Releasing a sugar brake generates sweeter tomato without yield penalty.

In tomato, sugar content is highly correlated with consumer preferences, with most consumers preferring sweeter fruit. However, the sugar content of commercial varieties is generally low, as it is inversely correlated with fruit size, and growers prioritize yield over flavour quality. Here we identified two genes, tomato (Solanum lycopersicum) calcium-dependent protein kinase 27 (SlCDPK27; also known as SlCPK27) and its paralogue SlCDPK26, that control fruit sugar content.

Mass Spectrometry Analysis of Nucleic Acid Modifications: From Beginning to Future.

Nucleic acids are fundamental biological molecules that encode and convey genetic information within living organisms. Over 150 modifications have been found in nucleic acids, which are involved in critical biological functions, including regulating gene expression, stabilizing nucleic acid structure, modulating protein translation, and so on. The dysregulation of nucleic acid modifications is correlated with many diseases such as cancers and neurological disorders.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this.

Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM.

Etiological diagnostic performance of probe capture-based targeted next-generation sequencing in bloodstream infection.

Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI.

Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China.

Structural basis for dimerization of a paramyxovirus polymerase complex.

The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

Background: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation.

Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

Background: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive.

Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

Background: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats.

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease.

Purpose: The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

Background: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation.

Methods: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days.

Lipidomic Signatures of Dairy Consumption and Associated Changes in Blood Pressure and Other Cardiovascular Risk Factors Among Chinese Adults.

Background: Omics data may provide a unique opportunity to discover dairy-related biomarkers and their linked cardiovascular health.

Methods: Dairy-related lipidomic signatures were discovered in baseline data from a Chinese cohort study (n=2140) and replicated in another Chinese study (n=212). Dairy intake was estimated by a validated food-frequency questionnaire.

Acceleration of Brain Susceptibility-Weighted Imaging with Compressed Sensitivity Encoding: A Prospective Multicenter Study.

Background And Purpose: While three-dimensional susceptibility-weighted imaging has been widely suggested for intracranial vessel imaging, hemorrhage detection, and other neuro-diseases, its relatively long scan time has necessitated the clinical verification of recent progresses of fast imaging techniques. Our aim was to evaluate the effectiveness of brain SWI accelerated by compressed sensitivity encoding to identify the optimal acceleration factors for clinical practice.

Materials And Methods: Ninety-nine subjects, prospectively enrolled from 5 centers, underwent 8 brain SWI sequences: 5 different folds of compressed sensitivity encoding acceleration (CS2, CS4, CS6, CS8, and CS10), 2 different folds of sensitivity encoding acceleration (SF2 and SF4), and 1 without acceleration.

Auditory Brainstem Response Wave I Amplitude Has Limited Clinical Utility in Diagnosing Tinnitus in Humans.

Animal studies have discovered that noise, even at levels that produce no permanent threshold shift, may cause cochlear damage and selective nerve degeneration. A hallmark of such damage, or synaptopathy, is recovered threshold but reduced suprathreshold amplitude for the auditory brainstem response (ABR) wave I. The objective of the present study is to evaluate whether the ABR wave I amplitude or slope can be used to diagnose tinnitus in humans.

Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis.

Objective: To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).

Methods: We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing-remitting MS with a median (interquartile range) follow-up of 23.9 (23.

A small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase improves obesity, nephropathy and cardiomyopathy in obese ZSF1 rats.

Prolyl hydroxylase (PH) enzymes control the degradation of hypoxia-inducible factor (HIF), a transcription factor known to regulate erythropoiesis, angiogenesis, glucose metabolism, cell proliferation, and apoptosis. HIF-PH inhibitors (HIF-PHIs) correct anemia in patients with renal disease and in animal models of anemia and kidney disease. However, the effects of HIF-PHIs on comorbidities associated with kidney disease remain largely unknown.

Effects of Itraconazole and Rifampin on the Pharmacokinetics of Mobocertinib (TAK-788), an Oral Epidermal Growth Factor Receptor Inhibitor, in Healthy Volunteers.

Mobocertinib (TAK-788) is an investigational oral tyrosine kinase inhibitor targeting epidermal growth factor receptor and human epidermal growth factor 2. A phase 1 open-label, 2-period, fixed-sequence, 2-part study (NCT03928327) characterized effects of a strong CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on the pharmacokinetics (PK) of mobocertinib and its active metabolites, AP32960 and AP32914. Healthy volunteers (n = 12 per part) received a single dose of mobocertinib alone (20 mg, part 1; 160 mg, part 2) and with multiple doses of itraconazole 200 mg once daily (part 1) or rifampin 600 mg once daily (part 2).

Single-Dose Pharmacokinetics and Tolerability of the Oral Epidermal Growth Factor Receptor Inhibitor Mobocertinib (TAK-788) in Healthy Volunteers: Low-Fat Meal Effect and Relative Bioavailability of 2 Capsule Products.

Mobocertinib (TAK-788) is a tyrosine kinase inhibitor under investigation for treatment of non-small cell lung cancer with activating EGFR exon 20 insertions. This study examined the safety; tolerability; pharmacokinetics (PK), including food effects; and bioavailability of mobocertinib in healthy volunteers. In part 1, fasted volunteers were randomized to placebo or mobocertinib in single-ascending-dose cohorts (20-160 mg).

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

Background: Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.

Acceleration of Brain TOF-MRA with Compressed Sensitivity Encoding: A Multicenter Clinical Study.

Background And Purpose: The clinical practice of three-dimensional TOF-MRA, despite its capability in brain artery assessment, has been hampered by the relatively long scan time, while recent developments in fast imaging techniques with random undersampling has shed light on an improved balance between image quality and imaging speed. Our aim was to evaluate the effectiveness of TOF-MRA accelerated by compressed sensitivity encoding and to identify the optimal acceleration factors for routine clinical use.

Materials And Methods: One hundred subjects, enrolled at 5 centers, underwent 8 brain TOF-MRA sequences: 5 sequences using compressed sensitivity encoding with acceleration factors of 2, 4, 6, 8, and 10 (CS2, CS4, CS6, CS8, and CS10), 2 using sensitivity encoding with factors of 2 and 4 (SF2 and SF4), and 1 without acceleration as a reference sequence (RS).

Values of Baseline Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score for Treatment Decision of Acute Basilar Artery Occlusion.

Background And Purpose: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion.

Methods: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable.