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1.
Proc Natl Acad Sci U S A ; 120(36): e2302490120, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37639584

RESUMEN

Pathological mutations in human mitochondrial genomes (mtDNA) can cause a series of neurological, behavioral, and developmental defects, but the underlying molecular mechanisms are poorly understood. We show here that the energy-sensing adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway plays a key role in mediating similar defects caused by different mtDNA mutations in Caenorhabditis elegans, including loss or reduction of osmotic, chemical and olfactory sensing, locomotion, and associative learning and memory, as well as increased embryonic lethality. mtDNA mutations cause reduced ATP (adenosine triphosphate) levels, activation of C. elegans AMPK AAK-2, and nuclear translocation of the FOXO transcription factor DAF-16. Activated DAF-16 up-regulates the expression of inositol triphosphate receptor ITR-1, an endoplasmic reticulum calcium channel, leading to increased basal cytosolic Ca2+ levels, decreased neuronal responsiveness, compromised synapses, and increased embryonic death. Treatment of mtDNA mutants with vitamin MK-4 restores cellular ATP and cytosolic Ca2+ levels, improves synaptic development, and suppresses sensory and behavioral defects and embryonic death. Our study provides crucial mechanistic insights into neuronal and developmental defects caused by mtDNA mutations and will improve understanding and treatment of related mitochondrial diseases.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Caenorhabditis elegans , Humanos , Animales , Femenino , Embarazo , Caenorhabditis elegans/genética , Transducción de Señal , Mutación , Adenosina Trifosfato , ADN Mitocondrial/genética , Pérdida del Embrión
2.
Nano Lett ; 24(34): 10519-10526, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39150339

RESUMEN

CrSbSe3─the only experimentally validated one-dimensional (1D) ferromagnetic semiconductor─has recently attracted significant attention. However, all reported synthesis methods for CrSbSe3 nanocrystals are based on top-down methods. Here we report a template selection strategy for the bottom-up synthesis of CrSbSe3 nanoribbons. This strategy relies on comparing the formation energies of potential binary templates to the ternary target product. It enables us to select Sb2Se3 with the highest formation energy, along with its 1D crystal structure, as the template instead of Cr2Se3 with the lowest formation energy, thereby facilitating the transformation from Sb2Se3 to CrSbSe3 by replacing half of the Sb atoms in Sb2Se3 with Cr atoms. The as-prepared CrSbSe3 nanoribbons exhibit a length of approximately 5 µm, a width ranging from 80 to 120 nm, and a thickness of about 5 nm. The single CrSbSe3 nanoribbon presents typical semiconductor behavior and ferromagnetism, confirming the intrinsic ferromagnetism in the 1D CrSbSe3 semiconductor.

3.
J Am Chem Soc ; 146(9): 6345-6351, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38377535

RESUMEN

Selenium (Se) discovered in 1817 belongs to the family of chalcogens. Surprisingly, despite the long history of over two centuries and the chemical simplicity of Se, the structure of amorphous Se (a-Se) remains controversial to date regarding the dominance of chains versus rings. Here, we find that vapor-deposited a-Se is composed of disordered rings rather than chains in melt-quenched a-Se. We further reveal that the main origin of this controversy is the facile transition of rings to chains arising from the inherent instability of rings. This transition can be inadvertently triggered by certain characterization techniques themselves containing above-bandgap illumination (above 2.1 eV) or heating (above 50 °C). We finally build a roadmap for obtaining accurate Raman spectra by using above-bandgap excitation lasers with low photon flux (below 1017 phs m-2 s-1) and below-bandgap excitation lasers measured at low temperatures (below -40 °C) to minimize the photoexcitation- and heat-induced ring-to-chain transitions.

4.
Anal Chem ; 96(17): 6523-6527, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38634570

RESUMEN

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

5.
Drug Metab Dispos ; 52(3): 210-217, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38195521

RESUMEN

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epilepsia , Humanos , Anticonvulsivantes/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Monitoreo de Drogas , Epilepsia/tratamiento farmacológico , Estudios Retrospectivos , Ácido Valproico/efectos adversos
6.
Angew Chem Int Ed Engl ; : e202413429, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252053

RESUMEN

The lanthanide contraction involves a reduction in atomic radius among f-block elements below the expected level. A similar contraction is observed in group-16 elements. The atomic radius of Se (117 pm) is slightly larger than that of S (104 pm) arising from the presence of d electrons, compared to the significant increase in atomic radius from O (73 pm) to S. This lanthanide-like contraction contributes to Se's robust oxidative resistance. Here we report a selective oxidation strategy utilizing Se's strong antioxidative property to remove coexisting narrow-bandgap Te impurities from Se feedstocks. This strategy selectively oxidizes volatile Te impurities into involatile TeO2 that remains in the evaporation source, while only volatile Se deposits onto the substrate during the thermal-evaporation deposition process. This enables the fabrication of high-purity Se films possessing a wide bandgap of 1.88 eV, ideally suited to the optimal bandgap for indoor photovoltaics (IPVs). The resulting Se photovoltaics exhibit an efficiency of 20.1% under 1000-lux indoor illumination, outperforming market-dominant amorphous silicon and all types of lead-free perovskite IPVs. Unencapsulated Se devices show no efficiency degradation after 20,000 hours of storage in ambient atmosphere.

7.
J Am Chem Soc ; 145(10): 5872-5879, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36872583

RESUMEN

Passivating defects using organic halide salts, especially chlorides, is an effective method to improve power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) arising from the stronger Pb-Cl bonding than Pb-I and Pb-Br bonding. However, Cl- anions with a small radius are prone to incorporation into the perovskite lattice that distorts the lead halide octahedron, degrading the photovoltaic performance. Here, we substitute atomic-Cl-containing organic molecules for widely used ionic-Cl salts, which not only retain the efficient passivation by Cl but also prevent the incorporation of Cl into the bulk lattice, benefiting from the strong covalent bonding between Cl atoms and organic frameworks. We find that only when the distance of Cl atoms in single molecules matches well with the distance of halide ions in perovskites can such a configuration maximize the defect passivation. We thereby optimize the molecular configuration to enable multiple Cl atoms in an optimal spatial position to maximize their binding with surface defects. The resulting PSCs achieve a certified PCE of 25.02%, among the highest PCEs for PSCs, and retain 90% of their initial PCE after 500 h of continuous operation.

8.
Opt Express ; 31(20): 33241-33252, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859108

RESUMEN

We proposed an optical fiber salinity sensor with a composite Fabry-Perot (F-P) cavity structure for simultaneous measurement of temperature and salinity based on microelectromechanical system (MEMS) technology. The sensor contains two sensing cavities. The silicon cavity is used for temperature sensing, and the seawater cavity processed by the glass microstructure is sensitive to the refractive index of seawater for salinity sensing. At the same time, the influence of the salinity-temperature cross-sensitivity error of the seawater cavity is effectively compensated by using the temperature single parameter sensitivity characteristics of the silicon cavity. The structural design of the sensor seawater cavity includes a cross-shaped groove and a cylindrical fluid cavity. The surface hydrophilicity treatment was performed on the interior of the cavity to solve the effect of no water injection in the cavity caused by the miniaturization of the sensor. The optical path difference (OPD) demodulation method is used to demodulate the two F-P cavities with large dynamic range and high resolution. In the range of 5∼40°C and 5∼ 40 ‰, the temperature and salinity sensitivity of the sensor can reach 110.25 nm/°C and 178.75 nm/‰, respectively, and the resolution can reach 5.02 × 10-3°C and 0.0138‰. It has the advantages of mass production, high stability, and small size, which give it great potential for marine applications.

9.
Nature ; 547(7664): 458-462, 2017 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-28723894

RESUMEN

The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge. CPR-4 is secreted from animals irradiated with ultraviolet or ionizing gamma rays, and is the major factor in the conditioned medium that leads to the inhibition of cell death and increased embryonic lethality in unirradiated animals. Moreover, CPR-4 causes these effects and stress responses at unexposed sites distal to the irradiated tissue. The activity of CPR-4 is regulated by the p53 homologue CEP-1 in response to radiation, and CPR-4 seems to exert RIBEs by acting through the insulin-like growth factor receptor DAF-2. Our study provides crucial insights into RIBEs, and will facilitate the identification of additional RIBE factors and their mechanisms of action.


Asunto(s)
Efecto Espectador/efectos de la radiación , Caenorhabditis elegans/enzimología , Caenorhabditis elegans/efectos de la radiación , Catepsina B/metabolismo , Animales , Caenorhabditis elegans/citología , Proteínas de Caenorhabditis elegans/metabolismo , Proteasas de Cisteína/metabolismo , Receptor de Insulina/metabolismo , Rayos Ultravioleta
10.
Angew Chem Int Ed Engl ; 62(4): e202216354, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36440597

RESUMEN

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

11.
Acta Pharmacol Sin ; 43(7): 1857-1864, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34737420

RESUMEN

Gefitinib has been available in the market for 20 years, but its pharmacokinetic mechanism of response is little known. In this study, we examined the pharmacokinetic and metabolomic profiles in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. A total of 216 advanced NSCLC patients were enrolled, and administered gefitinib at the standard dosage of 250 mg/day, which was established in heterogeneous subjects with non-sensitive mutations. We identified and quantified three main metabolites (named as M1, M2 and M3) in the plasma of patients, the correlations between the concentration of gefitinib/metabolites and efficacy were analyzed. In exploratory and validation set, gefitinib concentration was not correlated with clinical effects. Considering the result that the therapeutic effects of 250 mg/2-day was better than that of 250 mg/day in a multiple center clinical trial, the standard dose might be higher than that for maximal efficacy according to the hypothetical dose-response curve. Among the three metabolites, the IC50 of M2 in HCC827 and PC9 cell lines was significantly lower, and Conc.brain/Conc.plasma of M2 in mice was significantly higher than those of gefitinib, suggesting its higher potential to penetrate blood-brain barrier and might be more effective in the treatment of brain metastatic tumor than gefitinib. Consistently and attractively, higher M2 plasma concentration was found to be correlated with better clinical outcome in patients with brain metastases (the median PFS of CM2 < 12 ng/mL and CM2 ≥ 12 ng/mL were 17.0 and 27.1 months, respectively, P = 0.038). The plasma concentration of M2 ≥ 12 ng/mL was a strong predictor of the PFS of NSCLC patients. In conclusion, for NSCLC patients with EGFR sensitive mutations, the standard dose is suspectable and could be decreased reasonably. M2 plays an important role in efficacy and may be more effective in the treatment of metastatic tumor than gefitinib.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/farmacología , Quinazolinas/uso terapéutico
12.
Nano Lett ; 21(18): 7684-7690, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34435772

RESUMEN

Magnetic heterostructures offer great promise in spintronic devices due to their unique magnetic properties, such as exchange bias effect, topological superconductivity, and magneto-resistance. Although various magnetic heterostructures including core/shell, multilayer, and van der Waals systems have been fabricated recently, the construction of perfect heterointerfaces usually rely on complicated and high-cost fabrication methods such as molecular-beam epitaxy; surprisingly, few one-dimensional (1D) bimagnetic heterojunctions, which provide multidegrees of freedom to modulate magnetic properties via magnetic anisotropy and interface coupling, have been fabricated to date. Here we report a one-pot solution-based method for the synthesis of ferromagnetic/antiferromagnetic/ferromagnetic heterojunction nanorods with excellent heterointerfaces in the case of Cr2Te3/MnTe/Cr2Te3. The precise control of homogeneous nucleation of MnTe and heterogeneous nucleation of Cr2Te3 is a key factor in synthesizing this heterostructure. The resulting 1D bimagnetic heterojunction nanorods exhibit high coercivity of 5.8 kOe and exchange bias of 892.5 Oe achieved by the magnetic MnTe/Cr2Te3 interface coupling.

13.
Zhongguo Zhong Yao Za Zhi ; 47(2): 461-468, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-35178990

RESUMEN

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of ß-myosin heavy chain(ß-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of ß-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.


