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Northwest China has undergone notable alterations in climate and vegetation growth in recent decades. Nevertheless, uncertainties persist concerning the response of different vegetation types to climate change and the underlying mechanisms. This study utilized the Normalized Difference Vegetation Index (NDVI) and three sets of meteorological data to investigate the interannual variations in the association between vegetation and climate (specifically precipitation and temperature) from 1982 to 2015. Several conclusions were drawn. (1) RNDVI-GP (relationship between Growing Season NDVI and precipitation) decreased significantly across all vegetation, while RNDVI-GT (relationship between Growing Season NDVI and temperature) showed an insignificant increase. (2) Trends of RNDVI-GP and RNDVI-GT exhibited great variations across various types of vegetation, with forests displaying notable downward trends in both indices. The grassland exhibited a declining trend in RNDVI-GP but an insignificant increase in RNDVI-GT, while no significant temporal changes in RNDVI-GP or RNDVI-GT were observed in the barren land. (3) The fluctuations in RNDVI-GP and RNDVI-GT closely aligned with variations in drought conditions. Specifically, in regions characterized by VPD (vapor pressure deficit) trends less than 0.02 hpa/yr, which are predominantly grasslands, a rise in SWV (soil water volume) tended to cause a reduction in RNDVI-GP but an increase in RNDVI-GT. However, a more negative trend in SWV was associated with a more negative trend in both RNDVI-GP and RNDVI-GT when the VPD trend exceeded 0.02 hPa/yr, primarily in forests. Our results underscore the variability in the relationship between climate change and vegetation across different vegetation types, as well as the role of drought in modulating these associations.
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Changement climatique , Chine , Sécheresses , Saisons , Forêts , Température , Prairie , Climat , Pluie , Écosystème , Développement des plantes , PlantesRÉSUMÉ
BACKGROUND: The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. METHODS: This study included 1418 highly myopic eyes from 720 participants aged 18 - 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. RESULTS: DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P < 0.001). An increase in choroidal vascular index (CVI) was observed in all regions, except for the nasal perifoveal (N2) and inferior perifoveal (I2) regions (all P < 0.01). Multivariable logistic regression analysis revealed a negative association between the presence of DCA and increases in choroidal LA and SA (odds ratio ≤ 0.099, P < 0.001). Multivariable linear regression analysis showed that the mean deviation of the visual field test was positively associated with LA and SA at the vertical meridian (B = 1.512, P < 0.001 for LA; B = 1.956, P < 0.001 for SA). Furthermore, the receiver operating characteristic curve analyses showed the optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region, the LA was 0.076 mm2 and the SA was 0.049 mm2, with area under the curves of 0.916, 0.908, and 0.895, respectively. CONCLUSIONS: The results of this study indicated that both the presence of DCA and visual function impairment were associated with reductions in choroidal perfusion and stromal components. Moreover, we established threshold values for choroidal parameters in diagnosing pathological myopia, offering valuable references for clinical diagnosis and management.
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OBJECTIVE: Chronic ankle instability (CAI) is a common musculoskeletal injury associated with static balance deficits. The Balance Error Scoring System (BESS) is commonly used to assess static balance in individuals with CAI. However, the sensitivity of BESS in detecting balance deficits in CAI is unknown. This study compared BESS performance between people with CAI and controls and investigated which stances most effectively identified balance deficits in individuals with CAI. LITERATURE SURVEY: Seven electronic databases (Web of Science, CINAHL, Embase, PubMed, Scopus, SPORTDiscus, and Cochrane Library) were searched from July 13, 2023, to September 10, 2023, using the ankle instability and balance related terms as keywords to search original studies and perform a systematic review. METHODS: Studies that compared BESS scores between individuals with CAI and healthy controls were systematically identified. Extracted data included study characteristics, participant demographics, and assessment details. The risk of bias was assessed using the Newcastle-Ottawa Scale. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes to compare groups for the BESS components used to assess CAI. RESULTS: Six studies met the eligibility criteria. The double-leg foam stance yielded an SMD of -0.02 (95% CI: -0.32 to 0.29), with an I2 value of 3.5%. Significant differences between groups were noted in the single foam (SMD = 0.89; 95% CI: 0.33-1.45; I2 = 78.3%) and single firm (SMD = 0.62; 95% CI: 0.14-1.10; I2 = 72.1%) performances, although both demonstrated high heterogeneity. Conversely, the tandem foam (SMD = 0.77; 95% CI: 0.51-1.02; I2 = 0.0%) and tandem firm (SMD = 0.38; 95% CI: 0.11-0.68; I2 = 23.8%) performances showed small to moderate between-group differences with considerably lower heterogeneity. CONCLUSION: This review indicates that tandem stances on foam and firm surfaces in the BESS are reliable indicators of static balance deficits in individuals with CAI.
