Surgeon-modified fenestrated endovascular grafts and thoracoscope-assisted fixation for treatment of thoraco-abdominal aortic aneurysms.

BACKGROUND: Total endovascular technique with fenestrated endovascular graft might be hampered for the late dilatation of proximal landing zone, which may cause endografts migration. We describe a successful urgent hybrid procedure for extent III thoracoabdominal aortic aneurysm with aortic intramural hematoma. CASE PRESENTATION: A 55-year-old female with thoracoabdominal aortic aneurysm was considered at high surgical risk and unfit for open repair due to multiple comorbidities. Therefore, a hybrid procedure of surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted Transaortic epicardial fixation of endograft was finally chosen and performed in the endovascular operating room. A 3-port technique was performed through a left video-assisted thoracoscopic approach. After the first tampering stent-graft was deployed, a double-needle suture was penetrated both the aortic wall and stent-graft to fixate it in the proximal descending aorta. Then the second endograft, which had been fenestrated on table, was introduced and oriented extracorporeally by rotating superior mesenteric artery and left renal artery fenestration radiopaque markers and deployed with perfect apposition between the fenestrations and target visceral artery. Each vessel was sequentially stented using Viabahn self-expandable stent to finish target vessel stenting. An Ankura cuff stent was deployed in the distal abdominal aortic artery. CONCLUSION: Surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted fixation may be an innovative and viable alternative for selected high-risk patients with extent III thoracoabdominal aortic aneurysm. A longer follow-up is needed to ascertain the success of this approach.

Formation of Nitrogen-Doped Positively Curved Molecules by π-Extension.

Two nitrogen-doped positively curved aromatic molecules bearing doubly fused pentagonal rings were synthesized and characterized. Crystallographic analysis confirms the formation of a bowl-shaped structure, which is induced by the fusion of adjacent pentagons to the rigid aromatic planes. Both compounds demonstrate good photoluminescence. These electron-rich bowl-shaped molecules can associate with C60 to form complexes in 2:1 ratio in toluene with different association constants depending on the molecular dimension of the hosts.

Research on bronze wine vessel classification using improved SSA-CBAM-GNNs.

This article proposes an advanced classification algorithm for bronze drinking utensils, taking into account the complexity of their cultural characteristics and the challenges of dynasty classification. The SSA-CBAM-GNNs algorithm integrates the Sparrow Search Algorithm (SSA), Spatial and Spectral Attention (CBAM) modules, and Graph Neural Networks (GNNs). The CBAM module is essential for optimizing feature extraction weights in graph neural networks, while SSA enhances the weighted network and expedites the convergence process. Experimental results, validated through various performance evaluation indicators, illustrate the outstanding performance of the improved SSA-CBAM-GNNs algorithm in accurately identifying and classifying cultural features of bronze drinking utensils. Comparative experiments confirm the algorithm's superiority over other methods. Overall, this study proposes a highly efficient identification and classification algorithm, and its effectiveness and excellence in extracting and identifying cultural features of bronze drinking utensils are experimentally demonstrated.

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges.

Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1.

Purpose: Spermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. B-lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both in vitro and in vivo. Methods: Methyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2'-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality in vivo. Results: Analysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209. Conclusion: Analysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.

Polyphenols from Prunus mume: extraction, purification, and anticancer activity.

Prunus mume is an ancient medicinal herb and food that are commonly used in Asian countries with high nutritional ingredients and biological activities. Polyphenols are important functional components in Prunus mume. To obtain a more efficient extraction process of Prunus mume polyphenols, a single-factor test and response surface method were used. After extraction and purification, the final polyphenol content of Prunus mume (L1) was up to 90%. Biological experiments showed that L1 had high anticancer activity against HeLa (125.28 µg mL-1), HepG2 (117.24 µg mL-1), MCF-7 (170.19 µg mL-1), and A549 (121.78 µg mL-1) in vitro by MTT assay. The combination of DDP and DOX significantly enhanced the anticancer activity of the four cell lines, especially L1-DOX had the smallest IC50 value of 0.04 µg mL-1 against HepG2 cells, indicating the combination of drugs had synergistic effects. It is further demonstrated that L1 could inhibit cell proliferation by inducing apoptosis with ROS detection and confocal fluorescence images. The relative tumor proliferation rate (T/C) was 40.6%, and the tumor inhibition rate was 57.9%, indicating L1 to have no significant toxicity but high anti-HepG2 activity in vivo. Although the study is very limited, it is anticipated to provide a reference for further exploration of the functionality of the plant.

Efficacy of left subclavian artery revascularization strategies during thoracic endovascular aortic repair in patients with type B dissection: A single-center experience of 105 patients.

Background: Left subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method. Methods: In this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients. Results: The treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P < 0.05). The estimated blood loss, contrast agent volume, fluoroscopic time, operation time, and limb ischemia symptoms during the follow-up were significantly different in the four groups (P < 0.05). Pairwise comparison among groups indicated that the estimated blood loss and operation time in the CSB group were the highest (adjusted P < 0.0083; P < 0.05). The contrast agent volume and fluoroscopy duration were the highest in the SBSG groups, followed by PMF, CG, and CSB groups. The incidence of limb ischemia symptoms was the highest in the PMF group (28.6%) during the follow-up. The incidence of complications (except limb ischemia symptoms) during the perioperative and follow-up periods was similar among the four groups (P > 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P < 0.05), and the CSB group had the longest follow-up. Conclusion: Our single-center experience suggested that the PMF technique increased the risk of limb ischemia symptoms. The other three strategies effectively and safely restored LSA perfusion in patients with type B aortic dissection and had comparable complications. Overall, different LSA revascularization techniques have their advantages and disadvantages.

The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry.

Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L1) had antiproliferative effect on cervical cancer cells (Hela, 51.98 µg/mL), liver cancer cells (HepG2, 23.57 µg/mL), breast cancer cells (MCF-7, 113.39 µg/mL), and lung cancer cells (A549, 76.10 µg/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the IC50 value was 0.02 µg/mL. This was further evidence that L1 could inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be L1 interacting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that L1 extract can be used as a functional agent against hepatoma carcinoma cells.

Research on Anthocyanins from Rubus "Shuofeng" as Potential Antiproliferative and Apoptosis-Inducing Agents.

Blackberries have high nutritional value and strong biological activities, such as antiproliferative activity. Anthocyanins are important functional components in blackberries. We collected 25 kinds (lines) of blackberries from our nursery to investigate antiproliferative agents in natural foods. Among them, the Shuofeng variety had the highest anthocyanin content, with 2.54 mg/g of fresh fruit, which increased to 357.75 mg/g of dried powder through ultrasound-assisted solvent extraction and macroporous resin adsorption. Additional experiments showed that Shuofeng's anthocyanin content had high anti-HepG2 activity in vitro and in vivo, as well as activity against Hela (68.62 µg/mL), HepG2 (55.85 µg/mL), MCF-7 (181.21 µg/mL), and A549 cells (82.01 µg/mL), as determined by MTT assay. It also had no apparent toxic effects. The combination of DDP and DOX significantly enhanced the antiproliferative activity of the four cell lines. The IC50 value of Shuofeng's anthocyanin content combined with DOX in HepG2 cells was the lowest at only 0.08 µg/mL, indicating that the combination of drugs had additive and synergistic effects. Shuofeng's anthocyanin content might intercalate into DNA and alter or destroy DNA, causing apoptosis and inhibiting cell proliferation. Our results show that blackberry anthocyanins can inhibit the proliferation of cancer cells and their possible mechanisms. However, we must study the deeper mechanism and explore its targeting effects in the future.

π-Extended Pyrrole-Fused Heteropine: Synthesis, Properties, and Application in Organic Field-Effect Transistors.

Sulfur-embedded polycyclic aromatic compounds have been used as building blocks for numerous organic semiconductors over the past few decades. While the success is based on thiophene-containing compounds, aromatic compounds that contain thiepine, a sulfur-containing seven-membered-ring arene, has been less well investigated. Here we report the synthesis and properties of π-extended pyrrole-fused heteropine compounds such as thiepine and oxepine. A π-extended pyrrole-fused thiepine exhibited a "pitched π-stacking" structure in the crystal, and exhibited a high charge carrier mobility of up to 1.0 cm2 V-1 s-1 in single-crystal field-effect transistors.

A pigeon paramyxovirus type 1 isolated from racing pigeon as an inactivated vaccine candidate provides effective protection.

Pigeon paramyxovirus type 1 (PPMV-1), a variant of Newcastle disease virus (NDV), causes severe Newcastle disease (ND) in pigeons. However, there is no PPMV-1 vaccine available worldwide. In this study, a strain of PPMV-1 was isolated from outbreaks in a vaccinated racing pigeon (Columbia livia) loft in China, namely, PPMV-1/pigeon/Gansu/China/02/2020 (GS02). Experimental infection with GS02 showed mortality rates of 100% and 87.50% in 4- and 12-week-old pigeons, respectively, suggesting that GS02 is virulent and more sensitive to young pigeons. The whole genome of GS02 determined the fusion (F) protein possessing virulence cleavage site 112RRQKRF117. Phylogenetic analysis indicated that GS02 was a subgenotype VI.2.1.1.2.2 (VIk) of Class II NDV and more closely related to the JS/06/20/Pi (MW271791) strain, but it was far from the genetic distance from the commercial vaccine chicken-origin La Sota strain. Using inactivated GS02 as a vaccine candidate and inactivated vaccine La Sota to immunize the pigeons, both of them provided complete protection against GS02 challenge. The GS02 vaccine candidate induced higher antibody titers than the La Sota vaccine, and cross-reactivity testing showed antigenically slight differences between GS02 and La Sota. These results indicated that the GS02 candidate could be a potential pigeon-derived vaccine for the prevention and control of PPMV-1 in pigeons.

Stereoselective Synthesis of ß-Alkoxy-ß-amido Vinylbenziodoxoles via Iodo(III)etherification of Ynamides.

A trans-iodo(III)etherification reaction of ynamides with benziodoxole triflate and alcohols is reported. Despite the sensitivity of ynamides and enamides toward Brønsted acid, the reaction could be successfully performed under carefully controlled conditions to afford ß-alkoxy-ß-amido vinylbenziodoxoles in moderate to good yields. The products could be subjected to a sequence of cross-coupling via C-I(III) bond cleavage and electrophilic halogenation of the resulting α-alkoxyenamides, allowing for the preparation of densely functionalized esters.

Transthoracic minimally invasive closure for the treatment of ruptured sinus of Valsalva aneurysm: immediate and mid-term follow-up results.

BACKGROUND: We aimed to evaluate the immediate and mid-term outcomes of transthoracic minimally invasive closure (TMIC) of ruptured sinus of Valsalva aneurysm (RSVA), which is a rare and mostly congenital heart disease. METHODS: From January 2014 to November 2020, 19 patients (16 males, 3 females) with RSVA were selected for TMIC and were followed up at our centre. Data were analysed from our prospectively collected database and clinical mid-term follow-up was obtained. RESULTS: Among these 19 cases, transthoracic echocardiography showed rupture of the right coronary sinus to the right atrium in 9 patients, non-coronary sinus rupture to the right atrium in 7 patients, and right coronary sinus rupture to the right ventricle in 3 patients. Most (13/19) cases were New York Heart Association (NYHA) functional class III or IV. The mean diameters of the defect from the aortic end and ruptured site were 8.8±3.0 and 6.4±2.6 mm, respectively. TMIC was attempted using ventricular septal defect (VSD)/patent ductus arteriosus (PDA) occluders 2-7 mm larger than the aortic ends of the defects. All patients were successfully treated by TMIC and achieved complete closure at discharge after a mean hospital stay length of 6.2±2.5 days. Seventeen patients were NYHA class I while 2 patients were NYHA class II. No cases of residual shunts, device embolization, infective endocarditis, or aortic regurgitation were observed during a median follow-up of 36 months (range, 16-84 months). CONCLUSIONS: In appropriately selected cases with RSVA, TMIC is an attractive alternative to surgery, with a high technical success rate and encouraging short-term and mid-term outcomes. However, long-term follow-up is needed.

Fully conjugated azacorannulene dimer as large diaza[80]fullerene fragment.

A fully conjugated azacorannulene dimer with a large π-surface (76π system) was successfully synthesized from a fully conjugated bifunctional polycyclic aromatic azomethine ylide. This molecule represents an example of diaza[80]fullerene (C78N2) fragment molecule bearing two internal nitrogen atoms. X-ray crystallography analysis shows its boat-shaped structure with two terminal azacorannulenes bent in the same direction. The molecular shape leads to unique selective association with a dumbbell-shaped C60 dimer (C120) over C60 through shape recognition. Owing to its large π-surface and a narrow HOMO-LUMO gap, the azacorannulene dimer exhibits red fluorescence with a quantum yield of up to 31%. The utilization of the fully conjugated bifunctional azomethine ylide is a powerful method for the bottom-up synthesis of large multiazafullerene fragments, providing a step towards the selective total synthesis of multiazafullerenes.

High Hole Concentration and Diffusion Suppression of Heavily Mg-Doped p-GaN for Application in Enhanced-Mode GaN HEMT.

The effect of Mg doping on the electrical and optical properties of the p-GaN/AlGaN structures on a Si substrate grown by metal organic chemical vapor deposition was investigated. The Hall measurement showed that the activation efficiency of the sample with a 450 sccm Cp2Mg flow rate reached a maximum value of 2.22%. No reversion of the hole concentration was observed due to the existence of stress in the designed sample structures. This is attributed to the higher Mg-to-Ga incorporation rate resulting from the restriction of self-compensation under compressive strain. In addition, by using an AlN interlayer (IL) at the interface of p-GaN/AlGaN, the activation rate can be further improved after the doping concentration reaches saturation, and the diffusion of Mg atoms can also be effectively suppressed. A high hole concentration of about 1.3 × 1018 cm-3 can be achieved in the p-GaN/AlN-IL/AlGaN structure.

Transcatheter versus surgical aortic valve replacement in aortic stenosis patients with advanced chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been increasingly used in all levels of risk patients, which is less invasive and has fewer complications. However, the benefits of transcatheter and surgical methods of aortic valve replacement remain controversial for aortic stenosis (AS) patients with advanced chronic kidney disease (stage 3-5). METHODS: We comprehensively searched PubMed, Embase, the Cochrane Library, and the International Clinical Trials Registry Platform (ICTRP) from January 2000 to October 2020 and performed a systematic review to evaluate the two techniques. Two investigators independently conducted the literature searches, study eligibility assessment, and data extraction in duplicate. RESULTS: Compared to surgical aortic valve replacement (SAVR), TAVR had lower risk of in-hospital mortality [odds ratio (OR): 0.53; 95% confidence interval (CI): 0.36-0.78; P=0.001], lower stroke rate (OR: 0.68; 95% CI: 0.47-0.96; P=0.03), lower risk of acute kidney injury (AKI) (OR: 0.42; 95% CI: 0.34-0.52; P<0.00001) and AKI requiring dialysis (OR: 0.65; 95% CI: 0.58-0.73; P<0.00001), lower rate of bleeding (OR: 0.35; 95% CI: 0.31-0.38; P<0.00001) and blood transfusion (OR: 0.41; 95% CI: 0.32-0.52; P<0.00001), lower infection rate (OR: 0.23; 95% CI: 0.13-0.38; P<0.00001), lower risk of atrial fibrillation (AF) (OR: 0.37; 95% CI: 0.17-0.79; P=0.01) and cardiac tamponade (OR: 0.53; 95% CI: 0.37-0.75; P=0.0003), shorter ICU stay [weighted mean difference (WMD): -2.55; 95% CI: -4.13 to -0.98; P=0.002] and hospital stay (WMD: -7.06; 95% CI: -8.41 to -5.71; P<0.00001). DISCUSSION: TAVR is a safe, efficient, and feasible technique for AS patients with advanced CKD and probably a better solution for its advantage in reducing in-hospital mortality, postoperative complications, ICU, and hospital stay.

