Engaging Communities in Emerging Infectious Disease Mitigation to Improve Public Health and Safety.

The COVID-19 pandemic highlighted the need for potent community-based tools to improve preparedness. We developed a community health-safety climate (HSC) measure to assess readiness to adopt health behaviors during a pandemic. We conducted a mixed-methods study incorporating qualitative methods (e.g., focus groups) to generate items for the measure and quantitative data from a February 2021 national survey to test reliability, multilevel construct, and predictive and nomologic validities. The 20-item HSC measure is unidimensional (Cronbach α = 0.87). All communities had strong health-safety climates but with significant differences between communities (F = 10.65; p<0.001), and HSC levels predicted readiness to adopt health-safety behaviors. HSC strength moderated relationships between HSC level and behavioral indicators; higher climate homogeneity demonstrated stronger correlations. The HSC measure can predict community readiness to adopt health-safety behaviors in communities to inform interventions before diseases spread, providing a valuable tool for public health authorities and policymakers during a pandemic.

1,2,4-Triazolo-quinazolinones as Effective Antifoulants: Molecular Design, Synthesis, and Biological Evaluation.

A series of 1,2,4-triazolo-quinazolinones and 1,2-benzisothiazolone derivatives (S1-S12) were successfully synthesized as environmentally friendly alternatives to copper-based antifouling paints using N-alkylation, cyclocondensation, and one-pot three-component and amide coupling reactions. The monoclinic structure of single-crystal 1,2,4-triazolo-quinazolin-acetic acid (S8) was confirmed by single-crystal X-ray diffraction analysis. All the synthesized molecules were studied for their in silico molecular docking interactions with three target proteins, namely, RbmA, ToxR, and Bap. Following that, the antialgal activity was assessed against two types of marine algae: Chlorella sp. and Chaetoceros curvisetus. The minimal inhibitory concentration and zone of inhibition have been used to evaluate the antibacterial activities of S1-S12 against both marine Gram-positive (Staphylococcus aureus) and Gram-negative (Vibrio parahemolyticus and Vibrio vulnificus) bacteria. Additionally, antifouling studies have been done on all the compounds, and among them, 1,2,4-triazolo-quinazolinyl-acetate (S7), 1,2,4-triazolo-quinazolinyl-acetic acid (S8), 1,2,4-triazolo-quinazolinyl-oxobutanoate (S9), benzo[d]isothiazolyl butanoate (S10), benzo[d]isothiazolyl-acetic acid (S11), and 1,2,4-triazolo-quinazolinyl-acetyl-benzo[d]isothiazolone (S12) exhibited good antialgal, antibacterial, and antifouling activities.

Circulating tumor DNA: current implementation issues and future challenges for clinical utility.

Over the past decades, liquid biopsy, especially circulating tumor DNA (ctDNA), has received tremendous attention as a noninvasive detection approach for clinical applications, including early diagnosis of cancer and relapse, real-time therapeutic efficacy monitoring, potential target selection and investigation of drug resistance mechanisms. In recent years, the application of next-generation sequencing technology combined with AI technology has significantly improved the accuracy and sensitivity of liquid biopsy, enhancing its potential in solid tumors. However, the increasing integration of such promising tests to improve therapy decision making by oncologists still has complexities and challenges. Here, we propose a conceptual framework of ctDNA technologies and clinical utilities based on bibliometrics and highlight current challenges and future directions, especially in clinical applications such as early detection, minimal residual disease detection, targeted therapy, and immunotherapy. We also discuss the necessities of developing a dynamic field of translational cancer research and rigorous clinical studies that may support therapeutic strategy decision making in the near future.

Multimorbidity and associated informal care receiving characteristics for US older adults: a latent class analysis.

BACKGROUND: Older adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes. METHODS: Data are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership. RESULTS: A four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05-1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05-2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29-3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19-0.77). CONCLUSIONS: Results highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care.

Arene Ru(II) Complexes Acted as Potential KRAS G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress.

A series of arene Ru(II) complexes, [(η6-MeC6H5)Ru(L)Cl]Cl, (L=o-ClPIP, 1; m-ClPIP, 2 and p-ClPIP, 3) (o-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; m-ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; p-ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and investigated as a potential apoptosis inducer in chemotherapy. Spectroscopy and molecular docking simulations show that 1 exhibits moderated binding affinity to KRAS G-quadruplex DNA by groove mode. Further, in vitro studies reveal that 1 displays inhibitory activity against MCF-7 growth with IC50 = 3.7 ± 0.2 µM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that 1 can induce the apoptosis of MCF-7 cells and G0/G1 phase arrest through DNA damage. In summary, the prepared arene Ru(II) complexes can be developed as a promising candidate for targeting G-quadruplex structure to induce the apoptosis of breast cancer cells via binding and stabilizing KRAS G-quadruplex conformation on oncogene promoter.

Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers.

Phenanthroimidazole derivatives containing phenanthroline and imidazole heterocyclic aromatic rings are effective agents to inhibit tumor cell growth. Herein, halogen element-modified imidazo[4,5f][1,10]phenanthroline derivatives 1-6 (1, 4-fluorophenyl; 2, 4-chlorophenyl; 3, 4-bromobenyl; 4, 2,3-dichlorophenyl; 5, 3,4-dichlorophenyl; and 6, 2,4-dichlorophenyl) were synthesized, and their antitumor activities were investigated. All of the compounds, especially 4, exhibited an excellent inhibitory effect against nasopharyngeal carcinoma CNE-1 cells. This effect was better than that of doxorubicin. Compound 4 also markedly blocked the proliferation of the CNE-1 cells in a zebrafish xenograft model. The antitumor mechanisms might be attributed to apoptosis induction, which triggered ROS-mediated DNA damage and generated mitochondrial dysfunction by stabilizing c-myc G-quadruplex DNA structure. Results indicated that phenanthroimidazole derivatives could act as promising anticancer agents.

Fretting Wear Behaviors of Silicone Rubber under Dry Friction and Different Lubrication Conditions.

The fretting wear behaviors of silicone rubber under dry friction and different lubrication conditions are studied experimentally. Water, engine oil, dimethyl silicone oil (DSO), and dimethyl silicone oil doped with graphene oxide (DSO/GO) are selected as lubricants. Under the liquid lubrication conditions, the silicone rubber samples are always immersed in the same volume of lubricant. The contact model of a 440C steel ball and silicone rubber sample is the sphere-on-flat contact. The reciprocating fretting wear experiments are carried out using the reciprocating friction wear tester. A scanning electron microscope and three-dimensional white-light interference profilometer are used to detect the surface wear morphology and obtain the wear volume, respectively. The influences of normal force, lubrication condition, and displacement amplitude on fretting wear behavior are discussed. The fretting wear performances of silicone rubber under different fretting states and lubrication conditions are compared. The results show that for a small normal force, silicone rubber has the best wear resistance under DSO/GO lubrication. While for a large normal force, silicone rubber has the best wear resistance under engine oil lubrication.

Longitudinal Care Network Changes and Associated Healthcare Utilization Among Care Recipients.

This study examines caregiver networks, including size, composition, and stability, and their associations with the likelihood of hospitalization and skilled-nursing facility (SNF) admissions. Data from the National Health and Aging Trends Study linked to Center for Medicare and Medicaid Services data were analyzed for 3855 older adults across five survey waves. Generalized estimating equation models assessed the associations. The findings indicate each additional paid caregiver was associated with higher adjusted risk ratios (aRR) for hospitalization (aRR = 1.24, 95% CI 1.10-1.41) and SNF admission (aRR = 1.28, 95% CI 1.06-1.54) among care recipients, a pattern that is also observed with the addition of unpaid caregivers (hospitalization: aRR = 1.13, 95% CI 1.06-1.20; SNF: aRR = 1.12, 95% CI 1.02-1.23). These results suggest that policies and approaches to enhance the quality and coordination of caregivers may be warranted to support improved outcomes for care recipients.

A comprehensive overview of recent advances in generative models for antibodies.

Therapeutic antibodies are an important class of biopharmaceuticals. With the rapid development of deep learning methods and the increasing amount of antibody data, antibody generative models have made great progress recently. They aim to solve the antibody space searching problems and are widely incorporated into the antibody development process. Therefore, a comprehensive introduction to the development methods in this field is imperative. Here, we collected 34 representative antibody generative models published recently and all generative models can be divided into three categories: sequence-generating models, structure-generating models, and hybrid models, based on their principles and algorithms. We further studied their performance and contributions to antibody sequence prediction, structure optimization, and affinity enhancement. Our manuscript will provide a comprehensive overview of the status of antibody generative models and also offer guidance for selecting different approaches.

Green One-Pot Synthesis of Thiazole Scaffolds Catalyzed by Reusable NiFe2O4 Nanoparticles: In Silico Binding Affinity and In Vitro Anticancer Activity Studies.

A facile, green, one-pot multicomponent synthesis strategy was employed to fabricate novel thiazole scaffolds incorporating phthalazine, pyridazine, and pyrido-pyridazine derivatives (4a-4o). This synthetic route entailed the reaction of an α-halo carbonyl compound (1) with thiosemicarbazide (2) and various anhydrides (3a-3o), utilizing NiFe2O4 nanoparticles as a reusable catalyst in an ethanol:water (1:1) solvent system. The cytotoxicity of the synthesized compounds was meticulously assessed against three cancer cell lines, A375, HeLa, and MCF-7, employing IC50 values (µM) as the benchmark, and compared to the reference drug erlotinib. Compound 4n displayed remarkable efficacy against A375 (0.87 ± 0.31 µM), HeLa (1.38 ± 1.24 µM), and MCF-7 (1.13 ± 0.96 µM) cell lines, significantly surpassing erlotinib's IC50 values. Additionally, compounds 4k, 4l, 4m, and 4o demonstrated notable cytotoxicity across all tested cell lines, indicating their potential as effective anticancer agents. In silico docking studies against Hsp82 and Hsp90 proteins indicated that ligands 4k, 4m, 4c, 4j, 4o, and 4l had superior binding affinities compared to erlotinib. ADME analysis showed that compounds 4n, 4j, 4l, 4m, and 4o had favorable pharmacokinetic profiles, including nontoxicity, high human intestinal absorption, and low CYP inhibitory promiscuity. Structure-activity relationship analysis revealed that cyano and benzylidene substitutions significantly enhanced anticancer activity. Overall, the synthesized compounds, particularly 4n, demonstrated high efficacy, favorable binding interactions, and promising pharmacokinetic profiles, making them strong candidates for further development as anticancer agents.

Mental-somatic multimorbidity in trajectories of cognitive function for middle-aged and older adults.

INTRODUCTION: Multimorbidity may confer higher risk for cognitive decline than any single constituent disease. This study aims to identify distinct trajectories of cognitive impairment probability among middle-aged and older adults, and to assess the effect of changes in mental-somatic multimorbidity on these distinct trajectories. METHODS: Data from the Health and Retirement Study (1998-2016) were employed to estimate group-based trajectory models identifying distinct trajectories of cognitive impairment probability. Four time-varying mental-somatic multimorbidity combinations (somatic, stroke, depressive, stroke and depressive) were examined for their association with observed trajectories of cognitive impairment probability with age. Multinomial logistic regression analysis was conducted to quantify the association of sociodemographic and health-related factors with trajectory group membership. RESULTS: Respondents (N = 20,070) had a mean age of 61.0 years (SD = 8.7) at baseline. Three distinct cognitive trajectories were identified using group-based trajectory modelling: (1) Low risk with late-life increase (62.6%), (2) Low initial risk with rapid increase (25.7%), and (3) High risk (11.7%). For adults following along Low risk with late-life increase, the odds of cognitive impairment for stroke and depressive multimorbidity (OR:3.92, 95%CI:2.91,5.28) were nearly two times higher than either stroke multimorbidity (OR:2.06, 95%CI:1.75,2.43) or depressive multimorbidity (OR:2.03, 95%CI:1.71,2.41). The odds of cognitive impairment for stroke and depressive multimorbidity in Low initial risk with rapid increase or High risk (OR:4.31, 95%CI:3.50,5.31; OR:3.43, 95%CI:2.07,5.66, respectively) were moderately higher than stroke multimorbidity (OR:2.71, 95%CI:2.35, 3.13; OR: 3.23, 95%CI:2.16, 4.81, respectively). In the multinomial logistic regression model, non-Hispanic Black and Hispanic respondents had higher odds of being in Low initial risk with rapid increase and High risk relative to non-Hispanic White adults. CONCLUSIONS: These findings show that depressive and stroke multimorbidity combinations have the greatest association with rapid cognitive declines and their prevention may postpone these declines, especially in socially disadvantaged and minoritized groups.

In vitro interaction of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen in the asexual blood stage of Plasmodium falciparum 3D7.

Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies. IMPORTANCE: Pharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone-proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone-proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.

Metagenomic analysis reveals metabolic mechanism of enhancing lignocellulosic anaerobic digestion mediated by CO2/O2-nanobubble water.

Nanobubble water (NW) has been reported to enhance anaerobic digestion (AD), but its influence on the metabolic pathways of microorganisms remains unclear. In this study, the specific methane yields of rice straw in the CO2NW and O2NW treatments increased by 6.9% and 18.3%, respectively. The electron transport system (ETS) and coenzyme F420 activities were enhanced by the addition of NW. Metagenomic analysis showed that the abundances of most enzymes in the acidification were significantly increased by both CO2NW and O2NW. Regarding methanogenesis, CO2NW promoted the expression of genes encoding enzymes of hydrogenotrophic methanogenesis, while O2NW stimulated both the acetoclastic and hydrogenotrophic methanogenesis. With the addition of O2NW, the expressions of modules related to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation were enhanced, resulting in increased ATP production. This study provided fundamental evidence of the metabolic pathways of microorganisms mediated by NW at each stage of AD.

Immune checkpoint inhibitors rechallenge in non-small cell lung cancer: Current evidence and future directions.

Immunotherapy, remarkably immune checkpoint inhibitors (ICIs), has significantly altered the treatment landscape for non-small cell lung cancer (NSCLC). Despite their success, the discontinuation of ICIs therapy may occur due to factors such as prior treatment completion, disease progression during ICIs treatment, or immune-related adverse events (irAEs). As numerous studies highlight the dynamic nature of immune responses and the sustained benefits of ICIs, ICIs rechallenge has become an attractive and feasible option. However, the decision-making process for ICIs rechallenge in clinical settings is complicated by numerous uncertainties. This review systematically analyses existing clinical research evidence, classifying ICIs rechallenge into distinct clinical scenarios, exploring methods to overcome ICIs resistance in rechallenge instances, and identifying biomarkers to select patients likely to benefit from rechallenge. By integrating recent studies and new technologies, we offer crucial recommendations for future clinical trial design and provide a practical guideline to maximize the therapeutic benefits of immunotherapy for NSCLC patients.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

Impacts of Caregiving on Health of New Spousal Caregivers to Older Adults in the United States: A Coarsened Exact Matching Analysis.

OBJECTIVES: Spousal caregivers of older adults, especially new spousal caregivers, face increased risks of negative health outcomes due to the demands of caregiving and their own health decline. Estimating the impacts of caregiving on health without controlling for caregivers' own aging-related health decline could exaggerate the negative health consequences of caregiving, while focusing solely on caregivers could result in selection bias where healthier individuals enter and/or remain in caregiving. This study aims to estimate the impacts of caregiving on health of new spousal caregivers while controlling for observable confounders. METHODS: We utilized coarsened exact matching analysis to compare health outcomes between new spousal caregivers and spousal noncaregivers using pooled panel data from 2006 to 2018 in the Health and Retirement Study. We analyzed 242,123 person-wave observations from 42,180 unique individuals, among whom 3,927 were new spousal caregivers. Variables used for matching were classified into 3 categories: care needs, willingness to provide care, and ability to provide care. Two-year outcomes assessed are spouse's self-rated health, depressive symptoms, and cognitive functioning. RESULTS: A total of 3,417 (87.01%) new spousal caregivers were matched with 129,798 observations of spousal noncaregivers. Regression analysis indicated being a new spousal caregiver was associated with a 0.18- (standard error = 0.05) unit increase in number of depressive symptoms. No statistically significant results were identified for self-rated health and cognitive functioning. DISCUSSION: Our results highlighted the needs to address mental health among new spousal caregivers and emphasized the importance of addressing mental health in long-term care programs and policies.

The transformations of cellulose after concentrated sulfuric acid treatment and its impact on the enzymatic saccharification.

BACKGROUND: The dense structure of cellulose lowers its reactivity and hinders its applications. Concentrated sulfuric acid is an ideal solvent to dissolve cellulose and thus has been used widely to treat cellulose. However, the changes of cellulose after reaction with concentrated sulfuric acid at near-limit S/L ratio and its effect on enzymatic saccharification still need further investigation. RESULTS: In this study, the interactions between cellulose (Avicel) and 72% sulfuric acid at very low acid loading conditions of 1:2 to 1:3 (S/L ratio) were studied for the enhanced production of glucose. The Avicel gradually transformed from cellulose I structure to cellulose II structure during the sulfuric acid treatment. Other physicochemical characteristics of Avicel also changed dramatically, such as the degree of polymerization, particle size, crystallinity index, and surface morphology. After acid treatment, both the yield and productivity of glucose from cellulose increased significantly under a very low enzyme loading of 5 FPU/g-cellulose. The glucose yields for raw cellulose and acid-treated (30 min) were 57% and 85%, respectively. CONCLUSION: Low loadings of concentrated sulfuric acid were proven to be effective to break the recalcitrance of cellulose for enzymatic saccharification. A positive correlation between cellulose CrI and glucose yield was found for concentrated sulfuric acid-treated cellulose, which was opposite to previous reports. Cellulose II content was found to be an important factor that affects the conversion of cellulose to glucose.

