Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation.

INTRODUCTION: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated. OBJECTIVES: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation. METHODS: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation. RESULTS: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD). CONCLUSION: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.

LMNA Reduced Acquired Resistance to Erlotinib in NSCLC by Reversing the Epithelial-Mesenchymal Transition via the FGFR/MAPK/c-fos Signaling Pathway.

For patients exhibiting non-small-cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a first-line treatment. However, most patients who initially responded to EGFR-TKIs eventually developed acquired resistance, limiting the effectiveness of therapy. It has long been known that epithelial-mesenchymal transition (EMT) leads to acquired resistance to EGFR-TKIs in NSCLC. However, the mechanisms underlying the resistance dependent on EMT are unknown. This research aimed to reveal the effects of LMNA in the regulation of acquired resistance to erlotinib by EMT in NSCLC. The acquired erlotinib-resistant cells (HCC827/ER) were induced by gradual increase of concentrations of erlotinib in erlotinib-sensitive HCC827 cells. RNA sequencing and bioinformatics analysis were performed to uncover the involvement of LMNA in the EMT process that induced acquired resistance to erlotinib. The effect of LMNA on cell proliferation and migration was measured by clone-formation, wound-healing, and transwell assays, respectively. The EMT-related protein, nuclear shape and volume, and cytoskeleton changes were examined by immunofluorescence. Western blot was used to identify the underlying molecular mechanism of LMNA regulation of EMT. HCC827/ER cells with acquired resistance to erlotinib underwent EMT and exhibited lower LMNA expression compared to parental sensitive cells. LMNA negatively regulated the expression of EMT markers; HCC827/ER cells showed a significant up-regulation of mesenchymal markers, such as CDH2, SNAI2, VIM, ZEB1, and TWIST1. The overexpression of LMNA in HCC827/ER cells significantly inhibited EMT and cell proliferation, and this inhibitory effect of LMNA was enhanced in the presence of 2.5 µM erlotinib. Furthermore, a decrease in LMNA expression resulted in a higher nuclear deformability and cytoskeletal changes. In HCC827/ER cells, AKT, FGFR, ERK1/2, and c-fos phosphorylation levels were higher than those in HCC827 cells; Furthermore, overexpression of LMNA in HCC827/ER cells reduced the phosphorylation of AKT, ERK1/2, c-fos, and FGFR. In conclusion, our findings first demonstrated that downregulation of LMNA promotes acquired EGFR-TKI resistance in NSCLC with EGFR mutations by EMT. LMNA inhibits cell proliferation and migration of erlotinib-resistant cells via inhibition of the FGFR/MAPK/c-fos signaling pathway. These findings indicated LMNA as a driver of acquired resistance to erlotinib and provided important information about the development of resistance to erlotinib treatment in NSCLC patients with EGFR mutations.

[Toxicity mechanism of Rhododendri Mollis Flos: based on serum metabolomics and network toxicology].

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor ß(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.

Adolescent IgG4-related retroperitoneal fibrosis with left lower extremity edema as the first symptom: A case report. / 以左下肢水肿为首发症状的青少年IgG4ç›¸å ³æ€§è ¹è†œåŽçº¤ç»´åŒ–1例.

IgG4-related retroperitoneal fibrosis is a type of IgG4-related diseases. The etiology is still unclear. It is often classified as idiopathic retroperitoneal fibrosis, but the pathological process and clinical results between them are different. Therefore, the differential diagnosis of them is very important. An 18-year-old patient was admitted to the Second Xiangya Hospital of Central South University due to "left lower extremity edema for 1 and a half month" on December 19, 2019. In examination of PET/CT, the starting point of the left aorta-intra-thoracic artery showed a soft tissue density lump with increased sugar metabolism, which indicated a suspected malignant tumor, and dilatation of the left renal pelvis and ureter. On January 8, 2020, the patient was performed pelvic edema excision, ureterectomy and anastomosis. The postoperative examination results were considered as IgG4-related disease. As a rare systemic disease, early correct diagnosis and precise and individualized treatment can alleviate the suffering of patients and ensure that patients are minimally traumatized.

Future perspective: high-throughput construction of new ultrasensitive cytokine and virion liquid chips for high-throughput screening (HTS) of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases.

