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1.
Plant Cell ; 36(6): 2103-2116, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38445983

RESUMEN

Bacterial pathogens deliver effectors into host cells to suppress immunity. How host cells target these effectors is critical in pathogen-host interactions. SUMOylation, an important type of posttranslational modification in eukaryotic cells, plays a critical role in immunity, but its effect on bacterial effectors remains unclear in plant cells. In this study, using bioinformatic and biochemical approaches, we found that at least 16 effectors from the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 are SUMOylated by the enzyme cascade from Arabidopsis thaliana. Mutation of SUMOylation sites on the effector HopB1 enhances its function in the induction of plant cell death via stability attenuation of a plant receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1)-ASSOCIATED RECEPTOR KINASE 1. By contrast, SUMOylation is essential for the function of another effector, HopG1, in the inhibition of mitochondria activity and jasmonic acid signaling. SUMOylation of both HopB1 and HopG1 is increased by heat treatment, and this modification modulates the functions of these 2 effectors in different ways in the regulation of plant survival rates, gene expression, and bacterial infection under high temperatures. Therefore, the current work on the SUMOylation of effectors in plant cells improves our understanding of the function of dynamic protein modifications in plant-pathogen interactions in response to environmental conditions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Respuesta al Choque Térmico , Pseudomonas syringae , Sumoilación , Arabidopsis/microbiología , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Muerte Celular , Ciclopentanos/metabolismo , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico/genética , Interacciones Huésped-Patógeno , Calor , Células Vegetales/metabolismo , Células Vegetales/microbiología , Enfermedades de las Plantas/microbiología , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Pseudomonas syringae/patogenicidad , Pseudomonas syringae/fisiología , Transducción de Señal
2.
EMBO Rep ; 25(2): 489-505, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38177916

RESUMEN

Small peptides modulate multiple processes in plant cells, but their regulation by post-translational modification remains unclear. ROT4 (ROTUNDIFOLIA4) belongs to a family of Arabidopsis non-secreted small peptides, but knowledge on its molecular function and how it is regulated is limited. Here, we find that ROT4 is S-acylated in plant cells. S-acylation is an important form of protein lipidation, yet so far it has not been reported to regulate small peptides in plants. We show that this modification is essential for the plasma membrane association of ROT4. Overexpression of S-acylated ROT4 results in a dramatic increase in immune gene expression. S-acylation of ROT4 enhances its interaction with BSK5 (BRASSINOSTEROID-SIGNALING KINASE 5) to block the association between BSK5 and PEPR1 (PEP RECEPTOR1), a receptor kinase for secreted plant elicitor peptides (PEPs), thereby activating immune signaling. Phenotype analysis indicates that S-acylation is necessary for ROT4 functions in pathogen resistance, PEP response, and the regulation of development. Collectively, our work reveals an important role for S-acylation in the cross-talk of non-secreted and secreted peptide signaling in plant immunity.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Plantas/metabolismo , Péptidos/metabolismo , Acilación , Inmunidad de la Planta , Proteínas Quinasas/metabolismo
3.
Plant J ; 113(4): 819-832, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36579923

RESUMEN

Rosemary (Salvia rosmarinus) is considered a sacred plant because of its special fragrance and is commonly used in cooking and traditional medicine. Here, we report a high-quality chromosome-level assembly of the S. rosmarinus genome of 1.11 Gb in size; the genome has a scaffold N50 value of 95.5 Mb and contains 40 701 protein-coding genes. In contrast to other diploid Labiataceae, an independent whole-genome duplication event occurred in S. rosmarinus at approximately 15 million years ago. Transcriptomic comparison of two S. rosmarinus cultivars with contrasting carnosic acid (CA) content revealed 842 genes significantly positively associated with CA biosynthesis in S. rosmarinus. Many of these genes have been reported to be involved in CA biosynthesis previously, such as genes involved in the mevalonate/methylerythritol phosphate pathways and CYP71-coding genes. Based on the genomes and these genes, we propose a model of CA biosynthesis in S. rosmarinus. Further, comparative genome analysis of the congeneric species revealed the species-specific evolution of CA biosynthesis genes. The genes encoding diterpene synthase and the cytochrome P450 (CYP450) family of CA synthesis-associated genes form a biosynthetic gene cluster (CPSs-KSLs-CYP76AHs) responsible for the synthesis of leaf and root diterpenoids, which are located on S. rosmarinus chromosomes 1 and 2, respectively. Such clustering is also observed in other sage (Salvia) plants, thus suggesting that genes involved in diterpenoid synthesis are conserved in the Labiataceae family. These findings provide new insights into the synthesis of aromatic terpenoids and their regulation.


Asunto(s)
Diterpenos , Rosmarinus , Salvia , Rosmarinus/genética , Rosmarinus/metabolismo , Salvia/genética , Salvia/metabolismo , Abietanos/metabolismo , Diterpenos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Cromosomas
4.
Int J Cancer ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985144

RESUMEN

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

5.
Small ; : e2402783, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115100

RESUMEN

The excessive emission of greenhouse gases, which leads to global warming and alarms the world, has triggered a global campaign for carbon neutrality. Carbon capture and sequestration (CCS) technology has aroused wide research interest as a versatile emission mitigation technology. Metal-organic frameworks (MOFs), as a new class of high-performance adsorbents, hold great potential for CO2 capture from large point sources and ambient air due to their ultra-high specific surface area as well as pore structure. In recent years, MOFs have made great progress in the field of CO2 capture and separation, and have published a number of important results, which have greatly promoted the development of MOF materials for practical carbon capture applications. This review summarizes the most recent advanced research on MOF materials for carbon capture in various application scenarios over the past six years. The strategies for enhancing CO2 selective adsorption and separation of MOFs are described in detail, along with the development of MOF-based composites. Moreover, this review also systematically summarizes the highly concerned issues of MOF materials in practical applications of carbon capture. Finally, future research on CO2 capture by MOF materials is prospected.

6.
Small ; 20(6): e2306195, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37789582

RESUMEN

The poor reversibility and stability of Zn metal anode (ZMA) caused by uncontrolled Zn deposition behaviors and serious side reactions severely impeded the practical application of aqueous Zn metal battery. Herein, a liquid-dynamic and self-adaptive protective layer (LSPL) was constructed on the ZMA surface for inhibiting dendrites and by-products formation. Interestingly, the outer LSPL consists of liquid perfluoropolyether (PFPE), which can dynamically adapt volume change during repeat cycling and inhibit side reactions. Moreover, it can also decrease the de-solvation energy barrier of Zn2+ by strong interaction between C-F bond and foreign Zn2+ , improving Zn2+ transport kinetics. For the LSPL inner region, in-situ formed ZnF2 through the spontaneous chemical reaction between metallic Zn and part PFPE can establish an unimpeded Zn2+ migration pathway for accelerating ion transfer, thereby restricting Zn dendrites formation. Consequently, the LSPL-modified ZMA enables reversible Zn deposition/dissolution up to 2000 h at 1 mA cm-2 and high coulombic efficiency of 99.8% at 4 mA cm-2 . Meanwhile, LSPL@Zn||NH4 V4 O10 full cells deliver an ultralong cycling lifespan of 100 00 cycles with 0.0056% per cycle decay rate at 10 A g-1 . This self-adaptive layer provides a new strategy to improve the interface stability for next-generation aqueous Zn battery.

7.
Mol Carcinog ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092765

RESUMEN

The tumorigenesis of intrahepatic cholangiocarcinoma (ICC) has been identified to be exceptionally involved in dysregulated Hippo/Yes-associated protein (YAP) signaling pathway (Hippo/YAP). Hippo/YAP functions as a master regulator engaged in a plethora of physiological and oncogenic processes as well. Therefore, the aberrant Hippo/YAP could serve as an Achilles' heel regarding the molecular therapeutic avenues for ICC patients. Herein, we comprehensively review the recent studies about the underlying mechanism of disrupted Hippo/YAP in ICC, how diagnostic values could be utilized upon the critical genes in this pathway, and what opportunities could be given upon this target pathway.

8.
Microb Pathog ; 187: 106513, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38147968

RESUMEN

Since pseudorabies (PR) re-emerged and rapidly spread in China at the end of 2011, researchers have focused on effective vaccine strategies to prevent and control pseudorabies virus (PRV) infection in pig herds. Due to the extensive application of an attenuated vaccine based on the Bartha-K61 strain isolated in Hungary in 1961 and the variation of the PRV strain, it has been suggested that traditional vaccines based on the Bartha-K61 strain offer only partial protection against variant strains. It was therefore evaluated whether the Porcilis® Begonia vaccine, which is based on the NIA-3 strain with deletions in the gE and TK genes, is efficacious against experimental infection with the virulent, contemporary Chinese PRV strain ZJ01. In this study, piglets were vaccinated with Porcilis® Begonia through either the intradermal (ID) route or the intramuscular (IM) route and subsequently challenged intranasally with strain ZJ01 at 4 weeks post-vaccination. An unvaccinated challenge group and an unvaccinated/nonchallenged group were also included in the study. All animals were monitored for 14 days after challenge. Vaccinated and negative control pigs stayed healthy during the study, while the unvaccinated control animals developed lesions associated with PRV ZJ01 challenge, and 44% of these pigs died before the end of the experiment. This study demonstrated that ID or IM vaccination of pigs with a vaccine based on the NIA-3 strain Porcilis® Begonia clinically protects against fatal PRV challenge with the ZJ01 strain.


Asunto(s)
Begoniaceae , Herpesvirus Suido 1 , Enfermedades de los Porcinos , Vacunas Virales , Porcinos , Animales , Herpesvirus Suido 1/genética , Vacunas contra la Seudorrabia , Anticuerpos Antivirales , Vacunación/veterinaria , Vacunas Virales/genética
9.
Eur Radiol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122854

RESUMEN

OBJECTIVE: To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). METHODS: This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. RESULTS: A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. CONCLUSION: Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. CLINICAL RELEVANCE STATEMENT: Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. KEY POINTS: The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.

10.
Nanotechnology ; 35(47)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39163875

RESUMEN

Phosphorene has been widely used as anode material for batteries. However, the huge volume change during charging and discharging process, the semiconductor properties, and the high open circuit voltage limit its application. Based on this, by introducing the electron-deficient boron atoms into blue phosphorene, we proposed a P-rich sandwich-like BP4monolayer by density functional theory calculation and particle swarm optimization. The BP4monolayer shows good thermodynamic and dynamic stability, as well as chemical stability in O2atmosphere, mainly due to the strengthened P-P bond of the outer layer by the middle boron atoms adoptingsp3hybridization. According to the band structure, the BP4monolayer shows metallic property, which is beneficial to electron conductivity. Furthermore, compared with blue phosphorene and black phosphorene, the P-rich BP4monolayer shows higher theoretical capacity for Li, Na, and K of 1193.90, 1119.28, and 397.97 mA h g-1, respectively. The lattice constant of BP4monolayer increases only 3.73% (Li), 2.52% (Na) after Li/Na fully adsorbed on the anode. More importantly, the wettability of BP4monolayer in the electrolyte is comparable to that of graphene. These findings show that the stable sandwich-like BP4monolayer has potential as a lightweight anode material.

11.
Macromol Rapid Commun ; : e2400662, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264576

RESUMEN

Glioblastoma is one of the most aggressive and treatment-resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127-complexed PEGylated poly(glutamic acid)-cisplatin (PLG-PEG/PF127-CDDP). PLG-PEG/PF127-CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half-maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL-1 at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG-PEG/PF127-CDDP prolonged the circulation half-life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post-treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG-PEG/PF127-CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer-based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications.

12.
Phys Chem Chem Phys ; 26(7): 6208-6215, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38305386

RESUMEN

Two-dimensional (2D) materials with light weight and ultra-high electrical conductivity are expected to exhibit high capacity as anodes of batteries. We have explored the curved square lattice BS2 (b-BS2) monolayer possessing a space group similar to the transition metal chloride (space group: P4̄M2). The electrochemical performance of the b-BS2 monolayer as the anode for various metal-ion batteries (Li, Na, K, Mg, Ca, and Al) has been investigated. It exhibits low diffusion energy barrier, high theoretical capacity, and low open circuit voltage for Na/K-ion batteries (SIBs/PIBs). The ultrahigh energy densities of 2146.08 and 715.36 mA h g-1 can be achieved with the stoichiometries BS2Na6 and BS2K2, respectively. Furthermore, the b-BS2 monolayer may be synthesized on the surfaces of metal substrate materials (Ag(111), Al(111), and Au(111)). These results indicate that the b-BS2 monolayer is a good candidate for the anode material of SIBs/PIBs.

