Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self‐preservation ...mechanisms bestow cancer cells thermoresistance to protect them from the damage of PTT. To minimize the thermoresistance of cancer cells and improve the efficacy of PTT, an integrated on‐demand nanoplatform composed of a photothermal conversion core (gold nanorod, GNR), a cargo of a HSPs inhibitor (triptolide, TPL), a mesoporous silica based nanoreservoir, and a photothermal and redox di‐responsive polymer shell is developed. The nanoplatform can be enriched in the tumor site, and internalized into cancer cells, releasing the encapsulated TPL under the trigger of intracellular elevated glutathione and near‐infrared laser irradiation. Ultimately, the liberated TPL could diminish thermoresistance of cancer cells by antagonizing the PTT induced heat shock response via multiple mechanisms to maximize the PTT effect for cancer treatment.
A triptolide nanoreservoir, which can be in situ activated by near‐infrared light (NIR) laser irradiation and intracellular high redox potential, is developed to overcome the thermoresistance of cancer cells. Thanks to the inhibited photothermal therapy (PTT) induced heat shock response, the photothermal therapy efficacy of the gold nanorod/mesoporous nanocomplex is greatly improved.
The biomimetic enzyme activity of cerium oxide nanoparticles (CeNPs) prefers ultrasmall particle size and bare surface. Unfortunately, those two features are not favorable for its in vivo application ...due to easy aggregation and fast renal filtration. To take advantage of the activity of CeNP for cancer therapy, a homologous targeted cerium oxide nanoparticle system, targeted CeNP (T‐CeNP), with the integration of a biodegradable dendritic mesoporous silica nanoparticle, superoxide dismutase and catalase mimicking CeNPs, and the camouflage coating of cancer cell membrane has been developed. Attributed to the homologous targeting effect of cancer cell membrane, nanoparticles with camouflage coating are retained in the tumor in an orthotopic breast cancer metastatic model. Subsequently, T‐CeNP effectively hinders cancer‐associated fibroblast transdifferentiation and reprograms it back to a normal fibroblast. Consequently, T‐CeNP coupled with doxorubicin reduces the size of primary tumors and prevents the post‐surgery lung metastasis and liver metastasis of breast cancer.
A homologous targeted cerium oxide nanoparticle system (T‐CeNP) is developed for remodeling the tumor microenvironment by inhibiting cancer‐associated fibroblast transdifferentiation and reprogramming them back to normal fibroblasts. T‐CeNP coupled with doxorubicin reduces the size of the primary tumor and prevents post‐surgery lung metastasis and liver metastasis of cancer in an orthotopic breast cancer model.
Based on the data from six Chinese National Surveys on Students Constitution and Health (CNSSCH) from 1985 to 2010, we explored the secular trend in the prevalence of obesity in urban Chinese ...children over a period of 25 years. The aim of this study was to examine the gender disparities in the prevalence of childhood obesity over time. The standardized prevalence of obesity in Chinese children increased rapidly during the past 25 years from 0.2% in 1985 to 8.1% in 2010. The increasing trend was significant in all age subgroups (p<0.01). Although the prevalence of obesity continuously increased in both boys and girls, the changing pace in boys was faster than that in girls. Age-specific prevalence odds ratios (PORs) of boys versus girls for obesity increased over time during the 25 year period. The prevalence of obesity in boys was significantly higher than in girls in all age-specific subgroups from 1991 and after. The gradually expanding gender disparity suggests the prevalence of obesity in boys contribute to a large and growing proportion of obese children. Therefore, it is critical for developing and implementing gender-specific preventive guidelines and public health policies in China.
Differentiable programming is a fresh programming paradigm which composes parameterized algorithmic components and optimizes them using gradient search. The concept emerges from deep learning but is ...not limited to training neural networks. We present the theory and practice of programming tensor network algorithms in a fully differentiable way. By formulating the tensor network algorithm as a computation graph, one can compute higher-order derivatives of the program accurately and efficiently using automatic differentiation. We present essential techniques to differentiate through the tensor networks contraction algorithms, including numerical stable differentiation for tensor decompositions and efficient backpropagation through fixed-point iterations. As a demonstration, we compute the specific heat of the Ising model directly by taking the second-order derivative of the free energy obtained in the tensor renormalization group calculation. Next, we perform gradient-based variational optimization of infinite projected entangled pair states for the quantum antiferromagnetic Heisenberg model and obtain state-of-the-art variational energy and magnetization with moderate efforts. Differentiable programming removes laborious human efforts in deriving and implementing analytical gradients for tensor network programs, which opens the door to more innovations in tensor network algorithms and applications.
Down‐regulation of microRNA‐26a (miR‐26a) is associated with poor prognosis of hepatocellular carcinoma (HCC), but its functional mechanism in HCC remains unclear. In this study, we investigated the ...roles of miR‐26a in tumor growth and metastasis of HCC and found that miR‐26a was frequently down‐regulated in HCC tissues. Down‐regulation of miR‐26a correlated with HCC recurrence and metastasis. Through gain‐ and loss‐of‐function studies, miR‐26a was demonstrated to significantly inhibit in vitro cell proliferation, migration, and invasion. In addition, miR‐26a induced G1 arrest and promoted apoptosis of HCC cells. Importantly, miR‐26a suppressed in vivo tumor growth and metastasis in nude mice models bearing human HCC. Interleukin‐6 (IL‐6) was identified as a target of miR‐26a. Knockdown of IL‐6 induced effects on HCC cells similar to those induced by miR‐26a. In contrast, IL‐6 treatment abrogated the effects induced by miR‐26a up‐regulation. Moreover, miR‐26a dramatically suppressed expression of signal transducer and activator of transcription 3 (Stat3) target genes, including Bcl‐2, Mcl‐1, cyclin D1, and MMP2. IL‐6 treatment antagonized this effect, while knockdown of IL‐6 by IL‐6 short hairpin RNA (shIL‐6) induced inhibitory effects on the expression of p‐Stat3 and its main target genes, similar to miR‐26a. The messenger RNA and protein levels of IL‐6 inversely correlated with miR‐26a in HCCs. Patients with high miR‐26a or low IL‐6 in HCC tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR‐26a, IL‐6, and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Conclusion: miR‐26a could suppress tumor growth and metastasis of HCC through IL‐6‐Stat3 signaling and is a novel prognostic marker and therapeutic target for HCC. (HEPATOLOGY 2013)
Effects of MC4R variants in previous Chinese population studies were inconsistent. Gene-environment interactions might influence the effect of MC4R variants on obesity, which was still unclear. We ...performed the study to clarify the association of variants near MC4R gene with obesity-related phenotypes and gene-environment interactions in Chinese children and adolescents. Two common variants (rs12970134 and rs17782313) near MC4R were genotyped in 2179 children and adolescents aged 7-18 years in Beijing of China. Associations between the variants and obesity-related phenotypes together with gene-environment interactions were analyzed. The A-alleles of rs12970134 were nominally associated with risk of overweight/obesity (Odds Ratios (OR) = 1.21, 95%CI: 1.03-1.44, P = 0.025) and BMI (β = 0.33 kg/m2, 95%CI: 0.02-0.63, P = 0.025), respectively. The rs12970134 was also associated with HDL-C (β = -0.03mmol/L per A-allele, 95%CI: -0.05, -0.01, P = 0.013) independent of BMI. In the further analysis, we found the significant interaction of rs12970134 and physical activity/sedentary behaviors on BMI (Pinteraction = 0.043). The rs12970134 was found to be associated with BMI only in children with physical activity<1h/d and sedentary behaviors ≥2h/d (BMI: β = 1.27 kg/m2, 95%CI: 0.10-2.45, P = 0.034). The association was not detected in their counterparts with physical activity≥1h/d or sedentary behaviors <2h/d. We identified the effect of MC4R rs12970134 on overweight/obesity and BMI, and we also found physical activity and sedentary behaviors modified the association between the rs12970134 and BMI in Chinese children and adolescents.
In recent years, significant emphases and efforts have been placed on developing and implementing advanced driver assistance systems (ADAS). These systems need to work with human drivers to increase ...vehicle occupant safety, control, and performance in both ordinary and emergency driving situations. To aid such cooperation between human drivers and ADAS, driver models are necessary to replicate and predict human driving behaviors and distinguish among different drivers. This paper presents a combined driver model that is able to not only identify different individual driver behaviors, but also predict a driver's behavior in rare vehicle maneuvers such as collision avoidance (CA) based on his/her daily driving data. The driver model consists of a compensatory transfer function and an anticipatory component and is integrated with the design of the individual driver's desired path. It has been shown that the proposed driver model can replicate each driver's steering wheel angle signal for a variety of highway and in-city maneuvers. The utility of the proposed driver model is its ability to predict a driver's steering wheel angle signal for a CA maneuver from only daily nonemergency driving data. The driver model is then validated by comparing two different drivers' model parameter sets to the group average to show that each driver has a unique set of parameters. Finally, the driver model is validated by showing that its daily driving parameters differ from its predicted CA parameters.
Exposure to relatively low or high temperatures during the entire pregnancy significantly increase the risk of preterm birth, with hazard ratios (HRs) 95% confidence intervals (CIs) of 1.03 (95%CI: ...1.02, 1.04) for relatively low (9.1 ℃, the 5th percentile) temperature and 1.55 (95%CI: 1.48, 1.61) for relatively high (23.0 ℃, the 95th percentile) temperature in comparison with the thresholds (12.0 ℃)
Display omitted
Little is known about the effect of ambient temperature on preterm birth, especially for the trimester-specific effects.
To evaluate whether exposure to relatively low or high temperature during pregnancy is associated with increasing risk of preterm birth or not.
We analysed the data of a birth cohort with 1,281,859 singleton pregnancies during 2013–2014 and matched the home address of each pregnant women to the model based daily meteorological and air pollution data. Then we used the Cox proportional hazard regression models with random effect to estimate the non-linear associations between exposure to relatively low or high temperature at each trimester of pregnancy and the risk of preterm birth, after controlling for air pollution and individual-level covariates.
The overall preterm birth rate was 8.1% (104,493 preterm births). Exposure to relatively low or high temperatures during the entire pregnancy significantly increase the risk of preterm birth, with hazard ratios (HRs) 95% confidence intervals (CIs) of 1.03 (95%CI: 1.02, 1.04) for relatively low (9.1 ℃, the 5th percentile) temperature and 1.55 (95%CI: 1.48, 1.61) for relatively high (23.0 ℃, the 95th percentile) temperature in comparison with the thresholds (12.0 ℃). Pregnant women at the early pregnancy (the 1st and 2nd trimester) are more susceptible to high temperatures while pregnant women at the late pregnancy (the 3rd trimester) are more susceptible to low temperatures.
These findings provide new evidence that exposure to relatively low or high temperatures during pregnancy increases the risk of preterm birth, which can serve as scientific evidence for prevention of preterm birth.
•Each increase of 10 μg/m3 in PM1 was associated with decreased eGFR by 0.64%.•Each increase of 10 μg/m3 in PM2.5 was associated with decreased eGFR by 0.72%.•Associations between eGFR and PM were ...higher in females compared to males.•Association with PM1 were weaker than that with other fractions included in PM2.5.
Limited studies have examined the impact of airborne particulate matter of 2.5 μm or less (PM2.5) on renal function. No study has examined the effect of PM1, which is small enough to reach the blood circulation. We examined whether exposure to PM1 or PM2.5 affected renal function of young Han Chinese.
We included 2,546,047 young adults who were aged 18 to 45 years, being Han ethnicity and had no chronic disease from a Chinese national birth cohort. Serum creatinine (Scr) of each participant was measured during the baseline examination. Estimated glomerular filtration rate (eGFR) were calculated for each participant using the latest Chronic Kidney Disease Epidemiology Collaboration equation. One-year average exposure to PM1 and PM2.5 prior to the health examination for each participant were estimated using machine learning models with satellite remote sensing information. Generalized additive mixed models were used to estimate associations between PM1 or PM2.5 and renal function after adjusting for detailed individual variables.
A 10 μg/m3 increment in PM1 exposure was associated with −0.95% (95%CI: −1.04%, −0.87%) difference of eGFR in females and −0.37% (95%CI: −0.44%, −0.31%) in males. For PM2.5, the corresponding difference of eGFR was −0.99% (95%CI: −1.05%, −0.93%) in females and −0.48% (95%CI: −0.53%, −0.43%) in males, respectively. Associations between eGFR and PM were higher in females compared to males (p < 0.05 for interaction test). Association with PM1 were weaker than that with other fractions included in PM2.5. Participants who worked as farmers, were of normal weight, were not exposed to tobacco smoking, did not drink alcohol, had higher associations between eGFR and PM than their counterparts (p < 0.05 for interaction test).
Exposure to PM1 and PM2.5 was associated with reduced renal function among Han Chinese at reproductive age.
The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of ...it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.
We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal's exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.
Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
PDF
