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Luminescent CdSe-ZnS quantum dots (QDs) were modified with bovine serum albumin (BSA) and used as selective copper ion probe. The fluorescence of the water-soluble QDs can be quenched only by Cu2+ and Fe3+ in physiological buffer solution. Approximate concentrations of other physiologically important cations, such as Zn2+, Na+ and K+ etc. have no effect on the fluorescence. Adding F- to form the colorless complex FeF63- can eliminate the interference of Fe3+. The detection limit of Cu2+ ions was 10nM. The results can be explained in terms of strong binding of Cu2+ onto the surface of CdSe resulting in a chemical displacement of Cd2+ ions and the formation of CuSe on the surface of the QDs. [Copyright &y& Elsevier]

Monitoring the highly dynamic and complex immune response remains a great challenge owing to the lack of reliable and specific approaches. Here, we develop a strategy to monitor the cascade of tumor immune response through the cooperation of pore‐forming alginate gel with chemoenzymatic proximity‐labeling. A macroporous gel containing tumor‐associated antigens, adjuvants, and pro‐inflammatory cytokines is utilized to recruit endogenous DCs and enhance their maturation in vivo. The mature DCs are then modified with GDP‐fucose‐fucosyltransferase (GDP‐Fuc‐Fuct) via the self‐catalysis of fucosyltransferase (Fuct). Following the migration of the obtained Fuct‐DCs to the draining lymph nodes (dLNs), the molecular recognition mediated interaction of DCs and T cells leads to the successful decoration of T cells with GDP‐Fuc‐azide through the Fuct catalyzed proximity‐labeling. Therefore, the activated tumor‐specific T cells in dLNs and tumors can be identified through bioorthogonal labeling, opening up a new avenue for studying the immune mechanism of tumors in situ. [ABSTRACT FROM AUTHOR]

The responses of patients to tumor therapies vary due to tumor heterogeneity. Tumor stratification has been attracting increasing attention for accurately distinguishing between responders to treatment and non-responders. Nanoprobes with unique physical and chemical properties have great potential for patient stratification. This review begins by describing the features and design principles of nanoprobes that can visualize specific cell types and biomarkers and release inflammatory factors during or before tumor treatment. Then, we focus on the recent advancements in using nanoprobes to stratify various therapeutic modalities, including chemotherapy, radiotherapy (RT), photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), ferroptosis, and immunotherapy. The main challenges and perspectives of nanoprobes in cancer stratification are also discussed to facilitate probe development and clinical applications. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to examine the association between maternal oseltamivir treatment for influenza and infant outcomes during the 2009 HINI influenza pandemic. Study Design: This was a retrospective cohort study using a population-based maternal newborn database including women who gave birth to a singleton infant in the Canadian province of Ontario from November 2009 through April 2010. Risks of small for gestational age (SGA) (10th percentile and 3rd percentile), preterm birth (<37 weeks of gestation), very preterm birth (<32 weeks of gestation), and 5-minute Apgar score <7 associated with maternal exposure to oseltamivir were analyzed by multivariable regression. Results: A total of 55,355 women with a singleton birth were included in this study. Among them, 1237 (2.2%) women received oseltamivir for treatment or prevention of influenza during pregnancy. Women who took oseltamivir during pregnancy were less likely to have a SGA infant based on the 10th percentile for growth (adjusted risk ratio, 0.77; 95% confidence interval, 0.60–0.98). No association between maternal use of oseltamivir with SGA on 3rd percentile, preterm birth, very preterm birth, and low Apgar score was observed. Conclusion: There is no evidence of an association between maternal use of oseltamivir for influenza and early birth, low Apgar at birth, and poor fetal growth. [Copyright &y& Elsevier]

Oncolytic viruses hold great promise for cancer treatment but their practical applications are seriously impaired by a series of limitations. Herein, an engineered oncolytic adenovirus (OA) is constructed that can boost both the direct oncolysis and antitumor immune response of OA attributed to the increased tumor targeting and low‐pH responsive fusogenic activity. The tumor cell membranes are decorated with vesicular stomatitis virus glycoprotein (VSVG) via vesicular stomatitis virus (VSV) infection and then used to mask OA (V‐M@OA). After systemic administration, the engineered OA can target homologous tumors owing to the homing ability of tumor membranes. Then the unique low‐pH responsive fusogenic activity of VSVG significantly enhances the replication of OA by promoting the whole virus infection process, resulting in remarkable virus‐mediated tumoricidal effects and thus abundant in situ released tumor‐associated antigens (TAAs). Meanwhile, VSVG on V‐M@OA augments the adjuvanticity of OA and thus significantly enhancing the antitumor immune response. The synergism of virus‐mediated killing and immune effects leads to significant tumor inhibition with no obvious side effects. [ABSTRACT FROM AUTHOR]

