A CTL - Lys immune function maintains insect metamorphosis by preventing gut bacterial dysbiosis and limiting opportunistic infections.

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.

Ophthalmic Artery Morphology and Hemodynamics Associated with White Matter Hyperintensity.

Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.

Modulation of fried spring roll wrapper quality upon treatment of batter with maltogenic amylase, transglutaminase and bromelain.

BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Impact of total cerebral small vessel disease score on ophthalmic artery morphologies and hemodynamics.

BACKGROUND: Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score. METHODS: This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations. RESULTS: The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (ß = - 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001). CONCLUSIONS: The decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA.

Design of Cu-Substituted O3-Type NaFe0.5 Mn0.5 O2 Cathode Materials for Sodium-Ion Batteries.

O3-type Fe/Mn-based layered oxide cathode materials with abundant reserves have a promising prospect in sodium-ion batteries. However, the electrochemical reversibility of most O3-type Fe/Mn-based oxide cathode materials is still not high enough. Herein, the effect of different Cu contents on the electrochemical properties of O3-NaFe0.50 Mn0.50 O2 materials is systematically investigated. The as-prepared NaFe0.30 Mn0.50 Cu0.20 O2 cathode achieves the synergistic optimization of the interface and bulk phase. It shows superior electrochemical performance, with an initial discharge specific capacity of 114 mAh g-1 at 0.1 C, a capacity retention rate of 94 % after 100 cycles at 0.5 C, and excellent chemical stability in air and water. In addition, the sodium ion full battery based on NaFe0.30 Mn0.50 Cu0.20 O2 cathode and hard carbon anode has a capacity retention rate of 81 % after 100 cycles. This research provides a useful approach for the preparation of low-cost and high-performance O3-type layered cathode materials.

Effects of posterior staphyloma on choroidal structure in myopic adults: a retrospective study.

BACKGROUND: Studies on the choroid of myopic eyes with posterior staphyloma have shown that choroidal thickness decreased. This retrospective study further analysed the effects of posterior scleral staphyloma on choroidal blood vessels and matrix components compared to non-pathological myopia. METHODS: In this cross-sectional study, ninety-one eyes were divided into pathological (posterior staphyloma) and non-pathological myopia. The latter was further divided into three groups (Group 1: 26 mm ≤ axial length; Group 2: 24 mm ≤ axial length < 26 mm; Group 3: 22 mm ≤ axial length < 24 mm). Choroidal thickness, total choroidal area, luminal area, stromal area, and choroidal vascularity index were calculated. RESULTS: The CVI in N1, N2, I1, S2 of the posterior staphyloma group were lower than those of group 1 (both P < 0.05). The mean height of posterior staphyloma was associated with mean CT (Pearson correlation: r = -0.578, P = 0.039) but not with the mean CVI in posterior staphyloma group. In all groups, the mean choroidal thickness, total choroidal area, luminal area, and stromal area were significantly associated with axial length (P < 0.001), and the mean choroidal vascularity index was significantly associated with the mean choroidal thickness (P < 0.001). CONCLUSION: The choroidal structure of pathological myopia with posterior staphyloma and non-pathological myopia with longer axial length demonstrates alterations in which choroidal vessels are more impaired than the stroma. A lower choroidal vascularity index should be alert to pathological changes for myopia with axial length > 26 mm.

Prevalence of motoric cognitive risk syndrome among older adults: a systematic review and meta-analysis.

OBJECTIVE: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome. Several studies on the prevalence of MCR have been published; however, the data vary across studies with different epidemiological characteristics. Thus, this study aimed to quantitatively analyse the overall prevalence and associated epidemiological characteristics of MCR among older adults aged ≥ 60 years. METHODS: The Cochrane Library, PubMed, Web of Science, CINAHL, Embase, Scopus, PsycInfo, China National Knowledge Infrastructure, Weipu Database, China Biology Medicine disc and Wanfang Database were searched from their inception to January 2022. A modified Newcastle-Ottawa Scale evaluated the risk of bias. Statistical heterogeneity among the included studies was analysed using Cochran's Q and I2 tests. A random effect model calculated pooled prevalence owing to study heterogeneity. Begg's and Egger's tests were used to assess the publication bias. Additionally, subgroup analysis and meta-regression were performed based on different epidemiological characteristics to determine heterogeneity sources. RESULTS: Sixty-two studies comprising 187,558 samples were obtained. The pooled MCR prevalence was 9.0% (95% confidence interval: 8.3-9.8). A higher MCR prevalence was observed in females, older adults with a low educational level, depression and cardiovascular risk factors, South American populations, and studies with small sample sizes and cross-section designs. Furthermore, subjective cognitive complaint using scale score and gait speed using instrument gait showed higher MCR prevalence. CONCLUSION: MCR is common in older adults, and various epidemiological characteristics influence its prevalence. Thus, preventive measures are required for older adults with higher MCR prevalence.

Ophthalmic artery changes in type 2 diabetes with and without acute coronary syndrome.

BACKGROUND: Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS). METHODS: In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA. RESULTS: In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters. CONCLUSIONS: This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA.

Changes of retinal structure and function in patients with internal carotid artery stenosis.

BACKGROUND: To investigate the structural and functional changes of the retina in patients with different degrees of internal carotid artery (ICA) stenosis. METHODS: This cross-sectional study included patients with varying degrees ICA stenosis. Clinical characteristics of 41 patients were collected after being divided into four groups according to the ICA stenosis indicated by computed tomographic angiography (Group 0: without ICA stenosis, Group 1: ipsilateral slight ICA stenosis, Group 2: ipsilateral moderate ICA stenosis, Group 3: ipsilateral severe ICA stenosis). Retinal vessel caliber (RVC) was measured quantitatively with the Integrative Vessel Analysis software. The retinal sensitivity was examined with the MP-3 microperimeter. The relationships among central retinal artery equivalent (CRAE), central retinal vein equivalent, arteriole to venule ratio (AVR), mean retinal sensitivity (MS) and ICA stenosis degree were analysed. RESULTS: The CRAE in Group 3 were significantly smaller compared with Group 0, Group 1 and Group 2 (P < 0.001, P < 0.001, P = 0.002). Significant decrease was found between Group 3 with other groups in MS at fovea (P < 0.001, P < 0.001, P = 0.002). Moreover, there was a positive correlation found between MS and CRAE (Beta = 0.60, P < 0.001 at fovea; Beta = 0.64, P < 0.001 at 2 degree; Beta = 0.60, P < 0.001 at 4 degree; Beta = 0.55, P < 0.001 at 8 degree; Beta = 0.53, P < 0.001 at 12 degree). CONCLUSIONS: The present study revealed smaller CRAE and AVR in ipsilateral severe ICA stenosis patients. And the MS decreased in patients with severe ICA stenosis. In addition, MS had a positive correlation with CRAE.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Mechanism of Metarhizium rileyi evading cellular immune responses in Helicoverpa armigera.

Upon entry into the hemocoel of host insects, entomopathogenic fungi switch to yeast-like hyphal bodies that are not recognized by host hemocytes and replicate extensively in the hemolymph. The mechanism by which hyphal bodies evade host cellular immunity is not well understood. This study compares Metarhizium rileyi conidia and hyphal bodies with respect to elicitation of the immune response of Helicoverpa armigera and recognition by host pattern recognition receptors (PRRs). We found that the ability of host hemocytes to phagocytize and nodulate hyphal bodies was weaker than those responses against conidia, suggesting that hyphal bodies are more able to evade host cellular immunity. Additionally, we found that the binding affinity of H. armigera ß-1,3-glucan recognition proteins was much lower for hyphal bodies than for conidia. We observed no agglutination response of H. armigera C-type lectin 3 (HaCTL3) against hyphal bodies, and HaCTL3 bound significantly less to hyphal bodies than to conidia, indicating that host PRRs have a lower affinity for hyphal bodies than for conidia. This study provides direct evidence that the mechanism whereby entomopathogenic fungi escape host cellular immunity involves the inability of host PRRs to sufficiently recognize hyphal bodies to elicit the cellular immune response.