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The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro, it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC.
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Micro(nano)plastics (MNPs) have become a significant environmental concern due to their widespread presence in the biosphere and potential harm to ecosystems and human health. Here, we propose for the first time a MNPs capture, utilization, and storage (PCUS) concept to achieve MNPs remediation from water while meeting economically productive upcycling and environmentally sustainable plastic waste management. A highly efficient capturing material derived from surface-modified woody biomass waste (M-Basswood) is developed to remove a broad spectrum of multidimensional and compositional MNPs from water. The M-Basswood delivered a high and stable capture efficiency of >99.1% at different pH or salinity levels. This exceptional capture performance is driven by multiscale interactions between M-Basswood and MNPs, involving physical trapping, strong electrostatic attractions, and triggered MNPs cluster-like aggregation sedimentation. Additionally, the in vivo biodistribution of MNPs shows low ingestion and accumulation of MNPs in the mice organs. After MNPs remediation from water, the M-Basswood, together with captured MNPs, is further processed into a high-performance composite board product where MNPs serve as the glue for utilization and storage. Furthermore, the life cycle assessment (LCA) and techno-economic analysis (TEA) results demonstrate the environmental friendliness and economic viability of our proposed full-chain PCUS strategy, promising to drive positive change in plastic pollution and foster a circular economy.
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OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods. METHODS: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared. RESULTS: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence. CONCLUSION: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.
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Tumeurs du rein , Néphrectomie , Humains , Mâle , Femelle , Tumeurs du rein/anatomopathologie , Tumeurs du rein/chirurgie , Adulte d'âge moyen , Adulte , Pronostic , Néphrocarcinome/anatomopathologie , Néphrocarcinome/chirurgie , Néphrons/anatomopathologie , Durée opératoire , Études rétrospectivesRÉSUMÉ
Peripheral nerve injury (PNI) represents a serious clinical and public health problem due to its high incurrence and poor spontaneous recovery. Compared to autograft, which is still the best current practice for long-gap peripheral nerve defects in clinics, the use of polymer-based biodegradable nerve guidance conduits (NGCs) has been gaining momentum as an alternative to guide the repair of severe PNI without the need of secondary surgery and donor nerve tissue. However, simple hollow cylindrical tubes can barely outperform autograft in terms of the regenerative efficiency especially in critical sized PNI. With the rapid development of tissue engineering technology and materials science, various functionalized NGCs have emerged to enhance nerve regeneration over the past decades. From the aspect of scaffold design considerations, with a specific focus on biodegradable polymers, this review aims to summarize the recent advances in NGCs by addressing the onerous demands of biomaterial selections, structural designs, and manufacturing techniques that contributes to the biocompatibility, degradation rate, mechanical properties, drug encapsulation and release efficiency, immunomodulation, angiogenesis, and the overall nerve regeneration potential of NGCs. In addition, several commercially available NGCs along with their regulation pathways and clinical applications are compared and discussed. Lastly, we discuss the current challenges and future directions attempting to provide inspiration for the future design of ideal NGCs that can completely cure long-gap peripheral nerve defects.
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Régénération nerveuse , Lésions des nerfs périphériques , Structures d'échafaudage tissulaires , Régénération nerveuse/physiologie , Humains , Animaux , Lésions des nerfs périphériques/thérapie , Nerfs périphériques/physiologie , Matériaux biocompatibles , Ingénierie tissulaire/méthodes , Ingénierie tissulaire/tendances , Régénération tissulaire guidée/méthodes , Régénération tissulaire guidée/tendances , Régénération tissulaire guidée/instrumentationRÉSUMÉ
Silicon (Si) shows great potential as an anode material for lithium-ion batteries. However, it experiences significant expansion in volume as it undergoes the charging and discharging cycles, presenting challenges for practical implementation. Nanostructured Si has emerged as a viable solution to address these challenges. However, it requires a complex preparation process and high costs. In order to explore the above problems, this study devised an innovative approach to create Si/C composite anodes: micron-porous silicon (p-Si) was synthesized at low cost at a lower silver ion concentration, and then porous silicon-coated carbon (p-Si@C) composites were prepared by compositing nanohollow carbon spheres with porous silicon, which had good electrochemical properties. The initial coulombic efficiency of the composite was 76.51%. After undergoing 250 cycles at a current density of 0.2 A·g-1, the composites exhibited a capacity of 1008.84 mAh·g-1. Even when subjected to a current density of 1 A·g-1, the composites sustained a discharge capacity of 485.93 mAh·g-1 even after completing 1000 cycles. The employment of micron-structured p-Si improves cycling stability, which is primarily due to the porous space it provides. This porous structure helps alleviate the mechanical stress caused by volume expansion and prevents Si particles from detaching from the electrodes. The increased surface area facilitates a longer pathway for lithium-ion transport, thereby encouraging a more even distribution of lithium ions and mitigating the localized expansion of Si particles during cycling. Additionally, when Si particles expand, the hollow carbon nanospheres are capable of absorbing the resulting stress, thus preventing the electrode from cracking. The as-prepared p-Si utilizing metal-assisted chemical etching holds promising prospects as an anode material for lithium-ion batteries.
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Background and aims: There is limited and conflicting evidence about the association of erythrocyte fatty acids with coronary artery disease (CAD), particularly in China where the CAD rates are high. Our study aimed to explore the association between erythrocyte fatty acid composition and CAD risk in Chinese adults. Methods: Erythrocyte fatty acids of 314 CAD patients and 314 matched controls were measured by gas chromatography. Multivariable conditional logistic regression and restricted cubic spline models were used to explore the odds ratio with 95% confidence interval (OR, 95% CI) and potential association between erythrocyte fatty acids and CAD risk. Principal component analysis (PCA) was used to analyze further the potential role of various erythrocyte fatty acid patterns in relation to CAD risk. Results: Significant inverse associations were observed between high levels of erythrocyte total n-3 polyunsaturated fatty acids (n-3 PUFA) [ORT3-T1 = 0.18 (0.12, 0.28)], monounsaturated fatty acids (MUFA) [ORT3-T1 = 0.21 (0.13, 0.32)], and the risk of CAD. Conversely, levels of saturated fatty acids (SFAs) and n-6 polyunsaturated fatty acids (n-6 PUFAs) were positively associated with CAD risk [ORT3-T1 = 3.33 (2.18, 5.13), ORT3-T1 = 1.61 (1.06, 2.43)]. No significant association was observed between CAD risk and total trans fatty acids. Additionally, the PCA identifies four new fatty acid patterns (FAPs). The risk of CAD was significantly positively associated with FAP1 and FAP2, while being negatively correlated with FAP3 and FAP4. Conclusion: The different types of erythrocyte fatty acids may significantly alter susceptibility to CAD. Elevated levels of n-3-PUFAs and MUFAs are considered as protective biomarkers against CAD, while SFAs and n-6 PUFAs may be associated with higher CAD risk in Chinese adults. The risk of CAD was positively associated with FAP1 and FAP2, and negatively associated with FAP3 and FAP4. Combinations of erythrocyte fatty acids may be more important markers of CAD development than individual fatty acids or their subgroups.
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Maladie des artères coronaires , Érythrocytes , Acides gras , Humains , Maladie des artères coronaires/sang , Maladie des artères coronaires/épidémiologie , Maladie des artères coronaires/métabolisme , Mâle , Érythrocytes/métabolisme , Érythrocytes/composition chimique , Femelle , Adulte d'âge moyen , Chine/épidémiologie , Études cas-témoins , Acides gras/sang , Sujet âgé , Facteurs de risque , Adulte , Acides gras omega-3/sangRÉSUMÉ
BACKGROUND: The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We performed Mendelian randomization (MR) analysis to identify the causal effects of ligamentous knee injuries on the CST. HYPOTHESIS: Ligamentous knee injuries impair CST microstructure (ie, by reducing fractional anisotropy [FA] and increasing mean diffusivity [MD]). STUDY DESIGN: MR analysis. LEVEL OF EVIDENCE: Level 2. METHODS: MR uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Summary data for ligamentous injuries in knee and CST structure were obtained from genome-wide association study datasets. Significant and independent (5 × 10-6; r2 < 0.001; 10,000 kb) single-nucleotide polymorphisms were extracted for MR analysis. Three methods for MR analysis were used (hypothesis-driven 1-tailed inverse variance weighted, MR-Egger, and weighted median), and sensitivity analyses were conducted to test reliability and stability. RESULTS: Results from 3 MR methods consistently demonstrated that ligamentous knee injuries increased MD of the right CST (ß, 0.063; 90% CI, 0.003-0.123; P = 0.04), and weak statistical significance suggested increased MD of the left CST (ß, 0.060; 90% CI, -0.002 to -0.121; P = 0.05). However, no significant causal relationships were observed in CST FA, and no significant pleiotropy or heterogeneity was observed. Sensitivity analysis utilizing 2-tailed tests had no significant associations between ligamentous knee injuries and changes in CST structure. CONCLUSION: There is statistically weak genetic evidence that corticospinal pathway abnormalities may evolve after ligamentous knee injuries, which manifests as abnormally organized neurites. CLINICAL RELEVANCE: Ligamentous knee injuries require attention not only to damage to the structure of the knee joint itself but also to the process of maladaptive neuroplasticity that leads to structural and functional changes of the CST; novel interventions that target the corticospinal pathway may provide subsequent treatment of ligamentous knee injuries.
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Ewing sarcoma is a pediatric bone and soft tissue tumor treated with chemotherapy, radiation, and surgery. Despite intensive multimodality therapy, ~50% patients eventually relapse and die of the disease due to chemoresistance. Here, using phospho-profiling, we find Ewing sarcoma cells treated with chemotherapeutic agents activate TAM (TYRO3, AXL, MERTK) kinases to augment Akt and ERK signaling facilitating chemoresistance. Mechanistically, chemotherapy-induced JAK1-SQ phosphorylation releases JAK1 pseudokinase domain inhibition allowing for JAK1 activation. This alternative JAK1 activation mechanism leads to STAT6 nuclear translocation triggering transcription and secretion of the TAM kinase ligand GAS6 with autocrine/paracrine consequences. Importantly, pharmacological inhibition of either JAK1 by filgotinib or TAM kinases by UNC2025 sensitizes Ewing sarcoma to chemotherapy in vitro and in vivo. Excitingly, the TAM kinase inhibitor MRX-2843 currently in human clinical trials to treat AML and advanced solid tumors, enhances chemotherapy efficacy to further suppress Ewing sarcoma tumor growth in vivo. Our findings reveal an Ewing sarcoma chemoresistance mechanism with an immediate translational value.
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Protéines et peptides de signalisation intercellulaire , Janus kinase 1 , Récepteurs à activité tyrosine kinase , Sarcome d'Ewing , Transduction du signal , Sarcome d'Ewing/traitement médicamenteux , Sarcome d'Ewing/métabolisme , Sarcome d'Ewing/anatomopathologie , Sarcome d'Ewing/génétique , Humains , Janus kinase 1/métabolisme , Janus kinase 1/antagonistes et inhibiteurs , Janus kinase 1/génétique , Lignée cellulaire tumorale , Animaux , Transduction du signal/effets des médicaments et des substances chimiques , Récepteurs à activité tyrosine kinase/métabolisme , Récepteurs à activité tyrosine kinase/génétique , Récepteurs à activité tyrosine kinase/antagonistes et inhibiteurs , Souris , Protéines et peptides de signalisation intercellulaire/métabolisme , Axl Receptor Tyrosine Kinase , Protéines proto-oncogènes/métabolisme , Protéines proto-oncogènes/génétique , Protéines proto-oncogènes/antagonistes et inhibiteurs , Tumeurs osseuses/traitement médicamenteux , Tumeurs osseuses/métabolisme , Tumeurs osseuses/anatomopathologie , Tumeurs osseuses/génétique , Tests d'activité antitumorale sur modèle de xénogreffe , c-Mer Tyrosine kinase/métabolisme , c-Mer Tyrosine kinase/génétique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Résistance aux médicaments antinéoplasiques/génétique , Phosphorylation/effets des médicaments et des substances chimiques , Femelle , Facteur de transcription STAT-6RÉSUMÉ
Atractylodes macrocephala Koidz (AMK) is a perennial herb from the plant family Asteraceae (formerly Compositae). This herb is mainly distributed in mountainous wetlands in Zhejiang, Sichuan, Yunnan, and Hunan provinces of China. Its medicinal production and quality, however, are severely impacted by root rot disease. In our previous study, endophytic bacterium designated AM201 exerted a high biocontrol effect on the root rot disease of AMK. However, the molecular mechanisms underlying this effect remain unclear. In this study, the identity of strain AM201 as Rhodococcus sp. was determined through analysis of its morphology, physiological and biochemical characteristics, as well as 16S rDNA sequencing. Subsequently, we performed transcriptome sequencing and bioinformatics analysis to compare and analyze the transcriptome profiles of root tissues from two groups: AM201 (AMK seedlings inoculated with Fusarium solani [FS] and AM201) and FS (AMK seedlings inoculated with FS alone). We also conducted morphological, physiological, biochemical, and molecular identification analyses for the AM201 strain. We obtained 1,560 differentially expressed genes, including 187 upregulated genes and 1,373 downregulated genes. We screened six key genes (GOLS2, CIPK25, ABI2, egID, PG1, and pgxB) involved in the resistance of AM201 against AMK root rot disease. These genes play a critical role in reactive oxygen species (ROS) clearance, Ca2+ signal transduction, abscisic acid signal inhibition, plant root growth, and plant cell wall defense. The strain AM201 was identified as Rhodococcus sp. based on its morphological characteristics, physiological and biochemical properties, and 16S rDNA sequencing results. The findings of this study could enable to prevent and control root rot disease in AMK and could offer theoretical guidance for the agricultural production of other medicinal herbs.
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Atractylodes , Endophytes , Analyse de profil d'expression de gènes , Maladies des plantes , Racines de plante , Rhodococcus , Rhodococcus/génétique , Rhodococcus/métabolisme , Rhodococcus/physiologie , Atractylodes/microbiologie , Maladies des plantes/microbiologie , Maladies des plantes/prévention et contrôle , Racines de plante/microbiologie , Endophytes/génétique , Endophytes/métabolisme , Endophytes/classification , Endophytes/physiologie , Endophytes/isolement et purification , Transcriptome , Fusarium/génétique , Fusarium/physiologie , Chine , ARN ribosomique 16S/génétiqueRÉSUMÉ
To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable Micromonospora aurantiaca-derived chitinase, MaChi1, in Escherichia coli and subsequently purified, characterized, and evaluated it for its chitin-converting capacity. Our results indicated that MaChi1 is of the glycoside hydrolase (GH) family 18 with a molecular weight of approximately 57 kDa, consisting of a GH18 catalytic domain and a cellulose-binding domain. We recorded its optimal activity at pH 5.0 and 55 °C. It exhibited excellent stability in a wide pH range of 3.0-10.0. Mg2+ (5 mM), and dithiothreitol (10 mM) significantly promoted MaChi1 activity. MaChi1 exhibited broad substrate specificity and hydrolyzed chitin, chitosan, cellulose, soluble starch, and N-acetyl chitooligosaccharides with polymerization degrees ranging from three to six. Moreover, MaChi1 exhibited an endo-type cleavage pattern, and it could efficiently convert colloidal chitin into N-acetyl-D-glucosamine (GlcNAc) and (GlcNAc)2 with yields of 227.2 and 505.9 mg/g chitin, respectively. Its high chitin-degrading capacity and exceptional pH tolerance makes it a promising tool with potential applications in chitin waste treatment and bioactive oligosaccharide production.
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Chitine , Chitinase , Micromonospora , Chitinase/métabolisme , Chitinase/composition chimique , Chitinase/isolement et purification , Chitinase/génétique , Chitine/analogues et dérivés , Chitine/métabolisme , Chitine/composition chimique , Concentration en ions d'hydrogène , Spécificité du substrat , Micromonospora/enzymologie , Micromonospora/génétique , Hydrolyse , Escherichia coli/génétique , Chitosane/composition chimique , Stabilité enzymatiqueRÉSUMÉ
Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.
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Approximately 40% of limited-stage (stage I and II) diffuse large B-cell lymphoma (LS-DLBCL) presents with extranodal disease. Extranodal LS-DLBCL may have significant biological differences and associated with worse outcomes than nodal disease. Although rituximab based chemoimmunotherapy is standard of first-line treatment, the role of consolidative radiotherapy (RT) in this particular subgroup is controversial. In this multicenter retrospective study, we evaluated the survival benefit of consolidative RT in patients diagnosed with extranodal LS-DLBCL and received rituximab-based chemoimmunotherapy with or without consolidative RT. A total of 328 patients were included, 129 patients (39.3%) received chemoimmunotherapy and consolidative RT, and 199 patients (60.7%) received chemoimmunotherapy alone. With a median follow-up of 5.1 years (range, 0.3-14.8 years), 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 75.4% and 83.9%, respectively. In multivariate analyses, the addition of consolidative RT was associated with superior OS (P = 0.004) and PFS (P = 0.005). High stage-modified International Prognosis Index (SM-IPI) risk predicted worse OS (P = 0.001) and PFS (P = 0.005). Also, propensity score-matched analyses showed RT improved both OS (hazard ratio [HR] 0.228, 95% confidence index [CI] 0.111-0.467, P < 0.001) and PFS (HR 0.308, 95% CI 0.167-0.566, P < 0.001). Among patients who achieved CR, 49 patients (16.6%) developed disease relapse, of which 30.6% relapsed at local sites. Consolidative RT significantly reduced relapse risk (P = 0.002). Our results demonstrated that consolidative RT significantly improved outcomes in patients with extranodal LS-DLBCL in the rituximab era.
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Deep-sea equipment usually operates under dwell-fatigue condition, which means the equipped energy storage devices must survive under the changing pressure. Special mechanical designs should be considered to maintain the electrochemical performance of electrodes under this extreme condition. In this work, an effective assembly strategy is proposed to accommodate the dwell-fatigue loading using Ag decorated reduced graphene oxide (rGO) foam (denoted as AGF) as a superelastic and robust Zn host. The wet-press assembly process enables the formation of highly porous and robust framework. The strong synergetic effect between rGO and Ag further guarantees AGF's superelasticity and ultrahigh mechanical strength. Meanwhile, the homogeneously distributed Ag species on the rGO sheets act as zincophilic sites to effectively facilitate Zn plating. Furthermore, AGF offers enough space to address the expansion during the charge and discharge cycles. As expected, the symmetrical cell using this AGF@Zn host demonstrates a long lifespan over 400 h at a depth-of-discharge of 50%. It is worth mentioning that the superelastic AGF host realizes stable Zn plating/stripping under varying pressures.
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There is a growing consensus on expanding protected and conserved areas for biodiversity conservation. Nevertheless, it remains uncertain where to expand conserved areas as well as what appropriate management modalities to choose. Moreover, conserved areas expansion should be balanced with crop-related food security challenges. We developed a framework to identify cost-effective areas for expanding protected areas and other effective area-based conservation measures (OECMs), and applied it to China. By combining templates for biodiversity conservation priorities at global scale and the priority conservation areas based on 2413 vertebrates' extinction risk in China, we identified areas with high biodiversity conservation value. We then categorized the priority areas according to human impact, indicating the potential cost of management. As a result of combining the two aspects above, we identified the most cost-effective areas for expanding protected areas and OECMs while excluding both the current and predicted croplands that can be used for food security. The results show that China could expand its protected areas to 22.81 % of the country's land area and establish OECMs in areas accounting for 9.82 % and 17.37 % of the country's land area in a cost-effective approach in two scenarios. In the ambitious scenario, protected and conserved areas would account for a maximum of 40.18 % of terrestrial area, with an average 62.67 % coverage of the 2413 species' suitable habitat. To achieve the goals of protected and conserved areas in Kunming-Montreal Global Biodiversity Framework, countries could apply this framework to identify their protected areas and OECM expansion priorities.
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Biodiversité , Conservation des ressources naturelles , Analyse coût-bénéfice , Sécurité alimentaire , Conservation des ressources naturelles/méthodes , Chine , Sécurité alimentaire/méthodesRÉSUMÉ
Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.