Morus alba L. Leaves - Integration of Their Transcriptome and Metabolomics Dataset: Investigating Potential Genes Involved in Flavonoid Biosynthesis at Different Harvest Times.

The mulberry leaf is a classic herb commonly used in traditional Chinese medicine. It has also been used as animal feed for livestock and its fruits have been made into a variety of food products. Traditionally, mulberry (Morus alba L.) leaf harvesting after frost is thought to have better medicinal properties, but the underlying mechanism remains largely unsolved. To elucidate the biological basis of mulberry leaves after frost, we first explored the content changes of various compounds in mulberry leaves at different harvest times. Significant enrichment of flavonoids was observed with a total of 224 differential metabolites after frost. Subsequently, we analyzed the transcriptomic data of mulberry leaves collected at different harvest times and successfully annotated 22,939 unigenes containing 1,695 new genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 26, 20, and 59 unigenes related to flavonoids synthesis in three different groups harvested at different times. We found that the expression levels of flavonoid biosynthesis-related unigenes also increased when harvested at a delayed time, which was consistent with the flavonoid accumulation discovered by the metabolomic analysis. The results indicated that low temperature may be a key trigger in flavonoid biosynthesis of mulberry leaves by increasing the expression of flavonoid biosynthesis-related genes. This study also provided a theoretical basis for the optimal harvest time of mulberry leaves.

[Research Advances in Structural Characteristics,Identification Methods,and Functions of Telocytes].

Telocytes are novel interstitial cells with a specific structure:the body has an elliptical shape or a triangle shape,with slender and thin protrusions that connect with other cells to form a complex 3D network.This article summarizes the structural characteristics and identification Methods of Telocytes and demonstrates their potential functions as a new target for disease prevention and treatment.

Effectiveness of surgical resection for complicated liver cancer and its influencing factors: A retrospective study.

BACKGROUND: Surgical resection is the preferred method for patients with complex liver cancer. But the tumor is in a special position, the surgery is highly risky, postoperative complications can easily occur, and the prognosis is not ideal. AIM: To investigate the effectiveness of surgical resection for complex liver cancer and its influencing factors. METHODS: Fifty-seven patients who had complicated liver cancer and underwent surgical resection at our hospital from August 2015 to August 2016 were enrolled in this study. All patients were followed for three years, and their postoperative complications, survival, and factors that impacted their survival were analyzed. RESULTS: The total incidence of postoperative complications was 45.61%, and the incidence of pleural effusion was the highest at 28.07%. There were no correlations between the 2-year and 3-year survival rates and sex, age, and HbsAg of the patients (P > 0.05). In terms of pathological parameters, the 2-year and 3-year survival rates were significantly different according to the presence of a tumor capsule, degree of liver cirrhosis, satellite or focal lesions, hepatic vein thrombosis, portal vein tumor thrombus, and intraoperative blood loss (P < 0.05). CONCLUSION: The effectiveness of surgical resection for complex hepatocellular carcinoma may be affected by factors such as the presence of a tumor capsule, cirrhosis degree, satellite or focal lesions, hepatic vein embolization, portal vein tumor thrombus, and intraoperative blood loss. Therefore, these factors should be controlled and prevented during surgery to help improve patient survival after surgery.

[Distribution of Telocytes in Vital Organs of ApoE -/- Mice].

Objective To identify and verify the distribution of Telocytes derived from heterogeneous interstitial cells in the vital organs of ApoE -/- mice.Methods Heart,kidney,and liver tissues were harvested from ApoE -/- adult mice. Immunohistochemical assays were performed by using different immunobiological markers.Results Telocytes were found in these vital organs. The expressions of immunobiological markers differed among different organs. CD34,CD117,and CD28 were positively expressed in Telocytes in cardiac tissue;CD117 and plateled-derived growth factor-Α were negatively expressed in Telocytes in renal tissue;and CD117 and plateled-derived growth factor receptor-Α had negative expression in Telocytes in hepatic tissue. Furthermore,the distribution of Telocytes also differed in the same organ.Conclusions Telocytes exist in the vital organs of ApoE -/- mice,as demonstrated by immunohistochemisty assay. The expressions of immunobiological markers differ among Telocytes in different organs.

Corrigendum: High-rate aluminium yolk-shell nanoparticle anode for Li-ion battery with long cycle life and ultrahigh capacity.

This corrects the article DOI: 10.1038/ncomms8872.

High-rate aluminium yolk-shell nanoparticle anode for Li-ion battery with long cycle life and ultrahigh capacity.

Alloy-type anodes such as silicon and tin are gaining popularity in rechargeable Li-ion batteries, but their rate/cycling capabilities should be improved. Here by making yolk-shell nanocomposite of aluminium core (30 nm in diameter) and TiO2 shell (∼3 nm in thickness), with a tunable interspace, we achieve 10 C charge/discharge rate with reversible capacity exceeding 650 mAh g(-1) after 500 cycles, with a 3 mg cm(-2) loading. At 1 C, the capacity is approximately 1,200 mAh g(-1) after 500 cycles. Our one-pot synthesis route is simple and industrially scalable. This result may reverse the lagging status of aluminium among high-theoretical-capacity anodes.

A metal switch for controlling the activity of molecular motor proteins.

Kinesins are molecular motors that require a divalent metal ion (for example, Mg(2+)) to convert the energy of ATP hydrolysis into directed force production along microtubules. Here we present the crystal structure of a recombinant kinesin motor domain bound to Mn(2+) and ADP and report on a serine-to-cysteine substitution in the switch 1 motif of kinesin that allows its ATP hydrolysis activity to be controlled by adjusting the ratio of Mn(2+) to Mg(2+). This mutant kinesin binds ATP similarly in the presence of either metal ion, but its ATP hydrolysis activity is greatly diminished in the presence of Mg(2+). In human kinesin-1 and kinesin-5 as well as Drosophila melanogaster kinesin-10 and kinesin-14, this defect is rescued by Mn(2+), providing a way to control both the enzymatic activity and force-generating ability of these nanomachines.

Long-term effects of Xuezhikang on blood pressure in hypertensive patients with previous myocardial infarction: data from the Chinese Coronary Secondary Prevention Study (CCSPS).

Several previous trials from Western population studies have showed that statins may help reduce blood pressure (BP). However, randomized clinical data is limited. Xuezhikang, a partially extract of red yeast rice, contains a family of naturally occurring statins, and has a marked impact on lipids, but it is unknown whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese population. This is a post-hoc subgroup analysis of a randomized, double-blinded, placebo-controlled, parallel group clinical trial, Chinese Coronary Secondary Prevention Study (CCSPS). A total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (n = 1363) daily for an average of 4.5 years. The primary outcome was the unadjusted changes in mean arterial pressure (MAP) from baseline to 6 months. We also assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. Analysis of covariance was used to calculate the adjusted effects of treatment on changes in these outcomes at 6, 12, 24, and 48 months post-randomization, after controlling for potential confounders. This analysis included 2704/4870 (55.5%) hypertensive patients for whom BP was measured at baseline and at least one follow-up visit after randomization. Median duration of the follow-up was 4.5 years (54 months), and 25 patients (0.92%) were lost to the last follow-up because of adverse effects. The results showed that the unadjusted and adjusted changes in MAP, SBP, DBP, or pulse pressure from baseline were not significantly different for Xuezhikang or placebo recipients at 6, 12, 24, and 48 months after randomization. In this post-hoc subgroup analysis, we failed to demonstrate any significant reducing effects of Xuezhikang on BP in Chinese hypertensive patients with previous MI, suggesting that further prospective study on the effects of statins on BP would be needed, especially in high-risk patients.

Modulation of the kinesin ATPase cycle by neck linker docking and microtubule binding.

Kinesin motor proteins use an ATP hydrolysis cycle to perform various functions in eukaryotic cells. Many questions remain about how the kinesin mechanochemical ATPase cycle is fine-tuned for specific work outputs. In this study, we use isothermal titration calorimetry and stopped-flow fluorometry to determine and analyze the thermodynamics of the human kinesin-5 (Eg5/KSP) ATPase cycle. In the absence of microtubules, the binding interactions of kinesin-5 with both ADP product and ATP substrate involve significant enthalpic gains coupled to smaller entropic penalties. However, when the wild-type enzyme is titrated with a non-hydrolyzable ATP analog or the enzyme is mutated such that it is able to bind but not hydrolyze ATP, substrate binding is 10-fold weaker than ADP binding because of a greater entropic penalty due to the structural rearrangements of switch 1, switch 2, and loop L5 on ATP binding. We propose that these rearrangements are reversed upon ATP hydrolysis and phosphate release. In addition, experiments on a truncated kinesin-5 construct reveal that upon nucleotide binding, both the N-terminal cover strand and the neck linker interact to modulate kinesin-5 nucleotide affinity. Moreover, interactions with microtubules significantly weaken the affinity of kinesin-5 for ADP without altering the affinity of the enzyme for ATP in the absence of ATP hydrolysis. Together, these results define the energy landscape of a kinesin ATPase cycle in the absence and presence of microtubules and shed light on the role of molecular motor mechanochemistry in cellular microtubule dynamics.

Impact of Xuezhikang on coronary events in hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS).

BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk for cardiovascular disease improves clinical outcome. Xuezhikang has a marked impact on lipids. METHODS: In this randomized, double-blinded, placebo-controlled, parallel-group clinical trial, a total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (0.6 g twice daily, n = 1363) for an average of 4.5 years. The primary end-point was recurrent coronary events; the secondary end-point was all-cause mortality and other clinical events, including adverse effects. RESULTS: There were no differences between the Xuezhikang and placebo group in base-line characteristics. However, Xuezhikang treatment reduced the incidence of coronary events by 43.0% (P = 0.02), deaths from coronary heart disease (CHD) by 30.0% (P < 0.01), and all-cause mortality by 35.8% (P = 0.001). CONCLUSIONS: This study, for the first time, demonstrated that long-term Xuezhikang therapy resulted in significant reduction in cardiovascular events and death in Chinese hypertensive patients with previous MI in a safe manner.

Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS).

Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older. Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract of red yeast rice containing statin, has a marked impact on lipids. The purpose of this study, therefore, was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infarction (MI) enrolled in the Chinese Coronary Secondary Prevention Study. In this randomized trial, 1530 elderly hypertensive patients (> or = 65-years-old) with previous MI were assigned either to placebo (n = 758) or to Xuezhikang (n = 772) daily for an average of 4.5 years. The primary endpoint was recurrent coronary events; the secondary endpoint was all-cause mortality and other clinical events, including adverse effects. There were 68 cases of coronary events (8.8%) detected in the Xuezhikang group and 108 cases (14.3%) in the placebo group (38.2% risk reduction by Xuezhikang therapy). Death from coronary heart disease (CHD) totaled 49 cases in the Xuezhikang group (6.4%) and 68 cases in the placebo group (9.0%), indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2%. Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI. This finding may have an important implication for the treatment of elderly hypertensive patients with CHD.

Effect of xuezhikang on cardiovascular events and mortality in elderly patients with a history of myocardial infarction: a subgroup analysis of elderly subjects from the China Coronary Secondary Prevention Study.

OBJECTIVES: To evaluate whether lipid-lowering therapy with xuezhikang reduces the risk of coronary events and total mortality in patients with coronary heart disease (CHD) aged 65 and older. DESIGN: Subgroup analysis of the China Coronary Secondary Prevention Study, a randomized, double-blind, placebo-controlled, clinical trial. SETTING: Sixty-six hospitals in China. PARTICIPANTS: A total of 1,445 patients, aged 65 to 75, were chosen from 4,780 patients with a history of myocardial infarction. INTERVENTION: The patients were randomized to the xuezhikang (n=735) or the placebo (n=710) group and followed for a mean of 4 years. MEASUREMENTS: The primary endpoint was recurrent coronary events; the secondary endpoint was all-cause mortality and other clinical events, including adverse effects. RESULTS: Elderly patients were at greater risk for coronary events, death from coronary events, all-cause mortality, and malignancies than younger patients. Xuezhikang therapy reduced the incidence of coronary events 36.9% (P=.001), death from coronary heart disease 31.0% (P=.04), all-cause mortality 31.9% (P=.01), stroke 44.1% (P=.04), the need for a percutaneous coronary intervention or coronary artery bypass graft 48.6% (P=.07), and malignancies 51.4% (P=.03). Based on the treatment of elderly patients with xuezhikang for an average of 4 years, the number needed to treat (NNT) to prevent one coronary event, one coronary death, and one mortality due to all causes was estimated to be 18, 33, and 23, respectively. In a like manner, the estimated NNT to prevent one coronary event, one coronary death, and one mortality due to all causes in younger patients was 23, 82, and 51, respectively. There was not a significantly greater number of adverse effects in the xuezhikang group than in the placebo group. CONCLUSION: This is the first study demonstrating that treatment with xuezhikang capsules is safe and effective for the secondary prevention of CHD in older Chinese people.

Xuezhikang, an extract of cholestin, reduces cardiovascular events in type 2 diabetes patients with coronary heart disease: subgroup analysis of patients with type 2 diabetes from China coronary secondary prevention study (CCSPS).

Lipid-lowering therapy has been proven to reduce macrovascular complications of type 2 diabetes. Xuezhikang is an extract of cholestin and has a markedly modulating effect on lipids, but the effect of xuezhikang on reducing coronary events in diabetic patients with coronary heart disease (CHD) is less clear. A total of 591 diabetic patients with CHD were randomized to the xuezhikang group (n=306) and the placebo group (n=285). During the average 4 years of follow-up, there were 28 cases of CHD events (9.2%) in the xuezhikang group and 53 cases (18.6%) in the placebo group. Risk reduction for CHD events was 50.8% (P<0.001) by xuezhikang treatment. Xuezhikang decreased the risk of non-fatal MI by 63.8%, fatal MI by 58.5%, CHD sudden death by 26.9%, and other CHD death by 53.4%. CHD death totaled to 21 cases in the xuezhikang group (6.9%) and 35 cases in the placebo group (12.3%), indicating that xuezhikang significantly decreased the risk of CHD death by 44.1% (P<0.05). Seventy-two patients died from various causes, among which there were 27 patients in the xuezhikang group and 45 patients in the placebo group. The risk for all-cause death was 44.1% lower in the xuezhikang group than in the placebo group (P<0.01). This investigation demonstrates that xuezhikang therapy can be effective on reduction of cardiovascular events in diabetic patients with CHD with a reliable safety.