Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer.

Purpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.

A metal-organic framework (MOF) built on surface-modified Cu nanoparticles eliminates tumors via multiple cascading synergistic therapeutic effects.

Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl-d-tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8+ and CD4+ T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen (1O2) upon specific laser irradiation to effectively kill tumor cells. CaO2 on the outer layer generated oxygen (O2) and hydrogen peroxide (H2O2) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H2O2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment.

Electrochemical Trifluoromethylation and Sulfonylation of N-Allylamides: Synthesis of Oxazoline Derivatives.

We report a new method for the synthesis of trifluoromethylated and sulfonylated oxazolines by electrochemical radical cascade cyclizations of N-allylamides with sodium trifluoromethanesulfinate or sulfonylhydrazines. This protocol provides a green and useful strategy to synthesize trifluoromethylated and sulfonylated oxazolines with a broad substrate scope under ambient conditions.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

Characterization of Six Diamide Insecticides on Ryanodine Receptor: Resistance and Species Selectivity.

Ryanodine receptor (RyR) has been used as an insecticide target to control many destructive agricultural pests. The effectiveness of these insecticides has been limited by the spread of resistance mutations identified in pest RyRs, but the detailed molecular impacts of the individual mutations on the activity of different diamide compounds have not been fully explored. We created five HEK293 cell lines stably expressing wild type rabbit RyR1, wild type Spodoptera frugiperda RyR (Sf RyR), or Sf RyR carrying different resistance mutations, including G4891E, G4891E/I4734M, and Y4867F, respectively. R-CEPIA1er, a genetically encoded fluorescent protein, was also introduced in these cell lines to report the Ca2+ concentration in the endoplasmic reticulum. We systematically characterized the activities of six commercial diamide insecticides against different RyRs using the time-lapse fluorescence assay. Among them, cyantraniliprole (CYAN) displayed the highest activity against all three resistant Sf RyRs. The good performance of CYAN was confirmed by the toxicity assay using gene-edited Drosophila expressing the mutant RyRs, in which CYAN showed the lowest LD50 value for the double resistant mutant. In addition, we compared their acitivty between mammalian and insect RyRs and found that flubendiamide has the best insect-selectivity. The mechanism of the anti-resistance property and selectivity of the compounds was proposed based on the structural models generated by homology modeling and molecular docking. Our findings provide insights into the mechanism of insect resistance and guidance for developing effective RyR agonists that can selectively target resistant pests.

Electrochemical Decarboxylative Silylation of α,ß-Unsaturated Carboxylic Acids.

An electrochemical method for the decarboxylative silylation of α,ß-unsaturated carboxylic acids was developed. A variety of alkenylsilanes could be obtained in satisfactory yields and excellent selectivities under external oxidant- and metal-free conditions. Mechanistic studies showed that the formation of the silyl radical was mediated by NHPI, which produces the hydrogen atom transfer (HAT) reagent phthalimide N-oxyl (PINO) via multiple-site concerted proton-electron transfer (MS-CPET).

Annulation Reaction of Quinoxalin-2(1H)-ones Initiated by Electrochemical Decarboxylation of N-Arylglycines.

A new methodology for the synthesis of tetrahydroimidazo[1,5-a]quinoxalin-4(5H)-ones has been accomplished through annulation of quinoxalin-2(1H)-ones initiated by electrochemical decarboxylation of N-arylglycines catalyzed by ferrocene. With a pair of oxidative and reductive processes occurring among the substrates and intermediates instead of on the electrodes, the electricity consumption was decreased.

Electrochemically Enabled Sulfoximido-Oxygenation of Alkenes with NH-Sulfoximines and Alcohols.

An electrochemical oxidative sulfoximido-oxygenation of alkenes has been developed by using NH-sulfoximines and alcohols directly. This method proceeds regioselectively without metal catalysts and external chemical oxidants and shows broad substrate scope and diverse functional group compatibility. Based upon the preliminary mechanism studies, N-centered sulfoximidoyl radicals were involved in this electrochemical process.

Urban Management in the Dynamic Relationship between the Occurrence of Environmental Pollution Accidents and Economic Development in China.

