Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma: A case report and review of literature.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease. CASE SUMMARY: A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours. CONCLUSION: The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion.

BACKGROUND: For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. AIM: To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. METHODS: A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. RESULTS: Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. CONCLUSION: Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.

Application of contrast-enhanced ultrasound in renal space-occupying lesion puncture biopsy.

OBJECTIVE: The purpose of this study was to investigate the utility of contrast-enhanced ultrasound (CEUS) in percutaneous renal space-occupying lesion puncture biopsy. METHODS: Ultrasound (US)-guided percutaneous needle biopsies were performed on 55 patients with renal space-occupying lesions, and the results were analyzed retrospectively. The US group included 36 patients receiving conventional US, and the contrast-enhanced ultrasound (CEUS) group included 22 patients, including 19 patients receiving CEUS directly and 3 patients receiving additional enhanced ultrasound due to the first conventional ultrasound puncture failure. The relevant data were subjected to statistical analysis. RESULTS: The results of this study showed that the successful rate of obtaining effective tissue (100% vs. 75%) and the puncture accuracy (100% vs. 88.89%) in CEUS group were significantly higher than those in US group (P < 0.05). CEUS-guided puncture biopsy of renal mass, especially in the case of urothelial carcinoma of the renal pelvis, outperforms conventional ultrasound, and the difference was statistically significant (P < 0.05). CONCLUSION: Percutaneous renal space-occupying lesion puncture biopsies aided by CEUS yield more effective tissue and improved puncture accuracy.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound: Correlation with angiogenesis and prognostic significance.

BACKGROUND: Ultrasound is a vital tool for the diagnosis and management of colorectal cancer (CRC). Contrast-enhanced ultrasound (CEUS) is a non-invasive, safe, and cost-effective method for evaluating tumour blood vessels, that play a crucial role in tumour growth and progression. AIM: To explore CEUS's role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis. METHODS: This study prospectively enrolled 100 patients with CRC confirmed by histopathology. All patients received preoperative CEUS examinations. Quantitative parameters, such as peak intensity (PI), time to peak (TTP), and area under the curve (AUC), were derived from time-intensity curve (TIC) analysis. Tumour tissue samples were obtained during surgery and examined immunohistochemically to assess the expression of angiogenesis markers, including vascular endothelial growth factor (VEGF) and microvessel density (MVD). The correlation between CEUS parameters, angiogenesis markers, and clinicopathological features was evaluated using appropriate statistical tests. RESULTS: Quantitative CEUS parameters (PI, TTP, and AUC) showed significant correlations with VEGF expression (P < 0.001) and MVD (P < 0.001), indicating a strong link between tumour blood vessels and angiogenesis. Increased PI, reduced TTP, and expanded AUC values were significantly related to higher tumour stage (P < 0.001), lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). Furthermore, these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis (P < 0.001). CONCLUSION: CEUS has a high potential in guiding treatment planning and predicting patient outcomes. However, more comprehensive, multicentre studies are required to validate the clinical utility of CEUS in CRC management.

Liquid Chromatography-Tandem Mass Spectrometry Detection of Human and Veterinary Drugs and Pesticides in Surface Water.

Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C18 column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L-1) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L-1. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L-1. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.

Tyrosine phosphorylation of IRF3 by BLK facilitates its sufficient activation and innate antiviral response.

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.

Primary intra-abdominal paraganglioma: A case report.

BACKGROUND: Paragangliomas are rare neuroendocrine tumors. We hereby report a case of a localized paraganglioma found in the abdominal cavity, and review the relevant literature to improve the understanding of this disease. CASE SUMMARY: A 29-year-old Chinese female patient was referred to our hospital due to an abdominal mass found on physical examination. Imaging revealed a mass in the left upper abdomen, suggestive of either a benign stromal tumor or an ectopic accessory spleen. Laparoscopic radical resection was subsequently performed, and histopathological analysis confirmed the diagnosis of a paraganglioma. The patient was followed up 3 months post-operation, and reported good recovery with no metastasis. CONCLUSION: Radical resection can effectively treat intra-abdominal paragangliomas, with few side effects and low recurrence risk. In addition, early and accurate diagnosis and timely intervention are essential for the prognosis of this disease.

Patient-controlled intravenous administration of dexmedetomidine with nalbuphine versus sufentanil for post cesarean delivery analgesia: A retrospective observational study.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 µg/kg/h DEX in combination with 0.03 µg/kg/h SUF in Group I (n = 150) or 0.11 µg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

E3 ubiquitin ligase TRIM55 promotes metastasis of gastric cancer cells by mediating epithelial-mesenchymal transition.

BACKGROUND: Gastric cancer (GC) is considered a major global health problem. The role of TRIM55, a member of the three-domain protein family, in GC is unknown. AIM: To determine the expression of TRIM55 in GC tissues and its relationship with clinicopathological characteristics, and to investigate the effects of TRIM55 on the malignant biological behavior of GC cells. METHODS: Differential expression of TRIM55 in GC and para-cancer tissues was detected by immunohistochemistry, and the relationship between TRIM55 level and clinicopathological characteristics and prognosis was analyzed. Gain-of-function, loss-of-function, cell counting kit-8 assay, colony formation, transwell assay, wound healing assay, and western blot analysis were used to assess the potential role of TRIM55 in the development of GC. RESULTS: TRIM55 expression was significantly increased in GC tissues compared with adjacent normal tissues. High expression of TRIM55 was associated with advanced pathological stage and poor prognosis. Overexpression of TRIM55 promoted invasion and metastasis of GC cells in vitro by regulating epithelial-mesenchymal transition (EMT), whereas knockdown of TRIM55 had the opposite effect. Our data showed that TRIM55 is highly expressed in GC tissues, and is associated with poor prognosis. TRIM55 plays the role of an oncogene in GC, and it promotes metastasis of GC through the regulation of EMT. CONCLUSION: TRIM55 may be a possible target for the diagnosis and prognosis of GC patients.

[Comparative study of two elastic fixation systems in single-segment lumbar disc herniation surgery for nucleus pulposus extraction].

OBJECTIVE: To investigate the clinical application of two elastic pedicle internal fixation systems in single-segment lumbar disc herniation fenestration. METHODS: A retrospective analysis of 64 patients with lumbar intervertebral disc herniation treated by surgery from June 2019 to March 2021. According to the different elastic fixation systems placed during the operation, the patients were divided into ordinary pedicle screw elastic rod link group (elastic rod group) and a special elastic pedicle screw rigid rod fixed connection group (elastic screw group). There were 33 cases in the elastic rod group, including 18 males and 15 females, aged from 30 to 69 years old with an average of(49.18±10.23) years old;and 31 cases in the elastic screw group, including 16 males and 15 females, aged from 32 to 68 with an average of (49.81±9.24) years old. The operation time, intraoperative blood loss, postoperative wound drainage, and postoperative landing time of the two groups were recorded separately. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, and Oswestry Disability Index (ODI) were compared before and 3, 12 months after operation. The height of the adjacent vertebral space on the lateral DR film before and 12 months after the operation was measured. The clinical efficacy was evaluated by Macnab standard. RESULTS: All the patients successfully completed the operation, and were followed up. The operation time, intraoperative blood loss, postoperative wound drainage and postoperative landing time in the elastic rod group were(63.73±12.01) min, (89.55±16.07) ml, (81.67±16.00) ml, (3.45±0.75) d , while in the elastic nail group was (62.96±11.54) min, (88.35±17.14) ml, (82.29±15.40) ml, (3.29±0.78) d, the difference was not statistically significant. The symptoms of low back pain and lower extremity numbness were significantly improved in all patients after operation. There was no significant difference in VAS, JOA score and ODI between the two groups before and after surgery (P>0.05). At 12 months after operation, there was no significant difference in the height of the adjacent vertebral space between the upper adjacent vertebral body and the same segment before operation(P>0.05), and there was no significant difference between the groups before and after the operation. According to Macnab criteria, the elastic rod group was excellent in 30 cases, good in 2 cases, fair in 1 case, while the elastic nail group was excellent in 29 cases, good in 2 cases, fair in 0 cases, and there was no significant difference(Z=-0.42, P=0.68). CONCLUSION: In fenestrated nucleus pulposus extraction for lumbar disc herniation, the two elastic pedicle internal fixation systems are equally effective and can be used. The elastic screw internal fixation system has certain advantages when the distance between the two vertebral bodies is short, and the elastic rod cannot be placed or is difficult to be placed, and it is more widely used.

Hepatic resection prolongs overall survival in the selected patients with nasopharyngeal carcinoma liver metastases.

BACKGROUND: The role of surgery in nasopharyngeal carcinoma liver metastases (NCLM) remains elusive, and the current application is limited. We aim to investigate whether hepatic resection (HR) of NCLM improves survival compared with non-hepatic resection (NHR) treatment. METHODS: One hundred and thirty-three patients with NCLM from 2007 to 2017 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes. RESULTS: After PSM the median overall survival (OS) and the 1, 3 and 5-year OS rates in HR group were 32.60 months, 86.2%, 37.3% and 37.3%, respectively; while for NHR group these values were 19.57 months, 61.5%, 12.9% and 2.9%, respectively (P = 0.008). Multivariate analysis indicated hepatitis B virus infection (P = 0.029) and hepatic resection (P = 0.018) were independent prognostic factors. CONCLUSION: Our study revealed that hepatectomy yields a survival benefit safely compared with systemic treatments, especially for patients with the size of largest metastasis < 5 cm, unilobar distribution of liver tumor and received unanatomical hepatectomy.

LncRNA cancer susceptibility 20 regulates the metastasis of human gastric cancer cells via the miR-143-5p/MEMO1 molecular axis.

BACKGROUND: Gastric cancer (GC) is considered as one of the most widespread malignancies. Emerging evidence has shown that lncRNAs can function as important oncogenes or tumor suppressors during GC progression. AIM: To investigate the effect and mechanism of lncRNA cancer susceptibility 20 (CASC20) in the proliferation and metastasis of GC cells. METHODS: Data mining and clinical samples were used to evaluate the expression of CASC20 in GC and adjacent tissues. CASC20 was down-regulated in GC cells by short-interfering RNA. Cell proliferation was evaluated by CCK-8 assay, and cell migration and invasion were detected by wound healing and Transwell assays. The expressions of proteins related to epithelial-mesenchymal transition were detected by western blot assay. RESULTS: The expression of CASC20 was increased in GC tumor tissues and various GC cell lines. High CASC20 expression was correlated with a high risk of lymphatic metastasis and poor prognosis in GC patients. In vitro assays showed that silencing CASC20 reduced cell proliferation, migration, and invasion in GC cells. Mechanistic studies revealed that CASC20 exhibits oncogenic functions by regulating MEMO1 expression through competitive endogenous binding to miR-143-5p, leading to induction of epithelial-mesenchymal transition. CONCLUSION: Our findings indicate that CASC20 serves as a tumor promoter by regulating metastasis in GC via the miR-143-5p/MEMO1 axis. CASC20 may be a potential therapeutic target for GC.

The current scenario on anticancer activity of artemisinin metal complexes, hybrids, and dimers.

Cancer, the most significant cause of morbidity and mortality, has already posed a heavy burden on health care systems globally. In recent years, cancer treatment has made a significant breakthrough, but cancer cells inevitably acquire resistance, and the efficacy of the treatment is greatly reduced as the tumor progresses. To overcome the above issues, novel chemotherapeutics are needed urgently. Artemisinin and its derivatives-sesquiterpene lactone compounds possessing a unique peroxy bridge moiety-exhibit excellent safety and tolerability profiles. Mechanistically, artemisinin derivatives can promote cancer cell apoptosis, induce cell cycle arrest and autophagy, and inhibit cancer cell invasion and migration. Accordingly, artemisinin derivatives demonstrate promising anticancer efficacy both in vitro and in vivo, and even in clinical Phase I/II trials. The purpose of the present review article is to provide an emphasis on the current scenario (January 2017-January 2022) of artemisinin derivatives with potential anticancer activity, inclusive of artemisinin metal complexes, hybrids, and dimers. The structure-activity relationships and mechanisms of action are also discussed to facilitate the further rational design of more effective candidates.

Network pharmacology and in vitro experimental verification to explore the mechanism of Sanhua decoction in the treatment of ischaemic stroke.

CONTEXT: Stroke is an illness with high morbidity, disability and mortality that presents a major clinical challenge. Sanhua decoction (SHD) has been widely used to treat ischaemic stroke in the clinic. However, the potential mechanism of SHD remains unknown. OBJECTIVE: To elucidate the multitarget mechanism of SHD in ischaemic stroke through network pharmacology and bioinformatics analyses. MATERIALS AND METHODS: Network pharmacology and experimental validation approach was used to investigate the bioactive ingredients, critical targets and potential mechanisms of SHD against ischaemic stroke. Four herbal names of SHD, 'ischemic stroke' or 'stroke' was used as a keyword to search the relevant databases. SH-SY5Y cells were treated with various concentrations of SHD (12.5, 25, 50 or 100 µg/mL) for 4 h, exposed to oxygen and glucose deprivation (OGD) for 1 h, then reoxygenation for 24 h. The cell viability was detected by MTT, the lactate dehydrogenase (LDH) was evaluated by ELISA, and protein expression was detected by western blots. RESULTS: SHD treatment increased the survival rate from 65.9 ± 4.3 to 85.56 ± 5.7%. The median effective dose (ED50) was 47.1 µg/mL, the LDH decreased from 288.0 ± 12.0 to 122.8 ± 9.1 U/L and the cell apoptosis rate decreased from 33.6 ± 1.8 to 16.3 ± 1.2%. Western blot analysis revealed that SHD increased the levels of p-PI3k, p-Akt and p-CREB1, and decreased the expression of TNF-α and IL-6. DISCUSSION AND CONCLUSIONS: This study suggests that SHD protects against cerebral ischaemic injury via regulation of the PI3K/Akt/CREB1 and TNF pathways.

Aluminum-tolerant, growth-promoting endophytic bacteria as contributors in promoting tea plant growth and alleviating aluminum stress.

Unlike that of other crops, the growth of tea plants can be promoted by aluminum, but its regulation mechanism remains unclear. Some endophytes can also promote growth of plant hosts. In this paper, tea roots treated with aluminum were used to study the growth-promoting traits and aluminum tolerance of endophytes. Meta-16S rDNA analysis revealed that Burkholderia was enriched in tea roots after aluminum treatment, and it was the dominant strain for hydroponic tea roots and field tea roots. Actinomycetes constituted the dominant strains in hydroponic tea seedlings treated with aluminum. Sixteen endophytic bacteria, including 12 strains of Firmicutes, 2 strains of Proteobacteria and 2 strains of Actinomycetes, were isolated and identified from hydroponic tea roots treated with different aluminum concentrations. Growth-promoting activity analysis showed that the isolated endophytic bacteria all had more than one plant growth-promoting trait. Among them, B4 (Bacillus nealsonii), B8 (Brevibacterium frigoritolerans) and A2 (Nocardia nova) bacteria each had three growth-promoting traits. Aluminum tolerance ability analysis indicated that endophyte A1 (Leifsonia shinshuensis) had the strongest aluminum tolerance ability, up to 200 mg l-1 aluminum. Plant-bacteria interactions showed that endophytes A1, A2 and B4 and their synthetic community all had a growth-promoting effect on the growth of wheat lateral roots. Moreover, endophytes A1 and B4 alleviated aluminum stress in wheat. Endophyte A1 also promoted the growth of tea cuttings, especially lateral roots, with/without aluminum. Taken together, aluminum enhanced the distribution of aluminum-tolerant and growth-promoting bacteria, thereby promoting the growth of tea roots. This study provides a new aspect for research on the mechanism by which aluminum promotes tea plant growth.

Cardioprotective effects of Amentoflavone by suppression of apoptosis and inflammation on an in vitro and vivo model of myocardial ischemia-reperfusion injury.

Inflammation modulation is currently considered a promising therapeutic strategy to counteract the burden of cardiovascular disease. Amentoflavone (AME) is a natural biflavone with two apigenin molecules that, possess promising anti-inflammatory, anti-oxidative, and anti-cancer properties. In the present study, we aimed to investigate the effects of AME on myocardial ischemia-reperfusion injury in vivo and in vitro, and to elucidate the underlying mechanism. Our results showed that AME significantly reduced the levels of LDH, CK-MB, IL-6, IL-1ß, and TNF-α after hypoxia (H) 12 h/reoxygenation (R) 4 h treatment, and significantly increased the cell survival rate of H9c2 cardiomyocytes induced by H/R and inhibited their apoptosis rate. AME (25, 50, 100 mg·kg-1·d-1, i.g.) or a positive control drug diltiazem (DIZ) (16 mg·kg-1·d-1, i.g.) was used as pretreatment for 7 days; the myocardial ischemia-reperfusion(I/R) model was established. TTC staining results showed that the infarct volume was significantly reduced after AME and DIZ treatment. Oral administration of AME dose-dependently ameliorated I/R injury-induced increase in pro-inflammatory factors (IL-6, IL-1ß, and TNF-α) and levels of LDH and CK-MB. Results of TUNEL and HE staining showed that the I/R model had more induced apoptosis, but could be effectively reduced by pretreatment with AME. After surgery, the heart of the rat was examined via western blotting to detect inflammation-related proteins. Compared with the sham group, the p-AKT in the I/R group was significantly reduced and the content of p-NF-κBp65 was significantly increased. However, these changes could be reversed by AME treatment. DIZ treatment exerted similar beneficial effects in I/R rats as the high dose of AME did. This study highlights the excellent therapeutic potential of AME for managing myocardial ischemia-reperfusion injury.

Functional Analyses of Flavonol Synthase Genes From Camellia sinensis Reveal Their Roles in Anther Development.

Flavonoids, including flavonol derivatives, are the main astringent compounds of tea and are beneficial to human health. Many researches have been conducted to comprehensively identify and characterize the phenolic compounds in the tea plant. However, the biological function of tea flavonoids is not yet understood, especially those accumulated in floral organs. In this study, the metabolic characteristics of phenolic compounds in different developmental stages of flower buds and various parts of the tea flower were investigated by using metabolomic and transcriptomic analyses. Targeted metabolomic analysis revealed varying accumulation patterns of different phenolic polyphenol compounds during flowering; moreover, the content of flavonol compounds gradually increased as the flowers opened. Petals and stamens were the main sites of flavone and flavonol accumulation. Compared with those of fertile flowers, the content of certain flavonols, such as kaempferol derivatives, in anthers of hybrid sterile flowers was significantly low. Transcriptomic analysis revealed different expression patterns of genes in the same gene family in tea flowers. The CsFLSb gene was significantly increased during flowering and was highly expressed in anthers. Compared with fertile flowers, CsFLSb was significantly downregulated in sterile flowers. Further functional verification of the three CsFLS genes indicated that CsFLSb caused an increase in flavonol content in transgenic tobacco flowers and that CsFLSa acted in leaves. Taken together, this study highlighted the metabolic properties of phenolic compounds in tea flowers and determined how the three CsFLS genes have different functions in the vegetative and reproductive organs of tea plants. Furthermore, CsFLSb could regulated flavonol biosynthesis in tea flowers, thus influencing fertility. This research is of great significance for balancing the reproductive growth and vegetative growth of tea plants.