Cloning and Functional Analysis of a Zeaxanthin Epoxidase Gene in Ulva prolifera.

The xanthophyll cycle is a photoprotective mechanism in plants and algae, which protects the photosynthetic system from excess light damage under abiotic stress. Zeaxanthin is considered to play a pivotal role in this process. In this study, the relative content of xanthophylls was determined using HPLC-MS/MS in Ulva prolifera exposed to different salinities. The results showed that high-salt stress significantly increased the relative content of xanthophylls and led to the accumulation of zeaxanthin. It was speculated that the accumulated zeaxanthin may contribute to the response of U. prolifera to high-salt stress. Zeaxanthin epoxidase (ZEP) is a key enzyme in the xanthophyll cycle and is also involved in the synthesis of abscisic acid and carotenoids. In order to explore the biological function of ZEP, a ZEP gene was cloned and identified from U. prolifera. The CDS of UpZEP is 1122 bp and encodes 373 amino acids. Phylogenetic analysis showed that UpZEP clusters within a clade of green algae. The results of qRT-PCR showed that high-salt stress induced the expression of UpZEP. In addition, heterologous overexpression of the UpZEP gene in yeast and Chlamydomonas reinhardtii improved the salt tolerance of transgenic organisms. In conclusion, the UpZEP gene may be involved in the response of U. prolifera to high-salt stress and can improve the high-salt tolerance of transgenic organisms.

Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein.

Ulva prolifera, a type of green algae that can be consumed, was utilized in the production of an angiotensin-I converting enzyme (ACE) inhibitory peptide. The protein from the algae was isolated and subsequently hydrolyzed using a neutral protease. The resulting hydrolysate underwent several processes including Sephadex-G100 filtration chromatography, ultrafiltration, HPLC-Q-TOF-MS analysis, ADMET screening, UV spectrum detection test, molecular docking, and molecular dynamic simulation. Then, the ACE inhibitory peptide named KAF (IC50, 0.63 ± 0.26 µM) was identified. The effectiveness of this peptide in inhibiting ACE can be primarily attributed to two conventional hydrogen bonds. Additionally, it could activate endothelial nitric oxide synthase (eNOS) activity to promote the generation of nitric oxide (NO). Additionally, KAF primarily increased the intracellular calcium (Ca2+) level by acting on L-type Ca2+ channel (LTCC) and the ryanodine receptor (RyR) in the endoplasmic reticulum, and completed the activation of eNOS under the mediation of protein kinase B (Akt) signaling pathway. Our study has confirmed that KAF has the potential to be processed into pharmaceutical candidate functions on vasoconstriction.

Ionic liquids inhibit the dynamic transition from α-helices to ß-sheets in peptides.

Abnormalities in the transition between α-helices and ß-sheets (α-ß transition) may lead to devastating neurodegenerative diseases, such as Parkinson's syndrome and Alzheimer's disease. Ionic liquids (ILs) are potential drugs for targeted therapies against these diseases because of their excellent bioactivity and designability of ILs. However, the mechanism through which ILs regulate the α-ß transition remains unclear. Herein, a combination of GPU-accelerated microsecond molecular dynamics simulations, correlation analysis, and machine learning was used to probe the dynamical α-ß transition process induced by ILs of 1-alkyl-3-methylimidazolium chloride ([C n mim]Cl) and its molecular mechanism. Interestingly, the cation of [C n mim]+ in ILs can spontaneously insert into the peptides as free ions (n ≤ 10) and clusters (n ≥ 11). Such insertion can significantly inhibit the α-ß, transition and the inhibiting ability for the clusters is more significant than that of free ions, where [C10mim]+ and [C12mim]+ can reduce the maximum ß-sheet content of the peptide by 18.5% and 44.9%, respectively. Furthermore, the correlation analysis and machine learning method were used to develop a predictive model accounting for the influencing factors on the α-ß transition, which could accurately predict the effect of ILs on the α-ß transition. Overall, these quantitative results may not only deepen the understanding of the role of ILs in the α-ß transition but also guide the development of the IL-based treatments for related diseases.

Diurnal humidity cycle driven selective ion transport across clustered polycation membrane.

The ability to manipulate the flux of ions across membranes is a key aspect of diverse sectors including water desalination, blood ion monitoring, purification, electrochemical energy conversion and storage. Here we illustrate the potential of using daily changes in environmental humidity as a continuous driving force for generating selective ion flux. Specifically, self-assembled membranes featuring channels composed of polycation clusters are sandwiched between two layers of ionic liquids. One ionic liquid layer is kept isolated from the ambient air, whereas the other is exposed directly to the environment. When in contact with ambient air, the device showcases its capacity to spontaneously produce ion current, with promising power density. This result stems from the moisture content difference of ionic liquid layers across the membrane caused by the ongoing process of moisture absorption/desorption, which instigates selective transmembrane ion flux. Cation flux across the polycation clusters is greatly inhibited because of intensified charge repulsion. However, anions transport across polycation clusters is amplified. Our research underscores the potential of daily cycling humidity as a reliable energy source to trigger ion current and convert it into electrical current.

Fluorine Domains Induced Ultrahigh Nitrogen Solubility in Ionic Liquids.

Fluorinated ionic liquids (ILs) are well-known as electrolytes in the nitrogen (N2) electroreduction reaction due to their exceptional gas solubility. However, the influence of fluorinated functional group on N2 solvation and solubility enhancement remains unclear. Massive molecular dynamics simulations and free energy perturbation methods are conducted to investigate the N2 solubility in 11 traditional and 9 fluorinated ILs. It shows that the fluorinated IL of 1-Ethyl-3-methylimidazolium tris(pentafluoroethyl) trifluorophosphate ([Emim]FAP) exhibits ultrahigh solubility, 4.844 × 10-3, approximately 118 times higher than that of traditional IL 1-Ethyl-3-methylimidazolium nitrate ([Emim]NO3). Moreover, fluorinated ILs with more than 10 C-F bonds possess higher N2 solubility than others and show an exothermic nature during solvation. As the C-F bonds number in ILs decreases, the N2 solubility decreases significantly and displays the opposite endothermic behavior. To understand the ultrahigh N2 solubility in fluorinated ILs, we propose a concept of fluorine densification energy (FDE), referring to the average strength of interaction between atoms per unit volume in ILs with fluorine domains, demonstrating a linear relationship with C-F bonds. Physically, lower FDE results in lower N2-anion pair dissociation energy and higher free volume, finally enhancing the N2 solubility. Consequently, medium to long alkyl fluorine tails within a polar environment defines a distinct fluorine domain, emphasizing FDE's role in enhancing N2 solubility. Overall, these quantitative results will not only deepen the understanding of N2 solvation in ILs but may also shed light on the rational design of IL-based high-performance N2 capture and conversion technologies.

Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.

Molecular identification of Halomonas AZ07 and its multifunctional enzymatic activities to degrade Pyropia yezoensis under high-temperature condition.

BACKGROUND: Pyropia yezoensis a commercially important red seaweed species, is susceptible to various microorganisms infections, among which bacterial infections are the most prominent ones. Pyropia yezoensis is often affected by harmful bacterial communities under high temperatures that can lead to its degradation and economic losses. The current study aimed to explore Pyropia yezoensis-associated microbiota and further identify potential isolates, which can degrade Pyropia yezoensis under high-temperature conditions. METHODS AND RESULTS: The 16S rRNA gene sequencing was used to identify the agarolytic bacterial species. The results showed that Chromohalobacter sp. strain AZ6, Pseudoalteromonas sp. strain AZ, Psychrobacter sp. strain AZ3, Vibrio sp. strain AZ, and Halomonas sp. strain AZ07 exhibited algicidal properties as these strains were more abundant at high temperature (25 °C). Among the five isolated strains, the potential isolate Halomonas sp. strain AZ07 showed high production of agarolytic enzymes, including lipase, protease, cellulase, and amylase. This study confirmed that the isolated strain could produce these four different enzymes. The strain Halomonas AZ07 was co-treated with Pyropia yezoensis cells under two different temperature environments, including 13 °C and 25 °C. The degradation of Pyropia yezoensis occurred at the optimum temperature of 25 °C and effectively degraded their cell wall, proteins, lipids, and carbohydrates. CONCLUSION: The successful cultivation of Pyropia yezoensis in coastal farm environments is dependent on specific temperature and environmental factors, and lower temperatures have been observed to be particularly beneficial for the survival and growth of Pyropia yezoensis. The temperature below 13 °C was confirmed to be the best niche for the symbiotic relationship of microbiota associated with Pyropia yezoensis for its growth, development, and production.

Constructing static two-electron lithium-bromide battery.

