Assessment of acute, subacute genetic toxicities and immunomodulatory activity of palm (Trachycarpus fortunei) buds.

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.

Unveiling significant roles of phytohormone 6-benzylaminopurine in empowering Phaeodactylum tricornutum for high-salinity wastewater treatment and bioresource recovery.

High-salinity presents significant challenges in microalgal wastewater treatment and bioresource recovery due to salinity stress. This study explored the use of salt-tolerant microalgae in conjunction with phytohormone regulation. 1 µM 6-benzylaminopurine increased the biomass of Phaeodactylum tricornutum by 38.3 % and enhanced lipid production by 36.8 %. 6-benzylaminopurine significantly improved the removal of inorganic carbon, total nitrogen, and total phosphorus by 85.2 %, 27.4 %, and 31.9 %. Specifically, 6-benzylaminopurine improved K+ transportation by 71.0 %, increased the activity of Ca2+ transport ATPase and Ca2+ sensors by 49.0 %-83.0 %, optimized osmotic balance, and alleviated salt-induced damage. The contents of proline and extracellular polymers increased by 34.8 % and 35.5 %. A 38.4 % reduction in reactive oxygen species indicated that high-salinity stress was mitigated. The analysis of Sustainable Development Goals showed a 56.2 % improvement in Affordable and Clean Energy. Overall, these findings further highlighted the promising application of the phytohormone 6-benzylaminopurine in microalgal high-salinity wastewater treatment and lipid production.

Lats-IN-1 protects cardiac function and promotes regeneration after myocardial infarction by targeting the hippo pathway.

Introduction: Myocardial infarction (MI), a leading cause of heart failure, is characterized by the loss of cardiomyocytes, which severely limits the heart's regenerative capacity. The Hippo pathway, which regulates cell proliferation and apoptosis, presents a therapeutic target for cardiac regeneration. This study explores the efficacy of Lats-IN-1, a LATS1/2 kinase inhibitor targeting the Hippo pathway, as a novel treatment for MI. Methods: Using male C57BL/6 mice subjected to surgically induced MI, we administered Lats-IN-1 and evaluated the effects on cardiac function, infarct size, cardiomyocyte proliferation, and apoptosis through various assays and echocardiographic assessments. Results: Our results demonstrate that Lats-IN-1 significantly improves cardiac function, as evidenced by enhanced ejection fraction and reduced ventricular dimensions. Additionally, Lats-IN-1 decreased infarct size and apoptosis rates while promoting cardiomyocyte proliferation. These findings suggest that Lats-IN-1 promotes cardiac repair and regeneration. Discussion: By modulating the Hippo pathway and reducing apoptosis markers, Lats-IN-1 represents a promising therapeutic strategy for improving outcomes in heart diseases characterized by cardiomyocyte loss. This study highlights the critical role of the Hippo pathway in facilitating cardiac regeneration.

Bound phenolics extracts of jujube peel relieve cadmium-induced toxicity by reducing lipid accumulation of Caenorhabditis elegans.

To investigate the effect of bound phenolics extracts (BPEs) of jujube peel on relieving cadmium (Cd)-induced toxicity and its mechanism, the behavioral deficits, lipid accumulation, and fatty acid synthesis-related gene expression in Caenorhabditis elegans in Cd exposure group and BPEs improvement groups were determined and compared. The results showed that BPEs significantly improved Cd-induced behavioral deficits in C. elegans, and no significant differences could be found in low-dose (12.5 µg/mL) and high-dose (100 µg/mL) BPEs improvement groups. The treatment of BPEs effectively improved intestinal injury and lipofuscin and lipid accumulation. Especially, oil red O staining intensity in C. elegans treated with BPEs at 50 µg/mL was reduced by 12.60%. BPEs significantly controlled the increase in content of C16:0, C16:1, C18:0, C18:1, and C18:2 induced by Cd by regulating the lipid accumulation in Escherichia coli OP50. Cd exposure induced lipid accumulation in C. elegans by upregulating oleic acid synthesis-related gene expression in E. coli OP50. Furthermore, BPEs treatment significantly downregulated the fatty acid synthesis-related gene expression in C. elegans and E. coli OP50. This research could reveal the mechanism of BPEs of jujube peel in relieving Cd-induced toxicity and provide a theoretical basis for the development of functional foods rich in polyphenols. PRACTICAL APPLICATION: Jujube peel, a by-product of jujube processing, is usually discarded due to its coarse texture. However, jujube peel has been proven to possess abundant polyphenols, polysaccharides, and cyclic adenosine phosphate. In addition, in our previous research, bound phenolics extracts (BPEs) of jujube peel were found to perform better in lowering lipid accumulation than that of free phenolics extracts. This study further investigate the effect of BPEs of jujube peel on relieving Cd-induced toxicity and its mechanism on the base of our previous research. It could realize the comprehensive utilization of by-products of jujube processing.

Extremely efficient catalytic ozonation of ammonia N to N2 using Co/Mg(OH)2 as catalysts.

The development of highly efficient and selective ozonation catalysts is crucial for enhancing the treatment of nitrogen-containing wastewater. In this study, a Co/Mg(OH)2 nano-hexagonal sheets ozonation catalyst was prepared by one-pot hydrothermal method, and the structural characteristics of this catalyst were comprehensively analyzed. The OSur/O ratio of this catalyst was 41.06 %. Under the optimal conditions (22 â„ƒ, initial pH of 9.0, ozone dosage of 1.2 mg/L, catalyst dosage of 1.0 g/L, initial NH3-N concentration of 10.00 mg/L), NH3-N and total nitrogen (TN) removal efficiencies of 90.26 % and 63.44 % were respectively obtained, and the removal process exhibited pseudo-first-order kinetics. Moreover, at 4 â„ƒ, the NH3-N and TN removal efficiencies reached 95.49 ± 1.14 % and 65.61 ± 1.13 %. In a co-degradation process for the removal of both N and C, the ammonia and most organic compounds competed for active substances, but both pollutants were effectively removed. Hydroxyl radicals (•OH) were the main active substance involved in NH3 removal. However, the massive loss of Mg2+ experienced after three cycles reduced the NH3-N and TN removal efficiencies to 31.83 % and 6.55 %, respectively. Finally, the electron transfer generated by the variable-valence Co ion was determined to promote the selectivity of the reaction toward gaseous N products. These findings offer promising avenues for the development of more energy-efficient and effective nitrogen removal processes.

Efficacy and safety of esketamine hydrochloride adjunct to sufentanil in non-surgical patients under mechanical ventilation in the ICU (SENSATION trial): protocol for a multicentre, single-blind, randomised controlled trial.

INTRODUCTION: Pain is common in patients receiving mechanical ventilation in the intensive care unit (ICU). Intravenous opioids are recommended as first-line therapy for pain management; however, opioids have adverse side effects. Based on low-quality evidence, low-dose ketamine is therefore recommended as an opioid adjunct to reduce opioid consumption. Esketamine is an alternative to ketamine with greater efficacy and fewer side effects. However, evidence on the use of esketamine in patients receiving mechanical ventilation is lacking. This study investigates the efficacy and safety of esketamine as an adjunct to sufentanil for analgesic therapy in non-surgical ICU patients under mechanical ventilation. METHODS AND ANALYSIS: This ongoing multicentre, single-blind, randomised controlled trial is being conducted at six ICUs in China. 132 non-surgical patients under mechanical ventilation will be randomly assigned to the standard care and S-ketamine groups at a 1:1 ratio. Patients in the standard care group received a minimal dose of sufentanil as the sole analgesic agent. Patients in the S-ketamine group received a minimal dose of sufentanil in addition to an esketamine infusion at a fixed rate of 0.2 mg/kg/hour for analgesia. The primary outcome is mean hourly sufentanil consumption during the treatment period. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Chongqing University Cancer Hospital (CZLS2022067-A). Participants are required to provide informed consent. The results of this trial will be reported in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200058933.

