Opportunities and challenges for anti-CD47 antibodies in hematological malignancies.

CD47 is a cell-surface ligand that is overexpressed in various malignancies and that binds to SIRPα on macrophages to promote tumor cell evasion of phagocytosis. Blocking the CD47-SIRPα axis can increase the phagocytosis of macrophages to exert antitumor effects. CD47-based immunotherapy is a current research focus. The combination of anti-CD47 antibodies with other drugs has shown encouraging response rates in patients with hematological tumors, but side effects also occur. Bispecific antibodies and SIRPα/Fc fusion proteins appear to balance the efficacy and safety of treatment. We review the latest clinical research advances and discuss the opportunities and challenges associated with CD47-based immunotherapy for hematological malignancies.

Usefulness of magnetic resonance imaging characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in spinal cord.

AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.

Wireless Millimeter-Size Soft Climbing Robots with Omnidirectional Steerability on Tissue Surfaces.

Wirelessly actuated miniature soft robots actuated by magnetic fields that can overcome gravity by climbing soft and wet tissues are promising for accessing challenging enclosed and confined spaces with minimal invasion for targeted medical operation. However, existing designs lack the directional steerability to traverse complex terrains and perform agile medical operations. Here we propose a rod-shaped millimeter-size climbing robot that can be omnidirectionally steered with a steering angle up to 360 degrees during climbing beyond existing soft miniature robots. The design innovation includes the rod-shaped robot body, its special magnetization profile, and the spherical robot footpads, allowing directional bending of the body under external magnetic fields and out-of-plane motion of the body for delivery of medical patches. With further integrated bio-adhesives and microstructures on the footpads, we experimentally demonstrated inverted climbing of the robot on porcine gastrointestinal (GI) tract tissues and deployment of a medical patch for targeted drug delivery.

Aspects of a Suspended Bioprinting System Affect Cell Viability and Support Bath Properties.

Suspended hydrogel printing is a growing method for fabricating bioprinted hydrogel constructs, largely due to how it enables nonviscous hydrogel inks to be used in extrusion printing. In this work, a previously developed poly(N-isopropylacrylamide)-based thermogelling suspended bioprinting system was examined in the context of chondrocyte-laden printing. Material factors such as ink concentration and cell concentration were found to have a significant effect on printed chondrocyte viability. In addition, the heated poloxamer support bath was able to maintain chondrocyte viability for up to 6 h of residence within the bath. The relationship between the ink and support bath was also assessed by measuring the rheological properties of the bath before and after printing. Bath storage modulus and yield stress decreased during printing as nozzle size was reduced, indicating the likelihood that dilution occurs over time through osmotic exchange with the ink. Altogether this work demonstrates the promise for printing high-resolution cell-encapsulating tissue engineering constructs, while also elucidating complex relationships between the ink and bath, which must be taken into consideration when designing suspended printing systems.

Relation Between New York Heart Association Functional Class and Remnant Cholesterol, and Non-high Density Lipoprotein Cholesterol in Coronary Heart Disease Patients With Type 2 Diabetes Mellitus.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) are associated with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). However, the association between RC, non-HDL-C, and CHD patients with T2DM has not been comprehensively investigated. We analyzed the association between RC, non-HDL-C, and cardiac function in CHD patients with T2DM. Of the 22 022 CHD patients from six hospitals in Tianjin, 5373 (24.4%) patients with T2DM had higher levels of RC and non-HDL-C (P < .001) than those without T2DM. Among CHD patients with T2DM, RC and non-HDL-C were positively associated with New York Heart Association (NYHA) class Ⅱ [RC: odds ratio (OR), 1.74; 95% confidence interval (CI), 1.50-2.01; P < .01; non-HDL-C: OR, 1.23; 95% CI, 1.15-1.31; P < .01]. After adjusting for confounding factors, this association remained (RC: OR, 1.22; 95% CI, 1.03-1.45; P < .05; non-HDL-C: OR, 1.09; 95% CI, 1.02-1.17; P < .05). These findings provide evidence of an independent positive association between RC, non-HDL-C, and NYHA functional classes. More research is warranted to confirm these findings and determine the mechanisms involved.

Association of Serum γ-Glutamyltransferase With C-Reactive Protein Levels in Patients With Coronary Heart Disease.

Serum γ-glutamyltransferase (GGT) levels have been shown to be associated with C-reactive protein (CRP) levels. Nevertheless, studies on this relationship in coronary heart disease (CHD) populations are limited. This study retrospectively assessed 17 523 patients with CHD undergoing GGT and CRP testing. They were divided into 3 groups according to GGT tertiles. The critical points for high CRP levels was 10.0 mg/L, which corresponded to the 75th percentile. Logistic regression analysis was used to analyze the association between GGT and CRP levels in CHD patients. The baseline analysis showed significant differences in related parameters among patients with CHD. Compared with GGT tertile 1 (T1), the odds ratio (OR) of T3 for GGT in CHD patients was 2.15 (95% confidence interval [CI]: 1.96-2.36). The association between GGT and CRP was higher in males (OR: 2.23; 95% CI: 1.98-2.52) than in females (OR: 2.18; 95% CI: 1.89-2.51). This study showed an association between serum GGT and CRP levels in patients with CHD. GGT may be an inflammatory marker and an additional measure for assessing cardiovascular risk.

Pushing or clicking the grocery cart? Health and economic concerns during the COVID-19 pandemic.

Online Grocery Shopping (OGS) has grown dramatically during the COVID-19 pandemic. It is unknown, however, how consumers weighed pandemic situational factors versus household production considerations of timesaving and cost. We collect and analyze survey data from a nationally representative sample to examine how consumers with different health and socio-demographic profiles consider these factors for OGS choices and how their choices changed in the first seven months of the pandemic. We find that consumers with moderate-to-high income, white, having insurance, and not in the labor force value the timesaving and convenience of OGS more than pandemic situational factors. Still, some consumers with health risks choose to shop in person because of the cost of OGS. Lung disease, diabetes, mental health conditions, age, income, and college degree explain the dynamics of OGS choice as the pandemic evolved. Our findings shed light on the development of technology-assisted adaptation to future public health emergencies.

Slice-based and time-specific hemodynamic measurements discriminate carotid artery vulnerable atherosclerotic plaques.

BACKGROUND AND OBJECTIVE: Hemodynamic patterns play key roles in progression of carotid vulnerable plaques. However, most of previous studies utilized maximum or averaged value of hemodynamic measurements which is not an ideal representative of hemodynamic patterns. This study aimed to investigate the association of slice-based and time-specific hemodynamic measurements with carotid vulnerable plaque using magnetic resonance (MR) vessel wall imaging and histology. METHODS: Thirty-two patients (mean age: 63.9±8.1 years; 25 males) with carotid atherosclerotic stenosis (≥50% stenosis) referred to carotid endarterectomy were recruited and underwent MR vessel wall imaging. Carotid plaque burden was evaluated on MR images and vulnerable plaque features including calcification, lipid-rich necrotic core, and intra-plaque hemorrhage (IPH) were identified by histology. The slice-based and time-specific hemodynamic measurements were extracted from computational fluid dynamics simulation of 3D carotid arterial model. Correlation coefficients between hemodynamic measurements and carotid plaque features were calculated and the logistic regressions with generalized estimating equation (GEE) were conducted. The value in discriminating carotid vulnerable plaque features was determined by receiver-operating-characteristic analysis. RESULTS: Of 102 MR-histology matched slices from 32 patients, time-averaged wall shear stress (TAWSS) (r=0.263, p=0.008), oscillatory shear index (OSI) (r=-0.374, p<0.001), and peakWSS (r=0.232, p=0.019) were significantly associated with carotid IPH. The logistic regression with GEE revealed that peakWSS (OR, 1.206; 95% CI, 1.026-1.418; p, 0.023) and TAWSS (OR, 0.364, 95% CI, 0.138-0.959; p, 0.041) were significantly associated with presence of IPH after adjusting for age and BMI. In discriminating carotid IPH, the AUC of TAWSS, OSI, combined TAWSS with maximum wall thickness (MWT) and combined OSI with MWT was 0.656, 0.722, 0.761, and 0.764, respectively. CONCLUSIONS: Slice-based and time-specific hemodynamic characteristics could effectively discriminate carotid IPH. Combination of hemodynamic measurements with carotid plaque burden might be a stronger indicator for carotid vulnerable plaque features than each measurement alone.

Progress in understanding the mechanisms of resistance to BCL-2 inhibitors.

Venetoclax is a new type of BH3 mimetic compound that can target the binding site in the BCL-2 protein and induce apoptosis in cancer cells by stimulating the mitochondrial apoptotic pathway. Venetoclax is especially used to treat haematological malignancies. However, with the recent expansion in the applications of venetoclax, some cases of venetoclax resistance have appeared, posing a major problem in clinical treatment. In this article, we explored several common mechanisms of venetoclax resistance. Increased expression of the antiapoptotic proteins MCL-1 and BCL-XL plays a key role in conferring cellular resistance to venetoclax. These proteins can bind to the released BIM in the context of venetoclax binding to BCL-2 and thus continue to inhibit mitochondrial apoptosis. Structural mutations in BCL-2 family proteins caused by genetic instability lead to decreased affinity for venetoclax and inhibit the intrinsic apoptosis pathway. Mutation or deletion of the BAX gene renders the BAX protein unable to anchor to the outer mitochondrial membrane to form pores. In addition to changes in BCL-2 family genes, mutations in other oncogenes can also confer resistance to apoptosis induced by venetoclax. TP53 mutations and the expansion of FLT3-ITD promote the expression of antiapoptotic proteins MCL-1 and BCL-XL through multiple signalling pathways, and interfere with venetoclax-mediated apoptosis processes depending on their affinity for BH3-only proteins. Finally, the level of mitochondrial oxidative phosphorylation in venetoclax-resistant leukaemia stem cells is highly abnormal. Not only the metabolic pathways but also the levels of important metabolic components are changed, and all of these alterations antagonize the venetoclax-mediated inhibition of energy metabolism and promote the survival and proliferation of leukaemia stem cells. In addition, venetoclax can change mitochondrial morphology independent of the BCL-2 protein family, leading to mitochondrial dysfunction. However, mitochondria resistant to venetoclax antagonize this effect, forming tighter mitochondrial cristae, which provide more energy for cell survival.

A dual-gelling poly(N-isopropylacrylamide)-based ink and thermoreversible poloxamer support bath for high-resolution bioprinting.

Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex, bioactive or cell-laden scaffolds. However, due to the relatively high viscosity required to maintain shape fidelity during printing, many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers. In this work, we present a novel poly(N-isopropylacrylamide) (PNIPAAm)-based ink and poloxamer support bath system that produces precise, multi-layered structures on the tens of micrometers scale. The support bath maintains the structure of the ink in a hydrated, heated environment ideal for cell culture, while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction. Through the combination of the PNIPAAm-based ink and poloxamer bath, this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200 µm. A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated. As a whole, this work demonstrates the ability to produce precise, acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.

Association between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis.

The relationship between the severity of intracranial atherosclerotic disease and the circle of Willis integrity is unclear. In this brief report, we investigate the associations between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis. Patients with symptomatic intracranial atherosclerosis were enrolled and underwent intracranial artery magnetic resonance vessel wall imaging and time-of-flight angiography. The presence or absence of an intracranial atherosclerotic plaque and its maximum wall thickness and stenosis were evaluated. The presence or absence of the A1 segment of the bilateral anterior cerebral arteries (from the internal carotid artery to the anterior communicating artery segment is called anterior cerebral artery A1 segment), and anterior communicating artery, the P1 segment of the bilateral posterior cerebral arteries (The P1 segment of the posterior cerebral artery is a horizontally outward segment), and bilateral posterior communicating arteries were determined. The associations of the intracranial plaque features with the integrity of the circle of Willis were analyzed. Of the 110 recruited subjects (57.2 ± 11.1 years; 65% males), 51 had intracranial plaques, and 44 had stenosis. In patients with bilateral A1 and P1 segments (n = 85), intracranial stenosis was more severe in patients with an anterior communicating artery than those without an anterior communicating artery (19.7% ± 21.7% vs. 1.4% ± 3.3%, p = 0.046). In patients with bilateral A1 and P1 segments and an anterior communicating artery (n = 79), intracranial stenosis was more severe in patients with posterior communicating arteries than those without posterior communicating arteries (27.9% ± 23.7% vs. 13.5% ± 17.9%, p = 0.007). The odds ratio of intracranial stenosis was 1.214 (95% confidence interval (CI), 1.054-1.398; p = 0.007) in discriminating for the presence of posterior communicating arteries in patients with bilateral A1 and P1 segments and an anterior communicating artery after adjusting for confounding factors. The severity of intracranial atherosclerosis was independently associated with the presence of posterior communicating arteries in patients with a complete anterior part of the circle of Willis.

Low-/high-density lipoprotein cholesterol ratio and carotid plaques in patients with coronary heart disease: a Chinese cohort study.

BACKGROUND: Evidence on the relationship between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and carotid plaques remains limited. This study aimed to examine the association between LDL-C/HDL-C and carotid plaques in participants with coronary heart disease (CHD) and to further explore the extent to which a healthy lifestyle reduces the risk of LDL-C/HDL-C-related carotid plaques. METHODS: This large-scale and multi-centre retrospective study included 9426 CHD patients (aged 35-75 years) between January 1, 2014 and September 30, 2020. The LDL-C/HDL-C values were converted to the following tertiles: lowest (< 2.15), middle (2.15-3), and highest (> 3). Healthy lifestyle-related factors referred to whether or not the participant was a non-smoker and non-drinker. Participants were divided into an unfavourable group (those who did not adhere to healthy lifestyle factors), intermediate (only one unhealthy factor), and favourable (neither of the two unhealthy factors). Logistic regression was used for statistical analyses. RESULTS: Of the 9426 participants, 6989 (74.15%) CHD patients had carotid plaques. After adjustment for confounders, each unit increase in the LDL-C/HDL-C was significantly associated with carotid plaques (OR: 1.61; 95%CI: 1.43-1.84; P <  0.001). Multivariate logistic regression revealed that carotid plaques risk for the highest tertile (> 3) was 1.18 times that of the lowest quartile (< 2.15). Compared with an unfavourable lifestyle, an intermediate or a favourable lifestyle was associated with a significant 30% (OR: 0.70; 95%CI: 0.64-0.78; P <  0.001) or 67% (OR: 0.33; 95%CI: 0.29-0.37; P <  0.001) reduction in carotid plaques risk, respectively, among CHD patients with high LDL-C/HDL-C. There were significantly additive and multiplicative interactions between lifestyle and LDL-C/HDL-C with regards to carotid plaques. CONCLUSION: A high LDL-C/HDL-C is associated with a risk of carotid plaques developing in CHD patients. Adhering to a healthy lifestyle has additive beneficial effects on reducing the risk of carotid plaques, especially in relation to the highest LDL-C/HDL-C.

Effects of fertilizer practice on fungal and actinobacterial cellulolytic community with different humified particle-size fractions in double-cropping field.

Cellulose plays an important role in maintaining or improving soil carbon (C) cycling and soil fertility of paddy field. There had close relationship between functional cellulose genes (cbhI and GH48) with characterize of soil organic matter chemical components (fulvic acid and humic acid) and soil physical fractions. However, there is still limited information about how functional cellulose degradation response to long-term fertilizer management and their relative importance for C sequestration under the double-cropping rice paddy field in southern of China. Therefore, the objective of this study were investigated the effects of 34-years long-term fertilizer regime on community abundance of cbhI and GH48 genes in five soil particle-size fractions (> 2000 µm, 2000-200 µm, 200-50 µm, 50-2 µm and 2-0.1 µm) by using polarization magic angle spinning 13C nuclear magnetic resonance spectroscopy. The field experiment was included four different fertilizer treatments: chemical fertilizer alone (MF), rice straw and chemical fertilizer (RF), 30% organic manure and 70% chemical fertilizer (OM), and without fertilizer input as a control (CK). The results showed that distribution of soil humus and cellulolytic microbial community abundance was significant increased under long-term application of crop residue and organic manure condition. And the FA, HA and HM C contents in > 2000 µm and 2000-50 µm fractions with MF, RF and OM treatments were significant higher than that of CK treatment. Meanwhile, the alkyl C and Oalkyl C groups of FA and HA in > 2000 µm fraction with MF, RF, OM and CK treatments were higher than that of the other fractions. There had higher AL% and lower ARO% of FA and HA in different particle-size fractions with MF, RF, OM and CK treatments. The results indicated that abundance of cbhI and GH48 genes in different particle-size fractions with RF and OM treatments were significant increased, compared with CK treatment. There had significant positive correlation between soil humus C components (FA and HA) with abundance of cbhI and GH48 genes, and the o-alkyl C and AL% of FA were positively correlated with abundance of cbhI and GH48 genes. As a result, the community abundance of cbhI and GH48 genes were significant increased under combined application of crop residue and organic manure with chemical fertilizer condition.

Childhood socioeconomic status, adulthood obesity and health: The role of parental permanent and transitory income.

Children from low SES backgrounds experience long-term economic deprivation in addition to excessive income volatility during childhood. Little is known about whether parental income influences adulthood weight and health through either prolonged or transitory hardship. Using the intergenerational feature of the Panel Study of Income Dynamics (PSID), we link parents' income records from a 47-year panel (1968-2015 waves) to health outcomes of 3976 adult children (1999-2015 waves) in the United States. We calculate parental permanent income to measure prolonged disadvantages, as well as transitory income peaks and valleys at various early-life stages to measure transitory advantages and disadvantages, respectively. Our findings show that parental permanent income is negatively associated with obesity and adverse health outcomes in multiple adulthood stages. We also detect negative associations between transitory income peaks in adolescence and adverse weight and health outcomes. Our findings provide strong empirical support for the influence of prolonged material hardship on adverse weight and health outcomes and no support for the influence of transitory material hardship. Our findings also show that policies that improve parental permanent income and provide higher transitory income are essential to generate healthier adults.

Quantifying COVID-19 importation risk in a dynamic network of domestic cities and international countries.

Since its outbreak in December 2019, the novel coronavirus 2019 (COVID-19) has spread to 191 countries and caused millions of deaths. Many countries have experienced multiple epidemic waves and faced containment pressures from both domestic and international transmission. In this study, we conduct a multiscale geographic analysis of the spread of COVID-19 in a policy-influenced dynamic network to quantify COVID-19 importation risk under different policy scenarios using evidence from China. Our spatial dynamic panel data (SDPD) model explicitly distinguishes the effects of travel flows from the effects of transmissibility within cities, across cities, and across national borders. We find that within-city transmission was the dominant transmission mechanism in China at the beginning of the outbreak and that all domestic transmission mechanisms were muted or significantly weakened before importation posed a threat. We identify effective containment policies by matching the change points of domestic and importation transmissibility parameters to the timing of various interventions. Our simulations suggest that importation risk is limited when domestic transmission is under control, but that cumulative cases would have been almost 13 times higher if domestic transmissibility had resurged to its precontainment level after importation and 32 times higher if domestic transmissibility had remained at its precontainment level since the outbreak. Our findings provide practical insights into infectious disease containment and call for collaborative and coordinated global suppression efforts.

Impact of rating and praise campaigns on local government environmental governance efficiency: Evidence from the campaign of establishment of national sanitary cities in China.

BACKGROUND: Ecological and environmental protection is essential to achieving sustainable and high-quality development, which highlights the important role of environmental governance. In terms of the practical actions of environmental governance, the central government in China has carried out continuous rating and praise campaigns, and local governments have actively promoted this effort. However, the related performance consequences have not been empirically investigated. We aimed to verify whether this incentive policy can improve the efficiency of environmental governance and whether this governance method has long-term effects. In addition, we sought to identify mechanisms through which the policy can improve environmental governance. METHOD: We take the rating and praise campaign of the Establishment of National Sanitary Cities (EONSCs) as a quasi-natural experiment and use the panel data for 174 cities from 2004 to 2016 and the propensity score matching-difference in differences (PSM-DID) method to test the impact of rating and praise campaigns on environmental governance efficiency. RESULTS: EONSCs campaign can improve the efficiency of environmental governance by 0.7595 (p<0.01), which is significant at the 1% level; the effects are clearly significant during the evaluation process and the year in which cities are named National Sanitary Cities (NSCs) but decrease annually thereafter. The EONSCs campaign has a significant promoting effect on public services provision, such as public infrastructure investment, public transportation and education. CONCLUSIONS: (1) The rating and praise campaigns can effectively improve the efficiency of environmental governance; (2) the incentive effect is distorted and is not a long-term effect; (3) the impact of the rating and praise campaign of EONSCs on the efficiency of environmental governance is mainly realized through the provision of corresponding public services that are closely related to environmental protection. The findings of this paper provide empirical support for the effectiveness of the central government's rating and praise campaigns and could motivate local governments to actively participate in environmental governance. Moreover, the findings provide an important reference for further improving the rating and praise campaigns and the level of environmental governance.

Microbial carbon source utilization in rice rhizosphere soil with different tillage practice in a double cropping rice field.

Carbon (C) plays an important role in maintaining soil fertility and increasing soil microbial community, but there is still limited information about how source utilization characteristics respond to soil fertility changes under double-cropping rice (Oryza sativa L.) system in southern China paddy field. Therefore, the effects of different short-term (5-years) tillage management on characteristics of C utilization in rice rhizosphere and non-rhizosphere soils under double-cropping rice field in southern China were investigated by using 18O incorporation into DNA. Therefore, a field experiment were included four tillage treatments: conventional tillage with crop residue incorporation (CT), rotary tillage with crop residue incorporation (RT), no-tillage with crop residue retention (NT), rotary tillage with crop residue removed as control (RTO). The results showed that soil microbial biomass C content with CT, RT, NT treatments were increased by 29.71-47.27% and 3.77-21.30% in rhizosphere and non-rhizosphere soils, compared with RTO treatment, respectively. Compared with RTO treatment, soil microbial basal respiration and microbial growth rate with CT treatment were increased 30.56%, 30.94% and 11.91%, 12.34% in rhizosphere and non-rhizosphere soils, respectively. The soil microbial C utilization efficiency were promoted with NT treatment. Compared with RTO treatment, the metabolic capacity of soil microorganism to exogenous C source with CT, RT and NT treatments were increased. The largest type of exogenous C source was saccharides, followed by amino acid and polymers, and complex compounds was the smallest. The redundancy analysis results indicated that tillage treatments significantly changed the utilization characteristics of soil microorganism to exogenous C source. Compared with RTO treatment, the grain yield of early rice and late rice with CT treatment were increased by 409.5 kg ha-1 and 387.0 kg ha-1, respectively. Therefore, the CT and RT treatments could significantly increase soil microbial biomass C content, but the NT treatment promote microbial C utilization efficiency in the double-cropping paddy field of southern China.

The application of multifunctional nanomaterials in Alzheimer's disease: A potential theranostics strategy.

By virtue of their small size, nanomaterials can cross the blood-brain barrier and, when modified to target specific cells or regions, can achieve high bioavailability at the intended site of action. Modified nanomaterials are therefore promising agents for the diagnosis and treatment of neurodegenerative diseases such as Alzheimer's disease (AD). Here we review the roles and mechanisms of action of nanomaterials in AD. First, we discuss the general characteristics of nanomaterials and their application to nanomedicine. Then, we summarize recent studies on the diagnosis and treatment of AD using modified nanomaterials. These studies indicate that using nanomaterials is a potential strategy for AD treatment by slowing the progression of AD through enhanced therapeutic effects.

Assessment of pulmonary toxicity of potential antioxidant drug PEGylated nanoceria after intratracheal instillation in rats.

Cerium oxide (CeO2 ) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO2 nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO2 nanoparticles in vivo remains controversial and still needs intensive research. Therefore, the objective of this study is to investigate the pulmonary and systemic toxicity in rats after 14 days of exposure to the PEGylated CeO2 nanoparticles (abbreviated as CNPs; exposure dose of 2, 10, or 20 mg/kg) through a single intratracheal instillation (IT). We assessed the indicators of lung injury and the pathological damage degree of lung tissue. The bronchoalveolar lavage fluid (BALF) analysis and lung histopathology revealed the occurrence of slight pulmonary inflammation in the 20-mg/kg experimental group rats. However, the inflammation factors in the lung tissue of every group rats did not significantly increase, and the levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissue homogenate rose considerably in the experimental groups. Collectively, these results indicated that pulmonary exposure by the high dose of CNPs could induce mild pulmonary inflammation but did not cause severe systemic toxicity. Moreover, we speculate that the mechanism of pulmonary toxicity of CNPs in rats was due to the autophagic death of healthy lung epithelial cells mediated by endoplasmic reticulum stress. Our results implicate that CNPs can be safely used as an antioxidant drug for the oxidative stress pulmonary diseases.

An investigation of the antidepressant-like effect of Jiaotaiwan in rats by nontargeted metabolomics based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Depression is a mental disorder characterized by persistent unhappiness, lack of interest, with cognitive and sleep disorders. Jiaotaiwan is a traditional Chinese medicine for the treatment of insomnia and depressive-like symptoms. In this study, the major chemical components in Jiaotaiwan were qualitatively analyzed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry, and a model of depression in rats was subsequently established with chronic unpredictable mild stress followed by Jiaotaiwan intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after Jiaotaiwan administration were measured by multiple statistical approaches. Principal component analysis and partial least squares discriminant analysis indicated that the Jiaotaiwan treatment improved the metabolic phenotype depression. Moreover, the heatmap analysis identified the most important ten biomarkers involved in depression. According to the pathway analysis, the therapeutic effect of Jiaotaiwan on depression may involve the regulation of amino acid metabolism, glycerophospholipid metabolism, and energy metabolism. These findings help us understand the pathogenesis of depression in-depth, and discover targets for clinical diagnosis and treatment. And it also lays a foundation for the use of Jiaotaiwan as an antidepressant agent.