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Dissolved copper and iron ions are regarded as friendly and economic catalysts for peroxymonosulfate (PMS) activation, however, neither Cu(II) nor Fe(III) shows efficient catalytic performance because of the slow rates of Cu(II)/Cu(I) and Fe(III)/Fe(II) cycles. Innovatively, we observed a significant enhancement on the degradation of organic contaminants when Cu(II) and Fe(III) were coupled to activate PMS in borate (BA) buffer. The degradation efficiency of Rhodamine B (RhB, 20 µmol/L) reached up to 96.3% within 10 min, which was higher than the sum of individual Cu(II)- and Fe(III)- activated PMS process. Sulfate radical, hydroxyl radical and high-valent metal ions (i.e., Cu(III) and Fe(IV)) were identified as the working reactive species for RhB removal in Cu(II)/Fe(III)/PMS/BA system, while the last played a predominated role. The presence of BA dramatically facilitated the reduction of Cu(II) to Cu(I) via chelating with Cu(II) followed by Fe(III) reduction by Cu(I), resulting in enhanced PMS activation by Cu(I) and Fe(II) as well as accelerated generation of reactive species. Additionally, the strong buffering capacity of BA to stabilize the solution pH was satisfying for the pollutants degradation since a slightly alkaline environment favored the PMS activation by coupling Cu(II) and Fe(III). In a word, this work provides a brand-new insight into the outstanding PMS activation by homogeneous bimetals and an expanded application of iron-based advanced oxidation processes in alkaline conditions.
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Cobre , Peróxidos , Contaminantes Químicos del Agua , Cobre/química , Contaminantes Químicos del Agua/química , Peróxidos/química , Catálisis , Hierro/química , Rodaminas/química , Oxidación-ReducciónRESUMEN
The rice blast fungus Magnaporthe oryzae poses a significant challenge to maintaining rice production. Developing rice varieties with resistance to this disease is crucial for its effective control. To understand the genetic variability of blast isolates collected between 2015 and 2017, the 27 monogenic rice lines that carry specific resistance genes were used to evaluate blast disease reactions. Based on criteria such as viability, virulence, and reactions to resistance genes, 20 blast isolates were selected as representative strains. To identify novel resistance genes, a quantitative trait locus analysis was carried out utilizing a mixture of the 20 representative rice blast isolates and a rice population derived from crossing the blast-resistant cultivar 'Cheongcheong' with the blast-susceptible cultivar 'Nagdong'. This analysis revealed a significant locus, RM1227-RM1261 on chromosome 12, that is associated with rice blast resistance. Within this locus, 12 disease resistance-associated protein genes were identified. Among them, OsDRq12, a member of the nucleotide-binding, leucine-rich repeat disease resistance family, was chosen as the target gene for additional computational investigation. The findings of this study have significant implications for enhancing rice production and ensuring food security by controlling rice blast and developing resistant rice cultivars.
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AIMS: To explore the clinico-sero-pathological characteristics and risk prediction model of idiopathic inflammatory myopathy (IIM) patients with different muscular perifascicular (PF) changes. METHODS: IIM patients in our center were enrolled and the clinico-sero-pathological data were retrospectively analyzed. A decision tree model was established through machine learning. RESULTS: There were 231 IIM patients enrolled, including 53 with perifascicular atrophy (PFA), 39 with perifascicular necrosis (PFN), and 26 with isolated perifascicular enhancement of MHC-I/MHC-II (PF-MHCn). Clinically, PFA patients exhibited skin rashes and dermatomyositis-specific antibodies (DM-MSAs, 74.5%) except for anti-Mi2. PFN patients showed the most severe muscle weakness, highest creatine kinase (CK), anti-Mi2 (56.8%), and anti-Jo-1 (24.3%) antibodies. PF-MHCn patients demonstrated negative MSAs (48.0%) and elevated CK. Histopathologically, MAC predominantly deposited on PF capillaries in PFA but on non-necrotic myofiber in PFN (43.4% and 36.8%, p < 0.001). MxA expression was least in PF-MHCn (36.0% vs. 83.0% vs. 63.2%, p < 0.001). The decision tree model could effectively predict different subgroups, especially PFA and PFN. CONCLUSIONS: Three types of PF change of IIMs representing distinct clinico-serological characteristics and pathomechanism. Undiscovered MSAs should be explored especially in PF-MHCn patients. The three pathological features could be accurately predicted through the decision tree model.
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Miositis , Humanos , Miositis/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Autoanticuerpos/sangre , Necrosis , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Aprendizaje Automático , Árboles de DecisiónRESUMEN
BACKGROUND: The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML. METHODS: Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing. Individual mouse monoclonal antibodies (mAbs) were produced and characterized, from which we generated BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. Mutations in human IgG1 Fc were introduced to reduce FcγR binding. The antileukemic activity of BIF002 was characterized in vitro and in vivo using multiple cell lines and patient derived AML samples. RESULTS: IL1RAP was found to be highly expressed on most human AML cell lines and primary blasts, including CD34+ LSC-enriched subpopulation from patients with both de novo and relapsed/refractory (R/R) leukemia, but not on normal HSCs. In co-culture of T cells from healthy donors and IL1RAPhigh AML cell lines and primary blasts, BIF002 induced dose- and effector-to-target (E:T) ratio-dependent T cell activation and leukemic cell lysis at subnanomolar concentrations. BIF002 administered intravenously along with human T cells led to depletion of leukemic cells, and significantly prolonged survival of IL1RAPhigh MOLM13 or AML patient-derived xenografts with no off-target side effects, compared to controls. Of note, BiF002 effectively redirects T cells to eliminate LSCs, as evidenced by the absence of disease initiation in secondary recipients of bone marrow (BM) from BIF002+T cells-treated donors (median survival not reached; all survived > 200 days) compared with recipients of BM from vehicle- (median survival: 26 days; p = 0.0004) or isotype control antibody+T cells-treated donors (26 days; p = 0.0002). CONCLUSIONS: The novel anti-IL1RAP/CD3 TCE, BIF002, eradicates LSCs and significantly prolongs survival of AML xenografts, representing a promising, novel treatment for AML.
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Proteína Accesoria del Receptor de Interleucina-1 , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Linfocitos T , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/tratamiento farmacológico , Humanos , Animales , Ratones , Proteína Accesoria del Receptor de Interleucina-1/inmunología , Linfocitos T/inmunología , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Ratones Endogámicos NODRESUMEN
BACKGROUND: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. METHODS: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. FINDINGS: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. CONCLUSIONS: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. FUNDING: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.
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It is important to develop effective strategies for enhancing the removal capacity of aromatic volatile organic compounds (VOCs) by modifying conventional porous adsorbents. In this study, a novel HZSM-5 zeolite-supported sulfonic acid (ZSM-OSO3H) was prepared through ClSO3H modification in dichloromethane and employed for the elimination of gaseous o-xylene. The ClSO3H modification enables the bonding of -OSO3H groups onto the HZSM-5 support, achieving a loading of 8.25 mmol·g-1 and leading to a degradation in both crystallinity and textural structure. Within an active temperature range of 110-145 °C, ZSM-OSO3H can efficiently remove o-xylene through a novel reactive adsorption mechanism, exhibiting a removal rate exceeding 98% and reaching a maximum breakthrough adsorption capacity of 264.7 mg. The adsorbed o-xylene derivative is identified as 3,4-dimethylbenzenesulfonic acid. ZSM-OSO3H demonstrates superior adsorption performance for o-xylene along with excellent recyclability. These findings suggest that ClSO3H sulfonation offers a promising approach for modifying various types of zeolites to enhance both the elimination and resource conversion of aromatic VOCs.
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Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple-color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14-valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple-color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple-color PBNA offers an improved approach for large-scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Pruebas de Neutralización , Vacunas contra Papillomavirus , Humanos , Pruebas de Neutralización/métodos , Vacunas contra Papillomavirus/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacunas Sintéticas/inmunología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Inmunogenicidad Vacunal , Papillomaviridae/inmunología , Sensibilidad y EspecificidadRESUMEN
We report on the antileukemic activity of homoharringtonine (HHT) in T-ALL. We showed that HHT inhibited NOTCH/MYC pathway and induced a significantly longer survival in T-ALL mouse and patient-derived xenograft models, therefore supporting HHT as a promising agent for T-ALL.
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Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.
