So close, yet so far away: the relationship between MAM and cardiac disease.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Microfluidics-aided fabrication of 3D micro-nano hierarchical SERS substrate for rapid detection of dual hepatocellular carcinoma biomarkers.

The simultaneous analysis of trace amounts of dual biomarkers is crucial in the early diagnosis, treatment, and prognosis of hepatocellular carcinoma (HCC). In this study, we prepared SERS-active hydrogel microparticles (SAHMs) with 3D hierarchical gold nanoparticles (AuNPs) micro-nanostructures by microdroplet technology and in situ synthesis, which demonstrated high reproducibility and sensitivity. Compared with traditional 2D SERS substrates, this newly prepared 3D SERS substrate provided a high density of nano-wrinkled structures and numerous AuNPs. Furthermore, a newly designed SERS-active substrate was proposed for the simultaneous microfluidic detection of AFP and AFU. The Raman signals of sandwich immunocomplexes on the surface of the SAHMs were measured for the trace analysis of these biomarkers. The proposed microfluidic platform achieved AFP and AFU detection in the range of 0.1-100 ng mL-1 and 0.01-100 ng mL-1, respectively, which represents a good response. Indeed, this platform is easy to fabricate, of low cost and has short detection time and comparable detection limits to other methods. As far as we know, this is the first study to achieve the simultaneous detection of AFP and AFU on a microfluidic platform. Therefore, we proposed a new simultaneous detection platform for dual HCC biomarkers that shows strong potential for the early diagnosis of HCC.

Femtosecond laser printing-assisted etching tailored hard and brittle micro-convex surface.

We report a femtosecond laser print-assisted dry etching technology for high-efficiency, high-quality, and tailored fabricating of a micro-convex surface (MCS) on hard and brittle materials. Liquid ultraviolet curing adhesive (UVCA) was transferred from a donor substrate to a receiving substrate by femtosecond laser-induced forward transfer, and the transferred microdroplet spontaneously has a smooth surface under the action of surface tension. And then an MCS with a high-quality surface was formed on hard and brittle materials by UV curing and dry etching. The effects of laser parameters and receiving substrate surface free energy on MCS morphology were investigated. According to the variation of the numerical aperture, the two methods to change the morphology of the MCS were divided into independent/joint regulation of diameter and height. We showed that a hexagonal array containing a variety of MCS morphologies can be fabricated on a fused silica by setting the appropriate parameters. And the fabrication time of an MCS in a large-area array was only 1.1 s.

Dietary inflammation index is associated with dyslipidemia: evidence from national health and nutrition examination survey, 1999-2019.

BACKGROUND AND AIMS: This study aimed to investigate the association between the Dietary Inflammatory Index (DII) and dyslipidemia, as well as to evaluate the mortality risk associated with DII in participants with dyslipidemia. METHODS: Data from the National Health and Nutrition Examination Survey database were divided into dyslipidemia and non-dyslipidemia groups. The association between DII and dyslipidemia was investigated using the weighted chi-square test, weighted t-test, and weighted logistic regression. Weighted Cox proportional hazards models were used to estimate the hazard ratios and 95% confidence intervals for all-cause and cardiovascular disease-related mortality within the dyslipidemia group. RESULTS: A total of 17,820 participants, including 4,839 without and 12,981 with dyslipidemia were analyzed in this study. The results showed that DII was higher in the dyslipidemia group compared to the non-dyslipidemia group (1.42 ± 0.03 vs. 1.23 ± 0.04, P < 0.01). However, for energy, protein, carbohydrates, total fat, saturated fat, and iron, DII was lower in participants with dyslipidemia. Logistic regression analysis revealed a strong positive association between DII and dyslipidemia. The odds ratios for dyslipidemia from Q1 to Q4 were 1.00 (reference), 1.12 (0.96-1.31), 1.23 (1.04-1.44), and 1.33 (1.11-1.59), respectively. In participants with dyslipidemia, a high DII was associated with high all-cause and cardiovascular mortality. CONCLUSION: DII was closely associated with dyslipidemia. A pro-inflammatory diet may play a role in unfavorable consequences and is linked to both all-cause mortality and cardiovascular death in patients with dyslipidemia. Participants with dyslipidemia should pay attention to their anti-inflammatory dietary patterns.

Single-shot 3D shape measurement based on RGB dot patterns and stereovision: retraction.

The referenced article [Opt. Express30, 28220 (2022)10.1364/OE.466148] has been retracted by the authors.

Rapid simultaneous SERS detection of dual myocardial biomarkers on single-track finger-pump microfluidic chip.

