Dual-strategy engineered nickel phosphide for achieving efficient hydrazine-assisted hydrogen production in seawater.

Electrocatalytic hydrogen production in seawater to alleviate freshwater shortage pressures is promising, but is hindered by the sluggish oxygen evolution reaction and detrimental chloride electrochemistry. Herein, a dual strategy approach of Fe-doping and CeO2-decoration in nickel phosphide (Fe-Ni2P/CeO2) is rationally designed to achieve superior bifunctional catalytic performance for the hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR) in seawater. Notably, the two-electrode Fe-Ni2P/CeO2-based hybrid seawater electrolyzer realizes energy-efficient and chlorine-free hydrogen production with ultralow cell voltages of 0.051 and 0.597 V at 10 and 400 mA cm-2, which are significantly lower than those needed in the hydrazine-free seawater electrolyzer. Density functional theory calculations manifest that the combination of Fe doping and heterointerface construction between Fe-Ni2P and CeO2 can adjust the electronic structure of the Ni2P and optimize the water dissociation barrier and hydrogen adsorption free energy, leading to improvement of the intrinsic catalytic performance. This route affords a feasible solution for future large-scale hydrogen generation using abundant ocean water.

KIF2C: An important factor involved in signaling pathways, immune infiltration, and DNA damage repair in tumorigenesis.

BACKGROUNDS: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation. Research on KIF2C may be a new direction and target for anti-tumor therapy. OBJECT: The article aims at reviewing current literatures and summarizing the research status of KIF2C in malignant tumors as well as the oncogenic signaling pathways associated with KIF2C and its role in immune infiltration. RESULT: In this review, we summarize the KIF2C mechanisms and signaling pathways in different malignant tumors, and briefly describe its involvement in pathways related to classical chemotherapeutic drug resistance, such as MEK/ERK, mTOR, Wnt/ß-catenin, P53 and TGF-ß1/Smad pathways. KIF2C upregulation was shown to promote tumor cell migration, invasion, chemotherapy resistance and inhibit DNA damage repair. It was also highly correlated with microRNAs, and CD4 +T cell and CD8 +T cell tumor immune infiltration. CONCLUSION: This review shows that KIF2C may function as a new anticancer drug target with great potential for malignant tumor treatment and the mitigation of chemotherapy resistance.

Direct and Detailed Site-Specific Glycopeptide Characterization by Higher-Energy Electron-Activated Dissociation Tandem Mass Spectrometry.

Glycosylation is widely recognized as the most complex post-translational modification due to the widespread presence of macro- and microheterogeneities, wherein its biological consequence is closely related to both the glycosylation sites and the glycan fine structures. Yet, efficient site-specific detailed glycan characterization remains a significant analytical challenge. Here, utilizing an Orbitrap-Omnitrap platform, higher-energy electron-activated dissociation (heExD) tandem mass spectrometry (MS/MS) revealed extraordinary efficacy for the structural characterization of intact glycopeptides. HeExD produced extensive fragmentation within both the glycan and the peptide, including A-/B-/C-/Y-/Z-/X-ions from the glycan motif and a-/b-/c-/x-/y-/z-type peptide fragments (with or without the glycan). The intensity of cross-ring cleavage and backbone fragments retaining the intact glycan was highly dependent on the electron energy. Among the four electron energy levels investigated, electronic excitation dissociation (EED) provided the most comprehensive structural information, yielding a complete series of glycosidic fragments for accurate glycan topology determination, a wealth of cross-ring fragments for linkage definition, and the most extensive peptide backbone fragments for accurate peptide sequencing and glycosylation site localization. The glycan fragments observed in the EED spectrum correlated well with the fragmentation patterns observed in EED MS/MS of the released glycans. The advantages of EED over higher-energy collisional dissociation (HCD), stepped collision energy HCD (sceHCD), and electron-transfer/higher-energy collisional dissociation (EThcD) were demonstrated for the characterization of a glycopeptide bearing a biantennary disialylated glycan. EED can produce a complete peptide backbone and glycan sequence coverage even for doubly protonated precursors. The exceptional performance of heExD MS/MS, particularly EED MS/MS, in site-specific detailed glycan characterization on an Orbitrap-Omnitrap hybrid instrument presents a novel option for in-depth glycosylation analysis.

