SOCS1 acts as a ferroptosis driver to inhibit the progression and chemotherapy resistance of triple-negative breast cancer.

OBJECTIVES: Ferroptosis is involved in many types of cancers, including triple-negative breast cancer (TNBC). Suppressor of cytokine signaling 1 (SOCS1) has recently been implicated as a regulator of ferroptosis. We aim to explore whether targeting SOCS1 is a potential therapeutic strategy for TNBC therapy. METHODS: Stable cell lines were constructed using lentivirus transfection. Cell viability was determined using CCK-8 and cell colony formation assays, respectively. Assays including lactate dehydrogenase release, lipid peroxidation and malondialdehyde assays were conducted to evaluate ferroptosis. Real-time quantitative polymerase chain reaction and western blotting were performed to evaluate mRNA and protein expression, respectively. A xenograft animal model was established by subcutaneous injection of cells into the flank. RESULTS: Our results showed that SOCS1 overexpression inhibited cell proliferation and induced ferroptosis in TNBC cells, while SOCS1 knockdown promoted cell proliferation and reduced ferroptosis. We also found that SOCS1 regulated ferroptosis by modulating GPX4 expression. Furthermore, SOCS1 regulated cisplatin resistance in TNBC cells by promoting ferroptosis. Our in vivo data suggested that SOCS1 regulated tumor growth and cisplatin resistance in vivo. CONCLUSIONS: SOCS1 inhibits the progression and chemotherapy resistance of TNBC by regulating GPX4 expression.

Enhancing photon generation rate with broadband room-temperature quantum memory.

Photons with high generation rate is one of the essential resources for quantum communication, quantum computing and quantum metrology. Due to the naturally memory-built-in feature, the memory-based photon source is a promising route towards large-scale quantum information processing. However, such photon sources are mostly implemented in extremely low-temperature ensembles or isolated systems, limiting its physical scalability. Here we realize a single-photon source based on a far off-resonance Duan-Lukin-Cirac-Zoller quantum memory at broadband and room-temperature regime. By harnessing high-speed feedback control and repeat-until-success write process, the photon generation rate obtains considerable enhancement up to tenfold. Such a memory-enhanced single-photon source, based on the broadband room-temperature quantum memory, suggests a promising way for establishing large-scale quantum memory-enabled network at ambient condition.

Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity.

Whether a small GTPase RhoA plays a role in the pathology of abdominal aortic aneurysm (AAA) has not been determined. We show here that RhoA expression is reduced in human AAA lesions, compared with normal areas. Furthermore, incidence of AAA formation is increased in vascular smooth muscle cell (VSMC)-specific RhoA conditional knockout (cKO) mice. The contractility of the aortic rings and VSMCs from RhoA cKO mice is reduced, and expression of genes related to the VSMC contractility is attenuated by loss of RhoA. RhoA depletion activates the mitogen-activated protein (MAP) kinase signaling, including MAP4K4, in the aorta and VSMCs. Inhibition of MAP4K4 activity by DMX-5804 decreases AAA formation. Set, a binding protein to active RhoA, functions as an activator of MAP4K4 by sequestering PP2A, an inhibitor of MAP4K4, in the absence of RhoA. In conclusion, RhoA counteracts AAA formation through inhibition of MAP4K4 in cooperation with Set.

Association of CLTA-4 Gene Polymorphisms with Diabetes Mellitus: A Study Based on the Han Population of Northern China.

Objective: This study aimed to investigate the association of CLTA-4 gene polymorphism with Type 1 and 2 diabetes mellitus (DM) (T1DM and T2DM) in the Han population of northern China. Methods: A total of 234 Chinese Han DM patients and 187 non-diabetic subjects were included in the study. Two gene polymorphisms of the CLTA-4, including CTLA-4+49A/G (rs231775) and CTLA4-318C/T (rs5742909), were studied using polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) analysis. Chi-square analysis and Student's t-test were performed to determine the distribution of the gene polymorphism and alleles at the locus of CTLA4-318C/T and CTLA4+49A/G among T1DM and T2DM patients with or without diabetic ketosis (DK), diabetic nephropathy (DN) or autoantibodies (Ab). Results: Our results indicated that the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G and CTLA4-318C/T loci of T1DM patients were not significantly different from those of the controls. However, the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G loci of T2DM patients were significantly different from the controls (P=0.024 for genotypes and P=0.004 for A and G alleles). Besides, the A and G alleles at the CTLA4-318C/T loci of T2DM DK+ patients showed significantly different distribution frequencies compared to those of the T2DM DK patients (P=0.001). Conclusion: Our data suggest that the gene polymorphisms of CTLA-4, including CTLA-4+49A/G and CTLA4-318C/T, are important predictors of DM. CTLA-4 may be a susceptibility gene for T2DM. Patients with T2DM carrying the T allele at the CTLA4-318 C/T locus are more predisposed to diabetic ketosis.

Cardio- and reno-protective effects of dipeptidyl peptidase III in diabetic mice.

