Bimetallic Coordination Polymers: Synthesis and Applications in Biosensing and Biomedicine.

Bimetallic coordination polymers (CPs) have two different metal ions as connecting nodes in their polymer structure. The synthesis methods of bimetallic CPs are mainly categorized into the one-pot method and post-synthesis modifications according to various needs. Compared with monometallic CPs, bimetallic CPs have synergistic effects and excellent properties, such as higher gas adsorption rate, more efficient catalytic properties, stronger luminescent properties, and more stable loading platforms, which have been widely applied in the fields of gas adsorption, catalysis, energy storage as well as conversion, and biosensing. In recent years, the study of bimetallic CPs synergized with cancer drugs and functional nanomaterials for the therapy of cancer has increasingly attracted the attention of scientists. This review presents the research progress of bimetallic CPs in biosensing and biomedicine in the last five years and provides a perspective for their future development.

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.

A real-world study of treatment patterns following disease progression in epithelial ovarian cancer patients undergoing poly-ADP-ribose polymerase inhibitor maintenance therapy.

BACKGROUND: The efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status. METHODS: We analyzed real-world data from Peking University Cancer Hospital, subsequent therapy after progression to PARP inhibitor-maintenance therapy for epithelial ovarian cancer between January 2016 and December 2022. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The last follow-up was in May 2023. RESULTS: A total of 102 patients were included, of which 29 (28.4%) had a germline BRCA1/2 mutation and 73 (71.6%) exhibited BRCA1/2 wild-type mutations. The PARP inhibitors used were Olaparib (n = 62, 60.8%), Niraparib (n = 35, 34.3%), and others (n = 5, 4.9%). The overall response rate (ORR) was 41.2%, and the median time to second progression (mTTSP) was 8.1 months (95%CI 5.8-10.2). Of 91 platinum-sensitive patients (PFI ≥ 6 months) after progression to PARP inhibitor-maintenance therapy, 65 patients subsequently received platinum regimens. Among them, 30 had received one line of chemotherapy before PARP inhibitor-maintenance therapy. Analysis of these 30 patients by BRCA status showed an ORR of 16.7% versus 33.3% and mTTSP of 7.1 (95% CI 4.9-9.1) versus 6.2 months (95% CI 3.7-8.3, P = 0.550), for BRCA-mutant and wild-type patients, respectively. For the remaining 35 patients who had received two or more lines of chemotherapy before PARP inhibitor-maintenance therapy, ORR was 57.1% versus 42.9%, and mTTSP was 18.0 (95% CI 5.0-31.0) versus 8.0 months (95% CI 4.9-11.1, P = 0.199), for BRCA-mutant and wild-type patients, respectively. CONCLUSION: No differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.

Disparities in treatment modalities and survival among older patients with high-grade serous ovarian cancer.

BACKGROUND: Undertreatment of ovarian cancer is common among older women. We aimed to evaluate the treatment modalities offered to older patients and their impact on overall survival (OS). METHODS: The study identified 5,055 patients with high-grade serous ovarian cancer and 3584 patients with advanced stage (IIIC + IV) disease from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2017. We performed comparisons of OS and ovarian cancer-specific survival (OCSS) across age groups using a Cox proportional hazards model. RESULTS: Very elderly patients (≥ 75 years old) received treatment with significantly less surgical complexity, such as no lymphadenectomy (59.7% vs. 48.6%; p < 0.001) and a lower rate of optimal debulking surgery (44.0% vs. 52.7%; p < 0.001), as well as lower rates of chemotherapy (78.2% vs. 89.4%; P<0.001) and standard treatment (70.6% vs. 85%; p < 0.001). High proportions of both very elderly and elderly patients received neoadjuvant chemotherapy (NACT), with no significant difference (38.7% vs. 36.2%; P = 0.212). Patients aged ≥ 75 years had significantly worse OS and OCSS. CONCLUSION: With increasing age, the survival rate of women with ovarian cancer decreases significantly. Noticeably fewer ovarian cancer patients aged over 75 years receive standard treatments, and more very elderly patients are treated with NACT.

Size-matching compositing nanoprobe of AIE-type gold nanocluster supramolecular nanogels wrapped by hypergravity-tailored MnO2 nanosheets for cellular glutathione detection.

Compositing has been the main approach for material creation via wisely combining material components with different properties. MnO2 nanosheets (MNSs) with thin 2 D morphology are usually applied to composite molecules or nanomaterials for biosensing and bioimaging applications. However, such composition is actually structurally unmatched, albeit performance matching. Here, a series of benefits merely on the basis of structural match have been unearthed via tailoring MNSs with four sizes by synthesis under controllable hypergravity field. The classical fluorophore-quencher couple was utilized as the subject model, where the soft supramolecular nanogels based on aggregation-induced emission (AIE)-active gold nanoclusters were wrapped by MNSs of strong absorption. By comparative study of one-on-one wrapping and one-to-many encapsulation with geometrical selection of different MNSs, we found that the one-on-one wrapping model protected weakly-bonded nanogels from combination-induced distortion and strengthened nanogel networks via endowing exoskeleton. Besides, wrapping pattern and size-match significantly enhanced the quenching efficiency of MNSs towards the emissive nanogels. More importantly, the well-wrapped nanocomposites had considerable enhanced biological compatibility with much lower cytotoxicity and higher transfection capacity than the untailored MNSs composite and could serve as cellular glutathione detection.

Efficacy and Safety of Bilateral Ultrasound-Guided Erector Spinae Plane Block for Postoperative Analgesia in Spine Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery. METHODS: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables. RESULTS: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001). CONCLUSIONS: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery.

A Key-Points Based Anchor-Free Cervical Cell Detector.

