Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation.

Background: Although the risk of prostate cancer (PCa) varies across different ages and genetic risks, it's unclear about the effects of genetic-specific and age-specific prostate-specific antigen (PSA) screening for PCa. Methods: Weighed and unweighted polygenic risk scores (PRS) were constructed to classify the participants from the PLCO trial into low- or high-PRS groups. The age-specific and PRS-specific cut-off values of PSA for PCa screening were determined with time-dependent receiver-operating-characteristic curves and area-under-curves (tdAUCs). Improved screening strategies integrating PRS-specific and age-specific cut-off values of PSA were compared to traditional PSA screening on accuracy, detection rates of high-grade PCa (Gleason score ≥7), and false positive rate. Results: Weighted PRS with 80 SNPs significantly associated with PCa was determined as the optimal PRS, with an AUC of 0.631. After stratifying by PRS, the tdAUCs of PSA with a 10-year risk of PCa were 0.818 and 0.816 for low- and high-PRS groups, whereas the cut-off values were 1.42 and 1.62 ng/mL, respectively. After further stratifying by age, the age-specific cut-off values of PSA were relatively lower for low PRS (1.42, 1.65, 1.60, and 2.24 ng/mL for aged <60, 60-64, 65-69, and ≥70 years) than high PRS (1.48, 1.47, 1.89, and 2.72 ng/mL). Further analyses showed an obvious interaction of positive PSA and high PRS on PCa incidence and mortality. Very small difference in PCa risk were observed among subgroups with PSA (-) across different age and PRS, and PCa incidence and mortality with PSA (+) significantly increased as age and PRS, with highest risk for high-PRS/PSA (+) in participants aged ≥70 years [HRs (95%CI): 16.00 (12.62-20.29) and 19.48 (9.26-40.96)]. The recommended screening strategy reduced 12.8% of missed PCa, ensured high specificity, but not caused excessive false positives than traditional PSA screening. Conclusion: Risk-adapted screening integrating PRS-specific and age-specific cut-off values of PSA would be more effective than traditional PSA screening.

MaSMG7-Mediated Degradation of MaERF12 Facilitates Fusarium oxysporum f. sp. cubense Tropical Race 4 Infection in Musa acuminata.

Modern plant breeding relies heavily on the deployment of susceptibility and resistance genes to defend crops against diseases. The expression of these genes is usually regulated by transcription factors including members of the AP2/ERF family. While these factors are a vital component of the plant immune response, little is known of their specific roles in defense against Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) in banana plants. In this study, we discovered that MaERF12, a pathogen-induced ERF in bananas, acts as a resistance gene against Foc TR4. The yeast two-hybrid assays and protein-protein docking analyses verified the interaction between this gene and MaSMG7, which plays a role in nonsense-mediated RNA decay. The transient expression of MaERF12 in Nicotiana benthamiana was found to induce strong cell death, which could be inhibited by MaSMG7 during co-expression. Furthermore, the immunoblot analyses have revealed the potential degradation of MaERF12 by MaSMG7 through the 26S proteasome pathway. These findings demonstrate that MaSMG7 acts as a susceptibility factor and interferes with MaERF12 to facilitate Foc TR4 infection in banana plants. Our study provides novel insights into the biological functions of the MaERF12 as a resistance gene and MaSMG7 as a susceptibility gene in banana plants. Furthermore, the first discovery of interactions between MaERF12 and MaSMG7 could facilitate future research on disease resistance or susceptibility genes for the genetic improvement of bananas.

Adoptive transfer of Fe3O4-SWCNT engineered M1-like macrophages for magnetic resonance imaging and enhanced cancer immunotherapy.

