Research Progress on Helmet Liner Materials and Structural Applications.

As an important part of head protection equipment, research on the material and structural application of helmet liners has always been one of the hotspots in the field of helmets. This paper first discusses common helmet liner materials, including traditional polystyrene, polyethylene, polypropylene, etc., as well as newly emerging anisotropic materials, polymer nanocomposites, etc. Secondly, the design concept of the helmet liner structure is discussed, including the use of a multi-layer structure, the addition of geometric irregular bubbles to enhance the energy absorption effect, and the introduction of new manufacturing processes, such as additive manufacturing technology, to realize the preparation of complex structures. Then, the application of biomimetic structures to helmet liner design is analyzed, such as the design of helmet liner structures with more energy absorption properties based on biological tissue structures. On this basis, we propose extending the concept of bionic structural design to the fusion of plant stalks and animal skeletal structures, and combining additive manufacturing technology to significantly reduce energy loss during elastic yield energy absorption, thus developing a reusable helmet that provides a research direction for future helmet liner materials and structural applications.

Broadening the catalytic region from the cavity to windows by M6L12 nanospheres in cyclizations.

Supramolecular cages have received tremendous attention as they can contain catalysts that exhibit confinement effects in the cavity, leading to excellent performances. Herein, we report an example wherein the catalytic region is extended from the cage cavity to the windows, and investigate its confinement effect by utilizing the Pd6LAu12 cage that contains rigidly fixed and isolated gold complexes at the windows. Pd6LAu12 exhibit three features of particular interest while assessing their properties in gold-catalyzed cyclization reactions. First, the catalysts experience a cage effect as they display higher reactivity and selectivity compared to the monomeric analogue, as a result of substrate pre-organization at the windows. Second, the metal complexes are physically separated by the cage structure, preventing the formation of less active dinuclear gold complexes making it more stable under hydrous conditions. Third, the cage windows present the characteristics of enzymatic catalysis via Michaelis-Menten-type mechanism analysis. This contribution presents an alternative way to engineer supramolecular catalysts through extending the catalytic region.

Evaluation of Atherosclerotic Cardiovascular Risk Prediction Models in China: Results From the CHERRY Study.

Background: Updated American or Chinese guidelines recommended calculating atherosclerotic cardiovascular disease (ASCVD) risk using the Pooled Cohort Equations (PCE) or Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) models; however, evidence on performance of both models in Asian populations is limited. Objectives: The authors aimed to evaluate the accuracy of the PCE or China-PAR models in a Chinese contemporary cohort. Methods: Data were extracted from the CHERRY (CHinese Electronic health Records Research in Yinzhou) study. Participants aged 40 to 79 years without prior ASCVD at baseline from 2010 to 2016 were included. ASCVD was defined as nonfatal or fatal stroke, nonfatal myocardial infarction, and cardiovascular death. Models were assessed for discrimination and calibration. Results: Among 226,406 participants, 5362 (2.37%) adults developed a first ASCVD event during a median of 4.60 years of follow-up. Both models had good discrimination: C-statistics in men were 0.763 (95% confidence interval [CI]: 0.754-0.773) for PCE and 0.758 (95% CI: 0.749-0.767) for China-PAR; C-statistics in women were 0.820 (95% CI: 0.812-0.829) for PCE and 0.811 (95% CI: 0.802-0.819) for China-PAR. The China-PAR model underpredicted risk by 20% in men and by 40% in women, especially in the highest-risk groups. However, PCE overestimated by 63% in men and inversely underestimated the risk by 34% in women with poor calibration (both P < 0.001). After recalibration, observed and predicted risks by recalibrated PCE were better aligned. Conclusions: In this large-scale population-based study, both PCE and China-PAR had good discrimination in 5-year ASCVD risk prediction. China-PAR outperformed PCE in calibration, whereas recalibration equalized the performance of PCE and China-PAR. Further specific models are needed to improve accuracy in the highest-risk groups.

The combination of R2R3-MYB gene AmRosea1 and hairy root culture is a useful tool for rapidly induction and production of anthocyanins in Antirrhinum majus L.

