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1.
PeerJ ; 12: e17223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618573

RESUMO

Background: The beet armyworm, Spodoptera exigua (Hübner), is an important agricultural pest worldwide that has caused serious economic losses in the main crop-producing areas of China. To effectively monitor and control this pest, it is crucial to investigate its population dynamics and seasonal migration patterns in northern China. Methods: In this study, we monitored the population dynamics of S. exigua using sex pheromone traps in Shenyang, Liaoning Province from 2012 to 2022, combining these data with amigration trajectory simulation approach and synoptic weather analysis. Results: There were significant interannual and seasonal variations in the capture number of S. exigua, and the total number of S. exigua exceeded 2,000 individuals in 2018 and 2020. The highest and lowest numbers of S. exigua were trapped in September and May, accounting for 34.65% ± 6.81% and 0.11% ± 0.04% of the annual totals, respectively. The average occurrence period was 140.9 ± 9.34 days during 2012-2022. In addition, the biomass of S. exigua also increased significantly during these years. The simulated seasonal migration trajectories also revealed varying source regions in different months, primarily originated from Northeast China and East China. These unique insights into the migration patterns of S. exigua will contribute to a deeper understanding of its occurrence in northern China and provide a theoretical basis for regional monitoring, early warning, and the development of effective management strategies for long-range migratory pests.


Assuntos
Agricultura , Humanos , Animais , Spodoptera , Estações do Ano , Dinâmica Populacional , China/epidemiologia
2.
Vox Sang ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622920

RESUMO

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

3.
Mikrochim Acta ; 191(5): 266, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625578

RESUMO

A photoelectrochemical sensor for target detection of hydrogen peroxide was designed based on a new heterojunction nanocomposite which was sulfhydryl-borate ester-modified A1/B1-type pillar[5]arene (BP5)-functionalized Au NPs and multi-walled carbon nanotubes hybridized with bismuth bromide oxide (Au@BP5/MWNTs-BiOBr). The specific sensor was based on the direct induction of oxidation by hydrogen peroxide of the borate ester group of pillar[5]arene. Additionally, the local surface plasmon resonance (LSPR) of Au NPs enhanced visible light capture, the host-guest complexation of BP5 with H2O2 enhanced photocurrent response, the layer-by-layer stacked nanoflower structure of BiOBr provided large specific surface area with more active sites, and the conductivity of MWNTs enhanced the charge separation efficiency and significantly improves the stability of PEC. Their synthesis effect significantly increased the photocurrent signal and further enhanced the detection result. Under the optimal conditions, the linear concentration range of H2O2 detected by the Au@BP5/MWNTs-BiOBr sensor was from 1 to 60 pmol/L. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were 0.333 pmol/L and 1 pmol/L, respectively, and the sensitivity was 6.471 pmol/L. Importantly, the PEC sensor has good stability, reproducibility, and interference resistance and can be used for the detection of hydrogen peroxide in real cells.

4.
Heliyon ; 10(7): e29107, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623223

RESUMO

Background: To investigate the associations between retinal/choroidal microvasculature and carotid plaque in patients with CAD assessed by optical coherence tomography angiography (OCTA). Methods: This study included 127 CAD patients with and 79 without carotid plaque. Each patient had both OCTA taken and digitized to determine retinal/choroidal thickness, vessel density and flow area and carotid ultrasound for carotid plaque size and stability measurement. The superficial capillary plexus (SCP), deep capillary plexus (DCP), out retina and choriocapillaris vessel density, out retina and choriocapillaris flow area, and full retina thickness were analyzed in the fovea centered 6 × 6 mm area. The association between OCTA measurements and carotid plaque characteristics in patients with CAD were evaluated. Results: The duration of hypertension and diabetes mellitus (DM) was significantly longer in CAD patients with carotid plaque than that without (p < 0.001). The mean values for vessel density SCP and DCP (except fovea zone), and choriocapillaris nasal zone were significantly lower in plaque group (p < 0.05). Negative correlations between the carotid plaque width and vessel density SCP and DCP (except fovea zone) (p < 0.05) were also found in this study. Conclusions: In patients with CAD, carotid plaque, a risk factor and marker of atherosclerosis and stenosis, is significantly and independently associated with retinal and choroidal microvascular changes by OCTA.

5.
PLoS Pathog ; 20(4): e1012174, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630801

RESUMO

As a type of parasitic agent, satellite RNAs (satRNAs) rely on cognate helper viruses to achieve their replication and transmission. During the infection of satRNAs, helper virus RNAs serve as templates for synthesizing viral proteins, including the replication proteins essential for satRNA replication. However, the role of non-template functions of helper virus RNAs in satRNA replication remains unexploited. Here we employed the well-studied model that is composed of cucumber mosaic virus (CMV) and its associated satRNA. In the experiments employing the CMV trans-replication system, we observed an unexpected phenomenon the replication proteins of the mild strain LS-CMV exhibited defective in supporting satRNA replication, unlike those of the severe strain Fny-CMV. Independent of translation products, all CMV genomic RNAs could enhance satRNA replication, when combined with the replication proteins of CMV. This enhancement is contingent upon the recruitment and complete replication of helper virus RNAs. Using the method developed for analyzing the satRNA recruitment, we observed a markedly distinct ability of the replication proteins from both CMV strains to recruit the positive-sense satRNA-harboring RNA3 mutant for replication. This is in agreement with the differential ability of both 1a proteins in binding satRNAs in plants. The discrepancies provide a convincing explanation for the variation of the replication proteins of both CMV strains in replicating satRNAs. Taken together, our work provides compelling evidence that the non-template functions of helper virus RNAs create an optimal replication environment to enhance satRNA proliferation.

6.
Child Abuse Negl ; 152: 106796, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631188

RESUMO

BACKGROUND: While childhood maltreatment is understood to be a significant risk factor for adolescent internalizing problems (depression and anxiety), underlying mechanisms linking each type of maltreatment to internalizing problems in adolescents remain unclear. Moreover, the current state of knowledge regarding the associations between maladaptive cognitive emotion regulation strategies and each type of maltreatment, as well as their impact on adolescent internalizing problems, is limited. Additionally, it remains unclear whether these maladaptive strategies mediate this relationship. OBJECTIVE: This study sought to investigate the effects of childhood maltreatment types on adolescent internalizing problems and to explore whether the overall and specific types of maladaptive strategies mediate these associations. METHODS: Using a cross-sectional design, adolescents (N = 7071, Mage = 14.05 years, SDage = 1.54) completed online questionnaires assessing childhood maltreatment, maladaptive cognitive emotion regulation strategies (including rumination, catastrophizing, self-blame, and other-blame), anxiety, and depression. The hypothesized mediating effects were tested using the Lavaan package in R software (4.1.2). RESULTS: Different maltreatment types had varying effects on adolescent internalizing problems. Emotional neglect, emotional abuse, and sexual abuse significantly affected anxiety and depression, whereas physical neglect and physical abuse did not. Other than physical neglect and physical abuse, overall maladaptive strategies mediated the relationship between the other three types of maltreatment (emotional abuse, emotional neglect, and sexual abuse) and internalizing problems (anxiety and depression). For specific maladaptive strategies, rumination mediated the effects of physical abuse, emotional abuse, emotional neglect, and sexual abuse on internalizing problems (anxiety and depression). In contrast, catastrophizing mediated the relationship between physical neglect, emotional abuse, emotional neglect, sexual abuse and internalizing problems (anxiety and depression). CONCLUSIONS: These results suggest that the effects of maltreatment types on internalizing problems are different and that maladaptive strategies, particularly rumination and catastrophizing, are important mechanisms through which childhood maltreatment affects internalizing problems. This is a reminder that mental health workers need to consider the different effects of maltreatment types when intervening and recognize the importance of prioritizing interventions for rumination and catastrophizing.

8.
Chin J Traumatol ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38631945

RESUMO

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the Total Human Model for Safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities was conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

9.
Phys Rev E ; 109(3-1): 034311, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38632735

RESUMO

War and peace, spanning history, deeply affect society, economy, and individuals. Grasping their dynamics is vital to lessen harm and foster global peace. Yet, quantifying them remains hard. Our goal is to create a simple qualitative model using landscape and flux theory, exploring war and peace mechanisms. In this symmetric network, they appear as separate attraction basins, dynamically shifting. Analyzing landscape shape gives insights into global stability. Near critical points, indicators like cross correlations, autocorrelation times, and flickering frequency surge, as warnings. We also calculate the irreversible path between war and peace due to rotational flux. Global sensitivity analysis identifies history's role in system stability. In summary, our research unveils a way to understand war and peace complexities, enhancing knowledge of key elements that lead to conflict, aiding resolution.

10.
Biosens Bioelectron ; 256: 116278, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38608497

RESUMO

The DNA-based logic circuit, constructed to mimic biochemical reaction networks, is highly significant in detecting biomarkers at the molecular level. The differences in the expression levels of microRNAs (miRNAs) within different types of cells provide hope for distinguishing cell subtypes. However, reliance on a single miRNA often leads to unreliable results. Herein, we constructed an enzyme-triggered cascade logic circuit based on the AND gate, which is capable of generating corresponding fluorescence signals in the presence of target miRNAs. The introduction of apurinic/apyrimidinic (AP) sites effectively reduces the likelihood of false signal generation. Amplification of the fluorescence signal relies on the catalytic hairpin assembly and the repetitive reuse of the multicomponent nucleic acid enzyme (MNAzyme). We demonstrated that the logic circuit can not only distinguish cancer cells from normal cells but also identify different types of cancer cells. The programmability of the logic circuits and the simplicity of the assay system allow us to modify the functional sequences to recognize different types of biomarkers, thus providing a reference for the identification of various cell subtypes.

