number in their peripheral venous blood compared to the control group, suggesting mitochondrial dysfunction in this population. This conclusion was further validated through in vitro and in vivo experiments. Enrichment analyses revealed that the intersecting genes were closely related to metabolism. We observed that after mitochondrial function was preserved, the deposition of calcium oxalate crystals decreased, and the kidney damage and inflammation caused by them were also alleviated. Our research indicates that kidney stones can cause mitochondrial dysfunction. After clearing mtROS, the damage and inflammation caused by kidney stones are reversed, providing new insights into the prevention and treatment of kidney stones., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of self-powered sensors with interference-resistant detection is a priority area of research for the next generation of wearable electronic devices. Nevertheless, the presence of multiple stimuli in the actual environment will result in crosstalk with the sensor, thereby hindering the ability to obtain an accurate response to a singular stimulus. Here, we present a self-powered sensor composed of silk-based conductive composite fibers (CNFA@ESF), which is capable of energy storage and sensing. The fabricated CNFA@ESF exhibits excellent mechanical performance, as well as flexibility that can withstand various deformations. The CNFA@ESF provides a good areal capacitance (44.44 mF cm -2 ), high-rate capability, and excellent cycle stability (91 % for 5000 cycles). In addition, CNFA@ESF also shows good sensing performance for multiple signals including strain, temperature, and humidity. It was observed that the assembly of the symmetrical device with a stiff hydrogel surface layer for protection enabled the real-time, interference-free monitoring of temperature signals. Also, the CNFA@ESF can be woven into fabrics and integrated with a solar cell to form a self-powered sensor system, which has been proven to convert and store solar energy to power electronic watches, indicating its huge potential for future wearable electronics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14β-hydroxy- 3β-(β-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms., Methods: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed., Results: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis., Conclusion: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear., Methods: A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification., Results: A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC&#95;113622, RP24-496E14.1, etc ., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake)., Conclusion: In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhou et al.)

Background: Different approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation., Methods: Fifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient's quality of airway anesthesia grade during insertion of the tube into the trachea. The patients' tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented., Results: Patients' quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0-1] vs. 1 [0-1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1-1] vs. 1 [1-1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5-125.5] vs. 188 s [149.5-260], P < 0.001) than those in the transverse approach group. The incidence of sore throat 24 h after extubation was lower in the parasagittal group (8% vs. 36%, P = 0.041). Hoarseness occurred in more than half of the patients in parasagittal group before intubation (72% vs. 40%, P = 0.023)., Conclusions: Compared to the transverse approach, the ultrasound-guided parasagittal approach showed improved efficacy in terms of the quality of airway topical anesthesia and shorter total procedure time for superior laryngeal nerve block., Trial Registration: This prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20220425-014) and registered in the Chinese Clinical Trial Registry (19/6/2022, ChiCTR2200061287) prior to patient enrollment. Written informed consent was obtained from all participants in this trial., (© 2024. The Author(s).)

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy., (© 2024 Wiley‐VCH GmbH.)

Currently, the copolymer of dopamine (DA) and pyrrole (PY) via chemical and electrochemical oxidation usually requires additional oxidants, and lacks flexibility in regulating the size and morphology, thereby limiting the broad applications of DA-PY copolymer in biomedicine. Herein, the semiquinone radicals produced by the self-oxidation of DA is ingeniously utilized as the oxidant to initiate the following copolymerization with PY, and a series of quinone-rich polydopamine-pyrrole copolymers (PDA m -nPY) with significantly enhanced absorption in near-infrared (NIR) region without any additional oxidant assistance is obtained. Moreover, the morphology and size of PDA m -nPY can be regulated by changing the concentration of DA and PY, thereby optimizing nanoscale PDA 0.05 -0.15PY particles (≈ 150 nm) with excellent NIR absorption and surface modification activity are successfully synthesized. Such PDA 0.05 -0.15PY particles show effective photoacoustic (PA) imaging and photothermal therapy (PTT) against 4T1 tumors in vivo. Furthermore, other catechol derivatives can also copolymerize with PY under the same conditions. This work by fully utilizing the semiquinone radical active intermediates produced through the self-oxidation of DA reduces the dependence on external oxidants in the synthesis of composite materials and predigests the preparation procedure, which provides a novel, simple, and green strategy for the synthesis of other newly catechol-based functional copolymers., (© 2024 Wiley‐VCH GmbH.)

The content of gallic acid (GA) is positively correlated with the quality grade of tea. Here, we developed a colorimetric method based on raspberry-like N-doped Mn 3 O 4 nanospheres (N-Mn 3 O 4 NSs) with oxidase-like activity for GA assay. Modulating the electronic structure of Mn 3 O 4 by N doping could promote the catalysis ability, and the produced oxygen vacancies (OVs) can provide high surface energy and abundant active sites. The N-Mn 3 O 4 NSs presented low Michaelis-Menten constant (K m ) of 0.142 mM and maximum initial velocity (V max ) of 9.8 × 10 -6  M s -1 . The sensor exhibited excellent analytical performance towards GA detection, including low LOD (0.028 μM) and promising linear range (5 ∼ 30 μM). It is attributed that OVs and O 2 - participated in TMB oxidation. Based on the reaction color changes, a visualized semi-quantitative GA detection could be realized via a smartphone-based system. It could be applied for evaluating GA quality in market-purchased black tea and green tea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co., Ltd. (Nanjing, China). The curing conditions were divided into variable temperature (0-20 °C) and standard temperature (20 °C). CSM curing was carried out through a programmable curing box. The research results indicated that the variable temperature curing conditions reduced the strength and fatigue resistance of CSM and accelerated the modulus attenuation rate of CSM. At the same time, the drying shrinkage of CSM was greater. The temperature shrinkage coefficient and strain of CSM under variable temperature conditions were smaller than those under standard temperature conditions. The effect of variable temperature conditions on the cracking and durability of CSM could not be ignored in cold regions. Compared to standard temperature curing conditions, the indirect tensile strength of CSM reduced by 31.04% under variable temperature conditions, the coefficient of variation increased by 2.97 times, and the discrete type significantly increased. Compared with CSM without ESA, the dry and temperature shrinkage strains of CSM with 10% ESA were reduced by 24.65% and 26.10%, respectively. At a stress level of 0.6, compared to standard temperature curing conditions, the fatigue life of CSM decreased by 97.19% under variable temperature conditions. Under variable temperature conditions, the fatigue life of CSM with 10% ESA increased by 196 times compared to 0% ESA. Adding ESA enhanced the anti-shrinkage cracking, strength, and durability of CSM under variable temperatures. ESA incorporation effectively compensated for the weakened characteristics of CSM under variable temperature conditions. The study proposed a practical approach for boosting the durability of CSM in cold environments.

Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming., (© The Author(s) 2024. Published by Oxford University Press.)

Characteristic volatile organic compounds (VOCs) are anticipated to be used for the identification of lung cancer cells. However, to date, consistent biomarkers of VOCs in lung cancer cells have not been obtained through direct comparison between cancer and healthy groups. In this study, we regulated the glycolysis, a common metabolic process in cancer cells, and employed solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS) combined with untargeted analysis to identify the characteristic VOCs shared by cancer cells. The VOCs released by three types of lung cancer cells (A549, PC-9, NCI-H460) and one normal lung epithelial cell (BEAS-2B) were detected using SPME-GC-MS, both in their resting state and after treatment with glycolysis inhibitors (2-Deoxy-D-glucose, 2-DG/3-Bromopyruvic acid, 3-BrPA). Untargeted analysis methods were employed to compare the VOC profiles between each type of cancer cell and normal cells before and after glycolysis regulation. Our findings revealed that compared to normal cells, the three types of lung cancer cells exhibited three common differential VOCs in their resting state: ethyl propionate, acetoin, and 3-decen-5-one. Furthermore, under glycolysis control, a single common differential VOC-acetoin was identified. Notably, acetoin levels increased by 2.60-3.29-fold in all three lung cancer cell lines upon the application of glycolysis inhibitors while remaining relatively stable in normal cells. To further elucidate the formation mechanism of acetoin, we investigated its production by blocking glutaminolysis. This interdisciplinary approach combining metabolic biochemistry with MS analysis through interventional synthetic VOCs holds great potential for revolutionizing the identification of lung cancer cells and paving the way for novel cytological examination techniques., (© 2024. The Author(s).)

Background: Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus (T1DM). Teplizumab, a humanized anti-CD3 monoclonal antibody, may help T1DM. Its long-term implications on clinical T1DM development, safety, and efficacy are unknown., Aim: To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM., Methods: A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) were calculated, along with their 95%CI. We assessed heterogeneity using Cochrane Q and I 2 statistics and the appropriate P value., Results: There were 8 randomized controlled trials (RCTs) in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts, with 1361 patients receiving Teplizumab and 547 patients receiving a placebo. Teplizumab was found to have a substantial link with a decrease in insulin consumption, with an OR of 4.13 (95%CI: 1.72 to 9.90). Teplizumab is associated with an improved C-peptide response (OR 2.49; 95%CI: 1.62 to 3.81) and a significant change in Glycated haemoglobin A1c (HbA1c) levels in people with type 1 diabetes [OR 1.75 (95%CI: 1.03 to 2.98)], and it has a RR of 0.71 (95%CI: 0.53 to 0.95)., Conclusion: In type 1 diabetics, teplizumab decreased insulin consumption, improved C-peptide response, and significantly changed HbA1c levels with negligible side effects. Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Plant immune homeostasis is achieved through a balanced immune activation and suppression, enabling effective defense while averting autoimmunity. In Arabidopsis, disrupting a mitogen-activated protein (MAP) kinase cascade triggers nucleotide-binding leucine-rich-repeat (NLR) SUPPRESSOR OF mkk1/2 2 (SUMM2)-mediated autoimmunity. Through an RNAi screen, we identify PUB5, a putative plant U-box E3 ligase, as a critical regulator of SUMM2-mediated autoimmunity. In contrast to typical E3 ligases, PUB5 stabilizes CRCK3, a calmodulin-binding receptor-like cytoplasmic kinase involved in SUMM2 activation. A closely related E3 ligase, PUB44, functions oppositely with PUB5 to degrade CRCK3 through monoubiquitylation and internalization. Furthermore, CRCK3, highly expressed in roots and conserved across plant species, confers resistance to Fusarium oxysporum, a devastating soil-borne fungal pathogen, in both Arabidopsis and cotton. These findings demonstrate the antagonistic role of an E3 ligase pair in fine-tuning kinase proteostasis for the regulation of NLR-mediated autoimmunity and highlight the function of autoimmune activators in governing plant root immunity against fungal pathogens., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-β (transforming growth factor-β) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-β family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-βR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-β-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH., Methods: Bioinformatic analyses were used to explore the mechanism by which BRCC3 deubiquitinates ALK2. Cultured pulmonary artery smooth muscle cells (PASMCs), mouse models, and specimens from patients with idiopathic PAH were used to investigate the rebalance between BMP and TGF-β signaling in regulating ALK2 phosphorylation and ubiquitination in the context of pulmonary hypertension., Results: BRCC3 was significantly downregulated in PASMCs from patients with PAH and animals with experimental pulmonary hypertension. BRCC3, by de-ubiquitinating ALK2 at Lys-472 and Lys-475, activated receptor-regulated Smad1/5/9, which resulted in transcriptional activation of BMP-regulated PPARγ, p53, and Id1. Overexpression of BRCC3 also attenuated TGF-β signaling by downregulating TGF-β expression and inhibiting phosphorylation of Smad3. Experiments in vitro indicated that overexpression of BRCC3 or the de-ubiquitin-mimetic ALK2-K472/475R attenuated PASMC proliferation and migration and enhanced PASMC apoptosis. In SM22α-BRCC3-Tg mice, pulmonary hypertension was ameliorated because of activation of the ALK2-Smad1/5-PPARγ axis in PASMCs. In contrast, Brcc3 -/- mice showed increased susceptibility of experimental pulmonary hypertension because of inhibition of the ALK2-Smad1/5 signaling., Conclusions: These results suggest a pivotal role of BRCC3 in sustaining pulmonary vascular homeostasis by maintaining the integrity of the BMP signaling (ie, the ALK2-Smad1/5-PPARγ axis) while suppressing TGF-β signaling in PASMCs. Such rebalance of BMP/TGF-β pathways is translationally important for PAH alleviation., Competing Interests: None.

Detection of exhaled volatile organic compounds (VOCs) is promising for noninvasive screening of esophageal cancer (EC). Cellular VOC analysis can be used to investigate potential biomarkers. Considering the crucial role of methionine (Met) during cancer development, exploring associated abnormal metabolic phenotypes becomes imperative. In this work, we employed headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the volatile metabolic profiles of EC cells (KYSE150) and normal esophageal epithelial cells (HEECs) under a Met regulation strategy. Using untargeted approaches, we analyzed the metabolic VOCs of the two cell types and explored the differential VOCs between them. Subsequently, we utilized targeted approaches to analyze the differential VOCs in both cell types under gradient Met culture conditions. The results revealed that there were five/six differential VOCs between cells under Met-containing/Met-free culture conditions. And the difference in levels of two characteristic VOCs (1-butanol and ethyl 2-methylbutyrate) between the two cell types intensified with the increase of the Met concentration. Notably, this is the first report on VOC analysis of EC cells and the first to consider the effect of Met on volatile metabolic profiles. The present work indicates that EC cells can be distinguished through VOCs induced by Met regulation, which holds promise for providing novel insights into diagnostic strategies.

How many species of life are there on Earth? This is a question that we want to know but cannot yet answer. Some scholars speculate that the number of species may reach 2.2 billion when considering cryptic diversity and that each morphology-based insect species may contain an average of 3.1 cryptic species. With nearly two million described species, such high estimates of cryptic diversity would suggest that cryptic species are widespread. The development of molecular species delimitation has led to the discovery of a large number of cryptic species, and cryptic biodiversity has gradually entered our field of vision and attracted more attention. This paper introduces the concept of cryptic species, how they evolve, and methods by which they may be discovered and confirmed, and provides theoretical and methodological guidance for the study of hidden species. A workflow of how to confirm cryptic species is provided. In addition, the importance and reliability of multi-evidence-based integrated taxonomy are reaffirmed as a way to better standardize decision-making processes. Special focus on cryptic diversity and increased funding for taxonomy is needed to ensure that cryptic species in hyperdiverse groups are discoverable and described. An increased focus on cryptic species in the future will naturally arise as more difficult groups are studied, and thereby, we may finally better understand the rules governing the evolution and maintenance of cryptic biodiversity., (© 2024 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking., Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment., Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-195/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Objective: This study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma., Methods: The patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between January 2018 and March 2022. Propensity score matching was performed to balance the 2 groups., Results: A total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs 29.0%, P = .140) was similar in the 2 groups, whereas the lower major pathological response rate (44.4% vs 61.3%, P = .011) was observed in the neoadjuvant immunochemotherapy group. Neoadjuvant immunochemotherapy was associated with a lower rate of adverse events (42.7% vs 55.6%, P = .047) without additional postoperative complications (38.7% vs 35.5%, P = .693). The neoadjuvant immunochemotherapy group had lower distant metastasis (6.5% vs 16.1%, P = .027) and overall recurrence (11.3% vs 23.4%, P = .019) in the postoperative 1 year. Also, neoadjuvant immunochemotherapy was associated with better progression-free survival (hazard ratio, 0.50; 95% CI, 0.32-0.77; P = .002). Cox proportional hazard analysis showed that neoadjuvant immunochemotherapy (univariable: hazard ratio, 0.55; 95% CI, 0.37-0.82; P = .003; multivariable: hazard ratio, 0.44; 95% CI, 0.29-0.65; P < .001) was one of the independent prognostic factors for progression-free survival. The 2 groups had similar overall survival (hazard ratio, 0.62; 95% CI, 0.36-1.09; P = .094) at the latest follow-up., Conclusions: This retrospective study showed that neoadjuvant immunochemotherapy was safe and effective for patients with locally advanced esophageal squamous cell carcinoma. Further verification is needed in randomized controlled trials., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant ( p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.

While significant progress has been achieved in utilizing remote sensing technologies for landslide investigation in China, there remains a notable gap in consolidating information on applicable conditions, application stages, and workflows across various remote sensing methodologies. This paper proposes a comprehensive framework for active landslide detection, incorporating multiple stages and data sources, successfully implemented in a vast region of southwestern China. Furthermore, detailed discussions are provided on the effects of the geometric distortion, land cover type, and various InSAR methods on the accuracy of active landslide identification results. Additionally, the paper delves into the advantages of integrated remote sensing technology in active landslide investigation, encompassing the assessment of current landslide activity status, precise delineation of boundaries, identification of different deformation stages, and determination of damage patterns. Through comprehensive analysis of multisource data, it enhances understanding of the active landslide process, ultimately contributing to the mitigation of casualties and property damage., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alkyne annulation has been widely used in organic synthesis for the construction of azacycles with unique structural and physicochemical properties. However, the analogous transformation of fluoroalkynes remains a challenge and has seen limited progress. Herein we report a 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction of 5-7-membered ( E )-1,2-difluorovinyl azacycles. The use of the fluorine atom as a detachable "activator" not only obviates the use of any transition metal catalysts and oxidizing reagents, but also ensures the [3-5 + 2]-annulation and defluorinative functionalization of fluoroalkynes with high chemo-, regio-, and stereoselectivities. This method exhibits a broad substrate scope, good functional group tolerance, and excellent scalability, providing a modular platform for accessing fluorinated skeletons of medicinal and biological interest. The late-stage modification of complex molecules, the multi-component 1,2-diamination of fluoroalkyne, and the synthesis of valuable organofluorides from the obtained products further highlight the real-world utility of this fluoroalkyne annulation technology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chitosan, known for its appealing biological properties in packaging and biomedical applications, faces challenges in achieving a well-organized crystalline structure for mechanical excellence under mild conditions. Herein, we propose a facile and mild bioengineering approach to induce organized assembly of amorphous chitosan into mechanically strong bio-composite via incorporating a genetically engineered insect structural protein, the cuticular protein hypothetical-1 from the Ostrinia furnacalis (OfCPH-1). OfCPH-1 exhibits high binding affinity to chitosan via hydrogen-bonding interactions. Simply mixing a small proportion (0.5 w/w%) of bioengineered OfCPH-1 protein with acidic chitosan precursor induces the amorphous chitosan chains to form fibrous networks with hydrated chitosan crystals, accompanied with a solution-to-gel transition. We deduce that the water shell destruction driven by strong protein-chitosan interactions, triggers the formation of well-organized crystalline chitosan, which therefore offers the chitosan with significantly enhanced swelling resistance, and strength and modulus that outperforms that of most reported chitosan-based materials as well as petroleum-based plastics. Moreover, the composite exhibits a stretch-strengthening behavior similar to the training living muscles on cyclic load. Our work provides a route for harnessing the OfCPH-1-chitosan interaction in order to form a high-performance, sustainably sourced bio-composite., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)