The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study.

PURPOSE: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. METHODS: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. RESULTS: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. CONCLUSION: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. TRIAL REGISTRATION NUMBER: UMIN000031381, registered 20/02/2018.

Intravascular ultrasound enhances the PETTICOAT technique in endovascular therapy for complicated type B aortic dissection with malperfusion syndrome.

OBJECTIVE: To present the value of intravascular ultrasound (IVUS) in diagnosis and treatment of complicated type B aortic dissection (TBD) with malperfusion (MP). Especially the value of IVUS regarding the treatment strategy, reoperation rate, acute kidney injury (AKI) and false lumen thrombosis (FLT) was investigated. METHODS: Retrospective analysis of 25 TBD cases with MP treated with endovascular therapy from April 2019 to August 2022. In 17 cases angiography & IVUS were applied during the operation (IVUS group) and in 8 cases angiography was used without IVUS (control group) for final intraoperative control. IVUS was used to assess the true lumen collapse and to decide if additional bare stenting was necessary or not. Details from patients' charts and documentation from surgeries were analyzed. The endovascular technique included thoracic endovascular aortic repair (TEVAR) with primary entry sealing and -if needed- bare stenting of the true lumen distal of the entry tears using the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique. RESULTS: All patients presented with pain localized mostly (48%) in thorax and abdomen. In all patients the proximal entry tear of the dissection was covered using TEVAR. The PETTICOAT technique was applied in 13 cases (52%), whereas most combined procedures were applied in the IVUS group (12 compared to 1; p=0,02). A total of 3 patients (1 in the control group; 12,5% and 2 in the IVUS group; 11,8%) underwent a bowel resection. Totally 8 patients (32%) underwent a reoperation in aorta (3 during the hospital stay). There were no statistical differences between IVUS and control group regarding the preoperative findings, the reoperation rates and the postoperative complications. 5 patients died (4 during the hospital stay), 1 in control and 4 in IVUS group; p=0,53. The follow up included a clinical and a computed tomography angiography (CTA) examination. No statistically significant difference regarding occurrence and extension of FLT was observed between the two groups. CONCLUSIONS: The IVUS and control groups showed no difference in survival rates. The use of IVUS extended the indication for PETTICOAT technique with statistically significant difference. A milder form of AKI presented in the IVUS group compared to the control group. In addition, a stronger correlation between IVUS and the avoidance of an aorta reoperation was observed, though it did not reach statistical significance.

Metabolomic Profiling Reveals the Anti-Herbivore Mechanisms of Rice (Oryza sativa).

The use of secondary metabolites of rice to control pests has become a research hotspot, but little is known about the mechanism of rice self-resistance. In this study, metabolomics analysis was performed on two groups of rice (T1, with insect pests; T2, without pests), indicating that fatty acids, alkaloids, and phenolic acids were significantly up-regulated in T1. The up-regulated metabolites (p-value < 0.1) were enriched in linoleic acid metabolism, terpene, piperidine, and pyridine alkaloid biosynthesis, α-linolenic acid metabolism, and tryptophan metabolism. Six significantly up-regulated differential metabolites in T1 were screened out: N-trans-feruloyl-3-methoxytyramine (1), N-trans-feruloyltyramine (2), N-trans-p-coumaroyltyramine (3), N-cis-feruloyltyramine (4), N-phenylacetyl-L-glutamine (5), and benzamide (6). The insect growth inhibitory activities of these six different metabolites were determined, and the results show that compound 1 had the highest activity, which significantly inhibited the growth of Chilo suppressalis by 59.63%. Compounds 2-4 also showed a good inhibitory effect on the growth of Chilo suppressalis, while the other compounds had no significant effect. RNA-seq analyses showed that larval exposure to compound 1 up-regulated the genes that were significantly enriched in ribosome biogenesis in eukaryotes, the cell cycle, ribosomes, and other pathways. The down-regulated genes were significantly enriched in metabolic pathways, oxidative phosphorylation, the citrate cycle (TCA cycle), and other pathways. Eighteen up-regulated genes and fifteen down-regulated genes from the above significantly enriched pathways were screened out and verified by real-time quantitative PCR. The activities of detoxification enzymes (glutathione S-transferase (GST); UDP-glucuronosyltransferase (UGT); and carboxylesterase (CarE)) under larval exposure to compound 1 were measured, which indicated that the activity of GST was significantly inhibited by compound 1, while the activities of the UGT and CarE enzymes did not significantly change. As determined by UPLC-MS, the contents of compound 1 in the T1 and T2 groups were 8.55 ng/g and 0.53 ng/g, respectively, which indicated that pest insects significantly induced the synthesis of compound 1. Compound 1 may enhance rice insect resistance by inhibiting the detoxification enzyme activity and metabolism of Chilo suppressalis, as well as promoting cell proliferation to affect its normal growth and development process. The chemical-ecological mechanism of the insect resistance of rice is preliminarily clarified in this paper.

Plant growth-promoting rhizobacteria modulate induced corn defense against Spodoptera litura (Lepidoptera: Noctuidae).

Common cutworm, Spodoptera litura is an important pest of corn causing significant crop yield loss. Synthetic insecticides have mostly been used to combat this pest, raising human and environmental health concerns. Plant-growth promoting rhizobacteria (PGPR) could compensate for or augment the harmful effects of agrochemicals. Herein, we aimed to assess whether PGPR-induced defenses in corn plants impact the host-plant selection behavior of S. litura. Headspace volatile organic compounds (VOCs) were analyzed using Gas chromatography-mass spectrometry (GC-MS). Larvae fed inoculated corn exhibited lower weights and RGR than non-inoculated plants. Under choice experiments, PGPR-treated plants significantly reduced percentage leaf damage area and oviposition rate compared to untreated plants. VOC ratio emission varied significantly between control and PGPR treatments, which, in part, explains feeding and oviposition deterrence in PGPR-treated plants. The results demonstrate that PGPR inoculation can enhance corn resistance to S. litura, making it a promising candidate for crop protection strategies.

α-Cyanostilbene-based Molecule with the Synergistical Mechanisms of AIE, ESIPT and TICT: A New Schiff Base Probe for Selective Detection of Fe3+ and Reversible Response to HCl/NH3 Vapor.

We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states. Interestingly, the TLC-based test strip loaded with the target compound showed the reversible fluorescence response to amine/acid vapor and on-site visual fluorescence quenching response to Fe3+. In THF/water mixtures (fw = 90%, 10 µM, pH = 7.4), the detection limit (DL) and the binding constant (Ka) of the developed probe towards Fe3+ were evaluated as 5.50 × 10- 8 M and 1.69 × 105, respectively. The developed probe was successfully applied for the detection of Fe3+ with practical, reliable, and satisfying results.

Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"

Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system-a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide.

Development and applications of peri-implantitis mouse models.

OBJECTIVE: Peri-implantitis is one of the most common complications of implants. However, its pathogenesis has not been clarified. In recent years, mouse models are gradually being used in the study of peri-implantitis. This review aims to summarize the methods used to induce peri-implantitis in mice and their current applications. METHOD: Articles of peri-implantitis mouse models were collected. We analyzed the various methods of inducing peri-implantitis and their application in different areas. RESULTS: Most researchers have induced peri-implantitis by silk ligatures. Some others have induced peri-implantitis by Pg gavage and LPS injection. Current applications of peri-implantitis mouse models are in the following areas: investigation of pathogenesis and exploration of new interventions, comparison of peri-implantitis with periodontitis, the interaction between systemic diseases and peri-implantitis, etc. CONCLUSION: Silk ligature for 2-4 weeks, Pg gavage for 6 weeks, and LPS injection for 6 weeks all successfully induced peri-implantitis in mice. Mice have the advantages of mature gene editing technology, low cost, and short time to induce peri-implantitis. It has applications in the study of pathogenesis, non-surgical treatments, and interactions with other diseases. However, compared with large animals, mice also have a number of disadvantages that limit their application.

