Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.

In mammals, gonadal somatic cell lineage differentiation determines the development of the bipotential gonad into either the ovary or testis. Sertoli cells, the only somatic cells in the spermatogenic tubules, support spermatogenesis during gonadal development. During embryonic Sertoli cell lineage differentiation, relevant genes, including WT1, GATA4, SRY, SOX9, AMH, PTGDS, SF1, and DMRT1, are expressed at specific times and in specific locations to ensure the correct differentiation of the embryo toward the male phenotype. The dysregulated development of Sertoli cells leads to gonadal malformations and male fertility disorders. Nevertheless, the molecular pathways underlying the embryonic origin of Sertoli cells remain elusive. By reviewing recent advances in research on embryonic Sertoli cell genesis and its key regulators, this review provides novel insights into sex determination in male mammals as well as the molecular mechanisms underlying the genealogical differentiation of Sertoli cells in the male reproductive ridge.

Near-infrared light-driven asymmetric photolytic reduction of ketone using inorganic-enzyme hybrid biocatalyst.

Effective photolytic regeneration of the NAD(P)H cofactor in enzymatic reductions is an important and elusive goal in biocatalysis. It can, in principle, be achieved using a near-infrared light (NIR) driven artificial photosynthesis system employing H2O as the sacrificial reductant. To this end we utilized TiO2/reduced graphene quantum dots (r-GQDs), combined with a novel rhodium electron mediator, to continuously supply NADPH in situ for aldo-keto reductase (AKR) mediated asymmetric reductions under NIR irradiation. This upconversion system, in which the Ti-O-C bonds formed between r-GQDs and TiO2 enabled efficient interfacial charge transfer, was able to regenerate NADPH efficiently in 64 % yield in 105 min. Based on this, the pharmaceutical intermediate (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol was obtained, in 84 % yield and 99.98 % ee, by reduction of the corresponding ketone. The photo-enzymatic system is recyclable with a polymeric electron mediator, which maintained 66 % of its original catalytic efficiency and excellent enantioselectivity (99.9 % ee) after 6 cycles.

The Physical Mechanism of Linear and Nonlinear Optical Properties of Nanographene-Induced Chiral Inversion.

Based on density functional theory (DFT) and wave function analysis, the ultraviolet and visible spectrophotometry (UV-Vis) spectra and Raman spectra of 1-meso and 1-rac obtained by the chiral separation of chiral nanographenes are theoretically investigated. The electron excitation properties of 1-meso and 1-rac are studied by means of transition density matrix (TDM) and charge density difference (CDD) diagrams. The intermolecular interaction is discussed based on an independent gradient model based on Hirshfeld partition (IGMH). The interaction of 1-meso and 1-rac with the external environment is studied using the electrostatic potential (ESP), and the electron delocalization degree of 1-meso and 1-rac is studied based on the magnetically induced current under the external magnetic field. Through the chiral separation of 1-rac, two enantiomers, 1-(P, P) and 1-(M, M), were obtained. The electrical-magnetic interaction of the molecule is revealed by analyzing the electron circular dichroism (ECD) spectra of 1-meso, 1-(P, P) and 1-(M, M), the transition electric dipole moment (TEDM) and the transition magnetic dipole moment (TMDM). It is found that 1-(P, P) and 1-(M, M) have opposite chiral properties due to the inversion of the structure.

Ecological risks induced by consumption and emission of Pharmaceutical and personal care products in Qinghai-Tibet Plateau: Insights from the polar regions.

As the third pole of the world and Asia's water tower, the Tibetan Plateau experiences daily release of pharmaceutical and personal care products (PPCPs) due to increasing human activity. This study aimed to explore the potential relationship between the concentration and composition of PPCPs and human activity, by assessing the occurrence of PPCPs in areas of typical human activity on the Qinghai-Tibet Plateau and evaluating their ecological risk. The results indicate that 28 out of 30 substances were detected in concentrations ranging from less than 1 ng/L to hundreds of ng/L, with the average concentration of most PPCPs in the Tibet Autonomous Region being higher than that in Qinghai Province. Among the detected substances, CAF, NOR, CTC, CIP, TCN, OTC, AZN, and DOX accounted for over 90% of the total concentration. The emission sources of PPCPs were identified by analyzing the correlation coefficients of soil and water samples, with excess PPCPs used by livestock breeding discharged directly into soil and then into surface water through leaching or runoff. By comparing the concentration and composition of PPCPs with those in other regions, this study found that CIP, ENR, LOM, NOR, CTC, DOX, OTC, and TCN were the most commonly used PPCPs in the Qinghai-Tibet Plateau. To assess the ecological risk of PPCPs, organisms at different trophic levels, including algae, crustaceans, fish, and insects, were selected. The prediction of the no effect concentration of each PPCP showed that NOR, CTC, TCN, CAF, and CBZ may have deleterious effects on water biota. This study can assist in identifying the emission characteristics of PPCPs from different types and intensities of human activities, as well as their occurrence and fate during the natural decay of aquatic systems.

Construction of Magnetic Core-Large Mesoporous Satellite Immunosensor for Long-Lasting Chemiluminescence and Highly Sensitive Tumor Marker Determination.

Chemiluminescence immunoassay exhibits high sensitivity and signal-to-noise ratio, thus attracting great attention in the early diagnosis and dynamic monitoring of diseases. However, the collection of conventional flash-type chemiluminescence signal (<5 s) relies heavily on automatic sampling and reading instrument. Herein, a novel core-satellite multifunctional chemiluminescence immunosensor is designed for the efficient enrichment and highly sensitive determination of cancer biomarker carcinoembryonic antigen (CEA) with enhanced and long-lasting output signal that can be conveniently recorded by a simple microplate plate reading instrument. Anti-CEA monoclonal antibody 2 (Ab2) modified Fe3 O4 @SiO2 microspheres (Fe3 O4 @SiO2 -Ab2, 370 nm in diameter) are synthesized as the core for selectively capturing and enriching target CEA in solution, and anti-human CEA monoclonal antibody 1 (Ab1) and horseradish peroxidase (HRP) co-immobilized dendritic large-mesoporous silica nanospheres (MSNs-HRP/Ab1, 80 nm in diameter, pore size: 17 nm) are synthesized as the satellite for efficient immunological recognition and signal amplification. The as-designed core-satellite magnetic chemiluminescence immunosensors exhibit a broad linear range of 0.01-20 ng mL-1 and a low detection limit of 3.0 pg mL-1 for the convenient, highly specific, and sensitive determination of CEA in human serum. Such core-satellite chemiluminescence immunosensors are expected to act as a powerful tool for in vitro detection of various biomarkers, overcome the defect of conventional chemiluminescence relying heavily on expensive and bulky automatic instruments and popularize chemiluminescence analysis to primary medical institutions and remote areas.

Plasmonic scattering imaging of single Cu2-xSe nanoparticle for Hg2+ detection.

The development of new efficient contrast nanoprobe has been greatly concerned in the field of scattering imaging for sensitive and accurate detection of trace analytes. In this work, the non-stoichiometric Cu2-xSe nanoparticle with typical localized surface plasmon resonance (LSPR) properties originating from their copper deficiency as a plasmonic scattering imaging probe was developed for sensitive and selective detection of Hg2+ under dark-field microscopy. Hg2+ can compete with Cu(I)/Cu(II) which were sources of optically active holes coexisting in these Cu2-xSe nanoparticles for its higher affinity with Se2-. The plasmonic properties of Cu2-xSe were adjusted effectively. Thus, the color scattering images of Cu2-xSe nanoparticles was changed from blue to cyan, and the scattering intensity was obviously enhanced with the dark-field microscopy. There was a linear relationship between the scattering intensity enhancement and the Hg2+ concentration in the range of 10-300 nM with a low detection limit of 1.07 nM. The proposed method has good potential for Hg2+ detection in the actual water samples. This work provides a new perspective on applying new plasmonic imaging probe for the reliable determination of trace heavy metal substances in the environment at a single particle level.

Multi-Catcher Polymers Regulate the Nucleolin Cluster on the Cell Surface for Cancer Therapy.

Cell signal transduction mediated by cell surface ligand-receptor is crucial for regulating cell behavior. The oligomerization or hetero-aggregation of the membrane receptor driven by the ligand realizes the rearrangement of apoptotic signals, providing a new ideal tool for tumor therapy. However, the construction of a stable model of cytomembrane receptor aggregation and the development of a universal anti-tumor therapy model on the cellular surface remain challenging. This work describes the construction of a "multi-catcher" flexible structure GC-chol-apt-cDNA with a suitable integration of the oligonucleotide aptamer (apt) and cholesterol (chol) on a polymer skeleton glycol chitosan (GC), for the regulation of the nucleolin cluster through strong polyvalent binding and hydrophobic membrane anchoring on the cell surface. This oligonucleotide aptamer shows nearly 100-fold higher affinity than that of the monovalent aptamer and achieves stable anchoring to the plasma membrane for up to 6 h. Moreover, it exerts a high tumor inhibition both in vitro and in vivo by activating endogenous mitochondrial apoptosis pathway through the cluster of nucleolins on the cell membrane. This multi-catcher nano-platform combines the spatial location regulation of cytomembrane receptors with the intracellular apoptotic signaling cascade and represents a promising strategy for antitumor therapy.

Linear and Nonlinear Photon-Induced Cross Bridge/Space Charge Transfer in STC Molecular Crystals.

In this work, we theoretically studied the optical absorption properties of a layer-stacked cocrystal heterogeneous material Spe-TCNB cocrystal (STC) which is produced by supramolecular self-assembly of organic conjugated monomers SPE and TCNB. The highly ordered aggregate structure in the cocrystal STC will lead to intermolecular interactions such as π∼π, hydrogen bonds and van der Waals forces, resulting in significant charge transfer characteristics and large cross-sectional two-photon absorption characteristics. The physical mechanism of one-photon and two-photon charge transfer of cocrystal molecules is specifically discussed and the interaction between molecules and their role in charge transfer are quantitatively analyzed. We found that the charge transfer between molecular junctions composed of hydrogen bonds is mainly cross-bridge charge transfer, while the charge transfer between molecular junctions caused by accumulation is mainly cross-space charge transfer. This discovery is of great significance to the design of organic photoelectric functional materials.

Electrochemiluminescence Resonance Energy Transfer System Based on Silver Metal-Organic Frameworks as a Double-Amplified Emitter for Sensitive Detection of miRNA-107.

As a class of electrochemiluminescence (ECL) enhancers, silver-based materials have broad application prospects. In this work, a novel silver metal-organic framework (AgMOF) was developed as a self-enhanced ECL emitter by one-step mixing and standing at room temperature. The AgMOF could produce strong and stable ECL emissions based on a double-amplification method, which originated from the aggregation-induced ECL emission of ligands and catalyzing S2O82- to produce more SO4•- by silver. Moreover, an ECL resonance energy transfer (ECL-RET) biosensor with AgMOF as a donor and BHQ2 as an acceptor was fabricated by duplex-specific nuclease (DSN)-assisted target recycling amplification to detect miRNA-107. The biosensor exhibited a strong ECL-RET effect due to the higher ECL emission of the AgMOF and perfect match of spectra between the AgMOF and BHQ2. Upon the introduction of DSN and target miRNAs, the specific DNA-RNA binding and nuclease cleaving could trigger the detachment of BHQ2, resulting in an increased ECL signal of AgMOF. Benefiting from the ECL-RET and DSN-assisted target recycling amplification methods, this biosensor achieved a wide linear relationship range from 20 to 120 fM with a low limit of detection (4.33 fM). This research presents an effective emitter for self-enhanced ECL systems, which broadens the potential ECL applications of silver-based nanomaterials.

Self-Targeting Carbon Quantum Dots for Peroxynitrite Detection and Imaging in Live Cells.

Peroxynitrite (ONOO-), a highly reactive nitrogen species (RNS) generated mainly in mitochondria, has been identified to be associated with numerous pathophysiological processes, and thus accurate ONOO- imaging with superior sensitivity and selectivity is highly desirable. Herein, we prepared a new type of carbon quantum dots (CQDs) with mitochondria-targeting function without the aid of any targeting molecules via a simple one-step hydrothermal route. The as-prepared CQDs not only displayed relatively uniform size distribution, few surface defects, high photostability, and excellent biocompatibility but also exhibited good selective fluorescence turn-off response toward ONOO-, owing to the oxidation of amino groups on the surface of carbon dots. A great linear correlation between the quenching efficiency and ONOO- concentration in the range from 0.15 to 1.0 µM with a detection limit of 38.9 nM is shown. Moreover, the as-prepared CQDs acting as a functional optical probe through a self-targeting mechanism were successfully applied for in situ visualization of endogenous ONOO- generated in the mitochondria of live cells, providing great promise for elucidating the complex biological roles of ONOO- in related pathological processes.

Homo-FRET enhanced ratiometric fluorescence strategy for exonuclease III activity detection.

In this work, homo-FRET (Förster resonance energy transfer between the same kind of fluorophores) takes place in a hetero-FRET (FRET between two different fluorophores) system and can effectively improve the energy transfer efficiency. Herein, a novel ratiometric fluorescence method was developed for the detection of nuclease activity. Exonuclease III (Exo III), an enzyme which has a high exodeoxyribonuclease activity for double-stranded DNA (dsDNA) in the 3' to 5' direction, was chosen as a proof of concept of this strategy. In a linear dsDNA template, the occurrence of homo-FRET in two Cy3 donors enables the highly efficient transfer of energy to the Cy5 acceptor. The ratio of fluorescence intensity between Cy3 and Cy5 (FD/FA) increases in an Exo III concentration-dependent manner, which built the foundation of Exo III quantification. This method exhibits a linear range from 0.25 to 8 U mL-1 with a detection limit of 0.17 U mL-1. Importantly, this platform also shows the potential for screening Exo III inhibitors and detecting Exo III activity in complex samples.