Acute myocardial infarction (AMI) is a serious disease with high mortality that afflicts many people around the world. The main cause of death from AMI was the inaccurate early diagnosis, which resulted from the medical treatment might be a delay. Therefore, it is crucial to achieve the rapid detection of AMI. The cardiac troponin I (cTnI) level in human serum may significantly increase as the myocardial membrane ruptured, and the creatine kinase-MB (CK-MB) was also associated with the AMI recurrence and the infarct size of myocardial infarction. Both of them are regarded as important cardiac biomarkers for the early diagnosis of AMI. Therefore, we chose these two cardiac biomarkers as indicators for simultaneous detection. We proposed a single-track finger-pump microfluidic chip for simultaneous surface-enhanced Raman scattering (SERS) detection of cTnI and CK-MB. The entire detection process takes only 5 min without the cumbersome syringe pump. Meanwhile, it enables multiple reagent additions and removals of the unbonded reactants. This microfluidic sensor employed "sandwich" immunoassays based on SERS nanoprobes, AMI biomarkers, and magnetic beads. It is possible to detect two cardiac biomarkers simultaneously in a single measurement, greatly simplifying the detection process and reducing the detection time. Magnetic beads with SERS nanoprobes were separated and captured in the microchamber by a round magnet integrated into the chip. Our results showed that the detection limits of cTnI and CK-MB could reach to 0.01 ng mL-1, respectively. The limit of detections (LODs) match with the clinical threshold values for AMI biomarkers. It is believed that the proposed single-track finger-pump microfluidic chip can be used as an effective tool for determining early AMI.

Mitophagy in hypertension-mediated organ damage.

Hypertension constitutes a pervasive chronic ailment on a global scale, frequently inflicting damage upon vital organs, such as the heart, blood vessels, kidneys, brain, and others. And this is a complex clinical dilemma that requires immediate attention. The mitochondria assume a crucial function in the generation of energy, and it is of utmost importance to eliminate any malfunctioning or surplus mitochondria to uphold intracellular homeostasis. Mitophagy is considered a classic example of selective autophagy, an important component of mitochondrial quality control, and is closely associated with many physiological and pathological processes. The ubiquitin-dependent pathway, facilitated by PINK1/Parkin, along with the ubiquitin-independent pathway, orchestrated by receptor proteins such as BNIP3, NIX, and FUNDC1, represent the extensively investigated mechanisms underlying mitophagy. In recent years, research has increasingly shown that mitophagy plays an important role in organ damage associated with hypertension. Exploring the molecular mechanisms of mitophagy in hypertension-mediated organ damage could represent a critical avenue for future research in the development of innovative therapeutic modalities. Therefore, this article provides a comprehensive review of the impact of mitophagy on organ damage due to hypertension.

SERS-Based Immunoassay of Myocardial Infarction Biomarkers on a Microfluidic Chip with Plasmonic Nanostripe Microcones.

We developed a new plasmonic nanostripe microcone array (PNMA) substrate-integrated microfluidic chip for the simultaneous surface-enhanced Raman scattering (SERS)-based immunoassay of the creatine kinase MB isoenzyme (CK-MB) and cardiac troponin (cTnI) cardiac markers. The conventional immunoassay usually employs a microtiter plate as the solid capture plate to form the immunocomplexes. However, the two-dimensional (2D) surface of the microtiter plate limits the capture efficiency of the target antigens due to the steric hindrance effect. To address this issue, a gold film-coated microcone array with nanostripes was developed that can provide a large surface area for capture antibody conjugation and serve as a SERS-active substrate. This unique nano-microhierarchical structure showed an excellent light trapping effect and induced surface plasmon resonance to further enhance the Raman signals of the SERS nanoprobes. It significantly improved the sensitivity and applicability of SERS-based immunoassay on the microfluidic chip. With this integrated microfluidic chip, we successfully performed the simultaneous detection of CK-MB and cTnI, and the detection limit can reach 0.01 ng mL-1. It is believed that the PNMA substrate-integrated microfluidic chip would play a critical role in the rapid and sensitive diagnostics of cardiac diseases.

Single-shot 3D shape measurement based on RGB dot patterns and stereovision.

One-shot projection structured light 3D measurement is a method to establish the stereo matching relationship and reconstruct 3D shape by projecting one pattern. However, the traditional stereo matching algorithm does not solve the problem of low matching accuracy and matching efficiency, which fundamentally limits the accuracy of 3D measurement. As the projector and imaging systems have daily higher resolution and imaging quality, RGB dots projection has more application prospects because of its ability to establish a stereo matching relationship through one projection. In this work, we proposed a single-shot 3D measurement method using line clustering stereo matching, and model correction methods. The projected RGB dots are extracted by slope differenced distribution and area constrained erosion method. Area constrained erosion can solve the problem of the segmented connected blobs caused by insufficient projection resolution. The clustering stereo matching method is utilized to coarse match the segmented center red points. A model correction method is utilized to restore and constrain the pattern that cannot be imaged. Experimental results demonstrated that our method achieves the best accuracy of about 0.089mm, better than the traditional disparity and RGB line method, which may shed light on the proposed method can accurately reconstruct the 3D surface.