13.
Exp Appl Acarol ; 92(1): 109-122, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38172470

RESUMEN

With a generally warming global climate, the number of Tetranychus truncatus specimens in the Hexi region in China has been increasing. As ectotherms, the growth and development of T. truncatus are greatly affected by changes in environmental temperature. The effect of heatwaves on organisms depends on a delicate balance between damage and repair periods. Therefore, we simulated nine patterns of periodically recurring changes in the frequency of high-temperature days using an intraday gradual temperature change model to study and compare the effects on the development and reproduction of pyridaben-sensitive and -resistant strains of T. truncatus. The results showed that the influence of the frequency of high-temperature days on developmental stages, longevity and fecundity was different between the two strains. The egg and immature stages of the sensitive strain were all affected by hot days, whereas the adult stage was less affected by the frequency. The egg stage of the resistant strain was less affected; it was mainly affected in the immature and adult stages. Under the moderate condition of increasing the proportion of days at normal temperature, the longevity of the resistant strain gradually increased and reached a maximum at a 1:3 frequency, and then it decreased with the increase in high-temperature days. The longevity of the sensitive strain was less affected by frequency, and there was no significant difference between most treatment and control groups. In addition, both sensitive and resistant strains were able to complete growth and development under all nine frequencies of high-temperature days, but the reproductive rate was lower than it was at normal temperatures, indicating that both strains of T. truncatus adapted to high temperatures at the expense of reduced reproduction rates. This lays a key theoretical foundation for predicting the occurrence of agricultural pest populations under the background of climate warming and developing appropriate control strategies.


Asunto(s)
Rasgos de la Historia de Vida , Piridazinas , Tetranychidae , Animales , Temperatura , Reproducción , Fertilidad
14.
Molecules ; 29(5)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38474548

RESUMEN

Transient receptor potential vanilloid 4 (TRPV4) is a widely expressed cation channel that plays an important role in many physiological and pathological processes. However, most TRPV4 drugs carry a risk of side effects. Moreover, existing screening methods are not suitable for the high-throughput screening (HTS) of drugs. In this study, a cell model and HTS method for targeting TRPV4 channel drugs were established based on a calcium-activated chloride channel protein 1 Anoctamin 1 (ANO1) and a double mutant (YFP-H148Q/I152L) of the yellow fluorescent protein (YFP). Patch-clamp experiments and fluorescence quenching kinetic experiments were used to verify that the model could sensitively detect changes in intracellular Ca2+ concentration. The functionality of the TRPV4 cell model was examined through temperature variations and different concentrations of TRPV4 modulators, and the performance of the model in HTS was also evaluated. The model was able to sensitively detect changes in the intracellular Ca2+ concentration and also excelled at screening TRPV4 drugs, and the model was more suitable for HTS. We successfully constructed a drug cell screening model targeting the TRPV4 channel, which provides a tool to study the pathophysiological functions of TRPV4 in vitro.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Canales Catiónicos TRPV , Canales Catiónicos TRPV/metabolismo , Anoctamina-1 , Calcio/metabolismo
15.
Angew Chem Int Ed Engl ; 63(30): e202402371, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38763920

RESUMEN

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (⋅OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by ⋅OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mAh g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

16.
J Am Chem Soc ; 145(46): 25332-25340, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37944150

RESUMEN

Rational control and understanding of isomerism are of significance but still remain a great challenge in reticular frameworks, in particular, for covalent organic frameworks (COFs) due to the complicated synthesis and energy factors. Herein, reaction of 3,3',5,5'-tetra(4-formylphenyl)-2,2',6,6'-tetramethoxy-1,1'-biphenyl (TFTB) with 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) under different reaction conditions affords single crystals of two 3D COF isomers, namely, USTB-20-dia and USTB-20-qtz. Their structures with resolutions up to 0.9-1.1 Å have been directly solved by three-dimensional electron diffraction (3D ED) and synchrotron single crystal X-ray diffraction, respectively. USTB-20-dia and USTB-20-qtz show rare 2 × 2-fold interpenetrated dia-b nets and 3-fold interpenetrated qtz-b frameworks. Comparative studies of the crystal structures of these COFs and theoretical simulation results indicate the crucial role of the flexible molecular configurations of building blocks in the present interpenetrated topology isomerism. This work not only presents the rare COF isomers but also gains an understanding of the formation of framework isomerism from both single crystal structures and theoretical simulation perspectives.

17.
Ann Surg ; 277(4): 557-564, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36538627

RESUMEN

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Terapia Neoadyuvante/métodos , Resultado del Tratamiento , Capecitabina/uso terapéutico , Neoplasias del Recto/patología , Quimioradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias
18.
Small ; 19(47): e2304751, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37485645

RESUMEN

The dendrite growth and parasitic reactions that occur on Zn metal anode (ZMA)/electrolyte interface hinder the development of aqueous zinc ion batteries (AZIBs) in next-generation renewable energy storage systems. Fortunately, reconstructing the inner Helmholtz layer (IHL) by introducing an electrolyte additive, is viewed as one of the most promising strategies to harvest the stable ZMA. Herein, (4-chloro-3-nitrophenyl) (pyridin-4-yl) methanone (CNPM) with quadruple functional groups is introduced into the ZnSO4 electrolyte to reshape the interface between ZMA and electrolyte and change the solvation structure of Zn2+ . Density functional theory (DFT) calculations manifest that the ─C═O, ─Cl, ─C═N─, and ─NO2 functional groups of CNPM interact with metallic Zn simultaneously and adsorb on the ZMA surface in a parallel arrangement manner, thus forming a water-poor IHL and creating well-arranged ion transportation channels. Furthermore, theoretical calculations and experimental results demonstrate that CNPM absorbed on the Zn anode surface can serve as zincophilic sites for inducing uniform Zn deposition along the (002) plane. Benefiting from the synergistic effect of these functions, the dendrite growth and parasitic reactions are suppressed significantly. As a result, ZMA exhibits a long cycle life (2900 h) and high coulombic efficiency (CE) (500 cycles) in the ZnSO4 +CNPM electrolyte.

19.
Phys Rev Lett ; 131(3): 031603, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37540868

RESUMEN

In quantum field theory, the Dyson-Schwinger equations are an infinite set of coupled equations relating n-point Green's functions in a self-consistent manner. They have found important applications in nonperturbative studies, ranging from quantum chromodynamics and hadron physics to strongly correlated electron systems. However, they are notoriously formidable to solve. One of the main obstacles is that a finite truncation of the infinite system is underdetermined. Recently, Bender et al. [Phys. Rev. Lett. 130, 101602 (2023)PRLTAO0031-900710.1103/PhysRevLett.130.101602] proposed to make use of the large-n asymptotic behaviors and successfully obtained accurate results in D=0 spacetime. At higher D, it seems more difficult to deduce the large-n behaviors. In this Letter, we propose another avenue in light of the null bootstrap. The underdetermined system is solved by imposing the null state condition. This approach can be extended to D>0 more readily. As concrete examples, we show that the cases of D=0 and D=1 indeed converge to the exact results for several Hermitian and non-Hermitian theories of the gϕ^{n} type, including the complex solutions.

20.
Mol Pharm ; 20(1): 690-700, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36541699

RESUMEN

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) checkpoint blockade is a major breakthrough in cancer therapy, but identifying patients likely to benefit from this therapy remains challenging. Immunohistochemistry is not informative about PD-L1 expression heterogeneity because of the limitations of invasive tissue collection. Noninvasive SPECT imaging is an approach to patient selection and therapeutic monitoring by assessing the PD-L1 status throughout the whole body. Here, we radiolabeled a single-domain PD-L1 antibody with technetium-99m (99mTc) for immune-SPECT imaging to evaluate its feasibility of detecting PD-L1 expression. The radiochemical purity of [99mTc]Tc-HYNIC-KN035 was 99.40 ± 0.11% with a specific activity of 2.68 MBq/µg. [99mTc]Tc-HYNIC-KN035 displayed a high PD-L1 specificity both in vitro and in vivo and showed a high specific affinity for PD-L1 with an equilibrium dissociation constant (KD) of 31.04 nM. The binding of [99mTc]Tc-HYNIC-KN035 to H1975 cells (high expression of PD-L1) was much higher than to A549 cells (low expression of PD-L1). SPECT/CT imaging showed that H1975 tumors were visualized at 4 h post-injection and became clearer with time. However, mild tumor uptake was observed in A549 tumors and H1975 tumors of the blocking group at all time points. The uptake value of [99mTc]Tc-HYNIC-KN035 in H1975 tumors was increased continuously from 9.68 ± 0.91% ID/g at 4 h to 13.31 ± 2.23% ID/g at 24 h post-injection, which was higher than in A549 tumors with %ID/g of 4.59 ± 0.76 and 5.54 ± 0.28 at 4 and 24 h post-injection, respectively. These specific bindings were confirmed by blocking studies. [99mTc]Tc-HYNIC-KN035 can be synthesized easily and specifically targeted to PD-L1 in the tumor environment, allowing PD-L1 expression assessment noninvasively and dynamically with SPECT/CT imaging.


Asunto(s)
Antígeno B7-H1 , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Humanos , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Tecnecio/química , Tomografía Computarizada de Emisión de Fotón Único/métodos , Neoplasias/diagnóstico por imagen
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