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Although Type-I photodynamic therapy has attracted increasingly growing interest due to its reduced dependence on oxygen, the design of effective Type-I photosensitizers remains a challenge. In this work, we report a design strategy for Type-I photosensitizers by the involvement of hydrogen atom transfer (HAT). As a proof of concept, a HAT-involved Type-I PS, which simultaneously generates superoxide and carbon-centered radicals under light-irradiation, was synthesized. This photosensitizer is comprised of a fluorene-substituted BODIPY unit as an electron acceptor covalently linked with a triphenylamine moiety as an electron donor. Under light-irradiation, photo-induced intramolecular electron transfer occurs to generate the BODIPY anion radical and triphenylamine cation radical. The former transfers electrons to oxygen to generate O 2 - ⋅, while the latter loses a proton to produce a benzyl carbon-centered radical which is well characterized. The resulting carbon-centered radicals efficiently oxidize NADH by HAT reaction. This photosensitizer demonstrates remarkable photocytotoxicity even under hypoxic conditions, along with outstanding in vivo antitumor efficacy in mouse models bearing HeLa tumors. This work offers a novel strategy for the design of Type-I photosensitizers by involvement of HAT., (© 2024 Wiley-VCH GmbH.)

Herein we report on circularly polarized luminescence (CPL) emission originating from supramolecular chirality of organic microcrystals with a |g lum | value up to 0.11. The microcrystals were prepared from highly emissive difluoroboron β-diketonate (BF 2 dbk) dyes R-1 or S-1 with chiral binaphthol (BINOL) skeletons. R-1 and S-1 exhibit undetectable CPL signals in solution but manifest intense CPL emission in their chiral microcrystals. The chiral superstructures induced by BINOL skeletons were confirmed by single-crystal XRD analysis. Spectral analysis and theoretical calculations indicate that intermolecular electronic coupling, mediated by the asymmetric stacking in the chiral superstructures, effectively alters excited-state electronic structures and facilitates electron transitions perpendicular to BF 2 bdk planes. The coupling increases cosθ μ,m from 0.05 (monomer) to 0.86 (tetramer) and triggers intense optical activity of BF 2 bdk. The results demonstrate that optical activity of chromophores within assemblies can be regulated by both orientation and extent of intermolecular electronic couplings., (© 2024 Wiley-VCH GmbH.)

Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time ( t 1/2 = 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical X c - /GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.

We herein present an approach of photo-induced disproportionation for preparation of Type-I photodynamic agents. As a proof of concept, BODIPY-based photosensitizers were rationally designed and prepared. The photo-induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH 4 ), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O 2 - ⋅). One of our Type-I photodynamic agents not only self-assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O 2 ), with a half-maximal inhibitory concentration (IC 50 ) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors., (© 2024 Wiley-VCH GmbH.)

Chirality, with its intrinsic symmetry-breaking feature, is frequently utilized in the creation of acentric crystalline functional materials that exhibit intriguing optoelectronic properties. On the other hand, the development of chiral crystals from achiral molecules offers a solution that bypasses the need for enantiopure motifs, presenting a promising alternative and thereby expanding the possibilities of the self-assembly toolkit. Nevertheless, the rational design of achiral molecules that prefer spontaneous symmetry breaking during crystallization has so far been obscure. In this study, we present a series of six achiral molecules, demonstrating that when these conformationally flexible molecules adopt a cis-conformation and engage in multiple non-covalent interactions along a helical path, they collectively self-assemble into chiral superstructures consisting of single-handed supramolecular columns. When these homochiral supramolecular columns align in parallel, they form polar crystals that exhibit intense luminescence upon grinding or scraping. We therefore demonstrate our molecular design strategy could significantly increase the likelihood of symmetry breaking in achiral molecular synthons during self-assembly, offering a facile access to novel chiral crystalline materials with unique optoelectronic properties., (© 2024 Wiley-VCH GmbH.)

Objective: To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins. Methods: A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ 2 tests, and linear regression analysis. Results: One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M (IQR),3.0(4.3) vs. 4.0(5.8), Z =-2.038, P =0.040).Additionally, the chronic venous insufficiency patients' quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs. 82.5(17.0), Z =-2.627, P =0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs. 12.0(7.0) weeks, Z =-3.217, P <0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ 2 =0.453, P =0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ 2 =4.800, P =0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions: CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT ( P  < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT ( P  < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening., Competing Interests: Xiao‐Tian Yu is the Medical Director, Ning Lv is the Chief Technology Officer, and Yi‐You Chen is the Chief Scientist at Hangzhou New Horizon Health Technology Company. The other authors declare no conflicts of interest., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Purpose of Review: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment., Recent Findings: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

It is a challenge to design photosensitizers to balance between the tumor-targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, an ultra-small nano-photosensitizer 1a with excellent tumor-specific accumulation and renal clearance is reported. It is formed from the self-assembly of compound 1 bearing three triethylene glycol (TEG) arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal-to-background ratio reaching as high as 11.5 after tail intravenous injection. The ultra-small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self-assembly also endows 1a with an 18.2-fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano-PS 1a manifests an excellent photodynamic therapy efficacy on tumor-bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor-targeting ability., (© 2023 Wiley-VCH GmbH.)

A multifunctional undecapeptide, YYDPLGLADYY, was designed and synthesized for the photowrapping of silica-coated gold nanorods. The obtained nanocapsules, bearing a well-defined core-shell structure, were able to encapsulate a therapeutic drug, respond to an MMP-upregulated tumor microenvironment, and achieve NIR-triggered anticancer chemo-photothermal therapy with favorable efficacy.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability., Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes., Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276])., Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Fan, Xiao, Feng, Niu, Tan, Sun, Leng, Li, Wang and Wang.)

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED 50 ) of GEN-0828 (10.91 KIU·kg -1 ) and NovoSeven® (18.91 KIU·kg -1 ) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg -1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (C max ) and area under the plasma concentration-time curve (AUC last ) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

We report a multi-stimuli-responsive luminescent material containing rotor moieties. It forms two types of crystals, G and O. The emission of G can be modulated by multiple external stimuli, whereas O does not show such responsiveness. The X-ray structure analysis reveals that the rotors are critical for the polymorphic emission and stimuli response properties.

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical ( • OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic • OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

Without external chiral intervention, it is a challenge to form homochirality from achiral molecules with conformational flexibility. We here report on a rational strategy that uses multivalent noncovalent interactions to clamp the molecular conformations of achiral D-A molecules. These interactions overcome the otherwise dominant dipole-dipole interactions and thus disfavor their symmetric antiparallel stacking. It in turn facilitates parallel packing, leading to spontaneous symmetry breaking during crystallization and thus the formation of homochiral conglomerates. When this emergent homochirality is coupled with optical gain characteristics of the molecules, the homochiral crystals are explored as excellent circularly polarized micro-lasers with low lasing threshold (16.4 μJ cm -2 ) and high dissymmetry factor g lum (0.9). This study therefore provides a facile design strategy for supramolecular chiral materials and active laser ones without the necessity of intrinsic chiral element., (© 2022 Wiley-VCH GmbH.)

A bendable transmission line (TL) of spoof surface plasmon polaritons (SSPPs) is presented, which can maintain good transmission performance despite of the deformation caused by bending. Such a TL consists of flexible dielectric substrate and ultrathin metallic strip with zigzag decorations that are designed to support the propagation of SSPPs with strong field confinement and low radiation loss. Furthermore, the proposed SSPP TL is used to excite an amplifier chip efficiently, reaching high and stable gains with nearly no degradation of amplification in the bending states. Numerical and experimental results are demonstrated to verify the bendable merits of both passive TL and active amplifier from 12 GHz to 18 GHz. The flexible and stable characteristics of this design may find utility in novel applications like wearable electronics and conformal plasmonic circuits in the microwave frequencies.

Objective: Cyclooxygenase (COX) is critical in regulating cardiovascular function, but its role involved in the central control of blood pressure (BP) is uncovered. The tonic glutamatergic inputs to the rostral ventrolateral medulla (RVLM) are enhanced in hypertension. Here, the present study was designed to investigate the effect and mechanism of central COX on tonic glutamatergic inputs to the RVLM and BP regulation., Methods: Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) received RVLM microinjection of adeno-associated viral vectors to promote or inhibit the COX2 expression were subjected to subsequent experiments. Glutamate level and glutaminase expression were detected by ELISA and western blot, respectively. The function of tonic glutamatergic inputs was assessed by BP response to microinjection of the glutamate receptor antagonist into the RVLM. PC12 cells were used to detect the underlying signal pathway., Results: The RVLM COX2 expression and prostaglandin E2 level were significant higher in SHRs than in WKY rats. Overexpression of COX2 in the RVLM produced an increase in basal BP, RVLM glutamate level, and glutaminase expression in WKY rats, while they were significantly reduced by interfering with COX2 expression in SHRs. Microinjections of the glutamate receptor antagonist into the RVLM produced a significant BP decrease in WKY rats with COX2 overexpression pretreatment. Furthermore, the increased levels of BP, glutamate content, and glutaminase activity in the RVLM evoked by central infusion of angiotensin II were attenuated in COX2 knockout mice. It was also found that prostaglandin E2 increased supernatant glutamate level and phosphorylation of signal transducer and activator of transcription 3 in PC12 cells., Conclusion: Our findings suggest that upregulated COX2 expression enhances the tonically active glutamatergic inputs to the RVLM, which is associated with cardiovascular regulation in hypertension., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the application effect of the modified wire-loop snare technique in retrieving severely tilted inferior vena cava filters (IVCF). Methods: The clinical data of 18 patients (12 males and 6 females, aged (62.1±13.1) years (range: 29 to 78 years)) who underwent the modified wire-loop snare technique to retrieve IVCF at the Affiliated Hospital of Qingdao University, Qingdao Eighth People's Hospital, and Jimo District Hospital of Traditional Chinese Medicine from November 2017 to April 2022 were retrospectively analyzed. The applied filters included drum-type filters (OptEase in 7 cases, Aegisy in 2 cases) and conical filters (Celect in 6 cases and Denali in 3 cases). Preoperative CT angiography and intraoperative digital subtraction angiography showed that the filter was severely tilted and the hook was covered by hyperplastic intima of the vena cave vein. A modified wire-loop snare technique was used to retrieve drum-type filters and conical filters via femoral and jugular vein approaches, respectively. After successful puncture, the long sheath was placed, the 4 F (1 F≈0.33 mm) vertebral catheter and a snare were inserted through the long sheath, and the 5 F pigtail catheter was inserted simultaneously to guide a 0.035 inch soft guide-wire (260 cm in length) to pass through the top of the filter and turning back. The tip of the soft guide-wire was snared by the vertebral catheter and pulled out of the sheath. The 4 F vertebral catheter was inserted following the tip of the guide-wire to form a wire-loop using the vertebral catheter and the pigtail catheter. After fixing the tip and tail of the soft guide-wire in vitro , the long sheath was pushed forward to cut the hyperplastic intima and the hook was pulled away from the vena cava wall to retrieve the filter under the support of two catheters. Results: The filters were successfully retrieved in 17 cases, the operation time was (25.5±8.7) minutes (range: 15 to 45 minutes), no complication occured. The hook of one filter (Celect) penetrated out of the vena vava wall and the wire-loop could not pull the hook back into the vena cava. Then the filter was removed by laparotomy. Conclusion: The modified wire-loop snare technique could retrieve the severely tilted retrivable drum-type filters and conical filters, even when serve adhesion exists between the filter and the vena cava wall.

Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare Type-I PSs is of great importance, but remains a challenge. Here, we report a supramolecular strategy for the preparation of Type-I photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors to the existing Type-II PSs. As a proof-of-concept, three electron acceptors were designed and co-assembled with a classical PS to produce quadruple hydrogen-bonded supramolecular photodynamic agents. The photo-induced electron transfer from the PS to the adjacent electron acceptor occurs efficiently, leading to the generation of a strong oxidizing PS +• and an anionic radical of the acceptor, which further transfers an electron to oxygen to form O 2 -• . In addition, these photodynamic agents induce direct photocatalytic oxidation of NADH with a turnover frequency as high as 53.7 min -1 , which offers an oxygen-independent mechanism to damage tumors., (© 2022. The Author(s).)

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains unclear, making the diagnosis and treatment challenging. Cardiac oxidative and nitrative stress are strongly implicated in the pathogenesis of HFpEF. Herein, we present a unique three-channel fluorescent probe for evaluating cardiac oxidative and nitrative stress in HFpEF by simultaneous detection of NO and GSH. The probe exhibits a native green fluorescence (probe channel), while the presence of GSH and NO can sensitively turn the native green fluorescence into red fluorescence (GSH channel) and near-infrared fluorescence (NO channel), respectively. The probe clearly reveals that both GSH and NO levels are upregulated in cardiomyocytes and heart tissue with HFpEF. Moreover, it uncovers that the enhancement in NO and GSH levels are closely associated with increased level of iNOS (inducible nitric oxide synthase) and activation of the Keap1 (Kelch-like ECH-associated protein 1)/Nrf2 (nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response element) signaling pathway in cardiomyocytes, respectively. This work proposes a promising approach for distinguishing normal heart and HFpEF heart by in vivo noninvasive imaging of both GSH and NO, and greatly contributing to the improvement of the diagnosis and treatment of HFpEF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report J-aggregates of a boron dipyrromethene derivative (BDP-Nit) as an H 2 S-activatable nano-photosensitizer. The closely packed BDP-Nit in J-aggregates exhibits high selectivity to H 2 S over biothiols to produce an active photosensitizer.