11.
Plant Physiol Biochem ; 210: 108576, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608502

RESUMO

Low temperature severely affects the geographical distribution and production of potato, which may incur cold damage in early spring or winter. Cultivated potatoes, mainly derived from Solanum tuberosum, are sensitive to freezing stress, but wild species of potato such as S. commersonii exhibit both constitutive freezing tolerance and/or cold acclimation tolerance. Hence, such wild species could assist in cold hardiness breeding. Yet the key transcription factors and their downstream functional genes that confer freezing tolerance are far from clear, hindering the breeding process. Here, we used ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) alongside RNA-seq to investigate the variation in chromatin accessibility and patterns of gene expression in freezing-tolerant CMM5 (S. commersonii), before and after its cold treatment. Our results suggest that after exposure to cold, transcription factors including Dof3, ABF2, PIF4, and MYB4 were predicted to further control the genes active in the synthetic/metabolic pathways of plant hormones, namely abscisic acid, polyamine, and reductive glutathione (among others). This suggests these transcription factors could regulate freezing tolerance of CMM5 leaves. In particular, ScDof3 was proven to regulate the expression of ScproC (pyrroline-5-carboxylate reductase, P5CR) according to dual-LUC assays. Overexpressing ScDof3 in Nicotiana benthamiana leaves led to an increase in both the proline content and expression level of NbproC (homolog of ScproC). These results demonstrate the ScDof3-ScproC module regulates the proline content and thus promotes freezing tolerance in potato. Our research provides valuable genetic resources to further study the molecular mechanisms underpinning cold tolerance in potato.

12.
Br J Pharmacol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38613153

RESUMO

BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.

13.
Chemosphere ; : 141985, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614404

RESUMO

Carbonate radical (CO3•-) has been proved to be an important secondary radical in advanced oxidation processes due to various radical reactions involved HCO3-/CO32-. However, the roles and contributions of CO3•- in organic micropollutant degradation have not been explored systematically. Here, we quantified the impact of CO3•- on the degradation kinetics of propranolol, a representative pollutant in the UV/peroxymonosulfate (PMS) system, by constructing a steady-state radical model. Substantially, the measured values were coincident with the predictive values, and the contributions of CO3•- on propranolol degradation were the water matrix-dependent. Propranolol degradation increased by 130% in UV/PMS system containing 10 mM HCO3-, and the contribution of CO3•- was as high as 58%. Relatively high pH values are beneficial for propranolol degradation in pure water containing HCO3-, and the contributions of CO3•- also enhanced, while an inverse phenomenon was shown for the effects of propranolol concentrations. Dissolved organic matter exhibited significant scavenging effects on HO•, SO4•-, and CO3•-, substantially retarding the elimination process. The developed model successfully predicted oxidation degradation kinetics of propranolol in actual sewage, and CO3•- contribution was up to 93%, which in indicative of the important role of CO3•- in organic micropollutant removal via AOPs treatment.

14.
J Neuroimmune Pharmacol ; 19(1): 13, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613591

RESUMO

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5'-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5'-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.


Assuntos
Asma , Polifosfatos , Receptores Purinérgicos P2X4 , Ratos , Animais , Ratos Sprague-Dawley , Endotelina-1 , Ovalbumina/toxicidade , Asma/induzido quimicamente , Tronco Encefálico , Hipertonia Muscular , Trifosfato de Adenosina , Receptores de Endotelina , Adenosina
16.
Environ Sci Technol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627988

RESUMO

Photochemically generated reactive oxygen species (ROS) are widespread on the earth's surface under sunlight irradiation. However, the nonphotochemical ROS generation in surface water (e.g., paddy overlying water) has been largely neglected. This work elucidated the drivers of nonphotochemical ROS generation and its spatial distribution in undisturbed paddy overlying water, by combining ROS imaging technology with in situ ROS monitoring. It was found that H2O2 concentrations formed in three paddy overlying waters could reach 0.03-16.9 µM, and the ROS profiles exhibited spatial heterogeneity. The O2 planar-optode indicated that redox interfaces were not always generated at the soil-water interface but also possibly in the water layer, depending on the soil properties. The formed redox interface facilitated a rapid turnover of reducing and oxidizing substances, creating an ideal environment for the generation of ROS. Additionally, the electron-donating capacities of water at soil-water interfaces increased by 4.5-8.4 times compared to that of the top water layers. Importantly, field investigation results confirmed that sustainable •OH generation through nonphotochemical pathways constituted of a significant proportion of total daily production (>50%), suggesting a comparable or even greater role than photochemical ROS generation. In summary, the nonphotochemical ROS generation process reported in this study greatly enhances the understanding of natural ROS production processes in paddy soils.

