Association between Hypertrophic Cardiomyopathy and Variations in Sarcomere Gene and Calcium Channel Gene in Adults.

INTRODUCTION: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. METHODS: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. RESULTS: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77-13.2; p = 0.002). CONCLUSION: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations.

Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China.

INTRODUCTION: Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. METHODS: A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. RESULTS: Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32). CONCLUSION: Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.

Prevalence and risk factors for psychotic symptoms in young, first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder worldwide. Psychotic depression has been reported to be frequently under-diagnosed due to poor recognition of psychotic features. Therefore, the purpose of this study was to reveal the rate and risk factors of psychotic symptoms in young, drug-naïve patients with major depressive disorder at the time of their first episode. METHODS: A total of 917 patients were recruited and divided into psychotic and non-psychotic subgroups based on the Positive and Negative Syndrome Scale (PANSS) positive subscale score. Anxiety symptoms and depressive symptoms were measured by the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17), respectively. Several biochemical indicators such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were also measured. RESULTS: The rate of psychotic symptoms among young adult MDD patients was 9.1%. There were significant differences in TSH (p<0.001), FBG (p<0.001), TC (p<0.0001), TG (p = 0.001), HDL-C (p = 0.049), LDL-C (p = 0.010), diastolic blood pressure (DP) (p<0.001), systolic blood pressure (SP) (p<0.001), and HAMD total score (p<0.001) between young MDD patients with and without psychotic depression. HAMD, TSH, TC, and severe anxiety were independently associated with psychotic symptoms in young adult MDD patients. In addition, among young MDD patients, the rate of suicide attempts in the psychotic subgroup was much higher than in the non-psychotic subgroup (45.8% vs. 16.9%). CONCLUSIONS: Our findings suggest that psychotic symptoms are common in young MDD patients. Several clinical variables and biochemical indicators are associated with the occurrence of psychotic symptoms in young MDD patients.

Myocardial contractility characteristics of hypertrophic cardiomyopathy patients with and without sarcomere mutation.

Hypertrophic cardiomyopathy (HCM) patients with sarcomere mutations have an increased risk of heart failure and left ventricular (LV) systolic dysfunction. We hypothesize that sarcomere mutation carriers have abnormal myocardial contractility before LV dysfunction. Therefore, we aimed to associate myocardial contractility with identified sarcomere mutations and predict genotyped HCM patients with sarcomere mutation by three-dimensional speckle tracking imaging (3D-STI). A retrospective analysis of 117 HCM patients identified 32 genotype-positive (G +) and 85 genotype-negative (G-) patients. Genotype-positive patients had higher globe circumferential strain (GCS), globe longitudinal strain (GLS), and globe radial strain (GRS) (p < 0.05), and multivariate logistic regression revealed that these variables were associated with a positive genetic status (p < 0.05). After the propensity matches other possible influencing factors, we developed three models, named Model GCS, Model GLS, and Model GRS, which could identified genotype-positive HCM patients with excellent performance (AUC of 0.855, 0.833, and 0.870 respectively, all p < 0.001). Genotype-positive HCM patients show a higher myocardial hyper-contractility status than patients without sarcomere mutations. When combined with clinical and echocardiographic markers, the 3D-STI parameters can effectively identify the likelihood of genotype-positive HCM.

Feasibility and Safety of Percutaneous Intramyocardial Septal Cryoablation: A Canine Model with 6-month Follow-up.

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152,7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 %vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e'(8.09 ± 1.49 vs. 10.05 ±2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

Development of unigene-derived SSR markers from RNA-seq data of Uraria lagopodioides (Fabaceae) and their application in the genus Uraria Desv. (Fabaceae).

BACKGROUND: Uraria Desv. belongs to the tribe Desmodieae (Fabaceae), a group of legume plants, some of which have medicinal properties. However, due to a lack of genomic information, the interspecific relationships, genetic diversity, population genetics, and identification of functional genes within Uraria species are still unclear. RESULTS: Using RNA-Seq, a total of 66,026 Uraria lagopodioides unigenes with a total sequence content of 52,171,904 bp were obtained via de novo assembly and annotated using GO, KEGG, and KOG databases. 17,740 SSRs were identified from a set of 66,026 unigenes. Cross-species amplification showed that 54 out of 150 potential unigene-derived SSRs were transferable in Uraria, of which 19 polymorphic SSRs were developed. Cluster analysis based on polymorphisms successfully distinguished seven Uraria species and revealed their interspecific relationships. Seventeen samples of seven Uraria species were clustered into two monophyletic clades, and phylogenetic relationships of Uraria species based on unigene-derived SSRs were consistent with classifications based on morphological characteristics. CONCLUSIONS: Unigenes annotated in the present study will provide new insights into the functional genomics of Uraria species. Meanwhile, the unigene-derived SSR markers developed here will be invaluable for assessing the genetic diversity and evolutionary history of Uraria and relatives.