Photo-sensitive peptide inducing targeted cross-linking in a one-step and reagent-, enzyme- and antibody-free detection of SARS-Cov-2 marker protein.

Modern biosensing technology plays a crucial role in combating the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, the associated assays remain costly, considering their extensive daily use. In response, we developed a simplified one-step SARS-CoV-2 protease assay that reduces both time and financial expenses. This approach eliminates the need for extra reagents, enzymes, or antibodies. The simplification involves a photo-sensitive Bengal red-tagged substrate peptide, allowing specific cross-linking upon protease-substrate recognition. This process forms a di-tyrosine product with a distinctive fluorescence signal readout, enabling the detection of SARS-CoV-2 in patient serum samples. This method anticipates a major reduction in assay costs in the near future.

A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines.

CMC is the most frequently diagnosed cancer and one of the leading causes of death in non-spayed female dogs. Exploring novel therapeutic agents is necessary to increase the survival rate of dogs with CMC. MPOBA is a BZOP derivative that has a significant anticancer effect in a human cell line. The main goal of this study was to investigate the anticancer properties of MPOBA against two CMC cell lines (REM134 and CMGT071020) using a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, a wound healing assay, a transwell migration assay, an Annexin V-FITC apoptosis assay with a flow cytometry analysis, a mRNA expression analysis using quantitative real-time PCR (qRT-PCR), and an immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation and cell migration and induced apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes, including TP53, BCL-2, BAX, epidermal growth factor receptor (EGFR), snail transcription factor (SNAIL), snail-related zinc-finger transcription factor (SLUG), TWIST, E-cadherin, and N-cadherin, were investigated. The mRNA expression results revealed that MPOBA induced upregulation of TP53 and overexpression of the pro-apoptotic gene BAX, together with an inhibition of BCL-2. Moreover, MPOBA also suppressed the mRNA expression levels of SNAIL, EGFR, and N-cadherin and induced upregulation of E-cadherin, crucial genes related to the epithelial-to-mesenchymal transition (EMT). However, there was no significant difference in the IHC results of the expression patterns of vimentin (VT) and cytokeratin (CK) between MPOBA-treated and control CMC cells. In conclusion, the results of the present study suggested that MPOBA exhibited significant anticancer activity by inducing apoptosis in both CMCs via upregulation of TP53 and BAX and downregulation of BCL-2 relative mRNA expression. MPOBA may prove to be a potential candidate drug to be further investigated as a therapeutic agent for CMC.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Single-Atom Mn Catalysts via Integration with Mn Sub Nano-Clusters Synergistically Enhance Oxygen Reduction Reaction.

Integrating single atoms and clusters into one system represents a novel strategy for achieving the desired catalytic performance. In comparison to single-atom catalysts, catalysts combining single atoms and clusters harness the advantages of both, thus displaying greater potential. Nevertheless, constructing single-atom-cluster systems remains challenging, and the fundamental mechanism for enhancing catalytic activity remains elusive. In this study, a directly confined preparation of a 3D hollow sea urchin-like carbon structure (MnSA/MnAC-SSCNR) is developed. Mn single atoms synergistically interact with Mn clusters, optimizing and reducing energy barriers in the reaction pathway, thus enhancing reaction kinetics. Consequently, in contrast to Mn single-atom catalysts (MnSA-SSCNR), MnSA/MnAC-SSCNR exhibits significantly improved oxygen reduction activity, with a half-wave potential (E1/2) of 0.90 V in 0.1 m KOH, surpassing that of MnSA-SSCNR and Pt/C. This work demonstrates a strategy of remote synergy between heterogeneous single atoms and clusters, which not only contributes to electrocatalytic reactions but also holds potential for reactions involving more complex products.

Study on Low Thermal-Conductivity of PVDF@SiAG/PET Membranes for Direct Contact Membrane Distillation Application.

In order to enhance the separation performance and reduce the heat loss of transmembrane for membrane distillation, the thermal efficiency and hydrophobicity of the membrane distillation need to be simultaneously enhanced. In this work, a polyvinylidene difluoride/polyethylene glycol terephthalate (PVDF/PET) hydrophobic/hydrophilic membrane has been prepared by non-solvent phase induction method. Nanosized silica aerogel (SiAG) with high porosity has been added to the composite membranes. The modifying effects and operating conditions on permeate flux and thermal efficiency in direct contact membrane distillation (DCMD) are investigated. Furthermore, the latent heat of vaporization and the heat transfer across the membranes have been compared for SiAG addition, which indicates that the composite PVDF@SiAG/PET membranes demonstrate a great potential for distillation-separation application due to their high heat efficiency.

Tetracalcium phosphate/polycaprolactone composite scaffold: Mechanical reinforcement, biodegradability regulation and bioactivity induction.

Polycaprolactone (PCL) is considered a potential biomaterial due to its good biocompatibility, but its slow degradability and insufficient mechanical properties limit its wide application in bone tissue engineering. Tetracalcium phosphate's (TTCP) good degradability and inherent high stiffness are expected to compensate for the aforementioned defects of PCL and endow it with good biological activity. This goal of this study was to obtain bioactive PCL composite scaffolds with tuneable degradation properties and good mechanical strength via selective laser sintering technology (SLS). Composite porous scaffolds with TTCP contents of 0%, 5%, 10%, 15%, 20%, and 25% were prepared, and the experimental results showed that the addition of TTCP significantly improved the mechanical properties of the scaffold. Notably, the tensile strength of the composite scaffold with 20% TTCP content reached 15.2 MPa, which was 2.9 times that of pure PCL, and the best flexural strength was found in the scaffold with 15% TTCP content (4.7 MPa). More importantly, the introduced TTCP not only achieved the effective pH regulation of the soaking solution and the promotion of biodegradation, but also provided the scaffold with good bioactivity and biocompatibility.

The efficacy of prophylactic metoclopramide in preventing nausea and vomiting in patients with acute pain treated with intravenous tramadol: a randomized double-blinded, placebo-controlled trial.

OBJECTIVE: To examine the clinical efficacy of prophylactic metoclopramide in reducing the incidence of nausea and vomiting in emergency department (ED) patients with acute pain who were treated with intravenous tramadol. RESULTS: We conducted a single-center randomized, double-blinded, placebo-controlled trial. A total of 99 ED patients presented with acute pain were recruited. Sixty-four patients were randomized, 31 patients in the treatment arm and 33 in the control arm. Overall, there were no significant differences in baseline characteristics between treatment arm and control arm. Only one patient within each arm reported having nausea symptom. No patients reported vomiting episode. There was no statistically significant difference in the proportion of patients with nausea or vomiting symptoms between the two groups (3.2% in the treatment arm vs. 3.0% in the control arm, p = 1.000). The administration of prophylactic metoclopramide may not provide additional benefit in reducing the occurrence of nausea and/or vomiting episode in ED patients with acute pain treated with intravenous tramadol. Trial registration Randomized clinical trial TCTR20220525001; registration date: 21 October 2021. Retrospectively registered.

Discovery of novel phenothiazine derivatives as new agrochemical alternatives for treating plant viral diseases.

BACKGROUND: Plant viral diseases, namely 'plant cancer', are extremely difficult to control. Even worse, few antiviral agents can effectively control and totally block viral infection. There is an urgent need to explore and discover novel agrochemicals with high activity and a unique mode of action to manage these refractory diseases. RESULTS: Forty-one new phenothiazine derivatives were prepared and their inhibitory activity against tobacco mosaic virus (TMV) was assessed. Compound A8 had the highest protective activity against TMV, with a half-maximal effective concentration (EC50 ) of 115.67 µg/mL, which was significantly better than that of the positive controls ningnanmycin (271.28 µg/mL) and ribavirin (557.47 µg/mL). Biochemical assays demonstrated that compound A8 could inhibit TMV replication by disrupting TMV self-assembly, but also enabled the tobacco plant to enhance its defense potency by increasing the activities of various defense enzymes. CONCLUSION: In this study, novel phenothiazine derivatives were elaborately fabricated and showed remarkable anti-TMV behavior that possessed the dual-action mechanisms of inhibiting TMV assembly and invoking the defense responses of tobacco plants. Moreover, new agrochemical alternatives based on phenothiazine were assessed for their antiviral activities and showed extended agricultural application. © 2023 Society of Chemical Industry.

Investigating the AIE and water sensing properties of a concise naphthalimide fluorophore.

A simple naphthalimide fluorophore NAP-H2O was designed and synthesized. Basic photophysical properties were investigated, especially found that the probe showed robust green fluorescence in water compared with that in various organic solvents, and the specific mechanism was conformed to be the aggregation induced emission (AIE) through dynamic light scattering (DLS) analysis, solid-state luminescence and fluorescence imaging. Accordingly, the capability of NAP-H2O for water sensing was examined, and good linear relationships between fluorescence intensities at the green emission band and the water content were obtained, enabling quantitative detection of water in organic solvents. The detection limits were calculated to be 0.004 % (v/v) in ACN, 0.117 % (v/v) in 1,4-dioxane, 0.028 % (v/v) in THF, 0.022 % (v/v) in DMF and 0.146 % (v/v) in DMSO, respectively. In addition, the probe presented fast response time within 5 s to water and good photostability. Furthermore, the probe was successfully applied for fast and naked-eye detection of water in organic solvents via test papers. This work provides a rapid, sensitive and naked-eye method for trace amount detection of water in organic solvents and has potential for practical applications.

System comprehensive risk assessment of urban rainstorm-induced flood-water pollution disasters.

The urban rainstorm-induced flood-water pollution disaster is a kind of systematic risk, which may induce secondary disasters that can lead to more serious damage, so this paper first adopts the fuzzy comprehensive evaluation method to determine the flood risk by combining with the submergence depth derived from the risk field and other factors data, and then the grid environmental risk evaluation method, which is improved by increasing the induced possibility based on Bayesian theory, is used to evaluate the flood-induced water pollution risk, and the system comprehensive risk of rainstorm-induced flood-water pollution disasters is finally obtained by constructing risk level matrix, which can well depict the coupling superposition effect. Shenzhen City is selected as the study area, and the results showed that the area with high-risk of both flood and water pollution only accounts for about 0.14% of the total area, mainly distributed in the eastern junction of Longgang district and Pingshan district, where the rainstorms occur frequently and the enterprise risk sources are dense. The system comprehensive risk is mostly very low-low and very high-low, accounting for more than 76% of the total area. It is always necessary to pay attention not only to the areas with high risk level of both disasters, but also to the areas with high risk level of one disaster. The method proposed in this study can not only quantitatively reveal the formation of the induced risk, but also provide reference for early warning.

2,3-Butanediol from the leachates of pine needles induces the resistance of Panax notoginseng to the leaf pathogen Alternaria panax.

Compared with the use of monocultures in the field, cultivation of medicinal herbs in forests is an effective strategy to alleviate disease. Chemical interactions between herbs and trees play an important role in disease suppression in forests. We evaluated the ability of leachates from needles of Pinus armandii to induce resistance in Panax notoginseng leaves, identified the components via gas chromatography-mass spectrometry (GC-MS), and then deciphered the mechanism of 2,3-Butanediol as the main component in the leachates responsible for resistance induction via RNA sequencing (RNA-seq). Prespraying leachates and 2,3-Butanediol onto leaves could induce the resistance of P. notoginseng to Alternaria panax. The RNA-seq results showed that prespraying 2,3-Butanediol onto leaves with or without A. panax infection upregulated the expression of large number of genes, many of which are involved in transcription factor activity and the mitogen-activated protein kinase (MAPK) signaling pathway. Specifically, 2,3-Butanediol spraying resulted in jasmonic acid (JA) -mediated induced systemic resistance (ISR) by activating MYC2 and ERF1. Moreover, 2,3-Butanediol induced systemic acquired resistance (SAR) by upregulating pattern-triggered immunity (PTI)- and effector-triggered immunity (ETI)-related genes and activated camalexin biosynthesis through activation of WRKY33. Overall, 2,3-Butanediol from the leachates of pine needles could activate the resistance of P. notoginseng to leaf disease infection through ISR, SAR and camalexin biosynthesis. Thus, 2,3-Butanediol is worth developing as a chemical inducer for agricultural production.

The effect of ε-poly-l-lysine treatment on molecular, physiological and biochemical indicators related to resistance in longan fruit infected by Phomopsis longanae Chi.

Postharvest longan fruits are subjected to Phomopsis longanae Chi (P. longanae) infection that lead to fruit quality deterioration. We hypothesized that ε-poly-l-lysine (ε-PL) could enhance fruit disease resistance in longans. Through physiological and transcriptomic analyses, the results showed that, compared to P. longanae-infected longan fruit, ε-PL + P. longanae treatment reduced the disease development of longan fruits. Additionally, ε-PL + P. longanae treatment increased the contents of disease-resistant substances (lignin and H2O2) and the activities of disease-resistance enzymes (CHI, PAL, PPO, C4H, CAD, GLU, 4CL, and POD). Furthermore, the expressions of genes relevant to the phenylpropanoid biosynthesis pathway and plant-pathogen interaction pathway (Rboh, FLS2, WRKY29, FRK1, and PR1) were up-regulated by ε-PL + P. longanae treatment. These findings demonstrated that ε-PL treatment inhibited the disease development of postharvest longan fruits were associated with the increased accumulation of disease-resistant related substances, as well as the raised activities and genes expressions of disease-resistance related enzymes.

Discovery of novel benzamide derivatives bearing benzamidophenyl and phenylacetamidophenyl scaffolds as potential antitumor agents via targeting PARP-1.

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a crucial role in DNA damage repair and has been identified as a promising therapeutic target in cancer therapy. As a continuation of our efforts on the development of novel PARP-1 inhibitors with potent anticancer activity, a series of benzamide derivatives containing the benzamidophenyl and phenylacetamidophenyl scaffolds were designed and synthesized based on the structure optimization of our previously reported compound IX. All target compounds were screened for their in vitro antiproliferative activities against human colorectal cancer cells (HCT116, DLD-1 and SW480) and human normal colonic epithelial cells (NCM460). Among them, compound 13f exhibited the most potent anticancer activity against HCT116 cells and DLD-1 cells with IC50 = 0.30 µM and 2.83 µM, respectively. Moreover, 13f displayed significant selectivity in inhibiting HCT116 cancer cells over the normal NCM460 cells. Furthermore, 13f exhibited excellent PARP-1 inhibitory effect with IC50 = 0.25 nM. Besides, 13f was found to effectively inhibit colony formation and migration of HCT116 cells. Studies on the mechanisms revealed that 13f could arrest cell cycle at G2/M phase, accumulate DNA double-strand breaks, reduce mitochondrial membrane potential and ultimately induce apoptosis in HCT116 cells. In addition, molecular docking study indicated that 13f could combine firmly with the catalytic pocket of PARP-1 through multiple hydrogen bond interactions. Collectively, these findings demonstrated that 13f could serve as a promising anticancer candidate and deserves further investigation.