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Segmented filamentous bacteria drive the acquisition of the T H 17 phenotype in an antigen-specific manner; these findings begin to elucidate how gut-induced T H 17 cells can contribute to distal organ-specific autoimmune disease. T H 17 cell differentiation linked to intestinal bacteria Colonization of the small intestine by microbes such as segmented filamentous bacteria is known to enhance the induction of T-helper-17 (T H 17) cells, which are important factors in both mucosal defence and in autoimmune disease pathogenesis. Here Dan Littman and colleagues demonstrate that the vast majority of T H 17 cells in mice colonized with segmented filamentous bacteria are directed at antigens encoded by these bacteria, and identify specific bacterial epitopes that are recognized by T H 17 T-cell receptors. This work provides insights into how microbiota communicate with the host immune system, and suggests possible routes for developing novel mucosal vaccines. T-helper-17 (T H 17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis 1 , 2 , 3 . They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota 4 , 5 , 6 , 7 . Segmented filamentous bacteria (SFB) are sufficient to induce T H 17 cells and to promote T H 17-dependent autoimmune disease in animal models 8 , 9 , 10 , 11 , 12 , 13 , 14 . However, the specificity of T H 17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal T H 17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4 + T cells and that most T H 17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing T H 17 cells, even if SFB-colonized mice also harboured a strong T H 1 cell inducer, Listeria monocytogenes , in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

T-helper-17 (T^sub H^17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis. They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota. Segmented filamentous bacteria (SFB) are sufficient to induce T^sub H^17 cells and to promote T^sub H^17-dependent autoimmune disease in animal models. However, the specificity of T^sub H^17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal T^sub H^17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4^sup +^ T cells and that most T^sub H^17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing T^sub H^17 cells, even if SFB-colonized mice also harboured a strong T^sub H^1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

T-helper-17 ([T.sub.H]17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis (1-3). They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota (4-7). Segmented filamentous bacteria (SFB) are sufficient to induce [T.sub.H]17 cells and to promote [T.sub.H]17-dependent autoimmune disease in animal models (8-14). However, the specificity of [T.sub.H]17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal [T.sub.H]17 cells in SFB-colonized mice has minimal overlap with that of other intestinal [CD4.sup.+] T cells and that most [T.sub.H]17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing [T.sub.H]17 cells, even if SFB-colonized mice also harboured a strong [T.sub.H]1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

It is a question if large scale heating/cooling network could be applied in China economically, environmental protection and energy saving. Toward this question, this paper studied the optimization of large scale heating and cooling network. The components of the system are analyzed and modeled in detail including heating/cooling source, heating/cooling users and transmit system. And the system can be optimized through the way of Life Cycle Cost, which compared the cost of large scale heating and cooling system with conventional system. The optimization also takes efficiency and economy in to consideration.

This paper discussed the optimization of two cases of large scale heating and cooling system. One is the heating/cooling system with heating/cooling source with distance from load center, the other is the heating/cooling system with heating/cooling source located in the load center. The affect of the temperature difference between supply and return water, load density and the price of energy towards optimized radius and max radius was discussed using the existed model. The optimized radius and appropriate system parameters are got. It is a reference to the designers and operators related.

A tetranuclear Li2Cr2 acetylide precursor complex, [Li（Tp）crm（c=CSiMe3）2（/,t3-pz）]2· （n-pentane）2 （Tp = hydridotris（pyra- zolyl）borate, pz = pyrazolate） （1） has been synthesized and characterized. The X-ray structure analysis shows that the complex contains a Li2Cr2 core bridged by two ,u3-pyrazolates. The magnetic data exhibit the existence of weak antiferromagnetic in- teraction in the cluster.

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD—a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks. Decoy-state quantum key distribution from a satellite to a ground station is achieved with much greater efficiency than is possible over the same distance using optical fibres. Quantum security in orbit The laws of quantum physics give rise to protocols for ultra-secure cryptography and quantum communications. However, to be useful in a global network, these protocols will have to function with satellites. Extending existing protocols to such long distances poses a tremendous experimental challenge. Researchers led by Jian-Wei Pan present a pair of papers in this issue that take steps toward a global quantum network, using the low-Earth-orbit satellite Micius. They demonstrate satellite-to-ground quantum key distribution, an integral part of quantum cryptosystems, at kilohertz rates over 1,200 kilometres, and report quantum teleportation of a single-photon qubit over 1,400 kilometres. Quantum teleportation is the transfer of the exact state of a quantum object from one place to another, without physical travelling of the object itself, and is a central process in many quantum communication protocols. These two experiments suggest that Micius could become the first component in a global quantum internet.

Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.

Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intraportal injection model by reducing the infiltration of T cells. Mechanistically, tumor-associated macrophages (TAMs) activate NF-ĸB by secreting TNFα/IL-1β in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination. Disrupting the TAM-OTUD1-FGL1 axis inhibits metastatic tumor progression and synergizes with immune checkpoint blockade (ICB) therapy. Clinically, high plasma FGL1 levels predict poor outcomes and reduced ICB therapy benefits. Benzethonium chloride, an FDA-approved antiseptics, curbs FGL1 secretion, thereby inhibiting liver metastatic tumor growth. Overall, this study uncovers the critical roles and posttranslational regulatory mechanism of FGL1 in promoting metastatic tumor progression, highlighting the TAM-OTUD1-FGL1 axis as a potential target for cancer immunotherapy. The suppressive immune microenvironment in colorectal cancer (CRC) liver metastasis remains to be explored. Here, the authors find tumor-associated macrophages in the liver microenvironment induces elevated secretion of FGL1 from cancer cells and hepatocytes which promotes CRC metastasis by suppressing the infiltration of T cells.

BackgroundThe ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy.MethodsWhole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy.ResultsCompound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.Conclusion ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.