Efficacy and safety of Yangxinshi tablet for chronic heart failure: A systematic review and meta-analysis.

BACKGROUND: The specific benefits of Yangxinshi tablet (YXST) in the treating chronic heart failure (CHF) remain uncertain. AIM: To systematically evaluate the efficacy and safety of YXST in the treatment of CHF. METHODS: Randomized controlled trials (RCTs) investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023. Meta-analyses of the included clinical studies were conducted using Review Manager 5.3. RESULTS: Twenty RCTs and 1845 patients were included. The meta-analysis results showed that the YXST combination group, compared to the conventional drug group, significantly increased the clinical efficacy rate by 23% [relative risk (RR) = 1.23, 95%CI: 1.17-1.29], P < 0.00001), left ventricular ejection fraction by 6.69% [mean difference (MD) = 6.69, 95%CI: 4.42-8.95, P < 0.00001] and 6-min walk test by 49.82 m (MD = 49.82, 95%C: 38.84-60.80, P < 0.00001), and reduced N-terminal pro-B-type natriuretic peptide by 1.03 ng/L [standardized MD (SMD) = -1.03, 95%CI: -1.32 to -0.74, P < 0.00001], brain natriuretic peptide by 80.95 ng/L (MD = -80.95, 95%CI: -143.31 to -18.59, P = 0.01), left ventricular end-diastolic diameter by 3.92 mm (MD = -3.92, 95%CI: -5.06 to -2.78, P < 0.00001), and left ventricular end-systolic diameter by 4.34 mm (MD = -4.34, 95%CI: -6.22 to -2.47, P < 0.00001). Regarding safety, neither group reported any serious adverse events during treatment (RR = 0.54, 95%CI: 0.15-1.90, P = 0.33). In addition, Egger's test results indicated no significant publication bias (P = 0.557). CONCLUSION: YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile, suggesting its potential as a therapeutic strategy for CHF.

N-octylpyridine hydrogen sulphate ionic liquid for multifunctional fluorescent response in different solvents.

Ionic liquids (ILs) have attracted considerable interest in the last two decades owing to their unique fluorescent properties. Herein, N-octylpyridine hydrogen sulphate ([OP]HSO4) was synthesised and characterised using 1H NMR and infrared spectroscopies. In addition, the fluorescence spectra of [OP]HSO4 in water, methanol, ethanol and acetonitrile were studied. In a single solvent, as the concentration of the solvent (methanol, ethanol or acetonitrile) increases, the fluorescence intensity of the IL first increases and then decreases. A similar trend was observed in their mixed solvents with water. Moreover, the fluorescence intensity of [OP]HSO4 decreases with increasing temperature. A fluorescence intensity reduction of only 4.46% for [OP]HSO4 after continuous scanning for 40 cycles under the maximum excitation state was analysed. The lack of photobleaching observed in [OP]HSO4 indicates its good photobleaching resistance.

Great genetic diversity of vector-borne bacteria and protozoan in wild rodents from Guangxi, China.

BACKGROUND: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. METHODS: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. RESULTS: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. CONCLUSIONS: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.

T7 peptide-mediated co-delivery platform overcoming multidrug-resistant breast cancer: In vitro and in vivo evaluation.

P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.

Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis.

INTRODUCTION: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database. METHODS: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database. RESULTS: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation. CONCLUSION: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months. REGISTRATION: PROSPERO (CRD42022385274).

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.

USP15 promotes the progression of papillary thyroid cancer by regulating HMGB1 stability through its deubiquitination.

Purpose: Papillary thyroid cancer (PTC) stands as one of the most prevalent types of thyroid cancers, characterized by a propensity for in-situ recurrence and distant metastasis. The high mobility group protein (HMGB1), a conserved nuclear protein, plays a pivotal role in carcinogenesis by stimulating tumor cell growth and migration. Nevertheless, the underlying mechanism driving aberrant HMGB1 expression in PTC necessitates further elucidation. Materials and methods: Our study unraveled the impact of low and overexpression of USP15 on the proliferation, invasion, and metastasis of PTC cells. Through a comprehensive array of molecular techniques, we uncovered the intricate relationship between HMGB1 and USP15 in the progression of PTC. Results: In this study, we identified USP15, a deubiquitinase in the ubiquitin-specific proteases family, as a true deubiquitylase of HMGB1 in PTC. USP15 was shown to interact with HMGB1 in a deubiquitination activity-dependent manner, deubiquitinating and stabilizing HMGB1. USP15 depletion significantly decreased PTC cell proliferation, migration, and invasion. In addition, the effects induced by USP15 depletion could be rescued by further HMGB1 overexpression. But when HMGB1 is knocked down, even overexpression of USP15 could not promote the progression of PTC cells. Conclusion: In essence, our discoveries shed light on the previously uncharted catalytic role of USP15 as a deubiquitinating enzyme targeting HMGB1, offering a promising avenue for potential therapeutic interventions in the management of PTC.

Assisted reproductive technologies and postpartum depressive symptoms: A meta-analysis.

BACKGROUND: Assisted reproductive technologies (ARTs) have become the main treatment for infertility. ART treatment can be a stressful life event for infertile females. Whether there is an association between ARTs and postpartum depressive symptoms (PDS) has not been established. METHODS: PubMed, MEDLINE, EMBASE, PsycINFO, and CNKI were searched. The pooled outcome was the difference in incidence of PDS within 1 year postpartum between ARTs and the spontaneous pregnancy group. RESULTS: A total of 12 cohort studies, which were conducted in eight developed countries and two developing countries, were involved. In total, 106,338 pregnant women, including 4990 infertile females with ARTs treatment and 101,348 women with spontaneous pregnancy, were enrolled in our final analysis. ARTs women had a lower incidence of PDS compared to the spontaneous pregnancy group according to a random effect model (OR = 0.83, 95 % CI: 0.71-0.97, p = 0.022, I2 = 62.0 %). Subgroup analyses indicated that studies on late PDS (follow-up: 3-12 months postpartum) were more heterogeneous than those on early PDS (follow-up: <3 months postpartum) (I2 = 24.3 % vs. I2 = 0 %, interaction p-value < 0.001). There was a strong relationship between ARTs and late PDS (OR = 0.65, 95 % CI: 0.55-0.77, p < 0.001). Therefore, the possible source of heterogeneity was the postpartum evaluation time, which was confirmed by post-hoc meta-regression. LIMITATIONS: Some underlying confounders, such as previous psychiatric illness, the limited availability of ARTs, and ethnic disparities, cannot be ignored and may have biased interpretation of the results. CONCLUSION: The available data suggested that ARTs were associated with lower incidence of PDS, especially when follow-up lasted over 3 months. However, these findings should be interpreted with caution. Better-designed trials are needed to confirm this association.

Benchmarking online food delivery applications against menu labelling laws: a cross-sectional observational analysis.

OBJECTIVE: It is unknown how well menu labelling schemes that enforce the display of kilojoule (kJ) labelling at point-of-sale have been implemented on online food delivery (OFD) services in Australia. This study aimed to examine the prevalence of kJ labelling on the online menus of large food outlets with more than twenty locations in the state or fifty locations nationally. A secondary aim was to evaluate the nutritional quality of menu items on OFD from mid-sized outlets that have fewer locations than what is specified in the current scheme. DESIGN: Cross-sectional analysis. Prevalence of kJ labelling by large food outlets on OFD from August to September 2022 was examined. Proportion of discretionary ('junk food') items on menus from mid-sized outlets was assessed. SETTING: Forty-three unique large food outlets on company (e.g. MyMacca's) and third party OFD (Uber Eats, Menulog, Deliveroo) within Sydney, Australia. Ninety-two mid-sized food outlets were analysed. PARTICIPANTS: N/A. RESULTS: On company OFD apps, 35 % (7/23) had complete kJ labelling for each menu item. In comparison, only 4·8 % (2/42), 5·3 % (2/38) and 3·6 % (1/28) of large outlets on Uber Eats, Menulog and Deliveroo had complete kJ labelling at all locations, respectively. Over three-quarters, 76·3 % (345/452) of menu items from mid-sized outlets were classified as discretionary. CONCLUSIONS: Kilojoule labelling was absent or incomplete on a high proportion of online menus. Mid-sized outlets have abundant discretionary choices and yet escape criteria for mandatory menu labelling laws. Our findings show the need to further monitor the implementation of nutrition policies on OFD.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Anaplasma, Bartonella, and Rickettsia infections in Daurian ground squirrels (Spermophilus dauricus), Hebei, China.

