Thiosemicarbazone Mixed-Valence Cu(I/II) Complex against Lung Adenocarcinoma Cells through Multiple Pathways Involving Cuproptosis.

Induction of cuproptosis and targeting of multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([CuII(L)Cl] 1 and [CuII2CuI(L)2Cl3] 2, where HL is the (E)-N-methyl-2-(phenyl(pyridin-2-yl)methylene ligand), to assess their antilung cancer activities. Both copper complexes showed better anticancer activity than cisplatin and exhibited hemolysis comparable to that of cisplatin. In vivo experiments showed that complex 2 retarded the A549 cell growth in a mouse xenograft model with low systemic toxicity. Primarily, complex 2 kills lung cancer cells in vitro and in vivo by triggering multiple pathways, including cuproptosis. Complex 2 is the first mixed-valent Cu(I/II) complex to induce cellular events consistent with cuproptosis in cancer cells, which may stimulate the development of mixed-valent copper complexes and provide effective cancer therapy.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

Assessment of Mononuclear/Dinuclear copper acylhydrazone complexes for lung cancer treatment.

Non-platinum metal-based complexes have good potential for cancer treatment. Here, we designed and synthesized five hydrazone copper(II) complexes, [Cu2(HL)2Cl2] 1A, [Cu2(HL)2(NO3)H2O]·NO3 2A, [Cu2(HL)2Br2] 3A, [Cu(L)pyridine] 1B and [Cu(HL)(pyridine)Br] 3B, and evaluated their anti-lung cancer activities. MTT experiments revealed that these copper(II) complexes exhibit higher anticancer activity than cisplatin. Mechanism studies revealed that complex 3A induced G1 phase cell cycle arrest, and induced cell apoptosis via reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Scratch wound healing assay was also performed, revealing that complex 3A have good anti-cell migration activity. Hemolysis assays showed good blood biocompatibility of complex 3A. Furthermore, complex 3A can significantly inhibit the proliferation of A549 3D tumor spheroid. An in vivo anticancer study showed that complex 3A could delays the growth of A549 tumor xenografts with lower systemic toxicity. These results highlight the great possibility of developing highly active copper complexes as anti-lung cancer agents.

A highly accurate method for forecasting the compressor geometric variable system based on the data-driven method.

To make the puzzle of aero-engines complete, understanding the law of the compressor geometric variable system is a vital part. Modeling all aspects of aero-engines quickly has been a continuous area of research since the advent of artificial intelligence (AI). However, diagnosing or predicting faults is an ancient adage, and it is vital to explore key system forecast research, particularly since traditional forecasting techniques do not account for future information of non-target parameters. In this article, based on the feasibility of forecasting the compressor geometric variable system, an enhanced ConvNeXt model utilizing the Sliding Window Algorithm mechanism is proposed. And this method takes into account the future information of non-target parameters. With the novel strategy, the issue of the forecast's error increasing with forecast length is alleviated. As a result, in a particular condition, the error we obtained only accounts for 20.07% of that of the standard forecast approach. Additionally, it is verified that this method can be applied to various aero-engines. Finally, experiments on several aero-engine states involving the transition state and the steady state are conducted to strengthen the plausibility and credibility of our theories. It should be noted that the foundation of each experiment is data from actual flights.

The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis.

Background: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. Methods: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). Results: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). Conclusion: PHC has several advantages over atropine as an anticholinergic drug in AOPP.

6084 Cases of Adult Tetanus from China: A Literature Analysis.

Objective: To describe the clinical characteristics, treatments, and outcomes of tetanus and determine the most appropriate focus for tetanus prevention and treatment to reduce morbidity and mortality in China. Methods: Four databases, including the Chinese Bio-Medical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Data, were searched from 1 January, 2000 to 30 October, 2022. Results: In total, 151 articles including 6084 tetanus patients met the inclusion criteria. Additionally, 5925 patients had their gender recorded in detail, among which 66.67% (3950/5925) were male, and 33.33% (1975/ 5925) were female. The average age in the detailed records was reported in 4773 cases, with an overall average age of 46.69. The number of patients' places of residence was 580. Those from rural areas comprised the highest percentage with 88.62% (514 / 580). The causes of injury were recorded in 1592 cases in total; injuries caused by metals, wood, and wooden spikes accounted for the highest percentage with 54.52% (868/1592). Patient outcomes were recorded in 4305 cases, with a mortality of 9.34% (402/4305). The leading causes of death included treatment terminated by family members, asphyxia due to persistent spasms, respiratory failure, and autonomic dysfunction, family automatic abandonment and asphyxia accounted for the highest percentage, both 24.00% (54/225). Conclusion: The overall success rate of tetanus treatment in China has dramatically improved, but the prevention and control of non-neonatal tetanus is still challenging. Focus should be placed on the prevention of adult tetanus and standardizing the use of sedative and spasmolytic drugs. Additionally, medical professionals should popularize tetanus prevention and treatment knowledge among the people and strengthen training in grass-roots hospitals.