Pathogen-host cell interactions play an important role in many human infectious and inflammatory diseases. Several pathogens, including Escherichia coli (E. coli), Mycobacterium tuberculosis (M. tb), and even the recent 2019 novel coronavirus (2019-nCoV), can cause serious breathing and brain disorders, tissue injury and inflammation, leading to high rates of mortality and resulting in great loss to human physical and mental health as well as the global economy. These infectious diseases exploit the microbial and host factors to induce serious inflammatory and immunological symptoms. Thus the development of anti-inflammatory drugs targeting bacterial/viral infection is an urgent need. In previous studies, YojI-IFNAR2, YojI-IL10RA, YojI-NRP1,YojI-SIGLEC7, and YojI-MC4R membrane-protein interactions were found to mediate E. coli invasion of the blood-brain barrier (BBB), which activated the downstream anti-inflammatory proteins NACHT, LRR and PYD domains-containing protein 2(NLRP2), using a proteomic chip conjugated with cell immunofluorescence labeling. However, the studies of pathogen (bacteria/virus)-host cell interactions mediated by membrane protein interactions did not extend their principles to broad biomedical applications such as 2019-nCoV infectious disease therapy. The first part of this feature article presents in-depth analysis of the cross-talk of cellular anti-inflammatory transduction signaling among interferon membrane protein receptor II (IFNAR2), interleukin-10 receptor subunit alpha (IL-10RA), NLRP2 and [Ca2+]-dependent phospholipase A2 (PLA2G5), based on experimental results and important published studies, which lays a theoretical foundation for the high-throughput construction of the cytokine and virion solution chip. The paper then moves on to the construction of the novel GPCR recombinant herpes virion chip and virion nano-oscillators for profiling membrane protein functions, which drove the idea of constructing the new recombinant virion and cytokine liquid chips for HTS of leading drugs. Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection. Taken together, the combined overview of two of the most innovative and exciting developments in the immunoinflammatory field provides new insight into high-throughput construction of ultrasensitive cytokine and virion liquid chips for HTS of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases including infectious diseases, acute or chronic inflammation (acute gouty arthritis or rheumatoid arthritis), cardiovascular disease, atheromatosis, diabetes, obesity, tissue injury and tumors. It has significant value in the prevention and treatment of these serious and painful diseases. Graphical abstract.

Identification of 8-miRNAs as biomarkers for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) poses serious threats to humans. Several studies have studied the biomarkers associated with NAFLD; however, the results vary because of the differences in the sequencing platform, sample selection, and filter conditions. This study aimed to explore the key microRNAs (miRNAs) of NAFLD by a systematic bioinformatics analysis. A total of 10 qualified NAFLD miRNA data sets were selected through a literature review. Signature miRNAs were identified by overlap comparison. The target genes of miRNAs were predicted by TargetScan software and functional enrichment, and transcription factor (TF) binding analysis of target genes was carried out by the database for annotation, visualization, and integrated discovery and Tfacts database, respectively. A total of three upregulated miRNAs and five downregulated miRNAs were identified in the NAFLD tissue. The target genes of upregulated miRNAs mainly enriched in the RNA polymerase II promoter transcriptional regulation, chromatin remodeling process, and O-glycan synthesis, circadian rhythm, and endocytosis; the target genes of downregulated miRNAs mainly enriched in the transcriptional regulation of DNA as a template, negative regulation process of protein phosphorylation, and Fc epsilon RI signaling pathways, Ras signaling pathways and the interaction between cytokines and cytokines. Besides, 136 interactions were formed between 62 TFs and 45 target genes of upregulated miRNA, whereas 157 interactions were formed between 72 TFs and 45 target genes of downregulated miRNA. Both contained 102 TFs, and 32 TFs were present in both target genes. To summarize, we identified an eight-miRNA set as a signature for NAFLD, which will benefit the clinical treatment of NAFLD.

TDCPP protects cardiomyocytes from H2O2-induced injuries via activating PI3K/Akt/GSK3ß signaling pathway.

Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is a major type of organophosphorus flame retardants, and long-term exposure to TDCPP to normal cells or tissues under physiological conditions can induce toxic effects. But how TDCPP leads to the adverse effects is not yet clear, and the effect of TDCPP under pathological conditions such as reactive oxygen species assault is not well understood. The present study aimed to explore the potential effect of TDCPP against H2O2-induced oxidative stress in H9c2 cardiomyoblasts and rat neonatal cardiomyocytes. We found that H2O2-treatment decreased cell viability and increased lactate dehydrogenase and malondialdehyde generation of H9c2 cells. However, TDCPP could alleviate these effects. TDCPP alleviated Ca2+-overload caused by H2O2 through decreasing store-operated calcium entry. More importantly, TDCPP remarkably decreased H2O2-induced dephosphorylation of Akt and GSK3ß, and through this pathway TDCPP mitigated the H2O2-induced apoptosis and detrimental autophagy. Collectively, via mitigating Ca2+-overload and activating the Akt/GSK3ß signaling pathway, TDCPP may have a role in protecting cardiomyocytes from oxidative stress.