Anthocyanins are the largest group of water-soluble pigments and beneficial for human health. Although most plants roots have the potential to express natural biosynthesis pathways required to produce specialized metabolites such as anthocyanins, the anthocyanin synthesis is specifically silenced in roots. To explore the molecular mechanism of absence and production ability of anthocyanin in the roots, investigated the effect of a bHLH gene AmDelila, and an R2R3-MYB gene AmRosea1, which are the master regulators of anthocyanin biosynthesis in Antirrhinum majus flowers, by expressing these genes in transformed hairy roots of A. majus. Co-ectopic expression of both AmDelila and AmRosea1 significantly upregulated the expression of the key target structural genes in the anthocyanin biosynthesis pathway. Furthermore, this resulted in strongly enhanced anthocyanin accumulation in transformed hairy roots. Ectopic expression of AmDelila alone did not gives rise to any significant anthocyanin accumulation, however, ectopic expression of AmRosea1 alone clearly upregulated expression of the main structural genes as well as greatly promoted anthocyanin accumulation in transformed hairy roots, where the contents reached 0.773-2.064 mg/g fresh weight. These results suggest that AmRosea1 plays a key role in the regulatory network in controlling the initiation of anthocyanin biosynthesis in roots, and the combination of AmRosea1 and hairy root culture is a powerful tool to study and production of anthocyanins in the roots of A. majus.

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records.

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.

Lighting up metallohelices: from DNA binders to chemotherapy and photodynamic therapy.

The design of novel agents that specifically target DNA and interrupt its normal biological processes is an attractive goal in drug design. Among the promising metallodrugs, metal-directed self-assembled metallohelices with defined three-dimensional stereochemical structures display unique structure-inherent and unprecedented noncovalent targeting abilities towards DNA, resulting in excellent anticancer or antibiotic activities. A newly burgeoning hotspot is focusing on lighting them up by embedding luminescent metal ions as the vertices. The photoactive metallohelices that combine strong interactions toward DNA targets and efficient 1O2 quantum yield may provide new motivation in diagnostic and photodynamic therapy (PDT) areas. This perspective focuses on research progress on metallohelices as DNA binders and chemotherapeutic agents, and highlights recent advances in fabricating luminescent examples for PDT. The relative assembly strategies are also discussed and compared. Finally, perspectives on the future development of the lit-up metallohelices are presented.

Mitochondrial-DNA-Targeted IrIII -Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells.

The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear IrIII -containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd-even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting IrIII -containing metallohelices as PDT agents.

Multimorbidity of cardiometabolic diseases: prevalence and risk for mortality from one million Chinese adults in a longitudinal cohort study.

OBJECTIVES: The evolution of multimorbidity describes the continuum from a healthy status to the development of a single disease and further progression to multimorbidity with additional diseases. We investigated the evolution of cardiometabolic multimorbidity and risk for mortality in a Chinese population. DESIGN: Longitudinal cohort study using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study, with 5.43 million person-years follow-up (median 5.16 years). PARTICIPANTS: Data for 1 038 704 adults (total 22 750 deaths) were analysed. EXPOSURE: Cardiometabolic multimorbidity was defined as ever being diagnosed with two or more of three diseases: hypertension, diabetes and cardiovascular disease (CVD). PRIMARY AND SECONDARY OUTCOME MEASURES: Age-adjusted and sex-adjusted HRs were calculated for all-cause mortality. RESULTS: The cardiometabolic disease status of 105 209 (10.1%) individuals changed during the follow-up. The prevalence of cardiometabolic multimorbidity increased from 2.41% (95% CI: 2.38% to 2.44%) to 5.94% (95% CI: 5.90% to 5.99%). Baseline multimorbidity status showed the HR (95% CI) was 1.37 (1.33 to 1.42) in those with one disease, 1.71 (1.64 to 1.79) in those with two diseases and 2.22 (2.00 to 2.46) in those with three diseases. The highest HRs were observed for CVD only (3.31, 95% CI: 3.05 to 3.59) or diabetes and CVD (3.12, 95% CI: 2.37 to 4.11). Those with hypertension only had the lowest HR (1.26, 95% CI: 1.22 to 1.30). Longitudinal data showed the HRs (95% CI) in patients with one, two and three diseases were 1.36 (1.32 to 1.41), 2.03 (1.96 to 2.10) and 2.16 (2.05 to 2.29), respectively. CONCLUSIONS: The prevalence of cardiometabolic multimorbidity in a general Chinese population increased more than doubled over 5 years, indicating rapid evolution of cardiometabolic multimorbidity. A history of CVD dominates the risk for mortality. A complementary strategy for primary and secondary prevention of cardiometabolic diseases is needed in China.

Asymmetric Catalysis within the Chiral Confined Space of Metal-Organic Architectures.

The effective synthesis of chiral compounds in a highly enantioselective manner is obviously attractive. Inspired by the enzymatic reactions that occur in pocket-like cavities with high efficiency and specificity, chemists are seeking to construct catalysts that mimic this key feature of enzymes. Recent progress in supramolecular coordination chemistry has shown that metal-organic cages (MOCs) and metal-organic frameworks (MOFs) with chiral confined cavities/pores may offer a novel platform for achieving asymmetric catalysis with high enantioselectivity. The inherent chiral confined microenvironment is considered to be analogous to the binding pocket of enzymes, and this pocket promotes enantioselective transformations. This work focuses on the recent advances in MOCs and MOFs with chiral confined spaces for asymmetric catalysis, and each section is separated into two parts based on how the chirality is achieved in these metal-organic architectures. A special emphasis is placed on discussing the relationship between the enantioselectivity and the confined spaces of the chiral functional MOCs and MOFs rather than catalytic chemistry. Finally, current challenges and perspectives are discussed. This work is anticipated to offer researchers insights into the design of sophisticated chiral confined space-based metal-organic architectures for asymmetric catalysis with high enantioselectivity.

Using big data to improve cardiovascular care and outcomes in China: a protocol for the CHinese Electronic health Records Research in Yinzhou (CHERRY) Study.

INTRODUCTION: Data based on electronic health records (EHRs) are rich with individual-level longitudinal measurement information and are becoming an increasingly common data source for clinical risk prediction worldwide. However, few EHR-based cohort studies are available in China. Harnessing EHRs for research requires a full understanding of data linkages, management, and data quality in large data sets, which presents unique analytical opportunities and challenges. The purpose of this study is to provide a framework to establish a uniquely integrated EHR database in China for scientific research. METHODS AND ANALYSIS: The CHinese Electronic health Records Research in Yinzhou (CHERRY) Study will extract individual participant data within the regional health information system of an eastern coastal area of China to establish a longitudinal population-based ambispective cohort study for cardiovascular care and outcomes research. A total of 1 053 565 Chinese adults aged over 18 years were registered in the health information system in 2009, and there were 23 394 deaths from 1 January 2009 to 31 December 2015. The study will include information from multiple epidemiological surveys; EHRs for chronic disease management; and health administrative, clinical, laboratory, drug and electronic medical record (EMR) databases. Follow-up of fatal and non-fatal clinical events is achieved through records linkage to the regional system of disease surveillance, chronic disease management and EMRs (based on diagnostic codes from the International Classification of Diseases, tenth revision). The CHERRY Study will provide a unique platform and serve as a valuable big data resource for cardiovascular risk prediction and population management, for primary and secondary prevention of cardiovascular events in China. ETHICS AND DISSEMINATION: The CHERRY Study was approved by the Peking University Institutional Review Board (IRB00001052-16011) in April 2016. Results of the study will be disseminated through published journal articles, conferences and seminar presentations, and on the study website (http://www.cherry-study.org).

Engineering an iridium-containing metal-organic molecular capsule for induced-fit geometrical conversion and dual catalysis.

By introducing photoactive fac-tris(2-phenylpyridine)iridium moieties as a ligand backbone to constrain the coordination geometry of cobalt ions, a multifunctional Ir2Co3-type capsule was achieved and showed induced-fit capsule-capsule conversion by cooperative binding one carbonate anion with the equatorial Co(ii) centers. The capsule combined photocatalysis and transition metal activation synergistically and exhibited efficient catalytic ability on visible light-activated α-trichloromethylation.

Multicomponent self-assembly of a pentanuclear Ir-Zn heterometal-organic polyhedron for carbon dioxide fixation and sulfite sequestration.