WD repeat-containing protein 1 maintains ß-Catenin activity to promote pancreatic cancer aggressiveness.

BACKGROUND: The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. METHODS: Eight-plex isobaric tags coupled with two-dimensional liquid chromatography-tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation. RESULTS: A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/ß-Catenin pathway; ectopic expression of a stabilised form of ß-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of ß-Catenin. CONCLUSION: Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.

Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment.

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

Core-Shell Magnetic Mesoporous Silica Microspheres with Large Mesopores for Enzyme Immobilization in Biocatalysis.

Magnetic mesoporous silica microspheres with core-shell structure and large pores are highly desired in macromolecules delivery and biocatalysis, biospeparation, and adsorption. In this work, a controllable solvent evaporation induced solution-phase interface co-assembly approach was developed to synthesize core-shell structural magnetic mesoporous silica microspheres with ultralarge mesopore size (denoted as LP-MMS). The synthesis was achieved by employing large-molecular-weight amphiphilic block copolymers poly(ethylene oxide)- block-poly(methyl methacrylate) (PEO- b-PMMA) and small surfactant cetyltrimethylammonium bromide as co-templates, which can co-assemble with silica source in tetrahydrofuran/water solutions. The obtained LP-MMS microspheres possess uniform rasberry-like morphology with a diameter of 600 nm, large primary spherical mesopores (ca. 36 nm), large specific surface area (348 m2/g), high specific pore volume (0.59 cm3/g), and fast magnetic responsivity with high magnetization (15.9 emu/g). The mesopore morphology can be transformed from spherical to cylindrical through introducing a shearing force during the interfacial co-assembly in the synthesis system. The designed LP-MMS microspheres turn out to be good carriers for enzyme (trypsin) immobilization with a high loading capacity of 80 µg/mg and demonstrate excellent biocatalysis efficiency up to 99.1% for protein digestion within 30 min and good recycling stability with negligible decay in digestion efficiency after reuse for five times.

Portal vein resection and reconstruction with artificial blood vessels is safe and feasible for pancreatic ductal adenocarcinoma patients with portal vein involvement: Chinese center experience.

Evidence shows that portal vein resection (PVR) increase the resectability but does little benefit to overall survival in all pancreatic ductal adenocarcinoma (PDAC) patients. But for patients with portal vein involvement, PVR is the only radical choice. But whether the PDAC patients with portal vein involvement would benefit from radical pancreaticoduodenectomy with PVR or not is controversial. All 204 PDAC patients with portal vein involvement were enrolled in this study [PVR group, n=106; surgical bypass (SB) group, n=52; chemotherapy group, n=46]. Overall survival and prognostic factors were analyzed among three groups. Moreover, a literature review of 13 studies were also conducted. Among 3 groups, patients in PVR group achieved a significant longer survival (median survival: PVR group, 22.83 months; SB group, 7.26 months; chemotherapy group, 10.64 months). Therapy choice [hazard ratio (HR) =1.593, 95% confidence interval (CI) 1.323 to 1.918, P<0.001], body mass index (HR=0.772, 95% CI 0.559 to 0.994, P=0.044) and carbohydrateantigen 19-9 (HR=1.325, 95% CI 1.064 to 1.651, P=0.012) were independent prognostic factors which significantly affected overall survival. Pancreaticoduodenectomy combined with PVR and reconstruct with artificial blood vessels is a safe and an appropriate therapy choice for resectable PDAC patients with portal vein involvement.

Nanoengineering of Core-Shell Magnetic Mesoporous Microspheres with Tunable Surface Roughness.

Functional core-shell mesoporous microspheres with integrated functions, controlled structure, and surface properties and morphologies have received increasing attention due to their excellent physicochemical properties. Herein, core-shell magnetic mesoporous materials with cauliflower-like morphology and tunable surface roughness have been synthesized through a kinetics-controlled interface co-assembly and deposition of mesostructured nanocomposites on Fe3O4@RF microspheres (RF refers to resorcinol formaldehyde resin). The obtained microspheres, synthesized via this interface nanoengineering method, possess well-defined sandwich structure with a tunable rough morphology, uniform size (560-1000 nm), perpendicularly aligned mesopores (∼5.7 nm) in the outer shell, RF-protected magnetic responsive core, high surface area up to 382 m2/g, and large pore volume of 0.66 cm3/g. As a result of the unique surface features and magnetic properties, these microspheres exhibit excellent performance in stabilizing and oxygen-free manipulating aqueous solutions in petroleum ether by a magnetic field. They also exhibit superior cell uptake properties compared with traditional smooth core-shell magnetic mesoporous silica microspheres, opening up the possible applications in fast drug delivery in cancer therapy.