Type-I photosensitizers (PSs) generate cytotoxic oxygen radicals by electron transfer even in a hypoxic environment. Nevertheless, the preparation of type-I PSs remains a challenge due to the competition of triplet-triplet energy transfer with O 2 (type-II process). In this work, we report an effective strategy for converting the conventional type-II PS to a type-I PS by host-guest complexation. Electron-rich pillar[5]arenes are used as an electron donor and macrocyclic host to produce a host-guest complex with the traditional electron-deficient type-II PS, an iodide BODIPY-based guest. The host-guest complexation promotes intermolecular electron transfer from the pillar[5]arene moiety to BODIPY and then to O 2 by the type-I process upon light-irradiation, leading to efficient generation of the superoxide radical (O 2 - ˙). The results of anti-tumor studies indicate that this supramolecular PS demonstrates high photodynamic therapy efficacy even under hypoxic conditions. This work provides an efficient method to prepare type-I PSs from existing type-II PSs by using a supramolecular strategy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report N,O-boron-chelated dipyrromethene derivatives exhibiting circularly polarized luminescence (CPL) in the red/near-infrared region, both in solution and the aggregated state. The CPL is originated from the helical chirality through intramolecular substitution of fluorine by an alkenolic substituent. The self-assembly of the fluorophores significantly enhances the | g lum | values from 10 -4 to 10 -2 .

The modulation of the properties of emission from multiple emission states in a single-component organic luminescent material is highly desirable in data anticounterfeiting, information storage, and bioapplications. Here, a single-component luminescent organic crystal of difluoroboron diphenyl β-diketonate with controllable multiple emission colors is successfully reported. The temperature-dependent luminescence experiments supported by high-level theoretical calculations demonstrate that the ratio of the fluorescence between the monomer and excimer and the phosphorescence maxima of the excimer can be effectively regulated. In addition, the temperature-dependent fluorescence and afterglow dual-emission color changes provide a new strategy for the design of highly accurate double-checked temperature sensors.

Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type-I process. Herein, we report a series of α,β-linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O 2 -. ) by the Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S 1 ) to triplet (T 1 ) states via an intermediate triplet (T 2 ) state. The low reduction potential and ultralong lifetime of the T 1 state facilitate the efficient generation of O 2 -. by inter-molecular charge transfer to molecular oxygen. The energy gap of T 1 -S 0 is smaller than that between 3 O 2 and 1 O 2 thereby precluding the generation of singlet oxygen by the Type-II process. The trimer exhibits superior PDT performance under the hypoxic environment., (© 2021 Wiley-VCH GmbH.)

Objective: To examine the long-term efficacy of radiofrequency closure in the treatment of great saphenous vein varicose. Methods: The clinic data of 185 patients with varicose veins of lower limbs treated with radiofrequency closure admitted at Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University from July 2016 to January 2017 was analyzed retrospectively. A total of 203 limbs were treated by radiofrequency closure. The long-term efficacy of radiofrequency closure was evaluated by analyzing the closure rate, clinical-etiology- anatomy-pathophysiology (CEAP) grading, venous clinical severity score (VCSS), chronic venous insufficiency questionnaire (CIVIQ) score, and complications, using repeated measures analysis of variance. Results: All procedures were successful. The closure rate was 98.0% (199/203) at one year and two years postoperative, which was still maintained at 97.5% (198/203) at 3 years of follow-up. Postoperative CEAP grading was significantly downgraded compared with that before the operation. Totally 88.4% (76/86) of C5 to C6 grade patients downgraded to C2 to C4 grade at 6 months, and 95.3% (82/86) downgraded to C0 to C2 garde at 3 years postoperative. VCSS and CIVIQ score in both groups significantly improved at all follow-up time points compared to preoperative scores (VCSS: F =1 064.7, P =0.003; CIVIQ score: F =2 984.3, P =0.001). The most common complication was subcutaneous blood stasis (10.8%), most of which disappeared within 1 month after the surgery. Other complications included pigmentation and thrombophlebitis (5.9% and 3.9%, respectively). Conclusion: The long-term efficacy of radiofrequency closure of the great saphenous vein is satisfactory.

Excitation energy transfer (EET) as a fundamental photophysical process is well-explored for developing functional materials with tunable photophysical properties. Compared to traditional fluorophores, aggregation-induced emission luminogens (AIEgens) exhibit unique advantages for building EET systems, especially serving as energy donors, due to their outstanding photophysical properties such as bright fluorescence in aggregation state, broad absorption and emission spectra, large Stokes shift, and high photobleaching resistance. In addition, the photophysical properties of AIEgens can be modulated by energy transfer for improved luminescence performance. Therefore, a variety of EET systems based on AIEgens have been constructed and their applications in different areas have been explored. In this review, we summarize recent progress in the design strategy of AIE-based energy transfer systems for light-harvesting, fluorescent probes and theranostic systems, with an emphasis on design strategies to achieve desirable properties. The limitations, challenges and future opportunities of AIE-EET systems are briefly outlined. Design strategies and applications (light-harvesting, fluorescent probe and theranostics) of AIEgen-based excitation energy systems are discussed in this review.

