Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Dual immunotherapy alternating with anti-PD-1 antibody plus liposomal doxorubicin show good efficacy in prostate epithelioid hemangioendothelioma: a case report.

Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.

Mucoadhesive chitosan-catechol as an efficient vaccine delivery system for intranasal immunization.

The mucosal barrier and scavenging effect of the mucosal layer are two main obstacles in inducing mucosal immunization. To overcome these obstacles, we synthesized a bio-inspired mucoadhesive material, chitosan-catechol (ChiC), for surface modification of inactive porcine epidemic diarrhea virus (PEDV). Studies have revealed that PEDV particles can be facilely and mildly modified by Chi-C forming Chi-C-PEDV nanoparticles (Chic-Ps) through the covalent and electrostatic bond, which effectively prolongs the retention time of PEDV in the nasal mucosa. The cell co-culture model demonstrated that Chic-Ps exhibit enhanced recruitment of dendritic cells via the secretion of stimulating chemokine CCL20 and improving antigen permeability by disruption the distribution of ZO-1 protein in epithelial cells. Additionally, the flow cytometry (FCM) analysis revealed that Chic-Ps facilitate trafficking to lymph nodes and induce stronger cellular and humoral immune responses compared to unmodified PEDV. Notably, Chic-Ps induced a higher level of PEDV neutralizing antibody was induced by Chic-Ps in the nasal washes, as confirmed by a plaque reduction neutralization test. These results demonstrate that Chi-C is a promising nasal delivery system for vaccines. Proof of principle was obtained for inactivated PEDV, but similar delivery mechanisms could be applied in other vaccines when intranasal administration is needed.

Engineering a biomimicking strategy for discovering nonivamide-based quorum-sensing inhibitors for controlling bacterial infection.

The overuse of antibiotics over an extended period has led to increasing antibiotic resistance in pathogenic bacteria, culminating in what is now considered a global health crisis. To tackle the escalating disaster caused by multidrug-resistant pathogens, the development of new bactericides with new action mechanism is highly necessary. In this study, using a biomimicking strategy, a series of new nonivamide derivatives that feature an isopropanolamine moiety [the structurally similar to the diffusible signal factor (DSF) of Xanthomonas spp.] were prepared for serving as potential quorum-sensing inhibitors (QSIs). After screening and investigation of their rationalizing structure-activity relationships (SARs), compound A26 was discovered as the most optimal active molecule, with EC50 values of 9.91 and 7.04 µg mL-1 against Xanthomonas oryzae pv oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). A docking study showed that compound A26 exhibited robust interactions with Glu A: 161 of RpfF, which was strongly evidenced by fluorescence titration assay (KA value for Xoo RpfF-A26 = 104.8709 M-1). Furthermore, various bioassays showed that compound A26 could inhibit various bacterial virulence factors, including biofilm formation, extracellular polysaccharides (EPS), extracellular enzyme activity, DSF production, and swimming motility. In addition, in vivo anti-Xoo results showed that compound A26 had excellent control efficiency (curative activity: 43.55 %; protective activity: 42.56 %), surpassing that of bismerthiazol and thiodiazole copper by approximately 8.0%-37.3 %. Overall, our findings highlight a new paradigm wherein nonivamide derivatives exhibit potential in combating pathogen resistance issues by inhibiting bacterial quorum sensing systems though attributing to their new molecular skeleton, novel mechanisms of action, and non-toxic features.

Pathogen-Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization.

Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan-catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy.

PURPOSE: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). METHODS: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. RESULTS: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. CONCLUSIONS: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

Preoperative fasting glucose value can predict acute kidney injury in non-cardiac surgical patients without diabetes but not in patients with diabetes.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common and costly complication after non-cardiac surgery. Patients with or without diabetes could develop hyperglycemia before surgery, and preoperative hyperglycemia was closely associated with postoperative poor outcomes, but the association between preoperative fasting blood glucose level and postoperative AKI is still unclear. METHODS: Data from patients undergoing non-cardiac surgery in Chongqing University Cancer Hospital from January 1, 2017, to May 31, 2023, were collected, preoperative glucose value and perioperative variables were extracted, the primary exposure of interest was preoperative glucose value, and the outcome was postoperative AKI. RESULTS: Data from 39,986 patients were included in the final analysis, 741(1.9%) patients developed AKI, 134(5.6%) in the cohort with DM, and 607(1.6%) in the cohort without DM(OR 1.312, 95% CI 1.028-1.675, P = 0.029). A significant non-linear association between preoperative glucose and AKI exists in the cohort without DM after covariable adjustment (P = 0.000), and every 1 mmol/L increment of preoperative glucose level increased OR by 15% (adjusted OR 1.150, 95% CI 1.078-1.227, P = 0.000), the optimal cut-point of preoperative fasting glucose level to predict AKI was 5.39 mmol/L (adjusted OR 1.802, 95%CI 1.513-2.146, P = 0.000). However, in the cohort with DM, the relation between preoperative glucose and postoperative AKI was not significant after adjusting by covariables (P = 0.437). No significance exists between both cohorts in the risk of AKI over the range of preoperative glucose values. CONCLUSION: A preoperative fasting glucose value of 5.39 mmol/L can predict postoperative acute kidney injury after non-cardiac surgery in patients without diagnosed diabetes, but it is not related to AKI in patients with the diagnosis.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

