封面: 由于其建造和发射的技术壮举以及对探索宇宙的巨大承诺，JWST 被评为2022年度科学突破。在这幅插图中，太空望远镜的6.5米镜面镀金部分被描绘出来，这是其早期的一幅图像，展示了被称为“创世之柱”的巨大的恒星形成云。
推荐阅读
【脊椎动物异域物种形成过程中不同生态适应的作用】
【ATG9A 通过非经典溶酶体靶向途径阻止肿瘤坏死因子的细胞毒性】
【应变不敏感的生物电子脆性材料】刚而不折！
【合成基因环路对人类治疗性细胞功能的多维控制】
【应激信号促进干扰素诱导的巨噬细胞基因转录】
【蛋白质进入过氧化物酶体的过程有点像核孔转运物质的方式】
【内体脂质信号重塑内质网以控制线粒体功能】
【驱使T细胞进入免疫排除肿瘤的合成细胞因子环路】免疫排除肿瘤：这里指能够抵抗免疫 T 细胞的那些肿瘤，一般是实体瘤。T 细胞免疫疗法对于血液癌具有良好的效果，但由于某种原因，T 细胞难以进入实体肿瘤，本文报道的研究找到了这个“某种原因”，有望克服实体瘤免疫治疗的障碍。
SKIN INFLAMMATION
Hitting the brakes on fibrosis
-Claire Olingy
Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis【表皮调节蛋白是一种源于树突状细胞的 EGFR 配体，维持皮肤和肺纤维化】
-L. Bryan Ray
Chimeric antigen receptor T cell technology, in which cells of the immune system are modified with customized receptors, has proved effective in cancer therapy. To explore the range of cell responses that can be encoded in such receptors and to make their design more quantitative and predictive, Daniels et al. tested about 200 of 2400 possible combinations of 13 signaling motifs found in such receptors and used machine learning to predict other effective combinations. Using these design rules, the authors constructed receptors in human T cells with improved signaling characteristics that contributed to better tumor control in a mouse model.
Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning【利用组合信号基序库和机器学习解码 CAR-T 细胞表型】
-Marc S. Lavine
Zeolites are able to separate molecules with similar size and shape because of their well-defined, uniform pore size and specific adsorption properties. However, it has been a challenge to retain these features when blending a zeolite with a polymeric matrix support. Tan et al. developed a method to put high loadings of the aluminosilicate SSZ-39, which is known for its attraction of carbon dioxide, into a commercial polyimide selected for its compatibility with the zeolite. The resulting mixed matrix membranes were flexible and defect free, showing excellent separation of carbon dioxide that even exceeded the performance of pure zeolite membranes.
Truly combining the advantages of polymeric and zeolite membranes for gas separations【真正做到聚合物与沸石强强联合形成气体分离膜】
-Jake Yeston
Forming carbon–nitrogen (C–N) bonds is integral to pharmaceutical synthesis. Palladium (Pd) catalysis is an especially efficient means to this end, but alkyl amines can deactivate the catalyst by tight binding. Several recent approaches to circumventing this problem in allylic amination have focused on modifying either the amines or the Pd coordination environment. Cheung et al. report a distinct protocol that operates through photoinduced electron transfer to form versatile Pd(I) intermediates. This method is also compatible with more densely substituted carbon frameworks and can selectively produce just one of two mirror image products.
Asymmetric intermolecular allylic C–H amination of alkenes with aliphatic amines【烯烃与脂肪胺的不对称分子间烯丙基 C-H 胺化反应】
-Jelena Stajic
Spin ices have crystal lattices that consist of tetrahedra of magnetic ions. In a ground state, two of the four spins on each tetrahedron point in and two point out. When an excitation called the magnetic monopole is created, this rule is violated as the monopole moves through the crystal. Monopole dynamics are reflected in quantities such as magnetic noise, the measurements of which have shown a different frequency dependence from the one that the simplest model predicts. Hallén et al. solved this puzzle by realizing that the monopole motion is more restricted than previously thought and is limited to a cluster with a fractal structure (see the Perspective by Flicker).
Dynamical fractal and anomalous noise in a clean magnetic crystal【清洁磁性晶体中的动态分形与反常噪声】
-Bianca Lopez
The closely related Amazonian songbirds Lepidothrix iris (left) and L. natererei (right) evolved with similar traits despite living in different places. PHOTO: MAYA FACCIO © 2012 THE WEIR LAB ATTHE UNIVERSITY OF TORONTO AT SCARBOROUGH
Speciation often requires a period of allopatry, when populations are separated long enough to diverge into distinct species. Sister species may occupy different niches, but whether ecological divergence occurs during or after allopatric speciation is poorly understood. Anderson and Weir used trait data on more than 1000 pairs of sister taxa, including birds, mammals, and amphibians, to model trait divergence over time. They found few examples of clear divergent adaptation, with greater support for a model of sister taxa evolving under similar selective pressures toward similar trait optima.