Efficacy and safety of Transcranial Direct Current Stimulation (tDCS) on cognitive function in chronic schizophrenia with Tardive Dyskinesia (TD): a randomized, double-blind, sham-controlled, clinical trial.

OBJECTIVE: Previous studies have shown that transcranial direct current stimulation(tDCS) led to an improvement of cognitive function in patients with schizophrenia, but rare study has explored the effect of tDCS on long-term hospitalized chronic schizophrenia with tardive dyskinesia (TD). The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS. METHODS: This study is a randomized, double-blind, sham-controlled clinical trial. Of the 52 patients, 14 dropped out, and 38 completed the experiment. Thirty-eight patients on stable treatment regimens were randomly assigned to receive active tDCS(n = 21) or sham stimulation(n = 17) on weekdays of the first, third, and fifth weeks of treatment. Patients performed the Pattern Recognition Memory (PRM) and the Intra/Extradimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and the end of week 3, week 5. Clinical symptoms were also measured at the baseline and the fifth week using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). Side effects of tDCS were assessed with an experimenter-administered open-ended questionnaire during the whole experiment. RESULTS: There were no significant differences in PRM and IED performance metrics, SANS total score and PANSS total score between active and sham tDCS groups at the end of week 5 (p > 0.05). Furthermore, there was a significant difference in the adverse effects of the tingling sensation between the two groups (p < 0.05), but there was no significant difference in other side effects (p > 0.05). CONCLUSION: According to these findings, no evidence supports using anodal stimulation over the left dorsolateral prefrontal cortex to improve cognitive function in patients with long-term hospitalized chronic schizophrenia with TD.

Suicide attempt rate and the risk factors in young, first-episode and drug-naïve Chinese Han patients with major depressive disorder.

BACKGROUND: In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. METHODS: A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. RESULTS: The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p < 0.001). Patients with suicide attempts had significantly higher levels of TSH (p < 0.001), TgAb (p = 0.004), TPOAb (p < 0.001), TG (p = 0.016), TC (p < 0.001), LDL (p < 0.001), and fasting glucose (p < 0.001), but significantly lower levels of HDL (p < 0.001). Logistic regression analysis showed that marital status (OR = 0.515, 95%CI: 0.280-0.950, p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013-1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205-1.430, p < 0.001), CGI-S score (OR = 1.875, 95%CI: 1.339-2.624, p < 0.001), levels of FT3(OR = 0.717, 95%CI: 0.536-0.959, p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002-1.006, p < 0.001), TC (OR = 1.330, 95%CI: 1.011-1.750, p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558-0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. CONCLUSIONS: In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

Peripheral Interleukin-18 is negatively correlated with abnormal brain activity in patients with depression: a resting-state fMRI study.

BACKGROUND: Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. METHODS: Using a case-control design, 68 subjects (34 patients and 34 healthy controls) underwent clinical assessment, blood sampling, and resting-state functional Magnetic Resonance Imaging (fMRI). The total Hamilton depression-17 (HAMD-17) score was used to assess depression severity. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-18 levels. Rest-state fMRI was conducted to explore spontaneous brain activity. RESULTS: The level of IL-18 was higher in patients with depression in comparison with healthy controls. IL-18 was negatively correlated with degree centrality of the left posterior cingulate gyrus in the depression patient group, but no correlation was found in the healthy control group. CONCLUSION: This study suggests the involvement of IL-18 in the pathophysiological mechanism for depression and interference with brain activity.

[Analysis of phenotype and MYH7 gene variant in a family of patients with hypertrophic cardiomyopathy].

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION: The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.

Acute Toxicity of a Novel anti-fouling Material Additive DCOIT to Marine Chlorella sp.

