Mode Of Action Research Articles

Drug resistance and possible therapeutic options against influenza A virus infection over past years.

Influenza A virus infection, commonly known as the flu, has persisted in the community for centuries. Although we have yearly vaccinations to prevent seasonal flu, there remains a dire need for antiviral drugs to treat active infections. The constantly evolving genome of the influenza A virus limits the number of effective antiviral therapeutic options. Over time, antiviral drugs become inefficient due to the development of resistance, as seen with adamantanes, which are now largely ineffective against most circulating strains of the virus. Neuraminidase inhibitors have long been the drug of choice, but due to selection pressure, strains are becoming resistant to this class of drugs. Baloxavir marboxil, a drug with a novel mode of action, can be used against strains resistant to other classes of drugs but is still not available in many countries. Deep research into nanoparticles has shown they are effective as antiviral drugs, opening a new avenue of research to use them as antiviral agents with novel modes of action. As this deadly virus, which has killed millions of people in the past, continues to develop resistance, there is an urgent need for new therapeutic agents with novel modes of action to halt active infections in patients. This review article covers the available therapeutic antiviral drug options with different modes of action, their effectiveness, and resistance to various strains of influenza A virus.

Clinical profile, inhaler technique, and predictors of inhaler adherence among asthma and COPD patients who attended the outpatient emergency department for acute exacerbation.

Understanding the patients' clinical profile, barriers to optimal inhaler use, and adherence are crucial in achieving the treatment goal for asthma and chronic obstructive pulmonary disease (COPD). This study aimed to assess the inhaler technique and identify the predictors of inhaler adherence among asthma and COPD patients who presented to the Emergency Department (ED). This prospective cross-sectional study recruited patients who presented to the outpatient ED of a tertiary hospital for mild-to-moderate exacerbation from March 2022 to February 2023. Convenience sampling was used in this study. The inhaler techniques and adherence of all subjects were evaluated. Regression analysis was used to identify predictors of inhaler adherence. We recruited 120 subjects with a mean age of 47.8 ± 16.0 and were predominantly asthma patients (n = 85, 70.8%). Most were on regular follow-up (n = 72, 60.0%) and adhered to their inhaler(s) (n = 86, 71.7%). Less than half of the subjects use their inhaler(s) correctly (n = 45, 37.5%). Three predictors of inhaler adherence were identified: regular follow-up (aOR 2.072, p = 0.041), correct inhaler technique (aOR 3.071, p = 0.039), and ability to explain inhalers' mode of action (aOR 10.906, p = 0.031). The high rate of wrong inhaler techniques among asthma and COPD patients is worrisome. Identified predictors of inhaler adherence should be targeted when managing this group of patients. In addition to the exacerbation treatment in the ED, referrals to public primary health clinics for regular follow-ups, evaluation of inhaler techniques, and counseling to enhance patient knowledge are crucial.

MANTRACHIKITSA: FACTS AS MENTIONED IN THE AYURVEDIC CLASSICS

Mantra, indicates chanting of some prescribed verses for designated purposes, is a controversial but interesting and important topic. Scientific validation of mantra is difficult to establish due to the factors like – difficulty in (1) understanding the meaning of the verses, (2) understanding the mode of action, (3) understanding the effect scientifically etc. But traditional experience and classical references strongly support the use and efficacy of Mantra in different references. A number of researches are also already conducted in different levels with the aim to understand it scientifically. In the Ayurvedic classics a number of indications and benefits of Mantra are mentioned in different references like Vishachikitsa (in snakebite mentioned with top priority), Grahachikitsa (conditions that occur due to effect of some unseen, unundentifiable aetiologies etc.). The Ayurvedic scholars have discussed in detail about mantra with special reference to method of learning, practising etc. As a widely discussed noninvasive treatment procedure that is getting topmost priority in a condition like snakebite (a very dangerous and usually fatal poisoning) a discussion on Mantra basing upon the Ayurvedic classics is considered to be informative and thought provoking for the scientific forum.

Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of β-Lactam Antibiotics.

Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics. Remarkably, the β-lactam-peptide conjugates gained an up to 1000-fold increase in antimicrobial activity against vancomycin-susceptible and vancomycin-resistant enterococci. Even against β-lactam-resistant Gram-negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration-dependent activity in contrast to the parent β-lactam antibiotics that exhibited a time-dependent mode of action. In comparison to the parent β-lactams, the conjugates showed altered affinities to the penicillin-binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin-resistant enterococci, treatment with a β-lactam-peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of β-lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci.

Anacardium Occidentale-Derived Nanoparticles as a Biocompatible Targeted Therapy for Breast Cancer Cells

Breast cancer is a global health burden and therefore necessitates a continued exploration for new therapeutic mediators. In current scenario, nanotechnology has developed an interest in the application of nanoparticles in treating cancer. The need for new therapeutic agents against one of the global health burdens, breast cancer, is continuous. Nanoparticle application using nanotechnology for cancers has received increased interest in recent years. This review critically analyzes the bioactive compounds of Anacardium occidentale, commonly known as cashew, and their synthesized nanoparticles in relation to activities on cell lines responsible for breast cancer. These facts describe the phytochemical make-up of Anacardium occidentale's, approaches for nanoparticles synthesis, and their modes of action with respect to tumor cells; and implications for the elaboration of future approaches to the treatment of cancer.

Innovative perspectives on bacteriocins: advances in classification, synthesis, mode of action, and food industry applications.

Bacteriocins, natural antimicrobial peptides produced by bacteria, present eco-friendly, non-toxic, and cost-effective alternatives to traditional chemical antimicrobial agents in the food industry. This review provides a comprehensive update on the classification of bacteriocins in food preservation. It highlights the significant industrial potential of pediocin-like and two-peptide bacteriocins, emphasizing chemical synthesis methods like Fmoc-SPPS to meet the demand for bioactive bacteriocins. The review details the mode of action, focusing on mechanisms such as transmembrane potential disruption and pH-dependent effects. Furthermore, it addresses the limitations of bacteriocins in food preservation and explores the potential of nanotechnology-based encapsulation to enhance their antimicrobial efficacy. The benefits of nanoencapsulation, including improved stability, extended antimicrobial spectrum, and enhanced functionality, are underscored. This understanding is crucial for advancing the application of bacteriocins to ensure food safety and quality.

Autophagy is essential for somatic embryogenesis in citrus through regulating amyloplast degradation and lipid homeostasis.

Autophagy is a conserved degradation pathway that regulates the clearance of paternal substrate at the early embryogenesis stage of animals. However, its mode of action is likely different in plants, which can regenerate through apomixis without fertilisation. Somatic embryogenesis (SE) is a unique plant process widely used for plant propagation and germplasm utilisation. Here, we studied citrus as an example and found a higher autophagic activity after SE initiation. Interestingly, amyloplasts were frequently found inside autophagosomes, whereas the inhibition of autophagy blocks amyloplasts/starch degradation and hinders somatic embryo formation. Furthermore, the consumption of storage lipids was faster in autophagy mutants, suggesting lipid metabolism is activated when starch utilisation is blocked. Exogenous application of autophagy-inducing chemicals (e.g. spermidine) significantly promoted the formation of autophagosomes and increased SE efficiency, indicating a positive correlation between autophagy, energy metabolism, and somatic embryo formation in citrus. Taken together, our study unveils a pathway for the degradation of plant-specific organelles and provides an effective approach for plant propagation.

Active cardboard box with palm wood waste powder and orange oil to prevent browning and quality loss in cabbage: Mode of action and potential for reuse.

Browning, caused by enzymatic activity and storage conditions, affects cabbage during cold storage and is crucial for customer acceptance. This study investigated the effect of cardboard packaging containing low concentrations of nano-orange oil (ONE) at 0.006% in palm wood waste powder for anti-browning and extending the shelf life of cabbage. The incorporation of ONE into palm wood powder (PWP) using different methods (soaking, vapor, vapor with ultrasonic device, and control) was examined before using the active PWP to develop cardboard cabbage packaging. The reuse of the active cabbage box packaging was also investigated for up to three reuses. The results showed that a greater anti-browning effect was achieved with cardboard packaging made from active PWP with orange oil vapor and an ultrasonic device compared to other adsorption methods, with significantly higher inhibition of the key browning enzyme activities of polyphenol oxidase (PPO) and peroxidase (POD). Additionally, antioxidant activity and bioactive compounds were improved, maintaining the bright green color of cabbage after 21 days of storage. The shelf life of cabbage stored in active cardboard was extended to at least 21 days compared to 5 days for the control. The active cabbage box with PWP and ONE vapor with an ultrasonic device showed potential for reuse at least two times. Limonene was found on the surface of stored cabbage and may be a key factor in antimicrobial activity, helping to control microbial growth on the cabbage surface within standard limits during long-term storage. This finding provides valuable guidance for reducing cabbage waste during transportation and storage from farm to market. PRACTICAL APPLICATION: This research offers new insights into active cardboard packaging made from palm wood powder with a low concentration of orange oil vapor to prevent browning and microbial growth in storage boxes. The optimal method for producing this packaging uses nano-orange oil vapor at 0.006% with an ultrasonic device, which could be feasible for large-scale production. The packaging effectively reduced PPO and POD enzyme activity, delaying browning and extending cabbage shelf life by at least threefold compared to the control, while maintaining color and freshness. This cost-effective method promotes the sustainable use of agricultural waste in the fresh vegetable industry, as it can be reused at least twice, benefiting farmers and reducing cabbage waste.

A Comprehensive Review of Antimicrobial Agents Against Clinically Important Bacterial Pathogens: Prospects for Phytochemicals.

Antimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes. Therefore, in this review, we have addressed the challenges and focused on various phytochemicals as antimicrobial agents acting on the membranes of clinically important bacterial pathogens. Antibacterial phytochemicals comprise diverse group of agents found in a wide range of plants. These compounds have been found to disrupt cell membranes, inhibit enzymes, interfere with protein synthesis, generate reactive oxygen species, modulate quorum sensing, and inhibit bacterial adhesion, making them promising candidates for the development of novel antibacterial therapies. Recently, polyphenolic compounds have been reported to have proven efficacy against nosocomial multidrug-resistant pathogens. However, more high-quality studies, improved standards, and the adoption of rules and regulations are required to firmly confirm the clinical efficacy of phytochemicals derived from plants. Identifying potential challenges, thrust areas of research, and considering viable approaches is essential for the successful clinical translation of these compounds.

Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications.

In 2021 the European Food Safety Authority (EFSA) concluded that "A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out.". A detailed review of the genotoxicity of titanium dioxide (TiO2) was subsequently published by Kirkland et al. (2022) using a comprehensive weight of evidence (WoE) approach in which test systems and endpoints were allocated different levels of relevance. At that time only 34 publications met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity, and based on these it was concluded that the existing evidence did not support a direct DNA damaging mechanism for TiO2. Recently a number of regulatory opinions have been published, in which papers were cited that described in vitro DNA damage (mainly comet), mode of action, and cellular uptake studies that were not discussed in Kirkland et al. (2022). Furthermore, a number of additional papers have been published recently or have been identified from the regulatory opinions as a result of using extended search criteria. A total of 70 publications not previously reviewed in Kirkland et al. (2022) have been reviewed here, and again show that the published data on the genotoxicity of TiO2 are inconsistent, often of poor quality, and in some cases difficult to interpret. The cellular uptake studies show some evidence of cytoplasmic uptake, particularly in cells treated in vitro, but there is no convincing evidence of nuclear uptake. In terms of genotoxicity, the conclusions of Kirkland et al. (2022) that existing evidence does not support a direct DNA damaging mechanism for titanium dioxide (including nano forms), and that the main mechanism leading to TiO2 genotoxicity is most likely indirect damage to DNA through generation of reactive oxygen species (ROS), are still valid.

Antibacterial peptides from black soldier fly (Hermetia illucens) larvae: mode of action and characterization

Antibacterial peptides from black soldier fly larvae extract were prepared using Flash column chromatography. Three out of five fractions (F2, F3 and F4) showed antibacterial activity against Listeria monocytogenes DMST 17303 with a minimum inhibitory concentration (MIC) of 1 mM, followed by Salmonella enterica Enteritidis DMST 15679 and Escherichia coli O157:H7 DMST 12743 with a MIC ranging from 4 to 8 mM. Due to the higher yield, F2 and F3 were further analyzed on their mode of action against L. monocytogenes DMST 17303. Both fractions, particularly F2, exerted antibacterial activity through inducing bacterial cell membrane disintegration and interaction with intracellular compounds including fatty acids, proteins, and nucleic acids. The F3 did not show significant hemolytic activity up to 4 mM, while F2 showed lower than 5% hemolysis up to 8 mM. Time-to-kill analysis revealed that F2 was more effective and exerted a sustainable killing effect after 2 and 4 h, depending on the concentration of 1 and 2×MIC, respectively, while the F3 at 2×MIC could completely kill the test bacteria within 24 h. Among the identified peptides in the fractions, those with charged, either positively or negatively, and moderate hydrophobicity of ranging 6.68–15.70, namely CGPPRQGPFPR, HLEEELK, LEEAEERAD, TEELEEAKKK, and KGNSELEEAKKK, are potential antimicrobial peptides.

Fitness Costs in Diamondback Moth Plutella xylostella (L.) (Lepidoptera: Plutellidae) Resistant to Lufenuron, A Chitin-Synthesis Inhibitor Insecticide

The diamondback moth (DBM), Plutella xylostella, is the main pest of Brassicas crops worldwide, and its recorded resistance to 101 active ingredients indicates it is difficult to control. The purpose of this study was to investigate the hypothesis that P. xylostella has fitness costs associated with its resistance to lufenuron, a chitin-synthesis inhibitor insecticide. Thus, concentration–mortality bioassays were performed for susceptible (REC-S), resistant (BZR-R) populations, their progenies F1 and F1′, and one established population without selection pressure (BZR-Rns) after four generations. A fertility life table was used to assess the biological performance of the REC-S and BZR-R. BZR-Rns of P. xylostella. The larval stage, longevity, and survival differed between populations. The reproductive rate (R0) was significantly lower in the F1 (♀R × ♂S) (28.19) and F1′ (♀S × ♂R) (34.06) progenies compared with their parents, but not with the relaxed BZR-Rns (39.39). The mean generation time (T), intrinsic rate of population growth (rm), and doubling time (DT) differed between REC-S and progenies, with fitness of 0.52 and 0.64 for F1 and F1′, respectively. Overall, the results suggest that the resistance of P. xylostella to lufenuron is stable and that low fitness costs appear to be associated with resistance to lufenuron, although heterozygotes showed lower fitness than their parents. Strategies such as preserving refuge areas, rotation of modes of action, etc., are essential for resistance management and prolonging the efficacy of control agents; this highlights the importance of integrated insecticide resistance management.

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5'-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans.

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach. Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in in vitro cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5'-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, i.e. inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS). Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.

Assessing plasmatic transport inhibitors of thyroid hormone in mammals in the Xenopus Eleutheroembryonic Thyroid Assay (XETA).

The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD TG 248) was established as an alternative to the Amphibian Metamorphosis Assay (AMA, OECD TG 231) for the analysis of (anti-)thyroid activity of chemicals. The XETA is a New Approach Method (NAM) since the embryonic life stages used in the assay are not yet feeding independently, which renders the assay to be considered a non-animal test under many national laws. Physiologically, the used embryos are not fully developed yet, and thus there are limitations to the XETA for detecting certain mechanisms along the hypothalamic-pituitary-thyroid (HPT) axis. However, the plasmatic transport inhibition of thyroid hormone should physiologically be detectable in the XETA but has not yet been sufficiently investigated. Here, we tested three substances that are known, amongst others, to inhibit thyroid hormone transport by competitive binding to transthyretin in mammalian studies, namely pentachlorophenol (PCP), tetrabromo bisphenol A (TBBPA), and mefenamic acid. Following the test guideline, X. laevis eleutheroembryos of Nieuwkoop-Faber stage 45 were exposed for 72h at 21°C in 6-well plates to different concentrations of the test substances. For PCP and TBBPA, the XETA showed a decrease in fluorescence intensity, which would be expected for thyroid hormone transport inhibition amongst other, similar modes of action, while for the lower potency substance mefenamic acid, a trend was visible, but no statistically significant inhibition was detected. Overall, the results indicate that in the XETA, the plasmatic transport inhibition of thyroid hormone should be detectable alongside other inhibitory modes of action on the HPT axis.