Comparison of Secular Trends in Peptic Ulcer Diseases Mortality in China, Brazil and India during 1990-2019: An Age-Period-Cohort Analysis.

BACKGROUND: Peptic ulcer disease (PUD) is a common disease worldwide, especially in developing countries. China, Brazil, and India are among the world's fastest-growing emerging economies. This study aimed to assess long-term trends in PUD mortality and explore the effects of age, period, and cohort in China, Brazil, and India. METHODS: We collected data from the 2019 Global Burden of Disease Study and used an age-period-cohort (APC) model to estimate the effects of age, period, and cohort. We also obtained net drift, local drift, longitudinal age curve, and period/cohort rate ratios using the APC model. RESULTS: Between 1990 and 2019, the age-standardized mortality rates (ASMRs) of PUD and PUD attributable to smoking showed a downward trend in all countries and both sexes. The local drift values for both sexes of all ages were below zero, and there were obvious sex differences in net drifts between China and India. India had a more pronounced upward trend in the age effects than other countries. The period and cohort effects had a similar declining trend in all countries and both sexes. CONCLUSIONS: China, Brazil, and India had an inspiring decrease in the ASMRs of PUD and PUD attributable to smoking and to period and cohort effects during 1990-2019. The decreasing rates of Helicobacter pylori infection and the implementation of tobacco-restricting policies may have contributed to this decrease.

Investigating Microstructural Evolution and Its Influence on Tribological Behaviors of In-Situ Formed VCp Reinforced Iron-Based Composites with Variable Mn Content.

In this work, we fabricated VCp-reinforced iron-based composites (VCFCs) by adjusting the amount of Mn elements and investigated how the concentration of Mn affected the microstructural characteristics of Vanadium carbide (VC) and the texture of the iron matrix, and the influence of microstructure on tribological behaviors should be investigated. We demonstrated that VC changed from thick dendrite crystals (~50 µm) to tiny equiaxed crystals (~5 µm). Furthermore, the nucleation mechanism of VC also transformed from homogeneous nucleation to heterogeneous nucleation due to the lower Gibbs free energy of TiC and the tailoring effect of the Mn elements. In addition, γ-Fe in the FCC structure gradually increased and ascribed an increase of Mn content to the lower transformation temperature of martensite. Furtherly, particulate features and phase constitution could contribute to hardness and wear resistance. Higher hardness and excellent wear resistance occurred in the 3.0 Mn sample, which had a hardness of 869 HV and a wear rate of 1.77 × 10-6 mm3/(N·m). In addition, the adhesive wear could be the main wear mechanism in the 3.0 Mn sample, while the abrasive wear could be in the 4.5 Mn sample.

Comparison of Secular Trends in Esophageal Cancer Mortality in China and Japan during 1990-2019: An Age-Period-Cohort Analysis.

Esophageal cancer is a prevalent and often fatal malignancy all over the world, with China and Japan bearing a disproportionately high burden. Consequently, we explored and compared the long-term changes in esophageal cancer mortality in China and Japan from 1990 to 2019 to see if there were any etiological clues. From 1990 to 2019, data on mortality in China and Japan were gathered from the Global Burden of Disease Study 2019 (GBD 2019). The age-period-cohort (APC) model was utilized to evaluate the effects of age, period, and cohort. Between 1990 and 2019, the age-standardized mortality rates (ASMRs) for esophageal cancer fell in both nations, with China showing a tremendous reduction after 2005. The overall net drifts per year were more impressive in China (-5.22% [95% CI, -5.77 to -4.68] for females, -1.98% [-2.22 to -1.74] for males) than in Japan (-0.50% [-0.91 to -0.08] for females, -1.86% [-2.12 to -1.59] for males), and the local drift values in both countries were less than zero in all age groups for both sexes. The longitudinal age curves of esophageal cancer mortality increased as age advances and the sex disparity gradually exacerbates with age. The period and cohort effects were uncovered to have similar declining patterns for both sexes in both nations; however, the improvement of cohort effects for China's younger generation has stagnated. The ASMRs, period effects, and cohort effects have decreased for both countries and sexes over the 1990-2019 period. The decline in cohort effects for China's younger generation has plateaued, possibly due to the rising rates of smoking and obesity among Chinese youngsters. Comprehensive population-level treatments aimed at smoking cessation, obesity prevention, and gastrointestinal endoscopy screening should be carried out immediately, particularly for men and older birth cohorts at a higher risk of esophageal cancer.