The role of divergent ecological adaptation during allopatric speciation in vertebrates【脊椎动物异域物种形成过程中不同生态适应的作用】
Stella M. Hurtley
Tumor necrosis factor (TNF) is a central cytokine in inflammatory reactions and is a pharmacological target in several inflammatory disorders. Recent studies demonstrated that the pathological role of TNF in these diseases can originate from its ability to trigger cell death, an outcome that is normally actively repressed in cells. Huyghe et al. identified an unconventional lysosomal targeting process that prevents TNF cytotoxicity by degrading the caspase-8–activating complex that forms in response to TNF binding to TNF receptor 1 (TNFR1). Abrogating this detoxification mechanism caused TNFR1-mediated embryonic lethality or an inflammatory skin disease when locally inactivated in mice.
ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway【ATG9A 通过非经典溶酶体靶向途径阻止肿瘤坏死因子的细胞毒性】
-Marc S. Lavine
Most electrically conductive materials tend to be stiff and brittle, whereas human tissue is soft and compliant. It is thus a challenge to make conductive biomaterials that are sufficiently compliant but do not show a loss or distortion in performance. Zhao et al. used a three-layer design to couple strain-induced cracked films with a strain-isolated conductive pathway (see the Perspective by Rafeedi and Lipomi). Upon an initial prestrain to 100%, the brittle solid film on top cracks to dissipate the strain energy. However, this cracking permits a type of parallel, interconnected charge transport in which the charge carriers move between the layers to circumvent the cracks.
Soft strain-insensitive bioelectronics featuring brittle materials【应变不敏感的生物电子脆性材料】刚而不折！
-Valda Vinson
The promise of chimeric antigen receptor T cell therapy, in which human T cells are engineered to attack tumors, has heightened interest in cell-based therapies. Li et al. developed a toolkit of programmable synthetic transcription regulators that feature a compact, human protein–based design and allow transcription to be regulated by US Food & Drug Administration–approved small molecules. The authors engineered human immune cells that kill tumors when activated by the appropriate small molecule, and they also demonstrated a dual-switch system that allows sequential control of immune cell function. This platform could be adapted to design cell therapies in a variety of contexts.
Multidimensional control of therapeutic human cell function with synthetic gene circuits【合成基因环路对人类治疗性细胞功能的多维控制】
-Leslie K. Ferrarelli
Interferon (IFN) signaling stimulates the innate immune response to infection. Boccuni et al. investigated the interaction between IFN signaling and stress signaling mediated by the kinase p38. In IFN-treated macrophages, coincident stress signaling synergistically increased the expression of IFN-stimulated genes. In Listeria-infected cultured macrophages, this boost elicited greater production of pathogen-fighting factors, but it also increased cell death. Blocking p38 signaling preserved macrophage viability without sacrificing function.
Stress signaling boosts interferon-induced gene transcription in macrophages【应激信号促进干扰素诱导的巨噬细胞基因转录】
CELL BIOLOGY
Alike/similar pathways for import
-Stella M. Hurtley
Eukaryotic cells contain membrane-bounded organelles that import specific proteins from the cytosol. Organelles called peroxisomes are vital for human health because they house important metabolic enzymes. However, how enzymes are imported into peroxisomes has been mysterious, particularly because folded proteins and even protein oligomers can cross the peroxisomal membrane. Gao et al. found that multiple copies of a cohesive domain from the peroxisomal protein PEX13 form a dense meshwork within the membrane. Mobile import receptors can diffuse through this barrier to enter the organelle and bring bound cargo along. This mechanism resembles transport through the nuclear pore and explains how folded proteins are imported into peroxisomes.
Protein import into peroxisomes occurs through a nuclear pore–like phase【蛋白质进入过氧化物酶体的过程有点像核孔转运物质的方式】
-Stella M. Hurtley
Nutrient starvation triggers changes in metabolism that are coordinated across the cell and its organelles. Jang et al. studied how endosomal signaling lipid turnover through MTM1, a phosphoinositide 3-phosphatase mutated in X-linked centronuclear myopathy in humans, reshapes the endoplasmic reticulum to control mitochondrial morphology and oxidative metabolism. A lipid-controlled organellar relay transmits nutrient-triggered changes in endosomal signaling lipid levels to mitochondria to enable metabolic rewiring.
Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function【内体脂质信号重塑内质网以控制线粒体功能】
-L. Bryan Ray
T cells with modified receptors that recognize tumor antigens (chimeric antigen receptor or CAR T cells) have proved effective in treating B cell malignancies, but solid tumors create an immunosuppressive microenvironment that limits their function. To overcome this limitation, Allen et al. enhanced engineered T cells with a second synthetic receptor that could recognize a tumor antigen and cause the T cell to secrete the cytokine interleukin-2 . Interleukin-2 promoted local proliferation of the T cells despite the tumor’s immunosuppressive effects. Such engineered cells allowed effective treatment of solid tumors in mouse models.
Synthetic cytokine circuits that drive T cells into immune-excluded tumors【驱使T细胞进入免疫排除肿瘤的合成细胞因子环路】免疫排除肿瘤：这里指能够抵抗免疫 T 细胞的那些肿瘤，一般是实体瘤。T 细胞免疫疗法对于血液癌具有良好的效果，但由于某种原因，T 细胞难以进入实体肿瘤，本文报道的研究找到了这个“某种原因”，有望克服实体瘤免疫治疗的障碍。
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