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Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications information storage, anti-counterfeiting, and information encryption.
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AIM: The indications for performing retrograde intrarenal surgery (RIRS) have increased. However, no comparative studies have been conducted on the treatment of staghorn renal calculi using RIRS and percutaneous nephrolithotomy (PCNL). We aimed to compare the effectiveness and safety of RIRS and PCNL as treatments for staghorn renal calculi. METHODS: We conducted a retrospective analysis of patients with staghorn renal calculi who underwent either PCNL or RIRS at our hospital from January 2021 to July 2023. Patients with staghorn renal calculi and renal malformation, as well as those with interrupted treatment or irregular follow-up, were excluded from the study. We compared the perioperative outcomes and complications between the groups. RESULTS: Fifty patients were included in the RIRS group, whereas 48 patients were included in the PCNL group. 1. No significant differences were observed between the groups regarding the number of complete staghorn calculi, stone size, age, sex, or other demographic characteristics. 2. RIRS was associated with a shorter postoperative hospitalization time (2.14 ± 0.76 vs. 5.15 ± 1.98 days, p < 0.001). 3. RIRS was associated with a decrease in hemoglobin (0.1 [0, 0.2] vs. 0.65 [0.4, 1] g/dL, p < 0.001) and a lower pain score (1 [1, 2] vs. 2 [1, 3], p = 0.008). 4. Compared with PCNL, RIRS did not significantly differ in terms of the 1-stage stone-free rate (50% vs. 66.67%, p = 0.095) or total stone-free rate (84% vs. 89.58%, p = 0.415). 5. The overall complication rate was lower in the RIRS group (10% vs. 16.67%, p = 0.331). CONCLUSIONS: Compared with PCNL, RIRS can reduce bleeding and overall complications, shorten the hospitalization time, and achieve satisfactory stone-free rate. As a result, RIRS can be considered an alternative treatment option for staghorn renal calculi.
Subject(s)
Nephrolithotomy, Percutaneous , Staghorn Calculi , Humans , Nephrolithotomy, Percutaneous/methods , Retrospective Studies , Male , Female , Staghorn Calculi/surgery , Middle Aged , Length of Stay/statistics & numerical data , Treatment Outcome , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Kidney Calculi/surgery , AgedABSTRACT
BACKGROUND The tip-flexible suctioning ureteral access sheath (TFS-UAS) can be bent under flexible ureteroscopes, which facilitates removal of renal stone segments by irrigation and suctioning effects. Small-scale comparative studies found it safer and more efficacious than traditional UAS. However, complications such as renal abscess were not documented after TFS-UAS combined with digital FURS. CASE REPORT A 57-year-old woman had right lumbar pain that persisted for 1 year. A plain computed tomography (CT) scan revealed multiple renal pelvicalyceal stones (maximum diameter 20×9 mm). She was admitted to undergo elective surgery with a TFS-UAS combined with digital flexible ureteroscopic lithotripsy. The operation was deemed successful and she was given postoperative antibiotics for 2 days before discharge. Eight postoperative days later, she was admitted to the emergency department due to high fever (39.6°C). Plain CT revealed intact double-J stents and no abnormalities. She was readmitted to the urological department to receive antibiotic therapy, which progressed to septic shock (blood pressure 80/50 mmHg) and required immediate transfer to the intensive care unit. Contrast-enhanced CT revealed a right renal abscess. She was promptly resuscitated and given stronger antibiotics. She recovered well and was discharged with 2-week oral levofloxacin treatment. Follow-up ultrasound found no renal abscess. CONCLUSIONS While TFS-UAS with digital FURs is an effective approach for multiple renal stones, there is a risk of postoperative renal abscess, possibly due to altered intrarenal pressure.