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites.

Identification of Hedyotis diffusa Willd-specific mRNA-miRNA-lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification.

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

Genetic diversity of vector-borne zoonotic pathogens in companion dogs and cats, Tianjin, China.

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

Identification of a Clinical Spirometra mansoni Plerocercoid Isolate Using Molecular and Morphological Data.

Sparganosis has been a neglected parasitic zoonosis for a long time. The accurate identification of Spirometra tapeworms in clinical practice is poorly understood. A case of breast sparganosis was reported in Henan Province of central China. One plerocercoid approximately 3.5 cm in length was collected from the patient. The clinical isolate was identified as Spirometra mansoni based on the barcoding sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1). Finally, the epidemiology of sparganosis in central China was reviewed. Comprehensive public health education should be carried out, and the risky habit of eating live tadpoles must be discouraged in Henan Province.

Design, synthesis and biological evaluation of rhein-piperazine-furanone hybrids as potential anticancer agents.

Novel rhein-piperazine-furanone hybrids, 5, were designed and synthesized efficiently from rhein. Cytotoxicity of all hybrids 5a-j against A549 human lung cancer cells was superior to the parent rhein and the reference cytarabine (CAR). Hybrid 5e (IC50 = 5.74 µM), the most potent compound, was 46- and 35-fold more toxic against A549 cells than rhein (IC50 = 265.59 µM) and CAR (IC50 = 202.57 µM), respectively. Moreover, hybrid 5e (IC50 = 69.28 µM) was less toxic to normal WI-38 human lung fibroblast cells with good selectivity (WI-38/A549, SI ≈ 12), being much higher than rhein (SI ≈ 1) and CAR (SI ≈ 2). Structure-activity relationship (SAR) analysis showed that cytotoxicity and selectivity against A549 lung cancer cells were greatly enhanced when methoxy-containing furanone was introduced to the hybrids (5e and 5h). Further, hybrid 5e showed better cytotoxicity against four types of human lung cancer cells (H460, A549, PC-9, and Calu-1; IC50 = 4.35-15.39 µM) than six other types of human cancer cells (SK-BR-3, SK-OV-3, 786-O, Huh-7, HCT116, and HeLa; IC50 = 13.77-60.45 µM), showing specificity. In particular, hybrid 5e showed the highest cytotoxicity (IC50 = 4.35 µM) and the highest selectivity (WI-38/H460, SI ≈ 16) against H460 human lung cancer cells. Flow cytometric analysis showed that hybrid 5e induced apoptosis in a concentration-dependent manner in H460 cells. The results show that the cytotoxicity and selectivity of rhein can be greatly enhanced by hybridization with furanone. Hybrid 5e is expected to be a leading candidate for anti-lung cancer drugs.

Insomnia and creativity in Chinese adolescents: mediation through need for cognition.

BACKGROUND: Creativity is an essential cognitive ability that plays a crucial role in advanced thinking. While previous research has demonstrated the impact of insomnia on cognitive function, its effects on creativity in Chinese adolescents remain unclear. This study explored the relationship between insomnia (specifically, daytime and nighttime disturbances) and creativity in adolescents. Additionally, it examined the potential mediating effect of the need for cognition on this relationship. METHODS: Questionnaires were administered to 302 adolescents to measure their creativity, need for cognition, and insomnia levels using the Williams Creative Tendencies Scale, Need for Cognition Scale, and Bergen Insomnia Scale, respectively. Regression analysis was conducted to examine the direct impact of insomnia on creativity. Furthermore, a mediation model was constructed to investigate the role of the need for cognition in mediating the relationship between insomnia and creativity. RESULTS: The findings of the present study indicated that insomnia had a direct impact on the creativity of adolescents, demonstrating a time-of-day effect. Daytime disturbances were found to have a positive correlation with overall creativity and imagination, whereas no significant direct effect was found between nighttime disturbances and creativity. Further analysis revealed that insomnia, specifically daytime disturbances, might influence creativity by affecting the individual's need for cognition. However, no similar indirect effects were observed for the relationship between nighttime disturbances and creativity. CONCLUSIONS: Our findings indicate that adolescents might experience improved creativity as a result of daytime disruptions, and the level of need for cognition could play a crucial role in understanding the link between insomnia and creativity in adolescents.

Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.