Asunto(s)
Cardiomegalia , Hipertrofia Ventricular Izquierda , Angiotensina II/metabolismo , Animales , Cardiomegalia/etiología , Cardiomegalia/genética , Ácido Gálico/análogos & derivados , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/patología , Miocardio/patología , Ratas
14.
Angew Chem Int Ed Engl ; 61(25): e202204148, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35384201

RESUMEN

Defect passivation via post-treatment of perovskite films is an effective method to fabricate high-performance perovskite solar cells (PSCs). However, the passivation durability is still an issue due to the weak and vulnerable bonding between passivating functional groups and perovskite defect sites. Here we propose a cholesterol derivative self-assembly strategy to construct crosslinked and compact membranes throughout perovskite films. These supramolecular membranes act as a robust protection layer against harsh operational conditions while providing effective passivation of defects from surface toward inner grain boundaries. The resultant PSCs exhibit a power conversion efficiency of 23.34 % with an impressive open-circuit voltage of 1.164 eV. The unencapsulated devices retain 92 % of their initial efficiencies after 1600 h of storage under ambient conditions, and remain almost unchanged after heating at 85 °C for 500 h in a nitrogen atmosphere, showing significantly improved stability.

15.
J Am Chem Soc ; 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34133156

RESUMEN

Wide-bandgap semiconductors exhibiting a bandgap of ∼1.7-1.9 eV have generated great interest recently due to their important applications in tandem solar cells as top cells and emerging indoor photovoltaics. However, concerns about the stability and toxicity especially in indoor application limit the choice of these materials. Here we report a new member of this family, germanium monosulfide (GeS); this material displays a wide bandgap of 1.7 eV, nontoxic and earth-abundant constituents, and high stability. We find that the little success of GeS solar cells to date is primarily attributed to the challenge in fabricating high-quality polycrystalline GeS films, wherein the high thermal expansion coefficient (α = 3.1 × 10-5 K-1) combined with high crystallization temperature (375 °C) of GeS induces large tensile strain in the GeS film that peels off GeS from the substrate. By introducing a high-α buffer layer between GeS and substrate, we achieve a high-quality polycrystalline GeS thin film that compactly adheres to substrate with no voids. Solar cells fabricated by these GeS films show a power conversion efficiency of 1.36% under AM 1.5G illumination (100 mW cm-2). The unencapsulated devices are stable when stored in ambient atmosphere for 1500 h. Their efficiencies further increase to 3.6% under indoor illumination of 1000 lux.

16.
J Cell Sci ; 132(5)2019 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30683797

RESUMEN

The Caenorhabditis elegans aminophospholipid translocase TAT-1 maintains phosphatidylserine (PS) asymmetry in the plasma membrane and regulates endocytic transport. Despite these important functions, the structure-function relationship of this protein is poorly understood. Taking advantage of the tat-1 mutations identified by the C. elegans million mutation project, we investigated the effects of 16 single amino acid substitutions on the two functions of the TAT-1 protein. Two substitutions that alter a highly conserved PISL motif in the fourth transmembrane domain and a highly conserved DKTGT phosphorylation motif, respectively, disrupt both functions of TAT-1, leading to a vesicular gut defect and ectopic PS exposure on the cell surface, whereas most other substitutions across the TAT-1 protein, often predicted to be deleterious by bioinformatics programs, do not affect the functions of TAT-1. These results provide in vivo evidence for the importance of the PISL and DKTGT motifs in P4-type ATPases and improve our understanding of the structure-function relationship of TAT-1. Our study also provides an example of how the C. elegans million mutation project helps decipher the structure, functions, and mechanisms of action of important genes.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Intestinos/fisiología , Proteínas de Transferencia de Fosfolípidos/metabolismo , Secuencias de Aminoácidos/genética , Animales , Animales Modificados Genéticamente , Proteínas de Caenorhabditis elegans/genética , Biología Computacional , Endocitosis , Mutación/genética , Fenotipo , Proteínas de Transferencia de Fosfolípidos/genética , Conformación Proteica , Transporte de Proteínas , Relación Estructura-Actividad
17.
Nature ; 517(7533): 219-22, 2015 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-25567286

RESUMEN

Functional regeneration after nervous system injury requires transected axons to reconnect with their original target tissue. Axonal fusion, a spontaneous regenerative mechanism identified in several species, provides an efficient means of achieving target reconnection as a regrowing axon is able to contact and fuse with its own separated axon fragment, thereby re-establishing the original axonal tract. Here we report a molecular characterization of this process in Caenorhabditis elegans, revealing dynamic changes in the subcellular localization of the EFF-1 fusogen after axotomy, and establishing phosphatidylserine (PS) and the PS receptor (PSR-1) as critical components for axonal fusion. PSR-1 functions cell-autonomously in the regrowing neuron and, instead of acting in its canonical signalling pathway, acts in a parallel phagocytic pathway that includes the transthyretin protein TTR-52, as well as CED-7, NRF-5 and CED-6 (refs 9, 10, 11, 12). We show that TTR-52 binds to PS exposed on the injured axon, and can restore fusion several hours after injury. We propose that PS functions as a 'save-me' signal for the distal fragment, allowing conserved apoptotic cell clearance molecules to function in re-establishing axonal integrity during regeneration of the nervous system.


Asunto(s)
Apoptosis/fisiología , Axones/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citología , Caenorhabditis elegans/metabolismo , Glicoproteínas de Membrana/metabolismo , Regeneración Nerviosa/fisiología , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis , Axones/patología , Proteínas de Caenorhabditis elegans/genética , Proteínas Portadoras/metabolismo , Conos de Crecimiento/metabolismo , Mutación , Fagocitos/metabolismo , Fagocitosis , Fosfatidilserinas/metabolismo , Fosfoproteínas/metabolismo , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Espectrina/genética , Espectrina/metabolismo
18.
Acta Pharmacol Sin ; 42(4): 641-647, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32737470

RESUMEN

For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix® NLMETM. The first cycle trough concentration (C1-trough) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C1-trough was 13.60 µg/mL. Patients with grade 1/2 had significantly lower C1-trough compared with grade 3 (12.21 µg/mL vs. 23.45 µg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 µg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C1-trough, accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anciano , Antineoplásicos/farmacocinética , Ciclofosfamida/uso terapéutico , Relación Dosis-Respuesta a Droga , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método de Montecarlo , Prednisona/uso terapéutico , Estudios Prospectivos , Rituximab/farmacocinética , Vincristina/uso terapéutico , Adulto Joven
19.
Angew Chem Int Ed Engl ; 60(7): 3693-3698, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33174357

RESUMEN

Tin halide perovskites are rising as promising materials for lead-free perovskite solar cells (PSCs). However, the crystallization rate of tin halide perovskites is much faster than the lead-based analogs, leading to more rampant trap states and lower efficiency. Here, we disclose a key finding to modulate the crystallization kinetics of FASnI3 through a non-classical nucleation mechanism based on pre-nucleation clusters (PNCs). By introducing piperazine dihydriodide to tune the colloidal chemistry of the FASnI3 perovskite precursor solution, stable clusters could be readily formed in the solution before nucleation. These pre-nucleation clusters act as intermediate phase and thus can reduce the energy barrier for the perovskite nucleation, resulting in a high-quality perovskite film with lower defect density. This PNCs-based method has led to a conspicuous photovoltaic performance improvement for FASnI3 -based PSCs, delivering an impressive efficiency of 11.39 % plus improved stability.

20.
J Am Chem Soc ; 142(9): 4438-4444, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-31976663

RESUMEN

CrGeTe3 has recently emerged as a new class of two-dimensional (2D) materials due to its intrinsic long-range ferromagnetic order. However, almost all the reported synthesis methods for CrGeTe3 nanosheets are based on the conventional mechanical exfoliation from single-crystalline CrGeTe3, which is prepared by the complicated self-flux technique. Here we report a solution-processed synthesis of CrGeTe3 nanosheets from a non-van der Waals (vdW) Cr2Te3 template. This structure evolution from non-vdW to vdW is originated from the substitution of Ge atoms on the Cr sites surrounded by fewer Te atoms in the Cr2Te3 lattice due to their smaller steric hindrance and lower energy barrier. These CrGeTe3 nanosheets present regular hexagonal structures with a diameter larger than 1 µm and excellent stability. They exhibit soft magnetic behavior with a Curie temperature lower than 67.5 K. This non-vdW to vdW synthesis strategy promotes the development of CrGeTe3 in ferromagnetism while providing an effective route to synthesize other 2D materials.

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