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The development of efficient and sustainable methods for reducing carbon dioxide (CO2) and converting it into valuable hydrocarbons has gained significant attention. In this study, researchers focused on Ti4+-doped metal-organic framework (MOF-74) photocatalysts. The incorporation of Ti4+ ions into the MOF-74 structure was achieved through a one-pot hydrothermal method. By replacing Zn2+ ions with Ti4+ ions in a substitutional manner, researchers have aimed to enhance the photocatalytic activity of the CO2 reduction. The obtained Ti4+-doped MOF-74 photocatalysts exhibited a significantly improved performance in the reduction of CO2 into carbon monoxide (CO). The doping of Ti4+ ions induced energy bands below the conduction band minimum (CBM) of MOF-74, extending the visible response range and enabling the photocatalysts to utilize a broader spectrum of light for catalytic reactions. This extension of the visible response range enables photocatalysts to utilize a broader spectrum of light for catalytic reactions. The incorporation of Ti4+ ions not only extends the visible response range but also suppresses charge carrier recombination. This work provides valuable insights into the design principles of MOF-based photocatalysts and paves the way for their practical implementation in addressing the energy crisis and reducing greenhouse gas emissions.
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AIM: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. METHODS: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. RESULTS: Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. CONCLUSIONS: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.
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Músculo Esquelético , Enfermedades Musculares , Humanos , Masculino , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Enfermedades Musculares/patología , Enfermedades Musculares/metabolismo , Amiloidosis/patología , Amiloidosis/complicaciones , Amiloidosis/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Anciano de 80 o más Años , Adulto , BiopsiaRESUMEN
BACKGROUND: Cardiovascular disease (CVD) is a chronic disease with a serious prognosis, and obesity is a risk factor for CVD. Lipid accumulation product index (LAP) is a new indicator of obesity, waist circumference, and triglycerides were included in the formula, but its association with CVD is inconsistent. Therefore, this study researched the effect of LAP levels on CVD. METHODS: This prospective cohort study was based on the Kailuan cohort. A total of 95,981 participants who completed the first physical examination in 2006 and had no history of CVD or LAP absence were included. The participants were divided into four groups according to the LAP quartile (Q1 - Q4). Up until December 31, 2022, incidence density was calculated for each group. The hazard ratio (HR) and 95% confidence interval (CI) of CVD in each group were calculated by the Cox proportional hazards model. RESULTS: During a median follow-up period of 15.95 years, 9925 incident CVD events occurred (2123 myocardial infarction and 8096 stroke). There were differences in potential confounders among the four groups (P < 0.001). The incidence density and 95% CI of CVD in Q1-Q4 groups were 4.76(4.54, 5.00), 6 0.50(6.24, 6.77), 8.13(7.84, 8.44) and 9.34(9.02, 9.67), respectively. There were significant differences in the survival curves among the four groups by log-rank test (P < 0.001). After adjusting for potential confounders, Cox proportional hazards model results showed that compared with the Q1 group, the HR and 95% CI of CVD in the Q2, Q3, and Q4 groups were1.15(1.08, 1.23), 1.29(1.21, 1.38) and 1.39(1.30, 1.49), respectively. The HR and 95%CI of myocardial infarction were 1.28(1.10, 1.49), 1.71(1.47, 1.98) and 1.92(1.64, 2.23), respectively. The HR and 95%CI of stroke were 1.11 (1.03, 1.19), 1.20 (1.12, 1.29) and 1.28 (1.19, 1.38), respectively. After subgroup analysis by gender, there was no significant interaction (P = 0.169), and the relationship between LAP and CVD in different genders was consistent with the main results. After subgroup analysis by age, there was a significant interaction (P = 0.007), and the association between LAP and CVD in different age groups was consistent with the main results. After subgroup analysis by BMI, there was no significant interaction (P = 0.506), and the association between LAP and CVD in different BMI groups was consistent with the main results. The results remained robust after sensitivity analyses. For each unit increase in ln(LAP), the HR and 95%CI of CVD were 4.07 (3.92, 4.23). CONCLUSION: This study demonstrated that the risk of CVD increased with the increase of LAP level. The risk of CVD in group Q2 - Q4 was 1.15, 1.29, and 1.39 times higher than that in group Q1, respectively. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000029767.
