Intelligent Reconfiguration-Promoted Cellular Internalization of Core-Shell DNA Nanoprobe Equipped with Successive Dual Stimuli-Responsive Protective Satellites for Amplification Fluorescence Imaging of Tumor Cells.

Although DNA probes have attracted increasing interest for precise tumor cell identification by imaging intracellular biomarkers, the requirement of commercial transfection reagents, limited targeting ligands, and/or non-biocompatible inorganic nanostructures has hampered the clinic translation. To circumvent these shortcomings, a reconfigurable ES-NC (Na+-dependent DNAzyme (E)-based substrate (S) cleavage core/shell DNA nanocluster (NC)) entirely from DNA strands is assembled for precise imaging of cancerous cells in a successive dual-stimuli-responsive manner. This nanoprobe is composed of a strung DNA tetrahedral satellites-based protective (DTP) shell, parallelly aligned target-responsive sensing (PTS) interlayer, and hydrophobic cholesterol-packed innermost layer (HCI core). Tetrahedral axial rotation-activated reconfiguration of DTP shell promotes the exposure of interior hydrophobic moieties, enabling cholesterol-mediated cellular internalization without auxiliary elements. Within cells, over-expressed glutathione triggers the disassembly of the DTP protective shell (first stimulus), facilitating target-stimulated signal transduction/amplification process (second stimuli). Target miRNA-21 is detected down to 10.6 fM without interference from coexisting miRNAs. Compared with transfection reagent-mediated counterpart, ES-NC displays a higher imaging ability, resists nuclease degradation, and has no detectable damage to healthy cells. The blind test demonstrates that the ES-NC is suitable for the identification of cancerous cells from healthy cells, indicating a promising tool for early diagnosis and prediction of cancer.

Granulomatous orchitis: A case report of misdiagnosis and review of the literature.

Granulomatous orchitis is a relatively rare clinical testicular lesion. The imaging manifestations and clinical symptoms are similar to those of testicular tumors. In order to improve the understanding of this disease, this article reports the ultrasonographic manifestations of a case of granulomatous orchitis and reviews the relevant literature with.

Screening and Application of DNA Aptamers for Heparin-Binding Protein.

Rapid detection of heparin-binding protein (HBP) is essential for timely intervention in sepsis cases. Current detection techniques are usually antibody-based immunological methods, which have certain problems, such as complexity and slow detection, and fall short in meeting the urgency of clinical needs. The application of an aptamer can address these concerns well. In this study, HBP-specific DNA aptamers were screened first. Among which, Apt-01, Apt-02, and Apt-13 had a high affinity for HBP, exhibiting impressive KD values of 3.42, 1.44, and 1.04 nmol/L, respectively. Then, the aptamer of HBP and its partially complementary primer probe were combined to form double-stranded DNA (dsDNA) and synthesize a circular DNA template. The template is complementary to the primer probe, but due to the presence of dsDNA, ExoIII cleaves C2-13 as an RCA primer probe, rendering the template unable to recognize the primer probe and preventing the RCA reaction from proceeding. When the target is present, it competes with the adapter for recognition and releases C2-13, exposing its 3' end. After initiating the RCA at room temperature and reacting with SYBR GreenII at 37 °C for 20 min, fluorescence changes can be observed and quantitatively analyzed at a 530 nm wavelength, achieving quantitative biological analysis. Apt-01 was used to develop a fluorescent biosensor for HBP detection, which exhibited a good linear range (0.01 nmol/L to 10 nmol/L) and detection limit (0.0056 nmol/L). This advancement holds the potential to lay a solid groundwork for pioneering sensitive and specific methods for HBP detection and to significantly enhance the diagnostic processes for sepsis.

Evaluation of arsenic pollution in field-contaminated soil at the soil's actual pH.

The pollution and ecological risks posed by arsenic (As) entering the soil are the major environmental challenges faced by human beings. Soil phosphatase can serve as a useful indicator for assessing As contamination under specific soil pH conditions. However, the study of phosphatase kinetics in long-term field As-contaminated soil remains unclear, presenting a significant obstacle to the monitoring and evaluation of As pollution and toxicity. The purpose of this study was to determine phosphatase activity and explore enzyme kinetics in soils subjected to long-term field As contamination. Results revealed that the soil phosphatase activity varied among the tested soil samples, depending on the concentrations of As. The relationship between total As, As fractions and phosphatase activity was found to be significant through negative exponential function fitting. Kinetic parameters, including maximum reaction velocity (Vmax), Michaelis constant (Km) and catalytic efficiency (Vmax/Km), ranged from 3.14 × 10-2-53.88 × 10-2 mmol/(L·hr), 0.61-7.92 mmol/L, and 0.46 × 10-2-11.20 × 10-2 hr-1, respectively. Vmax and Vmax/Km of phosphatase decreased with increasing As pollution, while Km was less affected. Interestingly, Vmax/Km showed a significant negative correlation with all As fractions and total As. The ecological doses (ED10) for the complete inhibition and partial inhibition models ranged from 0.22-70.33 mg/kg and 0.001-55.27 mg/kg, respectively, indicating that Vmax/Km can be used as an index for assessing As pollution in field-contaminated soil. This study demonstrated that the phosphatase kinetics parameters in the soil's pH system were better indicators than the optimal pH for evaluating the field ecotoxicity of As.

Role of aquaporin 3 in reproductive performance of dairy goats after repeated estrus synchronization stimulation.

This study explored the specific molecular mechanisms through which repeated estrus synchronization (ES) treatments reduce the reproductive performance of dairy goats. Ninety-six goats (n = 24/group) were randomly assigned to two groups receiving ES treatments thrice every fortnight (3-equine chorionic gonadotropin [eCG] and 3-follicle stimulating hormone [FSH] groups) and two groups receiving one ES treatment (1-eCG and 1-FSH groups). ES treatments of 1- and 3-eCG goats were performed via the intravaginal insertion of a controlled internal drug release (CIDR) device containing 300 mg progesterone (P4), followed by 300 IU eCG injections 48 h before CIDR withdrawal. The 1- and 3-FSH goats received CIDR for 10 days, followed by 50 IU FSH and 100 µg PGF2α within 12 h of CIDR withdrawal. Ovaries of three goats in estrus from both groups were harvested for analysis. Subsequently, all the goats in estrus were artificially inseminated twice. Consequently, 3-eCG and 3-FSH goats showed a considerably reduced estrus rate and litter size than 1-eCG and 1-FSH goats. AQP3 mRNA and protein expression were significantly higher in the 3-eCG and 3-FSH groups than in the 1-eCG and 1-FSH groups. AQP3 overexpression led to cell apoptosis and decreased steroid hormone secretion ability of ovarian granulosa cells. Moreover, it resulted in a decrease in maturation and cleavage rates after parthenogenetic activation and in vitro fertilization, respectively. AQP3 gene was involved in reducing the reproductive performance of repeated ES-treated dairy goats. These findings provide a theoretical foundation for the effective use of reproductive hormones in breeding techniques for livestock.

CD36 deletion ameliorates diabetic kidney disease by restoring fatty acid oxidation and improving mitochondrial function.

Renal tubular epithelial cells (TECs) are vulnerable to mitochondrial dysregulation, which is an integral part of diabetic kidney disease (DKD). We found that CD36 knockout ameliorated mitochondrial dysfunction and diabetic kidney injury in mice, improved renal function, glomerular hypertrophy, tubular injury, tubulointerstitial fibrosis, and kidney cell apoptosis. Furthermore, CD36 knockout conferred protection against diabetes-induced mitochondrial dysfunction and restored renal tubular cells and mitochondrial morphology. CD36 knockout also restored mitochondrial fatty acid oxidation (FAO) and enhanced FAO-associated respiration in diabetic TECs. CD36 was found to alter cellular metabolic pathways in diabetic kidneys partly via PDK4 the -AMPK axis inactivation. Because CD36 protects against DKD by improving mitochondrial function and restoring FAO, it can serve as a potential therapeutic target.

Diagnosis of descending aorta-pulmonary venous fistula combined with pulmonary arteriovenous fistula by color Doppler ultrasound combined with CT: A case report.

Aorto-pulmonary venous fistula combined with pulmonary arteriovenous fistula is a rare condition with an unknown incidence. We experienced a case of descending aorto-pulmonary venous fistula combined with a pulmonary arteriovenous fistula, which was treated with pulmonary arteriovenous fistula embolization and improved.

Scd1 Deficiency in Early Embryos Affects Blastocyst ICM Formation through RPs-Mdm2-p53 Pathway.

Embryos contain a large number of lipid droplets, and lipid metabolism is gradually activated during embryonic development to provide energy. However, the regulatory mechanisms remain to be investigated. Stearoyl-CoA desaturase 1 (Scd1) is a fatty acid desaturase gene that is mainly involved in intracellular monounsaturated fatty acid production, which takes part in many physiological processes. Analysis of transcripts at key stages of embryo development revealed that Scd1 was important and expressed at an increased level during the cleavage and blastocyst stages. Knockout Scd1 gene by CRISPR/Cas9 from zygotes revealed a decrease in lipid droplets (LDs) and damage in the inner cell mass (ICM) formation of blastocyst. Comparative analysis of normal and knockout embryo transcripts showed a suppression of ribosome protein (RPs) genes, leading to the arrest of ribosome biogenesis at the 2-cell stage. Notably, the P53-related pathway was further activated at the blastocyst stage, which eventually caused embryonic development arrest and apoptosis. In summary, Scd1 helps in providing energy for embryonic development by regulating intra-embryonic lipid droplet formation. Moreover, deficiency activates the RPs-Mdm2-P53 pathway due to ribosomal stress and ultimately leads to embryonic development arrest. The present results suggested that Scd1 gene is essential to maintain healthy development of embryos by regulating energy support.

Early cleavage of preimplantation embryos is regulated by tRNAGln-TTG-derived small RNAs present in mature spermatozoa.

tRNA-derived small RNAs (tsRNAs) from spermatozoa could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation and demonstrated the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of antisense sequences into in vitro fertilized oocytes and subsequent single-cell RNA-seq of embryos, we identified a specific functional tsRNA group (termed here Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes and retrotransposons. We conclude that specific tsRNAs present in mature spermatozoa play significant roles in preimplantation embryo development.

ELOVL6 promoter binding sites directly targeted by sterol regulatory element binding protein 1 in fatty acid synthesis of goat mammary epithelial cells.

The elongation of long-chain fatty acid family member 6 (ELOVL6) gene plays an important role in the synthesis of long-chain saturated and monounsaturated fatty acids. Although some studies have revealed that ELOVL6 is the target of sterol regulatory element binding protein 1 (SREBP1; gene name SREBF1) in rodents, the mechanism underlying ELOVL6 regulation during lactation in dairy goats remains unknown. The present study aimed to investigate the transcriptional regulation mechanism of ELOVL6 in goat mammary epithelial cells (GMEC). We used PCR to clone and sequenced a 2,370 bp fragment of the ELOVL6 5' flanking region from goat genomic DNA. Deletion analysis revealed a core promoter region located -105 to -40 bp upstream of the transcriptional start site. Mutant sterol regulatory elements (SRE) 1 and 3 significantly reduced the ELOVL6 promoter activities in GMEC. Both SRE1 and SRE3 binding sites were required for the basal transcriptional activity of ELOVL6. Luciferase reporter assays showed that SREBF1 knockdown decreased ELOVL6 promoter activities in GMEC. Furthermore, SRE1 and SRE3 sites were simultaneously mutated completely abolished the stimulatory effect of SREBF1 and the repressive effect of linoleic acid on ELOVL6 gene promoter activities. Furthermore, chromatin immunoprecipitation assays confirmed that SREBP1 directly bound to SRE sites in the ELOVL6 promoter. In conclusion, these results indicate that SREBP1 regulates ELOVL6 transcription via the SRE elements located in the ELOVL6 promoter in goat mammary gland.

Latent Network Construction for Univariate Time Series Based on Variational Auto-Encode.

Time series analysis has been an important branch of information processing, and the conversion of time series into complex networks provides a new means to understand and analyze time series. In this work, using Variational Auto-Encode (VAE), we explored the construction of latent networks for univariate time series. We first trained the VAE to obtain the space of latent probability distributions of the time series and then decomposed the multivariate Gaussian distribution into multiple univariate Gaussian distributions. By measuring the distance between univariate Gaussian distributions on a statistical manifold, the latent network construction was finally achieved. The experimental results show that the latent network can effectively retain the original information of the time series and provide a new data structure for the downstream tasks.

Detecting epistasis within chromatin regulatory circuitry reveals CAND2 as a novel susceptibility gene for obesity.

BACKGROUND: Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS: We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI). Potential interacting SNP pairs were obtained based on Hi-C datasets, PreSTIGE (Predicting Specific Tissue Interactions of Genes and Enhancers) algorithm, and super enhancer regions. SNP × SNP analyses were next performed in three GWAS datasets, including 2286 unrelated Caucasians from Kansas City, 3062 healthy Caucasians from the Gene Environment Association Studies initiative, and 3164 Hispanic subjects from the Women's Health Initiative. RESULTS: A total of 16,643,227 SNP × SNP analyses were performed. Meta-analyses showed that two SNP pairs, rs6808450-rs9813534 (combined P = 2.39 × 10-9) and rs6808450-rs3773306 (combined P = 2.89 × 10-9) were associated with BMI after multiple testing corrections. Single-SNP analyses did not detect significant association signals for these three SNPs. In obesity relevant cells, rs6808450 is located in intergenic enhancers, while rs9813534 and rs3773306 are located in the region of strong transcription regions of CAND2 and RPL32, respectively. The expression of CAND2 was significantly downregulated after the differentiation of human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cells (P = 0.0241). Functional validation in the International Mouse Phenotyping Consortium database showed that CAND2 was associated with increased lean body mass and decreased total body fat amount. CONCLUSIONS: Detecting epistasis within chromatin regulatory circuitry identified CAND2 as a novel obesity susceptibility gene. We hope IACRC could facilitate the interaction analyses for complex diseases and offer new insights into solving the missing heritability problem.

Branched DNA Junction-Enhanced Isothermal Circular Strand Displacement Polymerization for Intracellular Imaging of MicroRNAs.

The microRNA profiles within living cells are informative for diagnosis and prognosis of human cancers. In the present work, we developed a new sensing strategy based on branched DNA junction-enhanced isothermal circular strand displacement polymerization (B-ICSDP) for the detection and intracellular imaging of microRNAs in living cells of interest. A circular DNA template consisting of three repetitive fragments serves as the scaffold for the self-assembly of sophisticated signaling probes, resulting a shrunk branched DNA junction. Target microRNA triggers the opening of molecular beacon, not only restoring the quenched fluorescence but also activating a circular polymerization-based strand displacement reaction. Thus, patulous branched DNA junction is abundantly formed, generating the amplified signal. It is noteworthy that great heaps of branched product assemblies can be also achieved in living cells, and the intracellular enzymatic assembly based strategy is able to be used to recognize specific microRNA-expressed cancer cells. Moreover, different microRNAs coexisting in the same living cells can be simultaneously screened without any interference from each other by confocal laser scanning microscopy. The measured data from confocal fluorescence imaging of different cancer cells demonstrates that the B-ICSDP-based system is a promising alternative for in vivo analysis of microRNAs in complicated biological samples.

Upregulation of UDP-Glucuronosyltransferases 1a1 and 1a7 Are Involved in Altered Puerarin Pharmacokinetics in Type II Diabetic Rats.

Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of puerarin in normal rats and rats with diabetes mellitus (DM), and the mechanism involved. DM was induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection. Plasma concentrations of puerarin in DM, HFD, and control rats were determined after intravenous (20 mg/kg) and oral administration (500 mg/kg) of puerarin, and pharmacokinetic parameters were estimated. The messenger RNA (mRNA) and protein expression levels of Ugt1a1 and Ugt1a7 in rat livers and intestines were measured using qRT-PCR and western blot, respectively. The area under the concentration⁻time curve and the clearance of puerarin in the DM rats statistically differed from those in the control rats (p <0.05) with both administration routes. The hepatic and intestinal gene and protein expressions of Ugt1a1 and Ugt1a7 were significantly increased in the DM rats (p <0.05). Therefore, the metabolic changes in diabetes could alter the pharmacokinetics of puerarin. This change could be caused by upregulated uridine diphosphate (UDP)-glucuronosyltransferase activity, which may enhance puerarin clearance, and alter its therapeutic effects.

Plasma Pharmacokinetic Determination of Canagliflozin and Its Metabolites in a Type 2 Diabetic Rat Model by UPLC-MS/MS.

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively. We identified three types of O-glucuronide metabolites (M5, M7 and M17), two kinds of oxidation metabolites (M8 and M9) and one oxidation and glucuronide metabolite (M16) using API 5600 triple-TOF-MS/MS. Following liquid⁻liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin and its metabolites were performed on a Waters XBridge BEH C18 column (100 × 2.1 mm, 2.5 µm) using 0.1% acetonitrile⁻formic acid (75:15, v/v) as the mobile phase at a flow rate of 0.7 mL/min. Selected ion monitoring transitions of m/z 462.00→191.10, 451.20→153.10, 638.10→191.10 and 478.00→267.00 were chosen to quantify canagliflozin, empagliflozin (IS), O-glucuronide metabolites (M5, M7 and M17), and oxidation metabolites (M9) using an API 5500-triple-MS/MS in the positive electrospray ionization mode. The validation of the method was found to be of sufficient specificity, accuracy and precision. The pathological condition of diabetes could result in altered pharmacokinetic behaviors of canagliflozin and its metabolites. The pharmacokinetic parameters (AUC0⁻t, AUC0⁻∞, CLz/F, and Vz/F) of canagliflozin were significantly different between the CTRL and DM group rats (p < 0.05 or p < 0.01), which may subsequently cause different therapeutic effects.

Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with bladder cancer: a meta-analysis.

PURPOSE: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy as compared with patients who underwent surgery alone. It has also been suggested as current standard of care in surgically-fit patients with MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival in patients with bladder cancer. SOURCE: PubMed, CENTRAL, and Embase were searched until November 22, 2016. Two-arm randomized controlled trials that compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the same local treatment without neoadjuvant chemotherapy were selected. Patients with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or squamous-cell carcinoma) were included. The primary outcome was overall survival (OS). PRINCIPAL FINDINGS: Of the 292 articles initially identified, 14 were included in the final analysis. Patients in the NAC group had similar OS as the local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No difference in progress-free survival between two groups was observed (P=0.725). Subgroup analysis showed that OS was similar in patients treated with NAC plus radiotherapy or cystectomy compared with patients who received local treatment alone. CONCLUSIONS: Platinum-based NAC was associated with similar survival benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can be drawn about the optimal platinum-based combination to be used in the neoadjuvant setting.

B-cell hub genes play a cardiovascular pathogenic role of in childhood obesity and Kawasaki disease as revealed by transcriptomics-based analyses.

The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990-1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.

High-throughput identification of meat ingredients in adulterated foods based on centrifugal integrated purification-CRISPR array.

Rapid, accurate, and sensitive analytical methods for the detection of food fraud are now an urgent requirement in the global food industry to ensure food quality. In response to this demand, a centrifugal integrated purification-CRISPR array for meat adulteration (CIPAM) was established. In detail, CIPAM system combines microneedles for DNA extraction and RAA-CRISPR/Cas12a integrated into a centrifugal microfluidic chip for the detection of meat adulteration. The RAA-CRISPR/Cas12a reaction reagents were pre-embedded into the different reaction chambers on the microfluidic chip to achieve the streamline of operations, markedly simplifying the detection process. The whole reaction was completed within 30 min with a detection limit of 0.1 % (w/w) in pig, chicken, duck, and lamb products. Referring to the results of the standard method, CIPAM system achieved 100 % accuracy. The automatic multiplex detection process implemented in the developed CIPAM system met the needs of food regulatory authorities.

Selective internal radiation therapy with yttrium-90 resin microspheres followed by anatomical hepatectomy: A potential curative strategy in advanced hepatocellular carcinoma.

About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34-year-old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium-90 resin microspheres was given. At three months post-SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post-surgery. This is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future.

Influence of repeated estrus synchronization treatment on hormone secretion, growth, and development of dairy goats.

In large-scale intensive farms, dairy goats often undergo frequent estrus synchronization (ES) treatment, which may result in a decline in reproductive performance; however, the underlying mechanism remains unclear. The present study aimed to investigate the effect of pregnant mare serum gonadotropin (PMSG) and progesterone (P4)-mediated ES treatment on fertility in dairy goats, while also identifying key metabolic and endocrine mechanisms that influence reproductive performance in does subjected to repeated ES treatment. Forty-eight Saanen does were randomly assigned to two groups (24 goats each) that received ES treatments either thrice fortnightly (3-PMSG) or once (1-PMSG) simultaneously with the third ES treatment of the 3-PMSG group during the breeding season. ES treatment was performed via the intravaginal insertion of a controlled internal drug release (CIDR) device impregnated with 300 mg P4, followed by 300 IU PMSG injections 48 h before CIDR withdrawal. Blood was collected to detect the level of hormones and blood biochemical indices. Additionally, estrus rate, fecundity rate, body weight, size, and lactation performance were measured. The results showed that repeated ES treatment markedly decreased the estrus rate and fecundity rate of goats. Among the does in all groups, there was no substantial difference in follicle stimulating hormone, luteinising hormone, gonadotropin-releasing hormone, melatonin, growth hormone, PMSG, total cholesterol, total protein, and glucose levels, as well as the body weight, body size, and lactation performance. Repeated ES treatment elevated estrogen (E2) levels 36, 48, and 72 h post-CIDR removal; increased P4 upon CIDR insertion; and raised PMSG antibody levels 24, 48, and 72 h post-CIDR removal. The results suggest that elevated anti-PMSG levels are the primary reason for the decline in ES efficiency, and that high E2 and P4 levels at some time points also impair reproductive performance. These findings provide novel insights into the metabolic effects of repeated PMSG stimulation in goats, guiding future reproductive hormone use in breeding practices.