A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Phase I Clinical Trial of CD19 CAR-T Cells Expressing CXCR5 Protein for the Treatment of Relapsed or Refractory B-cell Lymphoma.

Background: It is difficult for CD19 CAR-T cells to enter solid tumors, which is one reason for their poor efficacy in lymphoma treatment. The chemokine CXCL13 secreted by stro-mal cells of the lymph nodes induces the homing of B and T lymphocytes, which express its receptor CXCR5. Preclinical trials have shown that the expression of CXCR5 on CD19 CAR-T cells can increase their migration to the tumor microenvironment and enhance their antitumor function.

Multi-peptide characterization of plasma neurofilament light chain in preclinical and mild Alzheimer's disease.

Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.

Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.

Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21.

Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain.

Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections.

Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests.

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F.

LncRNA Instigates Vascular Inflammation to Aggravate Atherosclerosis.

Background: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, , has been implicated in the development of tumors. Nevertheless, the precise role of in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated.

Organ aging signatures in the plasma proteome track health and disease.

Animal studies show aging varies between individuals as well as between organs within an individual, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan.

 (Gesneriaceae), a new species from north Guizhou, China.

A new lithophytic species, T.Deng, F.Wen & R.

Visualizing dynamic competitive adsorption processes between iodine and methyl iodide within single covalent organic framework crystals.

Covalent organic frameworks (COFs) are important porous adsorbents for volatile iodine (I) and methyl iodide (CHI). In situ monitoring of the dynamic adsorption process of single COF crystals toward I and CHI is a critical and fundamental issue for understanding the reaction mechanism and improving the sorption performance. Here, we report operando real-time dark-field optical microscopy (DFM) imaging of visually studying the dynamic adsorption behavior of LZU-111 (LZU=Lanzhou University) COFs in the I/CHI binary gaseous mixture at the single-crystal level.

Growth, Physiology and Nutritional Quality of C Halophyte L. Grown Aeroponically in Different Percentages of Artificial Seawater under Different Light-Emitting Diode Spectral Qualities.

Edible halophyte L., known as purslane, was grown in two percentages of artificial seawater (ASW) under two combined red (R) and blue (B) LED spectra. High salinity (40% ASW) negatively affected shoot productivity and leaf growth of purslane compared to those grown in 10% ASW.

The phenotype-genotype reference map: Improving biobank data science through replication.

Population-scale biobanks linked to electronic health record data provide vast opportunities to extend our knowledge of human genetics and discover new phenotype-genotype associations. Given their dense phenotype data, biobanks can also facilitate replication studies on a phenome-wide scale. Here, we introduce the phenotype-genotype reference map (PGRM), a set of 5,879 genetic associations from 523 GWAS publications that can be used for high-throughput replication experiments.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease.

Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219).

Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.

Photochemically Aided Arteriovenous Fistula Creation to Accelerate Fistula Maturation.

Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation.

Monomer-Promoting Asymmetric Kinetic Resolution-Alternating Copolymerization To Afford AAB-Type Copolyesters.

Living copolymerization of mixed monomers can enrich the diversity of copolymer materials with well-defined performance via controlling both monomers and stereosequences. However, periodic sequence-controlled living copolymerization of same-type monomers with more than two components in synthetic polymer science remains a challenge. In this work, a new method of monomer-promoting asymmetric kinetic resolution-alternating copolymerization can let a tricomponent mixture of l-lactide (-LA or l-LA) and two enantiomeric isomers of racemic tropic acid cyclic esters (tropicolactone) be polymerized into sequence-controlled -(AAB)- type biodegradable copolyesters (the subscript S presents the configuration and A and B present lactic acid units and tropic acid units, respectively), and diblock copolymers of -(AAB)--(AAB)- can further be obtained upon addition of -LA (dLA).

The diversity of the glycan shield of sarbecoviruses related to SARS-CoV-2.

Animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Vaccines remain successful at limiting severe disease and death, but the potential for further coronavirus zoonosis motivates the search for pan-coronavirus vaccines. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins.

Experimental measurement of quadrature squeezing in quadripartite entanglement.

Multipartite entanglement is one of the most fundamental and important resources for quantum information processing in both discrete variable and continuous variable (CV) regimes. For its applications in the CV regime, such as the realization of quantum teleportation networks and quantum dense coding, the quadrature squeezing of multipartite entanglement plays a significant role. Here, we report the first, to the best of our knowledge, experimental measurement of the quadrature squeezing in the quadripartite entanglement generated by the two-beam pumped cascaded four-wave mixing process in a vapor cell.

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery.