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本文分享來自 Nature Nanotechnology / Immunity / Cancer Cell 等期刊的10篇 IF＞10的文獻摘要，讓我們一起欣賞這些文章吧。
文獻 1
[IF=25.606] Nature Immunology
DOI: 10.1038/s41590-022-01145-x
文獻引用抗體: bs-3330R | Anti-p-PERK(T980) pAb | FCM
Institution: 美國俄亥俄州克利夫蘭凱斯西儲大學(xué)醫(yī)學(xué)院病理學(xué)系
Abstract: Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.
文獻 2
[IF=17.173] Neuron
DOI: 10.1016/j.neuron.2022.01.012
文獻引用抗體：bs-11410R | Anti-mPRβ (PAQR8) pAb | Other
Institution : 法國巴黎索邦大學(xué)，巴黎腦研究所
Abstract : Optimizing reproductive fitness in mammalians requires behavioral adaptations during pregnancy. Maternal preparatory nesting is an essential behavior for the survival of the upcoming litter. Brain-wide immediate early gene mapping in mice evoked by nesting sequences revealed that phases of nest construction strongly activate peptidergic neurons of the Edinger-Westphal nucleus in pregnant mice. Genetic ablation, bidirectional neuromodulation, and in vitro and in vivo activity recordings demonstrated that these neurons are essential to modulate arousal before sleep to promote nesting specifically. We show that these neurons enable the behavioral effects of progesterone on preparatory nesting by modulating a broad network of downstream targets. Our study deciphers the role of midbrain CART+ neurons in behavioral adaptations during pregnancy vital for reproductive fitness.
文獻 3
[IF=16.806] Advanced Science
文獻引用抗體：bs-1806R | Anti-UTS2R pAb | ICC,IF
Institution : 中國科學(xué)院大學(xué),上海生物化學(xué)與細胞生物學(xué)研究所,分子細胞科學(xué)卓越中心,細胞生物學(xué)國家重點實驗室
Abstract : ntervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular applications of NP cells during IDD are currently limited due to the lack of in vivo studies showing whether NP cells are heterogeneous and contain ProNPs throughout postnatal stages. In this study, single-cell RNA sequencing of purified NP cells is used to map four molecularly defined populations and urotensin II receptor (UTS2R)-expressing postnatal ProNPs is identified, which are markedly exhausted during IDD, in mouse and human specimens. The lineage tracing shows that UTS2R+ProNPs preferentially resides in the NP periphery with its niche factor tenascin-C and give rise to functional NP cells. It is also demonstrated that transplanting UTS2R+ProNPs with tenascin-C into injured intervertebral discs attenuate the progression of IDD. The study provides a novel NP cell atlas, identified resident ProNPs with regenerative potential, and revealed promising diagnostic and therapeutic targets for IDD.
文獻 4
[IF=16.806] Advanced Science
文獻引用抗體：bs-5791R-Bio | Anti-Integrin Alpha V + Beta 6/Biotin pAb | IHC,IF
Institution : 美國約翰霍普金斯大學(xué)醫(yī)學(xué)院骨外科
文獻 5
[IF=15.881] ACS Nano
bs-1278R | Anti-8-OHdG/DNA/RNA damage pAb | Other
bs-8551R | Anti-3-nitrotyrosine pAb | Other
Institution : 中南大學(xué)湘雅藥學(xué)院
Abstract : Sepsis, a life-threating illness caused by deregulated host immune responses to infections, is characterized by overproduction of multiple reactive oxygen and nitrogen species (RONS) and excessive pyroptosis, leading to high mortality. However, there is still no approved specific molecular therapy to treat sepsis. Here we reported drug-free tea polyphenols nanoparticles (TPNs) with intrinsic broad-spectrum RONS scavenging and pyroptosis-blocking activities to treat endotoxin (LPS)-induced sepsis in mice. The RONS scavenging activities originated from the polyphenols-derived structure, while the pyroptosis blockage was achieved by inhibiting gasdermin D (GSDMD) mediating the pore formation and membrane rupture, showing multifunctionalities for sepsis therapy. Notably, TPNs suppress GSDMD by inhibiting the oligomerization of GSDMD rather than the cleavage of GSDMD, thus displaying high pyroptosis-inhibition efficiency. As a result, TPNs showed an excellent therapeutic efficacy in sepsis mice model, as evidenced by survival rate improvement, hypothermia amelioration, and the organ damage protection. Collectively, TPNs present biocompatible candidates for the treatment of sepsis.
文獻 6
[IF=14.919] Nature Communications
DOI: 10.1038/s41467-022-28533-z
文獻引用抗體：bs-1629R | Anti-CXCR2 pAb | Other
Institution : 新加坡國立大學(xué)楊潞齡醫(yī)學(xué)院生理學(xué)系
Abstract : Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.
文獻 7
[IF=14.919] Nature Communications
DOI : 10.1038/s41467-022-28509-z
文獻引用抗體：bs-1035R | Anti-CD86 pAb | IHC
Institution : 美國約翰霍普金斯大學(xué)醫(yī)學(xué)院醫(yī)學(xué)系
Abstract : In addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits more potent signatures of trained immunity including higher pro-inflammatory cytokine responses, greater myeloid cell reprogramming toward inflammatory and activated states, and enhances epigenetic and metabolomic changes. In a model of bladder cancer, we also show that re-engineered BCG induces trained immunity and improved functionality. These results indicate that trained immunity levels and antitumor efficacy may be increased by modifying BCG to express higher levels of key PAMP molecules.
文獻 8
[IF=14.593] Bioactive Materials
DOI: 10.1016/j.bioactmat.2022.02.006
文獻引用抗體：bs-0295G | Goat Anti-Rabbit IgG | WB
Institution : 重慶大學(xué)生物工程學(xué)院 生物流變科學(xué)與技術(shù)教育部重點實驗室
Abstract : To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.
文獻 9
DOI : 10.1016/j.bioactmat.2022.02.001
bs-0754R | Anti-PCNA pAb | Other
bs-2130R | Anti-Ki-67 pAb | Other
bs-0032R | Anti-Bcl-2 pAb | Other
bs-0033R | Anti-P53 pAb | Other
Institution : 山西大學(xué)生物技術(shù)研究所化學(xué)生物學(xué)與分子工程教育部重點實驗室
Abstract : Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomes and inhibiting protein synthesis. Nonetheless, its poor internalization ability to tumor cells has compromised the therapeutic promise of gelonin. In this study, a tumor acidity-responsive intracellular protein delivery system ─ functional gelonin (Trx-pHLIP-Gelonin, TpG) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP) and gelonin, was designed and obtained by genetic recombination technique for the first time. TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cell proliferation via triggering cell apoptosis and inhibiting protein synthesis. Most importantly, treatment by intravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much more effective than gelonin in curtailing tumor growth rates with negligible toxicity. Collectively, our present work suggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficient delivery of other bioactive substances to acidic diseased tissues.
文獻 10
[IF=13.281] Small
文獻引用抗體：C05-02001 | BCA protein assay kit | WB
Institution : 中南大學(xué)湘雅三醫(yī)院腦穩(wěn)態(tài)湖南省重點實驗室
Abstract : Alzheimer disease (AD) is the leading cause of dementia that affects millions of old people. Despite significant advances in the understanding of AD pathobiology, no disease modifying treatment is available. MicroRNA-124 (miR-124) is the most abundant miRNA in the normal brain with great potency to ameliorate AD-like pathology, while it is deficient in AD brain. Herein, the authors develop a DNA nanoflowers (DFs)-based delivery system to realize exogenous supplementation of miR-124 for AD therapy. The DFs with well-controlled size and morphology are prepared, and a miR-124 chimera is attached via hybridization. The DFs are further modified with RVG29 peptide to simultaneously realize brain-blood barrier (BBB) penetration and neuron targeting. Meanwhile, Rutin, a small molecular ancillary drug, is co-loaded into the DFs structure via its intercalation into the double stranded DNA region. Interestingly, Rutin could synergize miR-124 to suppress the expression of both BACE1 and APP, thus achieving a robust inhibition of amyloid β generation. The nanosystem could pro-long miR-124 circulation in vivo, promote its BBB penetration and neuron targeting, resulting in a significant increase of miR-124 in the hippocampus of APP/PS1 mice and robust therapeutic efficacy in vivo. Such a bio-derived therapeutic system shows promise as a biocompatible nanomedicine for AD therapy.