Nicotinamide-induced mouse embryo developmental defect rescued by resveratrol and I-CBP112.

Cell cycle of mouse embryo could be delayed by nicotinamide (NAM). Histone H3 lysine 56 (H3K56ac) acetylation plays an important role in mammalian genomic stability and the function of this modification in mouse embryos is not known. Hence, we designed to study the effects of NAM-induced oxidative stress on the developmental ability of mouse embryos, on the acetylation of H3K56ac and the possible functions of this modification related to mouse embryo development. Treatment with NAM (10, 20, or 40 mmol/L for 24 or 48 hr) during in vitro culture significantly decreased developmental rate of blastocyst (24 hr: 90.2 vs. 81.2, 43.2, and 18.2, with p > .05, p < .01, respectively; 48 hr: 89.3 vs. 53.2%, 12.1%, and 0% with p < .05, respectively). NAM treatment (20 mmol/L) for 6 and 31 hr resulted in increased intracellular reactive oxygen species levels in two-cell embryos, and apoptotic cell numbers in blastocysts. Resveratrol (RSV) and I-CBP112 rescued the 20 mmol/L NAM-induced embryo developmental defects. RSV and I-CBP112 increased the level of Sirt1 and decreased the level of H3K56ac induced by NAM in two-cell embryos (p < .05). These data suggest that NAM treatment decreases the expression of Sirt1, which induces high levels of H3K56 acetylation that may be involved in oxidative stress-induced mouse embryo defects, which can be rescued by RSV and I-CBP112.

TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Microwave-Assisted One-Pot Synthesis of Indole-Based Fluorescent Probe for Sensitive Detection of Copper (II).

In this study, a rapid, inexpensive and convenient microwave assisted synthesis of indole-3-propionic acid-bisphenol A diglycidyl ether (IPA-SR3) fluorescent probe was developed. This fluorescent probe has the dual illumination characteristics of photoinduced electron transfer and aggregation-induced emission for the specific detection of Cu2+ ion in water. The wavelength-dependent photoluminescence behavior of the aggregated IPA-SR3 was highly selective (Ksv = 1.5 × 104 M-1) and sensitive in Cu2+ ion detection, with a low limit of detection (2.9 µM). Therefore, it can be used to detect low-concentration Cu2+ in water samples. Details of the synthesis procedure and fluorescence characteristics are presented herein. Graphical Abstract.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Molecular characterization of immune responses of Helicoverpa armigera to infection with the mermithid nematode Ovomermis sinensis.

BACKGROUND: Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. RESULTS: Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. CONCLUSIONS: This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.

Short-term impact of breast cancer screening intervention on health-related quality of life in China: A multicentre cross-sectional survey.

OBJECTIVE: The impact of participating in breast cancer screening programmes on health-related quality of life (HRQoL)is poorly understood. METHODS: Based on a national breast cancer screening programme in China, a multicentre cross-sectional survey was conducted covering 12 provinces from September 2013 to December 2014. HRQoL of participants in the screening population and general population was evaluated by the three-levelEuroQol-five-Dimensions (EQ-5D-3L) instrument, and utility scores were generated through the Chinese value set. Univariate and multivariate regression analyses were performed to explore determinants of utility scores and anxiety/depression problems. RESULTS: For screening group and general population (n = 4756, mean age = 51.6 year old), the corresponding utility scores were 0.937 (95% CI, 0.933-0.941) and 0.953 (0.949-0.957) (P < .001). Pain/discomfort and anxiety/depression were the most common reported in both groups (51.4% and 34.3%, P < .001). Utility scores at prescreening, in-screening, and postscreening interview timings were 0.928 (0.921-0.935), 0.958 (0.948-0.969), and 0.938 (0.933-0.943), respectively (P < .001); the corresponding proportions of anxiety/depression reporting were 25.9%, 16.3%, and 21.1%, respectively (P = .004). Interview timing, geographical region, and insurance status were associated with HRQoL and anxiety/depression in women at high-risk of breast cancer. CONCLUSIONS: Utility scores of screening participants were significantly lower than that of general population in China, but the difference may be clinically insignificant. Further cohort studies using HRQoL measurements are needed.

Juvenile hormone and its receptor methoprene-tolerant promote ribosomal biogenesis and vitellogenesis in the Aedes aegypti mosquito.

Juvenile hormone (JH) controls many biological activities in insects, including development, metamorphosis, and reproduction. In the Aedes aegypti mosquito, a vector of dengue, yellow fever, chikungunya, and zika viruses, the metabolic tissue (the fat body, which is an analogue of the vertebrate liver) produces yolk proteins for developing oocytes. JH is important for the fat body to acquire competence for yolk protein production. However, the molecular mechanisms of how JH promotes mosquito reproduction are not completely understood. In this study we show that stimulation of the JH receptor methoprene-tolerant (Met) activates expression of genes encoding the regulator of ribosome synthesis 1 (RRS1) and six ribosomal proteins (two ribosomal large subunit proteins, two ribosomal small subunit proteins, and two mitochondrial ribosomal proteins). Moreover, RNAi-mediated depletion of RRS1 decreased biosynthesis of the ribosomal protein L32 (RpL32). Depletion of Met, RRS1, or RpL32 led to retardation of ovarian growth and reduced mosquito fecundity, which may at least in part have resulted from decreased vitellogenin protein production in the fat body. In summary, our results indicate that JH is critical for inducing the expression of ribosomal protein genes and demonstrate that RRS1 mediates the JH signal to enhance both ribosomal biogenesis and vitellogenesis.

Enediyne-activated, EGFR-targeted human ß-defensin 1 has therapeutic efficacy against non-small cell lung carcinoma.

Human ß-defensins contain an oncolytic motif that binds to tumor cell membranes and mediate permeabilization, rapid induction of cytolysis, and apoptosis. Previous studies have indicated that a fragment of the mature human ß-defensin-1 (HBD1) peptide (DF) has antitumor properties. While targeted drug treatments using fusion proteins have been shown to increase drug efficacy, this phenomenon has not been studied for this defensin. Thus, in this study, we designed and prepared a fusion protein containing this HBD1 fragment and an epidermal growth factor receptor (EGFR)-targeting oligopeptide (Ec) as well as lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, which consists of an apoprotein (LDP) and a highly active enediyne (AE). The fusion protein (Ec-LDP-DF) and its enediyne-integrated fusion protein (Ec-LDP(AE)-DF) were then purified and used to treat lung carcinoma cells in culture as well as lung carcinoma xenograft mouse models. The multifunctional fusion protein Ec-LDP-DF was shown to effectively bind to EGFR-expressing tumor cells. Furthermore, the enediyne-energized Ec-LDP(AE)-DF analog exhibited extremely potent cytotoxicity in NSCLC cell lines and an IC50 less than 10-10 mol/L. Ec-LDP(AE)-DF also significantly inhibited the growth of human carcinoma A549 and H460 xenografts in athymic mice at well-tolerated doses. Treatment resulted in cell cycle arrest and apoptosis in a dose-dependent manner. EGF-stimulated EGFR phosphorylation was also abolished by Ec-LDP(AE)-DF. In summary, our understanding of the role of defensins in cancer development and progression is continually expanding, and Ec-LDP(AE)-DF is a promising cancer cell-targeting agent for NSCLC.