ABSTRACT
As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.
Subject(s)
Antioxidants , Aortic Dissection , Cobalt , Catalysis , Cobalt/chemistry , Cobalt/pharmacology , Aortic Dissection/drug therapy , Aortic Dissection/pathology , Antioxidants/chemistry , Antioxidants/pharmacology , Animals , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Biomimetic Materials/chemical synthesis , Mice , Reactive Oxygen Species/metabolism , Humans , Oxidative Stress/drug effects , Metal Nanoparticles/chemistryABSTRACT
The tunable pore walls and skeletons render covalent organic frameworks (COFs) as promising absorbents for gold (Au) ion. However, most of these COFs suffered from low surface areas hindering binding sites exposed and weak binding interaction resulting in sluggish kinetic performance. In this study, COFs have been constructed with synergistic linker and linkage for high-efficiency Au capture. The designed COFs (PYTA-PZDH-COF and PYTA-BPDH-COF) with pyrazine or bipyridine as linkers showed high surface areas of 1692 and 2076 m2 gâ1, providing high exposed surface areas for Au capture. In addition, the Lewis basic nitrogen atoms from the linkers and linkages are easily hydronium, which enabled to fast trap Au via coulomb force. The PYTA-PZDH-COF and PYTA-BPDH-COF showed maximum Au capture capacities of 2314 and 1810 mg g-1, higher than other reported COFs. More importantly, PYTA-PZDH-COF are capable of rapid adsorption kinetics with achieving 95% of maximum binding capacity in 10 min. The theoretical calculation revealed that the nitrogen atoms in linkers and linkages from both COFs are simultaneously hydronium, and then the protonated PYTA-PZDH-COF are more easily binding the AuCl4 â, further accelerating the binding process. This study gives the a new insight to design COFs for ion capture.
ABSTRACT
In sixth generation (6G) communications, terahertz (THz) communication is one of the most important technologies in the future due to its ultra-bandwidth, where hybrid beamforming has been widely used to solve the severe transmission attenuation in the THz band. However, the use of frequency-flat phase shifters in hybrid beamforming leads to the beam split effect. To solve the beam split influence, we propose a novel optical true time delay compensation network (OTTDCN)-based phase precoding structure with low power consumption. In the proposed scheme, the OTTDCN pre-generates multiple beam compensation modes to achieve phase compensation for different frequencies. As a result, the compensated beams can be reoriented toward the target direction at different frequencies. Moreover, a low-complexity beam compensation mode-based hybrid precoding algorithm is proposed, where the selection of the optimal beam compensation modes used for all radio-frequency (RF) chains with finite beam compensation modes is considered. The results show that the OTTDCN-based phase precoding scheme can effectively alleviate the beam split effect with low power consumption and achieve near-optimal performance.
ABSTRACT
The efficient and precise extraction of target particles is a crucial prerequisite for achieving accurate detection and analysis in microfluidic cell analysis. In this study, a symmetrical contraction-expansion microchannel with sheath flow was designed, aiming to extract target larger particles from particles of different sizes within the channel. This paper conducted numerical simulations to investigate the three-dimensional migration mechanisms of particles and performed experimental studies to examine the separation performance of particles with different sizes under varying flow rate ratios and different numbers of contraction-expansion structures. The experimental results indicate that at moderate sample flow rates and higher flow rate ratios, microchannels with fewer contraction-expansion structures are likely to achieve better performance in extracting target particles compared to microchannels with a greater number of these structures. Our work advances the application of viscoelastic contraction-expansion microchannels in particle separation. This device is easy to set up in parallel and significantly enhances throughput, providing an accurate and efficient solution for future particle separation applications.
Subject(s)
Equipment Design , Microfluidic Analytical Techniques , Particle Size , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Computer Simulation , ViscosityABSTRACT
OBJECTIVES: To compare the outcomes and treatment burden of primary retroperitoneal lymph node dissection (pRPLND) alone versus pRPLND + adjuvant chemotherapy (AC) in patients with pathological stage II (PSII) non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified patients with PSII NSGCT after pRPLND between 1995 and 2020. The primary outcome was relapse-free survival (RFS). Secondary outcomes included disease-specific survival (DSS), burden of relapse treatment, and factors associated with relapse. RESULTS: A total of 109 PSII patients were included in the study. There were 96 patients treated with pRPLND alone and 13 treated with pRPLND + AC. The median follow-up was 61 months. The 5-year RFS was 72% for the pRPLND-only group vs 92% for the pRPLND + AC group (hazard ratio [HR] 4.372, 95% confidence interval [CI] 0.59-32.36; P = 0.11). Within the pRPLND-only group the 5-year RFS differed by pN stage (pN1 = 94% vs pN2/N3 = 67%, P = 0.03). Despite a higher relapse rate within the pRPLND-only group, the DSS was similar at 5 years (98% pRPLND only vs 100% pRPLND + AC, P = 0.48). Only 24 (25%) of the patients in the pRPLND-only group required any subsequent chemotherapy. Despite achieving similar survival, the cumulative post-RPLND treatment burden was less for the pRPLND-only group than the pRPLND+AC group overall (average 1.23 vs 2.46 cycles of chemotherapy per patient in group). CONCLUSION: The majority of patients with PSII NSGCT treated with pRPLND alone do not experience a recurrence or require chemotherapy. Despite a lower relapse risk when AC is given, no difference in survival was seen but higher chemotherapy burden was entertained. AC may constitute overtreatment for most patients with PSII NSGCT treated with pRPLND.
ABSTRACT
The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of â¼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of â¼46.36 MPa which is much higher than that of dTS (â¼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.
Subject(s)
Oligopeptides , Regeneration , Skin , Tilapia , Tissue Scaffolds , Transglutaminases , Animals , Tissue Scaffolds/chemistry , Tilapia/metabolism , Transglutaminases/metabolism , Transglutaminases/chemistry , Oligopeptides/chemistry , Oligopeptides/metabolism , Wound Healing , Cell Proliferation , Tissue Engineering , Porosity , Mice , Cell Adhesion , HumansABSTRACT
Despite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether. For patients with borderline kidney function, several strategies - such as the use of split-dose cisplatin, dose reductions, or extra hydration - may facilitate the use of cisplatin, but these need to be prospectively validated. This review highlights the critical need for a multidisciplinary team, including onco-nephrologists, to help manage renal complications and optimize delivery of cancer care in complex UC patients with CKD.
In patients with urothelial cancer, the presence of chronic kidney disease can significantly impact treatment options, eligibility for clinical trials, and overall patient outcomes. This review discusses key strategies and newer treatment options that can be used to optimize outcomes in patients who often can't receive standard treatments. Importantly, this article also highlights the critical importance and need for a multidisciplinary team of specialists, including kidney specialists with a focus on cancer patients, to help manage kidney function and deliver high-quality care to patients with urothelial cancer and chronic kidney disease.
ABSTRACT
BACKGROUND: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD: Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS: 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION: For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.
Subject(s)
Bile Duct Neoplasms , Klatskin Tumor , Margins of Excision , Humans , Male , Female , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/mortality , Retrospective Studies , Klatskin Tumor/surgery , Klatskin Tumor/pathology , Klatskin Tumor/mortality , Middle Aged , Aged , Prognosis , Follow-Up Studies , Survival Rate , Carcinoma in Situ/surgery , Carcinoma in Situ/pathology , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Adult , Cell Transformation, Neoplastic/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/epidemiology , Hepatectomy/methods , Hepatectomy/mortality , Aged, 80 and overABSTRACT
MaltAtt-1 is an antimicrobial peptide isolated from Monochamus alternatus with nematocidal activity against pine wood nematode. In this study, a eukaryotic expression system based on Komagataella phaffii GS115 was established, and its secretory expression of MaltAtt-1 was realized. The basic properties and secondary and tertiary structures of the antimicrobial peptide MaltAtt-1 were identified by bioinformatics analysis. MaltAtt-1 is a hydrophilic stable protein, mainly composed of an α-helix (Hh), ß-folds (Ee), and irregular curls (Cc). The optimal fermentation conditions for MaltAtt-1 were determined by a single-factor test and the Box-Behnken response surface method, including an induction time of 72 h, induction temperature of 30 °C, culture medium of pH 7.6, methanol volume fraction of 2.0%, and an initial glycerol concentration of 1%. The stability of MaltAtt-1 indicated its resistant to UV irradiation and repeated freezing and thawing, but the antibacterial activity decreased significantly under the influence of high temperature and a strong acid and base, and it decreased significantly to 1.1 cm and 0.83 cm at pH 2.0 and pH 10.0, respectively. The corrected mortality of B. xylophilus achieved 71.94% in 3 h at a concentration of 300 mg·L-1 MaltAtt-1 exposure. The results provide a theoretical basis for the antimicrobial peptide MaltAtt-1 to become a new green and efficient nematicide.
Subject(s)
Antimicrobial Peptides , Animals , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Nematoda/drug effects , Pinus/parasitology , Pinus/chemistry , Saccharomycetales/metabolism , Hydrogen-Ion Concentration , Fermentation , Protein Stability , Fungal Proteins/chemistry , Fungal Proteins/metabolism , Fungal Proteins/pharmacologyABSTRACT
Covalent organic frameworks (COFs) have attracted considerable attention as adsorbents for capturing and separating gold from electronic wastes. To enhance the binding capture efficiency, constructing hydrogen-bond nanotraps along the pore walls was one of the most widely adopted approaches. However, the development of absorbing skeletons was ignored due to the weak binding ability of the gold salts (Au). Herein, we demonstrated skeleton engineering to construct highly efficiently absorbs for Au capture. The strong electronic donating feature of diarylamine units enhanced the electronic density of binding sites (imine-linkage) and thus resulted in high capacities over 1750â mg g-1 for all three COFs. Moreover, the absorbing performance was further improved via the ionization of diarylamine units. The ionic COF achieved 90 % of the maximal adsorption capacity, 1.63â times of that from the charge-neutral COF within ten minutes, and showed remarkable uptakes of 1834â mg g-1 , exceptional selectivity (97.45 %) and cycling stability. The theoretical calculation revealed the binding sites altering from imine bonds to ionic amine sites after ionization of the frameworks, which enabled to bind the AuCl4 - via coulomb force and contributed to enhanced absorbing kinetics. This work inspires us to design molecular/ionic capture based on COFs.
ABSTRACT
BACKGROUND: Active surveillance after orchiectomy is the preferred management in clinical stage I (CSI) germ-cell tumours (GCT) associated with a 15 to 30% relapse rate. PATIENTS AND METHODS: In the IGCCCG Update database, we compared the outcomes of gonadal disseminated GCT relapsing from initial CSI to outcomes of patients with de novo metastatic GCT. RESULTS: A total of 1014 seminoma (Sem) [298 (29.4%) relapsed from CSI, 716 (70.6%) de novo] and 3103 non-seminoma (NSem) [626 (20.2%) relapsed from CSI, 2477 (79.8%) de novo] were identified. Among Sem, no statistically significant differences in PFS and OS were found between patients relapsing from CSI and de novo metastatic disease [5-year progression-free survival (5y-PFS) 87.6% versus 88.5%; 5-year overall survival (5y-OS) 93.2% versus 96.1%). Among NSem, PFS and OS were higher overall in relapsing CSI patients (5y-PFS 84.6% versus 80.0%; 5y-OS 93.3% versus 88.7%), but there were no differences within the same IGCCCG prognostic groups (HR = 0.89; 95% CI: 0.70-1.12). Relapses in the intermediate or poor prognostic groups occurred in 11/298 (4%) Sem and 112/626 (18%) NSem. CONCLUSION: Relapsing CSI GCT patients expect similar survival compared to de novo metastatic patients of the same ICCCCG prognostic group. Intermediate and poor prognosis relapses from initial CSI expose patients to unnecessary toxicity from more intensive treatments.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Neoplasms, Second Primary , Seminoma , Testicular Neoplasms , Male , Humans , Testicular Neoplasms/surgery , Prognosis , Progression-Free Survival , Seminoma/surgery , RecurrenceABSTRACT
OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.
Subject(s)
Anemia , Prostatic Neoplasms, Castration-Resistant , Male , Humans , BRCA1 Protein , Ribose , Prostatic Neoplasms, Castration-Resistant/pathology , BRCA2 Protein , Adenosine DiphosphateABSTRACT
Pine wilt disease is a devastating disease of pine caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus. Long-term use of chemical nematicides leads to the development of resistance in nematodes and harms the environment. Evaluations for green environmental protection agents, identified the antibacterial peptide, MaltDef1, from Monochamus alternatus which had nematicidal effect. We studied its nematicidal activity and action against PWN. In this study, the antibacterial peptide S-defensin was synthesized from M. alternatus. The results showed that S-defensin caused mortality to the PWN, causing shrinkage, pore, cell membrane dissolution and muscle atrophy. In addition, PWN reproduction was also affected by S-defensin; it decreased in a concentration dependent manner with increasing treatment concentration. By contrast, reactive oxygen species (ROS) in vivo increased in a concentration-dependent manner. We applied transcriptome to analyze the changes in gene expressions in S-defensin treated PWN, and found that the most significantly enriched pathway was the ERK/MAPK signaling pathway. RNAi was used to validate the functions of four differential genes (Let-23, Let-60, Mek-2 and Lin-1) in this pathway. The results showed that knockdown of these genes significantly decreased the survival rate and reproductive yield of, and also increased ROS in PWN. The antibacterial peptide S-defensin had a significant inhibitory effect on the survival and reproduction of PWN, shown by cell membrane damage and intracellular biological oxidative stress via regulating the ERK/MAPK signaling pathway. This indicates that S-defensin has a target in B. xylophilus, against which new green target pesticides can be developed.
Subject(s)
Coleoptera , Nematoda , Pinus , Tylenchida , Animals , Reactive Oxygen Species , Plant Diseases , Oxidative Stress , Antinematodal Agents/pharmacology , Signal Transduction , Reproduction , Tylenchida/genetics , DefensinsABSTRACT
BACKGROUND: The hepatic artery is the only blood source nourishing the biliary duct and associated with biliary complication after liver transplantation (LT). Gastroduodenal artery (GDA) disconnection increased proper hepatic artery flow. Whether this procedure attenuates biliary non-anastomotic stricture (NAS) is not clear. METHODS: A total of 241 patients with LT were retrospectively analyzed. The patients were divided into the GDA disconnection (GDA-) and GDA preservation (GDA+) groups. Propensity score matching (PSM) was administrated to reduce bias. Logistic regression was conducted to analyze risk factors for biliary NAS before and after PSM. Postoperative complications were compared. Kaplan-Meier survival analysis and log-rank tests were performed to compare overall survival. RESULTS: In all, 99 patients (41.1%) underwent GDA disconnection, and 49 (20.3%) developed NAS. Multivariate logistic regression revealed that GDA preservation (OR = 2.24, 95% CI: 1.11-4.53; P = 0.025) and model for end-stage liver disease (MELD) score > 15 (OR = 2.14, 95% CI: 1.12-4.11; P = 0.022) were risk factors for biliary NAS. PSM provided 66 pairs using 1:2 matching method, including 66 GDA disconnection and 99 GDA preservation patients. Multivariate logistic regression after PSM also showed that GDA preservation (OR = 3.15, 95% CI: 1.26-7.89; P = 0.014) and MELD score > 15 (OR = 2.41, 95% CI: 1.08-5.36; P = 0.031) were risk factors for NAS. When comparing complications between the two groups, GDA preservation was associated with a higher incidence of biliary NAS before and after PSM (P = 0.031 and 0.017, respectively). In contrast, other complications including early allograft dysfunction (P = 0.620), small-for-size graft syndrome (P = 0.441), abdominal hemorrhage (P = 1.000), major complications (Clavien-Dindo grade ≥ 3, P = 0.318), and overall survival (P = 0.088) were not significantly different between the two groups. CONCLUSIONS: GDA disconnection during LT ameliorates biliary NAS incidence and may be recommended for application in clinical practice.
Subject(s)
Constriction, Pathologic , Hepatic Artery , Liver Transplantation , Humans , Constriction, Pathologic/epidemiology , Constriction, Pathologic/prevention & control , End Stage Liver Disease/surgery , Hepatic Artery/surgery , Incidence , Liver Transplantation/adverse effects , Liver Transplantation/methods , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk FactorsABSTRACT
The efficiency of the rapidly exploring random tree (RRT) falls short when efficiently guiding targets through constricted-passage environments, presenting issues such as sluggish convergence speed and elevated path costs. To overcome these algorithmic limitations, we propose a narrow-channel path-finding algorithm (named NCB-RRT) based on Bi-RRT with the addition of our proposed research failure rate threshold (RFRT) concept. Firstly, a three-stage search strategy is employed to generate sampling points guided by real-time sampling failure rates. By means of the balance strategy, two randomly growing trees are established to perform searching, which improves the success rate of the algorithm in narrow channel environments, accelerating the convergence speed and reducing the number of iterations required. Secondly, the parent node re-selection and path pruning strategy are integrated. This shortens the path length and greatly reduces the number of redundant nodes and inflection points. Finally, the path is optimized by utilizing segmented quadratic Bezier curves to achieve a smooth trajectory. This research shows that the NCB-RRT algorithm is better able to adapt to the complex narrow channel environment, and the performance is also greatly improved in terms of the path length and the number of inflection points. Compared with the RRT, RRT* and Bi-RRT algorithms, the success rate is increased by 2400%, 1900% and 11.11%, respectively.