Cryo-EM structure of the human TACAN in a closed state.

TACAN is an ion channel-like protein that may be involved in sensing mechanical pain. Here, we present the cryo-electron microscopic structure of human TACAN (hTACAN). hTACAN forms a dimer in which each protomer consists of a transmembrane globular domain (TMD) containing six helices and an intracellular domain (ICD) containing two helices. Molecular dynamic simulations suggest that each protomer contains a putative ion conduction pore. A single-point mutation of the key residue Met207 greatly increases membrane pressure-activated currents. In addition, each hTACAN subunit binds one cholesterol molecule. Our data show the molecular assembly of hTACAN and suggest that wild-type hTACAN is in a closed state.

The association between chronic heart failure and frailty index: A study based on the National Health and Nutrition Examination Survey from 1999 to 2018.

Objective: This study aims to explore the association between the frailty index and chronic heart failure (CHF). Methods: We collected data from the National Health and Nutrition Examination Survey (NHANES) (1998-2018) database to assess the association between CHF and frailty. Demographic, inquiry, laboratory examinations, and characteristics were gathered to compare CHF and non-CHF groups. Multiple logistic regression analysis was performed to explore the relationship between frailty and CHF. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence interval (CI) for mortality from all causes and cardiovascular disease (CVD). Results: A total of 16,175 participants with cardiac and cerebrovascular disease were categorized into CHF (n = 1,125) and non-CHF (n = 15,050) groups. In patients with CHF, the prevalence of frailty, pre-frailty, and non-frailty were 66.31, 30.93, and 2.75%, respectively. In multiple logistic regression, patients with CHF who were male (OR = 0.63, 95% CI: 3.11-5.22), whose annual family income was over $20,000 (OR = 0.52, 95% CI: 0.37-0.72, p < 0.001), or with normal hemoglobin level (OR = 0.77, 95% CI: 0.68-0.88, P < 0.001) had a lower likelihood of frailty. CHF patients with hypertension (OR = 3.60, 95% CI: 2.17-5.99, P < 0.0001), coronary heart disease (OR = 1.76, 95% CI: 1.10-2.84, P = 0.02), diabetes mellitus (OR = 1.89, 95% CI: 1.28-2.78, P < 0.001), and stroke (OR = 2.52, 95% CI: 1.53-4.15, P < 0.001) tended to be frail. Survival analysis suggested that pre-frailty and frailty were related to poor all-cause deaths (HR = 1.48, 95% CI: 1.36-1.66; HR = 2.77, 95% CI: 2.40-3.18) and CVD mortality (HR = 1.58, 95% CI: 1.26-1.97; HR = 2.55, 95% CI: 2.02-3.21). CHF patients with frailty were strongly connected with all-cause death (HR = 2.14, 95% CI: 1.27-3.62). Conclusion: Frailty was positively associated with CHF. Patients with CHF who were male, whose annual family income was over $20,000, or with normal hemoglobin level were negatively correlated to frailty. For patients with cardiac and cerebrovascular disease as well as CHF, frailty was strongly connected with all-cause death.

The efficacy of ginseng-containing traditional Chinese medicine in patients with acute decompensated heart failure: A systematic review and meta-analysis.