High flavonoid accompanied with high starch accumulation triggered by nutrient starvation in bioenergy crop duckweed (Landoltia punctata).

BACKGROUND: As the fastest growing plant, duckweed can thrive on anthropogenic wastewater. The purple-backed duckweed, Landoltia punctata, is rich in starch and flavonoids. However, the molecular biological basis of high flavonoid and low lignin content remains largely unknown, as does the best method to combine nutrients removed from sewage and the utilization value improvement of duckweed biomass. RESULTS: A combined omics study was performed to investigate the biosynthesis of flavonoid and the metabolic flux changes in L. punctata grown in different culture medium. Phenylalanine metabolism related transcripts were identified and carefully analyzed. Expression quantification results showed that most of the flavonoid biosynthetic transcripts were relatively highly expressed, while most lignin-related transcripts were poorly expressed or failed to be detected by iTRAQ based proteomic analyses. This explains why duckweed has a much lower lignin percentage and higher flavonoid content than most other plants. Growing in distilled water, expression of most flavonoid-related transcripts were increased, while most were decreased in uniconazole treated L. punctata (1/6 × Hoagland + 800 mg•L-1 uniconazole). When L. punctata was cultivated in full nutrient medium (1/6 × Hoagland), more than half of these transcripts were increased, however others were suppressed. Metabolome results showed that a total of 20 flavonoid compounds were separated by HPLC in L. punctata grown in uniconazole and full nutrient medium. The quantities of all 20 compounds were decreased by uniconazole, while 11 were increased and 6 decreased when grown in full nutrient medium. Nutrient starvation resulted in an obvious purple accumulation on the underside of each frond. CONCLUSIONS: The high flavonoid and low lignin content of L. punctata appears to be predominantly caused by the flavonoid-directed metabolic flux. Nutrient starvation is the best option to obtain high starch and flavonoid accumulation simultaneously in a short time for biofuels fermentation and natural products isolation.

Using proteomic analysis to investigate uniconazole-induced phytohormone variation and starch accumulation in duckweed (Landoltia punctata).

BACKGROUND: Duckweed (Landoltia punctata) has the potential to remediate wastewater and accumulate enormous amounts of starch for bioethanol production. Using systematical screening, we determined that the highest biomass and starch percentage of duckweed was obtained after uniconazole application. Uniconazole contributes to starch accumulation of duckweed, but the molecular mechanism is still unclear. RESULTS: To elucidate the mechanisms of high starch accumulation, in the study, the responses of L. punctata to uniconazole were investigated using a quantitative proteomic approach combined with physiological and biochemical analysis. A total of 3327 proteins were identified. Among these identified proteins, a large number of enzymes involved in endogenous hormone synthetic and starch metabolic pathways were affected. Notably, most of the enzymes involved in abscisic acid (ABA) biosynthesis showed up-regulated expression, which was consistent with the content variation. The increased endogenous ABA may up-regulate expression of ADP-glucose pyrophosphorylase to promote starch biosynthesis. Importantly, the expression levels of several key enzymes in the starch biosynthetic pathway were up-regulated, which supported the enzymatic assay results and may explain why there is increased starch accumulation. CONCLUSIONS: These generated data linked uniconazole with changes in expression of enzymes involved in hormone biosynthesis and starch metabolic pathways and elucidated the effect of hormones on starch accumulation. Thus, this study not only provided insights into the molecular mechanisms of uniconazole-induced hormone variation and starch accumulation but also highlighted the potential for duckweed to be feedstock for biofuel as well as for sewage treatment.

Ferroptosis and ferroptosis-inducing nanomedicine as a promising weapon in combination therapy of prostate cancer.

Incidence and mortality of prostate cancer (PCa) rank in the top five among male tumors. However, single treatment modalities are often restricted due to biochemical recurrence and drug resistance, necessitating the development of new approaches for the combination treatment of castration-resistant and neuroendocrine PCa. Ferroptosis is characterized by the accumulation of iron-overload-mediated lipid peroxidation and has shown promising outcomes in anticancer treatment, prompting us to present a review reporting the application of ferroptosis in the treatment of PCa. First, the process and mechanism of ferroptosis are briefly reviewed. Second, research advances combining ferroptosis-inducing agents and clinical treatment regimens, which exhibit a "two-pronged approach" effect, are further summarized. Finally, the recent progress on ferroptosis-inducing nanomaterials for combination anticancer therapy is presented. This review is expected to provide novel insights into ferroptosis-based combination treatment in drug-resistant PCa.

Correlation of Differentially Expressed lncRNAs with Intestinal Flora Imbalance, Small Intestinal Permeability, and Glucose Uptake in T2DM Mice.

Diabetes is a major global health concern. This study aimed to investigate the correlation between differentially expressed lncRNAs in mice with type 2 diabetes mellitus (T2DM) and alterations in the intestinal flora and intestinal pathology. A T2DM mouse model was constructed by feeding mice a high-fat diet. Serum fat metabolism-related indices and insulin levels were biochemically detected. Serum inflammatory factors (IL-1ß, IL-6, TNF-α, IL-10) and endotoxin (LPS) were measured by ELISA. Histopathological changes in the small intestines of mice were observed by HE. The short-chain fatty acid (SCFA) content was analyzed using GC-MS. Analysis of altered intestinal flora in T2DM mice was performed using a 16sRNA sequencing assay. Differences in lncRNA expression profiles in small intestinal tissues were analyzed using RNA-seq assays. Spearman's correlation analysis was used to correlate the expression of candidate lncRNAs with changes in differential gut flora. Spearman's correlation analysis was used to analyze the correlation between the expression of candidate differentially expressed lncRNAs, small intestinal permeability, and glucose absorption. We found that serum levels of LPS, BUN, Scr, TC, TG, LDL-C, IL-1ß, IL-6, and TNF-α were elevated and levels of HDL-C, insulin, and IL-10 were decreased in T2DM mice. The ileal enterochromes of T2DM mice were disorganized and broken, the number of enterochromes was reduced, the local epithelial cells were necrotic, and the plasma membrane layer was locally absent. In addition, the protein expression of ZO-1 and occludin was decreased, and the protein expression of SGLT-1 and GLUT-2 was elevated in the model group compared to the control group. The levels of Acetic acid, Propionic acid and Butyric acid were decreased and the levels of Isobutyric acid and Isovaleric acid were increased, the abundance of beneficial bacteria was decreased and the abundance of harmful bacteria was increased in the feces of T2DM mice. RNA-seq identified nine differentially expressed lncRNAs (LINC00675, Gm33838, Gm11655, LOC6613926, LOC6613788, LOC6613791, LOC6613795, Arhgap27os3, and A330023F24Rik). In addition, we found significant correlations between differentially expressed lncRNAs and a variety of intestinal flora, as well as between small intestinal permeability and glucose absorption. A significant correlation was observed between differentially expressed lncRNAs in the intestinal tissues of T2DM mice and intestinal flora imbalance, small intestinal permeability, and glucose absorption.

Hippo signaling modulation and its biological implications in urological malignancies.

Although cancer diagnosis and treatment have rapidly advanced in recent decades, urological malignancies, which have high morbidity and mortality rates, are among the most difficult diseases to treat. The Hippo signaling is an evolutionarily conserved pathway in organ size control and tissue homeostasis maintenance. Its downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are key modulators of numerous physiological and pathological processes. Recent work clearly indicates that Hippo signaling is frequently altered in human urological malignancies. In this review, we discuss the disparate viewpoints on the upstream regulators of YAP/TAZ and their downstream targets and systematically summarize the biological implications. More importantly, we highlight the molecular mechanisms involved in Hippo-YAP signaling to improve our understanding of its role in every stage of prostate cancer, bladder cancer and kidney cancer progression. A better understanding of the biological outcomes of YAP/TAZ modulation will contribute to the establishment of future therapeutic approaches.

3D Printing of TPU-Liquid Metal Composite Inks for the Preparation of Flexible Sensing Electronics.

Direct 3D printing of liquid metal is difficult to form and easy to destroy. In this paper, we developed a 3D printed composite material consisting of a thermoplastic polyurethane (TPU) matrix and liquid metal (LM) dispersed droplets, and introduced the method for realizing 3D printed devices with this composite material: First, the LM is added to 10~50wt %TPU at 190~200 °C through ultrasonic blending to prepare blended ink. After solid cooling, the LM-TPU composite fiber with a diameter of 600 µm was prepared by Wellzoom desktop extruder at 190 °C at an extrusion speed of 400 mm/min. It has excellent elasticity, with a tensile limit of 0.637 N/m2, and the TPU could evenly wrap LM droplets. Finally, the LM-TPU fiber is 3D printed at 240 °C by using a 3D printer, and 2D/3D flexible electronic devices with heating and conductive functions could be prepared. The microcircuit has good electrical conductivity; after adding voltage, the circuit has heat release; it could be used as heating equipment to keep warm and used in various flexible wearable electronic products.

Transcriptome profiles reveal gene regulation of ginger flowering induced by photoperiod and light quality.

BACKGROUND: Under natural conditions, ginger (Zingiber officinale Rosc.) rarely blossom and has seed, which limits new variety breeding of ginger and industry development. In this study, the effects of different photoperiods and light quality on flowering induction in ginger were performed, followed by gene expression analysis of flower buds differentiation under induced treatment using RNA-seq technology. RESULTS: First, both red light and long light condition (18 h light/6 h dark) could effectively induce differentiation of flower buds in ginger. Second, a total of 3395 differentially expressed genes were identified from several different comparisons, among which nine genes, including CDF1, COP1, GHD7, RAV2-like, CO, FT, SOC1, AP1 and LFY, were identified to be associated with flowering in induced flower buds and natural leaf buds. Aside from four down-regulated genes (CDF1, COP1, GHD7 and RAV2-like), other five genes were all up-regulated expression. These differentially expressed genes were mainly classified into 2604 GO categories, which were further enriched into 120 KEGG metabolic pathways. Third, expression change of flowering-related genes in ginger indicated that the induction may negatively regulated expression of CDF1, COP1, GHD7 and RAV2-like, and subsequently positively regulated expression of CO, FT, SOC1, LFY and AP1, which finally led to ginger flowering. In addition, the RNA-seq results were verified by qRT-PCR analysis of 18 randomly selected genes, which further demonstrated the reliability of transcriptome analysis. CONCLUSION: This study revealed the ginger flowering mechanism induced by light treatment and provided abundant gene information, which contribute to the development of hybrid breeding of ginger.

Changes of intestinal microbiota in the giant salamander (Andrias davidianus) during growth based on high-throughput sequencing.

Despite an increasing appreciation of the importance of host-microbe interaction in healthy growth, information on gut microbiota changes of the Chinese giant salamander (Andrias davidianus) during growth is still lacking. Moreover, it is interesting to identify gut microbial structure for further monitoring A. davidianus health. This study explored the composition and functional characteristics of gut bacteria in different growth periods, including tadpole stage (ADT), gills internalization stage (ADG), 1 year age (ADY), 2 year age (ADE), and 3 year age (ADS), using high-throughput sequencing. The results showed that significant differences were observed in microbial community composition and abundance among different growth groups. The diversity and abundance of intestinal flora gradually reduced from larvae to adult stages. Overall, the gut microbial communities were mainly composed of Fusobacteriota, Firmicutes, Bacteroidota, and Proteobacteria. More specifically, the Cetobacterium genus was the most dominant, followed by Lactobacillus and Candidatus Amphibiichlamydia. Interestingly, Candidatus Amphibiichlamydia, a special species related to amphibian diseases, could be a promising indicator for healthy monitoring during A. davidianus growth. These results could be an important reference for future research on the relationship between the host and microbiota and also provide basic data for the artificial feeding of A. davidianus.

Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China.

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Photoredox-catalyzed stereo- and regioselective vicinal fluorosulfonyl-borylation of unsaturated hydrocarbons.

There has been considerable research on sulfur(vi) fluoride exchange (SuFEx) chemistry, which is considered to be a next-generation click reaction, and relies on the unique balance between reactivity and stability inherent in high valent organosulfur. The synthetic versatility of the bifunctional handles containing the fluorosulfonyl group presents great synthetic value and opportunity for drug discovery. However, the direct photoredox-catalyzed fluorosulfonyl-borylation process remains unexplored and challenging due to its system incompatibility and limited synthetic strategies. Herein, we developed a sequential photocatalytic radical difunctionalization strategy for the highly efficient stereoselective synthesis of vicinal fluorosulfonyl borides (VFSBs) with an integrated redox-active SO2F radical reagent. The VFSBs acted as orthogonal synthons, and were subjected to a range of convenient transformations via the cleavage of the C-B and S(vi)-F bonds, including halogenation, Suzuki coupling, hydrogenation, and the SuFEX click reaction, which demonstrated the great potential of the VFSB moieties for use in skeleton linkage and drug modification.