Subject(s)
Abscess , Kidney Calculi , Lithotripsy , Ureteroscopy , Humans , Female , Middle Aged , Ureteroscopy/adverse effects , Lithotripsy/adverse effects , Kidney Calculi/surgery , Abscess/etiology , Abscess/therapy , Suction , Postoperative Complications , Kidney DiseasesABSTRACT
Herein, we successfully synthesized a copper nanocluster, [Cu58(SeC6H5)24(Dppe)6Se16]2+. The Cu58 features a tetrahedral Cu4 core, surrounded by tetrahedral Se4 and octahedral Cu6 subunits, and further stabilized by Cu3Se3, Cu3(SeR)3, and DppeCu2 staples, which can be interpreted as an assembly of tetrahedral and octahedral units. Density functional theory (DFT) calculations were employed to investigate the electronic structure of Cu58. This nanocluster demonstrates excellent catalytic properties in copper-catalyzed [3+2] azide-alkyne cycloaddition (CuAAC) reactions. Additionally, Cu58 enriches the structural diversity of copper-based nanoclusters, providing valuable insights for future structural predictions.
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In order to investigate the composition and differences in volatile organic compounds (VOCs) in yak and cattle-yak meat and determine the key metabolites and metabolic pathways related to flavor formation. In this study, the VOCs and non-volatile metabolites in Longissimus dorsi muscle of two groups of samples were detected and analyzed by gas chromatography-ion migration spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS). The results showed that 31 VOCs were identified by GC-IMS, including 5 alcohols, 5 ketones, 5 esters, 3 aldehydes, 2 furans, 2 hydrocarbons, 1 amine, 1 acid, 1 thiazole, 1 pyrazine, and 5 others. Most of them were alcohols, ketones, esters, and aldehydes. A total of 75 non-volatile metabolites with significant differences were obtained by GC-MS screening, among which amino acid contents such as serine, glycine, phenylalanine, and aspartic acid were significantly up-regulated in cattle-yak, and glutamic acid and tyrosine were significantly up-regulated in yak. The non-volatile differential metabolites in the two groups were significantly enriched in the metabolic pathways of arginine biosynthesis and oxidative phosphorylation. By combining GC-IMS and GC-MS, this study comprehensively and intuitively reflected the differences in VOCs between yak and cattle-yak meat, and clarified the metabolomic reasons for the differences in VOCs, so as to provide a theoretical basis for meat quality improvement.
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Percutaneous nephrolithotomy (PCNL) is the primary choice for managing large renal stones and the establishment of mini-/micro-channels has been increasingly gaining practice. The smaller the channel, the easier it is to be lost, which may require a new puncture site and increase the risk of bleeding complications. In this study, we retrospectively reviewed 1,056 PCNL procedures in our single institute, The University of Hong Kong - Shenzhen Hospital, between March 2014 and August 2023. Twenty-three cases of nephrostomy channel loss during mini PCNL were identified, resulting in an incidence rate of 2.2%. Methylene blue was immediately injected into the ureteral catheter to facilitate location and retrieval of the channel. Once extravasation of the dye was identified under rigid ureteroscope, a first guidewire was introduced into the channel for maintenance, followed by another guidewire inserted in parallel to facilitate dilatation. The major reasons for PCNL channel loss were mild hydronephrosis and complete obstruction of the target calyx due to renal stones. Technical success, defined as the ability to retrieve the lost channel within 5 minutes, was 78.3% (n=18/23). Three channels were completely lost and 2 patients showed channel bleeding despite successful identification, all of which required establishment of a new PCNL channel. No major intraoperative nor postoperative complication was observed.
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Podocytopathies, such as focal segmental glomerulosclerosis (FSGS), are characterized by podocyte injury and can easily progress to end-stage kidney disease. However, the mechanisms underlying podocyte injury remain unclear. We observed podocyte injury along with pyroptosis in patients with FSGS. Bioinformatic analysis of public datasets revealed that transmembrane protein 30a (Tmem30a) might be associated with FSGS. The expression of Temem30a and the podocyte-related protein, nephrin, were significantly downregulated in patients with FSGS, adriamycin (ADR)-induced mice, and podocyte-specific Tmem30a lox P /loxP ; NPHS2-Cre mice, whereas the expression of NLR family pyrin domain containing 3 (NLRP3) and ASC, two pyroptosis-related proteins, were significantly upregulated. Meanwhile, the pyroptosis inhibitor MCC950 and disulfiram (DSF) increased Tmem30a and podocyte-related proteins expression, and inhibited pyroptosis-related proteins expression in ADR-induced mouse podocytes and Tmem30a knockdown (KD) mouse podocytes. Therefore, Tmem30a might protect against podocyte injury by inhibiting pyroptosis, suggesting a potential therapeutic target for podocytopathies.
