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A new 14-membered resorcylic acid lactone (RAL14), chaetolactone A (1), along with three known ones (2−4), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR),13C NMR chemical shifts calculations coupled with the DP4+ probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines. [ABSTRACT FROM AUTHOR]

Simple Summary: The present research investigates the counterintuitive effects of sublethal chemotherapy doses in non-small-cell lung cancer (NSCLC), focusing on their role in enhancing cancer cell malignancy and the role of Aldo-keto reductase family 1 member B10 (AKR1B10) in this process. This study is designed to understand how sublethal doses of chemotherapy drugs like taxol and doxorubicin lead to increased cancer cell migration, invasion, metastasis, and the consequent upregulation of AKR1B10. Our findings uncover the fact that AKR1B10 plays a crucial role in NSCLC progression and chemoresistance, with its increased expression being linked to enhanced malignancy. The results are significant for the research community as they provide insight into the currently paradoxical molecular mechanisms of chemotherapy-induced resistance in lung cancer. This could lead to the potential development of more effective treatment strategies that consider the impact of chemotherapy dosing on cancer cell behavior, potentially improving patient outcomes by preventing the unintentional enhancement of cancer aggressiveness. Chemotherapy remains a cornerstone in lung cancer treatment, yet emerging evidence suggests that sublethal low doses may inadvertently enhance the malignancy. This study investigates the paradoxical effects of sublethal low-dose chemotherapy on non-small-cell lung cancer (NSCLC) cells, emphasizing the role of Aldo-keto reductase family 1 member B10 (AKR1B10). We found that sublethal doses of chemotherapy unexpectedly increased cancer cell migration approximately 2-fold and invasion approximately threefold, potentially promoting metastasis. Our analysis revealed a significant upregulation of AKR1B10 in response to taxol and doxorubicin treatment, correlating with poor survival rates in lung cancer patients. Furthermore, silencing AKR1B10 resulted in a 1–2-fold reduction in cell proliferation and a 2–3-fold reduction in colony formation and migration while increasing chemotherapy sensitivity. In contrast, the overexpression of AKR1B10 stimulated growth rate by approximately 2-fold via ERK pathway activation, underscoring its potential as a target for therapeutic intervention. The reversal of these effects upon the application of an ERK-specific inhibitor further validates the significance of the ERK pathway in AKR1B10-mediated chemoresistance. In conclusion, our findings significantly contribute to the understanding of chemotherapy-induced adaptations in lung cancer cells. The elevated AKR1B10 expression following sublethal chemotherapy presents a novel molecular mechanism contributing to the development of chemoresistance. It highlights the need for strategic approaches in chemotherapy administration to circumvent the inadvertent enhancement of cancer aggressiveness. This study positions AKR1B10 as a potential therapeutic target, offering a new avenue to improve lung cancer treatment outcomes by mitigating the adverse effects of sublethal chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease is an inflammatory disease of periodontal tissues that is closely connected with systemic diseases. During periodontitis, the inappropriate recruitment and activation of monocytes–macrophages causes an increase in osteoclast activity and disrupts bone homeostasis. Therefore, it is a promising therapeutic strategy to treat periodontitis by regulating the functions of monocytes–macrophages. Litcubanine A (LA) is an isoquinoline alkaloid extracted from the traditional Chinese medicine Litsea cubeba, which was proven to have reproducible anti‐inflammatory effects, but its regulatory role on bone homeostasis in periodontitis is still not clear. Methods: In this study, zebrafish experiments and a mouse ligature‐induced periodontitis model were performed, and histological analysis was used to investigate the effect of LA on macrophage chemotaxis under the inflammatory environment. Real‐time PCR was used to detect the regulatory effect of LA (100 nM ~ 100 μM) on the chemotaxis function of macrophages induced by LPS. Apoptosis assay and flow cytometry were used to elucidate the influence of LA on macrophage apoptosis and proliferation. To further clarify the regulatory role of LA on macrophage osteoclast differentiation, real‐time PCR, histological analysis, western blot, and micro‐computed tomography (micro‐CT) were performed in vivo and in vitro to verify the impact of LA on bone homeostasis. Results: Compared with the control group, the chemotaxis function of macrophage was significantly attenuated by LA in vivo. LA could significantly inhibit the expression of genes encoding the chemokine receptors Ccr1 and Cxcr4, and its ligand chemokine Cxcl12 in macrophages, and suppresses the differentiation of osteoclastic precursors to osteoclasts through the MAPK signaling pathway. There were significantly lower osteoclast differentiation and bone loss in the LA group compared with the control in the ligature‐induced periodontitis model. Conclusion: LA is a promising candidate for the treatment of periodontitis through its reproducible functions of inhibiting monocyte–macrophage chemotaxis and osteoclast differentiation. Litcubanine A can significantly prevent periodontitis by inhibiting macrophage chemotaxis and osteoclast differentiation via the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy using immune checkpoint inhibitors (ICIs) (e.g., programmed cell death protein-1 (PD-1) inhibitors) combined with molecular targeted agents has been evaluated in clinical trials and has shown potential synergic effects and superior efficacy in unresectable hepatocellular carcinoma (uHCC). The optimal regimen for uHCC of combination therapy with a PD-1 inhibitor plus an MTKI remains controversial. A head-to-head comparison is still lacking regarding combination strategies involving the administration of PD-1 inhibitors with different MTKIs in uHCC. This highly original study evaluates the efficacy and safety of PD-1 inhibitors in combination with sorafenib or lenvatinib in a cohort of patients with uHCC. We observed that PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Our data on efficacy and tolerability may enable clinicians to select optimal treatment strategies for HCC therapy. Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results. [ABSTRACT FROM AUTHOR]