After the reform and opening up, China has developed into a world factory due to the bias of Chinese policies, the need for urban development, and the limitations of science and technology. As a world factory, on the one hand, it expanded the scale of China's economy, raised the level of science and technology, and improved the standard of people's daily life. On the other hand, China's technology level was backward at the beginning of the reform and opening-up period, and the world countries in a competitive relationship could not give China a high-end technology level. Most of the developed countries only transferred their rough industries to China, which led to the "three highs and one low" pattern of China's economic development. The efficiency of resource utilization is very low, which not only wastes resources but also causes great deterioration of the environment. Based on China's environmental development problems, this article summarizes and analyses the relationship between economic development and environmental pollution through the perspective of EKC curve research. Then, using the data of economic growth target published by government work report of 230 prefecture-level cities from 2004 to 2014 collected by hand, the constraint of economic growth target is described from three dimensions. In particular, the study of economic growth target constraints is extended in terms of the portrayal of the characteristics of soft and hard constraints of economic growth targets. Finally, combining with the normative research method, feasible countermeasures are proposed for developed cities as well as less developed cities, providing new insights for the coordinated development of the urban environment and economy in China.

Electrochemical Oxidative C(sp2)-H Amination of Aldehyde Hydrazones with Azoles.

A general and highly efficient method for the electrochemical C(sp2)-H amination of aldehyde hydrazones with azoles has been developed. This reaction proceeds under exogenous metal-, catalyst-, and oxidant-free conditions to provide aminated hydrazone derivatives in good to excellent yields. This strategy applies to both aromatic and aliphatic aldehyde hydrazones and tolerates a broad range of functional groups.

The effect of acupuncture on postpartum stress urinary incontinence: A protocol for systemic review and meta-analysis.

BACKGROUND: Postpartum stress urinary incontinence (PSUI) is a widespread complaint in postpartum women, which significantly affects their quality of life. Acupuncture has been widely used as an alternative complementary therapy for the treatment of PSUI. This protocol is carried out to comprehensively explore the effectiveness and safety of acupuncture for treating PSUI. METHODS: Randomized clinical trials related to acupuncture treatment of PSUI will be searched in Chinese and English literature databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, and the Technology Periodical Database. Changes in pelvic floor muscle strength compared with baseline will be accepted as the primary outcomes, and secondary outcomes will be the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score, the urodynamic indexes, the incontinence quality of life questionnaire, and adverse effects of acupuncture. All publications will be screened and extracted by 2 reviewers independently. Quality of the eligible publications will be assessed according to the Cochrane Risk of Bias tool and statistical analyses will be conducted by using the Review Manager V.5.3. RESULTS: This study will provide a high-quality comprehensive evaluation for the clinical efficacy and safety of acupuncture for PSUI. CONCLUSION: This systematic review will provide comprehensive evidence of acupuncture treatment on specific outcomes for PSUI. ETHICS AND DISSEMINATION: Because of the study will not collect personal information, ethical approval will not be required. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION: INPLASY 202220045.

Electrosynthesis of (hetero)aryl nitriles from α-imino-oxy acids via oxidative decarboxylation/N-O cleavage.

A new method for the synthesis of (hetero)aryl nitriles via iminyl radicals has been developed through the electrochemical oxidative decarboxylation of α-imino-oxy acids. This protocol provides an efficient approach to nitriles with a broad range of functional-group tolerance under ambient conditions and can be applied for one-pot gram-scale synthesis.

Hydropyridylation of α,ß-Unsaturated Esters through Electroreduction of 4-Cyanopyridine.

A mild and highly efficient method for the hydropyridylation of α,ß-unsaturated esters has been developed. This protocol provides the products smoothly with a wide substrate scope in an undivided cell under ambient conditions. Moreover, studies showed that the scope could be extended to other unsaturated compounds, including enones and aldehydes.

Acupuncture therapies for postherpetic neuralgia: a protocol for a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common sequela of herpes zoster, and it is often refractory to guideline-recommended treatments. Acupuncture therapy, a wildly applied complementary-alternative treatment, may help in the management of PHN. Diverse types of acupuncture therapy for PHN have been proposed, however, their comparative efficacies remain unclear. This study protocol plans to compare the efficacy and safety of different acupuncture therapies for PHN. METHODS AND ANALYSIS: Databases including MEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register and OpenGrey will be searched from their inception to January 2022. Randomised controlled trials (RCTs) assessing the effectiveness of acupuncture therapy on the management of PHN will be selected. The primary outcome is pain intensity. Secondary outcomes include negative emotions, sleep condition, quality of life and adverse events. Reviewers will conduct study selection, data extraction and risk of bias assessment procedures. Then, standard pair-wised meta-analysis and Bayesian network meta-analysis will be performed (if applicable). The Confidence in Network Meta-Analysis application will be used to assess the confidence in the evidence for the primary outcome. ETHICS AND DISSEMINATION: All data used for this study will be extracted from published RCTs, thus, no ethical approval will be required. The results of this systematic review will be disseminated through peer-reviewed journal and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020219576.

Acupuncture and related therapies for carpal tunnel syndrome: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral nerve compression syndrome of the upper limb. Plenty of studies showed the effects of acupuncture therapy on relieving pain and improving functional status for CTS patients. Diverse types of acupuncture therapies have been used in the treatment for CTS, but their relative treatment effects are poorly understood. This study will evaluate the effects of different acupuncture and related therapies for CTS by conducting a systematic review and Bayesian network meta-analysis (NMA). METHODS: We will search randomized controlled trials (RCTs) of acupuncture and related therapies for CTS in MEDLINE (via PubMed), EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register, and OpenGrey from inception to November 2021. Then, we will select eligible studies, extract data, and conduct risk of bias assessment using the Cochrane tool. Pairwise meta-analysis and Bayesian NMA will be performed in Stata 15.1 software and Aggregate Data Drug Information System 1.16.8 software. We will assess the quality of the evidence using the Confidence in Network Meta-Analysis application. RESULTS: In this study, the treatment effects and safety of different acupuncture and related therapies for CTS will be evaluated. CONCLUSION: This study will provide evidence for choosing the optimal acupuncture and related therapies in the treatment for CTS.

Iminyl-radicals by electrochemical decarboxylation of α-imino-oxy acids: construction of indole-fused polycyclics.

Iminyl radicals are reactive intermediates that can be used for the construction of various valuable heterocycles. Herein, the electrochemical decarboxylation of α-imino-oxy acids for the generation of iminyl radicals has been accomplished under exogenous-oxidant- and metal-free conditions through the use of nBu4NBr as a mediator. The resulting iminyl radicals undergo intramolecular cyclization smoothly with the adjacent (hetero)arenes to afford a series of indole-fused polycyclic compounds.

Double ryanodine receptor mutations confer higher diamide resistance in rice stem borer, Chilo suppressalis.

BACKGROUND: The striped rice stem borer, Chilo suppressalis (Lepidoptera: Pyraidae), is one of the most serious rice pests in China. Chlorantraniliprole was used extensively for C. suppressalis control over the past ten years, and some field populations have developed high resistance. In this study, we report the chlorantraniliprole resistance status of C. suppressalis in China and the resistance mechanism. RESULTS: Significant geographical variations of chlorantraniliprole susceptibility were observed among 28 C. suppressalis field populations in 2019-2020. The LC50 values varied from 2907.874 mg L-1 (XS19) to 1.524 mg L-1 (QW19). Most tested field populations collected from Zhejiang, Jiangxi, Hunan and Anhui provinces in 2020 showed a high level of resistance to chlorantraniliprole (RR = 311.9-2060.1), whereas Jiangsu and Sichuan province populations remained susceptible. Analysis of RyR mutations showed that mutations of I4758M, Y4667D, Y4667C and Y4891F were present in resistant populations of C. suppressalis with different levels of chlorantraniliprole resistance. The frequency of the Y4667C mutation was correlated with chlorantraniliprole resistance in YY19 (RR = 702.6) and YY20 (RR = 1426.8) populations, with the homozygous mutation frequencies of 15.6% and 29.4%, respectively. High contributions of the I4758M and Y4667C double mutation to diamide resistance was demonstrated with CRISPR/Cas9-modified D. melanogaster. Flies bearing the Y4667C mutation (I4758M and Y4667C double mutation in C. suppressalis) exhibited high resistance to chlorantraniliprole (RR = 172.1), and moderate resistance to cyantraniliprole (RR = 79.2) and tetra chlorantraniliprole (RR = 43.6), which were higher than that of single mutations. CONCLUSIONS: Chlorantraniliprole resistance in C. suppressalis is intensifying in China. RyR double mutations (i.e. I4758M and Y4667C) confer higher diamide resistance than single mutations.

