Insight into the Stability of Pentazolyl Derivatives based on Covalent Bond.

Pentazole is regarded as a unique inorganic molecule that possess organic heterocyclic structure. Therefore, the research on pentazolyl derivatives represents a cutting-edge direction in both contemporary inorganic chemistry and heterocyclic chemistry. Moreover, their synthesis is regarded as the most significant research topic in the field of energetic materials due to the great potential of pentazolyl derivatives to breakthrough the energy bottleneck of CHNO-based energetic materials. However, synthesizing pentazolyl derivatives is challenging. To provide a theoretical support for the synthesis, we conducted theoretical studies on six single-ring pentazolyl derivatives with different functional groups. The results suggest that derivatization reduces the bond strength and weakens the aromaticity of the pentazolate ring. Further analysis showed that derivatization mainly affects the π aromaticity of the pentazolate ring, and ultimately causing poor stability of the pentazolyl derivatives. Among the six derivatives investigated in this study, fluoro pentazole (cyclo-N5-F) and hydroxyl pentazole (cyclo-N5-OH) possess good aromaticity, which is similar to the reported cyclo-N5-NCHN(CH3)2. Further calculations show that the kinetic stability of cyclo-N5-OH is higher than that of cyclo-N5-F. These results collectively indicate that cyclo-N5-OH is a promising candidate for synthesizing single-ring pentazolyl derivatives.

Revisiting Pentazole: An Investigation into the Intriguing Molecule Exhibiting Dual Organic and Inorganic Characteristics.

Pentazole (cyclo-HN5) is a unique heterocycle categorized as both an organic and inorganic compound. However, attempts to synthesize and characterize cyclo-HN5 have been unsuccessful thus far. In this study, we synthesized a cyclo-HN5 solution and investigated the spectra, structure, aromaticity, acidity, and stability of cyclo-HN5. The lone pair of electrons on the protonated N atom of cyclo-HN5 participates in π-electron delocalization, forming two N═N bonds. Further investigations suggest that cyclo-HN5 exhibits significantly decreased π aromaticity and slightly lower σ aromaticity than cyclo-N5-. Experimental results suggest that pure cyclo-HN5 is unstable at ambient temperatures and pressures, but it can be isolated at high pressures or stabilized in solution by abundant hydrogen bonds. The pKa of cyclo-HN5 was determined as 1.63 (H2O, 25 °C) via potentiometric titration, indicating that cyclo-HN5 is a medium-strong acid. This study reveals the fundamental structure and properties of cyclo-HN5, thereby providing important data for advancing cyclo-HN5 chemistry.

7-Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24.

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

Cobalt-Catalyzed Enantioselective C-H Annulation of Benzylamines with Alkynes: Application to the Modular and Asymmetric Syntheses of Bioactive Molecules.

The transition metal-catalyzed enantioselective C-H functionalization strategy has revolutionized the logic of natural product synthesis. However, previous applications have heavily relied on the use of noble metal catalysts such as rhodium and palladium. Herein, we report the efficient synthesis of C1-chiral 1,2-dihydroisoquinolines (DHIQs) via enantioselective C-H/N-H annulation of picolinamides with alkynes catalyzed by a more sustainable and cheaper 3d metal catalyst, cobalt(II) acetate tetrahydrate. A wide range of enantiomerically enriched DHIQs were obtained in good yields with excellent enantioselectivities (up to 98% yield and >99% ee). The robustness and synthetic potential of this method were demonstrated by the modular and asymmetric syntheses of several tetrahydroisoquinoline alkaloids, including (S)-norlaudanosine, (S)-laudanosine, (S)-xylopinine, (S)-sebiferine, and (S)-cryptostyline II, and the asymmetric syntheses of key intermediates of (+)-solifenacin, FR115427, and (+)-NPS R-568.

A high high-density lipoprotein level is associated with Gleason score upgrade in Chinese patients diagnosed with high-grade prostate carcinoma.

BACKGROUND: The high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU. METHODS: Patients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups. RESULTS: A total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005-1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904-1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998-59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer. CONCLUSIONS: These laboratory examination data could provide urologists with information before making a therapeutic protocol.

Coelenterazine-Type Bioluminescence-Induced Optical Probes for Sensing and Controlling Biological Processes.