Despite their potential as conversion-type energy storage technologies, the performance of static lithium-bromide (SLB) batteries has remained stagnant for decades. Progress has been hindered by the intrinsic liquid-liquid redox mode and single-electron transfer of these batteries. Here, we developed a high-performance SLB battery based on the active bromine salt cathode and the two-electron transfer chemistry with a Br-/Br+ redox couple by electrolyte tailoring. The introduction of NO3- improved the reversible single-electron transition of Br-, and more impressively, the coordinated Cl- anions activated the Br+ conversion to provide an additional electron transfer. A voltage plateau was observed at 3.8 V, and the discharge capacity and energy density were increased by 142 and 159% compared to the one-electron reaction benchmark. This two-step conversion mechanism exhibited excellent stability, with the battery functioning for 1000 cycles. These performances already approach the state of the art of currently established Li-halogen batteries. We consider the established two-electron redox mechanism highly exemplary for diversified halogen batteries.

Protein Interface Regulating the Inserting Process of Imidazole Ionic Liquids into the Cell Membrane.

Ionic liquids (ILs) have shown promising potential in membrane protein extraction; however, the underlying mechanism remains unclear. Herein, we employed GPU-accelerated molecular dynamics (MD) simulations to investigate the dynamic insertion process of ILs into cell membranes containing membrane proteins. Our findings reveal that ILs spontaneously insert into the membrane, and the presence of membrane proteins significantly decelerates the rate of IL insertion into the membrane. Specifically, the relationship between the insertion rate and inserting free energy exhibits non-monotonic changes, which can be attributed to interfacial effects. The protein-water interface acts as trap for free ions and ionic clusters, while free ions preferentially insert into the membrane from the protein-lipid interface, which limits the insertion rate due to its narrowness. Thus, the insertion rate is governed by a combination of the free energy and interfacial effects. These findings provide valuable insights into the interfacial effects of protein-lipid bilayers and have implications for various biochemical-related applications.

Ionic Liquid Gating Induces Anomalous Permeation through Membrane Channel Proteins.

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.

Selective ion migration in a polyelectrolyte driving a high-performance flexible moisture-electric generator.

We propose a novel moisture-electric generator that utilizes the unique properties of a blended poly(4-styrene sulfonic acid) and poly(vinyl alcohol) with phytic acid by screen printing and scrape coating, achieving an impressive open-circuit voltage of 0.88 V from ambient humidity. This innovative design significantly enhances ion transport, moisture adsorption, and flexibility, making a marked improvement in converting environmental humidity to electrical energy.

Medicinal Value, Genetic Diversity, and Genetic Relationship Analysis of Auricularia cornea (Agaricomycetes) Based on ITS, ISSR, and SRAP Markers.

Wild resources of Auricularia cornea (A. polytricha) are abundant in China, and genetic diversity and genetic relationships analysis of A. cornea can provide basis for germplasm resource utilization and innovation and molecular marker-assisted breeding. In this study, 22 Auricularia strains collected were identified as A. cornea based on ITS sequence analysis, and its genetic diversity was examined by ISSR and SRAP markers. The results showed that a total of 415 bands were amplified by 11 selected ISSR primers, with an average amplification of 37.73 bands per primer, and the mean values of Ne, I, and H were 1.302, 0.368, and 0.219, respectively. A total of 450 bands were amplified by 10 SRAP primers, with an average of 45 bands per primer, and the average of Ne, I, and H were 1.263, 0.302, and 0.183, respectively. The unweighted pair-group method with arithmetic means analysis based on ISSR-SRAP marker data revealed that the genetic similarity coefficient between the tested strains was 0.73-0.97, and the strains could be divided into five groups at 0.742, which had a certain correlation with regional distribution. The results of PCOA and population structure analysis based on ISSR-SRAP data also produced similar results. These results demonstrate the genetic diversity and distinctness among wild A. cornea and provide a theoretical reference for the classification, breeding, germplasm innovation, utilization, and variety protection of A. cornea resources.

Simple, ultrasensitive detection of superoxide anion radical mutations in melanoma mice with SERS microneedles.

Elevated levels of superoxide anion radicals (O2·-) have been implicated in the pathogenesis of a variety of diseases, such as cancer, inflammatory diseases and autoimmune diseases. To determine the O2·- concentration for assisting disease detection, a method based on surface-enhanced Raman scattering (SERS) combined with transparent polymer microneedles has been developed. Photocrosslinked NOA61 is used to prepare microneedles with sulfhydryl group, which can contribute to anchor gold nanoparticles (Au NPs) functionalized by p-mercaptobenzoic acid (PATP). This work successfully constructed SERS microneedles for in situ detection. A REDOX reaction occurred between PATP and O2·-, resulting in the formation of dimethylaminoborane (DMAB) and a subsequent change in Raman signal. Based on the quantitative relationship between the change of peak area ratio at 1042 cm-1 and 1077 cm-1 and the concentration change of O2·-, a standard curve with a linear range of 0-480 ng/mL was constructed. The SERS microneedles were effectively employed to track melanoma progression in mice, establishing a fundamental correlation between O2·- concentration and melanoma stage, as confirmed by ELISA. The benefits of this approach, including convenience, in situ applicability, and low cost, are anticipated to offer novel insights for non-invasive in situ detection, potentially enhancing disease monitoring and diagnosis.

SERS-Based Microneedle Biosensor for In Situ and Sensitive Detection of Tyrosinase.

Tyrosinase (TYR) emerges as a key enzyme that exerts a regulatory influence on the synthesis of melanin, thereby assuming the role of a critical biomarker for the detection of melanoma. Detecting the authentic concentration of TYR in the skin remains a primary challenge. Distinguished from ex vivo detection methods, this study introduces a novel sensor platform that integrates a microneedle (MN) biosensor with surface-enhanced Raman spectroscopy (SERS) technology for the in situ detection of TYR in human skin. The platform utilized dopamine (DA)-functionalized gold nanoparticles (Au NPs) as the capturing substrate and 4-mercaptophenylboronic acid (4-MPBA)-modified silver nanoparticles (Ag NPs) acting as the SERS probe. Here, the Au NPs were functionalized with mercaptosuccinic acid (MSA) for DA capture. In the presence of TYR, DA immobilized on the MN is preferentially oxidized to dopamine quinone (DQ), a process that results in a decreased density of SERS probes on the platform. TYR concentration was detected through variations in the signal intensity emitted by the phenylboronic acid. The detection system was able to evaluate TYR concentrations within a linear range of 0.05 U/mL to 200 U/mL and showed robust anti-interference capabilities. The proposed platform, integrating MN-based in situ sensing, SERS technology, and TYR responsiveness, holds significant importance for diagnosing cutaneous melanoma.

SOX-1 antibodies positive Lambert-Eaton myasthenic syndrome with occult small cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

Water-induced strong isotropic MXene-bridged graphene sheets for electrochemical energy storage.

Graphene and two-dimensional transition metal carbides and/or nitrides (MXenes) are important materials for making flexible energy storage devices because of their electrical and mechanical properties. It remains a challenge to assemble nanoplatelets of these materials at room temperature into in-plane isotropic, free-standing sheets. Using nanoconfined water-induced basal-plane alignment and covalent and π-π interplatelet bridging, we fabricated Ti3C2Tx MXene-bridged graphene sheets at room temperature with isotropic in-plane tensile strength of 1.87 gigapascals and moduli of 98.7 gigapascals. The in-plane room temperature electrical conductivity reached 1423 siemens per centimeter, and volumetric specific capacity reached 828 coulombs per cubic centimeter. This nanoconfined water-induced alignment likely provides an important approach for making other aligned macroscopic assemblies of two-dimensional nanoplatelets.

Multi-target field control for matrix gradient coils.

OBJECTIVE: Conventional single-target field control for matrix gradient coils will add control complexity in MRI spatial encoding, such as designing specialized fields and sequences. This complexity can be reduced by multi-target field control, which is realized by optimizing the coil structure according to target fields. METHODS: Based on the principle of multi-target field control, the X, Y and Z gradient fields can be set as target fields, and all coil elements can then be divided into three groups to generate these fields. An improved simulated annealing algorithm is proposed to optimize the coil element distribution of each group to generate the corresponding target field. In the improved simulated annealing process, two swapping modes are presented, and randomly selected with certain probabilities that are set to 0.25, 0.5 and 0.75, respectively. The flexibility of the final designed structure is demonstrated by a spherical harmonic basis up to the full second order with single-target field control. An experimental platform is built to measure the gradient fields generated by the designed structure with multi-target target control. RESULTS: With three probabilities of swapping modes, three similar coil element distributions are optimized, and their maximum magnetic field errors for generating X, Y and Z gradients are all below 5%. The structure selected for the final design is the one with a probability of 0.75, considering the coil performance and structural symmetry. The maximum error for all target fields generated by single-target field control is also below 5%. The experimental results show that the measured gradient fields along the axes have enough strength and high linearity. CONCLUSIONS: With the proposed improved simulated annealing algorithm and swapping modes, multi-target field control for matrix gradient coils is verified and achieved in this study by optimizing the coil element distribution. Moreover, this study provides a solution to simplify the complexity of controlling the matrix gradient coil in spatial encoding.

Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis.

OBJECTIVE: This study aimed to investigate the possible role of granulin (GRN) in activating the TLR9-IFN-α pathway in renal tubular epithelial cells (RTECs) and explore clues that RTECs regulate the micro-environment of inflammatory response in lupus nephritis (LN). METHODS: Renal sections from 57 LN patients and 30 non-LN patients were sampled for histological study, and GRN overexpression RTECs were applied for cytological study. RESULTS: In the histological study, GRN is highly expressed in LN RTECs with tubulointerstitial inflammation (TII) and well co-localized with TLR9. ROC analysis suggested a potential relationship between GRN expression in RTECs and therapeutic response. Moreover, IFN-α also highly expressed in LN RTECs with TII, and the intensity of IFN-α is positively correlated with the co-localization intensity of GRN and TLR9. In the cytological study, LN serum, especially serum from LN with TII, activates the expression of TLR9 in RTECs, and GRN engages the interaction of TLR9 to activate the expression of IFN-α in RTECs. While TLR9 inhibitors can suppress the expression of IFN-α in RTECs, the degree of inhibition is dose-dependent. CONCLUSION: The expression of GRN in RTECs is associated with interstitial inflammation and therapeutic response. GRN may mediate the activation of the TLR9-IFN-α pathway in RTECs and involve in the micro-environment of inflammatory response in LN.

Nanofluid-Guided Janus Membrane for High-Efficiency Electricity Generation from Water Evaporation.

Harvesting electricity from widespread water evaporation provides an alternative route to cleaner power generation technology. However, current evaporation power generation (EPG) mainly depends on the dissociation process of certain functional groups (e.g., SO3H) in water, which suffers from low power density and short-term output. Herein, the Janus membrane is prepared by combining nanofluid and water-grabbing material for EPG, where the nanoconfined ionic liquids (NCILs) serve as ion sources instead of the functional groups. Benefiting from the selective and fast transport of anions in NCILs, such EPG demonstrates excellent power performance with a voltage of 0.63 V, a short-circuit current of 140 µA, and a maximum power density of 16.55 µW cm-2 while operating for at least 180 h consistently. Molecular dynamics (MD) simulation and surface potential analysis reveal the molecular mechanism, that is, the diffusion of Cl- anions during evaporation is much faster than that of cations, generating the voltage and current across the membrane. Furthermore, the device performs well in varying environmental conditions, including different water temperatures and sources of evaporating water, showcasing its adaptability and integrability. Overall, the nanofluid-guided Janus membrane can efficiently transform low-grade thermal energy in evaporation into electricity, showing a competitive advantage over other sustainable applied approaches.

Classification, Diagnosis, and Treatment of Obesity-Related Heart Diseases.

Evidence-based medicine shows that obesity is associated with a wide range of cardiovascular (CV) diseases. Obesity can lead to changes in cardiac structure and function, which can lead to obese cardiomyopathy, subclinical cardiac dysfunction, and even heart failure. It also increases the risk of atrial fibrillation and sudden cardiac death. Many invasive and noninvasive diagnostic methods can detect obesity-related heart disease at an early stage, so that appropriate measures can be selected to prevent adverse CV events. However, studies have shown a protective effect of obesity on clinical outcomes of CV disease, a phenomenon that has been termed the obesity paradox. The "obesity paradox" essentially refers to the fact that the classification of obesity defined by body mass index (BMI) does not consider the impact of obesity heterogeneity on CV disease prognosis, but simply puts subjects with different clinical and biochemical characteristics into the same category. In any case, indicators such as waist-to-hip ratio, ectopic body fat qualitative and quantitative, and CV fitness have been shown to be able to distinguish different CV risks in patients with the same BMI, which is convenient for early intervention in an appropriate way. A multidisciplinary approach, including lifestyle modification, evidence-based generic and novel pharmacotherapy, and surgical intervention, can improve CV outcomes in overweight/obese patients.