Investigation of the synergistic effect mechanism underlying sequential use of palbociclib and cisplatin through integral proteomic and glycoproteomic analysis.

Chemoresistance largely hampers the clinical use of chemodrugs for cancer patients, combination or sequential drug treatment regimens have been designed to minimize chemotoxicity and resensitize chemoresistance. In this work, the cytotoxic effect of cisplatin was found to be enhanced by palbociclib pretreatment in HeLa cells. With the integration of liquid chromatography-mass spectrometry-based proteomic and N-glycoproteomic workflow, we found that palbociclib alone mainly enhanced the N-glycosylation alterations in HeLa cells, while cisplatin majorly increased the different expression proteins related to apoptosis pathways. As a result, the sequential use of two drugs induced a higher expression level of apoptosis proteins BAX and BAK. Those altered N-glycoproteins induced by palbociclib were implicated in pathways that were closely associated with cell membrane modification and drug sensitivity. Specifically, the top four frequently glycosylated proteins FOLR1, L1CAM, CD63, and LAMP1 were all associated with drug resistance or drug sensitivity. It is suspected that palbociclib-induced N-glycosylation on the membrane protein allowed the HeLa cell to become more vulnerable to cisplatin treatment. Our study provides new insights into the mechanisms underlying the sequential use of target drugs and chemotherapy drugs, meanwhile suggesting a high-efficiency approach that involves proteomic and N-glycoproteomic to facilitate drug discovery.

Recent developments in ionization techniques for single-cell mass spectrometry.

The variation among individual cells plays a significant role in many biological functions. Single-cell analysis is advantageous for gaining insight into intricate biochemical mechanisms rarely accessible when studying tissues as a whole. However, measurement on a unicellular scale is still challenging due to unicellular complex composition, minute substance quantities, and considerable differences in compound concentrations. Mass spectrometry has recently gained extensive attention in unicellular analytical fields due to its exceptional sensitivity, throughput, and compound identification abilities. At present, single-cell mass spectrometry primarily concentrates on the enhancement of ionization methods. The principal ionization approaches encompass nanoelectrospray ionization (nano-ESI), laser desorption ionization (LDI), secondary ion mass spectrometry (SIMS), and inductively coupled plasma (ICP). This article summarizes the most recent advancements in ionization techniques and explores their potential directions within the field of single-cell mass spectrometry.

For a Better Quality of Beef: The Challenge from Growing Livestock on Limited Grasslands with a Production-Consumption Balance Perspective.

The growing population, the transition dietary towards animal-based products, and the preference for the brand of grass-feeding livestock are bringing increasing pressure on natural grasslands, especially for dry-land areas. The Xilingol League of China is famous for its free-range livestock product, however, overgrazing and herders' benefits damage are always serious issues for this semi-arid grassland region. This study focuses on the relationship between the supply of natural grassland and the consumption of free-range livestock in the Xilingol League, and this study employed the grassland carrying capacity as the index to judge the sustainability states and its trends of the local grass-feeding system. Satellite data production of net primary production was used for grassland production, statistical livestock data and the consumption model were used for actual forage consumption, and empirical key informant interview data were used to obtain a more comprehensive understanding. The results show that: (1) the natural grassland carrying capacity of the Xilingol League fluctuated, showing improvement from 2000 to 2021; (2) the grassland management needs to be more diversified in different regions with different natural conditions; and (3) while the demand for free-range, high-quality beef is increasing, attention should be paid to the carrying capacity of natural pastures and more consideration should be taken of the benefits of balancing the livelihood of herders, policy strategies, and the customers' preferences. Potential ways of doing this include employing technologies to improve livestock production, and further exploring and promoting the economic value of the free-range livestock and the geographical indication to get the economic-ecological win-win situation. The research framework and results would be beneficial to reveal the potential threats in pastoral areas and provide support for the optimization of the regional grass-feeding breeding system, especially in middle-income countries.

A 3D-printed freestanding graphene aerogel composite photocathode for high-capacity and long-life photo-assisted Li-O2 batteries.