Role of Hemodialysis in Acute Severe Alcohol Intoxication: A Meta-Analysis.

BACKGROUND: Hemodialysis therapy has been used in the treatment of acute alcohol intoxication for many years, especially acute severe alcohol intoxication. OBJECTIVES: This study aimed to evaluate whether the combination of conventional treatment and naloxone with hemodialysis has advantages over conventional treatment and naloxone alone in patients with acute severe alcohol intoxication. METHODS: After searching 12 databases and 2 clinical trial centers. According to the established inclusion and exclusion criteria, the qualified literatures were screened. The outcome indicators were length of hospital stay, coma time, time of symptom disappearance, the overall complication rate, the incidence of pancreatitis, the incidence of aspiration pneumonia, the incidence of hepatic and renal dysfunction. Analysis was performed using Revman 5.3. RESULTS: This meta-analysis included 13 studies, including 932 subjects. In the treatment of acute severe alcohol intoxication, the use of hemodialysis on the basis of conventional treatment and naloxone could reduce the length of hospital stay (WMD = -15.16, 95% CI: -17.45 to -12.86, p < 0.001) in hours and (WMD = -4.89, 95% CI: -5.53 to -4.25, p < 0.001) in days; coma time (WMD = -5.43, 95% CI: -6.43 to -4.43, p < 0.001); time of symptom disappearance (WMD = -3.92, 95% CI: -5.37 to -2.47, p < 0.001); the overall complication rate (RR = 0.39, 95% CI: 0.28-0.55, p < 0.001); the incidence of pancreatitis (RR = 0.14, 95% CI: 0.05-0.43, p = 0.0006); the incidence of aspiration pneumonia (RR = 0.15, 95% CI: 0.04-0.66, p = 0.01), and the incidence of hepatic and renal dysfunction (RR = 0.21, 95% CI: 0.06-0.72, p = 0.01). CONCLUSIONS: It can be concluded that compared with the use of conventional treatment and naloxone alone, the use of hemodialysis on the basis of conventional treatment and naloxone for acute severe alcohol intoxication can reduce the length of hospital stay, coma time, time of symptom disappearance, and the incidence of some complications rate. Large scale, multicenter, and well-designed RCTs are needed in the future to prove our conclusions.

C1orf74 positively regulates the EGFR/AKT/mTORC1 signaling in lung adenocarcinoma cells.

Background: Lung adenocarcinoma (LUAD) is a major type of lung cancer with poor prognosis and low 5-year survival rate, which urgently needs further investigation in order to elucidate its mechanisms completely and discover novel therapeutic targets. C1orf74 is a novel protein with unknown function either in normal cells or cancer cells. The aim of this study is to investigate the expression and function of C1orf74 in LUAD cells. Methods: The expression of C1orf74 in LUAD was analyzed using the LUAD datasets from public databases. The prognostic value of C1orf74 in LUAD was analyzed using Kaplan-Meier Plotter. C1orf74 expression in LUAD cell line A549, H1993 and HCC827 was silenced using small interfering RNA, and then the effects of C1orf74 knockdown on proliferation, migration and invasion of LUAD cells were detected by colony formation assay and Transwell assay, the role of C1orf74 in EGFR/AKT/mTORC1 signaling pathway was examined by Western blot, and the function of C1orf74 in cell cycle was detected by flow cytometry. Results: The results of LUAD clinical data showed that C1orf74 was upregulated in LUAD tissues, and its high expression was associated with poor prognosis. The results from cultured LUAD cells demonstrated that C1orf74 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and autophagy. Moreover, C1orf74 knockdown suppressed EGFR/AKT/mTORC1 signaling in LUAD cells. In conclusion, the present study revealed that C1orf74 is upregulated in LUAD tissues and plays an oncogenic role in LUAD, and that C1orf74 positively regulates cell proliferation and mobility through the EGFR/AKT/mTORC1 signaling pathway in LUAD cells.

