Phytochemical diversity and their adaptations to abiotic and biotic pressures in fine roots across a climatic gradient.

Phytochemicals and their ecological significance are long ignored in trait-based ecology. Moreover, the adaptations of phytochemicals produced by fine roots to abiotic and biotic pressures are less understood. Here, we explored the fine roots metabolomes of 315 tree species and their rhizosphere microbiome in southwestern China spanning tropical, subtropical, and subalpine forest ecosystems, to explore phytochemical diversity and endemism patterns of various metabolic pathways and phytochemical-microorganism interactions. We found that subalpine species showed higher phytochemical diversity but lower interspecific variation than tropical species, which favors coping with high abiotic pressures. Tropical species harbored higher interspecific phytochemical variation and phytochemical endemism, which favors greater species coexistence and adaptation to complex biotic pressures. Moreover, there was evidence of widespread chemical niche partitioning of closely related species in all regions, and phytochemicals showed a weak phylogenetic signal, but were regulated by abiotic and biotic pressures. Our findings support the Latitudinal Biotic Interaction Hypothesis, i.e., the intensity of phytochemical-microorganism interactions decreases from tropical to subalpine regions, which promotes greater microbial community turnover and phytochemical niche partitioning of host plants in the tropics than in higher latitude forests. Our study reveals the convergent phytochemical diversity patterns of various pathways and their interactions with microorganism, thus promoting species coexistence.

Associations of muscle mass and strength with new-onset diabetes among middle-aged and older adults: evidence from the China health and retirement longitudinal study (CHARLS).

BACKGROUND: The associations of muscle mass and strength with new-onset Type 2 diabetes mellitus (T2DM) remain controversial. We aimed to longitudinally evaluate muscle mass and strength in predicting T2DM among Chinese middle-aged and older adults. METHODS: We enrolled 6033 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS), a cohort survey, between 2011 and 2012. The appendicular skeletal muscle mass (normalized by weight, ASM/BW%), relative hand grip strength (normalized by weight, HGS/BW), and five-repetition chair stand test (5CST). were all categorized into tertiles (lowest, middle, and highest groups) at baseline, respectively. Individuals were followed up until the occurrence of diabetes or the end of CHARLS 2018, whichever happened first. Cox proportional hazards models to calculate hazard ratios with 95% confidence intervals (CI) and mediation analysis were used. RESULTS: During follow-up, 815 (13.5%) participants developed T2DM. After adjusting for covariates, lower ASW/BW% was not associated with a higher risk of diabetes. Compared with individuals in the highest tertile of HGS/BW, those in the lowest tertile had 1.296 (95%CI 1.073-1.567) higher risk of diabetes. Compared with individuals in the lowest tertile of 5CST, those in the highest tertile had 1.329 times (95%CI 1.106-1.596) higher risk of diabetes. By subgroup, both the lowest HGS/BW and highest 5CST were risk factors for diabetes among obesity. The mediation analysis revealed that the effect of HGS/BW on the risk of diabetes is mainly mediated by insulin resistance. CONCLUSIONS: Lower muscle strength is associated with an increased risk of diabetes, especially in obese populations.

Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

Associations of sarcopenia with peak expiratory flow among community-dwelling elderly population: based on the China Health and Retirement Longitudinal Study (CHARLS).

PURPOSE: To cross-sectionally and longitudinally investigate the correlations of sarcopenia and its components with peak expiratory flow (PEF) among Chinese community-dwelling elderly people. METHODS: The data were extracted from the China Health and Retirement Longitudinal Study (CHARLS). A total of 4053 participants aged ≥ 60 years were enrolled from CHARLS 2011, and 2810 were followed up until 2015. Participants were classified into no-sarcopenia, non-severe sarcopenia, and severe sarcopenia groups based on skeletal muscle mass index (SMI), hand grip strength (HGS), and physical performance [gait speed, five-repetition chair stand test (5CST) and short physical performance battery (SPPB)]. Multivariate linear and logistic regression analyses were used to evaluate the associations of sarcopenia and its components with PEF cross-sectionally and longitudinally. RESULTS: In the cross-sectional analysis, the prevalence of non-severe sarcopenia was 14.6% and severe sarcopenia was 4.9%. The results of linear regression analysis revealed that sarcopenia and its components were all correlated with PEF and PEF%pred. In the longitudinal analysis, compared with non-sarcopenia, subjects with severe sarcopenia were associated with a higher risk of PEF (OR = 2.05, 95%CI = 1.30-3.26) and PEF%pred (OR = 1.83, 95%CI = 1.17-2.86) decline. The changes in physical performance were correlated with changes in PEF and PEF%pred. No associations were observed between changes in SMI and PEF as well as PEF%pred. CONCLUSIONS: We demonstrated the associations of baseline sarcopenia status with PEF and longitudinal PEF decline. Also, the changes in physical performance were associated with changes in PEF during a 4-year follow-up. It indicates that improving sarcopenia, especially physical performance may increase PEF.

Phytochemical diversity impacts herbivory in a tropical rainforest tree community.

Metabolomics provides an unprecedented window into diverse plant secondary metabolites that represent a potentially critical niche dimension in tropical forests underlying species coexistence. Here, we used untargeted metabolomics to evaluate chemical composition of 358 tree species and its relationship with phylogeny and variation in light environment, soil nutrients, and insect herbivore leaf damage in a tropical rainforest plot. We report no phylogenetic signal in most compound classes, indicating rapid diversification in tree metabolomes. We found that locally co-occurring species were more chemically dissimilar than random and that local chemical dispersion and metabolite diversity were associated with lower herbivory, especially that of specialist insect herbivores. Our results highlight the role of secondary metabolites in mediating plant-herbivore interactions and their potential to facilitate niche differentiation in a manner that contributes to species coexistence. Furthermore, our findings suggest that specialist herbivore pressure is an important mechanism promoting phytochemical diversity in tropical forests.

Constructing a noble-metal-free 0D/2D CdS/SnS2heterojunction for efficient visible-light-driven photocatalytic pollutant degradation and hydrogen generation.

Semiconductor photocatalysis has attracted the attention of a wide audience for its outstanding capabilities in water purification and energy conversion. Herein, a noble-metal-free nanoheterojunction is created by planting zero-dimensional (0D) CdS nanograins, of 10-20 nm in size, on the surface of 2D SnS2nanosheets (NSs) using anin situchemical bathing deposition process, where SnS2NSs have an average diameter of 400 nm and thicknesses of less than 20 nm. The possible formation mechanism of the CdS/SnS2(CS/SS) heterogeneous nanostructure is elaborated upon. The catalytic activities over CS/SS nanocomposites for the photodegradation of organic dye and hydrogen evolution from photolysis water splitting are examined under visible light irradiation. The apparent rate constant (k) of the optimal CS/SS-3 composite in the decontamination of methylene blue (MB) is up to 3.34 and 1.87 times as high as that of pristine SnS2and pure CdS counterparts, respectively. The optimized CS/SS-3 sample consistently achieves the highest photocatalytic hydrogen production rate, at 10.3 and 5.7 folds higher than that of solo SnS2and CdS panels, respectively. The boosted photocatalytic capacities of CdS/SnS2heterostructures are essentially attributed to the formation of the closely interfacial incorporation of CdS and SnS2semiconductors, resulting in the effective charge transportation and spatial separation of the photoinduced electron-hole pairs. Furthermore, the traditional type-II charge transfer pathway is proposed based on the perfect band structure and the free radical experiment results.

DNA-Encoded Macrocyclic Peptide Libraries Enable the Discovery of a Neutral MDM2-p53 Inhibitor.