Mechanistic Insight into the Role of Peptides Secreted from Bacillus clausii and Future Opportunities.

Bacillus clausii is a commercial spore probiotic known to treat multiple diseases. An increased interest in exploring the nutraceutical and probiotic properties of various microorganisms has made researchers explore more about these bacteria. The current trends in the healthcare industry are majorly focused on devising new therapies to avoid drug and pathogen resistance in patients. Antimicrobial peptides have been considered a source of antibiotics for a long time. Still, getting new therapies into the market is a big challenge. Members of the genus Bacillus have been reported to have a broad spectrum of antimicrobial peptides. One of the least explored species under this genus is Bacillus clausii, concerning peptide drug therapy. The applications of Bacillus clausii in treating or preventing gut dysbiosis and respiratory infections have been largely supported in the past two decades. Yet research is lacking in explaining the pathways at molecular levels in targeting pathogens. In this mini-review, we are going to summarise the research that has been reported so far about peptide extraction from Bacillus clausii, their mode of action and advantages to mankind, and the challenges lying in the isolation of peptides.

Herbicide Formulation Affects Weed Control and Crop Tolerance in Greenhouse Ornamentals

Weed control in container-grown ornamentals can be improved by careful herbicide selection. Four studies were conducted in greenhouses at Oregon State University to improve the understanding of how differences in the mode of action and formulation of herbicides can affect bryophyte control efficacy and crop safety. Granular (G) formulations of pendimethalin and indaziflam were compared with sprayable liquid (L) formulations of pendimethalin, indaziflam, and dimethenamid-p as well as with a nontreated control on four perennial container-grown ornamentals. Indaziflam in the L formulation performed better than that in the G formulations for controlling hairy bittercress up to 20 weeks after the initial treatment. Dimethenamid-p was more effective than indaziflam for liverwort and moss control. Pendimethalin in the G formulation less effectively controlled hairy bittercress than the L formulation did, but it performed better against moss during a second study. The L formulation of indaziflam injured Japanese pachysandra and boxwood and reduced root and shoot growth by 10% to 29%. Dimethenamid-p provided excellent control of the weed species tested and was safe for the crops, indicating its potential use as an alternative to hand-weeding in greenhouses.

Homoharringtonine in the treatment of acute myeloid leukemia: A review.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the accumulation of immature myeloid precursor cells. Over half of AML patients fail to achieve long-term disease-free survival under existing therapy, and the overall prognosis is poor, necessitating the urgent development of novel therapeutic approaches. The plant alkaloid homoharringtonine (HHT), which has anticancer properties, was first identified more than 40 years ago. It works in a novel method of action that prevents the early elongation phase of protein synthesis. HHT has been widely utilized in the treatment of AML, with strong therapeutic effects, few toxic side effects, and the ability to enhance AML patients' prognoses. In AML, HHT can induce cell apoptosis through multiple pathways, exerting synergistic antitumor effects, according to clinical and pharmacological research. About its modes of action, some findings have been made recently. This paper reviews the development of research on the mechanisms of HHT in treating AML to offer insights for further research and clinical therapy.

Computational study of the HLTF ATPase remodeling domain suggests its activity on dsDNA and implications in damage tolerance.

The Helicase-Like Transcription Factor (HLTF) is member of the SWI/SNF-family of ATP dependent chromatin remodellers known primarily for maintaining genome stability. Biochemical and cellular assays support its multiple roles in DNA Damage Tolerance. However, the lack of sufficient structural data limits the comprehension of the molecular basis of its modes of action. In this work we have modelled and characterized the HLTF ATPase remodeling domain by using bioinformatic tools and all-atoms molecular dynamics simulations. In-silico results suggested that its binding to dsDNA is mainly mediated by the positively charged residues Arg563 and Lys913, found conserved in HLTF homologs, and Arg620 and Lys999, found only in HLTF. Interestingly, these residues are mutated in cancer cells. During translocation on dsDNA, HLTF remains persistently bound through the N-terminal ATPase subunit. However, DNA advancement occurs only in the presence of the synergic-anticorrelated action of both motor lobes. In contrast, the C-terminal facilitates substrate remodeling through DNA deformation and generation of bulges according to a wave-model. Finally, the large conformational change suggested between the two motor-remodeling subunits might be activated upon the release of PARP1 on stalled fork and be responsible for the intervention of HLTF-HIRAN in the formation of D-loop and 4-way junction DNA structures.

Christensenella minuta Mitigates Behavioral and Cardiometabolic Hallmarks of Social Defeat Stress

Psychological stress during early development and adolescence may increase the risk of psychiatric and cardiometabolic comorbidities in adulthood. The gut microbiota has been associated with mental health problems such as depression and anxiety and with cardiometabolic disease, but the potential role of the gut microbiota in their comorbidity is not well understood. We investigated the effects and mode of action of the intestinal bacterium Christensenella minuta DSM 32891 on stress-induced mental health and cardiometabolic disturbances in a mouse model of social defeat stress. We demonstrate that administered C. minuta alleviates chronic stress-induced depressive, anxiogenic and antisocial behavior. These effects are attributed to the bacterium’s ability to modulate the hypothalamic-pituitary-adrenal axis, which mediates the stress response. This included the oversecretion of corticosterone and the overexpression of its receptors, as well as the metabolism of dopamine (DA) and the expression of its receptors (D1, D2L and D2S). Additionally, C. minuta administration reduced chronically induced inflammation in plasma, spleen and some brain areas, which likely contribute to the recovery of physical and behavioral function. Furthermore, C. minuta administration prevented chronic stress-induced cardiovascular damage by regulating key enzymes mediating liver fibrosis and oxidative stress. Finally, C. minuta increased the abundance of bacteria associated with mental health. Overall, our study highlights the potential of microbiota-directed interventions to alleviate both the physical and mental effects of chronic stress.

Design, Synthesis, and Evaluation of Novel Thiazole-Containing Algicides Inspired by Bacillamide A

The pursuit of highly effective, low-toxicity, and eco-friendly algicides for controlling and eradicating harmful algal blooms (HABs) is of paramount importance. The natural allelochemical bacillamide A has displayed impressive algicidal activity against harmful algae with favorable safety profiles. However, the poor synthetic efficiency and large dose requirements of bacillamide A limit its further application. In this paper, 17 thiazole-containing bacillamide derivatives (BDs) were designed and synthesized in three linear steps as potential algicides. Eight compounds (6a, 6c, 6j, 7b, 7c, 7d, 7e, and 7g) displayed potent inhibitory effects against Prorocentrum minimum, Skeletonema costatum, and Alexandrium pacificum, and they had similar or better activity than the positive control (CuSO4) and bacillamide A. Compound 6a exhibited the most potent algicidal activity against S. costatum (half-maximal effective concentration [EC50] = 0.11 μg/mL), being 23-fold more potent than bacillamide A, 28-fold more potent than CuSO4, and 39-fold more potent than Diuron. Compound 6j exhibited significant algicidal activity against the toxic dinoflagellates P. minimum (EC50 = 1.0 μg/mL) and A. pacificum (EC50 = 0.47 μg/mL), being 3–5-fold more potent than natural bacillamide A, Diuron, and CuSO4. Micrographs and SEM images revealed that 6j induced cell wall rupture and cellular content leakage. Biochemical and physiological studies indicated that 6j might partially disrupt the antioxidant and photosynthetic systems in algal cells, resulting in morphological changes, cell wall rupture, and inclusion leakage. Our work suggests that 6j has a distinct mode of action from CuSO4 and provides a promising candidate for the development of new algicides, worthy of further investigation.