Identification of biomarkers and the mechanisms of multiple trauma complicated with sepsis using metabolomics.

Sepsis after trauma increases the risk of mortality rate for patients in intensive care unit (ICUs). Currently, it is difficult to predict outcomes in individual patients with sepsis due to the complexity of causative pathogens and the lack of specific treatment. This study aimed to identify metabolomic biomarkers in patients with multiple trauma and those with multiple trauma accompanied with sepsis. Therefore, the metabolic profiles of healthy persons designated as normal controls (NC), multiple trauma patients (MT), and multiple trauma complicated with sepsis (MTS) (30 cases in each group) were analyzed with ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS)-based untargeted plasma metabolomics using collected plasma samples. The differential metabolites were enriched in amino acid metabolism, lipid metabolism, glycometabolism and nucleotide metabolism. Then, nine potential biomarkers, namely, acrylic acid, 5-amino-3-oxohexanoate, 3b-hydroxy-5-cholenoic acid, cytidine, succinic acid semialdehyde, PE [P-18:1(9Z)/16:1(9Z)], sphinganine, uracil, and uridine, were found to be correlated with clinical variables and validated using receiver operating characteristic (ROC) curves. Finally, the three potential biomarkers succinic acid semialdehyde, uracil and uridine were validated and can be applied in the clinical diagnosis of multiple traumas complicated with sepsis.

Dithiocarbazate-FeIII, -CoIII, -NiII, and -ZnII Complexes: Design, Synthesis, Structure, and Anticancer Evaluation.

Non-platinum-metal complexes show great potential as anticancer agents. Herein, a series of dithiocarbazate non-Pt-metal complexes, including [FeIII(L)2]·Cl·2H2O 1, [CoIII(L)2]·NO3·2.5H2O 2, [NiII(L)2] 3, and [ZnII(L)2] 4, have been designed and evaluated for their efficacy as antineoplastic agents. Among them, complex 2 exhibited higher anticancer efficacy than complexes 1, 3, 4, and cisplatin against several cancer cell lines. Hemolysis assays revealed that complex 2 showed comparable hemolysis with cisplatin. In vivo anticancer evaluations showed that complex 2 could retard tumor xenograft growth effectively with low systemic toxicity. Further studies revealed that complex 2 suppressed cancer cells by triggering multiple mechanisms involving the simultaneous inhibition of mitochondria and glycolytic bioenergetics. Overall, our study provides new insights into the anticancer mechanism of Co complexes, which can be used as a good strategy to overcome the flexibility of cancer cells to chemotherapy adaptation.

Dithiocarbazate-Copper Complexes for Bioimaging and Treatment of Pancreatic Cancer.

Anticancer agents that present nonapoptotic cell death pathways are required for treating apoptosis-resistant pancreatic cancer. Here, we synthesized three fluorescent dithiocarbazate-copper complexes, {[CuII(L)(Cl)] 1, [CuII2(L)2(NO3)2] 2, and [CuII2CuI(L)2(Br)3] 3}, to assess their antipancreatic cancer activities. Complexes 1-3 showed significantly greater cytotoxicity toward several pancreatic cancer cell lines with better IC50 than those of the HL ligand and cisplatin. Confocal fluorescence imaging showed that complex 3 was primarily localized in the mitochondria. Primarily, compound 3 also can be applied to in vivo imaging. Further studies revealed that complex 3 kills pancreatic cancer cells by triggering multiple mechanisms, including ferroptosis. Complex 3 is the first copper complex to evoke cellular events consistent with ferroptosis in cancer cells. Finally, it significantly retarded the ASPC-1 cells' growth in a mouse xenograft model.

