Impact of coronavirus disease 2019 on the utilization of hospital services and development of optimal pandemic control strategy in Chinese tertiary hospitals during the Omicron wave.

BACKGROUND: This study aimed to assess the impact of coronavirus disease 2019 (COVID-19) on hospital service utilization and revenue in Chinese tertiary hospitals and develop an optimal pandemic control strategy (OPCS) for the peak period of the Omicron wave. METHODS: Retrospective data from three Chinese tertiary hospitals (provincial, city, and county level) were analyzed for three phases: pre-outbreak (Jan-Apr 2019), outbreak (Jan-Apr 2020), and post-outbreak (Jan-Apr 2021). OPCS was developed under the guidance of the China government pandemic control policy during post-break phase of COVID-19. A decision-tree model was constructed to compare OPCS to strict pandemic control strategy during outbreak phase for the hospital service utilization and hospital revenue in a provincial tertiary hospital during the Omicron wave. RESULTS: Outpatient, emergency room (ER) visits, hospitalizations, and intensive care admissions dropped by 33.8-53.4% during the outbreak, with the provincial hospital being the most affected. Hospital revenue also declined, especially for the provincial hospital (40.1%). Post-outbreak, most services recovered, but ER visits remained lower (11.6% decrease for provincial hospital, 46.5% for county hospital). Total income and expenditure decreased, with the provincial hospital experiencing the most significant revenue reduction (45.7%). OPCS showed greater utilization of medical services (31.6 times more outpatient visits; 1.7 times more inpatient days; 3.4% more surgery volume) and higher revenue (¥220.8 million more) compared to the strict pandemic control strategy. CONCLUSIONS: COVID-19 measures were associated with less hospital service utilization and revenue in Chinese tertiary hospitals. The developed OPCS in Chinese tertiary hospitals, focusing on isolating infected inpatients but not shutting down the hospital facilities exposed to virus, could be effective in optimizing hospital service utilization and hospital revenue during the Omicron wave.

Pyridinium-Based Fluorosulfonamide Reagents Enabled Photoredox-Catalyzed Radical Fluorosulfonamidation.

Sulfamoyl fluorides, as a crucial building block of SuFEx, have garnered extensive research interest due to their unique properties. However, the direct radical fluorosulfonamidation process for the synthesis of sulfamoyl fluorides has been overlooked. We herein disclosed a practical procedure for constructing a redox-active fluorosulfonamide radical reagent named fluorosulfonyl-N-pyridinium tetrafluoroborate (PNSF) from SO2F2. These reagents can facilitate a range of reactions, including the N-(fluorosulfonyl) sulfonamidation of (hetero)arenes, sequential radical stereoselective fluorosulfonamidation, and 1,2-difunctionalization of alkenes.

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.

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.

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.

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.

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.

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.

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.

A photoinduced transient activating strategy for late-stage chemoselective C(sp3)-H trifluoromethylation of azines.

The direct functionalization of C(sp3)-H bonds is an ultimately ideal synthetic strategy with high atom economy and step efficiency. However, the direct trifluoromethylation of electron-deficient heteroaryl adjacent C(sp3)-H bonds remains a formidable challenge. We have described a transient activating strategy involving a Tf-shift process and π-π stacking interaction for catalyst-free direct benzylic C(sp3)-H trifluoromethylation of azines, such as pyridine, pyrimidine, quinoline, dihydropyridinone, tetrahydroisoquinoline and tetrahydroquinazoline, with an air-stable crystalline imidazolium sulfonate reagent IMDN-Tf. This bench-stable cationic reagent offers a scalable and practical protocol for the late-stage modification of drug molecules with high site selectivity, which avoids the prefunctionalization and the use of stoichiometric metals and strong oxidants. Furthermore, comprehensive mechanistic studies revealed the determining effect of π-π stacking for the activation of azinylic C(sp3)-H bonds.

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.

[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.

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 Transcription Factor-Based Risk Model for Predicting the Prognosis of Prostate Cancer and Potential Therapeutic Drugs.

BACKGROUND: Prostate cancer (PC) is one of the most critical cancers affecting men's health worldwide. The development of many cancers involves dysregulation or mutations in key transcription factors. This study established a transcription factor-based risk model to predict the prognosis of PC and potential therapeutic drugs. MATERIALS AND METHODS: In this study, RNA-sequencing data were downloaded and analyzed using The Cancer Genome Atlas dataset. A total of 145 genes related to the overall survival rate of PC patients were screened using the univariate Cox analysis. The Kdmist clustering method was used to classify prostate adenocarcinoma (PRAD), thereby determining the cluster related to the transcription factors. The support vector machine-recursive feature elimination method was used to identify genes related to the types of transcription factors and the key genes specifically upregulated or downregulated were screened. These genes were further analyzed using Lasso to establish a model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for the functional analysis. The TIMER algorithm was used to quantify the abundance of immune cells in PRAD samples. The chemotherapy response of each GBM patient was predicted based on the public pharmacogenomic database, Genomics of Drug Sensitivity in Cancer (GDSC, http://www.cancerrxgene.org). The R package "pRRophetic" was applied to drug sensitivity (IC50) value prediction. RESULTS: We screened 10 genes related to prognosis, including eight low-risk genes and two high-risk genes. The receiver operating characteristic (ROC) curve was 0.946. Patients in the high-risk score group had a poorer prognosis than those in the low-risk score group. The average area under the curve value of the model at different times was higher than 0.8. The risk score was an independent prognostic factor. Compared with the low-risk score group, early growth response-1 (EGR1), CACNA2D1, AC005831.1, SLC52A3, TMEM79, IL20RA, CRACR2A, and FAM189A2 expressions in the high-risk score group were decreased, while AC012181.1 and TRAPPC8 expressions were increased. GO and KEGG analyses showed that prognosis was related to various cancer signaling pathways. The proportion of B_cell, T_cell_CD4, and macrophages in the high-risk score group was significantly higher than that in the low-risk score group. A total of 25 classic immune checkpoint genes were screened out to express abnormally high-risk scores, and there were significant differences. Thirty mutant genes were identified; in the high- and low-risk score groups, SPOP, TP53, and TTN had the highest mutation frequency, and their mutations were mainly missense mutations. A total of 36 potential drug candidates for the treatment of PC were screened and identified. CONCLUSIONS: Ten genes of both high-and low-risk scores were associated with the prognosis of PC. PC prognosis may be related to immune disorders. SPOP, TP53, and TTN may be potential targets for the prognosis of PC.

Electrochemical-Promoted Nickel-Catalyzed Oxidative Fluoroalkylation of Aryl Iodides.

This work describes a general strategy for metal-catalyzed cross-coupling of fluoroalkyl radicals with aryl halides under electrochemical conditions. The contradiction between anodic oxidation of fluoroalkyl sulfinates and cathodic reduction of low-valent nickel catalysts can be well addressed by paired electrolysis, allowing for direct introduction of fluorinated functionalities into aromatic systems.

Identification and expression profile of the soil moisture and Ralstonia solanacearum response CYPome in ginger (Zingiber officinale).

BACKGROUND: Cytochrome P450s play crucial roles in various biosynthetic reactions. Ginger (Zingiber officinale), which is often threatened by Ralstonia solanacearum, is the most economically important crop in the family Zingiberaceae. Whether the cytochrome P450 complement (CYPome) significantly responds to this pathogen has remained unclear. METHODS: Transcriptomic responses to R. solanacearum and soil moisture were analyzed in ginger, and expression profiles of the CYPome were determined based on transcriptome data. RESULTS: A total of 821 P450 unigenes with ORFs ≥ 300 bp were identified. Forty percent soil moisture suppressed several key P450 unigenes involved in the biosynthesis of flavonoids, gingerols, and jasmonates, including unigenes encoding flavonoid 3'-hydroxylase, flavonoid 3',5'-hydroxylase, steroid 22-alpha-hydroxylase, cytochrome P450 family 724 subfamily B polypeptide 1, and allene oxide synthase. Conversely, the expression of P450 unigenes involved in gibberellin biosynthesis and abscisic acid catabolism, encoding ent-kaurene oxidase and abscisic acid 8'-hydroxylase, respectively, were promoted by 40% soil moisture. Under R. solanacearum infection, the expression of P450 unigenes involved in the biosynthesis of the above secondary metabolites were changed, but divergent expression patterns were observed under different soil moisture treatments. High moisture repressed expression of genes involved in flavonoid, brassinosteroid, gingerol, and jasmonate biosynthesis, but promoted expression of genes involved in GA anabolism and ABA catabolism. These results suggest possible mechanisms for how high moisture causes elevated susceptibility to R. solanacearum infection.