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5‐aminolevulinate hydrochloride (HAL) and 3‐bromopyruvic acid (3BP) into microparticles collected from X‐ray‐irradiated tumor cells (X‐MP). After systemic administration, the developed HAL/3BP@X‐MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co‐localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes. [ABSTRACT FROM AUTHOR]

We have numerically studied the evolution of heavy ions that expand in a cold background plasma at a large scale. Two typical collective behaviors of the heavy ions are identified with the conditions where only the traversing heavy ions' initial total mass is different. Our work has demonstrated that a difference in the initial total mass of the moving heavy ions is able to induce completely different collective behaviors of the plasma. The simulation is performed via the hybrid model in which the ions and electrons are treated as classical particles and mass-less fluids, respectively. Due to the imbalance of the electric and magnetic force on the heavy ions, these particles will evolve into different collective patterns eventually. These patterns manifest a rather different stopping behavior of the moving ions and an opposite drifting direction of the electron fluid at the rim of the expanding plasma. Further numerical and analytical calculations show that the imbalance depends not only on the number densities of the plasma ions but also on the spatial variations of the magnetic fields. Our work reveals that the collective behavior of the heavy ions is highly non-linear, and the non-linearity is able to induce different phenomena in the evolution of the system at a large scale. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value. Materials and Methods: The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan–Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model. Results: CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls (P < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage (P = 0.039) and distant metastasis (P = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels (P = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS. Conclusion: Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

As natural adjuvants, the bacterial outer membrane vesicles (OMV) hold great potential in cancer vaccines. However, the inherent immunotoxicity of OMV and the rarity of tumor-specific antigens seriously hamper the clinical translation of OMV-based cancer vaccines. Herein, metal-phenolic networks (MPNs) are used to attenuate the toxicity of OMV, meanwhile, provide tumor antigens via the chemodynamic effect induced immunogenic cell death (ICD). Specifically, MPNs are assembled on the OMV surface through the coordination reaction between ferric ions and tannic acid. The iron-based "prison" is locally collapsed in the tumor microenvironment (TME) with both low pH and high ATP features, and thus the systemic toxicity of OMV is significantly attenuated. The released ferric ions in TME promote the ICD of cancer cells through Fenton reaction and then the generation of abundant tumor antigens, which can be used to fabricate in-situ vaccines by converging with OMV. Together with the immunomodulatory effect of OMV, potent tumor repression on a bilateral tumor model is achieved with good biosafety. • Metal-phenolic network is first used for not only attenuating the toxicity of OMV but also fabricating in situ vaccines. • The smart synergism of in situ vaccines with TME reprogramming leads to robust tumor repression and immunological memory. • This convenient and reliable engineering strategy can be popularized in the construction of different bioactive formulations. [ABSTRACT FROM AUTHOR]

Oncolytic virotherapy is one of promising tumor therapy modalities. However, its therapeutic efficacy is still limited due to the immunogenicity and poor tumor-targeting capability. In this report, an engineered oncolytic vaccinia virus (OVV) was constructed by site-specifically introducing azide groups to the envelope of OVV during the in situ assembling process of virions. Subsequently, dibenzocyclooctynes (DBCO) derivate T7 peptide and DBCO derivate self-peptide were simultaneously conjugated to the azide-modified OVV (azide-OVV) via copper-free click chemistry. The infectivity of peptide-conjugated virus was well kept. Meanwhile, both of the targeting capacity to transferrin receptor (TfR)-overexpressed tumor cells and the in vivo blood circulation time increased. Therefore, the growth of TfR-positive tumor could be significantly inhibited after intravenously injecting the engineered OVV, while no noticeable side effects. This construction strategy can be popularized to other enveloped oncolytic virus (OV), thus a universal engineering platform can be provided for OV cancer therapy.An engineered oncolytic vaccinia virus (OVV) was constructed by bioconjugating DBCO derivate T7 peptide and DBCO derivate self-peptide with azide-modified OVV via copper-free click chemistry. As a result, the tumor inhibit effect was significantly enhanced attributed to the prolonged in vivo circulation time and improved targeting recognition capability. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: For thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years. Objectives: Mutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti‐EGFR therapies. Methods: Genomic DNA was extracted from 61 histological samples of TCs. Real‐time polymerase chain reaction (PCR) and direct sequencing were used to assess the mutations in the EGFR downstream pathway. Results: Gene mutations were identified in seven patients (11.5%). In particular, the identified mutations included four mutations in the KRAS gene, one mutation in the BRAF gene, one mutation in the PIK3CA gene, and only one mutation in the EGFR gene itself. Gene mutations in the EGFR downstream pathway were associated with shorter survival time and were observed to be an independent prognostic factor for TC patients. Conclusion: Mutations in the EGFR downstream pathway are not rare in TCs. These data offer interesting possibilities for the future management of TCs, particularly in the era of new targeted therapies. [ABSTRACT FROM AUTHOR]

There is strong evidence of roles of the hypothalamus-pituitary-adrenal axis and nitric oxide ( NO) synthase- NO system in depression, but the relationship between them is unknown. The aim of this study, therefore, was to elucidate whether there is any correlation between NO and corticotropin-releasing hormone ( CRH) in major depressive disorder ( MDD) patients. In 16 outpatients with MDD and 18 healthy controls, the plasma amino acids citrulline (Cit) and arginine (Arg) were determined by high-performance liquid chromatography, and CRH levels was measured by radioimmunoassay. The Cit/Arg ratio was calculated as an index of NO synthesis. Correlations between NO and CRH were examined with the Spearman test. Before treatment, no significant correlation was observed between the plasma NO level and CRH levels in MDD patients. The plasma NO levels were significantly higher in MDD patients. A significant correlation was found between NO levels and Hamilton Depression Rating Scale ( HAMD) scores in MDD patients. The plasma CRH levels were significantly higher in MDD patients than in controls. After monotherapy for 2 months, the NO levels had dramatically declined but were also higher than those in the controls. This study is the first report of the absence of a significant correlation between plasma NO and CRH levels, although both levels are elevated in MDD patients. Furthermore, the strong links between the plasma NO levels and the HAMD scores, as well as the increased NO reduction after remission, suggest that NO plays a key role in depression and may be an indicator of therapeutic success. [ABSTRACT FROM AUTHOR]

PSA is a member of low abundance proteins and serves as a critical indicator of the development and therapy efficacy for prostate cancer. In this study, a facile and high sensitive method was developed for serum PSA detection by integrating the immunomagnetic separation and cation exchange based signal amplification. On the basis of nanoparticle preparation and immunoprobe construction, PSA in serum was captured, separated by the immunomagnetic probe and then interacted with the quantum dots (QDs) based immunofluorescence probe; Zn 2+ inside QDs was replaced by Ag + within seconds, after which fluorescence signal was amplified by Fluozin-3, the Zn 2+ responsive dye. Under optimized conditions, low detection limit (1.56 pg/mL), wide linear range (1.56–25 ng/mL) and good repeatability (intra-coefficient variation=3.18%) were achieved, which is superior to commercialized ELISA kit. These results demonstrated the potential of our high sensitive method for PSA detection in clinical. [ABSTRACT FROM AUTHOR]

Natural killer cells (NKs) hold great promise in cancer treatment, but their application in solid tumors remains a great challenge because current solutions hardly can overcome various difficulties that faced. Herein, we endow NKs with the phytochemical feature for effective immunotherapy of solid tumors. NKs are decorated with natural thylakoid (Tk) membranes through an efficient and convenient membrane fusion strategy. Tk engineering effectively activates NKs, because the antioxidase on Tk induce glycogen synthase kinase-3β inhibition, and subsequently increase the expression of activating receptor and cytotoxic effector molecules in NKs. After systemic administration, the phytochemical NKs (PC-NKs) can target tumor tissues, and then profoundly reprogram tumor microenvironment (TME) with the help of catalase on Tk, resulting in significantly enhanced direct killing of PC-NKs and immune activated TME. Therefore, potent therapeutic effects with few abnormalities are achieved, providing a novel idea for the development of highly efficient NKs for solid tumors. [ABSTRACT FROM AUTHOR]

