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<jats:p>Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.</jats:p>

<jats:p> We analyze the results of Zhao <jats:italic>et al</jats:italic> . (Reports, 17 September 2021, p. 1363) with a focus on the mechanical properties and microstructural evolution. We conclude that their results, together with the explanations and interpretations, are confusing, misleading, or even wrong. </jats:p>

<jats:p> We address the three main points of Guo <jats:italic>et al</jats:italic> . They claim that we should have used the engineering stress versus engineering strain curves to infer the mechanical properties of our nanotwinned titanium, question our sample design on the basis of a finite-element analysis, and doubt the immobility of some preexisting grain/twin boundaries in our electron backscatter diffraction micrographs. We find their analysis to be groundless and to contain many inconsistencies. </jats:p>

<jats:p>Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.</jats:p>

<jats:p>Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type–specific RNA splicing was discovered and analyzed across tissues within an individual.</jats:p>

<jats:p> Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8 <jats:sup>+</jats:sup> T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons. </jats:p>

<jats:p> Transcriptional recording by CRISPR spacer acquisition from RNA endows engineered <jats:italic>Escherichia coli</jats:italic> with synthetic memory, which through Record-seq reveals transcriptome-scale records. Microbial sentinels that traverse the gastrointestinal tract capture a wide range of genes and pathways that describe interactions with the host, including quantitative shifts in the molecular environment that result from alterations in the host diet, induced inflammation, and microbiome complexity. We demonstrate multiplexed recording using barcoded CRISPR arrays, enabling the reconstruction of transcriptional histories of isogenic bacterial strains in vivo. Record-seq therefore provides a scalable, noninvasive platform for interrogating intestinal and microbial physiology throughout the length of the intestine without manipulations to host physiology and can determine how single microbial genetic differences alter the way in which the microbe adapts to the host intestinal environment. </jats:p>

<jats:p>The Biden administration is sheepishly waving a checkered flag on the pandemic. If you look closely, you can see its members cringing as they do so. Chief Medical Advisor Anthony Fauci told the PBS Newshour that the United States was “out of the pandemic phase” and then walked it back, saying he meant that the “acute component” of the pandemic phase was over. President Biden attended the likely superspreading White House Correspondents’ Dinner last weekend but skipped cocktails and the meal, opting to just give his talk. Fauci avoided the whole affair. Meanwhile, Vice President Harris continued to isolate after her positive COVID-19 test, and many members of Congress and the administration announced positive test results as well. All of this happened while the White House allowed a renegade federal judge in Florida (where else?) to end the nationwide mask mandate without much of a fight. These mixed messages have been emanating from the administration for months now, and although those with resources have tools to manage COVID-19, care needs to be taken that those without such means are not forgotten.</jats:p>