ABSTRACT
Copper ions play a crucial role in the progression of cancers. Tumor tissue is rich in copper ions, and copper chelators could potentially scavenge these copper ions and thus exert an antitumor effect. In this study, we report the synthesis of a novel thieno[3,2-c]pyridine compound we have called "JYFY-001" that can act as the copper chelator thanks to the inclusion of an N-(pyridin-2-yl)acetamide moiety that targets copper ions. JYFY-001 potently inhibited cancer proliferation, inducing cell apoptosis and impairing the extracellular acidification rate and oxygen consumption rate of colorectal cancer (CRC) cells. JYFY-001 also inhibited the growth of a CRC-transplanted tumor in a dose-dependent manner, inducing apoptosis of the tumor cells and promoting the infiltration of lymphocytes in the CRC-transplanted tumor tissues. JYFY-001 also enhanced the antitumor effects of the programmed cell death protein 1 (PD-1) inhibitor. The relatively benign nature of JYFY-001 was demonstrated by the effect on normal cell viability and acute toxicity tests in mice. Our findings suggest that JYFY-001 is a prospective copper chelator to be used as a targeted drug and a synergist of immunotherapy for CRC treatments.
Subject(s)
Colorectal Neoplasms , Copper , Mice , Animals , Copper/pharmacology , Copper/therapeutic use , Prospective Studies , Apoptosis , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Chelating Agents/pharmacology , Chelating Agents/therapeutic use , Ions/pharmacology , Ions/therapeutic use , Cell Proliferation , Cell Line, TumorABSTRACT
Insects have evolved to form a variety of complex natural compounds to prevent pathogen infection in the process of a long-term attack and defense game with various pathogens in nature. Antimicrobial Peptides (AMPs) are important effector molecules of the insect immune response to the pathogen invasion involved in bacteria, fungi, viruses and nematodes. The discovery and creation of new nematicides from these natural compounds is a key path to pest control. A total of 11 AMPs from Monochamus alternatus were classified into 3 categories, including Attacin, Cecropin and Defensin. Four AMP genes were successfully expressed by Komagataella phaffii KM71. The bioassay results showed that the exogenous expressed AMPs represented antimicrobial activity against Serratia (G-), Bacillus thuringiensis (G+) and Beauveria bassiana and high nematicide activity against Bursaphelenchus xylophilus. All four purified AMPs' protein against B. xylophilus reached LC50 at 3 h (LC50 = 0.19 mg·mL-1 of MaltAtt-1, LC50 = 0.20 mg·mL-1 of MaltAtt-2 and MaltCec-2, LC50 = 0.25 mg·mL-1 of MaltDef-1). Furthermore, the AMPs could cause significant reduction of the thrashing frequency and egg hatching rate, and the deformation or fracture of the body wall of B. xylophilus. Therefore, this study is a foundation for further study of insect biological control and provides a theoretical basis for the research and development of new insecticidal pesticides.
Subject(s)
Coleoptera , Rhabditida , Animals , Coleoptera/genetics , Insecta , Antinematodal Agents/pharmacology , PeptidesABSTRACT
The concept of superheated steam (SS) was proposed over a century ago and has been widely studied as a drying method. SS processing of cereals and cereal products has been extensively studied in recent years for its advantages of higher drying rates above the inversion temperature, oxygen-free environment, energy conservation, and environmental protection. This review provides a brief introduction to the history, principles, and classification of SS. The applications of SS processing in the drying, enzymatic inactivation, sterilization, mycotoxin degradation, roasting, and cooking of cereals and cereal products are summarized and discussed. Moreover, the effects of SS processing on the physicochemical properties of cereals and the qualities of cereal foods are reviewed and discussed. The applications of SS for cereal processing and its effects on cereal properties have been extensively studied; however, issues such as the browning of cereal foods, thermal damage of starch, protein denaturation, and nutrition loss have not been comprehensively studied. Therefore, further studies are required to better understand the mechanism of the quality changes caused by SS processing and to expand the fields of application of SS in the cereal processing industry. This review enhances the understanding of SS processing and presents theoretical suggestions for promoting SS processing to improve the safety and quality of cereals and cereal products.
Subject(s)
Edible Grain , Steam , Edible Grain/chemistry , Food Contamination/analysis , Food Microbiology , CookingABSTRACT
Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6â µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2â µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50â hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.
ABSTRACT
Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.