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This study proposes a comprehensive evaluation method based on a two-stage model to assess greenhouse gas (GHG) emissions and reductions in high-food-waste-content (HFWC) municipal solid waste (MSW) landfills. The proposed method considers typical processes such as fugitive landfill gas (LFG), LFG collection, flaring, power generation, and leachate treatment. A case study of an HFWC MSW landfill in eastern China is considered to illustrate the evaluation. The findings revealed that the GHG emissions equivalent of the case landfill amounted to 21.23 million tons from 2007 to 2022, averaging 1.03 tons CO2-eq per ton of MSW. There was a potential underestimation of LFG generation at the landfill site during the initial stages, which led to delayed LFG collection and substantial fugitive LFG emissions. Additionally, the time distribution of GHG emissions from HFWC MSW was significantly different from that of low-food-waste-content (LFWC) MSW landfills, with peak emissions occurring much earlier. Owing to the rapid degradation characteristics of HFWC MSW, the cumulative LFG production of the landfill by 2022 (2 years after the final cover) was projected to reach 77 % of the total LFG potential. In contrast, it would take until 2030 for LFWC MSW landfills to reach this level. Furthermore, various scenarios were analyzed, in which if the rapid LFG generation characteristics of HFWC MSW are known in advance, and relevant facilities are constructed ahead of time, the collection efficiency can be improved from 31 % to over 78 %, resulting in less GHG emissions.
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BACKGROUND: Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer-related death in men. Previous studies have shown that the poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPis) improve the treatment response of patients with metastatic castration-resistant PCa (mCRPC). However, the efficacy and safety of various PARPis in mCRPC patients remain unclear, presenting a significant challenge for clinicians when making treatment decisions. To address this, this study conducted two indirect comparisons to evaluate the efficacy and safety of four PARPis (olaparib, niraparib, rucaparib, and talazoparib) in patients with mCRPC. METHODS: A systematic review and network meta-analysis (NMA) using Bayesian statistics was conducted. A comprehensive literature search was performed of the PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) databases to identify relevant studies from the inception to November 8, 2023, using search terms such as "PARP inhibitor", "olaparib", "rucaparib", "niraparib", "talazoparib", and "mCRPC". Phase 2/3 randomized controlled trials (RCTs) related to PARPi therapy and novel hormonal therapy in patients with mCRPC were included in the analysis. The targeted outcomes included radiographic progression-free survival (rPFS), overall survival (OS), adverse events (AEs), and grade ≥3 AEs. Four reviewers screened the titles and abstracts independently to assess the eligibility of each article. Two researchers independently extracted data from the included studies. The risk of bias and quality of the studies were assessed using the Risk-of-Bias 2 tool. RESULTS: Six high-quality phase 2/3 clinical trials, comprising 3,205 individuals, were selected for the systematic review and NMAs. Two NMAs were conducted due to the different designs of the six clinical trials. The indirect comparison with a random-effects model of olaparib, niraparib, and talazoparib showed that olaparib significantly improved rPFS with a hazard ratio (HR) of 0.67 [95% confidence interval (CI): 0.46-0.96]; however, no such significant difference was observed in relation to olaparib and rucaparib. In terms of OS, no significant difference was observed among olaparib, niraparib, and talazoparib. In relation to the AEs, the PARPi interventions using olaparib, niraparib, and talazoparib increased the rates of grade ≥3 AEs with odds ratios (ORs) of 2.0 (95% CI: 0.89-5.3), 3.0 (95% CI: 1.3-7.4), and 3.7 (95% CI: 1.1-12.0), respectively. In the rank probability analysis, according to the surface under the cumulative ranking (SUCRA), olaparib ranked first, followed by niraparib, and talazoparib. Most of the included studies were assessed to be at low risk of bias. CONCLUSIONS: Olaparib significantly improved rPFS among olaparib, niraparib, and talazoparib. Talazoparib exhibited the highest SUCRA value. Regarding safety, olaparib and rucaparib did not significantly increase the incidence of grade ≥3 AEs. When making personalized treatment decisions, clinicians should consider individual patient characteristics, treatment efficacy, and potential AEs.
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Méta-analyse en réseau , Inhibiteurs de poly(ADP-ribose) polymérases , Tumeurs de la prostate , Humains , Inhibiteurs de poly(ADP-ribose) polymérases/usage thérapeutique , Inhibiteurs de poly(ADP-ribose) polymérases/pharmacologie , Mâle , Tumeurs de la prostate/traitement médicamenteuxRÉSUMÉ
Genomic selection (GS) has emerged as an effective technology to accelerate crop hybrid breeding by enabling early selection prior to phenotype collection. Genomic best linear unbiased prediction (GBLUP) is a robust method that has been routinely used in GS breeding programs. However, GBLUP assumes that markers contribute equally to the total genetic variance, which may not be the case. In this study, we developed a novel GS method called GA-GBLUP that leverages the genetic algorithm (GA) to select markers related to the target trait. We defined four fitness functions for optimization, including AIC, BIC, R2, and HAT, to improve the predictability and bin adjacent markers based on the principle of linkage disequilibrium to reduce model dimension. The results demonstrate that the GA-GBLUP model, equipped with R2 and HAT fitness function, produces much higher predictability than GBLUP for most traits in rice and maize datasets, particularly for traits with low heritability. Moreover, we have developed a user-friendly R package, GAGBLUP, for GS, and the package is freely available on CRAN (https://CRAN.R-project.org/package=GAGBLUP).
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Algorithmes , Génomique , Sélection génétique , Zea mays , Génomique/méthodes , Zea mays/génétique , Oryza/génétique , Modèles génétiques , Amélioration des plantes/méthodes , Déséquilibre de liaison , Phénotype , Locus de caractère quantitatif , Génome végétal , Polymorphisme de nucléotide simple , LogicielRÉSUMÉ
Epitaxial growth of 2D transition metal dichalcogenides (TMDCs) on sapphire substrates has been recognized as a pivotal method for producing wafer-scale single-crystal films. Both step-edges and symmetry of substrate surfaces have been proposed as controlling factors. However, the underlying fundamental still remains elusive. In this work, through the molybdenum disulfide (MoS2) growth on C/M sapphire, it is demonstrated that controlling the sulfur evaporation rate is crucial for dictating the switch between atomic-edge guided epitaxy and van der Waals epitaxy. Low-concentration sulfur condition preserves O/Al-terminated step edges, fostering atomic-edge epitaxy, while high-concentration sulfur leads to S-terminated edges, preferring van der Waals epitaxy. These experiments reveal that on a 2 in. wafer, the van der Waals epitaxy mechanism achieves better control in MoS2 alignment (≈99%) compared to the step edge mechanism (<85%). These findings shed light on the nuanced role of atomic-level thermodynamics in controlling nucleation modes of TMDCs, thereby providing a pathway for the precise fabrication of single-crystal 2D materials on a wafer scale.
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Most of current prostheses can offer motor function restoration for limb amputees but usually lack natural and intuitive sensory feedback. Many studies have demonstrated that Transcutaneous Electrical Nerve Stimulation (TENS) is promising in non-invasive sensation evoking for amputees. However, the objective evaluation and mechanism analysis on sensation feedback are still limited. This work utilized multi-channel TENS with diverse stimulus patterns to evoke sensations on four able-bodied subjects and two transradial amputees. Meanwhile, electroencephalogram (EEG) was collected to objectively assess the evoked sensations, where event-related potentials (ERPs), brain electrical activity maps (BEAMs), and functional connectivity (FC) were computed. The results show that various sensations could be successfully evoked for both amputees and able-bodied subjects by customizing stimulus parameters. The ERP confirmed the sensation and revealed the sensory-processing-related components like N100 and P200; the BEAMs confirmed the corresponding regions of somatosensory cortex were activated by stimulation; the FC indicated an increase of interactions between the regions of sensorimotor cortex. This study may shed light on how the brain responds to external stimulation as sensory feedback and serve as a pilot for further bidirectional closed-loop prosthetic control.
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OBJECTIVE: To investigate the role of Parkin overexpression-induecd mitophagy in alleviating acute lung injury of exertional heat stroke(EHS) rats. METHODS: Eighty SD rats were divided into four groups: Control group (CON group), Control Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung Micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. Enzyme-linked immunosorbent assays(ELISA) were used to determine the levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), Tumor necrosis factor-α(TNF-α), and reactive oxygen species(ROS). The morphology of mitochondria in type II epithelial cells of lung tissue was observed using transmission electron microscopy. The apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, MFN2, PTEN-L, PTEN, p62, and microtubule associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by western blot. RESULTS: Compared with the CON group, there were more severe lung injury and more higher levels of IL-6, IL-1ß, TNF-α in EHS rats. Both of the LC3-II/LC3-I ratio and the co-localization of LC3 and Tom20 in the lung tissue of EHS rats decreased. Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly alleviated. The levels of IL-6, IL-1ß, TNF-α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying acute lung injury in rats with EHS, and activation of Parkin overexpression induced-mitophagy can alleviate acute lung injury caused by EHS.
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Lésion pulmonaire aigüe , Coup de chaleur , Poumon , Mitophagie , Rat Sprague-Dawley , Espèces réactives de l'oxygène , Ubiquitin-protein ligases , Animaux , Ubiquitin-protein ligases/métabolisme , Ubiquitin-protein ligases/génétique , Coup de chaleur/métabolisme , Coup de chaleur/complications , Coup de chaleur/anatomopathologie , Rats , Poumon/métabolisme , Poumon/anatomopathologie , Mâle , Lésion pulmonaire aigüe/métabolisme , Espèces réactives de l'oxygène/métabolisme , Modèles animaux de maladie humaine , Protein kinases/métabolisme , Protein kinases/génétique , Facteur de nécrose tumorale alpha/métabolisme , Interleukine-1 bêta/métabolisme , Apoptose , Interleukine-6/métabolisme , Interleukine-6/génétique , Mitochondries/métabolisme , Phosphohydrolase PTEN/métabolisme , Phosphohydrolase PTEN/génétiqueRÉSUMÉ
P-stereogenic phosphines, renowned for their utility as ligands and catalysts, have been instrumental in the field of asymmetric catalysis. However, the catalytic asymmetric synthesis of chiral ligands possessing both axial and phosphine chirality remains a significant challenge. Here, we present the successful demonstration of a Cu-catalyzed asymmetric C-P construction using in situ generated secondary phosphine and heteroaryl chloride. By introducing a chiral NHC ligand and an achiral diphosphine auxiliary ligand, we effectively alleviated the poisoning effect caused by phosphine(III) compounds and suppressed the nonenantioselective background reaction. The reaction exhibited excellent enantioselectivity, with up to 96% ee, and good diastereoselectivity, with up to 14:1 dr, when employing less sterically hindered secondary phosphines. This particular substrate poses a significant challenge due to its strong poisoning effect in copper catalysis.
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Flame-retardant epoxy resins with tough, transparent, ultraviolet shielding, and low dielectric properties have fascinating prospects in electronic and electrical applications, but it is still challenging at present. In this work, a bio-based macromolecule was synthesized from vanillin (a lignin derivative), phenyl dichlorophosphate, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), and poly(propylene glycol) bis(2-aminopropyl ether). The bio-based macromolecule, namely, MFR, was designed and added to the epoxy resin (EP). The cured EP containing 15 wt% MFR (i.e., EP/MFR15) exhibits excellent flame retardancy with an Underwriter Laboratory 94 (UL-94) V-0 rating and a limiting oxygen index (LOI) of 29.2 %. Furthermore, the peak heat release rate (PHRR) and total heat release rate (THR) are drastically reduced by 59.5 % and 40.7 %, respectively. Meanwhile, EP/MFR15 shows 20.3 % and 43.8 % improvements in tensile strength and toughness, respectively. Moreover, MFR simultaneously endows EP with accessional ultraviolet shielding performance and low dielectric constant without sacrificing transparency. This work provides a promising strategy for fabricating a bio-based macromolecular flame retardant and preparing a high-performance EP composite with versatile properties.
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Benzaldéhydes , Résines époxy , Ignifuges , Rayons ultraviolets , Benzaldéhydes/composition chimique , Résines époxy/composition chimique , Résistance à la traction , Structures macromoléculaires/composition chimiqueRÉSUMÉ
Dental age estimation is extensively employed in forensic medicine practice. However, the accuracy of conventional methods fails to satisfy the need for precision, particularly when estimating the age of adults. Herein, we propose an approach for age estimation utilizing orthopantomograms (OPGs). We propose a new dental dataset comprising OPGs of 27,957 individuals (16,383 females and 11,574 males), covering an age range from newborn to 93 years. The age annotations were meticulously verified using ID card details. Considering the distinct nature of dental data, we analyzed various neural network components to accurately estimate age, such as optimal network depth, convolution kernel size, multi-branch architecture, and early layer feature reuse. Building upon the exploration of distinctive characteristics, we further employed the widely recognized method to identify models for dental age prediction. Consequently, we discovered two sets of models: one exhibiting superior performance, and the other being lightweight. The proposed approaches, namely AGENet and AGE-SPOS, demonstrated remarkable superiority and effectiveness in our experimental results. The proposed models, AGENet and AGE-SPOS, showed exceptional effectiveness in our experiments. AGENet outperformed other CNN models significantly by achieving outstanding results. Compared to Inception-v4, with the mean absolute error (MAE) of 1.70 and 20.46 B FLOPs, our AGENet reduced the FLOPs by 2.7×. The lightweight model, AGE-SPOS, achieved an MAE of 1.80 years with only 0.95 B FLOPs, surpassing MobileNetV2 by 0.18 years while utilizing fewer computational operations. In summary, we employed an effective DNN searching method for forensic age estimation, and our methodology and findings hold significant implications for age estimation with oral imaging.
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As spores of Alicyclobacillus acidoterrestris can survive traditional pasteurization, this organism has been suggested as a target bacterium in the fruit juice industry. This study aimed to investigate the inactivation effect of cold plasma on A. acidoterrestris spores and the mechanism behind the inactivation. The inactivation effect was detected by the plate count method and described by kinetic models. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), the detection of dipicolinic acid (DPA) release and heat resistance detection, the detection and scavenging experiment of reactive species, and cryo-scanning electron microscopy were used to explore the mechanism of cold plasma inactivation of A. acidoterrestris. The results showed that cold plasma can effectively inactivate A. acidoterrestris spores in saline with a 3.0 ± 0.3 and 4.4 ± 0.8 log reduction in CFU/mL, for 9 and 18 min, respectively. The higher the voltage and the longer the treatment time, the stronger the overall inactivation effect. However, a lower gas flow rate may increase the probability of spore contact with reactive species, resulting in better inactivation results. The biphasic model fits the survival curves better than the Weibull model. SEM and TEM revealed that cold plasma treatment can cause varying degrees of damage to the morphology and structure of A. acidoterrestris spores, with at least 50 % sustaining severe morphological and structural damage. The DPA release and heat resistance detection showed that A. acidoterrestris spores did not germinate but died directly during the cold plasma treatment. 1O2 plays the most important role in the inactivation, while O3, H2O2 and NO3- may also be responsible for inactivation. Cold plasma treatment for 1 min reduced A. acidoterrestris spores in apple juice by 0.4 ± 0.0 log, comparable to a 12-min heat treatment at 95 °C. However, as the treatment time increased, the survival curve exhibited a significant tailing phenomenon, which was most likely caused by the various compounds in apple juice that can react with reactive species and exert a physical shielding effect on spores. Higher input power and higher gas flow rate resulted in more complete inactivation of A. acidoterrestris spores in apple juice. What's more, the high inactivation efficiency in saline indicates the cold plasma device provides a promising alternative for controlling A. acidoterrestris spores during apple washing. Overall, our study provides adequate data support and a theoretical basis for using cold plasma to inactivate A. acidoterrestris spores in the food industry.
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Alicyclobacillus , Jus de fruits et de légumes , Viabilité microbienne , Gaz plasmas , Spores bactériens , Alicyclobacillus/croissance et développement , Alicyclobacillus/physiologie , Spores bactériens/croissance et développement , Gaz plasmas/pharmacologie , Cinétique , Jus de fruits et de légumes/microbiologie , Microbiologie alimentaire , Numération de colonies microbiennes , Acides picoliniques/pharmacologie , Microscopie électronique à balayage , Conservation aliments/méthodes , Température élevéeRÉSUMÉ
This paper concerns the invasion dynamics of the lattice pioneer-climax competition model with parameter regions in which the system is non-monotone. We estimate the spreading speeds and establish appropriate conditions under which the spreading speeds are linearly selected. Moreover, the existence of travelling waves is determined by constructing suitable upper and lower solutions. It shows that the spreading speed coincides with the minimum wave speed of travelling waves if the diffusion rate of the invasive species is larger or equal to that of the native species. Our results are new to estimate the spreading speed of non-monotone lattice pioneer-climax systems, and the techniques developed in this work can be used to study the invasion dynamics of the pioneer-climax system with interaction delays, which could extend the results in the literature. The analysis replies on the construction of auxiliary systems, upper and lower solutions, and the monotone dynamical system approach.
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Modèles biologiques , Espèce introduite , Comportement compétitif/physiologie , Dynamique des populationsRÉSUMÉ
Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective constituent of A. catechu, arecoline, has been reported to affect the central nervous system. Less is known if it may affect pain and its related emotional responses. In this study, we found that oral application of arecoline alleviated the inflammatory pain and its induced anxiolytic and anti-depressive-like behavior. Arecoline also increased the mechanical nociceptive threshold and alleviated depression-like behavior in naïve mice. In the anterior cingulate cortex (ACC), which acts as a hinge of nociception and its related anxiety and depression, by using the multi-electrode field potential recording and whole-cell patch-clamp recording, we found that the evoked postsynaptic transmission in the ACC of adult mice has been inhibited by the application of arecoline. The muscarinic receptor is the major receptor of the arecoline in the ACC. Our results suggest that arecoline alleviates pain, anxiety, and depression-like behavior in both physiological and pathological conditions, and this new mechanism may help to treat patients with chronic pain and its related anxiety and disorder in the future.
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Anxiété , Arécoline , Comportement animal , Dépression , Transmission synaptique , Animaux , Transmission synaptique/effets des médicaments et des substances chimiques , Anxiété/traitement médicamenteux , Anxiété/physiopathologie , Arécoline/pharmacologie , Mâle , Dépression/traitement médicamenteux , Dépression/physiopathologie , Comportement animal/effets des médicaments et des substances chimiques , Nociception/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Gyrus du cingulum/effets des médicaments et des substances chimiques , Gyrus du cingulum/physiologie , Souris , Cortex cérébral/effets des médicaments et des substances chimiques , Cortex cérébral/physiologieRÉSUMÉ
With the increasing demand for multifunctional optoelectronic devices, flexible electrochromic energy storage devices are being widely recognized as promising platforms for diverse applications. However, simultaneously achieving high capacitance, fast color switching and large optical modulation range is very challenging. In this study, the MXene-based flexible in-plane microsupercapacitor was fabricated via a mask-assisted spray coating approach. By adding electrochromic ethyl viologen dibromide (EVB) into the electrolyte, the device showed a reversible color change during the charge/discharge process. Due to the high electronic conductivity of the MXene flakes and the fast response kinetics of EVB, the device exhibited a fast coloration/bleaching time of 2.6 s/2.5 s, a large optical contrast of 60%, and exceptional coloration efficiency. In addition, EVB acted as a redox additive to reinforce the energy storage performance; as a result, the working voltage window of the Ti3C2-based symmetric aqueous microsupercapacitor was extended to 1 V. Moreover, the device had a high areal capacitance of 12.5 mF cm-2 with superior flexibility and mechanical stability and showed almost 100% capacitance retention after 100 bending cycles. The as-prepared device has significant potential for a wide range of applications in flexible and wearable electronics, particularly in the fields of camouflage, anticounterfeiting, and displays.
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BACKGROUND: Pediatric inguinal hernia repair (IHR) is a common cause of obstructive azoospermia (OA). Yet, the surgical treatment for this kind of OA remains difficult with poor fertility outcome. OBJECTIVES: To evaluate the safety and effectiveness of totally extraperitoneal laparoscopy-assisted microsurgical vasovasostomy (VV) in the treatment of OA caused by pediatric bilateral IHR. MATERIALS AND METHODS: Totally, 37 patients with OA caused by pediatric bilateral IHR were enrolled in this study from March 2015 to December 2020 in Shanghai General Hospital. The clinical data and fertility outcomes were collected and analyzed. RESULTS: All patients enrolled had a history of bilateral IHR at the age of 1-10 years old. The mean age of patients was 27 ± 4.31 (range: 18-35) years. Totally extraperitoneal laparoscopy (TEP) was applied in 31 patients for the exploration and retrieval of pelvic vas deferens end, and 30 of them underwent microsurgical VV successfully. Among the six cases where TEP was not applied, five cases underwent microsurgical anastomosis. Intraoperative exploration revealed that the location of vas deferens injuries included scrotum (2.70%, 1/37), inguinal canal (5.41%, 2/37), pelvic cavity (78.37%, 29/37), and multiple sites (13.51%, 5/37). The mean operation time was 339 ± 96.73 min (range: 130-510 min). There were no surgical complications. Thirty-three cases were followed up for 5-48 months with four cases lost to follow-up. The overall patency rate, pregnancy rate, and natural pregnancy rate were 75.86% (22/29), 46.67% (14/30), and 36.84% (7/19, 3 patients without family planning), respectively. And seven couples conceived through the assisted reproductive technique, two of which using fresh sperm in the ejaculate. CONCLUSION: TEP laparoscopy-assisted microscopic VV is an effective treatment for patients with OA caused by pediatric bilateral IHR.
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The use of nanobodies (Nbs) in affinity chromatography for biomacromolecule purification is gaining popularity. However, high-performance Nb-based affinity resins are not readily available, mainly due to the lack of suitable immobilization methods. In this study, we explored an autocatalytic coupling strategy based on the SpyCatcher/SpyTag chemistry to achieve oriented immobilization of Nb ligands. To facilitate this approach, a variant cSpyCatcher003 (cSC003) was coupled onto agarose microspheres, providing a specific attachment site for SpyTagged nanobody ligands. The cSC003 easily purified from Escherichia coli through a two-step procedure, exhibits exceptional alkali resistance and structural recovery capability, highlighting its robustness as a linker in the coupling strategy. To validate the effectiveness of cSC003-derivatized support, we employed VHSA, a nanobody against human serum albumin (HSA), as the model ligand. Notably, the immobilization of SpyTagged VHSA onto the cSC003-derivatized support was achieved with a coupling efficiency of 90 %, significantly higher than that of traditional thiol-based coupling method. This improvement directly correlated to the preservation of the native conformation of nanobodies during the coupling process. In addition, the Spy-immobilized resin demonstrated better performance in the binding capacity, with a 3-fold improvement in capture efficiency, underscoring the advantages of the Spy immobilization strategy for oriented immobilization of VHSA ligands. Moreover, online purification and immobilization of SpyTagged VHSA from crude bacterial lysate was achieved using the cSC003-derivatized support. The resulting resin exhibited high binding specificity towards HSA, yielding a purity above 95 % directly from human serum, and maintained good stability throughout multiple purification cycles. These findings highlight the potential of the Spy immobilization strategy for developing Nb-based affinity chromatographic materials, with significant implications for biopharmaceutical downstream processes.
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Chromatographie d'affinité , Sérum-albumine humaine , Anticorps à domaine unique , Chromatographie d'affinité/méthodes , Anticorps à domaine unique/composition chimique , Anticorps à domaine unique/immunologie , Humains , Sérum-albumine humaine/composition chimique , Escherichia coli/composition chimique , Anticorps immobilisés/composition chimique , Anticorps immobilisés/immunologie , Ligands , Agarose/composition chimique , PeptidesRÉSUMÉ
Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.
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Prolifération cellulaire , Protéine du gène deleted in azoospermia 1 , ARN messager , Protéines de liaison à l'ARN , Spermatogenèse , Spermatogonies , Mâle , Spermatogonies/métabolisme , Prolifération cellulaire/génétique , Humains , Protéines de liaison à l'ARN/génétique , Protéines de liaison à l'ARN/métabolisme , ARN messager/génétique , ARN messager/métabolisme , Spermatogenèse/génétique , Protéine du gène deleted in azoospermia 1/génétique , Protéine du gène deleted in azoospermia 1/métabolisme , Animaux , Azoospermie/génétique , Azoospermie/métabolisme , AdulteRÉSUMÉ
OBJECTIVE: To investigate the role of Pink1/Parkin-mediated mitochondrial autophagy in exertional heat stroke-induced acute lung injury in rats. METHODS: Sixty SD rats were divided into four groups: normal group (CON group), normal Parkin overexpression group (CONâ+âParkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHSâ+âParkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. RESULTS: Compared with the EHS group, the survival rate of rats in the EHSâ+âParkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly reduced. The levels of inflammatory factors IL-6, IL-1ß, TNF- α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Impairment of Pink1/Parkin-mediated mitochondrial autophagy function is one of the mechanisms of exertional heat stroke-induced acute lung injury in rats. Activation of the Pink1/Parkin pathway can alleviate acute lung injury caused by exertional heat stroke.