Monitoring and mechanisms of insecticide resistance in Spodoptera exigua (Lepidoptera: Noctuidae), with special reference to diamides.

The beet armyworm, Spodoptera exigua, is a major lepidopteran pest of global importance in cultivation of numerous crops including cotton, maize, soybean, onion, cabbage, and ornamentals. It has evolved resistance to different insecticides. However, the current status of insecticide resistance in S. exigua has not been well examined in China. In this study, concentration-mortality responses of S. exigua to seven insecticides, including chlorantraniliprole, tetraniliprole, methoxyfenozide, indoxacarb, chlorfenapyr, emamectin benzoate and beta-cypermethrin were evaluated. The results showed that most of the tested populations had developed moderate to high resistance to chlorantraniliprole, with resistance ratios ranging from 6.3 to 2477.3-fold. Our results also showed that chlorantraniliprole have cross-resistance with tetraniliprole in S. exigua. The AY19 population collected from Anyang in Henan Province in 2019 exhibited a high resistance level to beta-cypermethrin (RR = 277.5). Methoxyfenozide and chlorfenapyr were highly effective against all of the tested populations with resistance ratios (RR) ranging from 0.1 to 2.2-fold. One of the tested populations showed moderate resistance to indoxacarb and emamectin benzoate. We detected the known ryanodine receptor target site resistance mutation, I4743M, in the field populations of S. exigua with different levels of diamide resistance.

Susceptibility of fall armyworm, Spodoptera frugiperda (J.E.Smmith), to eight insecticides in China, with special reference to lambda-cyhalothrin.

Fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is the main destructive insect pest of grain crops that occurs in all maize growing regions of the Americas. It has rapidly invaded the Southern China since January 2019. However, the current status of insecticide resistance in S. frugiperda has not been reported in China. In this study, we determined the susceptibility of eight populations of FAW to eight insecticides by an artificial diet incorporation method. The results showed that among eight insecticides, emamectin benzoate, spinetoram, chlorantraniliprole, chlorfenapyr, and lufenuron showed higher toxicity to this pest, while lambda-cyhalothrin and azadirachtin exhibited lower toxicity. Susceptibility of S. frugiperda to indoxacarb was significantly different (10.0-fold for LC50) across the various geographic populations. To investigate the biochemical mechanism of FAW to lambda-cyhalothrin, we performed the synergism tests and the results showed that piperonyl butoxide (PBO) and triphenyl phosphate (TPP) produced a high synergism of lambda-cyhalothrin effects in the two field populations. Sequencing of the gene encoding the acetylcholinesterase (AChE) gene in the two field populations identified two amino acid mutations, all of which have been shown previously to confer resistance to organophosphates (OPs) in several arthropod species. The results of this study provided valuable information for choosing alternative insecticides and for insecticide resistance management of S. frugiperda.

Venom serine proteinase homolog of the ectoparasitoid Scleroderma guani impairs host phenoloxidase cascade.

The ant-like bethylid ectoparasitoid Scleroderma guani (Hymenoptera: Bethylidae) envenomates host to suppress immune response. Yet, the roles of its venom in inhibiting melanization of the host hemolymph have not been fully characterized. Here, we demonstrated that S. guani envenomation induced strong inhibition of melanization of the hemolymph from Tenebrio molitor (Coleoptera: Tenebrionidae), permitting the successful development of parasitoid offspring. To reveal venom component associated with such function, a serine proteinase homolog (SguaSPH) rich in the venom of S. guani was characterized. It was found that one of the catalytic triad residues for serine proteinase is absent in the amino acid sequence of SguaSPH. This venom component was abundantly expressed in venom apparatus and adult stages. By enzymatic assays, SguaSPH displayed low trypsin and no chymotrypsin activity, and was able to inhibit phenoloxidase activity in the hemolymph of Ostrinia furnacalis (Lepidoptera: Crambidae). The findings suggest that SguaSPH is essential for interfering with hemolymph melanization of S. guani envenomated host via phenoloxidase cascade disruption.