Clarifying the signaling pathway associated with nitric oxide (NO) and glutathione (GSH) in cardiovascular disease therapy is important for understanding its physiological and pathological processes but is challenging due to the lack of efficient analytical techniques. Herein, we report a BODIPY-based fluorescent probe for recognition of NO and GSH in sequence with high sensitivity and selectivity. The probe exhibits turn-on fluorescence triggered by NO, followed by red-shifted emission in the presence of GSH. The sequentially activated mechanism allows the visualization of NO-induced GSH upregulation in drug-treated endothelial cells and zebrafish for the first time, revealing a signal pathway during the therapy. We hope that it can be used as a convenient and efficient tool for the study of the interplay between NO and GSH and for the screening of effective drugs for cardiovascular disease therapy.

To establish the method for determining non-volatile ingredients of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isochlorogenic acid A, rosmarinic acid, ferulic acid, rutin, luteoloside, isoquercitrin, hesperidin, diosmin, diosmetin, luteolin, acacetin and linarin in Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS, and analyze the correlation of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces. Shim-pack GIST C&#95;(18) column(2.1 mm×100 mm, 2 μm) was adopted with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution at the flow rate of 0.4 mL·min~(-1). The column temperature was set at 35 ℃. The quantitative analysis was performed using the electrospray ionization source and the multiple reaction monitoring. The linear relationship, resolution, repeatability and recovery of the 16 chemical components all met the requirements. The 16 non-volatile ingredients in traditional herbal pieces of Menthae Haplocalycis Herba could be tracked in formula granules. There were certain differences of the 16 chemical components among Menthae Haplocalycis Herba formula granules of different manufacturers and traditional herbal pieces of different producing areas. The UPLC-MS/MS method was simple, rapid and accurate, and could be used for the quality control of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces.

Photosensitizing agents are essential for precise and efficient photodynamic therapy (PDT). However, most of the conventional photosensitizers still suffer from limitations such as aggregation-caused quenching (ACQ) in physiological environments and toxic side-effects on normal tissues during treatment, leading to reduced therapeutic efficacy. Thus, integrating excellent photophysical properties and accurate carcinoma selectivity in a photosensitizer system remains highly desired. Herein, a "dual lock-and-key" supramolecular photosensitizer BIBCl-PAE NPs for specific and enhanced cancer therapy is reported. BIBCl-PAE NPs are constructed by encapsulating a rationally designed glutathione (GSH)-activatable photosensitizer BIBCl in a pH-responsive diblock copolymer. In normal tissues, BIBCl is "locked" in the hydrophobic core of the polymeric micelles due to ACQ. Under the "dual key" activation of low pH and high levels of GSH in a tumor microenvironment, the disassembly of micelles facilitates the reaction of BIBCl with GSH to release water-soluble BIBSG with ideal biocompatibility, enabling the highly efficient PDT. Moreover, benefiting from the Förster resonance energy transfer effect of BIBSG, improved light harvesting ability and 1 O 2 production are achieved. In vitro and vivo experiments have demonstrated that BIBCl-PAE NPs are effective in targeting and inhibiting carcinoma. BIBCl-PAE NPs show superior anticancer efficiency relative to non-activatable controls., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Biothiols and SO 2 derivatives, as essential reactive sulfur species (RSS), play vital roles in various physiological processes and have a close network of generation and metabolic pathways among them. To clarify their complex correlations, fluorescent probes to simultaneously detect GSH, Cys, and SO 2 derivatives are highly desirable. Herein, we develop the first fluorescent probe ( BO-HEM ) to simultaneously discriminate GSH, Cys, and SO 2 derivatives. The fluorescent probe is designed by integration of hemicyanine and BODIPY fluorophores through an ether bond. The ether bond of the probe is rapidly replaced by thiolates through nucleophilic aromatic substitution (S N Ar) to generate hemicyanine with NIR fluorescence and sulfur-BODIPY . The amino groups of Cys but not GSH then further replace the thiolate to form amino-BODIPY . As for SO 3 2- , nucleophilic addition to the double bond of BO-HEM generates adduct O-BODIPY with green fluorescence. To further improve the sensing performance, the nanoprobe with increased reactivity and biocompatibility is constructed by encapsulation of BO-HEM into the polymeric micelle. More importantly, by taking advantage of the hydrophilicity of the reaction products, the spectral discrimination was further enhanced to avoid signal interference. The nanoprobe is applied to discriminate biothiols and SO 2 derivatives in living cells through three-color fluorescence imaging.

An organic crystal of 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (pCBP) exhibits time-dependent afterglow color from blue to orange over 1 s. Both experimental and computational data confirm that the color evolution results from well-separated, long-persistent thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) with different but comparable decay rates. TADF is enabled by a small S 1 -T 1 energy gap of 0.7 kcal mol -1 . The good separation of TADF and RTP is due to a 11.8 kcal mol -1 difference in the S 0 energies of the S 1 and T 1 structures, indicating that apart from the excited-state properties, tuning the ground state is also important for luminescence properties. This afterglow color evolution of pCBP allows its applications in anticounterfeiting and data encryption with high security levels., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a series of difluoroboron β-diketonate fluorophores that manifest temperature-dependent emission wavelength accompanied by a change of fluorescence from green to orange. The distinct emission changes allow convenient and accurate measurements of temperature.

Background & Aims: The objective nutritional assessment indicators, body mass index (BMI), upper arm muscle circumference (MAMC), and triceps skinfold thickness (TSF), are often limited due to ascites. This study investigated the prognostic value of the third lumbar vertebrae skeletal muscle mass index (L3 SMI) in addition to the objective nutritional evaluation indicators (BMI, MAMC and TSF) in patients with liver cirrhosis and ascites., Methods: In this retrospective analysis, a total of 147 patients with liver cirrhosis and ascites were included. The L3 SMI, BMI, MAMC and TSF were detected in all patients. The severity of liver disease was assessed by the Model End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) classification. These variables were compared between non-surviving and surviving patients who were classified according to 5-year mortality., Results: Of the 147 patients, 62 (42.2%) died and 85 (57.8%) survived within 5 years. The L3 SMI of patients was significantly lower than that of the normal control group (39.58 ± 7.18 cm 2 /m 2 vs. 53.73 ± 7.92 cm 2 /m, 2 p < 0.001). The L3 SMI (OR 4.02; 95% CI 2.17-9.63; p < 0.001), MELD score (OR 2.11; 95% CI 1.12-4.13; p < 0.001) and CTP class (OR 2.69; 95% CI 1.09-5.06; p < 0.001) were independent predictive indicators of 5-year mortality. Furthermore, the performance of the two variables (L3 SMI and MELD) together (AUROC: 0.812) was significantly better than that of MELD alone (AUROC: 0.787) for prediction of 5-year mortality (p < 0.001)., Conclusion: Compared with MAMC, TSF and BMI, L3 SMI is an independent risk factor for 5-year mortality in patients with liver cirrhosis and ascites. Further nutritional intervention studies are needed to confirm the impact of the L3 SMI index on clinical outcomes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

SO2, an important gasotransmitter, plays significant roles in human physiological activities. The reported probes for the detection of SO2 derivatives are mostly based on the quenching or blue-shift of fluorescence, leading to interference from the background signal. Herein, we develop a novel FRET-based nanoprobe that shows turn-on fluorescence at 615 nm in the presence of SO32-/HSO3-. The nanoprobe consists of N,O,B-chelated dipyrromethene (BDP) as the energy donor, and hemicyanine derivatives of HEM-CO-Ph with a responsive site to SO32-/HSO3- as the energy acceptor. Initially, the fluorescence of BDP is quenched by HEM-CO-Ph due to the efficient FRET process. In the presence of sulfites, the nucleophilic addition interrupts the conjugation of HEM-CO-Ph and results in a 200 nm blue-shift of the absorption, leading to the suppression of the FRET process and recovery of the red fluorescence of BDP. The nanoprobe shows fast response to SO32-/HSO3- with high selectivity, great biocompatibility and cellular uptake. It is the first supramolecular nanoprobe for the detection of SO32-/HSO3- by using intermolecular energy transfer, ingeniously turning the nanoprobe from "OFF" state to "ON" state. The nanoprobe is applied to monitor exogenous and endogenous SO2 derivatives in the mitochondria of living cells.

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats' plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients., Competing Interests: The authors have declared no conflicts of interest.

We report an unexpected coupling-reduction tandem reaction as a general and efficient one-pot synthesis of alkenyl-substituted boron dipyrromethene (BODIPY) from chlorinated-BODIPY and alkyne. This unique synthesis combined the Sonogashira coupling reaction and reduction reaction without adding an additional reagent, which shows higher yields, broader substrate scope and faster reaction rate compared with the conventional methods of the Knoevenagel reaction and Heck coupling reaction.

Bacillus thuringiensis insecticidal proteins (Bt toxins) have been widely used in crops for agricultural pest management and to reduce the use of chemical insecticides. Here, we have engineered Bt toxin Cry2Ab30 and bioconjugated it with 4"-O-succinyl avermectin (AVM) to synthesize Cry2Ab-AVM bioconjugate. It was found that Cry2Ab-AVM showed higher insecticidal activity against Plutella xylostella , up to 154.4 times compared to Cry2Ab30. The binding results showed that Cry2Ab-AVM binds to the cadherin-like binding protein fragments, the 10th and 11th cadherin repeat domains in the P. xylostella cadherin (PxCR 10-11 ), with a much higher affinity (dissociation equilibrium constant K D = 3.44 nM) than Cry2Ab30 ( K D = 28.7 nM). Molecular docking suggested that the macrolide lactone group of Cry2Ab-AVM ligand docking into the PxCR 10-11 is a potential mechanism to enhance the binding affinity of Cry2Ab-AVM to PxCR 10-11 . These findings offer scope for the engineering of Bt toxins by bioconjugation for improved pest management.

Using a metamaterial consisting of metals with subwavelength surface patterning, one can mimic surface plasmon polaritons (SPPs) and achieve surface waves with subwavelength confinement at microwave and terahertz frequencies, thus bringing most of the advantages associated with the optical SPPs to lower frequencies. Due to the properties of strong field confinement and high local field intensity, spoof SPPs have demonstrated the improved performance for data transmission and device miniaturization in an intensively integrated environment. The distinctive abilities, such as suppression of transmission loss and bending loss, and increase of signal integrity, make spoof SPPs a promising candidate for future generation of electronic circuits and electromagnetic systems. This article reviews the progress in spoof SPPs with a special focus on their applications in circuits from transmission lines to passive and active devices in microwave and terahertz regimes. The integration of versatile spoof SPP devices on a single platform, which is compatible with established electronic circuits, is also discussed., (Copyright © 2019 Science China Press. Published by Elsevier B.V. All rights reserved.)

We report a series of organic fluorophores that undergo selective self-sensitized photooxidation upon light irradiation in air accompanied by a change of fluorescence from yellow to blue on the seconds timescale. The distinct emission changes allow the ratiometric quantitation of O 2 concentration.

Nitric oxide (NO) and glutathione (GSH) have interplaying roles in oxidant-antioxidant balance. In this work, we developed the first example of a single fluorescent probe that displayed a turn-on fluorescence response toward NO and GSH from dual emission channels. The probe was synthesized by introducing 4-amino-3-(methylamino)-phenol to a BODIPY scaffold. Specifically, the NO-mediated transformation of diamine into a triazole triggered the fluorescence in the green channel, and the GSH-induced S N Ar substitution reaction led to the red-shifted emission in the red channel. The probe was successfully applied to detect the exogenous and endogenous NO and GSH in macrophage cells. More importantly, the probe revealed that NO induced by interferon-γ (IFN-γ), lipopolysaccharide (LPS), and l-arginine (l-Arg) could also elicit the augmentation of intracellular GSH. We anticipate the probe would hold great potential for investigating the redox balance in biological processes.

Chemical research of the medicinal plant Hemsleya amabilis (Cucurbitaceae) yielded five new cucurbitane-type triterpenes hemslelis A⁻E ( 1 ⁻ 5 ) by silica gel column, ODS column, and semi-HPLC techniques. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Compounds 1 ⁻ 5 were evaluated for their cytotoxic activities against three human tumor cell lines, Hela, HCT-8, and HepG-2, with the IC 50 ranging from 5.9 to 33.9 μM compared to Cisplatin.

This present study aims to establish a UPLC method for simultaneously determining eleven components such as new chlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,artichoke,isochlorogenic acid A,isochlorogenic acid B,isochlorogenic acid C,rutin,hibisin and loganin in Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica and comparing the differences in the contents of phenolic acids,flavonoids and iridoid glycosides of Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.The method was carried out on an ACQUITY UPLC BEH C18column(2.1 mm×100 mm,1.7 μm) by a gradient elution using acetonitrile and 0.1% phosphoric acid.The flow rate was 0.3 mL·min-1.The column temperature was maintained at 30 ℃.The sample room temperature was 8 ℃.The wavelength was set at 326 nm for new chlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,artichoke,isochlorogenic acid A,isochlorogenic acid B and isochlorogenic acid C,352 nm for rutin and lignin,and 238 nm for loganin.The injection volume was 1 μL.The eleven components has good resolution and was separated to baseline.Each component had a wide linear range and a good linear relationship(r≥0.999 6),the average recovery rate(n=9) was 98.96%,100.7%,97.24%,97.06%,99.53%,96.78%,98.12%,95.20%,95.12%,100.2%,98.61%and with RSD was 2.5%,1.4%,1.9%,2.1%,1.7%,1.9%,1.6%,2.0%,1.4%,2.2%,2.0%,respectively.Based on the results of the content determination,the chemometric methods such as cluster analysis and principal component analysis were used to compare the Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.The results showed that Lonicerae Japonicae Flos and leaves of Lonicera japonica were similar in the chemical constituents,but both showed chemical constituents difference compored to Lonicerae Japonicae Caulis.The established multi-component quantitative analysis method can provide a reference for the quality control of Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.