Bioluminescence-based probes have long been used to quantify and visualize biological processes in vitro and in vivo. Over the past years, we have witnessed the trend of bioluminescence-driven optogenetic systems. Typically, bioluminescence emitted from coelenterazine-type luciferin-luciferase reactions activate light-sensitive proteins, which induce downstream events. The development of coelenterazine-type bioluminescence-induced photosensory domain-based probes has been applied in the imaging, sensing, and control of cellular activities, signaling pathways, and synthetic genetic circuits in vitro and in vivo. This strategy can not only shed light on the mechanisms of diseases, but also promote interrelated therapy development. Here, this review provides an overview of these optical probes for sensing and controlling biological processes, highlights their applications and optimizations, and discusses the possible future directions.

Mitoxantrone alleviates hepatic steatosis induced by high-fat diet in broilers.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a common nutritional metabolic disease in poultry that seriously compromises the health of chickens and reduces the economic benefits of the industry. In this study, we investigated the therapeutic effect of mitoxantrone (MTX) on hepatic steatosis in broilers. We constructed a steatosis cell model in vitro by adding oleic acid and palmitic acid to chicken hepatocytes (LMH cells), to examine influence of MTX on fat deposition on LMH cells. To determine the effects of MTX on hepatic steatosis in broiler livers in vivo, broilers were fed a high-fat diet to establish a fatty liver model. Our data show that MTX reduced the triglyceride (TG) levels and total cholesterol levels in LMH cells. In the MAFLD chick model, MTX decreased mRNA abundance of hepatic-lipid-synthesis-related gene such as FASN and increased mRNA abundance of fatty-acid-ß-oxidation-related genes such as CPT1, PPARα, and reduced hepatic TG levels. MTX also reduced serum lipid and the percentage of abdominal fat. These results suggest that MTX improves hepatic steatosis in broilers as well as reduces circulating lipid levels and fat accumulation in broilers. Our work provides a promising therapeutic strategy for MAFLD and excessive fat accumulation in broiler chickens.

Dietary supplementation with perillartine ameliorates lipid metabolism disorder induced by a high-fat diet in broiler chickens.

Lipid metabolism disorders affect the growth and jeopardize the health of poultry, thus, decreasing economic benefits. Perillartine, a sweetener derived from Perilla frutescens, has excellent potential in regulating lipid metabolism. In this study, we explored the effects of perillartine on lipid metabolism in broiler chickens by establishing a nonalcoholic fatty liver model induced by a high-fat diet. By using network pharmacology and molecular docking, we analyzed the potential molecular targets and pathways through which perillartine regulates lipid metabolism and alleviates fatty liver. Perillartine was found to regulate the expression of genes associated with lipogenesis, lipolysis, and lipid transport, including FASN, PPARα, CPT-1, ACCα, APOB, and APOA1 in the liver, and to decrease lipid accumulation in the liver and blood in broilers without affecting growth performance. In addition, we discovered 24 candidate targets of perillartine, including SRD5A2 and XDH, through network pharmacology analysis and successfully constructed a compound-target-pathway-disease network. Our results suggested that perillartine may be a promising, long-lasting therapeutic molecule for modulating lipid metabolism disorders in broilers.

Closely Packed Conductive Droplets with Polygon-Like Patterns Confined at the Interface in Ternary Polymer Blends.

This work reports on the formation of closely packed conductive droplets demonstrating polygon-like patterns at the interface in partially wetted ternary polymer systems prepared by melt blending and annealing treatment. The low-density polyethylene/poly(ether-block-amide)/poly(butylene-adipate-co-terephthalate) (LDPE/PEBA/PBAT) blend showed an intermediate partial wetting tendency where the interfacially localized conductive PEBA phase developed connected structure after blending but transformed into dispersed droplets upon annealing. The coalescence of the PEBA droplets appeared to be initiated by the Rayleigh-type instability in the thin PBAT film separating PEBA. However, the intrinsic coalescence rate of the PEBA droplets was very low due to the low interfacial tension of PEBA/PBAT. This slow coalescence of PEBA combined with the fast reduction in the interfacial area during annealing and the intermediate partial wetting state of the LDPE/PEBA/PBAT system resulted in a unique morphology of closely packed PEBA droplets with polygon-like patterns at a volume fraction of 50/10/40. Two other representative ternary polymer blends, LDPE/PEBA/polypropylene (PP) and compatibilized LDPE/PEBA/polystyrene (PS), with strong and weak partial wetting morphologies were also examined to highlight the mechanism for the morphology development in the LDPE/PEBA/PBAT blend.