By incorporating a fac-tris(4-(2-pyridinyl)phenylamine)iridium as the backbone of the tripodal ligand to constrain the coordination geometry of Zn(II) ions, a pentanuclear Ir-Zn heterometal-organic luminescent polyhedron was obtained via a subcomponent self-assembly for carbon dioxide fixation and sulfite sequestration.

Resveratrol attenuates the progress of liver fibrosis via the Akt/nuclear factor-κB pathways.

Liver fibrosis is a wound-healing response to chronic liver injury that results in the accumulation of extracellular matrix proteins. It eventually leads to cirrhosis of the liver and liver failure, and it is a critical threat to the health and lives of patients with chronic liver diseases. No effective treatment is currently available. Resveratrol is a polyphenol with antioxidant, anti­cancer and anti­inflammatory properties. It has been reported that resveratrol prevents liver fibrosis, possibly by inhibiting NF­κB activation. The present study investigated the mechanisms by which resveratrol prevented liver fibrosis, focusing on the possible involvement of the NF­κB pathway. Mice with carbon tetrachloride (CCl4)­induced liver fibrosis were treated with various concentrations of resveratrol. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor (TNF)­α were detected by ELISAs. Expression of α­smooth muscle actin (α­SMA), collagen I, inhibitor of NF­κB (IκB) and NF­κB were detected by western blot analysis. In addition, the present study examined the effects of resveratrol on the expression of fibrosis markers in LX­2 cells. Western blot analysis was further used to detect the levels of Akt and phosphorylated Akt, as well as the nuclear levels of IκB, phosphorylated IκB and NF­κB p65. The expression of α­SMA in resveratrol­treated LX­2 cells was detected by immunofluorescence and flow cytometry, which demonstrated that resveratrol decreased the expression of α­SMA in LX­2 cells. Resveratrol also decreased CCl4­induced upregulation of serum AST, ALT, TNF­α, α­SMA and collagen I. Finally, resveratrol prevented the activation of NF­κB and Akt. The results of the present study therefore indicated that resveratrol attenuates liver fibrosis via the Akt/NF-κB pathways.

Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: a phase II trial.

BACKGROUND: This study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB). MATERIAL AND METHODS: A phase II trial was performed in 158 patients with pulmonary TB (145 initially-treated and 13 re-treated) and 133 healthy subjects. Skin testing was carried out by injecting purified protein derivative (PPD) (on left forearm) or recombinant ESAT-6 protein at a dosage of 2, 5, or 10 µg/mL (on the right forearm) in each subject. Reaction activity and adverse events were monitored at 24, 48, and 72 h following the injection. Receiver operating characteristic curves were plotted to determine the areas under the curves (AUCs) and the cut-off induration diameters for the optimal diagnostic performance. RESULTS: The reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects. In pulmonary TB patients, the reaction was dose-dependent, and at 48 h, 10 µg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD. The AUCs for a 10 µg/mL dosage were 0.9823, 0.9552, and 0.9266 for 24 h, 48 h, and 72 h, respectively, and the induration diameters of 4.5-5.5 mm were the optimal trade-off values between true positive rates and false positive rates. No serious adverse events occurred in any subjects. CONCLUSIONS: Recombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB. Based on the reaction, performance, safety, and practicability, we recommend that 10 µg/mL at 48 h with an induration cut-off value of 5.0 mm be used.

Targeting transforming growth factor ßRII expression inhibits the activation of hepatic stellate cells and reduces collagen synthesis.

Abnormal production of extracellular matrix (ECM) components significantly contributes to the development of liver fibrosis. This study aimed at examining the effects of short-hairpin RNA (shRNA)-mediated transient knockdown of transforming growth factor ßRII (TGFßRII) expression on the proliferation and activation of hepatic stellate cells (HSCs) and synthesis of fibrogenic ECM components in HSC cells. Three different shRNA-expressing plasmids were constructed for the expression of shRNA-(a, b, c) targeting to the rat TGFßRII mRNA beginning at nucleotide position 339, 444 and 528 and they were transfected into a rat stellate cell line, HSC-T6 cells, respectively. The levels of TGFßRII, α-smooth muscle actin (α-SMA), and type I and III collagen expressions were characterized by reverse transcription polymerase chain reaction and Western blot assays. The concentrations of hyaluronic acid (HA) and type IV collagen in the supernatants of cultured cells were measured by enzyme-linked immunosorbent assay. Transfection with the TGFßRII-specific shRNAs resulted in varying levels of inhibition in the expression of TGFßRII in HSC-T6 cells, and transfection with the potent shRNA-c inhibited the expression of TGFßRII in a dose-dependent manner. Knockdown of TGFßRII expression significantly reduced the levels of α-SMA, type I, III and IV collagen, and HA expression in HSC-T6 cells (P < 0.01). In conclusion, our data indicated that knockdown of TGFßRII expression inhibited the activation of HSCs and the production of fibrogenic ECM components in HSC-T6 cells. Therefore, our findings support the notion that TGFßRII is an important factor of the pathogenic process of liver fibrosis.

Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L-methionine in treatment of pregnant woman with chronic hepatitis B: a pilot study.

BACKGROUND: There have been no studies evaluating the efficacy and potential risks of stronger neo-minophagen C (SNMC) in pregnant women with chronic hepatitis B CHB. MATERIAL/METHODS: A total of 36 pregnant women with CHB, but without severe complications, were randomized to intravenously receive SNMC or S-adenosyl-L-methionine (SAM) daily for 4 weeks or until birth. Normalization of serum alanine transaminase (ALT) and aspartate transaminase (AST) levels and changes in ALT and AST levels from baseline were determined. All neonates were regularly examined for up to 1 year. RESULTS: Treatment with SNMC and SAM resulted in normalization of ALT levels at 4 weeks in 64.3% and 21.4% of patients, respectively (OR=6.60, 95% CI: 1.23-35.44, P=0.0540). SNMC and SAM significantly decreased ALT (from 558.28+/-390.24 to 47.07+/-24.94 IU/L, P<0.0001 and from 525.61+/-483.87 to 117.43+/-85.44 IU/L, P=0.0041, respectively) and AST (from 419.72+/-409.49 to 38.14+/-18.87 IU/L, P=0.0016, and from 510.78+/-621.58 to 79.93+/-63.25 IU/L, P=0.0152, respectively) at 4 weeks relative to baseline values. Hypokalemia was observed in 4 SNMC-treated patients and in 2 SAM-treated patients and hypernatremia in 3 SNMC-treated and in 3 SAM-treated patients. Hypertension was observed in 1 SNMC-treated patient. There was no significant difference in the volume of amniotic fluid or meconium between SNMC-treated and SAM-treated groups. All the neonates were physically normal at birth and at the 1-year follow-up examination. CONCLUSIONS: Both SNMC and SAM improve liver function, with SNMC appearing more effective, in pregnant women with chronic hepatitis B without impact on fetal development.

Multifocal skeletal tuberculosis: experience in diagnosis and treatment.

OBJECTIVES: Multifocal skeletal tuberculosis (MSTB) is an uncommon presentation of skeletal tuberculosis. In order to provide more clinically meaningful information on the diagnosis and management of MSTB, we present a case of MSTB with multiple tuberculous lesions in multiple locations, along with a review of 13 MSTB cases from different studies. PATIENTS AND METHODS: A 29-year-old male patient with a one-year history of back pain was initially diagnosed with ankylosing spondylitis and arthritis deformans, and received treatment with oral glucocorticosteroid and leflunomide for 24 weeks. The back pain worsened with weight loss and fever one month prior to admission to our hospital. The diagnosis, MSTB, with 26 tuberculous lesions in 19 locations, was made by clinical findings, bone scan (computed topography and Tc-99m HDP scintigraphy), and bone marrow smear. RESULT: Multiple antituberculous drugs, with supportive and immune-enhancing therapies cured the patient. CONCLUSIONS: This case indicates that MSTB may develop in patients on long-term immunosuppressive drugs. In addition, our experience, along with previously reported data, suggest that strong clinical suspicion is required for an early diagnosis of MSTB, and chemotherapy, combined with supportive and immune-based therapies is effective for the treatment of MSTB.