The Simultaneous Detection of Dopamine and Uric Acid In Vivo Based on a 3D Reduced Graphene Oxide-MXene Composite Electrode.

Dopamine (DA) and uric acid (UA) are essential for many physiological processes in the human body. Abnormal levels of DA and UA can lead to multiple diseases, such as Parkinson's disease and gout. In this work, a three-dimensional reduced graphene oxide-MXene (3D rGO-Ti3C2) composite electrode was prepared using a simple one-step hydrothermal reduction process, which could separate the oxidation potentials of DA and UA, enabling the simultaneous detection of DA and UA. The 3D rGO-Ti3C2 electrode exhibited excellent electrocatalytic activity towards both DA and UA. In 0.01 M PBS solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.74 µA·µM-1·cm-2 and a detection limit of 0.056 µM (S/N = 3), while the linear range of UA was 0.5-60 µM and 80-450 µM, with sensitivity of 2.96 and 0.81 µA·µM-1·cm-2, respectively, and a detection limit of 0.086 µM (S/N = 3). In 10% fetal bovine serum (FBS) solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.41 µA·µM-1·cm-2 and a detection limit of 0.091 µM (S/N = 3). The linear range of UA was 2-500 µM with a sensitivity of 0.11 µA·µM-1·cm-2 and a detection limit of 0.6 µM (S/N = 3). The modified electrode exhibited advantages such as high sensitivity, a strong anti-interference capability, and good repeatability. Furthermore, the modified electrode was successfully used for DA measurement in vivo. This could present a simple reliable route for neurotransmitter detection in neuroscience.

Ultra-Wideband Transformer Feedback Monolithic Microwave Integrated Circuit Power Amplifier Design on 0.25 µm GaN Process.

This paper presents an ultra-wideband transformer feedback (TFB) monolithic microwave integrated circuit (MMIC) power amplifier (PA) developed using a 0.25 µm gallium nitride (GaN) process. To broaden the bandwidth, a drain-to-gate TFB technique is employed in this PA design, achieving a 117% relative -3 dB bandwidth, extending from 5.4 GHz to 20.3 GHz. At a 28 V supply, the designed PA circuit achieves an output power of 25.5 dBm and a 14 dB small-signal gain in the frequency range of 6 to 19 GHz. Within the 6 to 19 GHz frequency range, the small-signal gain exhibits a flatness of less than 0.78 dB. The PA chip occupies an area of 1.571 mm2. This work is the first to design a power amplifier with on-chip transformer feedback in a compound semiconductor MMIC process, and it enables the use of the widest bandwidth power amplifier on-chip transformer matching network.

Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy.

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.

Host genotype-specific rhizosphere fungus enhances drought resistance in wheat.