The construction of a high-performance photocathode is essential for improving Li-O2 battery performance and solar energy utilization. However, the single pore and few active reaction sites of the photocathode result in insufficient discharge capacity and unsatisfactory cycling durability. Herein, we designed and fabricated a self-standing 3D-printed multi-pore graphene-based photocathode via direct ink writing (DIW) featuring non-competitive three-phase transmission channels to promote the transport of Li+, e-, and O2. The macropore provides adequate space for storage of the Li2O2 discharge product; the mesopore facilitates the reactant transport, while the micropore stores the active ions. Furthermore, the photogenerated carriers of the photocathode promote overpotential reduction. Under illumination, the charging voltage of the Li-O2 battery with a reduced graphene oxide/titanium dioxide (rGO/TiO2) photocathode is decreased from 4.55 V to 3.77 V, and the battery exhibits stable cycling for 1000 hours. Notably, the photocathode's pore structure and specific surface area are further optimized after adding carbon nanotubes (CNTs). Compared with rGO/TiO2, the specific surface area of reduced graphene oxide/titanium dioxide/carbon nanotubes (rGO/TiO2/CNTs) is increased by 12 times to 194.13 m2 g-1, and the discharge capacity can reach up to 33.37 mA h cm-2. This self-standing 3D-printed photocathode structure paves a new way for developing high-performance energy storage systems.

The application of Aptamer in biomarker discovery.

Biomarkers are detectable molecules that can reflect specific physiological states of cells, organs, and organisms and therefore be regarded as indicators for specific diseases. And the discovery of biomarkers plays an essential role in cancer management from the initial diagnosis to the final treatment regime. Practically, reliable clinical biomarkers are still limited, restricted by the suboptimal methods in biomarker discovery. Nucleic acid aptamers nowadays could be used as a powerful tool in the discovery of protein biomarkers. Nucleic acid aptamers are single-strand oligonucleotides that can specifically bind to various targets with high affinity. As artificial ssDNA or RNA, aptamers possess unique advantages compared to conventional antibodies. They can be flexible in design, low immunogenicity, relative chemical/thermos stability, as well as modifying convenience. Several SELEX (Systematic Evolution of Ligands by Exponential Enrichment) based methods have been generated recently to construct aptamers for discovering new biomarkers in different cell locations. Secretome SELEX-based aptamers selection can facilitate the identification of secreted protein biomarkers. The aptamers developed by cell-SELEX can be used to unveil those biomarkers presented on the cell surface. The aptamers from tissue-SELEX could target intracellular biomarkers. And as a multiplexed protein biomarker detection technology, aptamer-based SOMAScan can analyze thousands of proteins in a single run. In this review, we will introduce the principle and workflow of variations of SELEX-based methods, including secretome SELEX, ADAPT, Cell-SELEX and tissue SELEX. Another powerful proteome analyzing tool, SOMAScan, will also be covered. In the second half of this review, how these methods accelerate biomarker discovery in various diseases, including cardiovascular diseases, cancer and neurodegenerative diseases, will be discussed.

Nanoliter atmospheric pressure photoionization-mass spectrometry for direct bioanalysis of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are a class of low-polarity environmental contaminants that have severe carcinogenic effects and have drawn worldwide attention. However, there remain challenges for current mass spectrometric ionization techniques in the analysis of low-polarity compounds in small-volume biosamples, such as single cells. In this work, we developed a nanoliter atmospheric pressure photoionization (nano-APPI) source and optimized its parameters for the detection of PAHs in small-volume samples. We evaluated the ionization performance of the source in direct and auxiliary gas-assisted photoionization modes and analyzed different PAH compounds as well as spiked biosamples. By combining the advantages of nano-electrospray ionization (nano-ESI) and atmospheric pressure photoionization (APPI), our newly developed nano-APPI source achieved high sensitivity for the analysis of PAHs down to the fmol level. Compared to conventional atmospheric pressure chemical ionization (APCI), the detection limit of PAHs was increased by 1-2 orders of magnitude. By optimizing various parameters, we achieved highly efficient ionization of PAHs, effective analysis of PAHs in mixed components, and sensitive detection of low-abundance PAHs in single-cell samples. Our optimized nano-APPI source was successfully applied for the sensitive analysis of PAHs in complex biological samples. Based on our study, we believe that nano-APPI holds great promise for toxicological studies on complex biological samples. The present work has implications for improving the detection sensitivity of low-polarity environmental contaminants and advancing the field of MS-based analysis of small-volume biosamples.

Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis.

