Patterns and correlates of potential range shifts of bat species in China in the context of climate change.

Climate change may diminish biodiversity; thus, it is urgent to predict how species' ranges may shift in the future by integrating multiple factors involving more taxa. Bats are particularly sensitive to climate change due to their high surface-to-volume ratio. However, few studies have considered geographic variables associated with roost availability and even fewer have linked the distributions of bats to their thermoregulation and energy regulation traits. We used species distribution models to predict the potential distributions of 12 bat species in China under current and future greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5) and examined factors that could affect species' range shifts, including climatic, geographic, habitat, and human activity variables and wing surface-to-mass ratio (S-MR). The results suggest that Ia io, Rhinolophus ferrumequinum, and Rhinolophus rex should be given the highest priority for conservation in future climate conservation strategies. Most species were predicted to move northward, except for I. io and R. rex, which moved southward. Temperature seasonality, distance to forest, and distance to karst or cave were the main environmental factors affecting the potential distributions of bats. We found significant relationships between S-MR and geographic distribution, current potential distribution, and future potential distribution in the 2050s. Our work highlights the importance of analyzing range shifts of species with multifactorial approaches, especially for species traits related to thermoregulation and energy regulation, to provide targeted conservation strategies.

Patrones y correlaciones de los cambios potenciales en la distribución de las especies de murciélago de China en el contexto del cambio climático Resumen El cambio climático puede disminuir la biodiversidad, por lo que es urgente pronosticar cómo puede cambiar en el futuro la distribución de las especies mediante la integración de múltiples factores que involucren a más taxones. Los murciélagos son particularmente sensibles al cambio climático debido a que tienen una gran proporción superficie­volumen. Sin embargo, hay pocos estudios que han considerado las variables asociadas con la disponibilidad de nidos y son todavía menos los que han conectado la distribución de los murciélagos con sus rasgos de termorregulación y regulación de energía. Usamos modelos de distribución de especies para pronosticar la distribución potencial de doce especies de murciélago en China bajo escenarios actuales y futuros de emisión de gases de efecto invernadero (SSP1­2.6 y SSP5­8.5) y analizamos los factores que podrían afectar el cambio en la distribución de las especies, incluyendo las variables climáticas, geográficas, de hábitat y de actividad humana y la proporción entre la superficie del ala y la masa (P S­M). Los resultados sugieren que Ia io, Rhinolophus ferrumequinum y R. rex deberían ser la mayor prioridad de conservación para las estrategias de conservación climáticas en el futuro. Pronosticamos que la mayoría de las especies se desplazarían al norte, a excepción de I. io y R. rex, que se desplazarían hacia el sur. Los principales factores que afectaron la distribución potencial de los murciélagos fueron la estacionalidad de la temperatura, la distancia al bosque y la distancia a la cueva o al karst. Encontramos una relación significativa entre la P S­M y la distribución geográfica, la distribución potencial actual y la distribución potencial para la década de 2050. Nuestra investigación destaca la importancia del análisis de los cambios de distribución de las especies con enfoques multifactoriales, especialmente para los rasgos de especie relacionados con la termorregulación y la regulación de energía, para proporcionar estrategias de conservación focalizadas.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

A chromosome-level genome assembly of an avivorous bat species (Nyctalus aviator).

Currently, three carnivorous bat species, namely Ia io, Nyctalus lasiopterus, and Nyctalus aviator, are known to actively prey on seasonal migratory birds (hereinafter referred to as "avivorous bats"). However, the absence of reference genomes impedes a thorough comprehension of the molecular adaptations of avivorous bat species. Herein, we present the high-quality chromosome-scale reference genome of N. aviator based on PacBio subreads, DNBSEQ short-reads and Hi-C sequencing data. The genome assembly size of N. aviator is 1.77 Gb, with a scaffold N50 of 102 Mb, of which 99.8% assembly was anchored into 21 pseudo-chromosomes. After masking 635.1 Mb repetitive sequences, a total of 19,412 protein-coding genes were identified, of which 99.3% were functionally annotated. The genome assembly and gene prediction reached 96.1% and 96.1% completeness of Benchmarking Universal Single-Copy Orthologs (BUSCO), respectively. This chromosome-level reference genome of N. aviator fills a gap in the existing information on the genomes of carnivorous bats, especially avivorous ones, and will be valuable for mechanism of adaptations to dietary niche expansion in bat species.

Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

A "turn-on" red cyclometalated iridium (III) complex for long-term tracking the diffusion of CORM-2 in cells and zebrafish.

Transition metal carbonyl compound of CO releasing molecules (CORMs) are widely used to treat arthritis, tumor and immune. They play a physiological role by directly acting on target tissues to release CO for disease treatment without matrix metabolism after dissolution. It is important to track the level and diffusion process of CORMs in vivo to control CO dose and distribution, facilitating to understand the roles of CORMs in disease treatment. Herein, we designed two red ring Ir1/2 complexes with a large stokes shift. Both Ir1 and Ir2 complexes probes can sensitively and selectively respond to CORM-2. The probe Ir1 exhibits rapid reaction with CORM-2 in Phosphate Buffered Saline within 1 min, showing a detection limitation of 0.13 µM and manifesting a linear relationship with the CORM-2 concentration from 0 to 70 µM at λem = 618 nm. Due to low toxicity even after 12 h exposure and fluorescence stability, this probe has been successfully used for continuous tracking the diffusion process of CORM-2 in living cells for up to 60 min and visualizing CORM-2 distribution in zebrafish. Additionally, this probe showed a good capacity for deep penetration (126 µm), suggesting the potential in detecting CORM-2 in living tissues.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients.

BACKGROUND: Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). METHODS: Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP's prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. RESULTS: Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages. CONCLUSION: The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Boric acid group-functional ruthenium complex as a novel fluorescence probe for robust detection of propyl gallate and tert-butyl hydroquinone by tuning the pH.

This study reported a ruthenium complex-based fluorescence probe, achieving rapid and sequential detection of propyl gallate (PG) and tert-butyl hydroquinone (TBHQ) for the first time by tuning pH only. Under 480 nm excitation, probe exhibited intensive emission at 620 nm, which was selectively quenched by PG at pH 7.0 due to the covalent binding between the boric acid of probe and o-diphenol hydroxyl of PG. Then pH was tuned to 7.4, the emission was significantly quenched by TBHQ because of the π-π stacking between aromatic rings of probe and paraquinone of TBHQ. This probe realized specific and sensitive detection of PG and TBHQ with wide range and low detection limit (0.26 µM for PG and 0.66 µM for TBHQ). Furthermore, a portable visual test paper detection platform was built based on this probe for rapid and sensitive detection of antioxidants in food, which was of great significance for market regulation.

Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

Preparation of functional material layers of TT-COFs with built-in formyl groups for efficient dyes removal.

There is no doubt that the wide application of COFs depends on the diversity and complexity of their structure and composition, as well as the feasibility and convenience of use. Herein, large area defect-free continuous functional material layers have been fabricated by compounding sub-stoichiometric tetratopic-tritopic covalent organic frameworks (TT-COFs) on graphene oxide (GO) via simply hot pressing. The one-step synthesis of TT-COFs with built-in formyl groups endowed the robust material layers with extraordinary host-guest interactions, so they can specifically reject cations dyes according to adsorption effect, molecular sieving and Donnan effect. Owing to the through-plane molecular transfer channels, large amounts of water molecules can pass through the internal channel rapidly. As a result, high rejection of 99.5% and large flux of 309.99 L·m-2·h-1·bar-1 for dye molecules have been realized. This simple and effective method provided more extensive practicality and greater convenience in recycling and reuse, and demonstrated the utility and high efficiency of TT-COFs with built-in formyl groups as an advanced material platform for dyes removal.

Consensus of Nonlinear Multiagent Systems With Grouping Via State-Constraint Impulsive Protocols.

In this article, the consensus problem of nonlinear multiagent systems with grouping via state-constraint impulsive protocols is investigated. Two types of cases with and without leader agent are studied by using two kinds of protocols. A judgement strategy is designed to decide to group in the nonlinear multiagent systems, and two kinds of state-constraint impulsive control protocols, which include partial state constraint and full state constraint, are proposed to make this system cut down the cost of communication and reduce irreversible damage to equipment. Then, based on the algebraic graph theory, the Lyapunov stability theory, and the matrix theory, some sufficient conditions are established to deal with the consensus problem in the nonlinear multiagent systems. The presented results can be used to solve the consensus problem in the nonlinear multiagent systems with grouping. Finally, some important simulations are presented to illustrate the feasibility of the theoretical results.

A Versatile Method for Functionalization of Covalent Organic Frameworks via Suzuki-Miyaura Cross-Coupling.

Post-synthetic modification (PSM) is a prevalent and powerful strategy to introduce desired functionalities into covalent organic frameworks (COFs) for functional products, expediting their applications vastly. Herein, we demonstrate a PSM strategy for functionalizing brominated COFs via the well-developed Suzuki-Miyaura cross-coupling. By this, a variety of functionalities were installed into COFs efficiently, while the crystallinity and porosity of COFs was well-retained. As a proof-of-concept, BrCOF-2 was modified with trifluoromethyl groups to produce a SF6 adsorbent with remarkably enhanced properties. This facile and versatile approach opens a new door for the synthesis of functional COFs, and greatly expands the scope of their structural design aiming for various properties and applications.

Ultrahigh Responsivity Photodetectors of 2D Covalent Organic Frameworks Integrated on Graphene.

2D materials exhibit superior properties in electronic and optoelectronic fields. The wide demand for high-performance optoelectronic devices promotes the exploration of diversified 2D materials. Recently, 2D covalent organic frameworks (COFs) have emerged as next-generation layered materials with predesigned π-electronic skeletons and highly ordered topological structures, which are promising for tailoring their optoelectronic properties. However, COFs are usually produced as solid powders due to anisotropic growth, making them unreliable to integrate into devices. Here, by selecting tetraphenylethylene monomers with photoelectric activity, elaborately designed photosensitive 2D-COFs with highly ordered donor-acceptor topologies are in situ synthesized on graphene, ultimately forming COF-graphene heterostructures. Ultrasensitive photodetectors are successfully fabricated with the COFETBC-TAPT -graphene heterostructure and exhibited an excellent overall performance with a photoresponsivity of ≈3.2 × 107 A W-1 at 473 nm and a time response of ≈1.14 ms. Moreover, due to the high surface area and the polarity selectivity of COFs, the photosensing properties of the photodetectors can be reversibly regulated by specific target molecules. The research provides new strategies for building advanced functional devices with programmable material structures and diversified regulation methods, paving the way for a generation of high-performance applications in optoelectronics and many other fields.

Lifetime-tunable room-temperature phosphorescence of polyaniline carbon dots in adjustable polymer matrices.

Despite the excellent room-temperature phosphorescence (RTP) property of carbon dot (CD)-based RTP composites, the development of these emerging materials with finely tunable afterglow lifetimes still remains a challenge. Herein, for the first time, we report a series of pure organic RTP composite materials based on adjustable polyaniline carbon dots (PACDs) and polymer matrices (polyacrylic acid, polyacrylamide, and polyvinyl alcohol) with tunable RTP lifetimes. By using different polymer matrices and adjusting the functional groups of PACDs, the strength of hydrogen bonding between each polymer matrix and PACDs was regulated, and green RTP emissions with a tunable average lifetime ranging from 184 ms to 652 ms were also realized. In addition, taking advantage of their different persistent afterglow lifetimes, naked-eye-observable and time-resolved anti-counterfeit and data encryption patterns were prepared using these PACDs/polymer composites, demonstrating the potential application of these materials.

Noninvasive and real-time pharmacokinetics imaging of polymeric nanoagents in the thoracoepigastric vein networks of living mice.

Noninvasive and real-time visualization of the thoracoepigastric veins (TVs) of living mice was demonstrated by using two-photon excitation (TPE) optical imaging with a Eu-luminescent polymeric nanoagent as the angiographic contrast. The spatiotemporal evolution of the polymeric nanoagent in TVs was monitored for up to 2 h by TPE time-resolved (TPE-TR) bioimaging, which is free from the interference of tissue autofluorescence. A wide field-of-view covering the thoracoabdominal region allowed the visualization of the entire TV network with an imaging depth of 1 to 2 mm and a lateral resolution of 80 µm at submillimeter. Detailed analysis of the uptake, transport, and clearance processes of the polymeric nanoagent revealed a clearance time constant of ∼30 min and an apparent clearance efficiency of 80% to 90% for the nanoagent in both axial and lateral TVs. TPE-TR imaging of the dissected internal organs proved that the liver is mainly responsible for the sequestration of the nanoagent, which is consistent with the apparent retention efficiency of liver, ∼32 % , as determined by the real-time in vivo TV imaging. We demonstrate the potency of TPE-TR modality in the pharmacokinetics imaging of the peripheral vascular systems of animal models, which can be beneficial for related nanotheranostics study.

Excitation Energy-Transfer Processes in the Sensitization Luminescence of Europium in a Highly Luminescent Complex.

The excitation energy transfer (EET) pathways in the sensitization luminescence of EuIII and the excitation energy migration between the different ligands in [Eu(fod)3dpbt] [where fod=6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione and dpbt=2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine], exhibiting well-separated fluorescence excitation and phosphorescence bands of the different ligands, were investigated by using time-resolved luminescence spectroscopy for the first time. The data clearly revealed that upon the excitation of dpbt, the sensitization luminescence of EuIII in [Eu(fod)3dpbt] was dominated by the singlet EET pathway, whereas the triplet EET pathway involving T1(dpbt) was inefficient. The energy migration from T1(dpbt) to T1(fod) in [Eu(fod)3dpbt] was not observed. Moreover, upon the excitation of fod, a singlet EET pathway for the sensitization of EuIII luminescence, including the energy migration from S1(fod) to S1(dpbt) was revealed, in addition to the triplet EET pathway involving T1(fod). Under the excitation of dpbt at 410 nm, [Eu(fod)3dpbt] exhibited an absolute quantum yield for EuIII luminescence of 0.59 at 298 K. This work provides a solid and elegant example for the concept that singlet EET pathway could dominate the sensitization luminescence of EuIII in some complexes.

Wide field of view, real time bioimaging apparatus for noninvasive analysis of nanocarrier pharmacokinetics in living model animals.

Understanding nanocarrier pharmacokinetics is crucial for the emerging nanopharmacy, which highly demands noninvasive and real-time visualization of the in vivo dynamics of nanocarriers. To this end, we have developed a 2-photon excitation and time-resolved (TPE-TR) bioimaging apparatus for the analysis of the spatial distribution and temporal evolution of nanocarriers in living model animals. The specific polymeric nanocarrier, Eu@pmma-maa doped with Eu-complexes luminescing in long persistence at ∼615 nm upon near-infrared 2-photon excitation, allows the complete rejection of tissue autofluorescence by selective luminescence detection. This together with a unique beam shaping scheme for homogeneous line excitation, a delicate timing strategy for single-shot line scanning, and an equal optical path design for in-plane scan endows the TPE-TR apparatus with the following prominent features: an imaging depth of ∼10 mm, a field of view (FOV) of 32 × 32 mm2 along with a horizontal resolution of ∼60 µm, a sub-10 s frame time, and negligible laser heating effect. In addition, a combination of the in-plane line scan with the 3D scan of a model animal offers the convenience for examining an interested FOV with a millimeter vertical resolution. Application of TPE-TR bioimaging to a living mouse reveals rich information on the dynamics of nanocarriers including the spatial distribution and temporal evolution and the kinetics of domains of interest. The noninvasive TPE-TR bioimaging instrumentation with a wide FOV and a large imaging depth will find applications in the pharmaceutical development of nanocarriers and relevant research fields.

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma Through PEBP1.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a major threat to human health. The condition carries a high risk of death; 45% of new cases occur in China. Surgical resection is the first choice for treatment of HCC, but 30.9% of patients experience recurrence within 6 months after the operation. To improve patient survival, we must determine how to reduce the probability of recurrence and metastasis and elucidate the underlying mechanism of disease. We therefore studied the effect of somatostatin octapeptide (octreotide) on the invasion and metastasis of HCC. METHODS: The migration and invasion cytological tests were used to detect the effect of octreotide on liver cancer cells (SK-Hep-1 and HepG2). PEBP1 RNAi was used to knockdown expression. Invasion and metastasis were measured with transwell migration and wound-healing assays. Western blotting was used to detect changes in levels of PEBP1 and invasion pathway proteins after octreotide treatment. The effect of octreotide was studied in vivo by establishing a pulmonary metastasis model using SK-Hep-1 cells in nude mice. In-vivo bioluminescence imaging and hematoxylin and eosin staining of lung tissue were used to verify the results. RESULTS: Increasing concentrations of octreotide were progressively more effective in halting the invasion and metastasis of liver cancer cells. Octreotide may upregulate PEBP1, TIMP-2, and E-cadherin while downregulating MMP-2 and Twist to inhibit cell invasion and metastasis. And downregulation of PEBP1 would also change the expression of MMP-2, TIMP-2 and Twist. The in-vivo experiments showed no cancer cell metastasis in 4 of the 6 mice in the octreotide-treatment group, while all of the mice in the control group displayed pulmonary metastasis of human HCC cells. And the survival period of the mice in the octreotide-treatment group was significantly prolonged. CONCLUSIONS: Octreotide may weaken invasion and metastasis through the upregulation of PEBP1. Octreotide may reduce the risk of recurrence and metastasis after surgery for liver cancer.

Secondary structure-induced aggregation by hydrogen peroxide: a stimuli-triggered open/close implementation by recombination.

The fabrication of reactive aggregation nanomaterials through assemblies in a facile and cost-effective manner is much desired but remains to be well explored. Here we show that exquisite and ultra-long (>2 µm) hybrid polymer nanorods (NRs) can be formed by a simple self-assembly of a phenylboronic acid modified genistein crosslinker (Ge-di(HMPBA-pin)) and d-α-tocopheryl polyethylene glycol 1000 (TPGS). The obtained NRs exhibit quantitative and sensitive colorimetric detection of H2O2 with a remarkable detection limit for different stromal materials. More significantly, the presence of H2O2 triggers a distinct morphological transformation of the polymer NR assembly into the secondary structure of micelles via the oxidative deboronation of boronate moieties in HMPBA-pin-SA. It spontaneously induces the aggregation of metal nanoparticles (Au NPs), metal nanorods (Au NRs), quantum dots (MoS2 QDs), metal ions (Cu2+), protein (ferritin) and tetraphenylethene (TPE) molecules, giving rise to a dramatic stimuli-triggered open/close switchable complexation and apparent colorimetric transitions in vitro. This study, for the first time, showcases the fascinating advantages of such unprecedented secondary structure-induced aggregation and uncovers the immense potential to design a plethora of other sensing systems by virtue of the alternate trigger-specific, sacrifice-aggregated building moieties.

[The effect of different hepatic vascular exclusion for massive hemorrhage in hepatectomy].

OBJECTIVE: To analyze the effect of different hepatic vascular exclusions for massive hemorrhage in hepatectomy. METHODS: The clinical data of 2238 cases with hepatectomy treated from January 1995 to August 2009 was analyzed retrospectively in the cause of massive hemorrhage (blood loss ≥ 1000 ml), blood loss during liver resection and massive hemorrhage incidence with different methods of hepatic vascular exclusion. RESULTS: Among 2238 cases received hepatectomy, 215 cases (9.6%) had massive hemorrhage because of portal vein tumor thrombus extraction (26.0%), extensive adhesions around the tumor (24.7%), section of liver hemorrhage (23.7%), hepatic vascular injury (15.8%), and tumor rupture (9.8%). Among 2182 cases received hepatectomy without portal vein tumor thrombus extraction, 159 cases (7.3%) had massive hemorrhage, 1257 cases (57.6%) which blood loss were less than 400 ml. Hepatectomy with different hepatic vascular exclusion methods had different blood loss and massive hemorrhage incidence. CONCLUSION: Pringle combined with clamping infrahepatic vena cava method and the liver double-hanging maneuver through the retrohepatic avascular tunnel on the right of the inferior vena cava method can reduce blood loss and massive hemorrhage incidence in hepatectomy more effectively, especially for huge liver tumor resection.