Safety and efficacy of treating post-burn pathological scars with extracorporeal shock wave therapy: A meta-analysis of randomised controlled trials.

The clinical application of shockwave therapy has expanded to the treatment of pathological scars. The objective of this systematic review and meta-analysis is to quantitatively evaluate the efficacy and safety of extracorporeal shockwave therapy combined with comprehensive rehabilitation therapy on post-burn pathological scars compared to comprehensive rehabilitation therapy alone. The randomised controlled trials of extracorporeal shockwave therapy for post-burn pathological scars published in English and Chinese languages before October 2021 were included. The methodological quality and risk of bias of the selected articles were assessed with the Cochrane Collaboration's 'risk of bias' tool. RevMan software was applied for data analysis. This is the first systematic review and meta-analysis considering the effectiveness and safety of extracorporeal shockwave therapy on post-burn pathological scars. And nine randomised controlled trials involving 422 patients were included in this meta-analysis. The meta-analysis results showed that, compared with comprehensive rehabilitation therapy alone, extracorporeal shockwave therapy combined with comprehensive rehabilitation therapy was more effective in relieving pain (standardized mean difference [SMD] = -0.59, 95% confidence interval [CI]: [-0.87 to -0.31], p < 0.0001) and pruritus related to pathological scars (SMD = -0.94; 95% CI: [-1.25 to -0.63], p = 0.004), improving scars' appearance (SMD = -1.78, 95% CI: [-3.37 to -0.19], p = 0.03) and elasticity (SMD = 0.25, 95% CI: [0.29-0.21], p < 0.00001), decreasing scars thickness (SMD = -0.13, 95% CI: [-0.25 to -0.01], p = 0.04) and promoting the maturation status of scars (SMD = -2.86, 95% CI: [-3.96 to -1.76], p < 0.00001). There were no reported serious adverse events during and after extracorporeal shockwave therapy in the included studies. Available data preliminarily suggested that the combination of extracorporeal shockwave therapy and comprehensive rehabilitation therapy had better therapeutic effect on post-burn pathological scars than comprehensive rehabilitation therapy alone, without obvious side effects. However, further clinical well-controlled randomised controlled trials are needed. Systematic review registration ID: PROSPERO CRD42022297573.

Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis.

BACKGROUND: Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China. METHODS: We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock. RESULTS: Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%-32.8%, I2 = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I2 = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%-46.0%, I2 = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed. CONCLUSIONS: Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).

Early implementation of intended exercise improves quality of life in Parkinson's disease patients.

OBJECTIVE: Recent data have shown that regular exercise may ameliorate motor symptoms in Parkinson's disease (PD). This study aims to investigate how intended exercise impacts motor and non-movement symptoms of PD. METHODS: Eighty-eight patients were randomly assigned to an early exercise group (E-EG), late exercise group (L-EG), or a control group (CG) using a randomized delayed-start design. The E-EG carried out a rigorous, formal exercise program for 1 h, twice per week, for 18 months (May 2018-November 2019). The L-EG took part in the exercise program in the final 6-12 months of the study. We assessed outcomes using the Unified Parkinson's Disease Rating Scale (UPDRS), PDQ-39 Questionnaire, Line A test, Line B test, Nine-hole column test, 30 s squat and stand-up test (30 s SST), 10-m walk test (10mW), Balance Evaluation Systems Mini Test (MiniBESTest), FAB, and Time Up and Go Test (TUG). RESULTS: The patients with PD in the E-EG had lower performance in the UPDRS and Line B test compared to those in the L-EG at post-exercise (p < 0.05). Moreover, the patients with PD in the E-EG had much lower performance in the PDQ-39 and 9-Hole Peg test compared to those in the L-EG at post-exercise (p < 0.01). CONCLUSION: Implementation of an exercise regimen improved the movement abilities and quality of life in PD patients, especially in the E-EG. This data supports the idea that intended exercise should be implemented as part of the treatment strategy for PD patients as early as possible.

Long-term high-risk drinking does not change effective doses of propofol for successful insertion of gastroscope in Chinese male patients.

BACKGROUND: Available literature indicates that long-term drinkers demand a higher dose of propofol for induction of anesthesia than non-drinkers. However, there is no study having assessed the influence of long-term high-risk drinking (LTHRD) on the effective doses of propofol for successful insertion of gastroscope with sedation. This study was designed to compare the effective doses of propofol for successful insertion of gastroscope between LTHRD and non-drinking (ND) Chinese male patients. METHODS: Thirty-one LTHRD patients and 29 ND male patients undergoing elective gastroscopy with propofol sedation were enrolled. The modified Dixon's up-and-down method was applied to determine the calculated median effective dose (ED50) of propofol for successful insertion of gastroscope. Furthermore, the isotonic regression analysis was used to establish the dose-response curve of propofol and assess the effective doses of propofol where 50% (ED50) and 95% (ED95) of gastroscope insertions were successful. RESULTS: The calculated ED50 of propofol for successful insertion of gastroscope was 1.55 ± 0.10 mg/kg and 1.44 ± 0.11 mg/kg in the LTHRD and ND patients. The isotonic regression analysis further showed that ED50 and ED95 of propofol for successful insertion of gastroscope was 1.50 mg/kg (95%CI, 1.40-1.63) and 1.80 mg/kg (95%CI, 1.74-1.90) in the LTHRD patients, respectively; 1.40 mg/kg (95% CI, 1.27-1.57) and 1.60 mg/kg (95%CI, 1.56-1.65) in the ND patients. The ED50 of propofol for successful insertion of gastroscope was not significantly different between LTHRD and ND patients. CONCLUSIONS: This study demonstrates that the difference in the estimated ED50 of propofol for successful insertion of gastroscope between LTHRD and ND Chinese male patients was not statistically significant. TRIAL REGISTRATION: The study was registered on November 28, 2020 ( ChiCTR2000040382 ) in the Chinese Clinical Trial Registry.

Osteoporotic vertebral compression fracture accompanied with thoracolumbar fascial injury: risk factors and the association with residual pain after percutaneous vertebroplasty.

BACKGROUND: To explore the risk factors involved in the induction of thoracolumbar fascia (TLF) injury by osteoporotic vertebral compression fracture (OVCF), and the association between the residual pain after percutaneous vertebroplasty (PVP) and fascial injury. METHODS: A total of 81 patients with single-segment OVCF, treated between January 2018 and January 2020 were included. The patients were grouped according to the existence of TLF injury. The patients' general, clinical, and imaging data were accessed. RESULTS: There were 47 patients in the TLF group and 34 in the non-injury group (NTLF group). In the TLF group, BMI (Body mass index) was significantly lower, while the prevalence of hypertension and sarcopenia were significantly higher (P < 0.05). The vertebral compression degree was higher, and the kyphosis angle of the injured vertebra was greater in the TLF group (P < 0.05). Cobb's angle was not significantly different between groups. At 3-d after the operation, the VAS (Visual analogue scale) was 4.64 ± 1.78 and 3.00 ± 1.71, and the ODI (Oswestry disability index) was 67.44 ± 11.37% and 56.73 ± 10.59% in TLF and NTLF group, respectively (P < 0.05). However, at 3-m after the operation, the differences in the VAS score and the ODI between groups were not statistically significant. The area of fascial edema was not significantly associated with the pre- and post-operative VAS or ODI, but was positively correlated with the vertebral body compression degree (R = 0.582, P = 0. 029). CONCLUSION: Residual back pain after PVP is associated with TLF injury. Low BMI, hypertension and sarcopenia are risk factors of TLF injury, and sarcopenia may be the major factor.

Bacteria-Based Live Vehicle for In Vivo Bioluminescence Imaging.

The anticancer therapy strategy mediated by tumor-targeting bacteria needs better visualization tools for imaging and monitoring bacteria in vivo. The probiotic strain Escherichia coli Nissle 1917 (EcN), one of the tumor-targeting bacteria, leads to the potential application for cancer therapy. Here, we report the development and application of a live, EcN-based imageable vehicle for noninvasive in vivo bioluminescence imaging in live mice. Firefly luciferase (Fluc) and luciferin-regenerating enzyme (LRE), an enzyme that contributes to stable bioluminescence, were functionally coexpressed in EcN. The recombinant EcN strain expressing the genomically integrated Fluc-LRE cassette was demonstrated to be a valuable tool for generating robust, continuous, and red-shifted bioluminescence for bacterial tracking in vitro and in vivo, thus providing an optical tumor-targeting system for the in vivo study of bacteria-assisted cancer therapy. Additionally, in vivo imaging of the recombinant EcN strain in the mouse intestinal tract indicated the potential of this strain to be used as a tool in the study of gut.

Controversies and consensus in transanal total mesorectal excision (taTME): Is it a valid choice for rectal cancer?

Transanal total mesorectal excision (taTME) is a novel approach to radical surgery for low rectal cancer. taTME is associated with the benefits of a higher rate of free distal resection margins (DRM) under direct visualization, better visualization of the mesorectal plane, and the feasibility of overcoming the restriction of the distal pelvis. Thus, it is increasingly used globally. In this review, we investigated whether taTME yields better short- and long-term outcomes than laparoscopic TME.

Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE: We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS: Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS: R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION: This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

Effect of different reinforcement methods on anastomotic leakage prevention after laparoscopic double anastomosis.

BACKGROUND AND OBJECTIVES: To investigate the effects of different suture reinforcement methods for anastomotic leakage and other postoperative complications after the use of a laparoscopic double stapling technique (DST). METHODS: We collected the data of 124 patients who underwent laparoscopic radical resection of colorectal cancer from July 2017 to September 2018 at our institution. Patients were divided into three groups according to the suture reinforcement methods: intermittent, continuous suture reinforcement, and non-reinforcement (n = 41, 41, and 42, respectively). One-way analysis of variance, χ2 , Fisher's exact, and nonparametric tests were used for statistical analysis. RESULTS: Among the 124 patients, there were no statistically significant differences in operation times, intraoperative blood loss, postoperative hospital stays and recovery of bowel movement. Nine patients were diagnosed with anastomotic leakage (AL). The incidences of serious AL in the intermittent and continuous suture reinforcement groups were lower than that in the control group, with lower reoperation rate, shorter average lengths of stay and lower treatment costs of two experimental groups. CONCLUSION: Intermittent and continuous sutures after laparoscopic DST is effective, safe, and feasible on anastomotic leakage prevention. These procedures could be popularized in rectal surgery on patients with high risk of AL.

Treatment of maxillofacial congenital melanocytic nevus with percutaneous radiofrequency thermal ablation: A case series study.

When congenital melanocytic nevus (CMN) is in the maxillofacial region, a safer, more effective and fewer side-effects treatment is needed for patients with high requirement for appearance. The objective of this study was to investigate the effectiveness of radiofrequency thermal ablation (RFA) for CMN in the maxillofacial region. We reviewed 21 patients treated with RFA for CMN followed by a blinded retrospective analysis of serial photographs taken during the course of their therapy. Questionnaires were used to evaluate perceived therapeutic response and complications of this treatment. Most CMNs stopped growing, faded in color and became smaller. Reduction in size of 90% to 100% was obtained in two patients (10%), 75% to 90% in six patients (29%), 50% to 75% in two patients (10%), <50% in eight patients (38%), and three had no reduction (13%). Clear effect of clinical response score was obtained in two patients (10%), excellent in four patients (19%), good in 14 patients (67%), and fair in one patient (4%). No serious complication, severe hypertrophic scarring, and evidence of recurrence was observed in any case. Percutaneous RFA, as a minimally invasive and safe treatment, may provide an alternative treatment for maxillofacial CMN.

Mechanistic insights into CED-4-mediated activation of CED-3.

Programmed cell death in Caenorhabditis elegans requires activation of the caspase CED-3, which strictly depends on CED-4. CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. Despite recent advances, major questions remain unanswered. Importantly, how CED-4 recognizes CED-3 and how such binding facilitates CED-3 activation remain completely unknown. Here we demonstrate that the L2' loop of CED-3 directly binds CED-4 and plays a major role in the formation of an active CED-4-CED-3 holoenzyme. The crystal structure of the CED-4 apoptosome bound to the L2' loop fragment of CED-3, determined at 3.2 Å resolution, reveals specific interactions between a stretch of five hydrophobic amino acids from CED-3 and a shallow surface pocket within the hutch of the funnel-shaped CED-4 apoptosome. Structure-guided biochemical analysis confirms the functional importance of the observed CED-4-CED-3 interface. Structural analysis together with published evidence strongly suggest a working model in which two molecules of CED-3 zymogen, through specific recognition, are forced into the hutch of the CED-4 apoptosome, consequently undergoing dimerization and autocatalytic maturation. The mechanism of CED-3 activation represents a major revision of the prevailing model for initiator caspase activation.