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1.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1997-2005, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39233430

RÉSUMÉ

Ecosystem regime shifts refer to the drastically changes of an ecosystem from one state to another after suffering disturbances that exceed the thresholds. Although land desertification and grassland degradation, which are common in the cold and arid regions, are gradual processes, sudden changes can also occur when the duration or intensity of disturbances exceed the thresholds. Therefore, the study of ecosystem regime shifts is of great significance to the management of ecosystems in cold and arid regions. In this review, we summarized the evolution of ecosystem regime shift theory and early warning signals, and analyzed the problems of land desertification and grassland degradation in cold and arid regions, as well as potential responses of ecosystems to different stresses. We further put forward research frameworks for the evolution and mutation characteristics of the rain-fed artificial sand fixation system and alpine meadows. The future research needed to be strengthened in identifying the key drivers of ecosystem regime shifts at different stages, determining the corresponding thresholds, emphasizing the mechanism of water-limited mutation induced by extreme climatic events and its early warning, and promoting the application of regime shift research to ecosystem management in arid and arid regions.


Sujet(s)
Conservation des ressources naturelles , Climat désertique , Écosystème , Conservation des ressources naturelles/méthodes , Prairie , Basse température , Chine , Changement climatique
2.
Front Immunol ; 15: 1409302, 2024.
Article de Anglais | MEDLINE | ID: mdl-39221255

RÉSUMÉ

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.


Sujet(s)
Aclarubicine , Protocoles de polychimiothérapie antinéoplasique , Maladie du greffon contre l'hôte , Facteur de stimulation des colonies de granulocytes , Transplantation de cellules souches hématopoïétiques , Leucémie aigüe myéloïde , Transplantation homologue , Humains , Leucémie aigüe myéloïde/thérapie , Leucémie aigüe myéloïde/mortalité , Transplantation de cellules souches hématopoïétiques/effets indésirables , Mâle , Femelle , Adulte , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Maladie du greffon contre l'hôte/prévention et contrôle , Maladie du greffon contre l'hôte/étiologie , Facteur de stimulation des colonies de granulocytes/administration et posologie , Aclarubicine/usage thérapeutique , Aclarubicine/administration et posologie , Jeune adulte , Cytarabine/usage thérapeutique , Cytarabine/administration et posologie , Idarubicine/administration et posologie , Idarubicine/usage thérapeutique , Récepteur-1 de mort cellulaire programmée/antagonistes et inhibiteurs , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Adolescent , Résultat thérapeutique , Récidive , Sujet âgé
3.
Phys Rev Lett ; 133(5): 050402, 2024 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-39159081

RÉSUMÉ

We study the interplay between measurement-induced dynamics and conditional unitary evolution in quantum systems. We numerically and analytically investigate commuting random measurement and feed forward (MFF) processes and find a sharp transition in their ability to generate entanglement negativity as the number of MFF channels varies. We also establish a direct connection between these findings and transitions induced by random dephasing from an environment with broken time-reversal symmetry. In one variant of the problem, we employ free probability theory to rigorously prove the transition's existence. Furthermore, these MFF processes have dynamic circuit representations that can be experimentally explored on current quantum computing platforms.

4.
Chem Commun (Camb) ; 60(67): 8908-8911, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39091214

RÉSUMÉ

A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[b]indoles and 6,7-dihydrodibenzo[a,c][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives.

5.
Proc Natl Acad Sci U S A ; 121(35): e2406787121, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39163337

RÉSUMÉ

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics.


Sujet(s)
Matériaux biocompatibles , Hydrogels , Muscles squelettiques , Animaux , Hydrogels/composition chimique , Matériaux biocompatibles/composition chimique , Muscles squelettiques/métabolisme , Souris , Mécanotransduction cellulaire , Cellules souches/métabolisme , Cellules souches/cytologie , Protéine G RhoA/métabolisme , Cellules cultivées
6.
PLoS Negl Trop Dis ; 18(8): e0012428, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39159234

RÉSUMÉ

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.


Sujet(s)
Curcumine , Histone acetyltransferases , Schistosoma japonicum , Animaux , Schistosoma japonicum/effets des médicaments et des substances chimiques , Curcumine/pharmacologie , Histone acetyltransferases/antagonistes et inhibiteurs , Histone acetyltransferases/métabolisme , Histone acetyltransferases/génétique , Femelle , Mâle , Antienzymes/pharmacologie , Microscopie électronique à balayage , Réaction de polymérisation en chaine en temps réel , Souris , Schistosomicides/pharmacologie
7.
Exp Gerontol ; 194: 112514, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38971132

RÉSUMÉ

Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.


Sujet(s)
Maladie d'Alzheimer , Transport axonal , Mitochondries , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/métabolisme , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/génétique , Maladie d'Alzheimer/métabolisme , Mitochondries/métabolisme , Animaux , Humains , Motifs d'acides aminés , Souris , Mitophagie , Apoptose , Précurseur de la protéine bêta-amyloïde/métabolisme , Précurseur de la protéine bêta-amyloïde/génétique , Mutation , Neurones/métabolisme
8.
Phys Rev Lett ; 132(25): 250401, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38996232

RÉSUMÉ

We propose a new approach to simulate the decoherence of a central spin coupled to an interacting dissipative spin bath with cluster-correlation expansion techniques. We benchmark the approach on generic 1D and 2D spin baths and find excellent agreement with numerically exact simulations. Our calculations show a complex interplay between dissipation and coherent spin exchange, leading to increased central spin coherence in the presence of fast dissipation. Finally, we model near-surface nitrogen-vacancy centers in diamond and show that accounting for bath dissipation is crucial to understanding their decoherence. Our method can be applied to a variety of systems and provides a powerful tool to investigate spin dynamics in dissipative environments.

9.
Lab Invest ; 104(8): 102090, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38830579

RÉSUMÉ

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.


Sujet(s)
Antinéoplasiques , Résistance aux médicaments antinéoplasiques , Immunothérapie , Oxaliplatine , Tumeurs de l'estomac , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/pharmacologie , Marqueurs biologiques tumoraux/métabolisme , Marqueurs biologiques tumoraux/génétique , Lignée cellulaire tumorale , Immunothérapie/méthodes , Oxaliplatine/usage thérapeutique , Oxaliplatine/pharmacologie , Pronostic , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/traitement médicamenteux , Tumeurs de l'estomac/génétique , Tumeurs de l'estomac/immunologie , Tumeurs de l'estomac/thérapie
10.
J Phys Chem A ; 128(27): 5243-5252, 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38937149

RÉSUMÉ

Direct methanol fuel cells (DMFCs) have attracted increasing attention as a very promising and important energy source. In this paper, density functional theory (DFT) is used to study the structure and O-H fracture mechanism of methanol adsorption on PtnCu4-n (111) (n = 1, 2, 3) binary metal catalyst surfaces under different coverages. By comparing the adsorption energy and dehydrogenation energy barriers of methanol, it is found that the adsorption strength and dehydrogenation energy barriers of methanol on Pt and Cu sites decreased with increasing coverage. At the same Pt and Cu ratio, methanol is more easily adsorbed on Cu sites. When Pt/Cu = 3:1 and 1:3, the PtCu binary catalyst has a significant impact on the energy barrier of breaking the O-H bond in methanol with the increase of coverage. Especially when Pt/Cu = 1:3 and the coverage is 1/4 ML, the energy barriers of O-H bond breaking in methanol on Pt and Cu sites are 0.63 and 0.61 eV, respectively, which are lower than that on pure Pt. It means that the Cu sites played a very important role in reducing the O-H fracture energy barrier of methanol. When Pt/Cu = 1:1, the change in the dehydrogenation energy barrier of methanol on Pt sites and Cu sites is not significant, indicating that the coverage has little effect on it.

11.
J Org Chem ; 89(13): 9381-9388, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38885147

RÉSUMÉ

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

12.
Biomed Environ Sci ; 37(4): 387-398, 2024 Apr 20.
Article de Anglais | MEDLINE | ID: mdl-38727161

RÉSUMÉ

Objective: Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP. Methods: Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays. Results: The M-RAP method had sensitivity rates of 1, 10, and 1 copies/µL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively ( P < 0.05). Conclusion: An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.


Sujet(s)
Bactériémie , Lectine liant le mannose , Humains , Lectine liant le mannose/sang , Bactériémie/diagnostic , Bactériémie/microbiologie , Bactériémie/sang , Recombinases/métabolisme , Acinetobacter baumannii/génétique , Acinetobacter baumannii/isolement et purification , Staphylococcus aureus/isolement et purification , Staphylococcus aureus/génétique , Pseudomonas aeruginosa/isolement et purification , Pseudomonas aeruginosa/génétique , Réaction de polymérisation en chaîne/méthodes , Sensibilité et spécificité , Bactéries/génétique , Bactéries/isolement et purification
13.
World J Gastroenterol ; 30(17): 2354-2368, 2024 May 07.
Article de Anglais | MEDLINE | ID: mdl-38813048

RÉSUMÉ

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.


Sujet(s)
Antibactériens , Association de médicaments , Infections à Helicobacter , Helicobacter pylori , Minocycline , Humains , Minocycline/effets indésirables , Minocycline/administration et posologie , Minocycline/usage thérapeutique , Infections à Helicobacter/traitement médicamenteux , Infections à Helicobacter/microbiologie , Helicobacter pylori/effets des médicaments et des substances chimiques , Antibactériens/effets indésirables , Antibactériens/usage thérapeutique , Antibactériens/administration et posologie , Association de médicaments/méthodes , Résultat thérapeutique , Inhibiteurs de la pompe à protons/effets indésirables , Inhibiteurs de la pompe à protons/usage thérapeutique , Inhibiteurs de la pompe à protons/administration et posologie , Adhésion au traitement médicamenteux
14.
J Clin Lab Anal ; 38(9): e25038, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38590133

RÉSUMÉ

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.


Sujet(s)
Klebsiella pneumoniae , Réaction de polymérisation en chaine multiplex , bêta-Lactamases , Klebsiella pneumoniae/génétique , Klebsiella pneumoniae/isolement et purification , bêta-Lactamases/génétique , Humains , Réaction de polymérisation en chaine multiplex/méthodes , Infections à Klebsiella/microbiologie , Infections à Klebsiella/diagnostic , Sensibilité et spécificité , Réaction de polymérisation en chaine en temps réel/méthodes , Protéines bactériennes/génétique , Recombinases/génétique , Recombinases/métabolisme
15.
Sci Adv ; 10(16): eadj8796, 2024 Apr 19.
Article de Anglais | MEDLINE | ID: mdl-38630825

RÉSUMÉ

The dispersive interaction between a qubit and a cavity is ubiquitous in circuit and cavity quantum electrodynamics. It describes the frequency shift of one quantum mode in response to excitations in the other and, in closed systems, is necessarily bidirectional, i.e., reciprocal. Here, we present an experimental study of a nonreciprocal dispersive-type interaction between a transmon qubit and a superconducting cavity, arising from a common coupling to dissipative intermediary modes with broken time reversal symmetry. We characterize the qubit-cavity dynamics, including asymmetric frequency pulls and photon shot noise dephasing, under varying degrees of nonreciprocity by tuning the magnetic field bias of a ferrite component in situ. We introduce a general master equation model for nonreciprocal interactions in the dispersive regime, providing a compact description of the observed qubit-cavity dynamics agnostic to the intermediary system. Our result provides an example of quantum nonreciprocal phenomena beyond the typical paradigms of non-Hermitian Hamiltonians and cascaded systems.

16.
J Mol Cell Biol ; 2024 Apr 08.
Article de Anglais | MEDLINE | ID: mdl-38587834

RÉSUMÉ

Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.