Abstract: Due to the high importance of detecting DNA with both fast speed and high sensitivity, we proposed a new dsDNA detection method relying on a novel single-color fluorescence “off–on” switch system. Water-soluble glutathione capped CdTe QDs (emission at 605nm) was prepared for taking advantage of the readily tunable emission property of QDs. Initially, QDs was completely quenched by the Ru(phen)2(dppz)2+, as the spontaneous formation of QDs-Ru assembling dyads. Then, in the case of the addition of dsDNA, the Ru(phen)2(dppz)2+ was removed away from the CdTe QDs, producing free CdTe QDs and the Ru-dsDNA complex. Both of them could be excited at the same wavelength and emit overlaid fluorescence. This single-color fluorescence “off–on” signal was sensitive to the concentration of dsDNA. Native dsDNA with the concentration of 10pg/mL could be detected when 0.5nM CdTe QDs was used, and ssDNA, RNA or BSA had no interference on it. With this system, the dsDNA samples of hepatitis B virus (HBV) patients were tested. The results were in good agreement with those detected by fluorescence quantitative PCR (P>0.05), and for those samples with very low DNA concentrations, this system could provide more accurate results, demonstrating the possible clinical applicability of this “off–on” switch system. For this system, chemical conjugation or labeling of probes is not required, and unmodified native DNA targets could be detected in less than half an hour. Therefore, a simple, fast, sensitive, low cost, highly selective and practically applicable detection system for dsDNA has been described. [Copyright &y& Elsevier]

The sialic acid (SA)-phenylboronic acid (PBA) recognition system is of particular interest in the bioconjugation field, because it is simple, fast, efficient, and biocompatible. In this paper, we report a novel method for reversibly labeling living virus with quantum dots (QDs) by taking advantage of this SA-PBA recognition system. The QDs were initially modified with PBA (QDs-PBA) to target them to the surface of vesicular stomatitis virus (VSV), which has abundant with SA on its envelope. The QDs-PBA was of good monodispersity and strong fluorescence, and could be conjugated with VSV by simply incubating with native VSV for 10 min at 37 °C, producing QDs-VSV that was capable of being imaged at the single virion level. The labeling efficiency attained 83 ± 4.3 % (mean ± SD); meanwhile, the activity and recognition ability of the labeled virus were minimally affected. This method was simple, rapid, and reversible. This work promotes the virus labeling development to a new step. That is, native viruses can be reversibly labeled without any modification. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Accurate and rapid recognition and separation of multiple types of biological targets such as molecules, cells, bacteria or viruses from complex sample mixtures is of great importance for a wide range of diagnostic and therapeutic strategies. To achieve this goal, a set of fluorescent, magnetic, dual-encoded multifunctional bioprobes has been constructed by co-embedding different-sized quantum dots and varying amounts of γ-Fe2O3 magnetic nanoparticles into swollen poly(styrene/acrylamide) copolymer nanospheres. The dual-encoded bioprobes, which possessed different photoluminescent property and magnetic susceptibility, were proven to be capable of simultaneously recognizing and separating multiple components from a complex sample when three kinds of lectins were used as the targets. The lectins were separated with high efficiency and kept their bioactivity during the process. Compared to the conventional batchwise separation, this method does not require a large number of sequential reaction steps, which is economical of time and can be very reagent-saving. By combining the multiplexing capability of quantum dots with the superparamagnetic properties of iron oxide nanoparticles, this dual-encoded technique is expected to open new opportunities in high-throughput and multiplex bioassays, such as cell sorting, proteomical and genomical applications, drug screening etc. [ABSTRACT FROM AUTHOR]

Abstract: Fluorophore-labeled bioprobes are the key for fluorescent-labeled imaging technology. In the present work, mouse liver hepatoma cell line BNL 1ME A.7R.1 (MEAR)-specific ssDNA aptamer TLS9a was used to fabricate quantum dot-labeled aptamer bioprobe (QD-Apt), which was obtained by conjugating streptavidin-modified quantum dots (SA-QDs) with biotin-derived aptamer via the interaction between biotin and streptavidin. The QD-Apt was of monodispersity and excellent fluorescence properties. When the optimum ratio of SA-QDs to aptamer, which is 1:16, was used in the preparation of the QD-Apt, the resultant QD-Apt was of satisfactory bioactivity. They could specifically recognize MEAR cells and could not recognize BNL cells and Hela cells. Particularly, the growth and viability of QD-Apt bound MEAR cells were not affected by QD-Apt within 84h compared to control cells, indicating that the probe was biocompatible and suitable for live cell imaging. [Copyright &y& Elsevier]

Abstract: Nanomaterial-based nanobiosensors (nanobiodevices or nanobioprobes) are increasingly emphasized. Here, quantum dots and γ-Fe2O3 magnetic nanoparticles were co-embedded into single swelling poly(styrene/acrylamide) copolymer nanospheres to fabricate fluorescent-magnetic bifunctional nanospheres. Subsequently, fluorescent-magnetic-biotargeting trifunctional nanobiosensors (TFNS) modified with wheat germ agglutinin (WGA), peanut agglutinin (PNA) or Dolichos biflorus agglutinin (DBA) were conveniently produced so as to bind with A549 cells which are surface-expressed with N-acetylglucosamine, d-galactosamine and N-acetylgalactosamine residues. The values of WGA, PNA and DBA on each nanobiosensor were calculated to be 40, 14 and 60, respectively. These three kinds of lectin-modified trifunctional nanobiosensors (lectin-TFNS) can be used for qualitative and quantitative analysis of the glycoconjugates on A549 cell surface. The fluorescence intensity of WGA-modified nanobiosensors related to N-acetylglucosamine on A549 cell surface was much higher than that of PNA-modified nanobiosensors corresponding to d-galactosamine and that of N-acetylgalactosamine-related DBA-modified nanobiosensors, which is consistent with the results detected by flow cytometry. Lectin-modified trifunctional nanobiosensors not only can quantify the different glycoconjugates on A549 cell surface, but also can recognize and isolate A549 cells. 0.5mg of WGA-modified fluorescent-magnetic trifunctional nanobiosensors could capture 7.0×104 A549 cells. Therefore, the lectin-modified trifunctional nanobiosensors may be applied in mapping the glycoconjugates on cell surfaces and for recognition and isolation of targeted cells. [Copyright &y& Elsevier]

Atherosclerosis, as a silent killer, remains one of the most common causes of human morbidity and mortality worldwide due to the lack of efficient strategy for early detection and targeted therapy. In this work, a self-driven bioinspired nanovehicle is developed, which can accurately manage early atherosclerosis with simultaneously multiple-targeting, dual-modality therapy as well as noninvasive magnetic resonance imaging (MRI). The magnetic nanoclusters (MNCs) with satisfactory superparamagnetism are camouflaged with leukocyte membranes, thus acquiring inherently targeting and transmigrating capabilities to intimal foam cells in early atherosclerotic lesions, which is validated using tailor-made microfluidic devices and transwell assays. Upon sequentially embedding an anti-inflammatory drug simvastatin (ST) and decorating a targetable apolipoprotein A-I mimetic 4F peptide (AP), the as-fabricated MNC@M-ST/AP exhibits excellent anti-atherosclerotic effects by alleviating inflammation and oxidative stress as well as promoting cholesterol efflux via RCT pathways. This bioinspired leukocyte membrane-hitchhiking strategy will open new perspectives for the future clinical translations of biocompatible nanosystem in early detection and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population., Methods: The translation and cross-cultural adaptation of SARC-F into Chinese were conducted following the methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. The Chinese version of SARC-F was validated through a diagnostic test, using diagnostic criteria of sarcopenia recommended by the revised 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, Asian Working Group for Sarcopenia (AWGS2019) consensus, the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium and the Sarcopenia Definition and Outcomes Consortium (SDOC). Additional analysis was done against the criteria of severe sarcopenia according to the revised EWGSOP2 and AWGS2019., Results: The Chinese version of SARC-F was well translated and demonstrated good reliability and acceptability. The diagnostic test included 1859 community-dwelling older individuals from two medical centers. Against five different definitions of sarcopenia, the Chinese version of SARC-F showed reasonable diagnostic accuracy for sarcopenia screening (AUC 0.614-0.821), and was demonstrated low sensitivity (13.7-37.9%) but high specificity (94.8-97.7%) with a cut-off value of ≥ 4. SARC-CalF significantly enhanced the diagnostic accuracy of SARC-F when using definitions of EWGSOP2, AWGS2019 and IWGS (all P ≤ 0.001). A score of ≥ 2 for SARC-F and ≥ 7 for SARC-CalF were established as optimal cut-off points for identifying older individuals as at risk of sarcopenia in Chinese population., Conclusions: The Chinese version SARC-F is of reasonable reliability and validity for sarcopenia screening. Despite its low sensitivity, it proves to be a useful tool to identify severe cases in community taking advantage of its simplicity. SARC-CalF appears to be a more suitable screening tool for clinical use in detecting sarcopenia., (© 2024. The Author(s).)

Monitoring the effector function of cytotoxic T lymphocytes (CTLs) in vivo remains a great challenge. Here, we develop a chemistry-enabled enzymatic labeling approach to evaluate the tumor-specific immune response of CTLs by precisely monitoring the interaction between CTLs and tumor cells. Staphylococcus aureus sortase A (SrtA) is linked to the CTL surface through bioconjugate chemistry and then catalyzes the transfer of fluorescent-labeled substrate, 5-Tamra-LPETG, to CTLs. Meanwhile, the tumor cells are specifically decorated with N-terminal glycine residues (G 5 peptide) through the inherent glycolmetabolism of cathepsin B-specific cleavable triacetylated N -azidoacetyl-d-mannosamine (CB-Ac 3 ManNAz) and click chemistry. After the infiltration of engineered CTLs into the tumor tissues, the immune-synapse-mediated specific interaction of CTLs and tumor cells leads to the accurate fluorescent labeling of tumor cells through the SrtA-catalyzed 5-Tamra-LPETG transfer. Therefore, the immune effect of CTLs as well as the performance of immune drugs can be determined, providing a novel strategy for pushing ahead immunotherapy.

Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, and limited tumor accumulation. Hence, engineering modification of NDSs aiming at promoting tumor-specific therapy and avoiding systemic toxicity is usually needed. An NDS integrating various functionalities, including flexible camouflage, specific biorecognition, and sensitive stimuli-responsiveness, into one sequence would be "smart" and highly effective. Herein, we systematically summarize the related principles, methods, and progress. At the end of the review, we predict the obstacles to precise nanoengineering and prospects for the future application of NDSs., (© 2024 Wiley-VCH GmbH.)

Background and Objectives: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference., Methods and Study Design: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China., Results: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%., Conclusions: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population., Competing Interests: The authors declare no personal or financial conflicts of interest

Organic near-infrared room temperature phosphorescence (RTP) materials offer remarkable advantages in bioimaging due to their characteristic time scales and background noise elimination. However, developing near-infrared RTP materials for deep tissue imaging still faces challenges since the small band gap may increase the non-radiative decay, resulting in weak emission and short phosphorescence lifetime. In this study, fused-ring pyrrole-based structures were employed as the guest molecules for the construction of long wavelength emissive RTP materials. Compared to the decrease of the singlet energy level, the triplet energy level showed a more effectively decrease with the increase of the conjugation of the substituent groups. Moreover, the sufficient conjugation of fused ring structures in the guest molecule suppresses the non-radiative decay of triplet excitons. Therefore, a near-infrared RTP material (764 nm) was achieved for deep penetration bioimaging. Tumor cell membrane is used to coat RTP nanoparticles (NPs) to avoid decreasing the RTP performance compared to traditional coating by amphiphilic surfactants. RTP NPs with tumor-targeting properties show favorable phosphorescent properties, superior stability, and excellent biocompatibility. These NPs are applied for time-resolved luminescence imaging to eliminate background interference with excellent tissue penetration. This study provides a practical solution to prepare long-wavelength and long-lifetime organic RTP materials and their applications in bioimaging., (© 2023 Wiley-VCH GmbH.)

Coronavirus disease 2019 (COVID-19) continues to threaten human health, economic development, and national security. Although many vaccines and drugs have been explored to fight against the major pandemic, their efficacy and safety still need to be improved. Cell-based biomaterials, especially living cells, extracellular vesicles, and cell membranes, offer great potential in preventing and treating COVID-19 owing to their versatility and unique biological functions. In this review, the characteristics and functions of cell-based biomaterials and their biological applications in COVID-19 prevention and therapy are described. First the pathological features of COVID-19 are summarized, providing enlightenment on how to fight against COVID-19. Next, the classification, organization structure, characteristics, and functions of cell-based biomaterials are focused on. Finally, the progress of cell-based biomaterials in overcoming COVID-19 in different aspects, including the prevention of viral infection, inhibition of viral proliferation, anti-inflammation, tissue repair, and alleviation of lymphopenia are comprehensively described. At the end of this review, a look forward to the challenges of this aspect is presented., (© 2023 Wiley-VCH GmbH.)

The intrinsic features and functions of platelets and mesenchymal stem cells (MSCs) indicate their great potential in the treatment of intracerebral hemorrhage (ICH). However, neither of them can completely overcome ICH because of the stealth process and the complex pathology of ICH. Here, we fabricate hybrid cells for versatile and highly efficient ICH therapy by fusing MSCs with platelets and loading with lysophosphatidic acid-modified PbS quantum dots (LPA-QDs). The obtained LPA-QDs@FCs (FCs = fusion cells) not only inherit the capabilities of both platelets and MSCs but also exhibit clearly enhanced proliferation activated by LPA. After systemic administration, many proliferating LPA-QDs@FCs rapidly accumulate in ICH areas for responding to the vascular damage and inflammation and then efficiently prevent both the primary and secondary injuries of ICH but with no obvious side effects. Moreover, the treatment process can be tracked by near-infrared II fluorescence imaging with highly spatiotemporal resolution, providing a promising solution for ICH therapy.

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy., (© 2023. The Author(s).)

Background: The cyclooxygenase-2 (COX-2) selective inhibitor parecoxib is widely used in the treatment of pain and inflammation. Parecoxib has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and dental surgery). Total knee or total hip arthroplasty (THA) surgery is mostly done in older patients, so postoperative analgesics need to be used more carefully, and the safety and efficacy of parecoxib in this type of surgery need to be further verified. The aim of this study was to investigate the effects of parecoxib on patient safety, cumulative morphine consumption and was at 24 and 48 hours in the analgesic treatment of total knee or THA for meta-analysis and systematic review, with few studies in this area so far., Methods: We searched the Online Database Cochrane Library, PubMed, Web of Science, EMBASE, and CBM (SinoMed), CNKI, VIP, WANFANG up to January 2021. According to the value of I2, the random-effect model or fixed-effect model was supposed to combine data from studies, respectively. Publication bias was assessed through funneling plot and Beggs test. Review Manager 5.3 and Stata 16.0 software were applied to perform the statistical analyses., Results: Eleven RCTs which involved 1690 participants were included in this study. The meta-analysis indicated parecoxib sodium could not significantly reduce the incidence of adverse events after total knee or THA compared with placebo. There was no statistical significance in incidence of nausea and vomiting. 24 hours resting VAS score was statistically significant between the group. The 48-hour resting VAS scores did not indicate a significant difference between the groups., Conclusion: Parecoxib can reduce the incidence of adverse events after total knee or total hip surgery to some extent but cannot reduce the incidence of nausea and vomiting. Twenty-four hour postoperative analgesia is better than placebo, but 48 hours after operation analgesia is the same as placebo., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Extracellular vesicles (EVs) exhibiting versatile biological functions provide promising prospects as natural therapeutic agents and drug delivery vehicles. For future clinical translation, revealing the fate of EVs in vivo, especially their accumulation at lesion sites, is very important. The continuous development of in vivo imaging technology has made it possible to track the real-time distribution of EVs. This article reviews the applications of mammal-, plant-, and bacteria-derived EVs in tumor therapy, the labeling methods of EVs for in vivo imaging, the advantages and disadvantages of different imaging techniques, and possible improvements for future work., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

Pathogens are serious threats to human health, and traditional detection techniques suffer from various limitations. The unique optical properties of photoluminescent inorganic nanomaterials, such as high photoluminescence quantum yields, good photostability, and tunable spectra, make them ideal tools for the detection of pathogens with high specificity and sensitivity. In this review, the design strategies, working mechanisms, and applications of photoluminescent inorganic nanomaterial-based probes in pathogen detection are introduced. In particular, the design and construction of stimuli-responsive nanoprobes and their potential in these fields are highlighted., (© 2022 Wiley-VCH GmbH.)

Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. Herein, we construct bacterial outer membrane vesicles (OMVs)-based in situ cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy. By simply fusing thylakoid membranes with OMVs, bacteria-plant hybrid vesicles (BPNs) are prepared. After systemic administration, BPNs can target tumor tissues and stimulate the activation of immune cells, including dendritic cells (DCs). The photodynamic effects derived from thylakoid lead to the disruption of local tumors and then the release of tumor-associated antigens that are effectively presented by DCs, inducing remarkable tumor-specific CD8 + T cell responses. Moreover, BPNs can efficiently ameliorate the immunosuppressive tumor microenvironment and further boost immune responses. Therefore, both tumor development and metastasis can be efficiently prevented. This work provides a novel idea for developing a versatile membrane-based hybrid system for highly efficient tumor treatment.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls., (© 2022. The Author(s).)

Background: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations., Methods: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns., Results: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs., Conclusions: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure., Method: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms., Results: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe., Conclusion: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients., (Copyright © 2021. Published by Elsevier Inc.)

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks., (© 2021. The Author(s).)

Background: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied., Methods: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes)., Results: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities., Limitations: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results., Conclusions: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are cell secretory native components with long-circulation, good biocompatibility, and physiologic barriers cross ability. EVs derived from different donor cells inherit varying characteristics and functions from their original cells and are favorable to serve as vectors for diagnosing and treating various diseases. However, EVs nanotheranostics are still in their infancy because of their limited accumulation at lesion sites and compromised therapy efficiency. Hence, engineering modification of EVs is usually needed to further enhance their stability, biological activity, and lesion-targeting capacity. Herein, we overview the characteristics of EVs from different sources, as well as the latest developments of surface engineering and cargo loading methods. We also focus especially on advances in EVs-based disease theranostics. At the end of the review, we predict the obstacles and prospects of the future clinical application of EVs.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Although the antimonene (AM) nanomaterial is recently emerging as a new photothermal therapy (PTT) agent, its rapid degradation in physiological medium immensely limits its direct utilization. To this end, we herein engineered AM by the cooperation of dimension optimization, size control, and cell membrane (CM) camouflage. Compared with traditional AM nanosheets, the resulting AM nanoparticles (∼55 nm) cloaked with the CM (denoted as CmNPs) exhibited significantly improved stability and increased photothermal efficacy as well as superior tumor targeting capacity. After intravenous injection, the CmNPs enabled satisfactory photoacoustic/photothermal multimodal imaging at tumor sites. Meanwhile, the PTT together with the newly explored function of photodynamic therapy (PDT) achieved a potent combination therapy with few side effects. The maximized theranostic performance thus strongly recommends CmNPs as a safe and highly reliable modality for anticancer therapy.

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

Steady labeling of amyloid beta (Aβ) is crucial for studying the ingestion and degradation of Aβ by astrocytes and unraveling a relevant regulation mechanism. Quantum dots (QDs) are an optimum labeling reagent for this because of their strong and steady fluorescence properties. In this paper, Aβ was labeled with QDs by a simple mixed incubation strategy, with a QD labeled Aβ complex (QDs-Aβ) being obtained. In the complex, QDs efficiently restrained the formation of β-folding and fibrils of Aβ, while the graininess, dispersivity and fluorescence properties of the QDs hardly changed. The fluorescence microscopy imaging results showed that the astrocytes could ingest the QDs-Aβ. The QDs and Aβ did not separate from each other during the ingestion process, and the Aβ could be degraded subsequently.

Objective: To investigate the prognostic factors for non-small cell lung cancer(NSCLC)in patients under 40 years of age., Methods: The clinicopathological data of 148 young patients with NSCLC were retrospectively analyzed. Kaplan-Meier and Cox regression analyses were used to analyze the relationship between prognostic factors and survival time., Results: The patients were followed-up for 6 - 148 months, and the follow-up rate was 100%. In the whole group, 122 patients died and 26 cases were surviving. The 1-, 3- and 5-year survival rates were 54.7%, 10.4% and 5.6%, respectively. The median survival time (MST) was 14.7 months. Kaplan-Meier analysis showed that Karnofsky performance status (KPS), clinical stage, treatment modality and serum CEA were related with prognosis (P < 0.05). Multivariate analysis indicated that KPS, clinical stage, treatment modality and serum CEA were independent prognostic factors (P < 0.05)., Conclusions: KPS, CEA, clinical stage and treatment modalities are independent prognostic factors in young NSCLC patients.

Lysyl oxidase-like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. Both down- and up-regulation of LOXL in tumor tissues and cancer cell lines have been described, suggesting paradoxical roles in cancer. However, LOXL2 expression and the clinical significance in non-small cell lung cancers (NSCLC) remain unresolved. Real-time PCR was performed to detect the expression of LOXL2 mRNA in lung tumor tissues (TT) and surrounding normal tissues (sNT). Moreover, the expression of the LOXL2 protein in specimens from 83 paraffin-embedded blocks was examined by immunohistochemical staining. Correlations between LOXL2 mRNA and protein expression and clinicopathological features were evaluated by statistical analysis. In the 137 patients examined, LOXL2 mRNA expression was significantly lower in lung TT than the sNT (P < 0.05). Forty-eight specimens (48/83) showed low expression of LOXL2, as characterized by immunohistochemical staining. By statistical analysis of the correlation between LOXL2 mRNA expression and clinical features of NSCLC patients, down-regulation of Loxl-2 mRNA expression was correlated with male patients (P = 0.008), a poorer N-stage (P = 0.032) and a poorer pathological TNM stage (P = 0.003). Statistical analysis of the correlation between LOXL2 protein expression and clinical features of NSCLC patients showed a statistically significant difference between low expression of the LOXL2 protein and a poorer N-stage (P = 0.036), a higher pathological TNM stage (P = 0.005) and poorer differentiation (P = 0.035). When stratified by histological types, significant differences at both the mRNA and protein levels were only found for lung adenocarcinomas patients, and not for lung squamous cell carcinomas patients. The level of LOXL2 mRNA expression was found to be significantly down-regulated in NSCLC, and the lower mRNA and protein expression levels correlated with poorer differentiation, higher N-stage and advanced pathologic TNM stage in patients with lung adenocarcinomas.

Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its significance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients.