Transcatheter arterial embolization with N-butyl cyanoacrylate for postoperative hemorrhage treatment following pancreatoduodenectomy.

PURPOSE: Postoperative hemorrhage (PPH) is a severe complication of pancreatoduodenectomy (PD) with a mortality rate of 5-20.2% and mortality due to hemorrhage of 11-58%. Transcatheter arterial embolization (TAE) has been widely recommended for PPH, however, TAE with N-butyl cyanoacrylate (NBCA) for PPH treatment has been reported rarely. Therefore, this study aimed to evaluate the safety and efficacy of TAE with NBCA for PPH treatment following PD. METHODS: This retrospective study included 14 male patients (mean age, 60.93 ± 10.97 years) with postoperative hemorrhage following PD treated with TAE using NBCA as the main embolic agent from October 2019 to February 2022. The clinical data, technical and success rate, and complications were analyzed. RESULTS: Among the 14 patients who underwent TAE, the technical and clinical success rates were 100 and 85.71%, respectively. Angiography revealed contrast extravasation in 12 cases and a pseudoaneurysm in 3 cases. One patient developed a serious infection and died 2 days after the TAE. CONCLUSION: TAE with NBCA for PPH treatment following PD, especially for massive hemorrhage caused by a pancreatic fistula, biliary fistula, or inflammatory corrosion, can result in rapid and effective hemostasis with high safety.

Comparison of Polyvinyl Alcohol Versus Combination of Lipiodol-Bleomycin Emulsion and NBCA-Lipiodol Emulsion for Renal Angiomyolipoma Embolization: A Prospective Randomized Study.

BACKGROUND. Consensus is lacking regarding optimal embolic agents for transcatheter arterial embolization (TAE) of renal angiomyolipomas (AMLs). OBJECTIVE. The purpose of our study was to compare the safety and efficacy of TAE with polyvinyl alcohol (PVA) and TAE with a combination of ethiodized oil (Lipiodol)-bleomycin emulsion and N-butyl cyanoacrylate (NBCA)-Lipiodol emulsion for the treatment of patients with large or symptomatic AMLs. METHODS. This prospective study enrolled patients referred for TAE of a large (> 4 cm) or symptomatic renal AML from July 2007 to December 2018. Patients were randomized to undergo TAE using PVA particles or a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Patients underwent serial clinical follow-up visits and follow-up CT or MRI examinations after TAE. Outcomes were compared between groups. RESULTS. Seventy-eight patients were enrolled. After exclusions, the analysis included 72 patients (15 men, 57 women; mean age, 35.0 years; 51 patients with hematuria, 66 patients with flank pain): 35 patients were randomized to treatment by PVA and 37 were randomized to treatment by a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Complete occlusion of all angiographically visible arterial supply was achieved in all patients. No major adverse event occurred in any patient. The mean follow-up after TAE was 77 ± 45 (SD) months (range, 37-180 months). The frequency of resolution of hematuria after initial TAE without recurrence was greater after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 80.0%, respectively; p = .03). At 12-month follow-up, the frequency of complete resolution of flank pain was higher after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 75.0%, p = .03). Mean reduction in AML volume at 36 months or longer after TAE versus at baseline was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than in those treated by PVA (98.0% vs 85.7%, respectively; p = .04). The frequency of complete response by modified RECIST (mRECIST) criteria at 36 months or longer after TAE was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (94.6% vs 74.3%, p = .04). The rate of repeat TAE was higher among patients treated by PVA than among those treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion (25.7% vs 8.1%, p = .04). CONCLUSION. Superior outcomes after TAE of AML were achieved using Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than using PVA. CLINICAL IMPACT. TAE using a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion is a safe and effective treatment option for large or symptomatic AMLs. TRIAL REGISTRATION. Chinese Clinical Trial Registry ChiCTR2100053296.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

Antibiotic pollution promotes dominance by harmful cyanobacteria: A case study examining norfloxacin exposure in competition experiments.

Cyanobacterial harmful algal blooms (cyanoHABs) in freshwater lakes across the globe are often combined with other stressors. Pharmaceutical pollution, especially antibiotics in water bodies, poses a potential hazard in aquatic ecosystems. However, how antibiotics influence the risk of cyanoHABs remains unclear. Here, we investigated the effects of norfloxacin (NOR), one of the most widely used antibiotics globally, to a bloom-forming cyanobacterium (Microcystis aeruginosa) and a common green alga (Scenedesmus quadricauda), under both mono- and coculture conditions. Taxon-specific responses to NOR were evaluated in monoculture. In addition, the growth rate and change in ratio of cyanobacteria to green algae when cocultured with exposure to NOR were determined. In monocultures of Microcystis, exposure to low concentrations of NOR resulted in decreases in biomass, chlorophyll a and soluble protein content, while superoxide anion content and superoxide dismutase activity increased. However, NOR at high concentration only slightly affected Scenedesmus. During the co-culture trials of Microcystis and Scenedesmus, the 5 µg · L-1 NOR treatment increased the ratio of Microcystis to co-cultured Scenedesmus by 47.2%. Meanwhile, although Scenedesmus growth was enhanced by 4.2% under NOR treatment in monoculture, it was conversely inhibited by 63.4% and 38.2% when co-cultured with Microcystis with and without NOR, respectively. Our results indicate that antibiotic pollution has a potential risk to enhance the perniciousness of cyanoHABs by disturbing interspecific interaction between cyanobacteria and green algae. These results reinforce the need for scientists and managers to consider the influence of xenobiotics in shaping the outcome of interactions among multiple species in aquatic ecosystems.

Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Bleomycin-Eluting versus Bland Microspheres in a Canine Model.

PURPOSE: To prospectively assess safety and efficacy of prostatic artery embolization (PAE) with bleomycin-eluting microspheres for benign prostatic hyperplasia (BPH) in a canine model. MATERIALS AND METHODS: Twelve adult male beagles (mean age, 1.6 y ± 0.2; range, 1.2-2.0 y) were randomly assigned to group A (n = 6; PAE with bleomycin-eluting 30-60-µm HepaSphere microspheres) and group B (n = 6; PAE with bland 30-60-µm HepaSphere microspheres) between April 2017 and November 2018. Plasma bleomycin concentration in group A was measured within 7 days. Prostate volume (PV) and ischemic volume after PAE were measured by magnetic resonance imaging. Prostates and adjacent organs were harvested after the last magnetic resonance study and histopathologically examined. RESULTS: Plasma bleomycin concentration peaked at 10 minutes at 2,055.0 ng/mL ± 606.1 and lasted for 1,440 min at low levels after PAE. PV reduction percentage was greater in group A than in group B at 1 month (74.1% ± 4.3 vs 63.7% ± 3.5; P = .006) and 3 months (61.5% ± 6.7 vs 46.1% ± 3.8; P = .001) after PAE. Proportion of prostate ischemic volume was greater in group A than in group B (75.3% ± 3.0 vs 62.0% ± 7.1; P = .006) at 1 month after PAE. Proportion of prostate ischemic volume at 1 month positively correlated with PV percentage reduction at 3 months in group A (r = 0.840, P = .036) and group B (r = 0.844, P = .035). There were no complications or nontarget embolization to surrounding organs after the procedures. CONCLUSIONS: In a canine model, PAE with bleomycin-eluting microspheres was feasible and well tolerated and caused ischemic necrosis and reduction in PV.

Effectiveness of Contrast-enhanced MR Angiography for Visualization of the Prostatic Artery prior to Prostatic Arterial Embolization.

Background A major technical challenge of prostatic arterial embolization (PAE) is the identification and catheterization of the prostatic arteries (PAs). Recently, MR angiography has been shown to help visualize PAs, but the clinical utility of MR angiography for this purpose is not known. Purpose To determine the efficacy of contrast material-enhanced MR angiography in identifying the PA and to evaluate its role in PAE for benign prostatic hyperplasia (BPH). Materials and Methods In this prospective study, 100 consecutive men who were scheduled to undergo PAE for BPH from January 2015 to May 2017 were assigned by using a randomized block design to either group A (n = 50; mean age, 71.7 years ± 11.9 [standard deviation]) without MR angiography or group B (n = 50; mean age, 72.3 years ± 12.2) with MR angiography prior to PAE. MR angiography findings of the PA anatomy were compared with those of digital subtraction angiography (DSA). The Student t test and Wilcoxon rank-sum test were used to compare the differences between the parameters indicating the performance of PAE. Results The mean age of the 100 men in the study was 72.0 years ± 11.8 (range, 51-88 years). Compared with DSA as the reference standard, MR angiography identified PAs with a sensitivity of 91.5% (97 of 106) and a positive predictive value of 100% (97 of 97). With the knowledge of tube obliquity and anatomy, group B had lower procedure times than group A (82.3 minutes ± 5.4 vs 123.9 minutes ± 12.4, P < .001) and shorter fluoroscopy times (13.8 minutes ± 2.7 vs 28.5 minutes ± 8.0, P < .001). Additionally, radiation dose was reduced for group A versus group B, from a median of 920 to 339 mGy (P = .004). Conclusion Contrast-enhanced MR angiography can accurately show anatomy for the prostate arteries, leading to shorter prostatic artery embolization times and lower radiation dose than when preprocedural prostate MR angiography is not performed. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Prince in this issue.

Comparison of Clinical Outcomes of Prostatic Artery Embolization with 50-µm Plus 100-µm Polyvinyl Alcohol (PVA) Particles versus 100-µm PVA Particles Alone: A Prospective Randomized Trial.

PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-µm and 100-µm polyvinyl alcohol (PVA) particles versus 100-µm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-µm plus 100-µm PVA particles (group A) or 100-µm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Qmax to < 7 mL/s. RESULTS: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Qmax (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group. CONCLUSIONS: PAE with 50-µm plus 100-µm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-µm PVA particles alone.

Effects of oxygen chemical potential on the anisotropy of the adsorption properties of Zr surfaces.

The anisotropy of metal oxidation is a fundamental issue, and the oxidation of Zr surfaces also attracts much attention due to the application of Zr alloys as cladding materials for nuclear fuels in nuclear power plants. In this study, we systematically investigate the diagram of O adsorption on low Miller index Zr surfaces by using first-principles calculations based on density functional theory calculations. We find that O adsorption on the basal surface, Zr(0001), is more favourable than that on the prism surfaces, Zr(112[combining macron]0) and Zr(101[combining macron]0), under strong O-reducing conditions, while O adsorption on the prism surface is more favourable than that of the basal surface under weak O-reducing conditions and the O-rich conditions. Our findings reveal that the anisotropy of adsorption properties of O on the Zr surfaces is dependent on the O chemical potential in the environment. Furthermore, the ability of the prism for O adsorption is stronger than that of the basal surface under the O-rich condition, which is consistent with the experimental observation that the oxidation of the prism Zr surface is easier than that of the basal surface. Systematic surveys show the adsorption ability of the surface under strong O-reducing conditions is determined by the low coordination numbers of surface atoms and surface geometrical structures, while the adsorption ability of the surface under weak O-reducing conditions and O-rich conditions is only determined by the low coordination number of surface atoms. These results can provide an atomic scale understanding of the initial oxidation of Zr surfaces, which inevitably affects the growth of protective passivation layers that play critical roles in the corrosion resistance of Zr cladding materials.

Seminal vesicle abnormalities following prostatic artery embolization for the treatment of benign prostatic hyperplasia.

BACKGROUND: Prostatic artery embolization (PAE) has been proved effective in the treatment of lower urinary tracts (LUTS) secondary to benign prostatic hyperplasia (BPH) with low complications, and most of the them are due to non-target embolization of adjacent organs, such as bladder, rectum, seminal vesicles and penis. Aim of this study was to present seminal vesicle (SV) abnormalities following prostatic artery embolization (PAE) for the treatment of symptomatic benign prostatic hyperplasia. METHODS: We reviewed 139 BPH patients who received PAE during the period of February 2009 and January 2015 at a single institution, highlighting seminal vesicle abnormalities and their clinical relevance after PAE. PAE was performed using 90~ 180-µm (mean 100-µm) polyvinyl alcohol foam particles. RESULTS: Nine of 139 patients with SV abnormalities (6.5%) were identified by magnetic resonance imaging (MRI), including subacute haemorrhage in 3 patients and ischaemia in 6 patients. Using cone-beam computed tomography (CB-CT), the seminal vesicle arteries were identified 8 of the 9 patients. All 9 patients complained of a few episodes of mild haematospermia during the 1-4 weeks after PAE; the haematospermia disappeared spontaneously without any treatment. CONCLUSION: SV haemorrhage and ischaemia may occur after PAE, and these patients may present with transient and self-limited haematospermia.

Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. METHODS: We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. FINDINGS: Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (p<0·0001). We recorded no statistical differences in other adverse reactions and laboratory tests across groups. Glycoprotein-specific antibody titres were significantly increased in participants in the low-dose and high-dose vaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; p<0·0001) and day 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2], respectively; p<0·0001). T-cell responses peaked at day 14 at a median of 465·0 spot-forming cells (IQR 180·0-1202·5) in participants in the low-dose group and 765·0 cells (400·0-1460·0) in those in the high-dose group. 21 (18%) participants had mild fever (n=9 in the placebo group, n=6 in the low-dose group, and n=6 in the high-dose group). No serious adverse events were recorded. INTERPRETATION: Our findings show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days. FUNDING: China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes.

Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population.

AIM: Adiponectin has been implicated in the development of chronic obstructive pulmonary disease (COPD). The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. METHODS: Ten single-nucleotide polymorphisms (SNP) in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models. RESULTS: Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, P=0.022). The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC (P<0.05). Haplotypes GC in block 1 (rs4783244-rs12922394) as well as GTAC and ATGT in block 3 (rs4783266-rs11640522-rs11646849-rs11860282) significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 (rs11646011- rs11640875) and ATGC in block 3 were protective against COPD. CONCLUSION: CDH13 genetic variants determine Chinese individuals' susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD.

Anti-phytopathogenic activity of sporothriolide, a metabolite from endophyte Nodulisporium sp. A21 in Ginkgo biloba.

Phytopathogenic fungi such as Rhizoctonia solani and Sclerotinia sclerotiorum caused multiple plant diseases resulting in severe loss of crop production. Increasing documents endorsed that endophytes are a striking resource pool for numerous metabolites with various bioactivities such as anti-fungal. Here we reported the characterization and anti-phytopathogenic activity of sporothriolide, a metabolite produced by Nodulisporium sp. A21-an endophytic fungus in the leaves of Ginkgo biloba. Among the total twenty-five endophytic fungi isolated from the healthy leaves of G. biloba, the fermentation broth (FB) of the strain A21 was found potently inhibitory activity against R. solani and S. sclerotiorum using mycelia growth inhibition method. A21 was then identified as Nodulisporium sp., the asexual stage of Hypoxylon sp., by microscopic examination and ITS rDNA sequence data comparison. Under the bioassay-guided fractionation, sporothriolide was isolated from the petroleum ether extract of the FB of A21, whose structure was established by integrated interpretation of HR-ESI-MS and (1)H- and (13)C-NMR. Furthermore, the crystal structure of sporothriolide was first reported. In addition, sporothriolide was validated to be potently antifungal against R. solani, S. sclerotiorum and inhibit conidium germination of Magnaporthe oryzae in vitro and in vivo, indicating that it could be used as a lead compound for new fungicide development.

Catalytic asymmetric 1,2-addition of α-isothiocyanato phosphonates: synthesis of chiral ß-hydroxy- or ß-amino-substituted α-amino phosphonic acid derivatives.

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of ß-hydroxy-α-amino phosphonic acid and α,ß-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.

Natural compounds target programmed cell death (PCD) signaling mechanism to treat ulcerative colitis: a review.

Ulcerative colitis (UC) is a nonspecific inflammatory bowel disease characterized by abdominal pain, bloody diarrhea, weight loss, and colon shortening. However, UC is difficult to cure due to its high drug resistance rate and easy recurrence. Moreover, long-term inflammation and increased disease severity can lead to the development of colon cancer in some patients. Programmed cell death (PCD) is a gene-regulated cell death process that includes apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. PCD plays a crucial role in maintaining body homeostasis and the development of organs and tissues. Abnormal PCD signaling is observed in the pathological process of UC, such as activating the apoptosis signaling pathway to promote the progression of UC. Targeting PCD may be a therapeutic strategy, and natural compounds have shown great potential in modulating key targets of PCD to treat UC. For instance, baicalin can regulate cell apoptosis to alleviate inflammatory infiltration and pathological damage. This review focuses on the specific expression of PCD and its interaction with multiple signaling pathways, such as NF-κB, Nrf2, MAPK, JAK/STAT, PI3K/AKT, NLRP3, GPX4, Bcl-2, etc., to elucidate the role of natural compounds in targeting PCD for the treatment of UC. This review used (ulcerative colitis) (programmed cell death) and (natural products) as keywords to search the related studies in PubMed and the Web of Science, and CNKI database of the past 10 years. This work retrieved 72 studies (65 from the past 5 years and 7 from the past 10 years), which aims to provide new treatment strategies for UC patients and serves as a foundation for the development of new drugs.

Supramolecular Chemotherapy: Complexation by Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Nitrogen Mustard to Normal Cells and Enhancing Its Antitumor Efficiency against Breast Cancer.

Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load chemotherapy medication, nitrogen mustard (NM), via forming a direct host-guest complex, as this helps to decrease the cytotoxicity of NM on normal mammary epithelial cells. Attributed to the stronger complexation ability of CP6A for endogenous spermine (SPM) than for NM, the complexed NM could be competitively released from the CP6A cavity via replacement with SPM. This chemotherapy strategy performed well in vitro and in vivo for SPM-overexpressed cancers. In comparison with free NM, antitumor efficiency of NM/CP6A was significantly enhanced, which originated from the synergistic effect of competitive release of NM and simultaneous trapping of SPM. This strategy might guide expansion to other first-line antitumor agents to improve therapeutic efficacy and decrease side effects, thereby replenishing the possibilities of supramolecular chemotherapy.

Increasing GSH-Px Activity and Activating Wnt Pathway Promote Fine Wool Growth in FGF5-Edited Sheep.

Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4-20.0 µm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding.

Effect of short-term exposure to high temperatures on the reproductive behavior and physiological enzyme activities in the fruit fly Zeugodacus tau (Walker).

Zeugodacus tau is an economically important invasive pest of various vegetables and fruits. In this study, we evaluated the effects of short-term (12 h) exposure to high temperatures on the reproductive behaviors and physiological enzyme activities of adult Z. tau flies. When compared to the control group, the mating rate in the treated group increased significantly after exposure to 34°C and 38°C. After 34°C exposure, the mating rate of the control♀-treated♂ mating was the highest (60.0%). The use of high temperatures for a short period reduced the pre-mating period and lengthened the duration of copulation. After 38°C exposure, the mating between treated♀ and treated♂ had the shortest pre-mating period of 39.0 min and the longest copulation duration of 67.8 min. Mating after a brief exposure to high temperatures had a negative impact on female reproduction, whereas mating with males who previously had a brief exposure to 34°C and 38°C significantly increased female fecundity. After 40 °C exposure, the mating between treated♀ and control♂ showed the lowest fecundity and hatching rate of 293.25 eggs and 25.71%, respectively. The mating between control♀ and treated♂ showed the highest fecundity of 1,016.75 eggs after exposure to 38°C. The SOD, POD, and CAT activities exhibited significant changes (increase or decrease) after the short-term exposure of Z. tau adults to high temperatures. After being exposed to 38°C, SOD activity increased by 2.64 and 2.10 times in females and males in the treated group, respectively, compared to the SOD activity in the control group. The AchE, CarE, and GST activities first increased and then decreased with the increase in temperature. CarE activity changed the most after exposure to 38°C, with females and males in the treated group increasing by 7.81 and 1.69 times, respectively, compared to the activity in the control group. In conclusion, mating strategy and physiological stress are important adaptive mechanisms of Z. tau for adapting to short-term heat stress in a sex-specific manner.

Development and evaluation of polyacrylamide microspheres loaded with phloretin and tantalum for transcatheter arterial embolization.

Transcatheter arterial embolization is an effective treatment for liver cancer. However, the development of novel embolic agents remains a challenge. In this study, we evaluated polyacrylic acid microspheres loaded with phloretin and tantalum as potential embolic agents for liver cancer treatment. Microspheres were synthesised via emulsion polymerisation and characterised in terms of size, shape, and drug-loading efficiency. Nanosized tantalum powder (0 to 15%) was added to the microspheres as an X-ray blocking agent. The maximum drug-loading capacity of the microspheres was approximately 20 mg g-1. The phloretin-loaded microspheres showed a sustained drug release profile in vitro. The microspheres were also evaluated for their in vivo anticancer efficacy in a rabbit VX2 liver tumour model. In conclusion, polyacrylic acid microspheres loaded with phloretin and tantalum have great potential as novel embolic agents for transcatheter arterial embolization for liver cancer treatment.

Prostate arterial chemoembolization for treatment of refractory hematuria and urinary retention in patients with localized advanced prostate cancer.

OBJECTIVES: To evaluate the safety and efficacy transcatheter arterial chemoembolization (TACE) for the treatment of refractory gross hematuria (RGH) and urinary retention (UR) secondary to localized advanced prostate cancer (PCa). PATIENTS AND METHODS: Thirty-two patients (mean age 72.5 years, range 60-89) with advanced PCa-related RGH that failed conventional therapy were included. Twenty-two of these patients had catheter-dependent due to PCa-related UR. TACE was performed with epirubicin (EPI)-eluting HepaSpheres (HS) plus intra-arterial (IA) infusion of docetaxel. Technical success, adverse events (AEs), overall survival (OS), control of RGH, removal of indwelling catheters, and local disease control, were evaluated. RESULTS: Technical success was achieved in 100% without major AEs. Mean follow up post-TACE was 27 months (range 8-56 months) with a mean OS of 30 months. GRH stopped within 5 days after TACE in all patients, 26 (86.7%) of these patients exhibited good bleeding control during a mean follow-up of 24 months; 17 (77.3%) of the 22 patients with UR had recovered spontaneous urination, 15 (88.2%) patients were catheter-free at their last follow-up with a mean of 24 months. BS was obtained in 73.3% (22/30) of patients at a mean follow-up of 29 months. At the last visit, 22 patients had a mean of 36 months follow-up and the mean percentage reduction in prostate volume was 55.5%, with a statistically different from baseline (P = 0.022). Negative biopsy results were obtained in 84.2% (16/19) of the patients at 12-47 months after TACE. Compared with baseline values, there was a significant improvements in IPSS, QoL, Qmax, and PVR (all P < 0.05). CONCLUSIONS: TACE using EPI-eluting HS plus IA infusion of docetaxel is a safe and effective treatment option for the advanced PCa patients with GRH and UR, and it could be considered as an alternative if there was no other therapeutic choice.