A review of the aromatic genus Adenosma: Geographical distribution, traditional uses, phytochemistry and biological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: The strongly scented genus Adenosma R. Brown (Plantaginaceae) comprises between 26 and 29 species with mainly southeast Asian distributions. Several species are used traditionally, mostly in Asian countries, for medicinal purposes including the treatment of colds and tumors, as well as stomach, liver, and skin disorders. Some species are also used as insecticides and/or insect repellents against mosquitoes or fleas. AIM OF THE REVIEW: Although the potential health benefits of Adenosma spp. are not yet well-known or well-studied in modern medicine, the aim of the present review is to provide a critical appraisal of the current state of knowledge regarding the geographical distribution, traditional uses, phytochemistry, phytochemicals and biological properties of Adenosma spp. MATERIALS AND METHODS: Electronic databases (Web of Science, Science Direct, Google Scholar, Scifinder, Microsoft Academic, eFloras), Biodiversity Heritage Library (BHL), and the China National Knowledge Infrastructure (CNKI), were searched using the key words "Adenosma", "", "", "", "nhân tran", as well as the scientific names of the species, and a library search was also conducted for articles and books related to the subject published in English, Chinese or Vietnamese, as well as Ph.D. theses and M.Sc. dissertations published before April 2020. RESULTS: Adenosma spp. is traditionally used to treat gastrointestinal disorders, hepatitis, colds, and skin problems. Phenolic acids, flavonoids, and terpenoids constitute the main phytochemicals in these plants. Several evaluations based on bioassays have demonstrated biological activity for Adenosma spp., including antidiabetic, anticancer, and insecticidal activities; extracts and isolated compounds have also shown effective biological activity. However, current research has focused only on a few species, and on limited geographical regions, mainly in China and Vietnam. More and broader ethnopharmacological studies are therefore needed to provide further evidence of the health benefits of these plants. CONCLUSIONS: Adenosma spp. are plants rich in essential oils, particularly terpenoids, and the crude extracts have valuable bioactive properties. Certain lines of research based on cell lines and animal models show the potential value in different areas of health management. Further investigation into the traditional knowledge in southeast Asian and Pacific island regions, as well as the into the toxicity and identity of the bioactive compounds and their mechanisms of action is necessary.

Ethnobotanical survey and evaluation of traditional mosquito repellent plants of Dai people in Xishuangbanna, Yunnan Province, China.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue is one of the most important pervasive diseases in many regions of the world, including China. There is an urgent need for new repellents, including plant derivatives, due to the resistance, toxicity, and non-degradability of synthetic insecticides. Traditional plant-based remedies may provide potential avenues for developing new strategies. AIMS OF THE STUDY: The aims of this study were to 1) document the traditional mosquitoes repellent plants used by the Dai people of Xishuangbanna, China; 2) screen out new efficient mosquito repellent plants as candidates for further study. MATERIALS AND METHODS: During the period August 2016 to July 2017, five field surveys were conducted in 16 villages of Xishuangbanna. A total of 81 informants (44 males and 37 females) were interviewed using semi-structured questions to collect detailed information on the plants they use to prevent mosquito bites. Ten plants with higher popularity and larger resource were collected and extracts were prepared by hydro-distillation or with petroleum ether. Extracts were tested for adult Aedes albopictus repellency using a human-bait cage. Firstly, repellency was determined as the Minimum Effective Dosage (MED) per minute at which 1% of the mosquito bite through the treated cloth. Secondly, five plant extracts with lower MEDs were tested the repellent longevity of different concentrations. RESULTS: Eighteen plants were documented as being used in traditional remedies against mosquitoes. The methods for controlling mosquitoes were diverse: direct burning was used for most plants (16 species), followed by smearing (5 species), and placing (5 species). Laboratory analyses confirmed that ten plants did exhibit mosquito repellent activity. Of them, Artemisia indica, Nicotiana tabacum, Blumea balsamifera, Vitex trifolia, and Chromolaena odorata showed good mosquito repellency with MEDs of 0.015, 0.061, 0.090, 0.090, and 0.105 mg/cm2, respectively. The protection rate provided by A. indica is also the highest among five plants. Although it provides complete protection time of only 30 min at 0.45 mg/cm2 concentration, its repellency within 2 h is not significantly different from that of DEET. CONCLUSION: Dai villagers in Xishuangbanna have a rich, diverse and scientific knowledge of plant-based mosquito repellents. Laboratory experiments screened out several plants as candidates for mosquito repellents, of which Artemisia indica was the most promising candidate plant.

Comparative proteomics reveals stress responses of Vibrio parahaemolyticus biofilm on different surfaces: Internal adaptation and external adjustment.

Vibrio parahaemolyticus is a kind of gram-negative marine pathogen, which usually adheres to stainless steel (SS), glass (GS) and other abiotic surfaces in aquaculture and food processing in the form of biofilm and causes the spread of gastrointestinal illness. However, the deeply survival adaptation mechanism of V. parahaemolyticus biofilm cells on these contact surface remained unclear. Here, proteomics was used to investigated the physiological response of the V. parahaemolyticus biofilms cells to different abiotic surfaces (SS, GS and polystyrene (PS)). In addition, the effect of contact materials on the physical-chemical properties of biofilms are also characterized. Results showed that the expression of proteins of biofilm cells established on the SS surface were mainly related to the alleviation of metal ion stress and toxicity. The up-regulated proteins in the biofilm cells formed on the GS surface were mainly involved in the biological processes of sugar uptake, protein synthesis and bacterial chemotaxis. Meanwhile, the significantly expressed proteins in the biofilm cells formed on the PS surface were mainly involved in the cellular physiological activity of aromatic compound metabolism, osmotic stress and nutrient transport. All functional proteins mentioned above were closely related to the interaction characteristics of the contact surface and biofilm. This study provided an in-depth comparison of V. parahaemolyticus biofilm formation on these three abiotic surfaces, and presented a model in first time for the adaptation behavior of biofilm cells on different surfaces as affected by metal ion stress, nutrition, osmotic stress, and sugar utilization, which could facilitate an efficient control strategy for biofilm formation in industrial field.

Ethnobotanical survey of plants traditionally used against hematophagous invertebrates by ethnic groups in the mountainous area of Xishuangbanna, Southwest China.

Hematophagous invertebrates such as mosquitoes, leeches, mites, ticks, lice and bugs cause various problems for humans. Considering reports on insecticide resistance and requirements for improved environmental and toxicological profiles, there is a continuing need to discover and develop new insecticides and repellents. Ethnobotanical surveys of traditional plant-based repellents provide a direct method of identifying plants for potential use. During five field surveys in Bulang, Jinuo and Lahu villages between August 2018 and July 2019, semi-structured interviews were conducted with 237 informants (151 male, 86 female; mean age 63). Frequency of citation, use value, informant consensus factor and Jaccard index were employed to statistically analyze the collected data. A total of 709 use reports relating to 32 plant species and 71 remedies were collected. Similarities and differences between the three groups, as well as the Dai and Hani of Xishuangbanna, who were studied earlier, were shown through network analysis. These five ethnic groups living in the same area have a common understanding of traditional botanical knowledge against hematophagous invertebrates, but each group also possesses unique knowledge. Recording and protecting this traditional knowledge is potentially useful for protecting this cultural diversity and related biodiversity and can also have important practical applications. In this study, traditional knowledge provided us with many new potential plants for follow-up research for the development of new insecticides and repellents, among which Artemisia indica, Nicotiana tabacum and Clausena excavata are the most promising.

Transcription factor FvTCP9 promotes strawberry fruit ripening by regulating the biosynthesis of abscisic acid and anthocyanins.

The plant-specific transcription factor TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING4 CELL FACTORS (TCP) plays a crucial role in plant growth and development. However, there have been no studies reporting on the function of strawberry TCP in regulating fruit development. In this study, FvTCP9, a woodland strawberry (Fragaria vesca) TCP gene, was isolated to explore its function in fruit ripening. The transcript accumulation levels of FvTCP9 were high in fruits, specifically in red fruits compared with other tissues or organs. Transient expression of the FvTCP9 gene in cultivated strawberry fruits revealed that over-expression of FvTCP9 promoted fruit ripening. Meanwhile, silencing FvTCP9, using tobacco rattle virus-induced gene silencing (VIGS), inhibited fruit ripening. The changes in ripening-related physiological conditions in transient fruits, such as the accumulation of anthocyanins and abscisic acid (ABA), and fruit firmness confirmed above results. Results suggested that FvTCP9 was involved in the biosynthesis of ABA and anthocyanins to regulate fruit ripening. Transcription analysis showed that the expression levels of ABA signaling-related genes (FaNCED1, FaPYR1, FaSnRK2, and FaABI5) were affected by FvTCP9. A yeast two-hybrid assay revealed that FvTCP9 interacted physically with FaMYC1 to modulate the biosynthesis process of anthocyanins. Taken together, this study demonstrated that FvTCP9 promoted fruit ripening by regulating the biosynthesis of ABA and anthocyanins.