Inflammatory Myofibroblastic Tumor of the Urinary Bladder: An 11-Year Retrospective Study From a Single Center.

Purpose: To share our experience in the diagnosis and treatment of an inflammatory myofibroblastic tumor of the urinary bladder (IMTUB). Materials and Methods: A database searches in the pathology archives by using the term "inflammatory myofibroblastic tumor" and" bladder" in our hospital department of pathology from 2010 to 2021. Patient characteristics, clinical features, histopathological results, immunohistochemical staining results, and treatment outcomes were reviewed. Results: Fourteen cases of IMTUB were retrieved. The mean age was 44.7 ± 18.9 years (range 12-74). Nine (64.3%) of the patients presented with hematuria, followed by seven (50%) with odynuria, five (35.7%) with urgent urination, and one (7.1%) with dysuria. Ten (71.4%) of the patients were treated with partial cystectomy (PC), three (21.4%) with transurethral resection of bladder tumor (TURBT), and one (7.1%) with radical cystectomy (RC). Histopathologically, eight (57.1%) had a compact spindle cell pattern. Anaplastic lymphoma kinase (ALK) staining was positive in six (75%) of 8 cases. During a mean follow-up period of 43.9 ± 38 months (range 3-117), a patient had recurrence within half a month. Then, the patient was treated with further TURBT surgery and had no recurrence within 6 months. Thirteen of the patients had no local recurrence or distant metastasis. Conclusion: Inflammatory myofibroblastic tumor of the urinary bladder (IMTUB) is clinically rare and has a good prognosis. The disease is mainly treated with surgery to remove the tumor completely. It can easily be misdiagnosed as bladder urothelial carcinoma, leiomyosarcoma, or rhabdomyosarcoma, which may result in overtreatment and poor quality of life of patients.

MicroRNA-665-3p exacerbates nonalcoholic fatty liver disease in mice.

Oxidative stress and chronic inflammation are major culprits of nonalcoholic fatty liver disease (NAFLD). MicroRNA-665-3p (miR-665-3p) is implicated in regulating inflammation and oxidative stress; however, its role and molecular basis in NAFLD remain elusive. Herein, we measured a significant upregulation of miR-665-3p level in the liver and primary hepatocytes upon high fat diet (HFD) or 0.5 mmol/L palmitic acid plus 1.0 mmol/L oleic acid stimulation, and the elevated miR-665-3p expression aggravated oxidative stress, inflammation and NAFLD progression in mice. In contrast, miR-665-3p inhibition by the miR-665-3p antagomir significantly prevented HFD-induced oxidative stress, inflammation and hepatic dysfunction in vivo. Manipulation of miR-665-3p in primary hepatocytes also caused similar phenotypic alterations in vitro. Mechanistically, we demonstrated that miR-665-3p directly bound to the 3'-untranslated region of fibronectin type III domain-containing 5 (FNDC5) to downregulate its expression and inactivated the downstream AMP-activated protein kinase alpha (AMPKα) pathway, thereby facilitating oxidative stress, inflammation and NAFLD progression. Our findings identify miR-665-3p as an endogenous positive regulator of NAFLD via inactivating FNDC5/AMPKα pathway, and inhibiting miR-665-3p may provide novel therapeutic strategies to treat NAFLD.

A practical fluorosulfonylating platform via photocatalytic imidazolium-based SO2F radical reagent.

Sulfonyl fluorides are key components in the fields of chemical biology, materials science and drug discovery. In this line, the highly active SO2F radical has been employed for the construction of sulfonyl fluorides, but the utilization of gaseous ClSO2F as radical precursor is limited due to the tedious and hazardous preparation. Meanwhile, the synthesis of sulfonyl fluorides from inert SO2F2 gas through a fluorosulfonyl radical (·SO2F) process has met with inevitable difficulties due to the high homolytic bond dissociation energy of the S(VI)-F bond. Here we report a radical fluorosulfonylation strategy for the stereoselective synthesis of alkenyl sulfonyl fluorides and functional alkyl sulfonyl fluorides with an air-stable crystalline benzimidazolium fluorosulfonate cationic salt reagent. This bench-stable redox-active reagent offers a useful and operational protocol for the radical fluorosulfonylation of unsaturated hydrocarbons with good yield and high stereoselectivity, which can be further transformed into valuable functional SO2F moieties.