Key role of NH4+-N in the removal of oxacillin during managed aquifer recharge: Reconsidering the recharge limitation.

Frequent occurrence of trace antibiotics in reclaimed water is concerning, which inevitably causes aquifer contamination in the case of managed aquifer recharge (MAR). Global governments have formulated strict reclaimed water standards to ensure the safety of water reuse. Recent studies have found that improved antibiotics removal is intimately associated with high ammonia-oxidizing activity. However, the role of NH4+-N in the removal of residual antibiotics of reclaimed water during MAR remains unknown. NH4+-N removal and the effects of ammonia oxidation on antibiotics biodegradation in the aquifer are the most significant facts for solving the above collision. In this work, the effects of NH4+-N (0, 1 and 5 mg/L) in a model refractory antibiotic (oxacillin (OXA), 100 µg/L) attenuation were deciphered by employing three individual simulated MAR columns, which so called N0, N1 and N5. The results showed that 5 mg/L NH4+-N in influent upregulated the abundance of amo genes by 28.9 %-68.0 % in N5. And the enriched functional genes encoding key degradation enzymes enhanced the OXA removal by 18.7 % and alleviated the oxidative stress caused by antibiotics. Subsequently, antibiotic resistance genes (ARGs), mobile gene elements (MGEs) and human bacterial pathogens (HBPs) abundance were all significantly decreased. Moreover, the intimate association between ammonia-oxidizing microorganisms (AOM) and candidate OXA degraders based on microbial network analysis further supported the significance of AOM on OXA biodegradation. This study provides comprehensive evidence that appropriate amounts of NH4+-N are beneficial in antibiotics and antibiotic resistance risk reduction, providing compelling insights for refine NH4+-N recharge limitation.

Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux.

Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.

Multi-omics analysis reveals the mechanisms by which C6-HSL enhances the resistance of typical functional bacteria in activated sludge to low-temperature stress.

Signaling molecules, particularly acyl-homoserine lactones (AHLs), can enhance microbial activity under low-temperature stress. However, the specific mechanisms underlying this effect remain unclear. This study identified a typical activated sludge functional bacterium that is sensitive to low temperatures and regulated by hexanoyl-L-homoserine lactone (C6-HSL), a representative of AHLs. It elucidates how C6-HSL modulates the bacterium's resistance to low-temperature stress. Experimental results indicated that C6-HSL significantly increased the levels of adenosine triphosphate (ATP), superoxide dismutase (SOD), peroxidase (POD) and glutathione peroxidase (GSH-Px) in strain LB-001 under low-temperature stress, while also decreasing the levels of reactive oxygen species (ROS). Additionally, C6-HSL markedly repaired the damage to cell membrane structure caused by low-temperature stress. At the genetic level, C6-HSL upregulated the expression of 20 key genes related to energy metabolism, antioxidation, and fatty acid synthesis. At the metabolic level, C6-HSL increased the levels of metabolites related to energy metabolism and antioxidation, boosted the content of unsaturated fatty acids, and reduced the content of saturated fatty acids. This study utilized C6-HSL and low-temperature induction in conjunction with 16S microbial diversity sequencing, genomics, transcriptomics, and metabolomics. These methods were employed to elucidate the molecular mechanisms by which exogenous C6-HSL regulates the resistance of activated sludge microbial communities to low-temperature stress. This research lays the foundation for the application of AHLs and cell communication in wastewater biological treatment, fostering deeper exploration and further innovation in related academic research.

Effects of Fermentation with Kombucha Symbiotic Culture of Bacteria and Yeasts on Antioxidant Activities, Bioactive Compounds and Sensory Indicators of Rhodiola rosea and Salvia miltiorrhiza Beverages.

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

A Chromosome-level genome assembly of giant river prawn (Macrobrachium rosenbergii).

The giant river prawn (Macrobrachium rosenbergii) is one of the most widely cultured crustacean species. In recent years, its aquaculture has faced challenges, including the degradation of germplasm resources and the emergence of viral diseases. Genomic information can be a valuable resource for developing molecular breeding programs for this important aquaculture species. Here we constructed a high-quality reference genome for M. rosenbergii by integrating Nanopore, Illumina, and high-throughput chromosome conformation capture (Hi-C) technologies. The final genome assembly is 3.18 Gb in size, with scaffold N50 and contig N50 of 62.73 Mb and 8.92 Mb, respectively. Approximately 98.6% of the assembled sequences were anchored into 59 pseudo-chromosomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of the genome assembly reached 94.5%. Repetitive sequences comprise 43.77% of the assembled genome, and 17,436 protein-coding genes were annotated. The high-quality genome of M. rosenbergii will empower molecular breeding efforts and provide invaluable resources for comparative genomic analysis of decapod species.

Trapped in Endosome PEGylated Ultra-Small Iron Oxide Nanoparticles Enable Extraordinarily High MR Imaging Contrast for Hepatocellular Carcinomas.

The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist-enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors <2 cm. Therefore, developing advanced MRI contrast agents is imperative for improving the diagnostic accuracy of HCCs in very-early-stage. To address this challenge, PEGylated ultra-small iron oxide nanoparticles (PUSIONPs) are synthesized and employed as liver-specific T1 MRI contrast agents. Intravenous delivery produces simultaneous hyperintense HCC and hypointense hepatic parenchyma signals on T1 imaging, creating an extraordinarily high tumor-to-liver contrast. Systematic studies uncover PUSIONP distribution in hepatic parenchyma, HCC lesions at the organ, tissue, cellular, and subcellular levels, revealing endosomal confinement of PUSIONP without aggregation. By mimicking such situations, the dependency of relaxometric properties on local PUSIONP concentration is investigated, emphasizing the key role of different endosomal concentrations in liver and tumor cells for high tumor-to-liver contrast and clear tumor boundaries. These findings offer exceptional imaging capabilities for early HCC diagnosis, potentially benefiting real HCC patients.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

In-situ rapid cultivation of aerobic granular sludge in A/O bioreactor by using Ca(ClO)2 pretreating sludge.

The efficient utilization of residual sludge and the rapid cultivation of aerobic granular sludge in continuous-flow engineering applications present significant challenges. In this study, aerobic granular cultivation was fostered in a continuous-flow system using Ca(ClO)2-sludge carbon (Ca-SC). Ca-SC retained the original sludge properties, contributing to granular growth in an A/O bioreactor. By day 40, the granule diameters increased to 0.8 mm with the SVI30 decreased by 2.7 times. Moreover, Ca-SC facilitated protein secretion, reaching 98.06 mg/g VSS and enhanced the hydrophobicity to 68.4 %. The continuous-flow aerobic granular sludge exhibited a nutrient removal rate above 90 %. Furthermore, Tessaracoccus and Nitrospira were enriched to promote granular formation and nitrogen removal. The residual sludge was carbonized and reused in the traditional wastewater treatment process to culture granular sludge in situ, aiming to achieve "self-production and self-consumption" of sludge and promote the innovative model of "treating waste with waste" in urban sewage environmental restoration.

[Determination of the derivatization reactivity between α/ß-dicarbonyl compounds and standard citrullinated peptides based on matrix-assisted laser desorption ionization-time-of-flight mass spectrometry].

Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two ß-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the ß-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the ß-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.

Carnosic acid: an effective phenolic diterpenoid for prevention and management of cancers via targeting multiple signaling pathways.

Cancer is a serious global public health issue, and a great deal of research has been made to treat cancer. Of these, discovery of promising compounds that effectively fight cancer always has been the main point of interest in pharmaceutical research. Carnosic acid (CA) is a phenolic diterpenoid compound widely present in Lamiaceae plants such as Rosemary (Rosmarinus officinalis L.). In recent years, there has been increasing evidence that CA has significant anti-cancer activity, such as leukaemia, colorectal cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, stomach cancer, lymphoma, prostate cancer, oral cancer, etc. The potential mechanisms involved by CA, including inhibiting cell proliferation, inhibiting metastasis, inducing cell apoptosis, stimulating autophagy, regulating the immune system, reducing inflammation, regulating the gut microbiota, and enhancing the effects of other anti-cancer drugs. This article reviews the biosynthesis, pharmacokinetics and metabolism, safety and toxicity, as well as the molecular mechanisms and signaling pathways of the anticancer activity of CA. This will contribute to the development of CA or CA-containing functional foods for the prevention and treatment of cancer, providing important advances in the advancement of cancer treatment strategies.

Genome assembly of redclaw crayfish (Cherax quadricarinatus) provides insights into its immune adaptation and hypoxia tolerance.

BACKGROUND: The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. RESULTS: We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. CONCLUSIONS: Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Feasibility of intimately coupled CaO-catalytic-ozonation and bio-contact oxidation reactor for heavy metal and color removal and deep mineralization of refractory organics in actual coking wastewater.

Considering the challenges for both single and traditional two-stage treatments, advanced oxidation and biodegradation, in the treatment of actual coking wastewater, an intimately coupled catalytic ozonation and biodegradation (ICOB) reactor was developed. In this study, ICOB treatment significantly enhanced the removal of Cu2+, Fe3+, and color by 39 %, 45 %, and 52 %, respectively, outperforming biodegradation. Catalytic ozonation effectively breaking down unsaturated organic substances and high-molecular-weight dissolved organic matter into smaller, more biodegradable molecules. Compared with biodegradation, the ICOB system significantly increased the abundances of Pseudomonas, Sphingopyxis, and Brevundimonas by âˆ¼ 96 %, ∼67 %, and âˆ¼ 85 %, respectively. These microorganisms, possessing genes for degrading phenol, aromatic compounds, polycyclic aromatics, and sulfur metabolism, further enhanced the mineralization of intermediates. Consequently, the ICOB system outperformed biodegradation and catalytic ozonation treatments, exhibiting chemical oxygen demand removal rate of âˆ¼ 58 % and toxicity reduction of âˆ¼ 47 %. Overall, the ICOB treatment showcases promise for practical engineering applications in coking wastewater treatment.

Liangxue Tongyu prescription attenuates neuroinflammation by increasing cholecystokinin octapeptide in acute intracerebral hemorrhage rats.

Inflammatory reactions after acute intracerebral hemorrhage (AICH) contribute significantly to a poor prognosis. Liangxue Tongyu Prescription (LTP) has been proven to be clinically effective in treating AICH. Numerous studies have shown that LTP suppresses brain inflammatory damage in AICH, while the internal mechanisms underlying its action remain unclear. The aim of this study was to verify the anti-inflammatory effects of LTP on an AICH rat model and investigate the potential mechanisms. The AICH rat models were created by injecting autologous blood into the right caudate nucleus. LTP markedly decreased cerebral hematoma and brain water content and recovered from neurological deficits. Meanwhile, LTP prevented microglial activation and reduced the inflammatory reaction caused by pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Notably, the expression of cholecystokinin octapeptide (CCK-8) in the brain and intestine was increased by LTP or CCK-8 treatment. LTP further suppressed nuclear factor kappa B (NF-κB) in the brains of rats with AICH. Moreover, LTP increased the protein and mRNA expression of Occludin and Claudin-1 in the intestine and decreased the levels of lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum. Furthermore, the results showed that LTP increased the protein and mRNA expression of Claudin-5 and zonula occludens-1 (ZO-1) in the brain. CCK-8 receptor antagonists increased the expression of NF-κB and the concentration of pro-inflammatory cytokines. These findings suggested that LTP attenuated neuroinflammation by increasing CCK-8 in the brain and intestine, and its mechanism might be related to alterations in the gut-brain axis (GBA).