A novel ruthenium polypyridyl complex for the selective imaging and photodynamic targeting of the Golgi apparatus.

A well-designed heteroleptic ruthenium(ii) polypyridyl complex demonstrated stable target-specific in vitro Golgi apparatus imaging abilities in HeLa cell lines. After utilizing photodynamic therapy via UV excitation, the Ru-SL complex could be triggered to generate singlet oxygen (1O2) and red fluorescence signals. 1O2 was highly cytotoxic and could induce DNA damage and the disappearance of the Golgi apparatus. The red fluorescence signals disappeared gradually, suggesting that the live or dead state of the cells can be estimated from the fluorescence signal intensity.

Off-pump versus on-pump redo coronary artery bypass grafting: a systematic review and meta-analysis.

BACKGROUND: Redo coronary artery bypass grafting (redo CABG) is associated with increased mortality and morbidity. The aim of this study was to systematically evaluate the evidence comparing the outcomes of off-pump with on-pump redo CABG. METHODS: Studies were systematically searched and identified using PubMed, EMBASE, the Cochrane Library, and the International Clinical Trials Registry Platform (ICTRP) by two researchers independently. The primary outcome was 30-day mortality, and the secondary outcomes were in-hospital mortality, post-operative complications, completeness of revascularization, blood transfusion rate, duration of mechanical ventilation, intensive care unit and hospital stays. RESULTS: The 21 studies including 4,889 patients were enrolled in our meta-analysis. Compared with on-pump, the off-pump technique was associated with significantly reduced 30-day mortality (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.26-0.72, p = 0.001). Moreover, a notably decreased in-hospital mortality (OR = 0.55, 95% CI = 0.39-0.76, p = 0.0004) and incidence of post-operative new-onset atrial fibrillation, myocardial infarction, acute kidney injury, low cardiac output state, blood transfusion rate (OR = 0.46, 95% CI = 0.35-0.60, p < 0.00001; OR = 0.54, 95% CI = 0.38-0.78, p = 0.0007; OR = 0.51, 95% CI = 0.37-0.70, p < 0.0001; OR = 0.31, 95% CI = 0.20-0.47, p < 0.00001; OR = 0.29, 95% CI = 0.14-0.61, p = 0.001) and significantly shortened duration of mechanical ventilation, intensive care unit and hospital stays (mean difference [MD] = -8.21 h, 95% CI = -11.74 to -4.68, p < 0.00001; MD = -0.77 d, 95% CI = -0.81 to -0.73, p < 0.00001; MD = -2.24 d, 95% CI = -3.17 to -1.32, p < 0.00001) could be observed when comparing the outcomes of off-pump with on-pump redo CABG. There was nonsignificant difference between off-pump and on-pump redo CABG in completeness of revascularization. CONCLUSION: In patients undergoing redo CABG surgery, the off-pump technique was associated with decreased mortality, less post-operative complications when compared to on-pump.

Magnesium-catalyzed hydroboration of organic carbonates, carbon dioxide and esters.

A low-valent magnesium(i) complex [(XylNacnac)Mg]2 was employed as a highly efficient precatalyst for the hydroboration of a variety of cyclic and linear organic carbonates, polycarbonates, CO2 and esters with HBpin under mild conditions. The resultant boronates can be used for the preparation of the corresponding value-added diols, triols or alcohols through hydrolysis.