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This phase I clinical study aimed to assess the safety, tolerability, and population pharmacokinetic-pharmacodynamics (PK-PD) target attainment analysis of etimicin sulfate in healthy participants and provide scientific reference for further development of clinical breakpoints. Twenty-four healthy Chinese subjects were enrolled and received etimicin sulfate infusion in this study. A population PK model was constructed for the estimation of the PK profiles of etimicin sulfate. The area under the concentration-time curve divided by minimum inhibitory concentration (AUC0-24h/MIC) and the peak concentration divided by MIC (Cmax/MIC) were selected as the PK/PD indices. The probability of target attainment (PTA) was calculated for each designed dosing regimen using Monte Carlo Simulations. The minimum MIC value with a PTA ≥ 90% for each regimen was considered as the PK/PD cutoff values. Etimicin sulfate demonstrated safety, tolerability and predictable PK characteristics. No deaths or serious adverse events appeared, and seven treatment emergent adverse events (TEAEs) were reported by five participants. All TEAEs were minor and relieved rapidly. A two-compartment model was developed and validated for describing the PK features of etimicin sulfate among Chinese healthy participants. The diagnostic goodness-of-fit plots and visual predictive check plots showed that this developed model could describe these data well. The PTA results showed that etimicin sulfate provided clinical improvement against strains with MIC of 0.5-1 mg/l and below, and antibacterial effect against strains with MIC of 0.25 mg/l and below. However, etimicin sulfate had limited clinical efficacy for clinical isolates with MIC values > 1 mg/l.
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The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.
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Aldehídos , Fármacos Antiobesidad , Hidrazonas , Obesidad , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/síntesis química , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/química , Hidrazonas/farmacología , Hidrazonas/química , Hidrazonas/síntesis química , Hidrazonas/farmacocinética , Hidrazonas/uso terapéutico , Ratones , Relación Estructura-Actividad , Aldehídos/química , Masculino , Obesidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Obesos , Estructura MolecularRESUMEN
In many real-world phenomena, such as the reconstruction of disaster areas after an earthquake or the stock market's recovery after an economic crisis, damaged networks are spontaneously active after receiving assistance. To reveal how the recovery process, the research of dynamic network recovery has become a hot topic in the field of network science. Previous studies on network recovery have been limited to simple networks with pairwise interactions. However, real-world systems are usually networks with higher-order interactions that are composed of multiple units. To better understand the recovery phenomenon on complex networks in the real world, we propose a novel spontaneous recovery model applied to hypergraphs. The model considers two types of recovery, internal recovery and fast recovery, where inactive nodes in the network can either recover internally with independent probabilities or receive sufficient resources from the hyperedge for fast recovery. We find that the number of active nodes in the system shows a phase change from continuous to discontinuous as the fast recovery condition is relaxed. Moreover, under the influence of higher-order interactions, increasing both average hyperedge cardinality and network heterogeneity contribute to increasing the network resilience. These findings help us understand the recovery mechanisms of complex networks and provide essential insights into designing highly resilient systems.
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Given that it was a once-in-a-century emergency event, the confinement measures related to the coronavirus disease 2019 (COVID-19) pandemic caused diverse disruptions and changes in life and work patterns. These changes significantly affected water consumption both during and after the pandemic, with direct and indirect consequences on biodiversity. However, there has been a lack of holistic evaluation of these responses. Here, we propose a novel framework to study the impacts of this unique global emergency event by embedding an environmentally extended supply-constrained global multi-regional input-output model (MRIO) into the drivers-pressure-state-impact-response (DPSIR) framework. This framework allowed us to develop scenarios related to COVID-19 confinement measures to quantify country-sector-specific changes in freshwater consumption and the associated changes in biodiversity for the period of 2020-2025. The results suggest progressively diminishing impacts due to the implementation of COVID-19 vaccines and the socio-economic system's self-adjustment to the new normal. In 2020, the confinement measures were estimated to decrease global water consumption by about 5.7% on average across all scenarios when compared with the baseline level with no confinement measures. Further, such a decrease is estimated to lead to a reduction of around 5% in the related pressure on biodiversity. Given the interdependencies and interactions across global supply chains, even those countries and sectors that were not directly affected by the COVID-19 shocks experienced significant impacts: Our results indicate that the supply chain propagations contributed to 79% of the total estimated decrease in water consumption and 84% of the reduction in biodiversity loss on average. Our study demonstrates that the MRIO-enhanced DSPIR framework can help quantify resource pressures and the resultant environmental impacts across supply chains when facing a global emergency event. Further, we recommend the development of more locally based water conservation measures-to mitigate the effects of trade disruptions-and the explicit inclusion of water resources in post-pandemic recovery schemes. In addition, innovations that help conserve natural resources are essential for maintaining environmental gains in the post-pandemic world.
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Gene delivery presents great potential in endothelium regeneration and prevention of vascular diseases, but its outcome is inevitably limited by high shear stress and instable microenvironment. Highly efficient nanosystems may alleviate the problem with strong dual-specificity for diseased site and targeted cells. Hence, biomimetic coatings incorporating EC-targeting peptides were constructed by platelets and endothelial cells (ECs) for surface modification. A series of biomimetic gene complexes were fabricated by the biomimetic coatings to deliver pcDNA3.1-VEGF165 plasmid (pVEGF) for rapid recovery of endothelium. The gene complexes possessed good biocompatibility with macrophages, stability with serum and showed no evident cytotoxicity for ECs even at very high concentrations. Furthermore, the peptide modified gene complexes achieved selective internalization in ECs and significant accumulation in endothelium-injured site, especially the REDV-modified and EC-derived gene complexes. They substantially enhanced VEGF expression at mRNA and protein levels, thereby enabling a wound to heal completely within 24â¯h according to wound healing assay. In an artery endothelium-injured mouse model, the REDV-modified and EC-derived gene complexes presented efficient re-endothelialization with the help of enhanced specificity. The biomimetic gene complexes offer an efficient dual-targeting strategy for rapid recovery of endothelium, and hold potential in vascular tissue regeneration.
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Péptidos , Factor A de Crecimiento Endotelial Vascular , Animales , Ratones , Péptidos/química , Péptidos/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Regeneración/efectos de los fármacos , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Endotelio Vascular/metabolismo , Endotelio Vascular/efectos de los fármacos , Técnicas de Transferencia de Gen , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Plásmidos/genética , MasculinoRESUMEN
Selenium (Se) is an essential trace element for human physiological metabolism. The application of organic Se as a source to cultivate Se-rich plants for micronutrient supplementation has been receiving increasing attention. In our study, a bacterial strain named H1 was isolated from the soil in Heilongjiang Province, China, and under optimal culture conditions, the unit Se content could reach 3000 µg·g-1 and its 16S ribosomal DNA sequence seemed to be a new molecular record of an Enterobacter species. After the domestication of Se tolerance and Se-rich experiments, H1 can be used as a Se source for cultivation of Se-rich Auricularia auricula. The results showed that soluble protein, soluble sugar, free amino acid and vitamin C contents in Auricularia auricula were notably increased by 28.7%, 21.8%, 32.5% and 39.2% under the treatment of Se concentration of 0.24 mg·kg-1, respectively. These findings enhance our understanding that H1 is more conducive to Se uptake and nutrient accumulation.
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This study examined the relationship between household environments and trajectories of cognitive function among middle-aged and older adults in China and its urban/rural, gender, and age variations. We estimated multi-level linear growth curve models using a representative sample of 16,111 respondents aged 45â years and over from the China Health and Retirement Longitudinal Study (2011-2018). Older people who lived with a spouse, but not with children, and those with higher living expenditures, better housing quality, and indoor clean fuels for cooking had a slower cognitive decline. Living arrangement more strongly predicted men's cognitive decline, while living expenditure, solid fuel use, and housing quality significantly predicted only women's cognitive decline. Only for older adults and rural residents, those living alone had significantly faster cognitive decline than those living with a spouse only. These findings underscore the importance of improving the living conditions of older adults to help alleviate their cognitive decline.
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In the context of China's freshwater crisis high-resolution data are critical for sustainable water management and economic growth. Yet there is a dearth of data on water withdrawal and scarcity regardless of whether total or subsector amount, for prefectural cities. In administrative and territorial scope, we accounted for water withdrawal of all 63 economic-socio-environmental sectors for all 343 prefectural cities in China, based on a general framework and 2015 data. Spatial and economic-sector resolution is improved compared with previous studies by partitioning general sectors into industrial and agricultural sub-sectors. Construction of these datasets was based on selection of 16 driving forces. We connected a size indicator with corresponding water-withdrawal efficiency. We further accounted for total blue-water withdrawal and quantitative water scarcity status. Then we compared different scopes and methods of official accounts and statistics from various water datasets. These disaggregated and complete data could be used in input-output models for municipal design and governmental planning to help gain in-depth insights into subsector water-saving priorities from local economic activities.