A new polyketide derivative containing a 3-hydroxydecanoic acid ester moiety, penicipurate A (1), was purified from the solid cultures of the fungus Penicillium purpurogenum, a fungal strain endophytic in the leaves of Edgeworthia chrysantha. The structure of 1 was established by spectroscopic methods, including UV, IR, HRESIMS, 1D, and 2D NMR and 13C NMR chemical shifts calculations coupled with DP4+ analysis, as well as the chemical degradation method. Compound 1 showed moderate inhibitory activity against pancreatic lipase (PL) with an IC50 value of 9.61 ± 1.42 µM. [ABSTRACT FROM AUTHOR]

This study aimed to comprehensively analyze the effect of empty-nest on mental health and behaviors of the older population and explore the urban-rural differences. Data from the Cohort of Older People Health and Environment Controllable Factors were used, including 1071 older people aged 60 or over from a rural and an urban. Mental health, daily life behaviors, chronic physical diseases, and activities of daily living were evaluated. Logistic regression was used. The prevalence of empty-nest in older people was 55.0% in urban and 58.7% in rural. The empty-nest older people in urban were more likely to participate in physical exercise (OR[95%CI]: 1.55[1.03–2.31]), while the empty-nest older people in rural had lower rate of smoking (OR[95%CI]: 0.46[0.28–0.76]) and religious belief (OR[95%CI]: 1.61[1.01–2.58]), and higher prevalence of depression (OR[95%CI]: 1.55[1.03–2.35]) and higher level of total cholesterol (OR[95%CI]: 1.51[1.03–2.19]) compared with the non-empty-nest older people. In conclusion, the prevalence of empty-nest in older people was high both in rural and urban in China. Empty-nest exerts greater influences on the older people in rural than in urban, which should be given more attention, especially the depression and high total cholesterol. [ABSTRACT FROM AUTHOR]

Characterizing the mechanistic interactions between exposures and diseases is one of the most critical issues in epidemiologic studies. Previous studies have proposed a stochastic sufficient component cause framework, under which each sufficient cause is treated as a stochastic process instead of a time-invariant random variable. However, different types of mechanistic interactions such as synergism and agonism cannot be further identified. In this study, we proposed a stochastic marginal sufficient component cause model to conceptualize and identify agonism and synergism by exploiting the additional information. We further provided six approaches to identify and estimate agonism and synergism based on an additive hazard model and a complementary log model. Researchers can easily adjust confounding factors by including appropriate covariates into a regression model. Simulations have proven that approaches under three models are all valid tests. The power of an additive hazard model increases as the total follow-up time increases and is higher than that of the other two models. We applied this method to a Taiwanese cohort data set to investigate the mechanistic interaction among hepatitis B and C viruses on the incidence of hepatocellular carcinoma. The hazard of people with agonistic interaction is 1.28×10-5 (95% CI: 6.97×10-6 , 1.87×10-5 ), and the cumulative hazard of those people is 7.41×10-2 (95% CI: 4.09×10-2 , 1.07×10-1 ), which is approximately 3.5 times stronger than that of synergistic interaction. The proposed method makes it possible to quantify different types of mechanistic interactions in longitudinal studies with censored data. [ABSTRACT FROM AUTHOR]

Background A blood urea nitrogen to creatinine ratio (BCR) of 20 or greater indicates various physiological conditions. Whether glomerular filtration rate (GFR) estimates obtained using the Modification of Diet in Renal Disease (MDRD) study equation and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equations are affected by a high BCR remains unknown. Methods Patients who underwent urine creatinine clearance (CrCl) and serum blood urea nitrogen (BUN) and creatinine assessments on the same day were enrolled in our study. Those with BCR of 20 or greater and less than 20 were categorized into high- and low-BCR groups. The concordance on diagnosing chronic kidney disease (CKD) stages by using urine CrCl level and serum GFR estimates was assessed. Results More disagreement in CKD stage diagnosis was observed in the high-BCR group (weighted κ = 0.600 and 0.541 for the MDRD and CKD-EPI study equations, respectively) than in the low-BCR group (weighted κ = 0.816 and 0.758, respectively). Conclusions A BCR of 20 or greater caused misestimation of the CKD stage. GFR estimates for patients with high BCR should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a rare disease characterized by pancytopenia and bone marrow failure. The incidence of AA tends to be higher in Asia than in the West, but real-world data about AA in Asia remain limited. We aimed to describe the basic data, treatment, and outcome of AA patients from our institute and evaluate the incidence of AA in Taiwan with a nationwide population-based cohort from National Health Insurance Research Database (NHIRD). We identified patients older than 2 years with AA in the Registry of Catastrophic Illness of NHIRD between 2001 and 2010 and excluded patients with any diagnosis suggestive of congenital or secondary bone marrow failure. With a total of 1270 patients, the overall incidence was 5.67 per million people per year, and there was a biphasic age distribution of incidence rate, highest in ≥ 70 years (19.83 per million people per year) and another peak at age 2-9 years (5.26 per million people per year). Overall, the 5-year survival was 60.0%. Hematopoietic stem cell transplantation (HSCT) and anti-thymocyte globulin-based immunosuppressive therapy (IST) were the major first-line treatments in patients younger than 40 years and were linked with good survival. In contrast, the majority of patients older than 60 years were treated with androgen, and the survival was poor. In multivariate analysis, "severe AA," "very severe AA," and "treatment other than HSCT, IST, or androgen" were independent risk factors for inferior survival. In conclusion, the incidence of AA in Taiwan is consistent with nearby Asian countries and is higher than in the West. Advanced age is associated with higher incidence and poorer outcome. [ABSTRACT FROM AUTHOR]

A new oxacyclododecindione-type macrolactone, (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclododecindione (1), has been obtained from the solid cultures of the fungus Exserohilum rostratum, a fungal strain endophytic in Gymnadenia conopsea. Its structure, including the absolute configuration, was extensively established by 1D and 2D NMR data, the modified Mosher method, and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. Compound 1 showed weak selective cytotoxicity against the A549 lung cell line with an IC50 value of 9.2 µM. [ABSTRACT FROM AUTHOR]

Background Little is known about the association between weight changes and adverse health outcomes among Chinese adults. Methods A total of 1715 Chinese adults, 45–60 years of age, have been recruited to participate in the Hefei Nutrition and Health Study started in 2012. Multivariate logistic regression analysis was performed to determine the association of weight changes since age 20 (loss ≥5.0 kg; maintain [±4.9 kg]; gain 5.0–9.9 kg; gain ≥10.0 kg) with cardiovascular risk factors. Results Men who gained 10.0 kg or more had increased risks of hypertension (odds ratios (OR) = 3.07; 95% CI: 1.98–4.76), impaired fasting glucose (OR = 1.74; 95% CI: 1.02–2.97), reduced high-density lipoprotein (HDL) cholesterol levels (OR = 2.77; 95% CI: 1.42–5.40) and elevated triglyceride levels (OR = 5.72; 95% CI: 2.94–11.12). Women who gained 10.0 kg or more had increased risks of hypertension, elevated low-density lipoprotein (LDL) cholesterol levels and elevated triglycerides levels of 2.01(95% CI: 1.18–3.42), 3.40 (95% CI: 1.18–9.82) and 5.60 (95% CI: 1.59–19.61), respectively. Conclusion Weight gain during adulthood was associated with increased risks of high triglycerides, hypertension, impaired fasting glucose and risk of reduced HDL cholesterol in men. Furthermore, weight gain was a predictor of high-risk triglycerides, hypertension and elevated LDL cholesterol in women. [ABSTRACT FROM AUTHOR]

Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and trichopyrone B (2), together with two known polyketides, sorbicillin (3) and penicillone A (4), have been isolated from the cultures broth of the fungus Penicillium decumbens. Their structures were elucidated by extensive spectroscopic analysis. All isolated compounds were evaluated for their antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal activity toward Candida albicans Y0109 with a MIC value of 50 μM. Moreover, compounds 3 and 4 exhibited selective cytotoxicity against the human hepatocellular carcinoma (QGY-7703) cell line with the IC50 values of 32.5 and 22.8 μM, respectively. [ABSTRACT FROM AUTHOR]

Six new indole alkaloid diglycosides named isatigotindolediosides A-F (1–6), along with three known analogs (7–9), were isolated from an aqueous extract of theIsatis indigoticaroots (ban lan gen). Their structures including the absolute configurations were determined by comprehensive spectroscopic data analysis, combined with enzyme or acid hydrolysis, and comparison of experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. In the preliminary assays, compounds3,5, and8showed antiviral activity against Coxsackie virus B3. [ABSTRACT FROM PUBLISHER]

The assessment of direct and indirect effects with time-varying mediators and confounders is a common but challenging problem, and standard mediation analysis approaches are generally not applicable in this context. The mediational g-formula was recently proposed to address this problem, paired with a semiparametric estimation approach to evaluate longitudinal mediation effects empirically. In this article, we develop a parametric estimation approach to the mediational g-formula, including a feasible algorithm implemented in a freely available SAS macro. In the Framingham Heart Study data, we apply this method to estimate the interventional analogues of natural direct and indirect effects of smoking behaviors sustained over a 10-year period on blood pressure when considering weight change as a time-varying mediator. Compared with not smoking, smoking 20 cigarettes per day for 10 years was estimated to increase blood pressure by 1.2 mm Hg (95% CI: -0.7, 2.7). The direct effect was estimated to increase blood pressure by 1.5 mm Hg (95% CI: -0.3, 2.9), and the indirect effect was -0.3 mm Hg (95% CI: -0.5, -0.1), which is negative because smoking which is associated with lower weight is associated in turn with lower blood pressure. These results provide evidence that weight change in fact partially conceals the detrimental effects of cigarette smoking on blood pressure. Our study represents, to our knowledge, the first application of the parametric mediational g-formula in an epidemiologic cohort study (see video abstract at, http://links.lww.com/EDE/B159.). [ABSTRACT FROM AUTHOR]

Three new minor valepotriate isomers, jatamanvaltrates Z1 (1), Z2 (2), and Z3 (3), have been isolated from the whole plants ofValeriana jatamansi(syn.Valeriana wallichii.). Their structures were elucidated by extensive spectroscopic analysis, especially 2D NMR and ESI-MS/MSn. All isolated compounds displayed moderate cytotoxicity against the lung adenocarcinoma (A549), metastatic prostate cancer (PC-3 M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines with IC50values of 2.8–8.3 μM. [ABSTRACT FROM PUBLISHER]

Drawing upon the ‘stimulus-organism-response’ framework, this paper examines how the ease of navigation (EON) of a website affects consumers' online impulse buying. We also compared the effects of various virtual layouts (i.e. grid, freeform, racetrack, and mix grid–freeform) on consumers' perceptions of EON, emotional responses, and the urge to buy impulsively. Based on questionnaire responses from 216 participants in a stratified survey, we found that EON significantly influences consumers' emotional responses, pleasantness, and arousal, which subsequently affects their urge to buy impulsively. We also found that compared with the other three layouts, manifestations of navigability, freeform is the easiest to navigate, and is able to elicit the highest level of pleasantness and the strongest urge to buy impulsively. The findings of this study provide important implications for impulse buying research and practice. [ABSTRACT FROM AUTHOR]

Childhood has been targeted as an especially important period for self-esteem formation. The aim of this study is to examine the change and associated factors of self-esteem among children in rural China. A two-year longitudinal study was conducted with a general elementary and secondary school population in Anhui Province, China including 816 children aged between 7 and 16 years. Generalized estimating equation (GEE) was used to examine relationships between low self-esteem and socio-demographic, family environment, and psychosocial factors. On average, self-esteem level among children was increased across three assessments. Multivariable analysis (GEE) showed that low self-esteem in children was clearly associated with male gender (OR = 1.45, 95%CI = 1.12–1.89), moderate and severe family dysfunction (OR = 1.88, 95%CI = 1.40–2.51; OR = 1.88, 95%CI = 1.25–2.83, respectively), quality of life (OR = .97, 95%CI = .96–.98), depression (OR = 1.89, 95%CI = 1.32–2.70), anxiety (OR = 2.05, 95%CI = 1.51–2.77), positive coping styles (OR = .91, 95%CI = .89–.94), and negative coping styles (OR = 1.05, 95%CI = 1.03–1.07). Self-esteem is a dynamic rather than a static construct during childhood. Low self-esteem among children was associated with a number of socio-demographic, family environment, and psychosocial factors. Further studies exploring the pathways and mechanisms by which the effect of these factors impact on self-esteem among children are warranted. [ABSTRACT FROM PUBLISHER]

Objective. To determine whether the vasodilatation effect of monochromatic infrared photo energy (MIRE) had the potential for the treatment of myofascial trigger spot (MTrS) in rabbits. Design. A randomized-controlled animal study. Subjects. Twelve adult New Zealand rabbits. Methods. For each rabbit, a MTrS (equivalent to a myofascial trigger point in humans) in one side of the biceps femoris muscle was randomly selected for MIRE treatment (experimental side), while another MTrS in the other side (control side) received a sham treatment. The intervention consisted of a daily 40 minutes treatment, three times per week for 2 weeks. The prevalence of endplate noise (EPN) loci in the MTrS was assessed before, immediately after, and one week after the completion of the 2-week treatment. Results. MIRE could suppress the prevalence of EPN in the MTrS. The degree of reduction in EPN prevalence in the MTrS between the experimental side and the control side was significantly different immediately after MIRE treatment, but not significantly different one week after MIRE treatment. Conclusion. Our study suggests that MIRE may be a useful therapeutic option for the management of the myofascial trigger point in humans. [ABSTRACT FROM AUTHOR]

Seven new glycosidic bisindole alkaloids, isatindigobisindolosides A–G (1–7), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory. In the NMR spectra of 1–3, it is found that integration of H-2 and intensity of C-2 are affected not only by a substitution group at C-2 but also by solvents. Influences of the glucopyranosyloxy on the calculated ECD spectra of the glycosidic bisindole alkaloids are discussed. Compounds 2, 5, and 6 showed antiviral activity against both the influenza virus A/Hanfang/359/95 (H3N2) and Coxsackie virus B3 with IC50 values of 8.4–100.0 μM. [ABSTRACT FROM AUTHOR]

Seven new C14-polyacetylene glucosides codonopilodiynosides A–G (1–7) were isolated from an aqueous extract of theCodonopsis pilosularoots. Their structures were determined by spectroscopic and chemical methods as (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranoside (1), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (2), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5,14-di-O-β-d-glucopyranoside (3), (–)-(5S,6E)-tetradeca-6-en-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranoside (4), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5-diol 5-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (5), (–)-(6S,4E,12E)-tetradeca-4,12-dien-8,10-diyn-1,6-diol 6-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (6), and (–)-(5S,6E)-tetradeca-6-en-1,5-epoxy-8,10-diyn-14-ol 14-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (7), respectively. The absolute configurations of1–7were assigned by enzymatic hydrolysis followed by isolation of glucose and aglycones (1aand4a–7a), and subsequent comparison of specific rotation, TLC, and1H NMR data of the glucose with an authentic sugar sample and application of modified Mosher's method based on the MPA determination rule of ΔδRSvalues for1aand4a,and ΔδSvalues for6a. The configuration of7was assigned by electronic circular dichroism calculations based on the quantum-mechanical time-dependent density functional theory. [ABSTRACT FROM AUTHOR]