BACKGROUND: The severity and frequency of drought are expected to increase substantially in the coming century and dramatically reduce crop yields. Manipulation of rhizosphere microbiomes is an emerging strategy for mitigating drought stress in agroecosystems. However, little is known about the mechanisms underlying how drought-resistant plant recruitment of specific rhizosphere fungi enhances drought adaptation of drought-sensitive wheats. Here, we investigated microbial community assembly features and functional profiles of rhizosphere microbiomes related to drought-resistant and drought-sensitive wheats by amplicon and shotgun metagenome sequencing techniques. We then established evident linkages between root morphology traits and putative keystone taxa based on microbial inoculation experiments. Furthermore, root RNA sequencing and RT-qPCR were employed to explore the mechanisms how rhizosphere microbes modify plant response traits to drought stresses. RESULTS: Our results indicated that host plant signature, plant niche compartment, and planting site jointly contribute to the variation of soil microbiome assembly and functional adaptation, with a relatively greater effect of host plant signature observed for the rhizosphere fungi community. Importantly, drought-resistant wheat (Yunhan 618) possessed more diverse bacterial and fungal taxa than that of the drought-sensitive wheat (Chinese Spring), particularly for specific fungal species. In terms of microbial interkingdom association networks, the drought-resistant variety possessed more complex microbial networks. Metagenomics analyses further suggested that the enriched rhizosphere microbiomes belonging to the drought-resistant cultivar had a higher investment in energy metabolism, particularly in carbon cycling, that shaped their distinctive drought tolerance via the mediation of drought-induced feedback functional pathways. Furthermore, we observed that host plant signature drives the differentiation in the ecological role of the cultivable fungal species Mortierella alpine (M. alpina) and Epicoccum nigrum (E. nigrum). The successful colonization of M. alpina on the root surface enhanced the resistance of wheats in response to drought stresses via activation of drought-responsive genes (e.g., CIPK9 and PP2C30). Notably, we found that lateral roots and root hairs were significantly suppressed by co-colonization of a drought-enriched fungus (M. alpina) and a drought-depleted fungus (E. nigrum). CONCLUSIONS: Collectively, our findings revealed host genotypes profoundly influence rhizosphere microbiome assembly and functional adaptation, as well as it provides evidence that drought-resistant plant recruitment of specific rhizosphere fungi enhances drought tolerance of drought-sensitive wheats. These findings significantly underpin our understanding of the complex feedbacks between plants and microbes during drought, and lay a foundation for steering "beneficial keystone biome" to develop more resilient and productive crops under climate change. Video Abstract.

Recent Progress in Mass Spectrometry-Based Single-Cell Metabolic Analysis.

Single-cell analysis enables the measurement of biomolecules at the level of individual cells, facilitating in-depth investigations into cellular heterogeneity and precise interpretation of the related biological mechanisms. Among these biomolecules, cellular metabolites exhibit remarkable sensitivity to environmental and biochemical changes, unveiling a hidden world underlying cellular heterogeneity and allowing for the determination of cell physiological states. However, the metabolic analysis of single cells is challenging due to the extremely low concentrations, substantial content variations, and rapid turnover rates of cellular metabolites. Mass spectrometry (MS), characterized by its high sensitivity, wide dynamic range, and excellent selectivity, is employed in single-cell metabolic analysis. This review focuses on recent advances and applications of MS-based single-cell metabolic analysis, encompassing three key steps of single-cell isolation, detection, and application. It is anticipated that MS will bring profound implications in biomedical practices, serving as advanced tools to depict the single-cell metabolic landscape.

Laser-induced forward transfer based laser bioprinting in biomedical applications.

Bioprinting is an emerging field that utilizes 3D printing technology to fabricate intricate biological structures, including tissues and organs. Among the various promising bioprinting techniques, laser-induced forward transfer (LIFT) stands out by employing a laser to precisely transfer cells or bioinks onto a substrate, enabling the creation of complex 3D architectures with characteristics of high printing precision, enhanced cell viability, and excellent technical adaptability. This technology has found extensive applications in the production of biomolecular microarrays and biological structures, demonstrating significant potential in tissue engineering. This review briefly introduces the experimental setup, bioink ejection mechanisms, and parameters relevant to LIFT bioprinting. Furthermore, it presents a detailed summary of both conventional and cutting-edge applications of LIFT in fabricating biomolecule microarrays and various tissues, such as skin, blood vessels and bone. Additionally, the review addresses the existing challenges in this field and provides corresponding suggestions. By contributing to the ongoing development of this field, this review aims to inspire further research on the utilization of LIFT-based bioprinting in biomedical applications.

Genome-wide association studies of peduncle length in wheat under rain-fed and irrigating field conditions.

Drought is one of the most destructive environmental factors limiting wheat production and food security globally. Peduncle length (PLE) is an important morphological trait to determine plant architecture, photosynthate transport, and yield formation, which is also considered a useful index for drought tolerance in wheat. However, the genetic basis of wheat PLE is not well studied at present. Here, a large-scale genome-wide association study (GWAS) of PLE was performed using a panel of 282 wheat accessions with the Wheat 660K SNP array genotyping under rain-fed and irrigating field conditions. Totally, 1,301 significant marker-trait associations (MTAs) were identified using the threshold of p-value < 4.16 × 10-4, five of which were high-confidence. Furthermore, combining GWAS intervals, previously reported QTLs, expression levels, homologous genes, and selected sweep analysis, a total of 5 candidate genes were detected to associate with drought stress. Moreover, the expression levels of TraesCS2A02G082100 were significantly up-regulated under drought conditions and co-localized in the selected sweep region, suggesting it is a drought-responsive gene. Our results shed light on the genetic basis underlying wheat drought tolerance, which accelerates the marker-assistant selection and genetic improvement through genomic breeding in wheat.

The preparation of novel AIE fluorescent microspheres by dispersion polymerization.

An approach to prepare monodisperse polystyrene microspheres with aggregation-induced emission (AIE) characteristics has been developed which shows promising applications in fluorescence-encoding. The micron-sized, monodisperse polystyrene microspheres with AIE molecules were perfectly synthesized by two-stage dispersion polymerization. Fluorescent AIE monomer was synthesized by Suzuki reaction, confirmed by nuclear magnetic resonance (NMR). These AIE fluorogens (AIEgens) exhibited unique properties such as bright green emission in solid state and increased emission in tetrahydrofuran (THF) solution with the increase of water content. The influence of the AIE molecules concentration to microspheres synthesis was well investigated. The reaction conditions were optimized to obtain the functional polystyrene microspheres with a size distribution around 3%. The novel microspheres were characterized by scanning electron microscopy (SEM), confocal fluorescence microscope and flow cytometry. According to these results, two-stage dispersion polymerization was proved to be an efficient pathway for the preparation of AIE fluorescent and functionalized microspheres, which could be used in many biomedical industries.

Integrate Small RNA and Degradome Sequencing to Reveal Drought Memory Response in Wheat (Triticum aestivum L.).

Drought has gradually become one of the most severe abiotic stresses on plants. Plants that experience stress training can exhibit enhanced stress tolerance. According to MicroRNA (miRNA) sequencing data, this study identified 195 candidate drought memory-related miRNAs in wheat, and targets of 64 (32.8%) candidate miRNAs were validated by degradome sequencing. Several drought memory-related miRNAs such as tae-miR9676-5p, tae-MIR9676-p3_1ss21GA, tae-miR171a, tae-miR531_L-2, tae-miR408_L-1, PC-3p-5049_3565, tae-miR396c-5p, tae-miR9778, tae-miR164a-5p, and tae-miR9662a-3p were validated as having a strong response to drought memory by regulating the expression of their target genes. In addition, overexpression of drought memory-related miRNA, tae-miR531_L-2, can remarkably improve the drought tolerance of transgenic Arabidopsisthaliana. Drought memory can regulate plant cellular signal transduction, plant biosynthetic processes, and other biological processes to cope with drought via transcriptional memory. In addition, drought memory-related miRNAs can promote starch and sucrose catabolism and soluble sugar accumulation and regulate proline homeostasis to improve plant drought resistance. Our results could contribute to an understanding of drought memory in wheat seedlings and may provide a new strategy for drought-resistant breeding.

The renin-angiotensin system biomolecular cascade: a 2022 update of newer insights and concepts.

A large body of evidence implicates the renin-angiotensin system in the pathogenesis of cardiovascular disease. However, not everyone understands that the magnitude of the risk reduction achieved in clinical trials with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is only a fraction of the residual risk for cardiovascular events and death. This paper addresses limitations of current therapeutic approaches based on renin-angiotensin system blockade for hypertension and cardiovascular disease by illustrating the complex biochemical physiology and mechanism of classical and alternate angiotensin peptide formation. Emerging evidence of alternate mechanisms that bypass both renin and angiotensin-converting enzyme to produce the angiotensins in tissues and cells is not currently universally recognized. Currently available treatment would benefit from further insights to help fully meet the aims of patient care, and the challenge is to delve more deeply into the renin-angiotensin system cascade, with the aim of enhancing therapeutics for renin-angiotensin system inhibition. This article provides a reappraisal of the renin-angiotensin-aldosterone cascade, highlighting newly elucidated intermediary components and interplay, and their consequent implications and relevance for understanding the long-term contribution of angiotensin II in cardiovascular diseases and their therapy.

The Landscape of Autophagy-Related (ATG) Genes and Functional Characterization of TaVAMP727 to Autophagy in Wheat.

Autophagy is an indispensable biological process and plays crucial roles in plant growth and plant responses to both biotic and abiotic stresses. This study systematically identified autophagy-related proteins (ATGs) in wheat and its diploid and tetraploid progenitors and investigated their genomic organization, structure characteristics, expression patterns, genetic variation, and regulation network. We identified a total of 77, 51, 29, and 30 ATGs in wheat, wild emmer, T. urartu and A. tauschii, respectively, and grouped them into 19 subfamilies. We found that these autophagy-related genes (ATGs) suffered various degrees of selection during the wheat's domestication and breeding processes. The genetic variations in the promoter region of Ta2A_ATG8a were associated with differences in seed size, which might be artificially selected for during the domestication process of tetraploid wheat. Overexpression of TaVAMP727 improved the cold, drought, and salt stresses resistance of the transgenic Arabidopsis and wheat. It also promoted wheat heading by regulating the expression of most ATGs. Our findings demonstrate how ATGs regulate wheat plant development and improve abiotic stress resistance. The results presented here provide the basis for wheat breeding programs for selecting varieties of higher yield which are capable of growing in colder, drier, and saltier areas.

Relações entre a Redução de Estrogênio, Obesidade e Insuficiência Cardíaca com Fração de Ejeção Preservada / Crossroads between Estrogen Loss, Obesity, and Heart Failure with Preserved Ejection Fraction

Resumo A prevalência de obesidade e insuficiência cardíaca com fração de ejeção preservada (ICFEP) aumenta significativamente em mulheres na pós-menopausa. Embora a obesidade seja um fator de risco para disfunção diastólica do ventrículo esquerdo (DDFVE), o mecanismo que liga a interrupção da produção de hormônios ovarianos, especialmente o estrogênio, ao desenvolvimento da obesidade, DDFVE, e ICFEP em mulheres em processo de envelhecimento não é claro. Estudos clínicos e epidemiológicos demonstram que mulheres na pós-menopausa com obesidade abdominal (definida pela circunferência de cintura) têm risco maior de desenvolver a ICFEP do que homens ou mulheres sem obesidade abdominal. Este estudo analisa dados clínicos que corroboram a existência de uma ligação de mecanismo entre a perda de estrogênio mais obesidade e o remodelamento ventricular esquerdo com ICFEP. Ele também discute os possíveis mecanismos celulares e moleculares para a proteção mediada por estrogênio contra tipos de células, depósitos de tecidos, função e metabolismo de adipócitos negativos que podem contribuir para a DDFVE e a ICFEP.

Abstract The prevalence of obesity and heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women. Although obesity is a risk factor for left ventricular diastolic dysfunction (LVDD), the mechanisms that link the cessation of ovarian hormone production, and particularly estrogens, to the development of obesity, LVDD, and HFpEF in aging females are unclear. Clinical, and epidemiologic studies show that postmenopausal women with abdominal obesity (defined by waist circumference) are at greater risk for developing HFpEF than men or women without abdominal obesity. The study presents a review of clinical data that support a mechanistic link between estrogen loss plus obesity and left ventricular remodeling with LVDD. It also seeks to discuss potential cell and molecular mechanisms for estrogen-mediated protection against adverse adipocyte cell types, tissue depots, function, and metabolism that may contribute to LVDD and HFpEF.

Crossroads between Estrogen Loss, Obesity, and Heart Failure with Preserved Ejection Fraction. / Relações entre a Redução de Estrogênio, Obesidade e Insuficiência Cardíaca com Fração de Ejeção Preservada.

The prevalence of obesity and heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women. Although obesity is a risk factor for left ventricular diastolic dysfunction (LVDD), the mechanisms that link the cessation of ovarian hormone production, and particularly estrogens, to the development of obesity, LVDD, and HFpEF in aging females are unclear. Clinical, and epidemiologic studies show that postmenopausal women with abdominal obesity (defined by waist circumference) are at greater risk for developing HFpEF than men or women without abdominal obesity. The study presents a review of clinical data that support a mechanistic link between estrogen loss plus obesity and left ventricular remodeling with LVDD. It also seeks to discuss potential cell and molecular mechanisms for estrogen-mediated protection against adverse adipocyte cell types, tissue depots, function, and metabolism that may contribute to LVDD and HFpEF.

A prevalência de obesidade e insuficiência cardíaca com fração de ejeção preservada (ICFEP) aumenta significativamente em mulheres na pós-menopausa. Embora a obesidade seja um fator de risco para disfunção diastólica do ventrículo esquerdo (DDFVE), o mecanismo que liga a interrupção da produção de hormônios ovarianos, especialmente o estrogênio, ao desenvolvimento da obesidade, DDFVE, e ICFEP em mulheres em processo de envelhecimento não é claro. Estudos clínicos e epidemiológicos demonstram que mulheres na pós-menopausa com obesidade abdominal (definida pela circunferência de cintura) têm risco maior de desenvolver a ICFEP do que homens ou mulheres sem obesidade abdominal. Este estudo analisa dados clínicos que corroboram a existência de uma ligação de mecanismo entre a perda de estrogênio mais obesidade e o remodelamento ventricular esquerdo com ICFEP. Ele também discute os possíveis mecanismos celulares e moleculares para a proteção mediada por estrogênio contra tipos de células, depósitos de tecidos, função e metabolismo de adipócitos negativos que podem contribuir para a DDFVE e a ICFEP.

Preparation of doxorubicin-loaded porous iron Oxide@ polydopamine nanocomposites for MR imaging and synergistic photothermal-chemotherapy of cancer.

Recently, the development of biosafe nanocomposites with integrated diagnosis and therapeutic modality is received great attention in anti-cancer drug delivery. In this sturdy, we developed a multifunctional PION@PDA-PEG nanocomposite that combines the functions of magnetic resonance (MR) imaging, photothermal therapy (PTT) and chemotherapy into one single nanoprobe. The spherical and uniform-sized porous iron oxide nanoparticles (PION) were synthesized via a simple solvothermal method. Subsequently, a near-infrared light (NIR) sensitive polydopamine (PDA) shell was directly coated on the surface of PIONs to form monodisperse and biosafe core-shell nanocomposites, Thereafter, the surface of nanocomposites was further modified with polyethylene glycol (PEG) to prolong their blood circulation lifetime. The prepared PION@PDA-PEG showed excellent biocompatibility and promising MR imaging contrast agent capability. Furthermore, the porous structure of PION and the abundant functional groups of PDA shell permitted the remarkable drug loading capacity of more than 24.1 wt%. In addition, the synergistic photothermal- chemotherapy exhibited obvious enhanced anti-tumor effect in in-vitro cell experiment. These results suggest that the developed PION@PDA-PEG nanocomposite can be utilized as an efficient drug nanocarrier for biomedical applications including MR imaging and photothermal-chemotherapy.

Amplifying effect of chronic lisinopril therapy on diastolic function and the angiotensin-(1-7) Axis by the G1 agonist in ovariectomized spontaneously hypertensive rats.

G protein-coupled estrogen receptor (GPER) activation by G1 attenuates diastolic dysfunction from estrogen loss, which may be partly due to suppression of angiotensin II pathological actions. We aimed to determine the independent effects of 8 weeks of G1 (100 µg/kg/d, subcutaneous pellet), ACE-inhibition (ACEi; lisinopril 10 mg/kg, drinking water), or combination therapy versus vehicle in the ovariectomized (OVX) spontaneously hypertensive rat (SHR) on cardiac function and morphometrics (echocardiography), serum equilibrium of angiotensins (mass spectroscopy) and cardiac components of the RAS (Western blotting). G1 alone and when combined with ACEi enhanced myocardial relaxation (é: 30 and 17%) and diastolic wall strain (DWS: 76 and 68%) while reducing relative wall thickness (RWT: 20 and 33%) and filling pressures (E/é: 30 and 37%). Cardiac expression levels of Mas receptor (Mas-R) and ACE2 also increased in the presence of G1. Strong antihypertensive effects of lisinopril monotherapy were associated with reductions in RWT, collagen deposition and E/é without overtly altering é or DWS. Chronic ACEi also increased cardiac levels of Mas-R and AT1-R and tilted the circulating RAS toward the formation of Ang-(1-7), which was amplified in the presence of G1. In vitro studies further revealed that an inhibitor to prolyl endopeptidase (PEP), but not to neprilysin, significantly reduced serum Ang-(1-7) levels in G1-treated rats, suggesting that G1 might be increasing Ang-(1-7) formation via PEP. We conclude that activating GPER with G1 augments components of the cardiac RAS and improves diastolic function without lowering blood pressure, and that lisinopril-induced blood pressure control and cardiac alterations in OVX SHR are permissive in facilitating G1 to augment Ang-(1-7) in serum, thereby strengthening its cardioprotective benefits.

Atrial appendage angiotensin-converting enzyme-2, aging and cardiac surgical patients: a platform for understanding aging-related coronavirus disease-2019 vulnerabilities.

PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.

The Angiotensin-(1-12)/Chymase axis as an alternate component of the tissue renin angiotensin system.

The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new knowledge of the importance of noncanonical mechanisms for renin independent generation of angiotensins. The human sequence of the dodecapeptide angiotensin-(1-12) [N-Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8-His9-Leu10-Val1-Ile12-COOH] is an endogenous substrate that in the rat has been documented to be present in multiple organs including the heart, brain, kidney, gut, adrenal gland, and the bone marrow. Newer studies have confirmed the existence of Ang-(1-12) as an Ang II-forming substrate in the blood and heart of normal and diseased patients. Studies to-date document that angiotensin II generation from angiotensin-(1-12) does not require renin participation while chymase rather than angiotensin converting enzyme shows high catalytic activity in converting this tissue substrate into angiotensin II directly.

Is Sex a Determinant of COVID-19 Infection? Truth or Myth?

PURPOSE OF REVIEW: Angiotensin-converting enzyme 2 (ACE2), a specific high-affinity angiotensin II-hydrolytic enzyme, is the vector that facilitates cellular entry of SARS-CoV-1 and the novel SARS-CoV-2 coronavirus. SARS-CoV-2, which crossed species barriers to infect humans, is highly contagious and associated with high lethality due to multi-organ failure, mostly in older patients with other co-morbidities. RECENT FINDINGS: Accumulating clinical evidence demonstrates that the intensity of the infection and its complications are more prominent in men. It has been postulated that potential functional modulation of ACE2 by estrogen may explain the sex difference in morbidity and mortality. We review here the evidence regarding the role of estrogenic hormones in ACE2 expression and regulation, with the intent of bringing to the forefront potential mechanisms that may explain sex differences in SARS-CoV-2 infection and COVID-19 outcomes, assist in management of COVID-19, and uncover new therapeutic strategies.