17.
BMJ Open ; 14(4): e080756, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569712

RESUMO

OBJECTIVE: There are differences between the floating population and the registered population in the awareness and use of the National Essential Public Health Services (NEPHS) due to the influence of China's household registration system. The Equalization of Basic Public Health and Family Planning Services (EBPHFPS) policy aims to reduce disparities among populations by enhancing the migrant population's access to basic public health services. The aim of this study is to examine the relationship between the EBPHFPS targeted at the floating population and the disparities in access to and utilisation of NEPHS between registered residents and the floating population. DESIGN: A cross-sectional study. SETTING: 8 cities (regions, autonomous prefectures) in China. PARTICIPANTS: 13 998 floating population and 14 000 registered residents in eight cities (regions, autonomous prefectures) were included in the analysis. OUTCOME MEASURES: Three binomial variables, including awareness of NEPHS, acceptance of health education and establishment of health records, were used as outcome indicators to examine the relationship between the EBPHFPS and the disparities between the floating and registered populations. METHODS: A linear regression model, fairness gap calculation and propensity score matching were used to explore the associations. RESULTS: The areas that implemented EBPHFPS exhibited an 8.3% increase in awareness of the NEPHS (p<0.01) and a 4.0% increase (p<0.05) in the likelihood of individuals having received health education within the previous year compared with the areas without the policy implementation. In contrast to registered residents, however, the floating population still faces significant disparities in NEPHS awareness and utilisation. Compared with areas without the equalisation policy, the inequality of opportunity in health education of the floating population in implementation areas is significantly lower (p<0.01), whereas no significant difference is observed in the inequality of opportunity regarding NEPHS awareness among the floating population (p>0.1). The floating population in the pilot areas of the policy encountered greater disparities in the establishment of health records (p<0.01). CONCLUSIONS: Positive associations between the EBPHFPS policy and NEPHS awareness and utilisation among the floating population were demonstrated to some extent; however, the floating population was still confronted with a degree of inequality of opportunity. The government needs to develop target-oriented policies and a guaranteed mechanism to ensure access to NEPHS among the floating population.


Assuntos
Serviços de Planejamento Familiar , Política Pública , Humanos , Estudos Transversais , China/epidemiologia , Saúde Pública
18.
Angew Chem Int Ed Engl ; : e202405197, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574245

RESUMO

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon-carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) site of N-protected pyridin-2-amines, and the other occurs by a pseudo-retro-aldol reaction after hydroxylation of a C(sp3) site. This is the first report of CYP3A-mediated C-C bond cleavage in drug metabolism via ipso-addition of oxygen mediated mechanism. CYP3A-mediated ipso-addition is also implicated in the regioselective C-C cleavages of several pexidartinib analogs. The regiospecificity of CYP3A-catalyzed oxygen ipso-addition under environmentally friendly conditions may be attractive and inspire biomimetic or P450-engineering methods to address the challenging task of C-C bond cleavages.

19.
J Hazard Mater ; 470: 134183, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38574663

RESUMO

Nanomaterials present a vast potential as functional materials in environmental engineering. However, there are challenges with nanocomplex for recyclability, reliable/stable, and scale-up industrial integration. Here, a versatile, low-cost, stable and recycled easily metal-polyphenolic-based material carried by wood powder (bioCar-MPNs) adsorption platform was nano-engineered by a simple, fast self-assembly strategy, in which wood powder is an excellent substrate serving as a scaffold and stabilizer to prevent the nanocomplex from aggregating and is easier to recycle. Life cycle analysis highlights a green preparation process and environmental sustainability for bioCar-MPNs. The metal-polyphenolic nanocomplex coated on the wood surface in bioCar-MPNs presents a remarkable surface adsorption property (1829.4 mg/g) at a low cost (2.4 US dollars per 1000 g bioCar-MPNs) for organic dye. Quartz crystal microbalance analysis (QCM) demonstrates an existing strong affinity between polyphenols and organic dyes. Furthermore, Independent Gradient Model (IGM) and Hirshfeld surface analysis reveal the presence of the electrostatic interactions, π-π interactions, and hydrogen bonding. Meanwhile, adsorption efficiency of bioCar-MPNs maintains over 95% in the presence of co-existing ions (Na+, 0.5 M). Importantly, the reasonable utilization of biomass for water treatment can contribute to achieving the high-value and resource utilization of biomass materials.

20.
Am Heart J ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575049

RESUMO

BACKGROUND: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multi-faceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. MATERIALS AND METHODS: The CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. 41 primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1600 patients aged 35-80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants' characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12-month. DISCUSSION: The CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, NCT05605418.

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