The first example of the synthesis of mono-N,O-B-chelated dipyrromethene (BODIPY) derivatives through an unexpected intramolecular nucleophilic displacement of the fluorine by alkenols in the presence of boron trifluoride as Lewis acid is reported. The chlorine in the indacene core allowed for further structural modifications through nucleophilic substitutions or palladium-catalysed coupling reactions to afford new fluorophores with tuneable photophysical properties. Their expanded conjugation structure resulted in distinct red-shifted absorption and emission spectra in organic solutions. Furthermore, the twisted steric hindrance of the benzene substitution patterns suppressed aggregation-induced quenching, leading to an enhanced NIR emission in the aggregate/solid state, which was rarely observed for BODIPY dyes. Nanoparticles of the fluorophores formed by the assembly with the polymeric surfactant F127 were successfully used for bioimaging of living cells and for tumour-targeted imaging in a tumour-bearing mouse model., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the switchable optical waveguide microfibers based on fluorescent supramolecular polymer for the first time. The pillar[5]arene-based supramolecular polymeric microfibers were prepared easily from the viscous solution of bispillar[5]arene host (bisP5A) and diphenylanthracene-derived guest (GD). The resulting microfibers  act as an active optical waveguide material with long propagation distance (400 μm) and low optical propagation loss (0.01 dB/μm). When photoresponsive dithienylethene-derived guest (GDTE) was added, the resulting ternary microfibers show switchable optical waveguide by the noninvasive control of UV/vis light with negligible fatigue over four cycles. This convenient preparation method is also applied for the quadruple-hydrogen-bonded fluorescent supramolecular polymeric microfibers which imply good light propagation property with an optical loss coefficient of 0.02 dB/μm.

We report a new molecular design for optically triggered nm-scale translation of a submolecular component relative to another. We used a rotaxane-like molecule terminated at one end with stiff stilbene that served both as a chromophore to trigger the translation of the pillar[5]arene "wheel" and as a stopper to prevent its dethreading.

Cry2Ab, a pore-forming toxin derived from Bacillus thuringiensis, is widely used as a bio-insecticide to control lepidopteran pests around the world. A previous study revealed that proteolytic activation of Cry2Ab by Plutella xylostella midgut juice was essential for its insecticidal activity against P. xylostella, although the exact molecular mechanism remained unknown. Here, we demonstrated for the first time that proteolysis of Cry2Ab uncovered an active region (the helices α4 and α5 in Domain I), which was required for the mode of action of Cry2Ab. Either the masking or the removal of helices α4 and α5 mediated the pesticidal activity of Cry2Ab. The exposure of helices α4 and α5 did not facilitate the binding of Cry2Ab to P. xylostella midgut receptors but did induce Cry2Ab monomer to aggregate and assemble a 250-kDa prepore oligomer. Site-directed mutagenesis assay was performed to generate Cry2Ab mutants site directed on the helices α4 and α5, and bioassays suggested that some Cry2Ab variants that could not form oligomers had significantly lowered their toxicities against P. xylostella. Taken together, our data highlight the importance of helices α4 and α5 in the mode of action of Cry2Ab and could lead to more detailed studies on the insecticidal activity of Cry2Ab., (© 2018 John Wiley & Sons Ltd.)

Proteolysis of Vip3Aa by insect midgut proteases is essential for their toxicity against target insects. In the present study, proteolysis of Vip3Aa was evaluated by Spodoptera exigua midgut proteases (MJ). Trypsin was verified involved in the activation of Vip3Aa and three potential cleavage sites (Lys 195 , Lys 197 and Lys 198 ) were identified. Four Vip3Aa mutants (KKK195197198AAA, KK197198AA, KK195198AA and KK195197AA) were designed and constructed by replacing residues Lys 195,197,198 , Lys 197,198 , Lys 195,198 and Lys 195,197 with Ala, respectively. Proteolytic processing assays revealed that mutants KK197198AA, KK195198AA and KK195197AA could be processed into 66kDa activated toxins by trypsin or MJ while mutant KKK195197198AAA was not cleaved by trypsin and less susceptible to MJ. Bioassays demonstrated that mutants KK197198AA, KK195198AA and KK195197AA were toxic against S. exigua resembled that of wild-type Vip3Aa, however, the LC 50 of mutant KKK195197198AAA against S. exigua was higher than wild-type. Those results suggested that proteolysis by MJ was associated with the insecticidal toxicity of Vip3Aa against S. exigua. It also revealed that trypsin played an important role in the formation of Vip3Aa activated toxin. Our studies characterized the proteolytic processing of Vip3Aa and provided new insight into the activation of this novel Bt toxin., (Copyright © 2017 Elsevier B.V. All rights reserved.)