Diabetes mellitus (DM) causes injury to tissues and organs, including to the heart and kidney, resulting in increased morbidity and mortality. Thus, novel potential therapeutics are continuously required to minimize DM-related organ damage. We have previously shown that dipeptidyl peptidase III (DPPIII) has beneficial roles in a hypertensive mouse model, but it is unknown whether DPPIII has any effects on DM. In this study, we found that intravenous administration of recombinant DPPIII in diabetic db/db mice for 8 weeks suppressed the DM-induced cardiac diastolic dysfunctions and renal injury without alteration of the blood glucose level. This treatment inhibited inflammatory cell infiltration and fibrosis in the heart and blocked the increase in albuminuria by attenuating the disruption of the glomerular microvasculature and inhibiting the effacement of podocyte foot processes in the kidney. The beneficial role of DPPIII was, at least in part, mediated by the cleavage of a cytotoxic peptide, named Peptide 2, which was increased in db/db mice compared with normal mice. This peptide consisted of nine amino acids, was a digested fragment of complement component 3 (C3), and had an anaphylatoxin-like effect determined by the Miles assay and chemoattractant analysis. The effect was dependent on its interaction with the C3a receptor and protein kinase C-mediated RhoA activation downstream of the receptor in endothelial cells. In conclusion, DPPIII plays a protective role in the heart and kidney in a DM animal model through cleavage of a peptide that is a part of C3.

A hybrid quantum memory-enabled network at room temperature.

Quantum memory capable of storage and retrieval of flying photons on demand is crucial for developing quantum information technologies. However, the devices needed for long-distance links are different from those envisioned for local processing. We present the first hybrid quantum memory-enabled network by demonstrating the interconnection and simultaneous operation of two types of quantum memory: an atomic ensemble-based memory and an all-optical Loop memory. Interfacing the quantum memories at room temperature, we observe a well-preserved quantum correlation and a violation of Cauchy-Schwarz inequality. Furthermore, we demonstrate the creation and storage of a fully-operable heralded photon chain state that can achieve memory-built-in combining, swapping, splitting, tuning, and chopping single photons in a chain temporally. Such a quantum network allows atomic excitations to be generated, stored, and converted to broadband photons, which are then transferred to the next node, stored, and faithfully retrieved, all at high speed and in a programmable fashion.

Quantum simulation of particle pair creation near the event horizon.

Though it is still a big challenge to unify general relativity and quantum mechanics in modern physics, the theory of quantum field related with the gravitational effect has been well developed and some striking phenomena are predicted, such as Hawking radiation. However, the direct measurement of these quantum effects under general relativity is far beyond present experiment techniques. Fortunately, the emulation of general relativity phenomena in the laboratory has become accessible in recent years. However, up to now, these simulations are limited either in classical regime or in flat space whereas quantum simulation related with general relativity is rarely involved. Here we propose and experimentally demonstrate a quantum evolution of fermions in close proximity to an artificial black hole on a photonic chip. We successfully observe the acceleration behavior, quantum creation, and evolution of a fermion pair near the event horizon: a single-photon wave packet with positive energy escapes from the black hole while negative energy is captured. Our extensible platform not only provides a route to access quantum effects related with general relativity, but also has the potentiality to investigate quantum gravity in future.

The effects of hyperuricemia on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells are implicated in the elevated risk of osteopenia and vascular calcification in gout: An in vivo and in vitro analysis.

BACKGROUND: In this study, we established both an animal model and a cellular model of hyperuricemia (HUC). Subsequently, we treated these models with allopurinol (ALLO) to study the effect of uric acid (UA) and ALLO on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells (VSMC). METHODS: Western Blot, immunohistochemistry assay, and real-time polymerase chain reaction were conducted to measure the changes in the expression of differentiation-related factors in osteoblasts and VSMCs in HUC and HUC+ALLO groups. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry were utilized to observe the changes in the proliferation of osteoblasts in HUC and HUC+ALLO groups. Von Kossa staining was performed along with calcium content measurement to investigate the effect of HUC/ALLLO on vascular calcification. RESULTS: In this study, the levels of Wnt3a and differentiation-related factors, including Runx2, Sp7, Ibsp, Bglap, Dmp1, and Col1a1, were all evidently decreased in HUC rats, while the presence of ALLO increased the levels of above factors. In addition, the viability of osteoblasts was reduced while their apoptosis was elevated in the HUC group, and ALLO treatment reduced the apoptosis and increased the viability of osteoblasts to a certain extent. Moreover, HUC elevated the levels of Wnt3a, Runx2, Sp7, Bglap, Col1a1, SM22a, and Acta2 in VSMCs of HUC rats, leading to greatly increased calcium content and obvious vascular calcification. In contrary, ALLO treatment reduced the effect of HUC. Furthermore, the effect of UA and ALLO on osteoblasts and VSMCs was also validated in cellular models treated with monosodium urate (MSU) crystals or MSU+ALLO. CONCLUSIONS: HUC can suppress the differentiation and proliferation of osteoblasts while promoting the differentiation of VSMCs both in vivo and in vitro. The treatment by ALLO exhibited a therapeutic effect on HUC by promoting the differentiation and proliferation of osteoblasts while reducing vascular calcification.

Parity-Induced Thermalization Gap in Disordered Ring Lattices.

The gaps separating two different states widely exist in various physical systems: from the electrons in periodic lattices to the analogs in photonic, phononic, plasmonic systems, and even quasicrystals. Recently, a thermalization gap, an inaccessible range of photon statistics, was proposed for light in disordered structures [Nat. Phys. 11, 930 (2015)NPAHAX1745-247310.1038/nphys3482], which is intrinsically induced by the disorder-immune chiral symmetry and can be reflected by the photon statistics. The lattice topology was further identified as a decisive role in determining the photon statistics when the chiral symmetry is satisfied. Being very distinct from one-dimensional lattices, the photon statistics in ring lattices are dictated by its parity, i.e., odd or even sited. Here, we for the first time experimentally observe a parity-induced thermalization gap in strongly disordered ring photonic structures. In a limited scale, though the light tends to be localized, we are still able to find clear evidence of the parity-dependent disorder-immune chiral symmetry and the resulting thermalization gap by measuring photon statistics, while strong disorder-induced Anderson localization overwhelms such a phenomenon in larger-scale structures. Our results shed new light on the relation among symmetry, disorder, and localization, and may inspire new resources and artificial devices for information processing and quantum control on a photonic chip.

Experimental Quantum-enhanced Cryptographic Remote Control.

The Internet of Things (IoT), as a cutting-edge integrated cross-technology, promises to informationize people's daily lives, while being threatened by continuous challenges of eavesdropping and tampering. The emerging quantum cryptography, harnessing the random nature of quantum mechanics, may also enable unconditionally secure control network, beyond the applications in secure communications. Here, we present a quantum-enhanced cryptographic remote control scheme that combines quantum randomness and one-time pad algorithm for delivering commands remotely. We experimentally demonstrate this on an unmanned aircraft vehicle (UAV) control system. We precharge quantum random numbers (QRN) into controller and controlee before launching UAV, instead of distributing QRN like standard quantum communication during flight. We statistically verify the randomness of both quantum keys and the converted ciphertexts to check the security capability. All commands in the air are found to be completely chaotic after encryption, and only matched keys on UAV can decipher those commands precisely. In addition, the controlee does not response to the commands that are not or incorrectly encrypted, showing the immunity against interference and decoy. Our work adds true randomness and quantum enhancement into the realm of secure control algorithm in a straightforward and practical fashion, providing a promoted solution for the security of artificial intelligence and IoT.

Novel Therapeutic Role for Dipeptidyl Peptidase III in the Treatment of Hypertension.

Dipeptidyl peptidase III (DPP III) cleaves dipeptide residues from the N terminus of polypeptides ranging from 3 to 10 amino acids in length and is implicated in pathophysiological processes through the breakdown of certain oligopeptides or their fragments. In this study, we newly identified the biochemical properties of DPP III for angiotensin II (Ang II), which consists of 8 amino acids. DPP III quickly and effectively digested Ang II with Km = 3.7×10(-6) mol/L. In the in vivo experiments, DPP III remarkably reduced blood pressure in Ang II-infused hypertensive mice without alteration of heart rate. DPP III did not affect hemodynamics in noradrenalin-induced hypertensive mice or normotensive mice, suggesting specificity for Ang II. When DPP III was intravenously injected every other day for 4 weeks after Ang II osmotic minipump implantation in mice, Ang II-induced cardiac fibrosis and hypertrophy were significantly attenuated. This DPP III effect was at least similar to that caused by an angiotensin receptor blocker candesartan. Furthermore, administration of DPP III dramatically reduced the increase in urine albumin excretion and kidney injury and inflammation markers caused by Ang II infusion. Both DPP III and candesartan administration showed slight additive inhibition in the albumin excretion. These results reveal a novel potential use of DPP III in the treatment of hypertension and its protective effects on hypertension-sensitive organs, such as the heart and kidneys.

Significance of serum Zn-α2-glycoprotein for the regulation of blood pressure.

Zn-α2-glycoprotein (ZAG) (molecular weight=41 kDa) is one component in the α2 fraction of human plasma, and is reported to be associated with several diseases, such as cancers and metabolic syndromes. ZAG is also considered to be an important modulator of lipid metabolism. However, little is known about the correlation of serum ZAG levels with indicators of metabolic syndrome. Serum ZAG concentrations analyzed by enzyme-linked immunoassay were positively correlated with systolic and diastolic blood pressure in 326 subjects (236 males and 90 females) aged 17-79 years who had an annual health examination. By luciferase reporter and electrophoretic mobility shift assays, the core promoter region to regulate the ZAG gene expression was found to exist between -110 and -101. The transcription factor Sp1 interacted with this region, and Sp1 knockdown experiments showed that Sp1 critically regulated ZAG expression. Furthermore, ZAG increased the active form of RhoA, which was determined by pull-down assay. Increased serum ZAG concentrations induced, at least partly, by Sp1 may cause an increase in vascular tone through the activation of RhoA and contribute to elevated blood pressure.