Objective: To evaluate the efficacy of ginseng-containing traditional Chinese medicine (TCM) for acute decompensated heart failure (ADHF). Methods: Seven databases were included from establishment until 10 July 2022. Pooled data were analyzed with random-effects model. The risk of bias was measured by the risk of bias tool for randomized trials (RoB 2). Modified Jadad scale score was used to assess the quality of including studies. The meta-analysis was performed with RevMan 5.3. Trial sequential analysis was assessed to avoid type I errors. We have registered our protocol in PROSPERO (CRD42021267742). Results: Twenty-eight articles were included. The results demonstrated that compared with conventional western therapy (WT), ginseng-containing TCM combined with WT further improved clinical efficacy (RR: 1.25, 95% CI: 1.20-1.29, p < 0.00001, I2 = 8%), left ventricular ejection fraction (LVEF) (MD: 5.80, 95% CI: 4.86-6.74, p < 0.00001, I2 = 89%), stroke volume (MD: 13.80, 95% CI: 12.66-14.95, p < 0.00001, I2 = 93%), 6-min walk test (MD: 53.03, 95% CI: 20.76-85.29, p = 0.001, I2 = 97%), decreased 6-month rehospitalization (RR: 0.44, 95% CI: 0.18-1.11, p = 0.08, I2 = 0%), brain natriuretic peptide (MD: 188.12, 95% CI: 248.13 to -128.11, p < 0.00001, I2 = 94%), N-terminal pro-B-type natriuretic peptide (MD = -503.29; 95% CI: 753.18 to -253.40, p < 0.0001, I2 = 89%) and Minnesota living heart failure questionnaire scores (MD: 9.68, 95% CI: 13.67 to -5.70, p < 0.00001, I2 = 83%). The ROB2 assessment and modified Jaded scores showed most studies included were with some concerns. Conclusion: Compared with WT alone, ginseng-containing TCM is a possible way to benefit ADHF patients. However, limited by the quality of including trials, more high-quality studies are needed to provide reliable evidence.

Huoxue Qianyang Qutan recipe attenuates cardiac fibrosis by inhibiting the NLRP3 inflammasome signalling pathway in obese hypertensive rats.

CONTEXT: HuoXue QianYang QuTan Recipe (HQQR) is used to manage hypertension and cardiac remodelling, but the mechanism is elusive. OBJECTIVE: To determine the mechanism of HQQR on obesity hypertension (OBH)-related myocardial fibrosis. MATERIALS AND METHODS: OBH models were prepared using spontaneously hypertensive rats (SHRs) and divided (n = 6) into saline, low-dose (19.35 g/kg/d) HQQR, high-dose (38.7 g/kg/d) HQQR, and valsartan (30 mg/kg/d) groups for 10 weeks. Systolic blood pressure (SBP), and Lee's index were measured. Heart tissues were examined by histology. HQQR's effects were examined on cardiac fibroblasts (CFs) stimulated with angiotensin II and treated with HQQR, a caspase-1 inhibitor, siNLRP3, and oeNLRP3. RESULTS: HQQR(H) reduced SBP (201.67 ± 21.00 vs. 169.00 ± 10.00), Lee's index (321.50 ± 3.87 vs. 314.58 ± 3.88), and left ventricle mass index (3.26 ± 0.27 vs. 2.71 ± 0.12) in vivo. HQQR reduced percentage of fibrosis area (18.99 ± 3.90 vs. 13.37 ± 3.39), IL-1ß (10.07 ± 1.16 vs. 5.35 ± 1.29), and inhibited activation of NLRP3/caspase-1/IL-1ß pathway. HQQR also inhibiting the proliferation (1.09 ± 0.02 vs. 0.84 ± 0.01), fibroblast to myofibroblast transition (14.74 ± 3.39 vs. 3.97 ± 0.53), and collagen deposition (Col I; 0.50 ± 0.02 vs. 0.27 ± 0.05 and Col III; 0.48 ± 0.21 vs. 0.26 ± 0.11) with different concentrations selected based on IC50 in vitro (all ps < 0.05). NLRP3 interference further confirmed HQQR inhibiting NLRP3 inflammasome signalling. CONCLUSION: HQQR blunted cardiac fibrosis development in OBH and suppressed CFs proliferation by directly interfering with the NLRP3/caspase-1/IL-1ß pathway.

Electric Field Assisted Femtosecond Laser Preparation of Au@TiO2 Composites with Controlled Morphology and Crystallinity for Photocatalytic Degradation.

TiO2 is popular in photocatalytic degradation dye pollutants due to its abundance and its stability under photochemical conditions. Au loaded TiO2 can achieve efficient absorption of visible light and deal with the problem of low conversion efficiency for solar energy of TiO2. This work presents a new strategy to prepare Au nanoparticles-loaded TiO2 composites through electric-field-assisted temporally-shaped femtosecond laser liquid-phase ablation of Au3+ and amorphous TiO2. By adjusting the laser pulse delay and electric field parameters, gold nanoparticles with different structures can be obtained, such as nanospheres, nanoclusters, and nanostars (AuNSs). AuNSs can promote the local crystallization of amorphous TiO2 in the preparation process and higher free electron density can also be excited to work together with the mixed crystalline phase, hindering the recombination between carriers and holes to achieve efficient photocatalytic degradation. The methylene blue can be effectively degraded by 86% within 30 min, and much higher than the 10% of Au nanoparticles loaded amorphous TiO2. Moreover, the present study reveals the crystallization process and control methods for preparing nanoparticles by laser liquid ablation, providing a green and effective new method for the preparation of high-efficiency photocatalytic materials.

Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.

Calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo-electron microscopy structures of full-length CaSR in distinct ligand-bound states. Ligands (Ca2+ and l-tryptophan) bind to the extracellular domain of CaSR and induce large-scale conformational changes, leading to the closure of two heptahelical transmembrane domains (7TMDs) for activation. The positive modulator (evocalcet) and the negative allosteric modulator (NPS-2143) occupy the similar binding pocket in 7TMD. The binding of NPS-2143 causes a considerable rearrangement of two 7TMDs, forming an inactivated TM6/TM6 interface. Moreover, a total of 305 disease-causing missense mutations of CaSR have been mapped to the structure in the active state, creating hotspot maps of five clinical endocrine disorders. Our results provide a structural framework for understanding the activation, allosteric modulation mechanism, and disease therapy for class C GPCRs.

Three-Dimensional Maskless Fabrication of Bionic Unidirectional Liquid Spreading Surfaces Using a Phase Spatially Shaped Femtosecond Laser.

Ubiquitous biological processes exhibit the ability to achieve spontaneous directionally guided droplet transport. Maskless three-dimensional (3D) fabrication of various miniature bionic structures, a method applicable to various materials, is subject to processing method limitations. This remains a large obstacle to realizing self-driven, continuous, and controllable unidirectional liquid spreading. Thus, we present a flexible maskless 3D method for fabricating bionic unidirectional liquid spreading surfaces by using a phase spatially shaped femtosecond laser. The laser can be transformed from having Gaussian distributions to having 3D bionic structure field distributions. Furthermore, we fabricated Syntrichia caninervis bionic structures with a spiculate end for unidirectional water spreading; 1 µL droplets had a 16 mm flow length on Si surfaces when the S. caninervis single structure was 34 (length), 8 (width), and 12 µm (height). Furthermore, various bionic structures-Nepenthes, cactus, and moth structures-were fabricated on Si, SiO2, and Ti. We also demonstrated the measurability of two-dimensional (S-shaped) curved flows on Si wafers as well as 3D curved flows on a Ti pipe turning 120° within 2320 ms. Our method can realize high-efficiency maskless 3D processing of various materials and structures (especially asymmetric structures); it is both flexible and fast, effectively expanding the processing capacity of micro-/nanostructures on patterned surfaces. This is of great significance to various domains such as microfluids, fog collection, and chemical reaction control.

Molecular understanding of calcium permeation through the open Orai channel.

The Orai channel is characterized by voltage independence, low conductance, and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane (PM). How the channel is activated and promotes Ca2+ permeation is not well understood. Here, we report the crystal structure and cryo-electron microscopy (cryo-EM) reconstruction of a Drosophila melanogaster Orai (dOrai) mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which 6 transmembrane 1 (TM1) helices in the center form the ion-conducting pore, and 6 TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation, and Ca2+ permeation.

In vitro and in vivo evaluation of antitumor drug-loaded aptamer targeted single-walled carbon nanotubes system.

OBJECTIVE: A multifunctional tumor-targeting drug delivery system employing single-walled carbon nanotubes (SWCNT) as drug carriers, AS1411 as targeting ligand and doxorubicine (DOX) as a model chemotherapy drug was constructed. METHODS: Firstly, SWCNT were modified with F68 (4.0 mg/ml) by ultrasonic dispersing technology due to the action of hydrophobic force and Van der Waals force, endowing SWCNT water dispersions and biocompatibility. Meanwhile, DOX could be easily absorbed on the surface of SWCNT by the π-π stacking, electrostatic adsorption and hydrophobic interactions. Finally, AS1411 was attached to the surface of DOX-SWCNT by the π-π stacking and electrostatic adsorption to obtain a tumor-targeting delivery system. Cellular uptake, anti-tumor effect in vitro and in vivo, cell cycle and apoptosis and biodistribution of AS1411-DOX-SWCNT were investigated, compared with the DOX solution. CONCLUSION: This AS1411-mediated DOX-loaded SWCNT (AS1411-DOX-SWCNT) delivery system not only retained both optical properties of SWCNT and cytotoxicity of DOX but also could accumulate in tumors, which facilitated combination of chemotherapy and photothermal therapy. AS1411-DOX-SWCNT could effectively promote DOX cellular uptake and then increase intracellular accumulation as a targeting delivery system. AS1411-DOX-SWCNT by NIR laser excited could trigger S phase arrest and the late stage apoptotic on PC3 cancer cells. The investigation in vivo further confirmed that this system possessed higher tumor targeting capacity and antitumor efficacy than DOX, especially with NIR laser irradiation.