Protective Effect of Resveratrol on Immortalized Duck Intestinal Epithelial Cells Exposed to H2O2.

Resveratrol is a polyphenolic compound with anti-oxidation effects. The mechanisms underlying the antioxidant effects of resveratrol in duck intestinal epithelial cells remain unclear. The protective effects of resveratrol against oxidative stress induced by H2O2 on immortalized duck intestinal epithelial cells (IDECs) were investigated. IDECs were established by transferring the lentivirus-mediated simian virus 40 large T (SV40T) gene into small intestinal epithelial cells derived from duck embryos. IDECs were morphologically indistinguishable from the primary intestinal epithelial cells. The marker protein cytokeratin 18 (CK18) was also detected in the cultured cells. We found that resveratrol significantly increased the cell viability and activity of catalase and decreased the level of intracellular reactive oxygen species and malondialdehyde, as well as the apoptosis rate induced by H2O2 (p < 0.05). Resveratrol up-regulated the expression of NRF2, p-NRF2, p-AKT, and p-P38 proteins and decreased the levels of cleaved caspase-3 and cleaved caspase-9 and the ratio of Bax to Bcl-2 in H2O2-induced IDECs (p < 0.05). Our findings revealed that resveratrol might alleviate oxidative stress by the PI3K/AKT and P38 MAPK signal pathways and inhibit apoptosis by altering the levels of cleaved caspase-3, cleaved caspase-9, Bax, and Bcl-2 in IDECs exposed to H2O2.

The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on "Gut-Brain Axis": Study Protocol for a Randomized Controlled Trial.

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).

HFBSurv: hierarchical multimodal fusion with factorized bilinear models for cancer survival prediction.

MOTIVATION: Cancer survival prediction can greatly assist clinicians in planning patient treatments and improving their life quality. Recent evidence suggests the fusion of multimodal data, such as genomic data and pathological images, is crucial for understanding cancer heterogeneity and enhancing survival prediction. As a powerful multimodal fusion technique, Kronecker product has shown its superiority in predicting survival. However, this technique introduces a large number of parameters that may lead to high computational cost and a risk of overfitting, thus limiting its applicability and improvement in performance. Another limitation of existing approaches using Kronecker product is that they only mine relations for one single time to learn multimodal representation and therefore face significant challenges in deeply mining rich information from multimodal data for accurate survival prediction. RESULTS: To address the above limitations, we present a novel hierarchical multimodal fusion approach named HFBSurv by employing factorized bilinear model to fuse genomic and image features step by step. Specifically, with a multiple fusion strategy HFBSurv decomposes the fusion problem into different levels and each of them integrates and passes information progressively from the low level to the high level, thus leading to the more specialized fusion procedure and expressive multimodal representation. In this hierarchical framework, both modality-specific and cross-modality attentional factorized bilinear modules are designed to not only capture and quantify complex relations from multimodal data, but also dramatically reduce computational complexity. Extensive experiments demonstrate that our method performs an effective hierarchical fusion of multimodal data and achieves consistently better performance than other methods for survival prediction. AVAILABILITY AND IMPLEMENTATION: HFBSurv is freely available at https://github.com/Liruiqing-ustc/HFBSurv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tumor-promoting mechanisms of macrophage-derived extracellular vesicles-enclosed microRNA-660 in breast cancer progression.

INTRODUCTION: Breast cancer metastasis is the main cause of cancer-related death in women worldwide. Current therapies have remarkably improved the prognosis of breast cancer patients but still fail to manage metastatic breast cancer. Here, the present study was set to explore the role of microRNA (miR)-660 from tumor-associated macrophages (TAMs) in breast cancer, particularly in metastasis. MATERIALS AND METHODS: We collected breast cancer tissues and isolated their polarized macrophages as well as extracellular vesicles (EVs), in which we measured the expression of miR-660, Kelch-like Protein 21 (KLHL21), and nuclear factor-κB (NF-κB) p65. Breast cancer cells were transfected with miR-660 mimic, miR-660 inhibitor, and sh-KLHL21 and then the cells were co-cultured with EVs or TAMs followed by detection of invasion and migration. Finally, mouse model of breast cancer was established to detect the effect of miR-660 or KLHL21 on metastasis by measuring the lymph node metastasis (LNM) foci in femur and lung. RESULTS: KLHL21 was poorly expressed, whereas miR-660 was highly expressed in breast cancer tissues and cells. Of note, low KLHL21 expression or high miR-660 expression was related to poor overall survival. EVs-contained miR-660 was identified to bind to KLHL21, reducing the binding between KLHL21 and inhibitor kappa B kinase ß (IKKß) to activate the NF-κB p65 signaling pathway. Interestingly, EV-loaded miR-660 from TAMs could be internalized by breast cancer cells. Moreover, silencing of KLHL21 increased the number of lung LNM foci in vivo, while EVs-contained miR-660 promoted cancerous cell invasion and migration. DISCUSSION: Taken altogether, our work shows that TAMs-EVs-shuttled miR-660 promotes breast cancer progression through KLHL21-mediated IKKß/NF-κB p65 axis.

LncRNA TMPO-AS1 serves as a sponge for miR-4731-5p modulating breast cancer progression through FOXM1.

OBJECTIVE: To investigate the function of IncRNA-TMPO-AS1 in breast cancer (BC) and to further explore its molecular mechanism. METHODS: TMPO-AS1, miR-4731-5p and FOXM1 were quantitatively determined using qRT-PCR. CCK-8 assays, plate cloning experiments, wound healing and Transwell assays, and flow cytometry were used to assess the biological behaviors of BC cells. Dual-luciferase reporter assays were used to assess the interactions between TMPO-AS1 and its downstream targets. The apoptosis and cell cycle-related proteins were quantitatively determined using Western blot. RESULTS: In the BC tissues and cells, TMPO-AS1 was significantly increased (P<0.05). Functional studies suggest that the knockdown of TMPO-AS1 tremendously restrains tumor cell growth and migration (P<0.05). Mechanically, TMPO-AS1 negatively regulates miR-4731-5p and influences the progression of BC through the miR-4731-5p/FOXM1 axis. CONCLUSION: LncRNA TMPO-AS1spongess miR-4731-5p to modulate BC progression through FOXM1.

Transcription factor KLF2 enhances the sensitivity of breast cancer cells to cisplatin by suppressing kinase WEE1.

Cisplatin is an effective chemotherapeutic agent in facilitating the inhibition of proliferation, migration, and invasion in cancerous cells. However, the detailed mechanism of the regulation by cisplatin of human breast cancer cells is still unclear. This study aimed to investigate the mechanism of kruppel-like factor 2 (KLF2) transcription factor in cisplatin therapy for breast cancer. RT-qPCR was performed to quantify the expression of KLF2 and WEE1 in clinical tissue samples from breast cancer patients and in MDA-MB-231 cells. ChIP assay and dual-luciferase reporter assay were used to analyze the potential-binding sites of KLF2 and WEE1 promoter. Gain- or loss-of-function approaches were used to manipulate KLF2 and WEE1 in cisplatin-treated MDA-MB-231 cells, and the mechanism of KLF2 in breast cancer was evaluated both via CCK-8 assay, flow cytometry, Transwell assay, and Western blot. Further validation of the KLF2 was performed on nude mouse models. Breast cancer tissues and cells showed a relative decline of KLF2 expression and abundant WEE1 expression. Cisplatin inhibited the proliferation, migration, and invasion of MDA-MB-231 cells. Overexpression of KLF2 enhanced the inhibitory effect of cisplatin on the malignant characteristics of MDA-MB-231 cells in vitro. KLF2 targeted WEE1 and negatively regulated its expression, thus enhancing the sensitivity to cisplatin of breast cancer cells as well as tumor-bearing mice. Overall, these results suggest that KLF2 can potentially inhibit WEE1 expression and sensitize breast cancer cells to cisplatin, thus presenting a promising adjunct treatment.

The Correlation Analysis of Microstructure and Tribological Characteristics of In Situ VCp Reinforced Iron-Based Composite.

In this study, four kinds of heat treatments were performed to obtain a certain amount of retained austenite, which can result in good toughness and low brittleness accompanied with wear resistance of an in situ VC particle reinforced iron-based composite (VCFC). Microstructure, mechanical properties and wear resistance of the samples under heat treatment of QP, QPT, MQP and MQPT were compared. The experimental results indicated that there is a huge difference in microstructure between MQPT and the other heat treatments. High-proportion retained austenite and white net-like precipitates of M7C3 carbide existed in the MQPT-treated sample, but thick M7C3 carbide with brittleness was discovered in the other sample. Thereby, high-proportion retained austenite contributed to its low hardness of 634 HV and high tensile strength of 267 MPa, while a maximum hardness of 705.5 HV and a minimum tensile strength of 205 MPa were exhibited in the QPT-treated sample with a V-rich carbide of high hardness, a Cr-rich carbide of brittleness and a high-proportion martensite. Meanwhile, a phase transformation from retained austenite to martensite could increase the hardness and enhance wear resistance based on the transformation-induced plasticity (TRIP) effect; its wear rate was only 1.83 × 10-6 mm-3/(N·m). However, the wear rates of the samples under QP, QPT and MQP heat treatments increased by 16.4%, 44.3% and 41.0%, respectively. The wear mechanism was a synergistic effect of the adhesive wear mechanism and the abrasive wear mechanism. The adhesive wear mechanism was mainly considered in the MQPT-treated sample to reduce the wear rate attributed to high-proportion retained austenite and the existence of wear debris with a W element on the surface of the wear track. However, the abrasive wear mechanism could exist in the other samples because of a lot of thick, brittle M7C3, thereby resulting in a higher wear rate due to immediate contact between the designed material and the counterpart.

GPDBN: deep bilinear network integrating both genomic data and pathological images for breast cancer prognosis prediction.

MOTIVATION: Breast cancer is a very heterogeneous disease and there is an urgent need to design computational methods that can accurately predict the prognosis of breast cancer for appropriate therapeutic regime. Recently, deep learning-based methods have achieved great success in prognosis prediction, but many of them directly combine features from different modalities that may ignore the complex inter-modality relations. In addition, existing deep learning-based methods do not take intra-modality relations into consideration that are also beneficial to prognosis prediction. Therefore, it is of great importance to develop a deep learning-based method that can take advantage of the complementary information between intra-modality and inter-modality by integrating data from different modalities for more accurate prognosis prediction of breast cancer. RESULTS: We present a novel unified framework named genomic and pathological deep bilinear network (GPDBN) for prognosis prediction of breast cancer by effectively integrating both genomic data and pathological images. In GPDBN, an inter-modality bilinear feature encoding module is proposed to model complex inter-modality relations for fully exploiting intrinsic relationship of the features across different modalities. Meanwhile, intra-modality relations that are also beneficial to prognosis prediction, are captured by two intra-modality bilinear feature encoding modules. Moreover, to take advantage of the complementary information between inter-modality and intra-modality relations, GPDBN further combines the inter- and intra-modality bilinear features by using a multi-layer deep neural network for final prognosis prediction. Comprehensive experiment results demonstrate that the proposed GPDBN significantly improves the performance of breast cancer prognosis prediction and compares favorably with existing methods. AVAILABILITYAND IMPLEMENTATION: GPDBN is freely available at https://github.com/isfj/GPDBN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Characterization of Kinesin Family Member 2C as a Proto-Oncogene in Cervical Cancer.

Kinesin family member 2C (KIF2C) is known as an oncogenic gene to regulate tumor progression and metastasis. However, its pan-cancer analysis has not been reported. In this study, we comprehensively analyzed the characteristics of KIF2C in various cancers. We found that KIF2C was highly expressed and corresponded to a poor prognosis in various cancers. We also found a significant correlation between KIF2C and clinicopathological characteristics, particularly in cervical cancer, which is the most common gynecological malignancy and is the second leading cause of cancer-related deaths among women worldwide. KIF2C mutation is strongly associated with the survival rate of cervical cancer, and KIF2C expression was significantly upregulated in cervical cancer tissues and cervical cancer cells. Moreover, KIF2C promoted cervical cancer cells proliferation, invasion, and migration in vitro and as well increased tumor growth in vivo. KIF2C knockdown promotes the activation of the p53 signaling pathway by regulating the expression of related proteins. The rescue assay with KIF2C and p53 double knockdown partially reversed the inhibitory influence of KIF2C silencing on cervical cancer processes. In summary, our study provided a relatively comprehensive description of KIF2C as an oncogenic gene and suggested KIF2C as a therapeutic target for cervical cancer.

Identification, Characterization, and Mutational Analysis of a Probable KEAP1 Ortholog in Rice (Oryza sativa L.).

The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2) module is a key component in the detoxification and antioxidant system in animals, which plays crucial roles in cell homeostasis and cytoprotection, and consequently in carcinogenesis and disease development. However, this system seems to have diverged throughout evolution across different organisms, and the question of whether a similar system exists in plants has thus far remained unresolved. In this study, a KEAP1 ortholog was identified in rice (Oryza sativa L., OsKEAP1) and its properties were characterized via in silico and laboratory studies. To reveal OsKEAP1's function, two knockdown mutants, oskeap1-1 and oskeap1-2, were generated by targeted mutagenesis in the 5' untranslated region (UTR) using the CRISPR-Cas9 system. In silico analysis showed that OsKEAP1 has a Kelch-repeat domain which is identical to those of animals and a plant-specific development and cell death (DCD) domain in place of the broad-complex, tramtrack, bric-a-brac (BTB) domain found in animals. Orthologs of OsKEAP1 are present across plant species and all have the DCD domain and the Kelch-repeat domain. OsKEAP1 was proven to be localized to both the cytoplasm and nucleus, in contrast to the exclusive cytoplasm localization of animal KEAP1. Single nucleotide insertions in the 5' UTR significantly reduced the transcription level of OsKEAP1 in the oskeap1-1 and oskeap1-2 mutants. The oskeap1 mutations greatly impaired plant growth and development, resulting in significant declines in a majority of agronomic and yield-related traits, i.e., plant height, panicle length, grain number per plant, and seed-set rate. The downregulation of OsKEAP1 increased the levels of H2O2, malondialdehyde, and proline while significantly decreasing the expression of two catalase genes in seedlings grown under normal and salt-stressed conditions. The changes in the above phenotypes are either positively or negatively correlated with the degree of OsKEAP1 downregulation. Altogether, we identified a probable KEAP1 ortholog in rice, revealed its unique subcellular localization, and demonstrated its important functions in vegetative and reproductive growth via regulation of the antioxidant response in plants.

KIF15 contributes to cell proliferation and migration in breast cancer.

A number of kinesin proteins (KIFs) have been implicated in the development of multiple cancers. However, little is known about the expression and function of KIF15 in human breast cancer. Herein, we detected KIF15 expression in breast cancer tissues and paired adjacent normal tissues using immunohistochemistry and quantitative real-time polymerase chain reaction analysis, and the correlation of KIF15 expression with clinicopathological parameters was evaluated statistically. The role of KIF15 in cell proliferation, migration, tumor growth and metastasis of breast cancer cells was investigated in vitro and in vivo, and we explored potential molecular mechanisms underlying the effects of KIF15 in breast cancer through western blot analysis. The results revealed that increased KIF15 expression in breast cancer tissues were positively related with tumor size, lymph node metastasis and TNM stage, and higher KIF15 expression predicts a worse prognosis of patients with breast cancer. Furthermore, KIF15 knockdown markedly attenuated breast cancer cell proliferation, migration, tumor growth and metastasis in vitro and in vivo, and silenced KIF15 expression significantly inhibited the expression of phosphorylated AKT, phosphorylated JNK, and cyclin D1, while both p53 and p21 protein expressions were strongly enhanced. These results suggest that KIF15 is a potential oncogene in human breast cancer.

Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis.

Elimination of airway inflammatory cells is essential for asthma control. As Bcl-2 protein is highly expressed on the mitochondrial outer membrane in inflammatory cells, we chose a Bcl-2 inhibitor, ABT-199, which can inhibit airway inflammation and airway hyperresponsiveness by inducing inflammatory cell apoptosis. Herein, we synthesized a pH-sensitive nanoformulated Bcl-2 inhibitor (Nf-ABT-199) that could specifically deliver ABT-199 to the mitochondria of bronchial inflammatory cells. The proof-of-concept study of an inflammatory cell mitochondria-targeted therapy using Nf-ABT-199 was validated in a mouse model of allergic asthma. Nf-ABT-199 was proven to significantly alleviate airway inflammation by effectively inducing eosinophil apoptosis and inhibiting both inflammatory cell infiltration and mucus hypersecretion. In addition, the nanocarrier or Nf-ABT-199 showed no obvious influence on cell viability, airway epithelial barrier and liver function, implying excellent biocompatibility and with non-toxic effect. The nanoformulated Bcl-2 inhibitor Nf-ABT-199 accumulates in the mitochondria of inflammatory cells and efficiently alleviates allergic asthma.

Responsive Assembly of Upconversion Nanoparticles for pH-Activated and Near-Infrared-Triggered Photodynamic Therapy of Deep Tumors.

Upconversion nanoparticle (UCNP)-mediated photodynamic therapy has shown great effectiveness in increasing the tissue-penetration depth of light to combat deep-seated tumors. However, the inevitable phototoxicity to normal tissues resulting from the lack of tumor selectivity remains as a major challenge. Here, the development of tumor-pH-sensitive photodynamic nanoagents (PPNs) comprised of self-assembled photosensitizers grafted pH-responsive polymeric ligands and UCNPs is reported. Under neutral pH conditions, photosensitizers aggregated in the PPNs are self-quenched; however, upon entry into a tumor microenvironment with lower pH, the PPNs not only exhibit enhanced tumor-cell internalization due to charge reversal but also are further disassembled into well-dispersed nanoparticles in the endo/lysosomes of tumor cells, enabling the efficient activation of photosensitizers. The results demonstrate the attractive properties of both UCNP-mediated deep-tissue penetration of light and high therapeutic selectivity in vitro and in vivo.

Catgut implantation at acupoints increases the expression of glutamate aspartate transporter and glial glutamate transporter-1 in the brain of rats with spasticity after stroke.

Catgut implantation at acupoints has been shown to alleviate spasticity after stroke in rats. However, the underlying mechanisms are poorly understood. In this study, we used the rat middle cerebral artery occlusion model of stroke. Three days after surgery, absorbable surgical catgut sutures were implanted at Dazhui (GV14), Jizhong (GV6), Houhui, Guanyuan (CV4) and Zhongwan (CV12). The Zea Longa score was used to assess neurological function. The Modified Ashworth Scale was used to evaluate muscle tension. The 2,3,5-triphenyl-tetrazolium chloride assay was used to measure infarct volume. Immunohistochemical staining was performed for glutamate aspartate transporter (GLAST) and glial glutamate transporter-1 (GLT-1) expression. Western blot assay was used to analyze the expression of GLAST and GLT-1. Reverse transcription and polymerase chain reaction were carried out to assess the expression of GLAST and GLT-1 mRNAs. After catgut implantation at the acupoints, neurological function was substantially improved, muscle tension was decreased, and infarct volume was reduced in rats with spasticity after stroke. Furthermore, the expression of GLAST and GLT-1 mRNAs was increased on the injured (left) side. Our findings demonstrate that catgut implantation at acupoints alleviates spasticity after stroke, likely by increasing the expression of GLAST and GLT-1.