Palbociclib is a specific CDK4/6 inhibitor that has been widely applied in multiple types of tumors. Different from cytotoxic drugs, the anticancer mechanism of palbociclib mainly depends on cell cycle inhibition. Therefore, the resistance mechanism is different. For clinical cancer patients, drug resistance is inevitable for almost all cancer therapies including palbociclib. We have trained palbociclib resistant cells in vitro to simulate the clinical situation and applied LC-MS multi-omics analysis methods including proteomic, metabolomic, and glycoproteomic techniques, to deeply understand the underly mechanism behind the resistance. As a result of proteomic analysis, the resistant cells were found to rely on altered metabolic pathways to keep proliferation. Metabolic processes related to carbohydrates, lipids, DNA, cellular proteins, glucose, and amino acids were observed to be upregulated. Most dramatically, the protein expressions of COX-1 and NDUFB8 have been detected to be significantly overexpressed by proteomic analysis. When a COX-1 inhibitor was hired to combine with palbociclib, a synergistic effect could be obtained, suggesting the altered COX-1 involved metabolic pathway is an important reason for the acquired palbociclib resistance. The KEGG pathway of N-glycan biosynthesis was identified through metabolomics analysis. N-glycoproteomic analysis was therefore included and the global glycosylation was found to be elevated in the palbociclib-resistant cells. Moreover, integration analysis of glycoproteomic data allowed us to detect a lot more proteins that have been glycosylated with low abundances, these proteins were considered to be overwhelmed by those highly abundant proteins during regular proteomic LC-MS detection. These low-abundant proteins are mainly involved in the cellular biology processes of cell migration, the regulation of chemotaxis, as well as the glycoprotein metabolic process which offered us great more details on the roles played by N-glycosylation in drug resistance. Our result also verified that N-glycosylation inhibitors could enhance the cell growth inhibition of palbociclib in resistant cells. The high efficiency of the integrated multi-omics analysis workflow in discovering drug resistance mechanisms paves a new way for drug development. With a clear understanding of the resistance mechanism, new drug targets and drug combinations could be designed to resensitize the resistant tumors.

Proteomics reveals that cell density could affect the efficacy of drug treatment.

In vitro cell biology study plays a fundamental role in biological and drug development research, but the repeatability and accuracy of cell studies remain to be low. Various uncertainties during the cell culture process could introduce bias into drug research. In this study, we evaluate the potential effects and underlying mechanisms induced by cell number differences in the cell seeding process. Normally, drug experiments are initiated 24 h after cell seeding, and the difference in the cell number at the time of inoculation leads to the difference in cell confluence (cell density) when drug research is conducted. While cell confluence is closely related to intercellular communication, surface protein interaction, cell autocrine as well as paracrine protein expression of cells, it might have a potential impact on the effect of biological studies such as drug treatment. This study used proteomics technology to comprehensively explore the different protein expression patterns between cells with different confluences. Due to the high sensitivity and high throughput of liquid chromatography-mass spectrometry (LC-MS/MS) detection, it was hired to evaluate the protein expression differences of Hep3B cells with 3 different confluences (30%, 50%, and 70%). The differential expressed proteins were analyzed by the Reactome pathway and the Gene Ontology (GO) pathway. Significant differences were identified across three confluences in terms of the number of proteins identified, the protein expression pattern, and the expression level of certain KEGG pathways. We found that those proteins involved in the cell cycle pathway were differently expressed: the higher the cell confluence, the higher these proteins expressed. A cell cycle inhibitor palbociclib was selected to further verify this observation. Palbociclib in the same dose was applied to cells with different confluence, the results indicated that the growth inhibition effect of palbociclib increases along with the increasing trend of cell cycle protein expression. The result indicated that cell density did influence the effect of drug treatment. Furthermore, three other drugs, cisplatin, paclitaxel, and imatinib, were used to treat the three liver cancer cell lines Hep3B, SUN387, and MHCC97, and a similar observation was obtained that drug effect would be different when the cell confluences were different. Therefore, selecting an appropriate number of cells for plating is vitally important at the beginning of a drug study.

Aptamer nucleotide analog drug conjugates in the targeting therapy of cancers.

Aptamers are short single-strand oligonucleotides that can form secondary and tertiary structures, fitting targets with high affinity and specificity. They are so-called "chemical antibodies" and can target specific biomarkers in both diagnostic and therapeutic applications. Systematic evolution of ligands by exponential enrichment (SELEX) is usually used for the enrichment and selection of aptamers, and the targets could be metal ions, small molecules, nucleotides, proteins, cells, or even tissues or organs. Due to the high specificity and distinctive binding affinity of aptamers, aptamer-drug conjugates (ApDCs) have demonstrated their potential role in drug delivery for cancer-targeting therapies. Compared with antibodies which are produced by a cell-based bioreactor, aptamers are chemically synthesized molecules that can be easily conjugated to drugs and modified; however, the conventional ApDCs conjugate the aptamer with an active drug using a linker which may add more concerns to the stability of the ApDC, the drug-releasing efficiency, and the drug-loading capacity. The function of aptamer in conventional ApDC is just as a targeting moiety which could not fully perform the advantages of aptamers. To address these drawbacks, scientists have started using active nucleotide analogs as the cargoes of ApDCs, such as clofarabine, ara-guanosine, gemcitabine, and floxuridine, to replace all or part of the natural nucleotides in aptamer sequences. In turn, these new types of ApDCs, aptamer nucleotide analog drug conjugates, show the strength for targeting efficacy but avoid the complex drug linker designation and improve the synthetic efficiency. More importantly, these classic nucleotide analog drugs have been used for many years, and aptamer nucleotide analog drug conjugates would not increase any unknown druggability risk but improve the target tumor accumulation. In this review, we mainly summarized aptamer-conjugated nucleotide analog drugs in cancer-targeting therapies.

Nucleic acid therapy in pediatric cancer.

The overall survival, progress free survival, and life quality of cancer patients have improved due to the advance in minimally invasive surgery, precision radiotherapy, and various combined chemotherapy in the last decade. Furthermore, the discovery of new types of therapeutics, such as immune checkpoint inhibitors and immune cell therapies have facilitated both patients and doctors to fight with cancers. Moreover, in the context of the development in biocompatible and cell type targeting nano-carriers as well as nucleic acid-based drugs for initiating and enhancing the anti-tumor response have come to the age. The treatment paradigms utilization of nucleic acids, including short interfering RNA (siRNA), antisense oligonucleotides (ASO), and messenger RNA (mRNA), can target specific protein expression to achieve the therapeutic effects. Over ten nucleic acid therapeutics have been approved by the FDA and EMA in rare diseases and genetic diseases as well as dozens of registered clinical trails for varies cancers. Though generally less dangerous of pediatric cancers than adult cancers was observed during the past decades, yet pediatric cancers accounted for a significant proportion of child deaths which hurt those family very deeply. Therefore, it is necessary to pay more attention for improving the treatment of pediatric cancer and discovering new nucleic acid therapeutics which may help to improve the therapeutic effect and prognoses in turns to ameliorate the survival period and quality of life for children patient. In this review, we focus on the nucleic acid therapy in pediatric cancers.

Tailored Plasmonic Ru/OV-MoO2 on TiO2 Catalysts via Solid-Phase Interface Engineering: Toward Highly Efficient Photoassisted Li-O2 Batteries with Enhanced Cycling Reliability.

The photoassisted electrochemical reactions are considered an effective method to reduce the overpotential of Li-O2 batteries. However, achieving long-term cell cycling stability remains a challenge. Here, we report a solid-phase interfacial reaction (SPIR) strategy that introduces both oxygen vacancies (OV) and metal centers (Ru) into the MoO2 to synthesize the surface plasmon (i.e., Ru/OV-MoO2). Then, Ru/OV-MoO2 can be uniformly loaded on the TiO2 nanowires by the hydrothermal method. The plasma effect of Ru/OV-MoO2 demonstrates the effective reduction of the photoexcited electron and hole recombination to improve visible light-harvesting ability. The lifetime of electrons and holes can be extended by Ru nanoparticles, which is beneficial for promoting the formation and decomposition of Li2O2. In addition, the generated OV further enhanced the migration of electrons and Li+, thus improving the ORR performance. The Ru/OV-MT/CC cathode corroborates excellent stability and catalytic performance in the photoassisted Li-O2 battery, with an overpotential value of 0.47 V, achieving the highest energy efficiency of 93.94%, retaining at 89.13% after 800 h. This work offers a platform for preparing a stable, bifunctional catalyst with the high total activity of a photoassisted Li-O2 battery.

Exploring adaptive approaches for social-ecological sustainability in the Belt and Road countries: From the perspective of ecological resource flow.