Radical resection and enucleation in Chinese adolescents with pancreatic tumors: A 15-year case series.

Pancreatic tumors rarely occur in adolescents, and the appropriateness of radical resection for these patients remains controversial.Medical records were retrospectively reviewed for patients younger than 19 years who underwent radical resection or limited resection (enucleation) between 2000 and 2015. Patient demographics, clinical characteristics, operative details, growth, and survival were analyzed.During the study period, 11 adolescents (mean age, 16.18 years; standard deviation, 1.99; interquartile range, 15.0-18.0) underwent radical resection (n = 7) or enucleation (n = 4) to treat solid pseudopapillary tumors (n = 5), pancreatic neuroendocrine tumors (n = 5), or pancreatic ductal adenocarcinoma (n = 1). None of the 7 patients who underwent radical resection experienced recurrence or serious complications, while 3 of 4 patients who underwent enucleation experienced recurrence (P = 0.02). Recurrence-free survival was slightly longer in patients who underwent radical resection, and this procedure did not appear to affect adolescent growth and development.Radical resection might be safe and effective for adolescents with pancreatic tumors.

Reducing postoperative complications and improving clinical outcome: Enhanced recovery after surgery in pancreaticoduodenectomy - A retrospective cohort study.

BACKGROUND: An enhanced recovery after surgery (ERAS) programme aims to reduce the stress response to surgery and thereby accelerate recovery. The experience of implementing the ERAS programmes in pancreatoduodenectomy (PD) is relatively limited. The aim of this study was to evaluate the feasibility, safety and clinical outcomes of the ERAS programme after PD at a high-volume Chinese university referral centre. METHODS: Between September 2014 and July 2016, a retrospective analysis of 166 consecutive patients who underwent PD at a tertiary referral care center was carried out. Ninety-eight patients who received conventional perioperative management (the conventional group) were compared with 68 patients who received ERAS programme (the ERAS group). The incidences of postoperative complications, length of stay, expenses, postoperative readmissions, and reoperation rates were compared. RESULTS: A total of 166 patients who underwent PD were analysed (68 patients in the ERAS group, and 98 patients in the conventional group). There were no significant differences in mortality, reoperation, and readmission rates. The ERAS group had a lower morbidity rate than the conventional group (50% vs. 90.8%; P = 0.00), as well as a shorter length of hospital stay (7.5 vs 12 days; P = 0.00). Delayed gastric emptying was significantly reduced in the ERAS group (0 vs. 11.2%; P = 0.011). Pancreatic fistula (grade B,C) was significantly reduced in the ERAS group (14.7 vs 30.6%; P = 0.018). The median total hospital cost was also significantly reduced in the ERAS group (¥79790.40 vs ¥102982.81; P = 0.000). CONCLUSION: The ERAS programme is feasible and safe in patients who underwent PD, and it can reduce postoperative complications and improve clinical outcomes.

Magnetic mesoporous nanospheres anchored with LyP-1 as an efficient pancreatic cancer probe.

Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging. After systematic administration, these LyP-1 immobilized nanospheres are found to actively target to mouse orthotopic xenograft of pancreatic cancer, which opens up the door for applications in early probing and diagnosis of pancreatic cancer by the multimodal imaging.

The evolution of crop cultivation and paleoenvironment in the Longji Terraces, southern China: Organic geochemical evidence from paleosols.

The Longji ancient agricultural terraces in the Longji Mountain area (Guilin, southern China), which still remain in use, are famous for their magnificent terraced landscape with a mix of ecosystem and human inhabitation. Previous research has revealed the genesis and preliminary paleoenvironmental record of the agricultural terraces, but little is known about variations in crop cultivation over time. In this study, organic geochemical analyses and radiocarbon dating of an aggradational cultivated soil from a terrace profile were used to explore crop type variation and relevant paleoenvironmental change during the period of cultivation on the Longji Terraces. Hydroponic farming with rice (C3) planting has been the dominant cultivation mode since the initial construction of the terraces. Warm-dry climate contributed to the growth of drought-tolerant crop (C4) cultivation in the late 15th century. Temperature deterioration during the Little Ice Age had a negative impact on dry and hydroponic farming activities from the late 15th century to the late 19th century, while climate warming after the Little Ice Age promoted the redevelopment of hydroponic farming.