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main ingredient in SeaNine-211, a new antifouling agent that replaces organotin compounds to prevent the growth of fouling organisms on board. Biocides from antifoulants can cause problems for marine ecosystems by destroying non-target algal species. This study evaluated the potential adverse effects DCOIT using the Marine Chlorella sp. The concentration of DCOIT were set according to the semi-inhibitory concentrations for acute exposure experiments, and relevant oxidative stress indicators were measured to assess the acute toxic effects. The results showed that the inhibition concentrations (IC50) of DCOIT against Marine Chlorella sp was 2.522 mg/L. The genes related to photosynthesis and antioxidant capacity showed the effect of promoting low concentration and inhibiting high concentration. In addition, based on the ultrastructural observation and the expression analysis of photosynthesis related genes, it was found that DCOIT had a significant effect on plant photosynthesis.

Nucleolin-Targeted Ratiometric Fluorescent Carbon Dots with a Remarkably Large Emission Wavelength Shift for Precise Imaging of Cathepsin B in Living Cancer Cells.

As one of the most promising biomarkers for numerous malignant tumors, accurate and reliable reporting of Cathepsin B (CTSB) activity is of great significance to achieve efficient diagnosis of cancers at an early stage and predicting metastasis. Here, we report a vigorous ratiometric fluorescent method integrating a cancer-targeting recognition moiety with a remarkably large emission wavelength shift into a single matrix to report CTSB activity sensitively and specifically. As a proof of concept, we synthesized amine-rich carbon quantum dots (CQDs) with a blue fluorescence, which offered an efficient scaffolding to covalently assemble the nucleolin-targeting recognition nucleic acid aptamer AS1411 and a CTSB-cleavable peptide substrate Gly-Arg-Arg-Gly-Lys-Gly-Gly-Cys-COOH that tethered with a near-infrared (NIR) fluorophore chlorin e6 (Ce6-GRRGKGGC, Ce6-Pep), enabling a cancer-targeting and CTSB stimulus-responsive ratiometric nanoprobe AS1411-Ce6-CQDs. Owing to the efficient fluorescence resonance energy transfer (FRET) process from the CQDs to Ce6 inside the assembly of nanoprobe, the blue fluorescence of CQDs at ∼450 nm was remarkably quenched, along with an obvious NIR fluorescence enhancement of Ce6 at ∼650 nm. After selective entry into cancer cells via nucleolin-mediated endocytosis, the overexpressed CTSB in lysosome could cleave Ce6-Pep and trigger the Ce6 moiety dissociation from AS1411-Ce6-CQDs, thus leading to the termination of FRET process, achieving the efficient ratiometric fluorescence response toward endogenous CTSB with a remarkably large emission wavelength shift of ∼200 nm from NIR to blue emission region. Notably, the nanoprobe AS1411-Ce6-CQDs exhibited an excellent specificity for ratiometric fluorescent sensing of CTSB activity with an ultralow detection limit of 0.096 ng/mL, demonstrating its promising use for early precise cancer diagnosis in the near future.

Predictors of cardiac involvement and survival in patients with primary systemic light-chain amyloidosis: roles of the clinical, chemical, and 3-D speckle tracking echocardiography parameters.

BACKGROUND: Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality. METHODS: We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained. RESULTS: The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4-25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e', GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival. CONCLUSIONS: STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

A multifunctional AIE gold cluster-based theranostic system: tumor-targeted imaging and Fenton reaction-assisted enhanced radiotherapy.

BACKGROUND: As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations. RESULTS: In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au4-iron oxide nanoparticle (Au4-IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au4 cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au4-IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group. CONCLUSIONS: The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform.

Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K.

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

Stereospecific interactions between chiral inorganic nanomaterials and biological systems.

Chirality is ubiquitous in nature and plays mysterious and essential roles in maintaining key biological and physiological processes. As biological systems display high selectivity for chiral biomolecules, chiral bio-nanoscience has become a popular research field during the last decade. Homochirality, as an essential attribute of natural compounds (l-amino acids, d-sugars, etc.), inspired the emergence of synthetic chiral nanomaterials, which in turn impacted their biological functions and fates. This review is a comprehensive overview of the interactions between chiral inorganic nanostructures and biosystems. We start with the recent progress in biocompatible chiral nanomaterials and focus on stereospecific biological interactions ranging from enantioselective reactions in applications such as sensing and catalysis to chirality-dependent controllable manipulation of cell behaviours and finally to enantiopure nanoplatforms for improved disease therapy. We also discuss the current challenges and future potential of these chiral nanotechnologies in biomedicine and bioengineering, provide strategies to overcome these barriers and offer a future perspective.

Quantitative Analysis of Left Ventricular Flow Dynamics in Latent Obstructive Hypertrophic Cardiomyopathy Using Vector Flow Mapping.

OBJECTIVES: This study aimed to assess left ventricular (LV) energy loss (EL), circulation and vortex area using vector flow mapping (VFM) in patients with latent obstructive hyper-trophic cardiomyopathy (LOHCM) and nonobstructive hypertrophic cardiomyopathy (NOHCM). METHODS: Fourteen LOHCM patients, 10 NOHCM patients, and 11 healthy individuals were evaluated by transthoracic echocardiography. An offline VFM workstation was used to analyze the LV blood flow patterns and fluid dynamics. The hemodynamic parameters, EL, circulation, and vortex area in 7 cardiac phases were calculated and analyzed. RESULTS: Compared with controls and NOHCM patients, EL was significantly higher in -LOHCM patients during the rapid ejection phase, slow ejection (SE) phase, and isovolumetric relaxation phase (p < 0.05). LOHCM patients also showed increased circulation during SE compared to the other two groups (p < 0.05). The ability to discriminate between NOHCM and LOHCM was assessed by the area under the receiver-operating characteristic curve (AUC), and EL during SE was found to have the largest AUC (0.964); the best cutoff value was 6.34 J/m3/s, with a sensitivity of 100% and specificity of 80%. CONCLUSIONS: The VFM technique can detect abnormal changes of LV EL and vortex characteristics in hypertrophic cardiomyopathy patients. Compared with controls and NOHCM patients, the LOHCM patients have worse systolic and diastolic functions.

The Design of a Frame-Like ZnO FBAR Sensor for Achieving Uniform Mass Sensitivity Distributions.

In this paper, an infinite circular ZnO thin film bulk acoustic resonator (FBAR) with a frame-like electrode operating at the thickness-extensional (TE) mode is studied. Two-dimensional scalar differential equations established for the problem in the Cartesian coordinate system are successfully solved by transforming them into normal Bessel equations and modified Bessel equations in the cylindrical coordinate system. Resonant frequencies and vibration distributions are obtained for this frame-like FBAR sensor. A nearly uniform mass sensitivity distribution in the active area is achieved by designing proper electrode size and mass ratio of the driving electrode to the ZnO film. Numerical results show that compared with the reported ring electrode FBAR sensor, the novel frame-like electrode FBAR can achieve a maximum optimization ratio (up to 97.90%) on the uniformity of the mass sensitivity distribution in the active area under the same structural parameters, which is also higher than the optimization ratio 77.63% obtained by the reported double-ring electrode design. Moreover, the mechanism to achieve a very uniform mass sensitivity distribution in the active area by the frame-like electrode is explained in detail according to dispersion curves. Namely, when the resonant frequency of the FBAR sensor is close to the cut-off frequency of the active region in the dispersion curve, the mass sensitivity distribution is nearly uniform. These conclusions provide a theoretical guidance for the design and optimization of ZnO FBAR mass sensors with high performance.

Two new compounds from Streptomyces sp. HS-NF-813.

Two new derivatives of cytotoxic substance BE-52211, designed as BE-52211D (1) and BE-52211E (2), were isolated from the fermentation broth of the strain Streptomyces sp. HS-NF-813. Their structures were determined by 1D and 2D NMR techniques, ESI-MS and comparison with data from the literature. The absolute stereochemistry of 1 was elucidated by NMR data of the Mosher ester derivatives. Compounds 1 and 2 showed moderate cytotoxic activity against three human tumor cell lines.

AIE Triggers the Circularly Polarized Luminescence of Atomically Precise Enantiomeric Copper(I) Alkynyl Clusters.

Atomically precise enantiomeric metal clusters are scarce, and copper(I) alkynyl clusters with intense circularly polarized luminescence (CPL) responses have not been reported. A pair of chiral alkynyl ligands, (R/S)-2-diphenyl-2-hydroxylmethylpyrrolidine-1-propyne (abbreviated as R/S-DPM) we successfully prepared and single crystals were characterized of optically pure enantiomeric pair of atomically-precise copper(I) clusters, [Cu14 (R/S-DPM)8 ](PF6 )6 (denoted as R/S-Cu14 ), which feature bright red luminescence and CPL with a high luminescence anisotropy factor (glum ). A dilute solution containing R/S-Cu14 was nonluminescent and CPL inactive at room temperature. Crystallization- and aggregation-induced emission (CIE and AIE, respectively) contribute to the triggering of the CPL of R/S-Cu14 in the crystalline and aggregated states. Their AIE behavior and good biocompatibility indicated applications of these copper(I) clusters in cell imaging in HeLa and NG108-15 cells.