Three new decomposition products of valepotriates, valtrals A–C (1–3), and two known products, baldrinal and homobaldrinal, are formed during the isolation procedure of the ethanol extract of the whole plants ofValeriana jatamansi. Their structures were determined by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. Compounds1–3showed selective cytotoxicity against metastatic prostate cancer (PC-3M) and colon cancer (HCT-8) cell lines. [ABSTRACT FROM PUBLISHER]

Seven new aromatic acid derivatives (1–7), together with five known analogs, were isolated from the lateral roots ofAconitum carmichaelii. Structures of the new compounds were determined by spectroscopic and chemical methods as 4-methyl ( − )-(R)-hydroxyeucomate (1), 4-butyl ( − )-(R)-hydroxyeucomate (2), 4-butyl-1-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (3), 1-butyl-4-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (4), dimethyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (5), dimethyl (+)-(R)-2-O-(4′-hydroxybenzoyl)malate (6), and methyl ( ± )-3-(4′-hydroxy-3′-methoxyphenyl)-3-sulfopropionate (7), respectively. Compounds1and2are 2-benzylmalates (eucomate derivatives),3–6belong to 2-O-benzoylmalates, and7is a rare phenylpropionate containing a sulfonic acid group. The absolute configurations of eucomate derivatives were confirmed by X-ray crystallographic analysis of 4-methyl eucomate (11). [ABSTRACT FROM PUBLISHER]

Purpose This study investigates the handwriting performance of patients with carpal tunnel syndrome (CTS) and healthy controls in office and administrative support occupations, adopting both biomechanical and functional perspectives. This work also explores how surgical intervention altered the performance of the CTS patients. Methods Fourteen CTS patients and 14 control subjects were recruited to complete a self-reported survey and participate in sensory tests, hand strength, dexterity and handwriting tasks using a custom force acquisition pen along with motion capture technology. Based on the results of these, the sensory measurements, along with functional and biomechanical parameters, were used to determine the differences between the groups and also reveal any improvements that occurred in the CTS group after surgical intervention. Results The CTS patients showed significantly poorer hand sensibility and dexterity than the controls, as well as excessive force exertion of the digits and pen tip, and less efficient force adjustment ability during handwriting. After surgery and sensory recovery, the hand dexterity and pen tip force of the CTS patients improved significantly. The force adjustment abilities of the digits also increased, but these changes were not statistically significant. Conclusions This study provides the objective measurements and novel apparatus that can be used to determine impairments in the handwriting abilities of office or administrative workers with CTS. The results can also help clinicians or patients to better understand the sensory-related deficits in sensorimotor control of the hand related to CTS, and thus develop and implement more suitable training or adaptive protocols. [ABSTRACT FROM AUTHOR]

Objective: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. Methods: Thirty-five patients were enrolled, including 18 with “yang deficiency syndrome” and 17 with “yin deficiency syndrome.” Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor −1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Results: Counts for leukocytes, absolute neutrophils and platelets in “yin deficiency syndrome” were lower than those found in “yang deficiency syndrome” ( P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in “yin deficiency syndrome” ( P<0.01 or P<0.05). “Yin deficiency syndrome” displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to “yang deficiency syndrome” ( P<0.05). Levels of IL-4 and IL-6 were higher in AA ( P<0.01), but IL-10 was decreased ( P<0.05). High TNF-α expression was seen in “yang deficiency syndrome” and IFN-γ expression was decreased in “yin deficiency syndrome” as compared with normals ( P <0.01 and P<0.05, respectively). Conclusion: AA patients have lower MVD than normals, especially in “yin deficiency syndrome.” MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD. [ABSTRACT FROM AUTHOR]

Despite the consistent presence of performance deficits on the Wisconsin Card Sorting Test (WCST) in schizophrenia patients, whether poorer performance is also present in their nonpsychotic relatives is not certain. This study aimed to estimate both the recurrence risk ratio (λs) and the heritability of WCST scores in simplex and multiplex families, respectively, and to examine the influence of familial loading on these estimates. Participants were patients with schizophrenia and their nonpsychotic first-degree relatives from 168 simplex families and 653 multiplex families as well as 440 normal comparisons. On the basis of adjusted z scores, both the λs at a series of cutoff points and heritability estimates based on variance component modeling in the nonpsychotic relatives of schizophrenia patients were estimated. The WCST deficits in schizophrenia patients were more prominent in multiplex families than in simplex ones. Among relatives, WCST deficits were limited to parents of multiplex families for most WCST scores and siblings from multiplex families for total errors, perseverative responses, and perseverative errors. Pertaining to λs, the estimates for multiplex families (highest estimates ranging from 7.9 to 11.0) were greater than those for simplex ones (<2.5). Nevertheless, the heritability estimates were very similar between simplex (ranging from 0% to 17%) and multiplex (ranging from 0% to 21%) families, with the latter having slightly greater values than the former. There is only a small-to-modest familial aggregation on part of WCST scores in families of schizophrenia patients, and this may limit its use as endophenotypic markers to schizophrenia susceptibility. [ABSTRACT FROM PUBLISHER]

Six new butanolide derivatives with long aliphatic side chains (1–6), together with 23 known lipophilic constituents, were isolated from the bark of Machilus yaoshansis. Their structures were elucidated by spectroscopic and chemical methods. All the isolates were evaluated for cytotoxic and anti-inflammatory activities. [ABSTRACT FROM PUBLISHER]

Nine new fatty acid derivatives, including seven methoxylated (1, 2, and 4–8) and two hydroxylated (3 and 9) fatty acids, have been isolated from the ethanol extract of the stem bark of Fraxinus sieboldiana. Their structures were determined by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. The 3- or 9-methoxylated fatty acids are reported for the first time in nature. [ABSTRACT FROM PUBLISHER]

Objectives: To assess the prevalence of psychological symptoms (depression, anxiety) among Chinese medical students and to find the possible relationships between psychological symptoms and social relationships. Methods: A sample of 10,140 medical students was investigated with a structured questionnaire, that included the Beck Depression Inventory, Beck Anxiety Inventory, Social Support Rating Scale, and Family APGAR Index (adaptability, partnership, growth, affection, resolve). Results: The present study revealed that 16.8% of the medical students suffered from depressive symptoms and 14.1% from anxiety symptoms. Female students were more likely to have anxiety, the second-year students had higher levels of psychological symptoms than the first-year students. Likewise, significant differences were found among college, satisfaction of specialty, and economic condition of the family in anxiety and depression symptoms. Social support, family function, and all dimensions were significantly negatively associated with depression and anxiety symptoms. Multivariable ordinal logistic regression showed that less social support, poor family function, the second-year students, and unsatisfactory specialty were associated with more psychological symptoms, after adjusting the effects of sex, age, and college. Conclusions: Medical students have a relatively high level of depression and anxiety symptoms. These findings support the hypothesis that if medical students are better supported and cared for, negative psychosocial consequences might be prevented or at least reduced. [ABSTRACT FROM AUTHOR]

Five new 9,10-anthraquinones (1–5) were isolated from an ethanol extract of the roots of Knoxia valerianoides. Their structures including absolute configuration of 1 were determined by spectroscopic analysis. Compounds 4 and 5 showed moderate activity against nitrogen oxide production in macrophages induced by lipopolysaccharide, at 10− 5 M, with inhibition ratios of 50.4 ± 3.6 and 41.7 ± 2.1%, respectively. [ABSTRACT FROM PUBLISHER]

A novel medical image quality index using grey relational coefficient calculation is proposed in this study. Three medical modalities, DR, CT and MRI, using 30 or 60 images with a total of 120 images used for experimentation. These images were first compressed at ten different compression ratios (10 ∼ 100) using a medical image compression algorithm named JJ2000. Following that, the quality of the reconstructed images was evaluated using the grey relational coefficient calculation. The results were shown consistent with popular objective quality metrics. The impact of different image aspects on four grey relational coefficient methods were further tested. The results showed that these grey relational coefficients have different slopes but very high consistency for various image areas. Nagai's grey relational coefficient was chosen in this study because of higher calculation speed and sensitivity. A comparison was also made between this method and other windows-based objective metrics for various window sizes. Studies found that the grey relational coefficient results are less sensitive to window size changes. The performance of this index is better than some windows-based objective metrics and can be used as an image quality index. [ABSTRACT FROM AUTHOR]

The interferon-γ enzyme-linked immunospot assay (ELISPOT) has been demonstrated to be useful in the diagnosis of active tuberculosis (TB). In this study we aimed to evaluate the diagnostic performance of the ELISPOT assay in cancer patients with suspected pulmonary TB. Eighty-one cancer patients with suspected pulmonary TB were prospectively enrolled from April 2007 to December 2008, to investigate the diagnostic sensitivity and specificity of the ELISPOT assay. Of the 38 patients with TB, 33 (86.8%) had positive ELISPOT results. Of the 43 patients without TB, the results of the ELISPOT assay were negative in 35 (81.3%) patients. The overall sensitivity was 86.8%, specificity 81.3%, positive predictive value 80.5% and negative predictive value 87.5%. No significant difference was noted for the diagnostic performance of the ELISPOT assay for diagnosing TB between solid cancer and haematological cancer patients. In addition, a quantitative study did not show that TB patients with solid cancers have a better response than haematological cancer patients as measured by spot-forming cells per 106 peripheral blood mononuclear cells after exposure to early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10). In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB among cancer patients, irrespective of cancer type. [ABSTRACT FROM AUTHOR]

The effect of 1-alkanols upon the main phase-transition temperature of phospholipid vesicle membranes between gel and liquid-crystalline phases was not a simple monotonic function of alkanol concentration. For instance, 1-decanol decreased the transition temperature at low concentrations, but increased it at high concentrations, displaying a minimal temperature. This concentration-induced biphasic effect cannot be explained by the van't Hoff model on the effect of impurities upon the freezing point. To explain this nonlinear response, a theory is presented which treats the effect of 1-alkanols (or any additives) on the transition temperature of phospholipid membranes in a three-component mixture. By fitting the experimental data to the theory, the enthalpy of the phase transition delta H* and the interaction energy, epsilon*AB between the additive and phospholipid molecules may be estimated. The theory predicts that when epsilon*AB greater than 2 (where epsilon*AB = epsilon AB/RT0, T0 being the transition temperature of phospholipid), both minimum and maximum transition temperatures should exist. When epsilon*AB = 2, only one inflection point exists. When epsilon*AB less than 2, neither maximum nor minimum exists. The alkanol concentration at which the transition temperature is minimum (Xmin) depends on the epsilon*AB value: the larger the epsilon*AB values, the smaller the Xmin. When epsilon*AB is large enough, Xmin values become so small that the plot delta T vs. X shows positive delta T in almost all alkanol concentrations. The interaction energy between 1-alkanols and phospholipid molecules increased with the increase in the carbon chain-length of 1-alkanols. In the case of the dipalmitoylphosphatidylcholine vesicle membrane, the carbon chain-length of 1-alkanols that caused predominantly positive delta T was about 12. [ABSTRACT FROM AUTHOR]

Breast cancer is a major cause of death in Western women, with a 10% lifetime risk of the disease. Most breast cancers are estrogen-dependent. Molecular therapies for breast cancer have developed rapidly in the past few decades and future treatment strategies are being investigated. The selective estrogen receptor (ER) modulator tamoxifen, which until now has served as a standard therapy, functions not only as an estrogen antagonist but also as an estrogen agonist in terms of bone maintenance. Aromatase inhibitors have performed well in international trials and have become a new standard therapy for estrogen-dependent breast cancer. The systematic study of estrogen activation pathways suggests that the enzymes steroid sulfatase and 17beta-hydroxysteroid dehydrogenase type 1, which both have pivotal roles in estrogen biosynthesis, are promising targets; the results of a phase I trial of steroid sulfatase inhibitors are encouraging. The activity of the human epidermal growth factor receptor (HER) pathway correlates negatively with that of the ER. HER2 is overexpressed in 22% of all breast cancers. In the decade since HER2 began being targeted, the monoclonal antibody trastuzumab has been used as well as pertuzumab and HER2 vaccines. Among the estrogen-independent breast cancers, the basal-like subtype has low survival, and therapeutic improvement is a priority. Crosstalk between ER and HER2 signaling pathways means that combinatory therapies may hold the key to enhancement of treatment responses. Other molecular therapies involving functional genomics and RNA interference studies also hold promise. [ABSTRACT FROM AUTHOR]