Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been proposed to underlie the pathophysiology of schizophrenia, suggesting that promoting NMDAR activity may alleviate the negative or cognitive symptoms associated with schizophrenia. To circumvent excitotoxicity that may accompany direct agonism of the glutamate binding site on the NMDAR, therapeutic trials have focused on targeting the glycine binding site on the NMDAR. Direct administration of either glycine or D-serine, both of which are endogenous coagonists at the NMDAR glycine site, has yielded mixed outcomes across an array of clinical trials investigating different doses or patient populations.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Engineered cyanobacteria-FeO hybrid system as oxygen generator and photosensitizer production factory for synergistic cancer PDT-immunotherapy.

The combination of photodynamic therapy (PDT)-immunotherapy has brought much hope for cancer patients. However, the hypoxia tumor microenvironment (TME) can regulate tumor angiogenesis and inhibit immune response, thus limiting the therapeutic effects. In this paper, engineered cyanobacteria-M2-like tumor-associated macrophages (TAMs) targeting peptide modified FeO nanoparticles hybrid system (ECyano@FeO-M2pep) was constructed for alleviating hypoxia and relieving immune suppression to achieve synergistic cancer PDT-immunotherapy.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Background: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.

Patients And Methods: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021.

Risk of carditis among adolescents after extending the interdose intervals of BNT162b2.

Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive.

Logical Magic State Preparation with Fidelity beyond the Distillation Threshold on a Superconducting Quantum Processor.

Fault-tolerant quantum computing based on surface code has emerged as an attractive candidate for practical large-scale quantum computers to achieve robust noise resistance. To achieve universality, magic states preparation is a commonly approach for introducing non-Clifford gates. Here, we present a hardware-efficient and scalable protocol for arbitrary logical state preparation for the rotated surface code, and further experimentally implement it on the Zuchongzhi 2.

SARS-CoV-2 infection establishes a stable and age-independent CD8 T cell response against a dominant nucleocapsid epitope using restricted T cell receptors.

The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8 T cells play a vital role. Nonetheless, the characterization of the specificity and TCR composition of CD8 T cells targeting non-spike protein of SARS-CoV-2 before and after infection remains incomplete. Here, we analyzed CD8 T cells recognizing six epitopes from the SARS-CoV-2 nucleocapsid (N) protein and found that SARS-CoV-2 infection slightly increased the frequencies of N-recognizing CD8 T cells but significantly enhanced activation-induced proliferation compared to that of the uninfected donors.

Effectiveness of BNT162b2 after extending the primary series dosing interval in children and adolescents aged 5-17.

Extended intervals between the first and second doses of mRNA Covid-19 vaccines may reduce the risk of myocarditis in children and adolescents. However, vaccine effectiveness after this extension remains unclear. To examine this potential variable effectiveness, we conducted a population-based nested case-control study of children and adolescents aged 5-17 years who had received two doses of BNT162b2 in Hong Kong.

Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort.

Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort.

Tackling Dialysis Burden around the World: A Global Challenge.

CKD is a global problem that causes significant burden to the healthcare system and the economy in addition to its impact on morbidity and mortality of patients. Around the world, in both developing and developed economies, the nephrologists and governments face the challenges of the need to provide a quality and cost-effective kidney replacement therapy for CKD patients when their kidneys fail. In December 2019, the 3rd International Congress of Chinese Nephrologists was held in Nanjing, China, and in the meeting, a symposium and roundtable discussion on how to deal with this CKD burden was held with opinion leaders from countries and regions around the world, including Australia, Canada, China, Hong Kong, Singapore, Taiwan, the UK, and the USA.

Impacts of Short-Term Fine Particulate Matter Exposure on Blood Pressure Were Modified by Control Status and Treatment in Hypertensive Patients.

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Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.

Background: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture.

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

Background And Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.

Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).

Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19.

Data Sources: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020.

A Novel Next-Generation Sequencing and Analysis Platform to Assess the Identity of Recombinant Adeno-Associated Viral Preparations from Viral DNA Extracts.

Recombinant adeno-associated virus (rAAV) vectors are increasingly popular gene delivery tools in biological systems. They are safe and lead to high-level, long-term transgene expression. rAAV are available in multiple serotypes, natural or engineered, which enable targeting to a wide array of tissues and cell types.

RESCUE-AF in Patients Undergoing Atrial Fibrillation Ablation: The RESCUE-AF Trial.

Background: Although contact force (CF)–sensing catheters improve procedural effectiveness and safety of atrial fibrillation ablation, recent reports documented a higher incidence of atrioesophageal fistula formation relative to ablation with non–CF-sensing catheters.The present study was to assess whether restricting CF to <20 g reduced risk for esophageal injury (EI) in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation.

Methods: This prospective, single-center, randomized study enrolled 89 consecutive patients (mean age, 57.

sp. nov., a chitin-degrading strain isolated from saline-alkaline soil.

Strains of , thought to play vital roles in the environment for their high enzyme production capacity, are ubiquitous in various ecosystems. During an analysis of bacterial diversity in saline soil, a Gram-stain-negative, aerobic, chitin-degrading bacterial strain, designated SJ-36, was isolated from saline-alkaline soil sampled at Tumd Right Banner, Inner Mongolia, PR China. Strain SJ-36 grew at 4-40 °C (optimum, 30 °C), pH 5.

Acute Effects of High-Level PM Exposure on Central Blood Pressure.

Central aortic blood pressure (BP) has been increasingly recognized as having a closer relationship with cardiovascular risks than peripheral BP. However, the effects of particulate matter pollution on central aortic BP have not been clearly demonstrated. In this study, we assessed the association between short-term ambient fine particulate matter (with an aerodynamic diameter ≤2.

Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

Background: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown.

Methods: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia.

Multi-platform discovery of haplotype-resolved structural variation in human genomes.

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome.

P53 ICE CRIM mouse: a tool to generate mutant allelic series in somatic cells and germ lines for cancer studies.

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology facilitates somatic genome editing to reveal cooperative genetic interactions at the cellular level without extensive breeding between different mutant animals. Here we propose a transgenic inducible Cas9 effector-CRISPR mutagen ( ICE CRIM) mouse model in which CRISPR/Cas9-mediated somatic mutagenesis events can occur in response to Cre expression. The well-known tumor suppressor gene, Trp53, and 2 important DNA mismatch repair genes, Mlh1 and Msh2, were selected to be our somatic mutagenesis targets.

Use of Atropine for Prevention of Childhood Myopia Progression in Clinical Practice.

Objective: The most effective strategy to reduce myopia-related complications is to prevent myopia progression during childhood. This review article examines the latest published evidence on the use of atropine in childhood myopia control and discusses practical aspects of applying the findings to clinical practice. Future directions including possible forms of combination therapy are examined.