Macrophage-based tumor immunotherapy can effectively kill tumor cells in a direct manner when tumor specific antigens are idle or unknown. However, the presence of M2-like tumor associated macrophages (TAMs) would limit the treatment efficiency. Therefore, reversing the M2-like TAMs phenotype to regulate the immunosuppressive tumor microenvironment (TME) is crucial. Herein, we proposed nano-sized ferroferric oxide/single wall carbon nanotubes composites (Fe3O4-SWCNT) to engineer the macrophages species for powerful cancer therapy. The synthesized Fe3O4-SWCNT revealed good magnetic resonance imaging (MRI) performance, which enabled in vivo tracking of macrophage mediated immunotherapy. In addition, Fe3O4-SWCNT engineered M1-like macrophages (Fe3O4-SWCNT@M1) could maintain M1 phenotype, migrate to tumor cells and release nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). A series of experimental results showed that Fe3O4-SWCNT@M1 could effectively promote the polarization of endogenous M2-like macrophages to M1-like macrophages, activate tumor immune response and inhibit tumor progression. This work is expected to provide a new vision for macrophage-based tumor immunotherapy.

Fusaric acid inhibits proliferation and induces apoptosis through triggering endoplasmic reticulum stress in MCF-7 human breast cancer cells.

Breast cancer has replaced lung cancer to be the leading cancer in the world. Currently, chemotherapy is still the major method for breast cancer therapy, but its overall effect remains unsatisfactory. Fusaric acid (FSA), a mycotoxin derived from fusarium species, has shown potency against the proliferation of several types of cancer cells, but its effect on breast cancer cells has not been examined. Therefore, we explored the possible effect of FSA on the proliferation of MCF-7 human breast cancer cells and uncovered the underlying mechanism in the present study. Our results showed that FSA has a strong anti-proliferative effect on MCF-7 cells through inducing ROS production, apoptosis and arresting cell cycle at G2/M transition phase. Additionally, FSA triggers endoplasmic reticulum (ER) stress in the cells. Notably, the cell cycle arrest and apoptosis inducing effect of FSA can be attenuated by ER stress inhibitor, tauroursodeoxycholic acid. Our study provide evidence that FSA is a potent proliferation inhibition and apoptosis inducing agent against human breast cancer cells, and the possible mechanism involves the activation of ER stress signaling pathways. Our study may highlight that FSA is promising for the future in vivo study and development of potential agent for breast cancer therapy.

Associations between disrupted functional brain network topology and cognitive impairment in patients with rectal cancer during chemotherapy.

Introduction: Cognitive impairment has been identified in patients with non-central nervous system cancer received chemotherapy. Chemotherapy-induced changes in the brain are considered as the possible causes of the cognitive deficits of patients. This study aimed to explore chemotherapy-related functional brain changes and cognitive impairment in rectal cancer (RC) patients who had just finished chemotherapy treatment. Methods: In this study, RC patients after chemotherapy (on the day patients received the last dose of chemotherapy) (n=30) and matched healthy controls (HCs) (n=30) underwent cognitive assessments, structural magnetic resonance imaging (MRI) and resting-state functional MRI. The functional brain networks were constructed by thresholding the partial correlation matrices of 90 brain regions in the Anatomical Automatic Labeling template and the topologic properties were evaluated by graph theory analysis. Moreover, correlations between altered topological measures and scores of cognitive scales were explored in the patient group. Results: Compared with HCs, RC patients had lower scores of cognitive scales. The functional brain network had preserved small-world topological features but with a tendency towards higher path length in the whole network. In addition, patients had decreased nodal global efficiency (Eglo(i)) in the left superior frontal gyrus (dorsolateral), superior frontal gyrus (orbital part), inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part) and right inferior frontal gyrus (triangular part). Moreover, values of Eglo(i) in the superior and inferior frontal gyrus were positively associated with cognitive function in the patient group. Conclusion: These results suggested that cognitive impairment was associated with disruptions of the topological organization in functional brain networks of RC patients who had just finished chemotherapy, which provided new insights into the pathophysiology underlying acute effects of chemotherapy on cognitive function.

Functional changes of the prefrontal cortex, insula, caudate and associated cognitive impairment (chemobrain) in NSCLC patients receiving different chemotherapy regimen.

Introduction: Chemotherapy-induced cognitive impairment (CICI), termed "chemobrain", is highly prevalent in cancer patients following the administration of chemotherapeutic agents. However, the potential pathophysiological mechanisms underlying CICI remain unknown. This study aimed to explore the functional changes of the brain and associated cognitive impairment in non-small cell lung cancer (NSCLC) patients receiving different chemotherapy regimen. Methods: A total of 49 NSCLC patients (25 patients receiving pemetrexed plus carboplatin chemotherapy (PeCC) and 24 patients receiving paclitaxel plus carboplatin chemotherapy (PaCC)) and 61 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning, as well as cognitive function tests including Mini Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Brain functional activities were measured by regional homogeneity (ReHo) values, which were calculated and compared between groups. In addition, the associations between ReHo values of changed brain regions and scores of cognitive scales were evaluated. Results: NSCLC patients showed decreased scores of MMSE, MoCA and FACT-Cog and decreased ReHo values in the bilateral superior frontal gyrus (medial), middle frontal gyrus, left inferior frontal gyrus (orbital part) and increased ReHo values in the bilateral insula and caudate. Compared with HCs, patients receiving PeCC demonstrated decreased ReHo values in the right superior frontal gyrus (dorsolateral), left superior frontal gyrus (medial orbital), middle frontal gyrus, insula and rectus gyrus while patients receiving PaCC presented increased ReHo values in the right rolandic operculum, left insula and right caudate. Compared with patients receiving PaCC, patients receiving PeCC had decreased ReHo values in the left superior frontal gyrus (orbital part), middle frontal gyrus and increased ReHo values in the left inferior temporal gyrus, lingual gyrus. Moreover, positive relationships were found between ReHo values of the left and right superior frontal gyrus (medial) and the total scores of FACT-Cog in the patient group. Conclusion: The findings provided evidences that carboplatin-based chemotherapy could cause CICI accompanied by functional changes in the prefrontal cortex, insula, caudate. These might be the pathophysiological basis for CICI of NSCLC patients and were affected by the differences of chemotherapeutic agent administration through different biological mechanisms.

Spatial- and Valence-Matched Neutralizing DNA Nanostructure Blocks Wild-Type SARS-CoV-2 and Omicron Variant Infection.

Natural ligand-receptor interactions that play pivotal roles in biological events are ideal models for design and assembly of artificial recognition molecules. Herein, aiming at the structural characteristics of the spike trimer and infection mechanism of SARS-CoV-2, we have designed a DNA framework-guided spatial-patterned neutralizing aptamer trimer for SARS-CoV-2 neutralization. The ∼5.8 nm tetrahedral DNA framework affords precise spatial organization and matched valence as four neutralizing aptamers (MATCH-4), which matches with nanometer precision the topmost surface of SARS-CoV-2 spike trimer, enhancing the interaction between MATCH-4 and spike trimer. Moreover, the DNA framework provides a dimensionally complementary nanoscale barrier to prevent the spike trimer-ACE2 interaction and the conformational transition, thereby inhibiting SARS-CoV-2-host cell fusion and infection. As a result, the spatial- and valence-matched MATCH-4 ensures improved binding affinity and neutralizing activity against SARS-CoV-2 and its varied mutant strains, particularly the current Omicron variant, that are evasive of the majority of existing neutralizing antibodies. In addition, because neutralizing aptamers specific to other targets can be evolved and assembled, the present design has the potential to inhibit other wide-range and emerging pathogens.

Chemotherapy-induced functional brain abnormality in colorectal cancer patients: a resting-state functional magnetic resonance imaging study.

Introduction: Chemotherapy-induced cognitive impairment (i.e., "chemobrain") is a common neurotoxic side-effect experienced by many cancer survivors who undergone chemotherapy. However, the central mechanism underlying chemotherapy-related cognitive impairment is still unclear. The purpose of this study was to investigate the changes of intrinsic brain activity and their associations with cognitive impairment in colorectal cancer (CRC) patients after chemotherapy. Methods: Resting-state functional magnetic resonance imaging data of 29 CRC patients following chemotherapy and 29 matched healthy controls (HCs) were collected in this study, as well as cognitive test data including Mini Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). The measure of fractional amplitude of low-frequency fluctuation (fALFF) was calculated and compared between groups. The correlations between the fALFF of impaired brain region and cognitive performance were also analyzed. Results: Compared with HCs, CRC patients following chemotherapy showed decreased fALFF values in the left anterior cingulate gyrus (ACG) and middle frontal gyrus, as well as increased fALFF values in the left superior frontal gyrus (orbital part) and middle occipital gyrus. Moreover, positive associations were identified between fALFF values of the left ACG and the total scores of MMSE, MoCA and FACT-Cog in the patient group. Conclusion: These findings indicated that CRC patients after chemotherapy had decreased intrinsic brain activity in the left ACG, which might be vulnerable to the neurotoxic side-effect of chemotherapeutic drugs and related to chemotherapy-induced cognitive impairment.

DNA aptamer-based dual-responsive nanoplatform for targeted MRI and combination therapy for cancer.

Accurate drug delivery is a common topic, and it has always been an aim that scientists strive to achieve. To address this need, multifunctional and stimulus-sensitive nanoplatforms have attracted significant attention. Here we fabricated a glutathione (GSH) and adenosine-5'-triphosphate (ATP) dual-sensitive nanoplatform for controlled drug release and activatable MRI of tumors based on DNA aptamer and manganese dioxide (MnO2) nanosheets. Cleverly utilizing the DNA tunability, AS1411 aptamer which binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, was designed with ATP aptamer and its cDNA to load the anticancer drug, doxorubicin (Dox). The formed DNA-Dox complex was delivered to the tumor region with the help of MnO2 nanosheets and AS1411 aptamer. Then, the on-demand drug release in tumor cells was realized with the co-effect of the ATP aptamer and GSH reduction. It was found that without the structure of the MnO2 nanosheets being broken by GSH, Dox almost could not be released even in the presence of ATP. Similarly, without ATP, Dox was still maintained in the duplex even with GSH. Further combining the MRI ability and chemodynamic therapy of the produced Mn2+, an improved effect of the inhibition of tumor growth and imaging was achieved. Our designed DNA aptamer-based dual-responsive nanoplatform can realize the targeted drug delivery and MRI of breast tumor cells both in vitro and in vivo.

Residues of Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes), Cultivation as a Potential Source of Functional Skin Substitute with Multiple Bioactivities.

Residues generated during the cultivation of edible mushroom Flammulina velutipes are abundant and utilized with low efficiency. In this study, the composition and bioactivities of a skin substitute named TG05 obtained from residues of the F. velutipes cultivation process were investigated. The main composition of TG05 was considered to be chitin and it inhibited growth of Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. TG05 also suppressed the inflammatory response through the inducible nitric oxide synthase signaling pathway. Inflammation was attenuated by reducing the expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 at the transcription level. Furthermore, TG05 exhibited antioxidant activities based on hydroxyl, 2,2-diphenyl-1-picryl-hydrazy, 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid), superoxide anion radical scavenging activity, and reducing power assays. However, the effect of TG05 was independent of hyaluronidase inhibitory activity. Taken together, specific mechanisms related to the notable wound-healing-promoting activity of TG05 were demonstrated, mainly attributable to its antimicrobial, anti-inflammatory, and antioxidant activities. Therefore, TG05 may have potential for use as a functional biomaterial in various applications.

Topological Abnormalities of Pallido-Thalamo-Cortical Circuit in Functional Brain Network of Patients With Nonchemotherapy With Non-small Cell Lung Cancer.

INTRODUCTION: Some previous studies in patients with lung cancer have mainly focused on exploring the cognitive dysfunction and deficits of brain function associated with chemotherapy. However, little is known about functional brain alterations that might occur prior to chemotherapy. Therefore, this study aimed to evaluate brain functional changes in patients with nonchemotherapy before chemotherapy with non-small cell lung cancer (NSCLC). METHODS: Resting-state functional MRI data of 35 patients with NSCLC and 46 matched healthy controls (HCs) were acquired to construct functional brain networks. Graph theoretical analysis was then applied to investigate the differences of the network and nodal measures between groups. Finally, the receiver operating characteristic (ROC) curve analysis was performed to distinguish between NSCLC and HC. RESULTS: Decreased nodal strength was found in the left inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part), inferior occipital gyrus, and right inferior frontal gyrus (triangular part) of patients with NSCLC while increased nodal strength was found in the right pallidum and thalamus. NSCLC also showed decreased nodal betweenness in the right superior occipital gyrus. Different hub regions distribution was found between groups, however, no hub regions showed group differences in the nodal measures. Furthermore, the ROC curve analysis showed good performance in distinguishing NSCLC from HC. CONCLUSION: These results suggested that topological abnormalities of pallido-thalamo-cortical circuit in functional brain network might be related to NSCLC prior to chemotherapy, which provided new insights concerning the pathophysiological mechanisms of NSCLC and could serve as promising biological markers for the identification of patients with NSCLC.

ß-Elemene Restrains PTEN mRNA Degradation to Restrain the Growth of Lung Cancer Cells via METTL3-Mediated N6 Methyladenosine Modification.

Lung cancer is one of the most fatal malignancies and the leading cause of cancer death worldwide. ß-Elemene, a well-known anticancer drug, has drawn a great deal of attention from researchers attributed to its limited side impacts. N6-Methyladenosine (m6A) modification is the most common RNA modification and plays a vital role in the pathogenesis of multiple tumors. However, the functional link between ß-elemene and the m6A modification in lung cancer development remains unexplored. In this study, we investigated whether m6A modification was responsible for the impacts of ß-elemene on lung cancer. Firstly, outcomes suggested that ß-elemene restrained the malignant behaviors of A549 together with H1299 cells. Thereafter, we observed that ß-elemene markedly regulated METTL3, YTHDF1, and YTHDC1 among various m6A modulators. METTL3 was selected for further study because of its oncogenic function in lung cancer. RT-qRCR and western blot assays exhibited that the mRNA and protein expression levels of METTL3 were lessened by the administration of ß-elemene. Mechanistically, ß-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. More importantly, ß-elemene contributed to the augmented PTEN expression via suppressing its m6A modification. To sum up, we provided strong clues that ß-elemene promoted PTEN expression to retard lung cancer progression by the regulation of METTL3-mediated m6A modification.

Abnormal topological characteristics of brain white matter network relate to cognitive and emotional deficits of non-small cell lung cancer (NSCLC) patients prior to chemotherapy.

INTRODUCTION: Cancer and chemotherapy are correlated with brain functional and structural changes in cancer patients, which may lead to cognitive dysfunction. However, little is known about the structural abnormalities of brain in patients with non-small cell lung cancer (NSCLC). The aim of this study was to explore the topological properties within the brain white matter network of NSCLC patients prior to chemotherapy. METHODS: To explore the neurobiological biomarkers of NSCLC, brain magnetic resonance imaging (MRI) data were acquired in 24 non-nervous system metastatic NSCLC patients and 25 matched healthy controls. The topological properties of the brain structural networks of NSCLC were measured by the parameters of local and global efficiency. RESULTS: Treatment-naïve NSCLC patients showed cognitive and emotional deficits. In addition, NSCLC patients also exhibited decreased global efficacy in the left inferior frontal gyrus (triangular part), left inferior frontal gyrus (orbital part), right rolandic operculum, right gyrus rectus, right lenticular nucleus (putamen), left superior temporal gyrus and right inferior temporal gyrus. Decreased local efficacy were found in the left middle frontal gyrus (orbital part) and left superior temporal gyrus in NSCLC patients. Moreover, the aberrant brain regions were associated with the impaired cognitiion and emotion of NSCLC patients. CONCLUSION: Overall our results suggested that altered local and global efficiency of brain white matter network were associated with cancer-induced cognitive and emotional deficits of NSCLC patients. These findings demonstrated that disrupted topological characteristics of the brain network might underlie the impaired cognition and emotion in NSCLC.

Theranostic nanoplatform to target macrophages enables the inhibition of atherosclerosis progression and fluorescence imaging of plaque in ApoE(-/-) mice.

BACKGROUND: Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task. RESULTS: In this study, we presented the development of composite mesoporous silica nanoparticle (Ru(bpy)3@SiO2-mSiO2, CMSN)-based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis (AS). In vitro cell experiments showed that both RAW264.7 and oxidized low density lipoprotein (ox-LDL)-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to Class II scavenger receptor, CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, which might benefit from the upregulated expression of CD36 on macrophages after ox-LDL treatment. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post-treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group. CONCLUSIONS: The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.

The M35 Metalloprotease Effector FocM35_1 Is Required for Full Virulence of Fusarium oxysporum f. sp. cubense Tropical Race 4.

Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes Fusarium wilt of banana, the most devastating disease on a banana plant. The genome of Foc TR4 encodes many candidate effector proteins. However, little is known about the functions of these effector proteins on their contributions to disease development and Foc TR4 virulence. Here, we discovered a secreted metalloprotease, FocM35_1, which is an essential virulence effector of Foc TR4. FocM35_1 was highly upregulated during the early stages of Foc TR4 infection progress in bananas. The FocM35_1 knockout mutant compromised the virulence of Foc TR4. FocM35_1 could interact with the banana chitinase MaChiA, and it decreased banana chitinase activity. FocM35_1 induced cell death in Nicotiana benthamiana while suppressing the INF1-induced hypersensitive response (HR), and its predicted enzymatic site was required for lesion formation and the suppression to INF1-induced HR on N. benthamiana leaves. Importantly, treatment of banana leaves with recombinant FocM35_1 accelerates Foc TR4 infection. Collectively, our study provides evidence that metalloprotease effector FocM35 seems to contribute to pathogen virulence by inhibiting the host immunity.

IL-33 Promotes the Growth of Non-Small Cell Lung Cancer Cells Through Regulating miR-128-3p/CDIP1 Signalling Pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, and it is also the most frequently diagnosed cancer. Previous studies indicate that IL-33 plays a crucial role in the development of NSCLC. In recent years, the role of miRNAs in cancer has become increasingly clear. However, reports focused on the relation between IL-33 and miRNAs in NSCLC have been limited. METHODS: The expression of IL-33 and miR-128-3p was detected by qPCR. MTT, EdU, and colony formation assays were used to detect the proliferation ability of NSCLC cells. Transwell assay was used to investigate the migration and invasion of NSCLC cells. The expression of bax, cyt-c, and caspase 3 was detected by Western blot. Finally, in vivo tumor xenograft was used to detect the effects of IL-33 and miR-128-3p on tumor growth capacity. RESULTS: IL-33 was notably increased in the serum and tumor tissue of NSCLC patients. The in vitro function study revealed that IL-33 significantly promotes the proliferation, migration, and invasion of the NSCLC cells. In vivo experiments further confirmed the pro-tumor effect of IL-33 on NSCLC. The study on the underlying mechanism elucidated that IL-33 regulates the expression of miR-128-3p, which can directly target and inhibit the expression of CDIP1. Furthermore, IL-33 regulates the expression of downstream apoptotic proteins such as bax, cyt-c, and caspase3. Rescue experiments demonstrated that miR-28-3p can reverse the effect of IL-33. CONCLUSION: These findings indicated that IL-33 and miR-128-3p may play a potential role in the diagnosis and treatment of NSCLC.

The Opportunities and Challenges of Silica Nanomaterial for Atherosclerosis.

Atherosclerosis (AS) as the leading cause of cardiovascular and cerebrovascular events has been paid much attention all the time. With the continuous development of modern medical drug treatment, surgical treatment, interventional treatment and other methods, the mortality rate of AS has shown a downward trend, while the morbidity rate is still increasing. Oral lipid-lowering or anti-inflammatory drugs are generally used for early AS, but the relatively low accumulation efficiency in lesions and the unavoidable side effects required researchers to develop more effective drug delivery approaches for the therapy of AS. Mesoporous silica nanoparticles as nanocarrier for drug delivery have received extensive attentions due to their flexible size, high specific surface area, controlled pore volume, high drug loading capacity and excellent biocompatibility. Series of good reviews about the mesoporous silica nanoparticles loaded drugs for cancer therapy have been well documented. However, their roles as nanocarrier for drug delivery to treat AS have few reports. In this review, the applications and challenges of mesoporous silica nanomaterials in the field of the diagnosis and therapy of AS have been summarized. The classification, synthesis, formation mechanism, surface modification and functionalization of mesoporous silica nanomaterials which were closely related to the theranostic effect of AS have also been included. Last but not the least, the future prospects' suggestions of mesoporous silica nanomaterial-based drug delivery system for AS are also provided.

Development of a low-cost UAV-based system for CH4 monitoring over oil fields.

The recent booming of oil and gas production in the U.S. sparks a growing concern about greenhouse gas emissions from the petroleum industry. This study aimed to develop a low-cost UAV-based system for CH4 monitoring over oil fields. The system consisted of an airborne sensor node, a ground station, and a laptop. The sensor node was comprised of low-cost gas sensors, a microcontroller, a LoRa wireless transceiver, a GPS module, and an SD card reader. The ground station included a microcontroller and a LoRa transceiver. Both the sensor node and the ground station were programmed using Arduino. A graphic user interface was created using LabVIEW for data logging and visualization on the laptop. A preliminary test showed that the system was capable of measuring CH4 concentrations, along with temperature, humidity, and GPS location; while sending the real-time data to the ground station up to ∼1 km away without any loss. The system was further tested at two oil production sites in North Dakota. The results revealed a heterogeneous distribution of CH4 over the sites due to flares and road traffic, demonstrating a potential application of the system for air quality survey and gas leakage detection. The advantage of this system lies in its light weight (∼540 g), low cost (∼$300), expandability, ease of deployment and operation. Data quality collected by the system depended on the gas sensors chosen. With advancement in sensor technologies, it is expected that the quality of monitoring data can be considerably improved in the near future.

Cancer-associated changes of emotional brain network in non-nervous system metastatic non-small cell lung cancer patients: a structural connectomic diffusion tensor imaging study.

BACKGROUND: Emotional distress frequently occur in cancer patients following diagnosis. Previous neuroimaging studies have demonstrated that depression and anxiety are associated with functional and structural brain abnormalities. However, little is known about the cancer-associated changes of emotional brain network in non-small cell lung cancer (NSCLC) patients. The aim of this study was to assess the topological features of brain structural network and emotions in non-nervous system metastatic NSCLC patients prior to chemotherapy. METHODS: Twenty-four treatment-naïve patients with non-nervous system metastatic NSCLC and 25 healthy controls (HC) matched for gender, age and education participated in this study. All subjects underwent diffusion tensor imaging (DTI), and were assessed with the 17 item hamilton depression rating scale (HAMD-17) and hamilton anxiety rating scale (HAMA). Properties of brain network were examined by the method of graph-theoretic analysis. The assessments included small-worldness, clustering coefficient and shortest path length. RESULTS: NSCLC patients had higher scores of HAMD-17 and HAMA when compared with HC. Additionally, we found a small-world topology of brain white matter network in both NSCLC and HC. NSCLC patients had significantly reduced clustering coefficient compared to healthy controls in the left hippocampus. Moreover, increased shortest path length were identified in NSCLC patients, which included the left middle frontal gyrus (orbital part), superior temporal gyrus and right Rolandic operculum, rectus gyrus, lenticular nucleus (putamen). However, no correlations were found between the impaired brain regions and HAMD-17, HAMA scores of NSCLC patients. CONCLUSIONS: Our results indicated impaired topological characteristics in the brain structural network of non-nervous system metastatic NSCLC patients prior to chemotherapy, which might account for the cancer-related emotional distress. Our findings demonstrated that NSCLC might affect brain regions involved in the process of emotion, which identified the basis of emotional changes associated with cancer.