Caregiving Burden Among Caregivers of People With Dementia Through the Lens of Intersectionality.

BACKGROUND AND OBJECTIVES: Caregivers may be at different risks of various types of burdens by virtue of their gender and racial/ethnic status. This article explores the differences in caregiving burdens across the intersectionality of race and gender. RESEARCH DESIGN AND METHODS: Using Round 5 (conducted in 2015) and Round 7 (conducted in 2017) of National Study of Caregiving and National Health and Aging Trends Study data, the study examined differences in caregiver burdens across and within different gender and racial/ethnic groups, within the realms of financial, emotional, and physical burdens. The sample consisted of 1,206 caregivers who provided services to Medicare beneficiaries. Logistic regressions were performed to assess the 3 types of burdens each subgroup was experiencing. RESULTS: Results indicated that within the intersectionality framework, compared to White female caregivers, Black male caregivers were 3.3 times (95% confidence interval [CI] 1.77-6.22) more likely to experience financial burden, and Black female caregivers were 54% less likely to experience physical burden. Surprisingly, compared to White female caregivers, all the other groups were 37% (95% CI 0.41-0.95) to 71% (95% CI 0.15-0.56) less likely to have emotional burden. DISCUSSION AND IMPLICATIONS: The findings highlighted that Black male caregivers are experiencing financial burden and White female caregivers are experiencing emotional burden disproportionately. To develop effective interventions and programs for dementia caregivers, a special focus should be put on monitoring the differences in the types of burdens that the above-mentioned population subgroups experience.

Acute and subacute oral toxicity assessment of Gancao Xiexin decoction in Sprague-Dawley rats.

Gancao Xiexin decoction (GCXXD), a well-known classic traditional Chinese medicine prescription, is used to treat various oral ulcers, Behcet disease, gastrointestinal ulcers, etc. However, there is very little information on its safety. This study aimed to investigate the acute and subacute oral toxicity of GCXXD in Sprague-Dawley rats. In the acute toxicity study, rats were orally administered 10 g/kg GCXXD three times a day. Clinical signs of abnormality and mortality were observed daily for 14 days. In the subacute toxicity study, rats were orally administered 0, 1.47, 3.83, or 10 g/kg GCXXD for 28 days. The rats' clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and pathological morphology were analyzed. The acute toxicity study showed that GCXXD is safe in rats without any obvious toxicity via an oral dose of 30 g/kg/day (3 × 10 g/kg). After 28 days of administration, slightly decreased RBC, HGB, and HCT were observed in female rats at 10 g/kg, suggesting that repeated doses of high-dose GCXXD may cause mild anemia in female rats. The no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of oral administration of GCXXD for 28 days in rats are considered to be 3.83 g/kg and 10 g/kg, respectively. Long-term toxicity studies are recommended to strengthen the findings.

Microwave-assisted synthesis of ruthenium(ii) complexes containing levofloxacin-induced G2/M phase arrest by triggering DNA damage.

Ru(ii) complexes have attracted increasing attention as promising antitumor agents for their relatively low toxicity, high affinity to DNA molecules, and correlation with multiple targets. Meanwhile, quinolones are synthetic antibacterial agents widely used in the clinical practice. In this paper, two novel Ru(ii) complexes coordinated by levofloxacin (LOFLX), [Ru(bpy)2(LOFLX)]·2ClO4 (1), and [Ru(dmbpy)2(LOFLX)]·2ClO4 (2) (bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine) were synthesized with high efficiency under microwave irradiation and characterized by ESI-MS, 1H NMR, and 13C NMR. The binding behavior of these complexes with double-strand calf thymus DNA(CT-DNA) was investigated using spectroscopy, molecular docking, and density functional theory calculations. Results showed that 2 exhibited higher binding affinity than 1 and LOFLX. Further studies showed that 2 could induce the G2/M phase arrest of A549 cells via DNA damage. In summary, these results indicated that 2 could be developed as a potential anticancer agent in treatment of lung cancer through the induction of cell cycle arrest at G2/M phase by triggering DNA damage.