Synthetic macrocyclic peptides are an emerging molecular class for both targeting intracellular protein-protein interactions (PPIs) and providing an oral modality for drug targets typically addressed by biologics. Display technologies, such as mRNA and phage display, often yield peptides that are too large and too polar to achieve passive permeability or oral bioavailability without substantial off-platform medicinal chemistry. Herein, we use DNA-encoded cyclic peptide libraries to discover a neutral nonapeptide, UNP-6457, that inhibits MDM2-p53 interaction with an IC50 of 8.9 nM. X-ray structural analysis of the MDM2-UNP-6457 complex revealed mutual binding interactions and identified key ligand modification points which may be tuned to enhance its pharmacokinetic profile. These studies showcase how tailored DEL libraries can directly yield macrocyclic peptides benefiting from low MW, TPSA, and HBD/HBA counts that are capable of potently inhibiting therapeutically relevant protein-protein interactions.

Diffusion tensor and kurtosis imaging reveal microstructural changes in the trigeminal nerves of patients with trigeminal neuralgia.

OBJECTIVES: To evaluate the use of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) for detection of microstructural changes in the trigeminal nerves of trigeminal neuralgia (TN) patients. METHODS: Forty TN patients and 40 healthy controls were examined using 3 T magnetic resonance imaging (MRI) to evaluate DTI and DKI parameters in trigeminal nerves. One-way ANOVA was used to test the differences in age, sex, and DTI and DKI parameters between the TN-affected sides, TN-unaffected sides, and controls. For parameters with inter-group differences, pairwise comparisons were performed. Then, the difference ratios (DRs) of the parameters with statistical differences were calculated and used for the receiver operating characteristic (ROC) analysis to assess their diagnostic performance. In addition, for the DTI and DKI parameter values with differences, we used pure DTI and DKI values to perform the ROC analysis. RESULTS: Compared to the unaffected sides and controls, the FA, MK, and Kr of the affected sides of TN patients were significantly reduced, while ADC was significantly increased (p < 0.05). The diagnostic efficiency of the FA DRs (AUC: 0.974; cutoff value: 0.038; sensitivity: 100%; specificity: 95.0%) was the highest among all DTI and DKI parameters. The DRs of FA and MK more efficiently diagnosed TN than pure FA and MK values. CONCLUSIONS: DTI and DKI allowed detection of microstructural changes in TN-affected trigeminal nerves. FA DR was the best independent predictor of microstructural changes in TN. CLINICAL RELEVANCE STATEMENT: Both DTI and DKI can be used for noninvasive quantitative evaluation of the changes in the microstructure of the cisternal segment of the cranial nerves in clinical practice. KEY POINTS: • Diffusion tensor imaging (DTI) can be used to evaluate the in vivo integrity of white matter and nerve fiber pathway. • Diffusion kurtosis imaging (DKI) has been shown to be considerable sensitive to microstructural changes. • DTI combined with DKI can comprehensively evaluate the status of the TN-affected trigeminal nerve.

Ontogenetic trait variation and metacommunity effects influence species relative abundances during tree community assembly.

Predicting species abundance is one of the most fundamental pursuits of ecology. Combining the information encoded in functional traits and metacommunities provides a new perspective to predict the abundance of species in communities. We applied a community assembly via trait selection model to predict quadrat-scale species abundances using functional trait variation on ontogenetic stages and metacommunity information for over 490 plant species in a subtropical forest and a lowland tropical forest in Yunnan, China. The relative importance of trait-based selection, mass effects, and stochasticity in shaping local species abundances is evaluated using different null models. We found both mass effects and trait selection contribute to local abundance patterns. Trait selection was detectable at all studied spatial scales (0.04-1 ha), with its strength stronger at larger scales and in the subtropical forest. In contrast, the importance of stochasticity decreased with spatial scale. A significant mass effect of the metacommunity was observed at small spatial scales. Our results indicate that tree community assembly is primarily driven by ontogenetic traits and metacommunity effects. Our findings also demonstrate that including ontogenetic trait variation into predictive frameworks allows ecologists to infer ecological mechanisms operating in community assembly at the individual level.

Frailty as a predictor of all-cause mortality in elderly patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Frailty has been proposed as a poor prognostic indicator for elderly patients with coronary artery diseases (CAD). The objective of this meta-analysis was to evaluate the effects of frailty on all-cause mortality in elderly patients with CAD following percutaneous coronary intervention (PCI). METHODS: PubMed, Embase, the Cochrane library, Web of science, and ClinicalTrial.gov were searched for associated studies from their inception to April 30, 2021. Odds ratios (OR) were calculated to estimate the in-hospital and short-term outcomes, whereas the hazard ratios (HR) were pooled for long-term mortality using random-effects by Revman 5.3. RESULTS: A total of nine studies including 2658 elderly participants were included in this meta-analysis. It was identified that the prevalence of frailty ranged from 12.5 to 27.8%. Frailty was associated with increased in-hospital mortality (OR 3.59, 95% CI 2.01 - 6.42; I2 = 35%), short-term mortality (OR 6.61, 95% CI 2.89 - 15.16; I2 = 0%), as well as long-term mortality (HR 3.24, 95% CI 2.04- 5.14; I2 = 70%) in patients undergoing PCI. Besides, we also found that prefrailty was a predictor of all-cause mortality. CONCLUSIONS: Frailty was associated with in-hospital, short-term and long-term mortality in elderly patients with PCI. The results may consolidate the importance of routine frailty screening in risk stratification in elderly patients with CAD who are considered for PCI.

LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increased ubiquitination of thioredoxin-interacting protein.

Numerous studies have revealed that hyperglycemia is a pivotal driver of diabetic vascular complications. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). In this study, a downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanistically, SNHG15 reduced thioredoxin-interacting protein (TXNIP) expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of lncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. In conclusion, SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.

LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increasing ubiquitination of thioredoxin-interacting protein.

OBJECTIVE: Numerous evidence indicates that hyperglycemia is a pivotal driver of the vascular complications of diabetes. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). MATERIALS AND METHODS: Cell proliferation, migration, apoptosis, and tube formation were measured by cell counting kit-8 assay, transwell assay, flow cytometry, and tube formation assay, respectively. RNA pull-down and RNA-binding protein immunoprecipitation were used to detect the interaction between lncRNA SNHG15 and thioredoxin-interacting protein (TXNIP). Co-immunoprecipitation was used to detect the ubiquitination level of TXNIP and the interaction between TXNIP and E3 ubiquitin ligase ITCH. RESULTS: A downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanically, SNHG15 reduced TXNIP expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of LncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. CONCLUSION: SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.

Ethiopian vegetation types, climate and topography.

Ethiopia is land of geographical contrasts with elevations that range from 125 m below sea level in the Danakil Depression to 4533 m above sea level in the Semien Mountains, a world heritage site. The diverse climate of various ecological regions of the country has driven the establishment of diverse vegetation, which range from Afroalpine vegetation in the mountains to the arid and semi-arid vegetation type in the lowlands. The formation of Ethiopian vegetation is highly connected to the climate and geological history of the country. Highland uplift and rift formation due to volcanic forces formed novel habitats with different topography and climatic conditions that have ultimately become drivers for vegetation diversification. Due to Ethiopia's connection with the temperate biome in the north and the Arabian Peninsula during the dry glacial period, the biotic assemblage of Ethiopian highlands consists of both Afrotropical and palearctic biota. In general, eight distinct vegetation types have been identified in Ethiopia, based mainly on elevation and climate gradients. These vegetation types host their own unique species, but also share several common species. Some of the vegetation types are identified as centers of endemism and have subsequently been identified globally as the East African Afromontane hotspot. Ethiopia is biologically rich, with more than 6500 vascular plant species. Of these species, 12% are endemic mainly due to geographical isolation and unique climatic conditions. However, researchers have yet to extensively investigate the ecology, phenology, as well as the evolutionary, genetics, and conservation status of Ethiopian vegetations at community and species level over space and time. This lack of research is a barrier to achieving the goal of zero global plant extinctions. Taxa extinction risk assessment has not been extensively carried out for majority of Ethiopian species. Detailed research is needed to explore how vegetation and species respond to rapidly growing environmental change. Currently, human-induced climate change and habitat fragmentation are severely threatening the country's biodiversity, and the consequences of these effects have not been studied at large. Furthermore, we still lack scientific evidence on how micro- and macro-ecological and evolutionary processes have been shaping vegetation structures in this climatically, topographically, and geologically diverse country. These gaps in our knowledge represent an opportunity for ecologists, geneticists, evolutionary biologists, conservation biologists, and other experts to investigate the biodiversity status and the complex ecological processes involved in structuring vegetation dynamics so as to help take effective conservation actions.

Relationship between pulmonary function and albuminuria in type 2 diabetic patients with preserved renal function.

BACKGROUND: Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN. METHODS: A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients' general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function. RESULTS: The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred < 80, FEV1%pred < 80, and DLCOc%pred < 80 was higher in T2DM subjects than controls (all P < 0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18 ± 13.45, 93.95 ± 14.51, 90.64 ± 9.97, 87.27 ± 13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94 ± 14.12, 99.20 ± 14.25, 93.79 ± 10.36, 92.62 ± 13.45, all P < 0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r = - 0.143, P = 0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944-0.988), FEV1%pred (OR 0.975, 95%CI 0.954-0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951-0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG. CONCLUSION: Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.

Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation.

Hair cell stereocilia tip-links function to sense mechanical forces generated by sound waves and maintain the structure of stereocilia by rooting the tail of cadherins to highly dense structures known as tip-link densities. Although the molecular components are largely known, the mechanisms underlying the tip-link density formation are unknown. Here, we show that Myosin VIIB (MYO7B), USH1C, and ANKS4B, which form a specific complex stabilizing tip-links in intestine microvilli, could form dense condensates via liquid-liquid phase separation in vitro and in cells. The MYO7A, USH1C, and USH1G complex also undergoes phase separation in cells. Formation of the MYO7A/USH1C/USH1G and MYO7B/USH1C/ANKS4B condensates requires strong and multivalent interactions between proteins in both tripartite complexes. Point mutations of MYO7A found in Usher syndrome patients weaken or even disrupt the multivalent interactions of the MYO7A/USH1C/USH1G complex and impair its phase separation. Thus, the stereocilia tip-link densities may form via phase separation of the MYO7A/USH1C/USH1G complex.

The Comparison of Different Obesity Indexes and the Risk of Lung Cancer: A Meta-Analysis of Prospective Cohort Studies.

To evaluate the relationship between obesity, analyzed by different indicators, and lung cancer incidence, literature search was conducted in the PubMed, Web of Science, EBSCO, Ovid, and China National Knowledge Infrastructure databases for articles published until December 2018. Twenty-eight prospective cohort studies were identified, with 28 784,269 participants and 127,161 lung cancer cases were included in the analysis. The combined relative risks (RRs) with 95% CIs for the highest versus normal category of body mass index (BMI) were RR = 0.77 (95% CI: 0.72-0.82), but the inverse association disappeared for never smokers or small cell carcinoma after stratifying the smoking status or histological cancer types, respectively. Further analysis considered lag time and excluded the effects of preclinical cancer, there is no statistically significant inverse association between BMI and lung cancer risk, RR = 0.89 (95% CI: 0.66-1.19). In contrast, the combined RRs with 95% CIs for the highest versus lowest category of waist circumference (WC) were RR = 1.26 (95% CI: 1.14-1.39). Therefore, due to multiple confounders existed, BMI might not be an appropriate indicator for obesity when study lung cancer risk. The significantly positive relationship between WC and lung cancer risk indicated there might have an etiological connection between central obesity and lung cancer development.

A new phenolic glycoside from the Idesia polycarpa Maxim. leaves.

Phytochemical investigation on the ethyl acetate extract of Idesia polycarpa Maxim. Leaves led to the isolation of four phenolic glycoside isomers (1-4). Compound 2 appeared to be new reported phenolic glycoside, while compound 1 was the first time isolated from the titled species. Their structures were established by IR, UV, HRESI-MS and 1D and 2D NMR spectroscopies analysis and comparison of spectral data with previously reported data. The compounds 3 and 4 showed stronger activity of scavenging the DPPH free radical than the other two compounds, while the compounds 1 and 2 showed a significant activity of scavenging the ABTS free radical. Compounds 2 and 4 exhibited stronger cytotoxicity against HepG2 cell lines compared to compounds 1 and 3. Moreover, compound 3 presented the highest cytotoxicity against MCF cell lines with IC50 value of 37.17 ± 0.26 µg/mL than compounds 1, 2 and 4.

Dietary Cholesterol Intake and Risk of Lung Cancer: A Meta-Analysis.

Multiple epidemiologic studies have evaluated the relationship between dietary cholesterol and lung cancer risk, but the association is controversial and inconclusive. A meta-analysis of case-control studies and cohort studies was conducted to evaluate the relationship between dietary cholesterol intake and lung cancer risk in this study. A relevant literature search up to October 2017 was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Sinomed, and VIP Journal Integration Platform. Ten case-control studies and six cohort studies were included in the meta-analysis, and the risk estimates were pooled using either fixed or random effects models. The case-control studies with a total of 6894 lung cancer cases and 29,736 controls showed that dietary cholesterol intake was positively associated with lung cancer risk (Odds Ratio = 1.70, 95% Confidence Interval: 1.43-2.03). However, there was no evidence of an association between dietary cholesterol intake and risk of lung cancer among the 241,920 participants and 1769 lung cancer cases in the cohort studies (Relative Risk = 1.08, 95% Confidence Interval: 0.94-1.25). Due to inconsistent results from case-control and cohort studies, it is difficult to draw any conclusion regarding the effects of dietary cholesterol intake on lung cancer risk. Carefully designed and well-conducted cohort studies are needed to identify the association between dietary cholesterol and lung cancer risk.

Blood lipids profile and lung cancer risk in a meta-analysis of prospective cohort studies.

BACKGROUND: Emerging evidence has connected lipid metabolism disturbance with lung diseases, but the relationship between blood lipid profile and lung cancer risk is controversial and inconclusive. OBJECTIVE: We conducted a meta-analysis of prospective cohort studies to evaluate the relationship between blood lipids profile and lung cancer incidence. METHODS: Relevant studies were identified by searching PubMed, Cochrane Library, Web of Science, EBSCO, Ovid, CNKI, VIP, and WANGFANG MED through August 2016. Nine prospective cohort studies were included in the meta-analysis, and fixed or random effects model was used to calculate pooled relative risk (RRs). The RR was calculated using either highest vs lowest categories, or upper quantile vs lowest quantile. The thresholds were determined by the authors of each original publication, based on either predefined cut-offs or the distributions within their study population. RESULTS: Analysis of 18,111 lung cancer cases among 1,832,880 participants showed that serum total cholesterol levels were inverse associated with lung cancer risk (RR = 0.93, 95% confidence interval [CI]: 0.85-1.03). Further analysis considered the lag time and excluded the effects of preclinical cancer, with totally 1,239,948 participants and 14,052 lung cancer cases, found a significantly inverse association between total cholesterol and lung cancer risk (RR = 0.89, 95% CI: 0.83-0.94). Analysis of 3067 lung cancer cases among 59,242 participants found that the high-density lipoprotein cholesterol levels (RR = 0.76, 95% CI: 0.59-0.97) was negatively associated with lung cancer risk and 4673 lung cancer cases among 685,852 participants showed that the total triglyceride (RR = 1.68, 95% CI: 1.44-1.96) was positively associated with lung cancer risk. CONCLUSION: Cholesterol and fatty acid metabolism might present different and specific mechanism on lung cancer etiology and needs further elucidation.

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins.

Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.