The countries along the Belt and Road (B&R) are characterized by fragile ecosystems and underdevelopment economy. International trade usually transferred the eco-environmental negative impacts to developing countries. How to avoid the conflict between economic development and eco-environmental protection is the primary concern of building the Green Silk Road. To discover the adaptive strategies for ensuring the sustainability of the social-ecosystem in countries along the B&R, this study analyzes the supply-consumption relationship of ecological resources by simulating the flow of net primary productivity between the ecosystem and the social system. The results show that: (1) The flow of ecological resources between agricultural and husbandry systems have effectively alleviated the local ecological pressure caused by animal husbandry in countries along the B&R. Animal husbandry in developed countries economize the local ecological resources by importing feed, while mitigating the grazing pressure by utilizing the local crop residues in underdeveloped agricultural countries. (2) International trade not only enables countries with insufficient ecological resources to meet their demands by importing ecological products and thus alleviate ecosystem pressure, but also promotes countries with sufficient ecological resources to transform their resource advantages into economic advantages by exporting without at the expense of ecological sustainability. (3) For underdeveloped countries, the dependence of economic development on ecological resources is at the expense of the living demands of residents, only if the economy could have leap-forward improvement the allocation of ecological resources within the social system would be inclined to living demands. These adaptive approaches not only provide the evidences of ecological-social sustainable development by promoting the reasonable flow and allocation of ecological resources, but also imply the necessary assistance for the underdeveloped countries to guarantee the basic human well-being in economic development.

Preparation of C3N4/montmorillonite composite photocatalyst for effective removal of organic pollutants.

Due to the good photocatalytic performance, which ensures the decomposition of pollutants under light, g-C3N4 is considered as an ideal photocatalytic material. Montmorillonite has a high adsorption capacity and layered structure, which has positive effects on increasing the specific surface area of g-C3N4 and avoid its polymerization agglomeration. In this paper, montmorillonite was used as carrier for g-C3N4 to obtain a new photocatalytic composite g-C3N4/Mt. Then the morphological and (micro)structural properties were characterized. The well-characterized materials were evaluated for the photocatalytic activity in degradation of methylene blue and Bisphenol A. The effects of the mass fraction of g-C3N4, light irradiation time, and pollutant concentration on the photocatalytic performance of g-C3N4/Mt composites were studied. Under the optimal experimental plan, the rate of photocatalytic degradation can reach to 99.3% within 120 min. Through the MS spectrum, it can be found that methylene blue molecule were catalysed and degraded into many harmless substances with low-molecular weight. Finally, based on the obtained reaction products, the mechanism by which the pollutants are removed was proposed. This study provides a new strategy to improve the photocatalysis ability of g-C3N4, which is of great significance for a sustainable pollution treatment.

Longitudinal evaluation of five nasopharyngeal carcinoma animal models on the microPET/MR platform.

PURPOSE: We longitudinally evaluated the tumour growth and metabolic activity of three nasopharyngeal carcinoma (NPC) cell line models (C666-1, C17 and NPC43) and two xenograft models (Xeno76 and Xeno23) using a micropositron emission tomography and magnetic resonance (microPET/MR). With a better understanding of the interplay between tumour growth and metabolic characteristics of these NPC models, we aim to provide insights for the selection of appropriate NPC cell line/xenograft models to assist novel drug discovery and evaluation. METHODS: Mice were imaged by 18F-deoxyglucose ([18F]FDG) microPET/MR twice a week for consecutive 3-7 weeks. [18F]FDG uptake was quantified by standardized uptake value (SUV) and presented as SUVmean tumour-to-liver ratio (SUVRmean). Longitudinal tumour growth patterns and metabolic patterns were recorded. SUVRmean and histological characteristics were compared across the five NPC models. Cisplatin was administrated to one selected optimal tumour model, C17, to evaluate our imaging platform. RESULTS: We found variable tumour growth and metabolic patterns across different NPC tumour types. C17 has an optimal growth rate and higher tumour metabolic activity compared with C666-1. C666-1 has a fast growth rate but is low in SUVRmean at endpoint due to necrosis as confirmed by H&E. NPC43 and Xeno76 have relatively slow growth rates and are low in SUVRmean, due to severe necrosis. Xeno23 has the slowest growth rate, and a relative high SUVRmean. Cisplatin showed the expected therapeutic effect in the C17 model in marked reduction of tumour size and metabolism. CONCLUSION: Our study establishes an imaging platform that characterizes the growth and metabolic patterns of different NPC models, and the platform is well able to demonstrate drug treatment outcome supporting its use in novel drug discovery and evaluation for NPC.

Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients.

Diabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new opportunity for the understanding of T2D; however, the underlying proteomic characteristics of T2D have not been thoroughly investigated yet. Here, using proteomic and glycoproteomic profiling, we provided a comprehensive landscape of molecular alterations in the fasting plasma of the 24 Chinese participants, including eight T2D patients, eight prediabetic (PDB) subjects, and eight healthy control (HC) individuals. Our analyses identified a diverse set of potential biomarkers that might enhance the efficiency and accuracy based on current existing biological indicators of (pre)diabetes. Through integrative omics analysis, we showed the capability of glycoproteomics as a complement to proteomics or metabolomics, to provide additional insights into the pathogenesis of (pre)diabetes. We have newly identified systemic site-specific N-glycosylation alterations underlying T2D patients in the complement activation pathways, including decreased levels of N-glycopeptides from C1s, MASP1, and CFP proteins, and increased levels of N-glycopeptides from C2, C4, C4BPA, C4BPB, and CFH. These alterations were not observed at proteomic levels, suggesting new opportunities for the diagnosis and treatment of this disease. Our results demonstrate a great potential role of glycoproteomics in understanding (pre)diabetes and present a new direction for diabetes research which deserves more attention.

Therapeutic evaluation of palbociclib and its compatibility with other chemotherapies for primary and recurrent nasopharyngeal carcinoma.

BACKGROUND: Recent genomic analyses revealed that druggable molecule targets were only detectable in approximately 6% of patients with nasopharyngeal carcinoma (NPC). However, a dependency on dysregulated CDK4/6-cyclinD1 pathway signaling is an essential event in the pathogenesis of NPC. In this study, we aimed to evaluate the therapeutic efficacy of a specific CDK4/6 inhibitor, palbociclib, and its compatibility with other chemotherapeutic drugs for the treatment of NPC by using newly established xenograft models and cell lines derived from primary, recurrent, and metastatic NPC. METHODS: We evaluated the efficacies of palbociclib monotherapy and concurrent treatment with palbociclib and cisplatin or suberanilohydroxamic acid (SAHA) in NPC cell lines and xenograft models. RNA sequencing was then used to profile the drug response-related pathways. Palbociclib-resistant NPC cell lines were established to determine the potential use of cisplatin as a second-line treatment after the development of palbociclib resistance. We further examined the efficacy of palbociclib treatment against cisplatin-resistant NPC cells. RESULTS: In NPC cells, palbociclib monotherapy was confirmed to induce cell cycle arrest in the G1 phase in vitro. Palbociclib monotherapy also had significant inhibitory effects in all six tested NPC tumor models in vivo, as indicated by substantial reductions in the total tumor volumes and in Ki-67 proliferation marker expression. In NPC cells, concurrent palbociclib treatment mitigated the cytotoxic effect of cisplatin in vitro. Notably, concurrent treatment with palbociclib and SAHA synergistically promoted NPC cell death both in vitro and in vivo. This combination also further inhibited tumor growth by inducing autophagy-associated cell death. NPC cell lines with induced palbociclib or cisplatin resistance remained sensitive to treatment with cisplatin or palbociclib, respectively. CONCLUSIONS: Our study findings provide essential support for the use of palbociclib as an alternative therapy for NPC and increase awareness of the effective timing of palbociclib administration with other chemotherapeutic drugs. Our results provide a foundation for the design of first-in-human clinical trials of palbociclib regimens in patients with NPC.

Impact assessment of land use functions on the sustainable regional development of representative Asian countries - A comparative study in Bangladesh, China and Japan.

Sustainable land use is a fundamental research field for land use planning. However, regional policymakers often lack access to the theoretical impacts that a land use policy might have on local development, especially in remote agricultural areas. Furthermore, knowledge exchange is important, especially in the context of globalization. This research employed the Framework of Participatory Impact Assessment and household surveys to combine multilevel stakeholders and comprehensively assessed the impacts of different land management scenarios on land use functions (LUFs) and local sustainable development. We completed this comparative study in typical remote agricultural areas in Godagari upazila of Bangladesh, Guyuan of China and Noto of Japan, which all have gradient differences in terms of their economic and social aspects, natural conditions and main land use issues. The selected scenarios were business as usual, increase in agricultural input and reform of rural development mode. The main conclusions are as follows: (1) the farmers at the three study sites all showed a decreasing dependence on their land and a relevant level of stress on environmental LUFs, but the rooted reasons were different and even opposing; (2) scenarios with a high aggregate impact on LUFs might not enable a sustainable development model, and the assessment of land management measures should consider the balance among environmental, economic and social dimensions; and (3) land use and management practices should be conducted with consideration of local conditions, and protecting agricultural development and enacting appropriate agricultural reforms could revitalize local agricultural development. The results revealed the demand for location-specific land management practices and underlined the knowledge of agricultural management on an international scale.

Assessing the influences of ecological restoration on perceptions of cultural ecosystem services by residents of agricultural landscapes of western China.

Landscape change caused by ecological restoration projects has both positive and negative influences on human livelihoods, yet surprisingly little research on the cultural consequences of ecological restoration in agricultural landscapes has taken place. Cultural consequences can be captured in the ecosystem services framework as cultural ecosystem services (CES). However, assessment and valuation of these services to support decision-making for this essential ecosystem is lacking. To help fill this gap, we assessed the opinions of Chinese rural communities about CES and the changes in their perception under the Grain for Green program (GFG), a nationwide program to relieve the pressure on ecosystems (soil erosion and land degradation) by converting cultivated land or barren land on steep slopes into grassland and forests. We used Guyuan City in China's Ningxia Hui Autonomous Region as a case study, using a workshop to identify the CES provided by the agricultural landscape, followed by semi-structured household interviews to quantify perceptions of these CES. We found that all eight CES types identified by the workshop were perceived by the rural communities. Reforestation changed their perceptions of CES directly due to land cover change and indirectly due to the resulting economic changes and migration of mostly young workers in search of better jobs. Cultivated land was perceived as more important than forest for CES provision. In addition, residential areas were perceived as providing significant CES because of local traditions that produce close and highly social neighborhood bonds in agricultural landscapes.

Low-Work-Function, ITO-Free Transparent Cathodes for Inverted Polymer Solar Cells.

A low-work-function, indium tin oxide (ITO)-free transparent cathode having a tin oxide (SnOX)/Ag/SnOX/bismuth oxide (Bi2O3) (SASB) structure is developed without using annealing treatment. This represents the first time that Bi2O3 has been introduced to lower the work function of transparent electrodes. The SASB transparent cathode exhibits excellent photoelectric properties with a maximum transmittance of ∼88%, a low sheet resistance of ∼9.0 Ω·sq(-1), and a suitable work function of 4.22 eV that matches the lowest unoccupied molecular orbital level of the acceptor for exacting electrons efficiently. The power conversion efficiency of the polymer solar cell with the SASB electrode is 6.21%, which is comparable to that of ITO-based devices. The results indicate that SASB is a good alternative to ITO as transparent cathodes in optoelectronic devices.

High-performance NiO/Ag/NiO transparent electrodes for flexible organic photovoltaic cells.

Transparent electrodes with a dielectric-metal-dielectric (DMD) structure can be implemented in a simple manufacturing process and have good optical and electrical properties. In this study, nickel oxide (NiO) is introduced into the DMD structure as a more appropriate dielectric material that has a high conduction band for electron blocking and a low valence band for efficient hole transport. The indium-free NiO/Ag/NiO (NAN) transparent electrode exhibits an adjustable high transmittance of ∼82% combined with a low sheet resistance of ∼7.6 Ω·s·q(-1) and a work function of 5.3 eV after UVO treatment. The NAN electrode shows excellent surface morphology and good thermal, humidity, and environmental stabilities. Only a small change in sheet resistance can be found after NAN electrode is preserved in air for 1 year. The power conversion efficiencies of organic photovoltaic cells with NAN electrodes deposited on glass and polyethylene terephthalate (PET) substrates are 6.07 and 5.55%, respectively, which are competitive with those of indium tin oxide (ITO)-based devices. Good photoelectric properties, the low-cost material, and the room-temperature deposition process imply that NAN electrode is a striking candidate for low-cost and flexible transparent electrode for efficient flexible optoelectronic devices.