Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.

Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields.

Agronomic biofortification of genetically biofortified wheat genotypes with zinc, selenium, iodine, and iron under field conditions.

Inherently low concentrations of zinc (Zn), iron (Fe), iodine (I), and selenium (Se) in wheat ( L.) grains represent a major cause of micronutrient malnutrition (hidden hunger) in human populations. Genetic biofortification represents a highly useful solution to this problem.

[Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus].

To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA.

[Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line].

The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.

RNA modifications in plant adaptation to abiotic stresses.

Epitranscriptomic chemical modifications of RNAs have emerged as potent regulatory mechanisms in the plant stress adaptation process. Currently, over 170 distinct chemical modifications have been identified in mRNAs, tRNAs, rRNAs, microRNAs (miRNAs), and long-noncoding RNAs (lncRNAs). The genetic and molecular studies have identified the genes responsible for adding and removing chemical modifications on RNA molecules, known as "writers" and "erasers," respectively.

Association between physical activity-related metabolic signature and cardiometabolic diseases and multimorbidity: A cohort study from UK biobank.

Objective: Physical activity has protective effects on cardiometabolic diseases (CMDs), but the role of metabolism related to physical activity in this process is unclear.

Methods: In the prospective cohort study from UK Biobank between 2006 and 2022, participants free of CMDs at baseline were included (n = 73,990). We identified physical activity-related metabolites and constructed metabolic signature using linear regression and elastic net regression.

Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a prospective multicenter clinical study.

Background: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) has been widely utilized to select euploid embryos in patients carrying balanced chromosomal rearrangements (BCRs) by chromosome copy number analysis. However, reliable and extensively validated PGT-SR methods for selecting embryos without BCRs in large-cohort studies are lacking.

Methods: In this prospective, multicenter, cohort study, carriers with BCRs undergoing PGT-SR were recruited across 12 academic fertility centers within China.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Interlaboratory variability of HER2 fluorescence in situ hybridization testing in breast cancer: results of a multicenter proficiency-testing ring study in China.

Background: Accurate detection of human epidermal growth factor receptor 2 (HER2) gene amplification via fluorescence in situ hybridization (FISH) is necessary to determine HER2 status. Although many attempts have been made to increase the consistency of the results, the actual situation still needs to be determined. To investigate the latest interlaboratory variability of HER2 FISH testing for breast cancer, a multicenter proficiency-testing ring study was conducted in China.

Co-occurrence of SARS-CoV-2 variants in rivers and sewage in India and Brazil.

The genomic monitoring of SARS-CoV-2 variants of concern (VOCs) in riverine and sewage water has been widely used as an epidemiological tool worldwide. But its utility for epidemiological assessments still needs to be evaluated in some areas. Our study encompassed thirteen Brazilian rivers spanning a vast urban expanse across the states of Rio de Janeiro, São Paulo, and Paraná.

Evolutionary engineering of : Crafting a synthetic methylotroph via self-reprogramming.

Methanol, as a non-edible feedstock, offers a promising sustainable alternative to sugar-based substrates in biochemical production. Despite progress in engineering methanol assimilation in nonmethylotrophs, the full transformation into methanol-dependent synthetic methylotrophs remains a formidable challenge. Here, moving beyond the conventional rational design principle, we engineered a synthetic methylotrophic through genome rearrangement and adaptive laboratory evolution.

Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.

Asthenoteratozoospermia is a common cause of male infertility. To further define the genetic causes underlying asthenoteratozoospermia, we performed whole-exome sequencing in a cohort of Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of MYCBPAP were first identified in two unrelated Chinese cases.

Changes in Cardiovascular Health, Genetic Risk, and Cardiometabolic Diseases: Evidence From a Large-Scale Cohort Study.

Background: Evidence has firmly established the association between superior cardiovascular health (CVH) and reduced susceptibility to cardiometabolic diseases (CMDs). In reality, CVH experiences dynamic fluctuations throughout individuals' lifespans. However, the association between changes in CVH and the impact on CMDs among individuals with different genetic risks remains unclear.

Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells.

Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20.

Variations in Furin SNPs, a Major Concern of SARS-CoV-2 Susceptibility Among Different Populations: An - Approach.

COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) had an adverse effect globally because it caused a global pandemic with several million deaths. This virus possesses spike protein that is cleaved or activated by Furin-like protease enzymes occurring by mammalian lung or respiratory cells to enter the mammalian body. The addition of the Furin cleavage site in SARS-CoV-2 makes it a more infectious and emerging virus than its ancestor's viruses.

Alkhumra Hemorrhagic Fever Virus (AHFV): A Concise Overview.

Alkhumra fever is a viral disease caused by the Alkhumra hemorrhagic fever virus (AHFV). It belongs to family , genus . AHFV is primarily transmitted to humans through the bite of infected ticks, for example, .

Monkeypox (Mpox): Diagnosis and Emerging Challenges.

Monkeypox (Mpox) has once again been designated a Public Health Emergency of International Concern (PHEIC) as of August, 2024. The severity of the disease is underscored by its significant mortality rate, and unfortunately, there are no targeted therapeutics currently available for this viral infection. Management relies on preventive measures and the use of existing smallpox vaccines due to their genetic similarity to the Mpox virus.

AMPK Activates Cellulase Secretion in Penicillium funiculosum by Downregulating P-HOG1 MAPK Levels.

Cellulase production for hydrolyzing plant cell walls is energy-intensive in filamentous fungi during nutrient scarcity. AMP-activated protein kinase (AMPK), encoded by snf1, is known to be the nutrient and energy sensor in eukaryotes. Previous studies on AMPK identified its role in alternate carbon utilization in pathogenic fungi.

Integration of metabolomics and other omics: from microbes to microbiome.

Metabolomics is a cutting-edge omics technology that identifies metabolites in organisms and their environments and tracks their fluctuations. This field has been extensively utilized to elucidate previously unknown metabolic pathways and to identify the underlying causes of metabolic changes, given its direct association with phenotypic alterations. However, metabolomics inherently has limitations that can lead to false positives and false negatives.

The exploration of high production of tiancimycins in Streptomyces sp. CB03234-S revealed potential influences of universal stress proteins on secondary metabolisms of streptomycetes.

Background: Universal stress proteins (USPs) are prevalent in various bacteria to cope with different adverse stresses, while their possible effects on secondary metabolisms of hosts are unclear. Tiancimycins (TNMs) are ten-membered endiynes possessing excellent potential for development of anticancer antibody-drug conjugates. During our efforts to improve TNMs titer, a high-producing strain Streptomyces sp.

Designing strong inducible synthetic promoters in yeasts.

Inducible promoters are essential for precise control of target gene expression in synthetic biological systems. However, engineering eukaryotic promoters is often more challenging than engineering prokaryotic promoters due to their greater mechanistic complexity. In this study, we describe a simple and reliable approach for constructing strongly inducible synthetic promoters with minimum leakiness in yeasts.

The crosstalks between vascular endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts in vascular remodeling.

Pathological vascular remodeling (VR) is characterized by structural and functional alterations in the vascular wall resulting from injury, which significantly contribute to the development of cardiovascular diseases (CVDs). The vascular wall consists primarily of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and adventitial fibroblasts (AFs), whose interactions are crucial for both the formation of the vascular system and the maintenance of mature blood vessels. Disruptions in the communication between these cell types have been implicated in the progression of VR.