Isolation of endophytes from Dioscorea nipponica Makino for stimulating diosgenin production and plant growth.

KEY MESSAGE: Both bacterial and fungal endophytes exhibited one or more plant growth-promoting (PGP) traits. Among these strains, the Paenibacillus peoriae SYbr421 strain demonstrated the greatest activity in the direct biotransformation of tuber powder from D. nipponica into diosgenin. Endophytes play crucial roles in shaping active metabolites within plants, significantly influencing both the quality and yield of host plants. Dioscorea nipponica Makino accumulates abundant steroidal saponins, which can be hydrolyzed to produce diosgenin. However, our understanding of the associated endophytes and their contributions to plant growth and diosgenin production is limited. The present study aimed to assess the PGP ability and potential of diosgenin biotransformation by endophytes isolates associated with D. nipponica for the efficient improvement of plant growth and development of a clean and effective approach for producing the valuable drug diosgenin. Eighteen bacterial endophytes were classified into six genera through sequencing and phylogenetic analysis of the 16S rDNA gene. Similarly, 12 fungal endophytes were categorized into 5 genera based on sequencing and phylogenetic analysis of the ITS rDNA gene. Pure culture experiments revealed that 30 isolated endophytic strains exhibited one or more PGP traits, such as nitrogen fixation, phosphate solubilization, siderophore synthesis, and IAA production. One strain of endophytic bacteria, P. peoriae SYbr421, effectively directly biotransformed the saponin components in D. nipponica. Moreover, a high yield of diosgenin (3.50%) was obtained at an inoculum size of 4% after 6 days of fermentation. Thus, SYbr421 could be used for a cleaner and more eco-friendly diosgenin production process. In addition, based on the assessment of growth-promoting isolates and seed germination results, the strains SYbr421, SYfr1321, and SYfl221 were selected for greenhouse experiments. The results revealed that the inoculation of these promising isolates significantly increased the plant height and fresh weight of the leaves and roots compared to the control plants. These findings underscore the importance of preparing PGP bioinoculants from selected isolates as an additional option for sustainable diosgenin production.

Fas ligand regulate nerve injury and repair by affecting AKT, ß-catenin, and NF-κB pathways.

Objective: To investigate the regulatory effect of Fas-L on the repair and regeneration of peripheral extension injury in rats. Methods: This study aimed to explore the effects of Fas-L on apoptosis and axonal regeneration of dorsal root ganglion (DRG) cells in rat peripheral nerve repair and regeneration by using several relevant experimental techniques from the injured nerve animal model, cell biology, and molecular biology. Results: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Interference with Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis, while the overexpression of Fas-L is contrary to it. Moreover, Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in Sprague Dawley (SD) rats by affecting several signaling pathways, such as p-AKT/AKT, ß-catenin, and NF-κB. Conclusion: Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves. Significance statement: The expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis. Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in SD rats by affecting several signaling pathways, such as p-AKT/AKT, ß-catenin, and NF-κB. Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves.

Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy via apoptosis and ferroptosis.

Rationale: Cancer continues to be a significant public health issue. Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects. Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy. Successful cancer treatment is achieved when regulated cell death (RCD) of cancer cells, which includes apoptotic and non-apoptotic processes such as ferroptosis, is fundamental to successful cancer treatment. The developing field of nanozymes holds considerable promise for innovative cancer treatment approaches. Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed to combat tumors by depleting glutathione (GSH) and concurrently liberating DOX. The initial phase of the study examined the GSH oxidase-mimicking function of the dimetallic nanozyme (ZIF-8/SrSe) through enzyme kinetic assays and Density Functional Theory (DFT) simulations. Following this, we probed the ability of ZIF-8/SrSe@DOX to release DOX in response to the tumor microenvironment in vitro, alongside examining its anticancer capabilities and mechanisms prompting apoptosis or ferroptosis in cancer cells. Moreover, we established tumor-bearing animal models to corroborate the anti-tumor effectiveness of our nanozyme complex and to identify the involved apoptotic and ferroptotic pathways implicated. Results: Enzyme kinetic analyses demonstrated that the ZIF-8/SrSe nanozyme exhibits substantial GSH oxidase-like activity, effectively oxidizing reduced GSH to glutathione disulfide (GSSG), while also inhibiting glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). This inhibition led to an imbalance in iron homeostasis, pronounced caspase activation, and subsequent induction of apoptosis and ferroptosis in tumor cells. Additionally, the ZIF-8/SrSe@DOX nanoparticles efficiently delivered DOX, causing DNA damage and further promoting apoptotic and ferroptotic pathways. Conclusions: This research outlines the design of a novel platform that combines chemotherapeutic agents with a Fenton reaction catalyst, offering a promising strategy for cancer therapy that leverages the synergistic effects of apoptosis and ferroptosis.

Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.

Complete mitochondrial genome of the endangered Prunus pedunculata (Prunoideae, Rosaceae) in China: characterization and phylogenetic analysis.

Introduction: Prunus pedunculata (Prunoideae: Rosaceae), a relic shrub with strong resistance and multiple application values, is endangered in China. Extensive research had been devoted to gene expression, molecular markers, plastid genome analysis, and genetic background investigations of P. pedunculata. However, the mitochondrial genome of this species has not been systematically described, owing to the complexity of the plant mitogenome. Methods: In the present research, the complete mitochondrial genome of P. pedunculata was assembled, annotated, and characterized. The genomic features, gene content and repetitive sequences were analyzed. The genomic variation and phylogenetic analysis have been extensively enumerated. Results and discussion: The P. pedunculata mitogenome is a circular molecule with a total length of 405,855 bp and a GC content of 45.63%, which are the smallest size and highest GC content among the known Prunus mitochondrial genomes. The mitogenome of P. pedunculata encodes 62 genes, including 34 unique protein-coding genes (PCGs, excluding three possible pseudogenes), three ribosomal RNA genes, and 19 transfer RNA genes. The mitogenome is rich in repetitive sequences, counting 112 simple sequence repeats, 15 tandem repeats, and 50 interspersed repetitive sequences, with a total repeat length of 11,793 bp, accounting for 2.91% of the complete genome. Leucine (Leu) was a predominant amino acid in PCGs, with a frequency of 10.67%, whereas cysteine (Cys) and tryptophan (Trp) were the least adopted. The most frequently used codon was UUU (Phe), with a relative synonymous codon usage (RSCU) value of 1.12. Selective pressure was calculated based on 20 shared PCGs in the mitogenomes of the 32 species, most of which were subjected to purifying selection (Ka/Ks < 1), whereas ccmC and ccmFn underwent positive selection. A total of 262 potential RNA editing sites in 26 PCGs were identified. Furthermore, 56 chloroplast-derived fragments were ascertained in the mitogenome, ranging from 30 to 858 bp, and were mainly located across IGS (intergenic spacer) regions or rRNA genes. These findings verify the occurrence of intracellular gene transfer events from the chloroplast to the mitochondria. Furthermore, the phylogenetic relationship of P. pedunculata was supported by the mitogenome data of 30 other taxa of the Rosaceae family. Understanding the mitochondrial genome characteristics of P. pedunculata is of great importance to promote comprehension of its genetic background and this study provides a basis for the genetic breeding of Prunus.

Pogocablenes A-O, fifteen undescribed sesquiterpenoids with structural diversity from Pogostemon cablin.

Fifteen previously undescribed sesquiterpenoids (pogocablenes A-O), three first discovered natural patchoulol-type ones, coupled with fourteen known ones, were isolated from the aerial parts of Pogostemon cablin. Among them, pogocablenes A and B, a pair of C2 epimers, possessed an unusual carbon skeleton with bicyclo[4.3.1]decane core. Pogocablene C, originated from eudesmane-type sesquiterpenoid, had an unprecedented bicyclo[5.4.0]undecane scaffold with a peroxy hemiactetal moiety. Pogocablene D possessed a rare tricyclo[5.2.2.01,5]undecane carbon skeleton derived from guaiane-type sesquiterpenoid. Pogocablene E was a 4,5-seco-guaiane derivative owning a peroxy hemiactetal unit and a spirocyclic skeleton. Pogocablene M was a nor-patchoulol-type sesquiterpenoid with α,ß-unsaturated ketone moiety. Their structures with absolute configuration were determined by extensive spectroscopic analysis, in combination with quantum chemical calculation. In addition, the plausible biogenetic pathways of pogocablenes A-E were proposed. Furthermore, all isolates were evaluated for anti-influenza virus and anti-inflammatory effects.

Photothermal-Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction.

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.

Nickel-doped iridium echinus-like nanosheets for stable acidic water splitting.

Nickel-doped iridium echinus-like nanosheets (NiIr-ENS) have a superior acidic oxygen evolution reaction (OER) activity with a TOF of 1.72 s-1 at an overpotential of 300 mV, 8.6-fold higher than that of IrO2.

Natural Products-Based Botanical Bactericides Discovery: Novel Abietic Acid Derivatives as Anti-Virulence Agents for Plant Disease Management.

The discovery of natural product-based pesticides is critical for agriculture. In this work, a series of novel tricyclic diterpenoid derivatives decorated with an amino alcohol moiety were elaborately prepared from natural abietic acid, and their antibacterial behavior was explored. Bioassay results indicated that compound C2 exhibited the most promising bioactivity (EC50 = 0.555 µg mL-1) against Xanthomonas oryzae pv. oryzae (Xoo), about 73 times higher than the effect of commercial thiodiazole copper (TC). Results of in vivo bioassays showed that compound C2 displayed significantly higher control of rice bacterial leaf blight (curative activity: 63.8%; protective activity: 58.4%) than TC (curative activity: 43.6%; protective activity: 40.8%), and their bioactivity could be improved maximally 16% by supplementing the auxiliaries. Antibacterial behavior suggested that compound C2 could suppress various virulence factors. Overall, these findings suggested that new botanical bactericide candidates could control intractable plant bacterial diseases by suppressing virulence factors.

Novel Benzothiazole Derivatives as Potential Anti-Quorum Sensing Agents for Managing Plant Bacterial Diseases: Synthesis, Antibacterial Activity Assessment, and SAR Study.

As quorum sensing (QS) regulates bacterial pathogenicity, antiquorum sensing agents have powerful application potential for controlling bacterial infections and overcoming pesticide/drug resistance. Identifying anti-QS agents thus represents a promising approach in agrochemical development. In this study, the anti-QS potency of 53 newly prepared benzothiazole derivatives containing an isopropanolamine moiety was analyzed, and structure-activity relationships were examined. Compound D3 exhibited the strongest antibacterial activity, with an in vitro EC50 of 1.54 µg mL-1 against Xanthomonas oryzae pv oryzae (Xoo). Compound D3 suppressed QS-regulated virulence factors (e.g., biofilm, extracellular polysaccharides, extracellular enzymes, and flagella) to inhibit bacterial infection. In vivo anti-Xoo assays indicated good control efficiency (curative activity, 47.8%; protective activity, 48.7%) at 200 µg mL-1. Greater control efficiency was achieved with addition of 0.1% organic silicone or orange peel essential oil. The remarkable anti-QS potency of these benzothiazole derivatives could facilitate further novel bactericidal compound development.

Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery.

Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs'/pesticides' bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1H)-one derivatives and evaluated their antibacterial behaviors. Compound B6 exhibited the highest bioactivity, with half-maximal effective concentration (EC50) values ranging fro9m 10.03 to 30.16 µg mL-1 against three plant pathogenic bacteria. The antibacterial mechanism showed that it could considerably reduce various virulence factors (such as extracellular enzymes, biofilm, and T3SS effectors) and inhibit the expression of virulence factor-related genes. In addition, the control efficiency of compound B6 against rice bacterial leaf blight at 200 µg mL-1 was 46.15-49.15%, and their control efficiency was improved by approximately 12% after the addition of pesticide additives. Thus, a new class of bactericidal candidates targeting bacterial virulence factors was developed for controlling plant bacterial diseases.

Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

The optimal approach to locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment remains controversial. For non-resectable LAHNSCC, the clinical interest of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) or radiotherapy has been questioned. With the approval of immunotherapy and targeted therapy for this disease, treatment options have become more complex. Although new trial data have appeared every year, the results are still inconclusive. In this review, we provide readers with information on new strategies for LAHNSCC induction therapy, which will facilitate evidence-based decision making in LAHNSCC treatment.