17.
Eur J Med Res ; 29(1): 180, 2024 Mar 17.
Article de Anglais | MEDLINE | ID: mdl-38494472

RÉSUMÉ

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.


Sujet(s)
Tumeurs de l'estomac , Humains , Tumeurs de l'estomac/génétique , Tumeurs de l'estomac/thérapie , Pronostic , Marqueurs biologiques , Immunothérapie , Microenvironnement tumoral/génétique , Complexe IV de la chaîne respiratoire
18.
Biotechnol J ; 19(3): e2300706, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38479984

RÉSUMÉ

4-cyanobenzoic acid serves as a crucial intermediate for the synthesis of various high-value organic compounds. The enzymatic hydrolysis of terephthalonitrile to produce 4-cyanobenzoic acid using nitrilase offers the advantages of a simple reaction pathway, environmental friendliness, and easy product separation. In order to efficiently develop nitrilases that meet industrial production requirements, the virtual screening method used in the study is established and mature. From a total of 371 amino acids in the nitrilase AfNIT, which exhibits activity in terephthalonitrile hydrolysis, three candidate sites (F168, S192, and T201) were identified, and a "small and accurate" mutant library was constructed. The triple mutant F168V/T201N/S192F was screened from this small mutant library with a specific activity of 227.3 U mg-1 , which was 3.8 times higher than that of the wild-type AfNIT. Using the whole-cell biocatalyst containing the mutant F168V/T201N/S192F, terephthalonitrile was successfully hydrolyzed at a concentration of 150 g L-1 to produce 4-cyanobenzoic acid with a final yield of 170.3 g L-1 and a conversion rate of 98.7%. The obtained nitrilase mutant F168V/T201N/S192F in this study can be effectively applied in the biomanufacturing of 4-cyanobenzoic acid using terephthalonitrile as a substrate. Furthermore, the results also demonstrate the significant improvement in predictive accuracy achieved through the latest AI-assisted computer simulation methods. This approach represents a promising and feasible new technological pathway for assisting enzyme engineering research, laying a theoretical foundation for other related studies.


Sujet(s)
Aminohydrolases , Benzoates , Simulation numérique , Aminohydrolases/génétique , Aminohydrolases/composition chimique
19.
J Hazard Mater ; 465: 133081, 2024 Mar 05.
Article de Anglais | MEDLINE | ID: mdl-38016321

RÉSUMÉ

A large number of natural and anthropogenic wastes were landfilled, and dissolved organic matter (DOM) were formed during landfill. However, the composition, transformation, and coexistence characteristics of natural and anthropogenic DOM in leachate remain unclear. Fourier transform ion cyclotron resonance mass spectrometry, size exclusion chromatography, gas chromatography coupled with mass spectrometry, and three-dimensional excitation-emission matrix spectrum were employed to clarify comprehensively the abovementioned question. The results showed that natural DOM in young leachate constituted mainly straight-chain organic acids, protein substances, and building blocks of humic substances (BB). Straight-chain organic acids vanished in old leachates, and the concentration of protein substances and BB decreased from 44% to 26% and from 47% to 12%, respectively, while CHON and CHONS were degraded to CHO and CHOS during the process. As to anthropogenic DOM, its types and relative content in leachate increased during landfill, and aromatic acids, terpenes, halogenated organics, indoles, and phenols became the main organic components in old leachate. Compared to natural DOM, anthropogenic DOM was degraded slowly and accumulated in leachate, and some of the natural DOM facilitated the dechlorination of dichlorinated organic compounds. This study demonstrates that landfill led to an increase in humic substances and halogenated organic compounds in old leachate, which was intensified with concentrated leachate recirculation.

20.
J Asian Nat Prod Res ; 26(1): 102-111, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-38126332

RÉSUMÉ

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.


Sujet(s)
Short chain dehydrogenase-reductases , Stachybotrys , Oxidoreductases , Catalyse , Alcools/composition chimique
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