Search

Circularly polarized luminescence (CPL) film attracted considerable attention in information storage and encryption, three-dimensional display, and chiral recognition. However, due to the limited molecular mobility within thin film, achieving a high asymmetry factor and non-contact modulation of CPL remain challenging. In this work, color-switchable homochiral CPL films with high luminescence asymmetry factor (g lum ~0.11) were constructed based on the co-assembly of a liquid crystal block copolymer (poly (ethylene oxide)-b-poly (methyl methacrylate) bearing cyanostilbene group) with axial chiral dinaphthalene diamine derivatives (R/S-DINBPA). Mechanistic investigation revealed that the efficient stacking of R/S-DINBPA with cyanostilbene groups and the liquid crystal field provide the driving force for chiral transfer and amplification. The dynamic covalent bonds of the cyanostilbene groups endow the film with chiral fixation ability and enable precise modulation of CPL luminescence bands under UV light irradiation, making it suitable for chiral patterned anti-counterfeit encryption. This facile strategy provides a general platform for designing intelligent chiroptical materials., (© 2024 Wiley-VCH GmbH.)

Background: Hyperuricemia (HUA) is a condition characterized by excessive uric acid production and/or inadequate uric acid excretion due to abnormal purine metabolism in the human body. Uric acid deposits resulting from HUA can lead to complications such as renal damage. Currently, drugs used to treat HUA lack specificity and often come with specific toxic side effects., Objective: This study aimed to investigate the renal protective effects of an optimized tea polyphenol formula and allopurinol in a rat model of hyperuricemia following renal resection. The goal was to explore the mechanisms underlying these effects., Methods: Initially, a blend was formulated based on the distinctive functions of catechins, thearubigins, tea polysaccharides, and theanine. Orthogonal experiments were then employed to select a rational combination. A 5/6 renal resection rat model was successfully established, and the animals were fed a 2% oxonic acid diet to induce hyperuricemia. Urinary protein content was measured using the biuret method, and serum levels of uric acid, creatinine, and urea nitrogen were determined biochemically. Kidney pathology was examined through HE staining and renal tubulointerstitial pathological scoring. The expression of α-SMA, CD34, PCNA, and TGF-β in renal tissue was detected using immunohistochemistry. Apoptosis of renal tubular epithelial cells was assessed using the TUNEL method., Results: Hyperuricemia markedly worsens renal damage in rats following nephrectomy, while tea polyphenols demonstrate the ability to reduce levels of blood uric acid, urea nitrogen, creatinine, and urinary protein. Additionally, tea polyphenols enhance smooth muscle proliferation in renal glomerular arterioles, prevent the loss of interstitial capillaries, alleviate apoptosis of renal tubular epithelial cells, promote their proliferation, and reduce interstitial fibrosis. A significant improvement in the severity of renal damage is observed in rats subjected to nephrectomy combined with hyperuricemia, and this effect surpasses that of allopurinol., Conclusion: Tea polyphenols could effectively alleviate renal damage in rats with nephrectomy combined with hyperuricemia. They demonstrate high cost-effectiveness and minimal side effects, positioning them as a promising new therapeutic option for hyperuricemia- induced renal damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study investigates the impact of integrating g-C 3 N 4 into CuCo 2 O 4 electrodes on electrochemical performance working as binder-free electrodes. Flower-like CuCo 2 O 4 nanostructures on nickel foam are decorated with few-layer g-C 3 N 4 using a secondary hydrothermal process. The hierarchical g-C 3 N 4 /CuCo 2 O 4 nanoflower electrode demonstrates a specific capacity of 247.5 mA h g -1 at a current density of 1 A g -1 , while maintaining a capacity of 87.0 mA h g -1 at a heightened current density of 5 A g -1 . Notably, this electrode exhibited remarkable durability, retaining 98% of its capacity after 1000 cycles. The g-C 3 N 4 /CuCo 2 O 4 heterostructure shows promise for high-performance energy storage devices., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background and Objective: The incidence of central precocious puberty (CPP) in girls increased significantly during the COVID-19 pandemic. This study aimed to explore the impact of perfluorinated endocrine disruptors on CPP through metabolomics analysis in girls from Hainan Province, China., Methods: Serum samples from 100 girls with CPP and 100 healthy controls were collected. Untargeted metabolomics profiling was performed using ultra-high performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS). Differentially expressed metabolites (DEMs) were screened, and pathway enrichment analysis was conducted., Results: Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) revealed distinct metabolic profiles between the CPP and control groups. A total of 511 metabolites were identified, including 296 up-regulated DEMs and 255 down-regulated DEMs. Three perfluorinated compounds-PFSM-perfluoroalkyl_sulfonamide_Me, PFSM-FSAA, and PFCA-unsaturated-were significantly upregulated in the CPP group. KEGG pathway enrichment analysis suggested the involvement of multiple pathways in the CPP process regulated by these compounds., Conclusions: Perfluorinated compounds may promote CPP in girls by interfering with various pathways and affecting the hypothalamic-pituitary-gonadal axis function. This study highlighted the need for further research and public health measures to address environmental endocrine disruptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xie, Luo, Cai, Liu, Li, Hai, Ren, Xue, He, Huang and Xiang.)

Background: This research aimed to identify risk factors contributing to premature maturation of arteriovenous fistulas (AVF) in elderly diabetic patients and develop a clinical prediction model., Methods: We conducted a retrospective review of 548 geriatric diabetic patients who underwent AVF creation for maintenance hemodialysis (MHD) at Baoding No 1 Central Hospital between January 2011 and December 2023. Patients were divided into mature (386) and immature (162) groups based on AVF maturation status. Univariate logistic regression analysis and the least absolute shrinkage and selection operator were used to identify independent risk factors, including D-dimer levels, low-density lipoprotein cholesterol levels, internal radial meridian, radial artery plaque presence, and cephalic vein indwelling needle use history. A predictive nomogram was developed specifically for immature AVF in elderly diabetic patients. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC)., Results: Among elderly patients with diabetes mellitus, the incidence of immature AVF was 29.56%, affecting 162 of 548 individuals. The five-variable model demonstrated an AUROC value of 0.922, with a 95% confidence interval (CI) of 0.870 to 0.947 in the training dataset, and an AUROC of 0.912, accompanied by a 95% CI of 0.880 to 0.935 in the internal validation dataset. The calibration curve, derived from 1000 bootstrap samples, showed good agreement between predicted and observed outcomes. Additionally, both the DCA and CIC exhibited favorable clinical utility and net benefits., Conclusions: The nomogram prediction model, based on independent risk factors, serves as a valuable tool for accurate prognosis and has potential to aid in establishing and preserving hemodialysis access in elderly diabetic patients, ultimately optimizing their healthcare outcomes., Competing Interests: The authors declare no conflicts of interest. The research was conducted independently of any commercial or financial relationships that could be perceived as a potential conflict of interest., (© 2024 Liu et al.)

Understanding protein-protein interactions (PPIs) is critical for elucidating cellular functions and disease mechanisms. We present the hybridization-enhanced proximity ligation assay (HPLA), a novel approach incorporating a prehybridization step to improve the ligation efficiency of DNA probes on antibody-oligonucleotide conjugates. This step involves a splint probe hybridizing with complementary sequences on the DNA probes bound to interacting protein complexes, forming V-shaped overhangs that facilitate the circularization of two circle probes. These circularized DNA templates undergo localized rolling circle amplification, producing amplification products that can be visualized as fluorescent dots upon hybridization with dye-labeled detection probes. We demonstrated the utility of HPLA in various biological contexts, including cancer-associated protein interactions and signaling pathways, achieving clearer, more precise visualization of PPIs and enabling robust quantitative analysis.

Background: The increasing incidence of childhood obesity annually has led to a surge in physical and mental health risks, making it a significant global public health concern. This study aimed to discover novel biomarkers of childhood simple obesity through integrative multi-omics analysis, uncovering their potential connections and providing fresh research directions for the complex pathogenesis and treatment strategies., Methods: Transcriptome, untargeted metabolome, and 16 S rDNA sequencing were conducted on subjects to examine transcripts, metabolites in blood, and gut microflora in stool., Results: Transcriptomic analysis identified 599 differentially expressed genes (DEGs), of which 25 were immune-related genes, and participated in immune pathways such as antimicrobial peptides, neutrophil degranulation, and interferons. The optimal random forest model based on these genes exhibited an AUC of 0.844. The metabolomic analysis examined 71 differentially expressed metabolites (DEMs), including 12 immune-related metabolites. Notably, lauric acid showed an extremely strong positive correlation with BMI and showed a good discriminative power for obesity (AUC = 0.82). DEMs were found to be significantly enriched in four metabolic pathways, namely "Aminoacyl-tRNA biosynthesis", "Valine leucine and isoleucine biosynthesis, and Glycine", "Serine and threonine metabolism", and "Biosynthesis of unsaturated fatty acids". Microbiome analysis revealed 12 differential gut microbiotas (DGMs) at the phylum and genus levels, with p_Firmicutes dominating in the obese group and g_Escherichia-Shigella in the normal group. Subsequently, a Random Forest model was developed based on the DEMs, immune-related DEGs, and metabolites with an AUC value of 0.912. The 14 indicators identified by this model could potentially serve as a set of biomarkers for obesity. The analysis of the inter-omics correlation network found 233 pairs of significant correlations. DEGs BPIFA1, BPI, and SAA1, DEMs Dimethy(tetradecyl)amine, Deoxycholic acid, Pathalic anhydride, and DL-Alanine, and DGMs g_Intestinimonas and g_Turicibacter showed strong connectivity within the network, constituting a large proportion of interactions., Conclusion: This study presents the first comprehensive description of the multi-omics characteristics of childhood simple obesity, recognizing promising biomarkers. Immune-related markers offer a new perspective for researching the immunological mechanisms underlying obesity and its associated complications. The revealed interactions among these biomarkers contribute to a deeper understanding the intricate biological regulatory networks associated with obesity., Competing Interests: Declarations. Ethics approval and consent to participate: Our study was approved by the Medical Ethics Committee of HK Hospital of the Maternal and Child Health (Batch number: [2019]01001). Parents or legal guardians of all participants signed informed consent for the use of blood and stool specimen and clinical data for research purposes, and assent from over 12-year-old children was obtained. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: We declare that we have no competing interests., (© 2024. The Author(s).)

Background: Accurate and comprehensive genomic annotation, including the full list of protein-coding genes, is vital for understanding the molecular mechanisms of human biology. We have previously shown that the genome contains a multitude of yet hidden functional exons and transcripts, some of which might represent novel mRNAs. These results resonate with those from other groups and strongly argue that two decades after the completion of the first draft of the human genome sequence, the current annotation of human genes and transcripts remains far from being complete., Results: Using a targeted RNA enrichment technique, we showed that one of the novel functional exons previously discovered by us and currently annotated as part of a long non-coding RNA, is actually a part of a novel protein-coding gene, InSETG-4, which encodes a novel human protein with no known homologs or motifs. We found that InSETG-4 is induced by various DNA-damaging agents across multiple cell types and therefore might represent a novel component of DNA damage response. Despite its low abundance in bulk cell populations, InSETG-4 exhibited expression restricted to a small fraction of cells, as demonstrated by the amplification-based single-molecule fluorescence in situ hybridization (asmFISH) analysis., Conclusions: This study argues that yet undiscovered human protein-coding genes exist and provides an example of how targeted RNA enrichment techniques can help to fill this major gap in our knowledge of the information encoded in the human genome., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

A novel series of donor-donor-π-acceptor (D-D-π-A) 9,9'-dihexylfluorene-based dianchoring organic dyes, each featuring distinct bridging electron-donating moieties, have been synthesized and characterized. Their performances in photocatalytic hydrogen evolution (PHE) were evaluated, taking into account of their photophysical and electrochemical attributes. Remarkably, ( Z )-3-(5-(4-((4-(5-(( E )-2-carboxy-2-cyanovinyl)thiophen-2-yl)phenyl)(9,9-dihexyl- 9H -fluoren-2-yl)amino)phenyl)thiophen-2-yl)-2-cyanoacrylic acid achieved an active and robust H 2 generation system with a turnover number (TON) of up to 17 400 in 126 h, with a production of 1090 μmol (26.3 mL) of hydrogen. The initial turnover frequency (TOF i ), initial activity (activity i ), and initial apparent quantum yield (AQY i ) were 808 h -1 , 505 mmol g -1 h -1 , and 8.65%, respectively, under visible light irradiation in water. This photosensitizer is considered one of the most effective and durable systems for photocatalytic hydrogen production that attached to molecular Pt-TiO 2 , as stated out in the literature using organic dyes under visible light, when compared the TOF and TON values. The experimental results demonstrated that the dianchoring dyes with bridging units could significantly enhance PHE performance, maintaining justifiable durability over prolonged irradiation.

Introduction: Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia., Case Presentation: A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes., Conclusion: The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates., (© 2024. The Author(s).)

Background: Endobronchial ultrasound (EBUS)-guided transbronchial biopsy with or without a guide sheath (EBUS-GS or EBUS-nGS) is commonly utilized for the diagnosis of peripheral pulmonary lesions (PPLs). The primary objective of this meta-analysis is to assess the diagnostic yield, surgical time, and safety of EBUS-GS and EBUS-nGS in patients presenting with PPLs, providing valuable insights for clinical decision-making., Methods: We conducted a systematic search of four databases (PubMed, Embase, Web of Science, Cochrane Library) up to January 2024. Two researchers independently screened the retrieved articles, extracted the data, assessed the quality of the studies, and conducted statistical analysis through Review Manager 5.4 and STATA 14.0. Subgroup analysis was used to explore potential sources of heterogeneity. Publication bias was assessed through funnel plot tests. Sensitivity analyses were also performed to evaluate the robustness of the combined results., Results: The meta-analysis included data from nine studies comprising 2,898 patients. No publication bias was detected. There was no difference in the overall diagnostic rate of EBUS-GS and EBUS-nGS for PPLs [odds ratio (OR): 0.83, 95% confidence interval (CI): 0.64-1.08, Z-score (Z) =1.37, P=0.17]. Conversely, in cases utilizing a bronchoscope with an outer diameter of 3.0 mm (OR: 0.58, 95% CI: 0.40-0.84, Z=2.86, P=0.004), a 1.7-mm bronchoscope channel (OR: 0.70, 95% CI: 0.51-0.96, Z=2.21, P=0.03), or lesions ≤30 mm in size, or lesions situated in the lower lobe of the lung (OR: 0.59, 95% CI: 0.38-0.91, Z=2.36, P=0.02), the diagnostic rate was higher in the EBUS-nGS group. However, the EBUS-GS group demonstrated a tremendous advantage in terms of safety (OR: 0.64, 95% CI: 0.44-0.93, Z=2.33, P=0.02)., Conclusions: EBUS-GS and EBUS-nGS showed no significant difference in the overall diagnostic rate for PPLs. When using a bronchoscope with an outer diameter of 3.0 mm or a channel diameter of 1.7 mm, or when lesions are ≤30 mm or located in the lower lobe of the lung, EBUS-nGS demonstrated a higher diagnostic rate, and EBUS-nGS demonstrated a higher diagnostic rate. However, EBUS-GS exhibited more tremendous advantages in terms of safety., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-845/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Aberrant activation of fibroblast growth factor receptors (FGFRs) contributes to the development and progression of multiple types of cancer. Although many FGFR inhibitors have been approved by the FDA, their long-term therapeutic efficacy is hampered by acquired resistance to gatekeeper mutations and low subtype selectivity. FGFR2 has been found to be frequently amplified or mutated in many tumors. In this study, we designed several PROTACs with different E3 ligands based on LY2874455. By screening the length of the linker and the binding site in various degraders, we obtained a novel and highly efficient FGFR2-selective degrader 28e (DC 50  = 0.645 nM, DC max  = 86 %). Compound 28e selectively degraded FGFR2 and essentially avoided degradation of FGFR1,3,4 isoforms (DC 50  > 300 nM). Compound 28e significantly inhibited the proliferation of FGFR2-overexpressing cell lines, including KATOIII, SNU16, and AN3CA (IC 50  = 0.794 nM/0.207 nM/4.626 nM), comparable to parental inhibitors. At the same time, the preferred compound showed superiority over the parental inhibitor in kinase inhibitory activity against the gatekeeper mutant isoform FGFR2 V564F (IC 50  = 0.121 nM). In summary, we identified 28e as a novel selective degrader of FGFR2 with high potency and high potential to overcome resistance to gatekeeper mutation. The discovery of 28e provides new evidence for the strategy of pan-inhibitor-based development of selective degrading agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Circularly polarized luminescence (CPL) materials are highly demanded due to their great potential in optoelectronic and chiroptical elements. However, the preparation of CPL films with high luminescence dissymmetry factors (g lum ) remains a formidable task, which impedes their practical application in film-based devices. Herein, a facile strategy to prepare solid CPL film with a high g lum through exogenous chiral induction and amplification of liquid crystal polymers is proposed. Amplification and reversion of the CPL appear when the films are annealed at the chiral nematic liquid crystalline temperature and the maximal g lum up to 0.30 due to the enhancement of selective reflection. Thermal annealing treatment at different liquid crystalline states facilitates the formation of the chiral liquid phase and adjusts the circularly polarized emission. This work not only provides a straightforward and versatile platform to construct organic films capable of exhibiting strong circularly polarized emission but also is helpful in understanding the exact mechanism for the liquid crystal enhancement of CPL performance., (© 2024 Wiley‐VCH GmbH.)

Autogenous arteriovenous fistula (AVF) is considered the preferred vascular access choice for individuals undergoing maintenance hemodialysis (MHD) and is widely utilized in China, as reported by the Dialysis Outcomes and Practice Patterns Study. Despite its popularity, the significant incidence of poor AVF maturation often leads to the need for central venous catheter insertion, increasing the risk of complications like superior vena cava stenosis and catheter-related infections, which in turn raises the overall mortality risk. With the prevalence of diabetes rising globally among the elderly and diabetic kidney disease being a leading cause of end-stage renal disease necessitating renal replacement therapy, our retrospective review aims to explore the various factors affecting AVF maturation in this specific patient population. While there have been numerous studies examining AVF complications in MHD patients, including issues like failure, patency loss, stenosis, thrombosis, poor maturation, and other influencing factors, there remains a gap in large-scale clinical studies focusing on the incidence and risk factors for immature AVF specifically in elderly diabetic patients. This paper delves into the pathophysiological mechanisms, diagnostic criteria, and unique considerations surrounding AVF maturation in elderly diabetic patients, distinguishing them from the general population. Our literature review reveals that elderly diabetic patients exhibit a higher risk of AVF immaturity compared to the general population. Additionally, there exists a continuing discourse regarding several aspects related to this group, including the choice of dialysis access, timing of AVF surgery, and surgical site selection. Furthermore, we delve into the management strategies for vascular access within this specific group with the goal of providing evidence-based guidance for the establishment and maintenance of functional vascular access in elderly diabetic patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Hepatocellular carcinoma (HCC) poses a serious threat to human health worldwide. lncRNA dysregulation is frequently observed in various cancers, including HCC. However, the function of LINC01370 in HCC progression and its underlying mechanisms remain unclear., Methods: LINC01370 expression in HCC tissues with cells was analyzed by applying the GEO and GEPIA databases and qRT-PCR. CCK-8 and Transwell assays were used to assess HCC cell proliferation, migration, and invasion. The PI3K, AKT, with p-AKT protein expression were analyzed by western blotting., Results: Gene Expression Omnibus (GEO) and Gene Expression Profiling Interactive Analysis (GEPIA) showed that LINC01370 expression was significantly lower in HCC tissues than in normal tissues. LINC01370 overexpression markedly repressed HepG2 SMMC-7721 cells proliferation, migration, and invasion. To understand the downstream mechanism of LINC01370 regulation, we further analyzed the genes co-expressed with LINC01370 in GSE136247 and GSE132037 and then performed KEGG analysis. The PA pathway was found to be a downstream pathway regulated by LINC01370 in GSE136247 and GSE132037 via gene co-expression and KEGG analysis. Furthermore, PI3K and p-AKT protein levels decreased after LINC01370 overexpression. Importantly, rescue experiments showed that activation of the PI3K/AKT pathway disrupted the repressive effect of LINC01370 overexpression on the proliferation, migration, and invasion of HepG2 of SMMC-7721 cells., Conclusions: This study verified that LINC01370 suppresses HCC proliferation with metastasis by regulating the PI3K/AKT pathway., (© 2024. The Author(s).)

Obesity is often associated with low-grade inflammation. The incidence of obesity has increased annually worldwide, which seriously affects human health. A previous study indicated that long noncoding RNA SNHG12 was downregulated in obesity. Nevertheless, the role of SNHG12 in obesity remains to be elucidated. In this study, qRT-PCR, western blot, and ELISA were utilized to examine the gene and protein expression. Flow cytometry was employed to investigate the M2 macrophage markers. RNA pull-down assay and RIP were utilized to confirm the interactions of SNHG12, hnRNPA1, and HDAC9. Eventually, a high-fat diet-fed mouse model was established for in vivo studies. SNHG12 overexpression suppressed adipocyte inflammation and insulin resistance and promoted M2 polarization of macrophages that was caused by TNF-α treatment. SNHG12 interacted with hnRNPA1 to downregulate HDAC9 expression, which activated the Nrf2 signaling pathway. HDAC9 overexpression reversed the effect of SNHG12 overexpression on inflammatory response, insulin resistance, and M2 phenotype polarization. Overexpression of SNHG12 improved high-fat diet-fed mouse tissue inflammation. This study revealed the protective effect of SNHG12 against adipocyte inflammation and insulin resistance. This result further provides a new therapeutic target for preventing inflammation and insulin resistance in obesity., (© 2024 Federation of American Societies for Experimental Biology.)

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) is a rare systemic immunological condition that predominantly impacts small arteries, veins, and capillaries, often leading to kidney damage and pulmonary injury. It is important to note that individuals primarily presenting with peripheral neuropathy (PN) are uncommon in AASV, which can result in significant misdiagnosis or undiagnosed cases. The severity and location of PN can vary among patients. In this article, we present a case of an AASV patient initially showing signs of PN. This case highlights the significance of considering AASV as a potential cause of unexplained neurological symptoms. Timely identification and proper treatment are essential for improving the survival rate and functional prognosis of AASV patients., (Copyright: © Pakistan Journal of Medical Sciences.)

Resistance to chemotherapy leads to poor prognosis for osteosarcoma (OS) patients. However, due to the high metastasis of tumor and the decrease in sensitivity of tumor cells to cisplatin (DDP), the 5-year survival rate of OS patients is still unsatisfactory. This study explored a mechanism for improving the sensitivity of OS cells to DDP. A DDP-resistant OS cell model was established, and we have found that circORC2 and TRIM2 were upregulated in DDP-resistant OS cells, but miR-485-3p was downregulated. The cell viability and proliferation of the OS cells decreased gradually with the increase of DDP dose, but a gradual increase in apoptosis was noted. CircORC2 promoted OS cell proliferation and DDP resistance and upregulated TRIM2 expression by targeting miR-485-3p. Functionally, circORC2 downregulated miR-485-3p to promote OS cell proliferation and inhibit DDP sensitivity. Additionally, it promoted cell proliferation and inhibited the sensitivity of DDP by regulating the miR-485-3p/TRIM2 axis. In conclusion, circORC2 promoted cell proliferation and inhibited the DDP sensitivity in OS cells via the miR-485-3p/TRIM2 axis. These findings indicated the role of circORC2 in regulating the sensitivity of OS cells to DDP., Competing Interests: There are no conflicts of interest to declare., (© 2024 The Authors. Journal of Cell Communication and Signaling published by John Wiley & Sons Ltd.)

Purpose: To investigate the association between DNA methylation and childhood simple obesity., Methods: Genome-wide analysis of DNA methylation was conducted on peripheral blood samples from 41 children with simple obesity and 31 normal controls to identify differentially methylated sites (DMS). Subsequently, gene functional analysis of differentially methylated genes (DMGs) was carried out. After screening the characteristic DMGs based on specific conditions, the methylated levels of these DMS were evaluated and verified by pyrosequencing. Receiver operating characteristic (ROC) curve analysis assessed the predictive efficacy of corresponding DMGs. Finally, Pearson correlation analysis revealed the correlation between specific DMS and clinical data., Results: The overall DNA methylation level in the obesity group was significantly lower than in normal. A total of 241 DMS were identified. Functional pathway analysis revealed that DMGs were primarily involved in lipid metabolism, carbohydrate metabolism, amino acid metabolism, human diseases, among other pathways. The characteristic DMS within the genes Transcription factor A mitochondrial ( TFAM ) and Piezo type mechanosensitive ion channel component 1( PIEZO1 ) were recognized as CpG-cg05831083 and CpG-cg14926485, respectively. Furthermore, the methylation level of CpG-cg05831083 significantly correlated with body mass index (BMI) and vitamin D., Conclusions: Abnormal DNA methylation is closely related to childhood simple obesity. The altered methylation of CpG-cg05831083 and CpG-cg14926485 could potentially serve as biomarkers for childhood simple obesity., Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00275-w., Competing Interests: Conflict of interestAll authors declare that no conflict of interest., (© The Author(s) 2024.)

Biological age could be reflective of an individual's health status and aging degree. Limited estimations of biological aging based on physical examination data in the Chinese population have been developed to quantify the rate of aging. We developed and validated a novel aging measure (Balanced-AGE) based on readily available physical health examination data. In this study, a repeated sub-sampling approach was applied to address the data imbalance issue, and this approach significantly improved the performance of biological age (Balanced-AGE) in predicting all-cause mortality with a 10-year time-dependent AUC of 0.908 for all-cause mortality. This mortality prediction tool was found to be effective across different subgroups by age, sex, smoking, and alcohol consumption status. Additionally, this study revealed that individuals who were underweight, smokers, or drinkers had a higher extent of age acceleration. The Balanced-AGE may serve as an effective and generally applicable tool for health assessment and management among the elderly population., Competing Interests: There is no competing interest to declare., (© 2024 The Author(s).)

Introduction: Pulmonary adenoid cystic carcinoma (PACC) is a rare, low-grade malignant salivary gland-type tumor characterized by a dormant onset and slow progression, often leading to misdiagnosis. Due to its rarity, limited cases have been reported in the literature. This report aimed to enhance clinicians' understanding of this infrequent disease., Case Presentation: We present the case of a 41-year-old female patient diagnosed with PACC. Our report provides a comprehensive analysis of the patient's imaging, pathology, and treatment, with a particular focus on immunohistochemical results. Importantly, we emphasize the significance of considering foreign bodies and tumors in the bronchus when encountering asthma-like symptoms unresponsive to conventional treatments. Due to the uncertain etiology and pathophysiology of PACC, there are currently no established guidelines for chemotherapy and radiotherapy., Conclusion: PACC predominantly manifests as bronchial lesions without significant clinical heterogeneity. Therefore, it is crucial to consider foreign bodies and tumors in the bronchus when dealing with asthma-like symptoms, especially in patients without chronic lung disease who do not respond to anti-infective, antispasmodic, and antiasthmatic treatments. Additionally, meticulous examination of lesions is essential for timely diagnosis and intervention, ultimately improving patient survival rates., Competing Interests: None of the authors have any conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: As an immune/inflammatory indicator, the application of monocyte-lymphocyte ratio (MLR) in the treatment of severe burns is lacking. The aim of this study was to investigate the dynamic changes of the MLR value in the early stage of severe burns and its clinical value., Methods: This is a 5-year retrospective cohort study involving 100 patients with severe burns (II-III degree and total body surface area (TBSA) >50%), in which the lymphocyte count, monocyte count, MLR value, C-reactive protein (CRP), creatinine (Scr), and capillary leakage index (CLI) were evaluated soon after injury, and 30-day mortality rates were investigated., Results: The MLR values in non-survivors with severe burns were higher than those in survivors in the first two days after injury, while the values on the 3 rd , 5 th , 6 th and 7 th day after injury were lower than those in survivors. The differences between the 6 th and 7 th days after injury were statistically significant. According to the results of logistic and Cox regression analysis, the MLR values on the 6 th day after injury were independent predictors of mortality, and the area under the ROC curve of the 6 th day MLR for severe burn-delayed death prediction was 0.658 (95% confidence interval, 0.541-0.774), and the optimal cut-off value was 0.991. The 30-day mortality rates differed significantly between the MLR6 ≥0.991 group and the MLR6≤0.991 group ( P <0.05). Within one week after injury, the MLR values were negatively correlated with Scr, CRP and CLI levels for severe burns., Conclusions: Our results revealed the dynamic characteristics of the MLR value in the early stage of severe burns, reflecting important changes in the immune/inflammatory related stress response soon after injury, low MLR level was associated with the worsening of disease condition., (© 2024 by the Association of Clinical Scientists, Inc.)

Aggravated endoplasmic reticulum stress (ERS) and apoptosis in podocytes play an important role in lupus nephritis (LN) progression, but its mechanism is still unclear. Herein, the role of SMURF1 in regulating podocytes apoptosis and ERS during LN progression were investigated. MRL/lpr mice was used as LN model in vivo . HE staining was performed to analyze histopathological changes. Mouse podocytes (MPC5 cells) were treated with serum IgG from LN patients (LN-IgG) to construct LN model in vitro . CCK8 assay was adopted to determine the viability. Cell apoptosis was measured using flow cytometry and TUNEL staining. The interactions between SMURF1, YY1 and cGAS were analyzed using ChIP and/or dual-luciferase reporter gene and/or Co-IP assays. YY1 ubiquitination was analyzed by ubiquitination analysis. Our results found that SMURF1, cGAS and STING mRNA levels were markedly increased in serum samples of LN patients, while YY1 was downregulated. YY1 upregulation reduced LN-IgG-induced ERS and apoptosis in podocytes. Moreover, SMURF1 upregulation reduced YY1 protein stability and expression by ubiquitinating YY1 in podocytes. Rescue studies revealed that YY1 knockdown abrogated the inhibition of SMURF1 downregulation on LN-IgG-induced ERS and apoptosis in podocytes. It was also turned out that YY1 alleviated podocytes injury in LN by transcriptional inhibition cGAS/STING/IFN-1 signal axis. Finally, SMURF1 knockdown inhibited LN progression in vivo . In short, SMURF1 upregulation activated the cGAS/STING/IFN-1 signal axis by regulating YY1 ubiquitination to facilitate apoptosis in podocytes during LN progression.

Background: Delayed wound healing, a common problem in patients with diabetes mellitus (DM), is associated with impaired keratinocyte autophagy. Epigallocatechin gallate (EGCG), a catechin, has been proven to promote diabetic wound healing. This study aims to explore the therapeutic mechanism of EGCG on diabetic wound healing., Methods: High glucose (HG)-induced keratinocytes and streptozotocin (STZ)-induced DM rats were prepared and intervened with EGCG to examine its therapeutic effects in in vivo and in vitro settings. The AMPK inhibitor, Compound C, was utilized to determine whether EGCG exerted its therapeutic effects through the AMPK/ULK1 pathway., Results: In vitro , EGCG improved HG-induced autophagy impairment in keratinocytes by increasing LC3II/LC3I, Becline1, and ATG5 levels and decreasing p62 level. Mechanically, EGCG activated the AMPK/ULK1 pathway, thereby promoting keratinocyte autophagy through the phosphorylation of AMPK and ULK1. Notably, EGCG promoted the proliferation, migration, synthesis and release of C-C motif chemokine ligand 2 (CCL2) in HG-treated keratinocytes. Furthermore, EGCG indirectly promoted the activation of fibroblasts, as evidenced by increased alpha-smooth muscle actin (α-SMA) and Collagen I levels. In vivo , EGCG promoted wound healing in DM rats, primarily by reducing inflammatory infiltration and increasing granulation tissue to promote wound epithelialization. Besides, EGCG promoted ATG5, KRT10, KRT14, TGF-β1, Collagen I, and α-SMA expressions in the neonatal epithelial tissues of DM rats. However, the use of Compound C reversed the effects of EGCG., Conclusions: These findings indicated that EGCG restored keratinocyte autophagy to promote diabetic wound healing through the AMPK/ULK1 pathway., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Fibroblast growth factor receptor 4 (FGFR4) has been proved to be an effective target for cancer therapy. Aberration in FGF19/FGFR4 signaling is oncogenic driving force in human hepatocellular carcinoma (HCC). FGFR4 gatekeeper mutations induced acquired resistance remains an unmet clinical challenge for HCC treatment. In this study, a series of 1H-indazole derivatives were designed and synthesized as new irreversible inhibitors of wild-type and gatekeeper mutant FGFR4. These new derivatives showed significant FGFR4 inhibitory and antitumor activities, among which compound 27i was demonstrated to be the most potent compound (FGFR4 IC 50  = 2.4 nM). Remarkably, compound 27i exhibited no activity against a panel of 381 kinases at 1 μM. Additionally, compound 27i displayed nanomolar IC 50 s against huh7 (IC 50  = 21 nM) and two mutant cell lines, BaF3/ETV6-FGFR4-V550L and BaF3/ETV6-FGFR4-N535K (IC 50  = 2.5/171 nM). Meanwhile, compound 27i exhibited potent antitumor potency (TGI: 83.0%, 40 mg/kg, BID) in Huh7 xenograft mouse models with no obvious toxicity observed. Overall, compound 27i was identified as a promising preclinical candidate for overcoming FGFR4 gatekeeper mutations for HCC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Great and continuous efforts have been made to discover high-performance engineering plastics with specific properties to replace traditional engineering materials in many fields. The utilization of machine learning (ML) has brought more opportunities for the discovery of high-performing engineering plastics. However, hindered by either the relatively small database or a lack of accurate structure descriptors with clear physical and chemical meanings relating to polymer properties, the current ML studies show some flaws in the accuracy and efficiency in polymer development. Herein, we collected a dataset of 878 polyimides (PI), one of the best engineering plastics, with experimentally measured glass-transition temperature ( T g ) values, and developed a rapid and accurate ML approach to design PI candidates with the desired T g value. After the conversion from PI structures into "mechanically identifiable" SMILES (Simplified molecular input line entry system) language, the eight most critical descriptors were ultimately obtained by multiple analysis methods. The physiochemical meaning of the key descriptors was further analyzed carefully to translate the implicit "machine language" to chemical knowledge. The artificial neural network (ANN)-based model gave the most accurate results with a root-mean-square error of ∼11 K among the studied ML methods. More importantly, three potential PI candidates with desired T g (DPIs) were designed according to the chemical insight of the key descriptors, which were then verified by experiments. The experimental and predicted T g values of DPIs have an acceptable average deviation of ca. 3.66%. This accuracy has reached the level of the traditional molecular simulation, but the time consumption and hold-up computing resource are tremendously reduced. Furthermore, the current ML approach could offer a scalable and adaptable framework in future engineer plastics innovation.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with insulin resistance (IR). Triglyceride glucose waist circumference (TyG-WC) is a novel index of IR that reflects both visceral fat and hepatic steatosis. However, it is not known whether TyG-WC and NAFLD exhibit a nonlinear relationship in Japanese subjects with normal plasma glucose level. Thus, we examined the relationship between TyG-WC and NAFLD, in addition to determining the threshold level of TyG-WC associated with NAFLD., Methods: A secondary analysis was performed based on a previous study that extracted medical examination records from Murakami Memorial Hospital between 2004 and 2015 in order to detect chronic diseases and their risk factors. TyG-WC was determined at baseline. NAFLD is the dependent variable. Univariate and multivariate logistic regression models were used to evaluate the risk of NAFLD incidence. Based on the smoothing plot, a two-piecewise linear regression model was used to examine the threshold effect of TyG-WC on NAFLD. A subgroup analysis was carried out in order to study other factors that may influence the association between TyG-WC and NAFLD., Results: 14,280 met the criteria for inclusion in the current secondary analysis. The adjusted OR (95% CI) for NAFLD in all subjects was 1.007 (95% CI 1.006-1.009, P < 0.001). The relationship between TyG-WC and NAFLD in Japanese subjects with normal plasma glucose level is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. In subgroup analyses, there was a significant interaction between BMI and TyG-WC associated NAFLD risk (P for interaction <0.001)., Discussion: The relationship between TyG-WC and NAFLD is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. There is potential clinical significance for the TyG-WC in identifying groups at high risk for NAFLD in subjects with normal plasma glucose level., 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 He, Huang, Qian and Sun.)

The vascularization of dermal substitutes is a key challenge in efforts to heal deep skin defects. In this study, dual gene-activated dermal scaffolds (DGADSs-1) were fabricated by loading nanocomposite particles of polyethylenimine (PEI)/multiple plasmid DNAs (pDNAs) encoding vascular endothelial growth factor and angiopoietin-1 at a ratio of 1:1. In a similar manner, DGADSs-2 were loaded with a chimeric plasmid encoding both VEGF and Ang-1. In vitro studies showed that both types of DGADSs released PEI/pDNA nanoparticles in a sustained manner; they demonstrated effective transfection ability, leading to upregulated expression of VEGF and Ang-1. Furthermore, both types of DGADSs promoted fibroblast proliferation and blood vessel formation, although DGADSs-1 showed a more obvious promotion effect. A rat full-thickness skin defect model showed that split-thickness skin transplanted using a one-step method could achieve full survival at the 12th day after surgery in both DGADSs-1 and DGADSs-2 groups, and the vascularization time of dermal substitutes was significantly shortened. Compared with the other three groups of scaffolds, the DGADSs-1 group had significantly greater cell infiltration, collagen deposition, neovascularization, and vascular maturation, all of which promoted wound healing. Thus, compared with single-gene-activated dermal scaffolds, DGADSs show greater potential for enhancing angiogenesis. DGADSs with different loading modes also exhibited differences in terms of angiogenesis; the effect of loading two genes (DGADSs-1) was better than the effect of loading a chimeric gene (DGADSs-2). In summary, DGADSs, which continuously upregulate VEGF and Ang-1 expression, offer a new functional tissue-engineered dermal substitute with the ability to activate vascularization., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Background: Central precocious puberty (CPP) is a common disease in prepubertal children and results mainly from disorders in the endocrine system. Emerging evidence has highlighted the involvement of gut microbes in hormone secretion, but their roles and downstream metabolic pathways in CPP remain unknown., Methods: To explore the gut microbes and metabolism alterations in CPP, we performed the 16S rRNA sequencing and untargeted metabolomics profiling for 91 CPP patients and 59 healthy controls. Bioinformatics and statistical analyses, including the comparisons of alpha and beta diversity, abundances of microbes, were undertaken on the 16S rRNA gene sequences and metabolism profiling. Classifiers were constructed based on the microorganisms and metabolites. Functional and pathway enrichment analyses were performed for identification of the altered microorganisms and metabolites in CPP., Results: We integrated a multi-omics approach to investigate the alterations and functional characteristics of gut microbes and metabolites in CPP patients. The fecal microbiome profiles and fecal and blood metabolite profiles for 91 CPP patients and 59 healthy controls were generated and compared. We identified the altered microorganisms and metabolites during the development of CPP and constructed a machine learning-based classifier for distinguishing CPP. The Area Under Curves (AUCs) of the classifies were ranged from 0.832 to 1.00. In addition, functional analysis of the gut microbiota revealed that the nitric oxide synthesis was closely associated with the progression of CPP. Finally, we investigated the metabolic potential of gut microbes and discovered the genus Streptococcus could be a candidate molecular marker for CPP treatment., Conclusions: Overall, we utilized multi-omics data from microorganisms and metabolites to build a classifier for discriminating CPP patients from the common populations and recognized potential therapeutic molecular markers for CPP through comprehensive analyses., (© 2023. The Author(s).)

Angiogenesis plays a critical role in the survival, progression and metastasis of malignant tumors. Multiple factors are known to induce tumor angiogenesis, vascular endothelial growth factor (VEGF) is the most important one. Lenvatinib is an oral multi-kinase inhibitor of VEGFRs which has been approved for the treatment of various malignancies as the first-line agent by the Food and Drug Administration (FDA). It shows excellent antitumor efficacy in clinical practice. However, the adverse effects of Lenvatinib may seriously impair the therapeutic effect. Here we report the discovery and characterization of a novel VEGFR inhibitor (ZLF-095), which exhibited high activity and selectivity for VEGFR1/2/3. ZLF-095 displayed apparently antitumor effect in vitro and in vivo. We discovered that Lenvatinib could provoke fulminant ROS-caspase3-GSDME-dependent pyroptosis in GSDME-expressing cells by loss of mitochondrial membrane potential, which may be one of the reasons for Lenvatinib's toxicity. Meanwhile, ZLF-095 showed less toxicity than Lenvatinib by switching pyroptosis to apoptosis. These results suggest that ZLF-095 could become a potential angiogenesis inhibitor for cancer therapy., Competing Interests: The authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

Background and Objectives: Amino acids (AAs) are crucial nutrients and fundamental building blocks of organisms that can be utilized to assess nutritional status and detect diseases. However, insufficient information has been reported on plasma AA in the Eastern Chinese population., Methods and Study Design: 1859 persons who underwent physical examination in our hospital from January to December 2020 were enrolled. Plasma AA levels were determined by ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS.), and the effects of age and sex on 19 plasma AA profiles were analyzed. The Python language was used for data analysis and graphic visualization., Results: Plasma arginine, proline, threonine, as-paragine, phenylalanine, and glycine in males, and plasma lysine, leucine, proline, valine, isoleucine, alanine, tyrosine, phenylalanine, and hydroxyproline levels in females increased with age. The 2-aminobutyric acid and serine levels in both sexes, and isoleucine, valine, leucine, and histidine levels in males decreased with age. Glycine level was higher in females than in males, and other 17 AAs except arginine and aspartate were higher in males than in females., Conclusions: Our study indicated that plasma AA levels can reflect the nutritional status and dietary structure of the population, with high obesity rate and high incidence of chronic diseases in eastern China. Age has certain effects on plasma AA levels, especially compared with sex.

Myocardial ischemia/reperfusion (I/R) injury seriously threats the health and life of patients with ischemia heart disease. Herein, we probed the potential influence of myosin 1b (myo1b) on hypoxia/reoxygenation- (H/R-) stimulated cardiomyocyte H9c2 cell apoptosis and autophagy. After H/R stimulation, the myo1b mRNA level in H9c2 cells was tested via qRT-PCR. Myo1b overexpression plasmid (OE-myo1b) and small interfering RNA (siRNA) targeting myo1b (si-myo1b) were transfected into H9c2 cells to alter myo1b expression in H9c2 cells. Following H/R stimulation and/or OE-myo1b (or si-myo1b) transfection, H9c2 cell apoptosis, proliferation, and autophagy were detected, respectively. We found that H/R stimulation reduced the mRNA level of myo1b in H9c2 cells and resulted in H9c2 cell apoptosis, proliferation inhibition, and autophagy. Overexpression of myo1b reversed the H/R-resulted H9c2 cell apoptosis, proliferation inhibition, and autophagy. Silence of myo1b had opposite effects, which promoted H9c2 cell apoptosis, reduced cell proliferation, and accelerated cell autophagy. Taken together, Myo1b took part in the modulation of H/R-stimulated cardiomyocyte apoptosis and autophagy, which might be serve as a potential endogenous target for prevention and therapy of I/R injury., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Jing Xu et al.)

Background: Renal interstitial fibrosis (RIF) is the main pathological change of a variety of chronic kidney diseases (CKD). Epigenetic modifications of fibrosis-prone genes regulate RIF progression. This study aimed to investigate long non-coding RNA (lncRNA) N6-methyladenosine (m 6 A) modification and its role in regulating RIF progression., Methods: Unilateral ureteral occlusion (UUO) was employed to construct the RIF in vivo model; and TGF-β1-treated HK-2 and HKC-8 cells were used for in vitro experiments. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The proliferation and migration were evaluated by EdU assay and transwell assay, respectively. In addition, levels of inflammatory cytokines were determined by ELISA assay and qRT-PCR. Moreover, lncRNA GAS5 m 6 A level was detected using Me-RIP assay. HE and Masson staining were employed to evaluate fibrotic lesions of the kidney., Results: FTO expression was elevated in HK-2 and HKC-8 cells after TGF-β1 treatment and mouse kidney tissue following UUO, and lncRNA GAS5 was downregulated. LncRNA GAS5 overexpression or FTO silencing suppressed TGF-β1-induced the increase of EMT-related proteins (Vimentin, Snail and N-cadherin) and inflammatory cytokines (IL-6, IL-1β and TNF-α) levels in HK-2 cells. FTO suppressed lncRNA GAS5 expression by reducing the m6A modification of lncRNA GAS5. Additionally, FTO knockdown could suppress EMT process and inflammation response induced by TGF-β1 and UUO in vitro and in vivo. As expected, FTO knockdown abrogated the promotion effects of lncRNA GAS5 silencing on TGF-β1-induced EMT process and inflammation response in HK-2 and HKC-8 cells., Conclusion: FTO promoted EMT process and inflammation response through reducing the m 6 A modification of lncRNA GAS5., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objective: To study the relationship between fasting plasma amino acids and obesity in the physical examination population., Methods: A total of 1859 persons who underwent physical examination in the Second Affiliated Hospital Zhejiang University School of Medicine from January to December 2020 were enrolled. Fasting plasma amino acids concentrations and body fat ratio(BFR) were respectively determined by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) and Inbody instrument. According to body mass index and gender grouping, Python language was used for data analysis and graphic visualization to explore the relationship between body mass index, gender and plasma amino acids levels., Results: The plasma levels of glycine, serine and asparagine in the overweight and obesity groups were significantly lower than those in the normal group, especially the levels in the obesity group were lower than those in the overweight group in males(P&lt;0.05). There was no significant difference in plasma levels of lysine, tryptophan, arginine and hydroxyproline among normal, overweight and obesity groups(P&gt;0.05). The plasma levels of leucine, valine, tyrosine, phenylalanine(in males), isoleucine(in females) and alanine in the overweight and obesity groups were significantly higher than those in the normal group, and the levels in the obesity group were higher than those in the overweight group except alanine(P&lt;0.05). BFR was positively correlated with body mass index. BFR in females increased significantly with age after 50 years old(P&lt;0.05)., Conclution: The rate of overweight and obesity among the health screening population is high.

Red Sour Soup (RSS) is a traditional fermented food in China. After two rounds of fermentation, sour soup has a mellow flavor. However, the microbial composition and flavor formation processes in post-fermentation in RSS are unclear. This study investigates the bacteria composition of RSS during the post-fermentation stage (0-180 days) using high-throughput sequencing. The results show that lactic acid bacteria (LAB) are dominant during the post-fermentation process, and their abundance gradually increases with fermentation time. Additionally, gas chromatography-mass spectrometry was used to detect volatile flavor compounds in the post-fermentation process. Seventy-seven volatile flavor compounds were identified, including 24 esters, 14 terpenes, 9 aromatic hydrocarbons, 9 alkanes, 6 heterocyclic compounds, 3 alcohols, 3 acids, 3 ketones, 2 phenols, 2 aldehydes, 1 amine, and 1 other. Esters and aromatic hydrocarbons are the main volatile compounds in RSS during the post-fermentation process. Orthogonal partial least squares screening and correlation analysis derived several significant correlations, including 48 pairs of positive correlations and 19 pairs of negative correlations. Among them, Acetobacter spp ., Clostridium spp. and Sporolactobacillus spp. have 15, 14, 20 significant correlation pairs, respectively, and are considered the most important bacterial genera post-fermentation. Volatile substances become abundant with increasing fermentation time. LAB are excessive after more than 120 days but cause a drastic reduction in volatile ester levels. Thus, the post-fermentation time should be restricted to 120 days, which retains the highest concentrations of volatile esters in RSS. Overall, these findings provide a theoretical basis to determine an optimal post-fermentation time duration, and identify essential bacteria for manufacturing high-quality starter material to shorten the RSS post-fermentation processing time., Competing Interests: Author XF was employed by Shenzhen Shanggutang Food Development Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhou, He, Deng, Li, Li, Feng, Zhang and Zhao.)

Background: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). Systemic inflammation is intimately associated with DR. The neutrophil-to-lymphocyte ratio (NLR) index is a relatively new indicator of inflammation., Methods: This cross-sectional study was carried out among adults with DM based on the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. NLR was presented as absolute neutrophil counts/ absolute lymphocyte counts. The relationship of NLR levels to DR was analyzed using multivariable logistic regression., Results: There were 2772 eligible subjects extracted from the NHANES. In the multivariate analysis, NLR was related to the risk of DR after adjustment for potential confounders. The association between NLR levels and DR was nonlinear, with an inflection point of 4.778. Compared with the baseline values, NLR was not statistically significant on the right side of the inflection point (1.000, 0.914 to 1.094, 0.9974) but was positively associated with DR on the left side (1.236, 1.132 to 1.349, < 0.0001)., Conclusions: NLR reflects systemic inflammation that may increase the risk of DR. NLR positively correlates with DR when its value is less than 4.778., (© 2022. The Author(s).)

Weak light absorption of common Ir(III) complexes (e. g., using phenylpyridine as the ligand) has hindered their applications in photocatalytic hydrogen generation from water as an efficient photosensitizer. To address this issue, a series of cyclometalated Ir(III) complexes (Ir1-Ir5), featuring different electron-donating substituents to enhance the absorptivity, have been synthesized and studied as photosensitizers (PSs) for light-driven hydrogen production from water. Ir6-Ir7 were prepared as fundamental systems for comparisons. Electron donors, including 9-phenylcarbazole, triphenylamine, 4,4'-dimethoxytriphenylamine, 4,4'-di(N-hexylcarbazole)triphenylamine moieties were introduced on 6-(thiophen-2-yl)phenanthridine-based cyclometalating (C^N) ligands to explore the donor effect on the hydrogen evolution performance of these cationic Ir(III) complexes. Remarkably, Ir4 with 4,4'-dimethoxytriphenylamine achieved the highest turn-over number (TON) of 12 300 and initial turnover frequency (TOF i ) of 394 h -1 , with initial activity (activity i ) of 547 000 μmol g -1  h -1 and initial apparent quantum yield (AQY i ) of 9.59 %, under the illumination of blue light-emitting diodes (LEDs) for 105 hours, which demonstrated a stable three-component photocatalytic system with high efficiency. The TON (based on n(H 2 )/n(PSr)) in this study is the highest value reported to date among the similar photocatalytic systems using Ir(III) complexes with Pt nanoparticles as catalyst. The great potential of using triphenylamine-based Ir(III) PSs in boosting photocatalytic performance has also been shown., (© 2022 Wiley-VCH GmbH.)

Background: Among patients with diabetic retinopathy (DR), no proof was available to confirm the prognostic significance of the neutrophil percentage-to-albumin ratio (NPAR). We hypothesized that NPAR plays a role in the incidence of DR in diabetic patients., Methods: We extracted all diabetes mellitus (DM) data from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2018, NPAR was expressed as neutrophil percentage/albumin. Multivariable logistic regression and generalized additive model were utilized for the purpose of examining the correction between NPAR levels and DR. Subgroup analysis of the associations between NPAR and DR was carried out to investigate if the impact of the NPAR varied among different subgroups., Results: An aggregate of 5850 eligible participants were included in the present research. The relationship between NPAR levels and DR was positive linear. In the multivariate analysis, following the adjustment for confounders (gender, white blood cell, age, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, body mass index, iron, glucose, basophils percent, total bilirubin, creatinine, and chloride), higher NPAR was an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00-1.39; 1.24, 1.04-1.48). For the purpose of sensitivity analysis, we found a trend of consistency (p for trend: 0.0190). The results of the subgroup analysis revealed that NPAR did not exert any statistically significant interactions with any of the other DR risk variables., Conclusions: Elevated NPAR is associated with an elevated risk of occurrence of DR in diabetic patients., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background and Objectives: The underlying mechanism of IgA vasculitis (IgAV) and IgA vasculitis with nephritis (IgAVN) remains unclear. Therefore, there are no accurate diagnostic methods. Lipid metabolism is related to many immune related diseases, so this study set out to explore the relationship of lipids and IgAV and IgAVN., Methods: Fifty-eighth patients with IgAV and 28 healthy controls were recruited, which were divided into six separate pools to investigate the alterations of serum lipids according to the clinical characteristics: healthy controls group (HCs) and IgAV group (IgAVs), IgAVN group (IgAV-N) and IgAV without nephritis group (IgAV-C), initial IgAV group (IgAV0) and IgAV in treatment with glucocorticoids group (IgAV1)., Results: 31 identified lipid ions significantly changed in IgAVs with p < 0.05, variable importance of the projection (VIP) > 1 and fold change (FC) > 1.5. All these 31 lipid ions belong to 6 classes: triacylglycerols (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine, ceramide, and lysophosphatidylcholine. TG (16:0/18:1/22:6) +NH4 over 888875609.05, PC (32:1) +H over 905307459.90 and PE (21:4)-H less than 32236196.59 increased the risk of IgAV significantly (OR>1). PC (38:6) +H was significantly decreased (p < 0.05, VIP>1 and FC>1.5) in IgAVN. PC (38:6) less than 4469726623 conferred greater risks of IgAV (OR=45.833, 95%CI: 6.689~341.070)., Conclusion: We suggest that lipid metabolism may affect the pathogenesis of IgAV via cardiovascular disease, insulin resistance, cell apoptosis, and inflammation. The increase of TG(16:0/18:1/22:6) + NH4, and PC(32:1) + H as well as PE (21:4)-H allow a good prediction of IgAV. PE-to-PC conversion may participate in the damage of kidney in IgAV. PC (38:6) + H may be a potential biomarker for IgAVN., (© 2022. The Author(s).)

Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch-Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae . Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides , Dialister , and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Dang, Feng, He, Li, Liu and He.)

The study is aimed at exploring the application of artificial intelligence algorithm-based magnetic resonance imaging (MRI) in the diagnosis of acute cerebral infarction, expected to provide a reference for diagnosis and effect evaluation of acute cerebral infarction. In this study, 80 patients diagnosed with suspected acute cerebral infarction per Diagnostic Criteria for Cerebral Infarction were selected as the research subjects. MRI images were reconstructed by deep dictionary learning to improve their recognition ability. At the same time, the same diagnostic operation was performed by Computed Tomography (CT) images to compare with MRI. The results of the interalgorithm comparison showed the image reconstruction effect of the deep dictionary learning model is significantly better than SAE reconstruction, single-layer dictionary reconstruction model, and KAVD reconstruction. After comparison, the results of MRI based on artificial intelligence algorithm and CT evaluation were statistically significant ( P < 0.05). In the lesion image, the diameter of MRI lesions (3.81 ± 0.77 cm) based on artificial intelligence algorithm and the diameter of lesions in CT (3.66 ± 1.65 cm) also had significant statistical significance ( P < 0.05). The results showed that MRI based on deep learning was more sensitive than CT imaging for diagnosis and evaluation of patients with acute cerebral infarction, with only 1 case misdiagnosed. The rate of disease detection and lesion image quality had a higher improvement. The results can provide effective support for the clinical application of MRI based on artificial intelligence algorithm in the diagnosis of acute cerebral infarction., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Xiaojie He et al.)

Alopecia is a common problem that affects almost every age group and is considered to be an issue for cosmetic or psychiatric reasons. The loss of hair follicles (HFs) and hair caused by alopecia impairs self-esteem, thermoregulation, tactile sensation and protection from ultraviolet light. One strategy to solve this problem is HF regeneration. Many signalling pathways and molecules participate in the morphology and regeneration of HF, such as Wnt/β-catenin, Sonic hedgehog, bone morphogenetic protein and Notch. Non-coding RNAs (ncRNAs), especially microRNAs and long ncRNAs, have significant modulatory roles in HF development and regeneration via regulation of these signalling pathways. This review provides a comprehensive overview of the status and future prospects of ncRNAs in HF regeneration and could prompt novel ncRNA-based therapeutic strategies., 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 © 2021 Yang, Weng, Zhang, Zhang, He, Han and Wang.)

Plasmacytoid dendritic cells (pDCs) play a key role in the initiation and amplification of systemic lupus erythematosus (SLE)-associated vascular injury. In this study, we found that dsDNA induced dose- and time-dependent increase in IFN-α and Toll-like receptor 7 (TLR7), TLR9 and IRF7 expression in pDCs. Co-cultured circulating endothelial cells (ECs) with activated pDCs significantly decreased proliferation, tube formation and migration in ECs. The elevated level of cellular IFN-α increased cell adhesion, promoted cell apoptosis, induced cell senescence and arrested cells at G0/G1 phase of endothelial progenitor cells (EPCs). Additionally, the co-culture system activated MAPK and inactivated PI3K. Pristane was used to establish a in vivo SLE-like mouse model. Importantly, we showed that INF-α-neutralizing antibody (IFN-α-NA) rescued all the changes induced by IFN-α in vitro and prevented vascular injury in pristane-induced SLE model in vivo. In conclusion, we confirmed that activated pDCs promoted vascular damage and the dysfunction of ECs/EPCs via IFN-α production. IFN-α-neutralizing antibody may be a clinical implication for preventing vascular injury. PI3K signalling and AMPK signalling were associated with SLE-associated vascular functions., (© 2021 John Wiley & Sons Ltd.)

Aberrant signaling of fibroblast growth factor receptors (FGFRs) has been identified as a driver of tumorigenesis and the development of many solid tumors, making FGFRs a compelling target for anticancer therapy. Herein, we describe the design and synthesis of pyrido[1,2-a]pyrimidinone derivatives as potent FGFR inhibitors. Examination of structure-activity relationships and preliminary assessment identified 23d as a novel FGFR inhibitor that displayed excellent potency in vitro. Candidate 23d suppressed the phosphorylation of FGFR signaling pathways and induced cell cycle arrest and apoptosis at low nanomolar concentration. In the kinase inhibition profile, 23d showed excellent kinase selectivity for the FGFR family. Furthermore, 23d showed higher aqueous solubility than Erdafitinib. Moreover, 23d exhibited potent antitumor activity (tumor growth inhibition = 106.4%) in FGFR2-amplified SNU-16 gastric cancer xenograft model using a daily oral dose of 30 mg/kg. These results suggest that 23d is a promising candidate for further drug development., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas . Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2021 Min Wen et al.)

Purpose: To explore the pathological features and clinical significance of three types of neovascularization elsewhere (NVE) in proliferative diabetic retinopathy., Methods: Neovascularization elsewhere was classified based on the origins and morphologic features using fluorescein angiography and angiographic and structural optical coherence tomography. The topographical distribution, vitreoretinal interface, and responsiveness to panretinal photocoagulation were compared among three types of NVE., Results: One hundred and twenty-seven NVEs were classified into three types. Type 1 NVE was concentrated along or adjacent to vascular arcades; Type 2 was distributed more peripherally than were Types 1 and 3 NVE. The arch bridge-like vitreoretinal interface accounted for 79% of Type 1 NVE. The flat and flat-forward vitreoretinal interface accounted for 95% and 100% in Type 2 and Type 3 NVE, respectively. At 3 months after panretinal photocoagulation, the regression rates for Types 1, 2, and 3 NVE were 82%, 100%, and 80%, respectively. Type 2 NVE showed best regression rate after panretinal photocoagulation (both P < 0.01)., Conclusion: Three types of NVE determine the distinctly topographical distributions, vitreoretinal interface features, and differential responsiveness to panretinal photocoagulation treatment. This new concept may have important clinical implications in assessing the treatment and prognosis of proliferative diabetic retinopathy.

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) and a major risk factor for morbidity and mortality. The abundant cell-free nucleic (DNA/RNA) in SLE patients, especially dsDNA, is a key substance in the pathogenesis of SLE and LN. The deposition of DNA/RNA-immune complexes (DNA/RNA-ICs) in the glomerulus causes a series of inflammatory reactions that lead to resident renal cell disturbance and eventually renal fibrosis. Cell-free DNA/RNA is the most effective inducer of type I interferons (IFN-I). Resident renal cells (rather than infiltrating immune cells) are the main source of IFN-I in the kidney. IFN-I in turn damages resident renal cells. Not only are resident renal cells victims, but also participants in this immunity war. However, the mechanism for generation of IFN-I in resident renal cells and the pathological mechanism of IFN-I promoting renal fibrosis have not been fully elucidated. This paper reviews the latest epidemiology of LN and its development process, discusses the mechanism for generation of IFN-I in resident renal cells and the role of IFN-I in the pathogenesis of LN, and may open a new perspective for the treatment of LN., 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 © 2021 Ding, Ren and He.)

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis. Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis. Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference ( p < 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences ( p < 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage. Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP., 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 © 2021 Wen, Feng, Dang, Ding, Xu, Huang, Lin, Xiang, Li and He.)