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Owing to the significant attention directed toward alloy metal nanoclusters, it is crucial to explore the relationship between their structures and their performance during the electrocatalytic CO2 reduction reaction (eCO2RR) and discover potential synergistic effects for the design of novel functional nanoclusters. However, a lack of suitable analogs makes this investigation challenging. In this study, we synthesized a well-defined pair of structural analogs, [Au8Cu1(SAdm)4(Dppm)3Cl]2+ and [Au8Ag1(SAdm)4(Dppm)3Cl]2+ (Au8Cu1 and Au8Ag1, respectively), and characterized them. Single-crystal X-ray diffraction analysis revealed that Au8M1 (M=Cu/Ag) consists of a tetrahedral Au3M1 core capped by three (Dppm)Au staples, one Au2(SR)3 staple, one lone SR ligand, and a terminal Cl ligand. Ag and Cu were doped at the same site in the Au8M1 nanoclusters, which has rarely been reported. Au8Cu1 exhibited a significantly higher CO Faradaic efficiency (FECO; ~82.2 %) during eCO2RR than that of Au8Ag1 (FECO; ~33.1 %). Density functional theory calculations demonstrated that *COOH is the key intermediate in the reduction of CO2 to CO. The formation of *COOH on Au8Cu1 is more thermodynamically stable than on Au8Ag1, and Au8Cu1 shows a smaller *CO formation energy than that on Au8Ag1, which promotes the reduction of CO2. We believe that the structural analogs Au8Cu1 and Au8Ag1 offer a suitable template for the in-depth investigation of structure-property correlations at the atomic level.
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Human immunodeficiency virus prevalence was increasing worldwide. Medication-associated urinary calculi are very commonly caused by medications used to treat HIV-positive patients. We present a case of an HIV-positive 39-year-old male with ureteral stent encrustation and kidney stone. Ureterolithotripsy using a disposable flexible ureteroscope is performed. The postoperative evolution was favorable. The disposable flexible ureteroscope is effective in the treatment of HIV combined with ureteral stent encrustation.
Subject(s)
HIV Infections , Kidney Calculi , Lithotripsy , Stents , Ureteroscopy , Humans , Male , Adult , HIV Infections/complications , Stents/adverse effects , Ureteroscopes , Kidney Calculi/diagnostic imaging , Kidney Calculi/surgery , Lithotripsy/adverse effects , Lithotripsy/methods , Ureteroscopy/adverse effects , Disposable Equipment , Laparoscopy , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Cattle-yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle-yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle-yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle-yak and yak versus cattle-yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle-yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA-circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle-yaks.
Subject(s)
Gene Regulatory Networks , MicroRNAs , RNA, Circular , RNA, Messenger , Testis , Cattle/genetics , Cattle/metabolism , Animals , Male , Testis/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Spermatogenesis/genetics , Transcriptome , RNA, Competitive EndogenousABSTRACT
Alternative splicing is a prevalent phenomenon in testicular tissues. Due to the low assembly accuracy of short-read RNA sequencing technology in analyzing post-transcriptional regulatory events, full-length (FL) transcript sequencing is highly demanded to accurately determine FL splicing variants. In this study, we performed FL transcriptome sequencing of testicular tissues from 0.5, 1.5, 2.5, and 4-year-old yaks and 4-year-old cattle-yaks using Oxford Nanopore Technologies. The obtained sequencing data were predicted to have 47,185 open reading frames (ORFs), including 26,630 complete ORFs, detected 7645 fusion transcripts, 15,355 alternative splicing events, 25,798 simple sequence repeats, 7628 transcription factors, and 35,503 long non-coding RNAs. A total of 40,038 novel transcripts were obtained from the sequencing data, and the proportion was almost close to the number of known transcripts identified. Structural analysis and functional annotation of these novel transcripts resulted in the successful annotation of 9568 transcripts, with the highest and lowest annotation numbers in the Nr and KOG databases, respectively. Weighted gene co-expression network analysis revealed the key regulatory pathways and hub genes at various stages of yak testicular development. Our findings enhance our comprehension of transcriptome complexity, contribute to genome annotation refinement, and provide foundational data for further investigations into male sterility in cattle-yaks.
Subject(s)
Molecular Sequence Annotation , Testis , Transcriptome , Animals , Male , Cattle , Testis/metabolism , Testis/growth & development , Transcriptome/genetics , Open Reading Frames/genetics , Gene Expression Profiling/methods , Alternative Splicing , RNA, Long Noncoding/genetics , Gene Regulatory Networks , Sequence Analysis, RNA/methodsABSTRACT
The study of structural isomerism in copper nanoclusters has been relatively limited compared to that in gold and silver nanoclusters. In this work, we present the controlled synthesis and structures of two isomeric copper nanoclusters, denoted as Cu22-1 and Cu22-2, whose compositions were determined to be Cu22(SePh)10(Se)6(P(Ph-4F)3)8 through single-crystal X-ray diffraction (SCXRD). The structural isomerism of Cu22-1 and Cu22-2 arises from the different arrangements of a few Cu(SeR)(PR3) motifs on the surface structure. These subtle changes in the surface structure also influence the distortion of the core and the spatial arrangement of the clusters, and affect the electronic structure. Furthermore, due to their distinct structures, Cu22-1 and Cu22-2 exhibit different catalytic properties in the copper-catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC). Notably, Cu22-1 demonstrates efficient catalytic activity for photoinduced AAC, achieving a yield of 90% within 1 hour. This research contributes to the understanding of structural isomerism in copper nanoclusters and offers insights into the structure-function relationship in these systems.
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BACKGROUND Double-J (D-J) ureteric stents are widely applied in urological operations as they play a vital role in maintaining postoperative functionality of the patient's urinary system and thereby accelerating recovery. D-J stent encrustation may occur due to prolonged retention and lead to secondary complications. We report the case of a forgotten D-J stent that gradually formed into a bladder stone. CASE REPORT A 54-year-old man was referred to the Urology Department due to intermittent hematuria, left flank pain, and lower urinary tract symptoms that persisted for 2 weeks. His history was significant for undergoing left ureterolithotripsy followed by the implantation of an ipsilateral D-J stents 2 years ago in a local hospital. The patient did not follow-up regularly or actively seek medical attention for his urinary tract symptoms. Computed tomographic urography revealed a hyperdense tubular object protruding from the left distal ureter to the bladder. The patient underwent cystolithotripsy, left ureteric stent removal, and left ureteroscopy to clear away the bladder stone and its D-J stent core. CONCLUSIONS Formation of bladder stones secondary to prolonged indwelling D-J stent and its encrustation is not uncommon in developing countries where the level of public education is low. Prompt D-J stent removal can prevent complications associated with its retention and avoid unnecessary secondary procedures. Endoscopic urologic procedures are safe and feasible management options, and doctor-to-patient communication is vital for a better prognosis.
Subject(s)
Stents , Urinary Bladder Calculi , Humans , Male , Middle Aged , Stents/adverse effects , Urinary Bladder Calculi/surgery , Urinary Bladder Calculi/therapy , Ureter/surgery , Device Removal , Foreign Bodies/surgery , Ureteroscopy , LithotripsyABSTRACT
BACKGROUND: There is no consensus as to the origin of the domestic yak (Bos grunniens). Previous studies on yak mitochondria mainly focused on mitochondrial displacement loop (D-loop), a region with low phylogenetic resolution. Here, we analyzed the entire mitochondrial genomes of 509 yaks to obtain greater phylogenetic resolution and a comprehensive picture of geographical diversity. RESULTS: A total of 278 haplotypes were defined in 509 yaks from 21 yak breeds. Among them, 28 haplotypes were shared by different varieties, and 250 haplotypes were unique to specific varieties. The overall haplotype diversity and nucleotide diversity of yak were 0.979 ± 0.0039 and 0.00237 ± 0.00076, respectively. Phylogenetic tree and network analysis showed that yak had three highly differentiated genetic branches with high support rate. The differentiation time of clades I and II were about 0.4328 Ma, and the differentiation time of clades (I and II) and III were 0.5654 Ma. Yushu yak is shared by all haplogroups. Most (94.70%) of the genetic variation occurred within populations, and only 5.30% of the genetic variation occurred between populations. The classification showed that yaks and wild yaks were first clustered together, and yaks were clustered with American bison as a whole. Altitude had the highest impact on the distribution of yaks. CONCLUSIONS: Yaks have high genetic diversity and yak populations have experienced population expansion and lack obvious phylogeographic structure. During the glacial period, yaks had at least three or more glacial refugia.
Subject(s)
Genetic Variation , Genome, Mitochondrial , Haplotypes , Phylogeny , Phylogeography , Animals , Cattle/genetics , Maternal Inheritance , Female , DNA, Mitochondrial/geneticsABSTRACT
As the sole carbonaceous renewable energy source, biomass is distinguished by its abundant yield, widespread distribution, and carbon neutrality. It is integral to the achievement of zero and negative carbon production via conventional carbonaceous pellet technology. This study introduces a cradle-to-gate life cycle assessment methodology for biomass preparation in carbonaceous pellets. We prepare high-quality biochar through a process combining hydrothermal carbonization and pyrolytic carbonization. Biomass high molecular weight extracts are obtained via organic pyrolytic extraction, while biomass high-temperature binders result from the modification and treatment of biochar. Biomass carbonaceous pellets are then formed using hot press technology. The ReCiPe model facilitates a comprehensive life cycle assessment of biomass carbonaceous pellets used in blast furnace production. The study leverages two comprehensive evaluation indicators - renewability, and environmental performance - to enhance the environmental performance of the process system and to maximize energy-saving and emission reduction potential.
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To investigate the correlation between nucleolar spindle-associated protein 1 (NUSAP1) and cancer immunotherapy across 33 different types of human cancers. We conducted an analysis of The Cancer Genome Atlas (TCGA) database to retrieve gene expression data and clinical characteristics for 33 different cancer types. The immunotherapy cohorts encompassed GSE67501, GSE78220, and IMvigor210. Relevant information was extracted from the gene expression repository. We assessed the prognostic significance of NUSAP1 by examining various clinical parameters. The single-sample gene-set enrichment analysis (ssGSEA) method was utilized to gauge NUSAP1 activity and to contrast NUSAP1 transcriptome and protein levels. We delved into the correlation between NUSAP1 and various immune processes and components to gain insights into NUSAP1's role. We also discussed coherent pathways associated with NUSAP1 signal transduction and its impact on immunotherapy biomarkers. To authenticate and validate the differential expression patterns of NUSAP1 in bladder tumor tissues versus normal bladder counterparts, we utilized Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry (IHC) techniques. NUSAP1 exhibits overexpression across a spectrum of malignancies, and its expression levels correlate with overall survival (OS), disease-specific survival, and tumor stage in specific cancer types. Furthermore, NUSAP1 expression is linked to mutations, methylation patterns, and immunotherapy responses in human cancers. Meanwhile, our experiments, involving WB, RT-qPCR, and IHC, consistently demonstrated significantly higher NUSAP1 expression in bladder tumor tissues compared to normal controls. Our study underscores the potential of NUSAP1 as a promising prognostic indicator and immunotherapeutic target for a range of malignant tumors.
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Background: Percutaneous nephrolithotomy (PCNL) is the first-line treatment for large renal stones. However, multi-tract or staged procedures may be necessitated in bilateral or anatomically-complex stones to achieve stone clearance. Endoscopic combined intrarenal surgery (ECIRS) integrates the advantages of PCNL and retrograde intrarenal surgery. In this article, we detail a hybrid surgical technique adopted for the management of complex simultaneous bilateral upper urinary tract stones. In addition, we discuss the advantages and disadvantages of combining a variety of new techniques that may improve post-operative outcomes and patient satisfaction. Case Description: We report the case of a 36-year-old male with a large left renal pelvis stone, right proximal ureteric stone, and bilateral renal stones. Biochemical results showed raised inflammatory markers but he denied pre-stenting and staged surgery. After receiving 3-day antibiotic prophylaxis, he underwent an elective hybrid procedure. Under split-leg prone position, we performed a hybrid procedure that included left ECIRS with tubeless single-tract mini PCNL and left flexible ureteroscopy, and right flexible ureteroscopic lithotripsy. Hemostasis was achieved by electrocauterization with a novel device. The patient made an uneventful recovery. Follow-up computed tomography (CT) at 1-month revealed complete stone clearance. Conclusions: Unilateral ECIRS with tubeless single-tract mini PCNL with electrocoagulation hemostasis and adjacent retrograde intrarenal surgery in split-leg prone position is a safe, feasible, and efficient technique to manage large renal stones.
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It has been 11 years since ferroptosis, a new mode of programmed cell death, was first proposed. Natural products are an important source of drug discovery. In the past five years, natural product-derived ferroptosis regulators have been discovered in an endless stream. Herein, 178 natural products discovered so far to trigger or resist ferroptosis are classified into 6 structural classes based on skeleton type, and the mechanisms of action that have been reported are elaborated upon. If pharmacodynamic data are sufficient, the structure and bioactivity relationship is also presented. This review will provide medicinal chemists with some effective ferroptosis regulators, which will promote the research of natural product-based treatment of ferroptosis-related diseases in the future.
Subject(s)
Biological Products , Ferroptosis , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/pharmacology , Lipid Peroxidation , Apoptosis , Biological Products/pharmacologyABSTRACT
Renal cell carcinoma (RCC) is the most common renal malignancy with a rapidly increasing morbidity and mortality rate gradually. RCC has a high mortality rate and an extremely poor prognosis. Despite numerous treatment strategies, RCC is resistant to conventional radiotherapy and chemotherapy. In addition, the limited clinical efficacy and inevitable resistance of multiple agents suggest an unmet clinical need. Therefore, there is an urgent need to develop novel anti-RCC candidates. Nowadays many promising results have been achieved with the development of novel small molecule inhibitors against RCC. This paper reviews the recent research progress of novel small molecule inhibitors targeting RCC. It is focusing on the structural optimization process and conformational relationships of small molecule inhibitors, as well as the potential mechanisms and anticancer activities for the treatment of RCC. To provide a theoretical basis for promoting the clinical translation of novel small molecule inhibitors, we discussed their application prospects and future development directions. It could be capable of improving the clinical efficacy of RCC and improving the therapy resistance for RCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Prognosis , Treatment OutcomeABSTRACT
Ruminant rumen plays an important role in the digestibility of cellulose, hemicellulose, starch and fat. In this study, the yaks under graze and stall feeding were chosen as the models of different rumen bacteria and intramuscular fat (IMF). The characteristics of IMF deposition, serum indexes in yaks were detected; the bacteria, metabolites in rumen was explored by 16S rRNA sequencing technology, untargeted metabolomics based on liquid chromatography-mass spectrometer and gas chromatography, respectively; the transcriptome of longissimus thoracis was identified by RNA-Sequencing analysis. Based on above results, a hypothesis that yak IMF deposition is regulated by the combined action of microbiome-gut-brain and muscle axis was proposed. The short-chain fatty acids (SCFAs) and neurotransmitters precursors like acetylcholine produced in yak rumen promoted insulin secretion via central nervous system. These insulin resulted in the high expression of SREBF1 gene by gut-brain axis; SCFAs can directly arrive to muscular tissue via blood circulation system, then activated the expression of PPARγ gene by gut-muscle axis. The expression of lipogenesis gene SCD, FABP3, CPT1, FASN and ACC2 was accordingly up-regulated. This study firstly introduce the theory of microbiome-gut-brain/muscle axis into the study of ruminant, and comprehensively expounded the regulatory mechanism of yak IMF deposition.