Novel Brain-Tumor-Inhibiting Copper(II) Compound Based on a Human Serum Albumin (HSA)-Cell Penetrating Peptide Conjugate.

It is a great challenge to design drugs that penetrate the blood-brain barrier to inhibit brain tumor growth by acting against multiple targets and also improve their delivery efficacy and targeting ability to cancer cells. To overcome the above problems, we designed a multitarget metal agent for treating brain tumors based on an human serum albumin (HSA)-cell penetrating peptide conjugate. Thus, we rationally screened copper (Cu) and 2-acetyl-3-ethylpyrazine thiosemicarbazones to synthesize six compounds, and we investigated their structure-activity relationships and confirmed multiple mechanisms for brain glioma cells. The HSA-6b complex structure indicated that 6b binds to the IIA subdomain of HSA and His242 replaces the Br ligand in 6b in coordination with Cu2+. In vivo data suggested that both 6b and the HSA-6b-peptide conjugate penetrate the blood-brain barrier and inhibit brain tumor growth with few side effects. Furthermore, the HSA-peptide conjugate also improved the delivery efficacy and targeting ability of 6b in vivo.

CRISPR-Cas9 knockout of qseB induced asynchrony between motility and biofilm formation in Escherichia coli.

Generally, cell motility and biofilm formation are tightly regulated. The QseBC two-component system (TCS) serves as a bridge for bacterial signal transmission, in which the protein QseB acts as a response regulator bacterial motility, biofilm formation, and virulence. The mechanisms that govern the interaction between QseBC and their functions have been studied in general, but the regulatory role of QseB on bacterial motility and biofilm formation is unknown. In this study, the CRISPR-Cas9 system was used to construct the Escherichia coli MG1655ΔqseB strain (strain ΔqseB), and the effects of the qseB gene on changes in motility and biofilm formation in the wild type (WT) were determined. The motility assay results showed that the ΔqseB strain had higher (p < 0.05) motility than the WT strain. However, there was no difference in the formation of biofilm between the ΔqseB and WT strains. Real-time quantitative PCR illustrated that deletion of qseB in the WT strain downregulated expression of the type I pili gene fimA. Therefore, we might conclude that the ΔqseB induced the downregulation of fimA, which led to asynchrony between motility and biofilm formation in E. coli, providing new insight into the functional importance of QseB in regulating cell motility and biofilm formation.

Mitochondria-localizing N-heterocyclic thiosemicarbazone copper complexes with good cytotoxicity and high antimetastatic activity.

Although many N-heterocyclic thiosemicarbazone copper complexes have been proposed as potential anticancer agents, little is known about their intracellular localization in cells. In the present study, we synthesized two fluorescent N-heterocyclic thiosemicarbazone copper complexes, ([CuII(L)(Br)] 1 and [CuII2CuI(L)2(Br)3] 2, where HL is (E)-N,N-dimethyl-2-(quinolin-8-ylmethylene)hydrazinecarbothioamide), to assess their intracellular distribution. Our fluorescence studies demonstrated that complex 1 showed an intense emission band at ca. 510 nm (λex = 405 nm) similar to that of complex 2, albeit with about four times lower emission intensity. Both copper complexes showed significantly greater cytotoxicity toward several tumor cell-types with better IC50 (0.27-0.91 µM) than the HL ligand and cisplatin. Scratching wound healing assay and invasion assay were performed, revealing that the copper complexes have good antimetastatic activity. Confocal fluorescence imaging allowed ascertaining that complex 2 was primarily localized to mitochondria. Further studies revealed that the anticancer mechanisms of complex 2 might involve the mitochondrial-mediated apoptotic pathway, probably caused by the reducing mitochondrial membrane potential and induction of ROS (reactive oxygen species) production. Furthermore, complex 2 exhibited promising cytostatic effects in a three-dimensional HeLa spheroid model.