Cervical cell detection is crucial to cervical cytology screening at early stage. Currently most cervical cell detection methods use anchor-based pipeline to achieve the localization and classification of cells, e.g. faster R-CNN and YOLOv3. However, the anchors generally need to be pre-defined before training and the detection performance is inevitably sensitive to these pre-defined hyperparameters (e.g. number of anchors, anchor size and aspect ratios). More importantly, these preset anchors fail to conform to the cells with different morphology at inference phase. In this paper, we present a key-points based anchor-free cervical cell detector based on YOLOv3. Compared with the conventional YOLOv3, the proposed method applies a key-points based anchor-free strategy to represent the cells in the initial prediction phase instead of the preset anchors. Therefore, it can generate more desirable cell localization effect through refinement. Furthermore, PAFPN is applied to enhance the feature hierarchy. GIoU loss is also introduced to optimize the small cell localization in addition to focal loss and smooth L1 loss. Experimental results on cervical cytology ROI datasets demonstrate the effectiveness of our method for cervical cell detection and the robustness to different liquid-based preparation styles (i.e. drop-slide, membrane-based and sedimentation).

A deregulated m6A writer complex axis driven by BRD4 confers an epitranscriptomic vulnerability in combined DNA repair-targeted therapy.

Aberrant transcripts expression of the m6A methyltransferase complex (MTC) is widely found across human cancers, suggesting a dysregulated signaling cascade which integrates m6A epitranscriptome to drive tumorigenesis. However, the responsible transcriptional machinery directing the expression of distinct MTC subunits remains unclear. Here, we identified an unappreciated interplay between the histone acetyl-lysine reader BRD4 and the m6A writer complex across human cancers. BRD4 directly stimulates transcripts expression of seven MTC subunits, allowing the maintenance of the nuclear writer complex integrity. Upon BET inhibition, this BRD4-MTC signaling cascade accounts for global m6A reduction and the subsequent dynamic alteration of BRD4-dependent transcriptome, resulting in impaired DNA damage response that involves activation of homologous recombination (HR) repair and repression of apoptosis. We further demonstrated that the combined synergy upon BET/PARP inhibition largely relies on disrupted m6A modification of HR and apoptotic genes, counteracting PARP inhibitor (PARPi) resistance in patient-derived xenograft models. Our study revealed a widespread active cross-talk between BRD4-dependent epigenetic and MTC-mediated epitranscriptomic networks, which provides a unique therapeutic vulnerability that can be leveraged in combined DNA repair-targeted therapy.

Impact of hematological and radiation parameters on the clinical prognosis of esophageal cancer patients treated with definitive chemoradiotherapy.

This study aimed to conduct a survival analysis of thoracic esophageal squamous cell carcinoma (ESCC) patients treated with radical chemoradiotherapy and identify prognostic variables from among the hematological and radiation parameters. Cases of patients with ESCC receiving definitive chemoradiotherapy at Jiangsu Cancer Hospital between January 2018 and September 2020 were screened. A Cox proportional hazards model was used to assess the effect of hematological and radiation parameters on the overall survival (OS). The neutrophil-to-lymphocyte ratio (NLR) was calculated by dividing the absolute neutrophil count (ANC) by the absolute lymphocyte count (ALC) in the week prior to radical chemoradiotherapy. Variables associated with radiation were gathered based on dose-volume histograms (DVH). X-tile software was used to determine the optimal cutoff values for pretreatment NLR and posttreatment ALC nadir. Associations between lymphopenia and dose-volume parameters were analyzed using multivariate logistic regression. The study included 104 ESCC patients. The median follow-up of surviving patients was 45.0 months (interquartile range: 40.2-52.2), with 1- and 3-year OS rates of 88.0% and 62.7%, respectively. Multivariate Cox regression analysis demonstrated a significant survival benefit in patients with low baseline NLR (≤ 2.2), high ALC nadir (> 0.24*109/L), and desirable radiation parameters for the heart and thoracic vertebrae. Increased dose-volume parameters of the heart, lungs, and thoracic vertebrae were correlated with a high probability of radiation-induced lymphopenia (RIL) risk (P < 0.05). Baseline NLR and RIL are significantly related to survival outcomes in ESCC patients. Optimization of radiation parameters of cardiopulmonary and thoracic vertebrae can be effective in the prevention of RIL.

Bovine Serum Albumin-Protected Gold Nanoclusters for Sensing of SARS-CoV-2 Antibodies and Virus.

An approach to assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (and past infection) was developed. For virus detection, the SARS-CoV-2 virus nucleocapsid protein (NP) was targeted. To detect the NP, antibodies were immobilized on magnetic beads to capture the NPs, which were subsequently detected using rabbit anti-SARS-CoV-2 nucleocapsid antibodies and alkaline phosphatase (AP)-conjugated anti-rabbit antibodies. A similar approach was used to assess SARS-CoV-2-neutralizing antibody levels by capturing spike receptor-binding domain (RBD)-specific antibodies utilizing RBD protein-modified magnetic beads and detecting them using AP-conjugated anti-human IgG antibodies. The sensing mechanism for both assays is based on cysteamine etching-induced fluorescence quenching of bovine serum albumin-protected gold nanoclusters where cysteamine is generated in proportion to the amount of either SARS-CoV-2 virus or anti-SARS-CoV-2 receptor-binding domain-specific immunoglobulin antibodies (anti-RBD IgG antibodies). High sensitivity can be achieved in 5 h 15 min for the anti-RBD IgG antibody detection and 6 h 15 min for virus detection, although the assay can be run in "rapid" mode, which takes 1 h 45 min for the anti-RBD IgG antibody detection and 3 h 15 min for the virus. By spiking the anti-RBD IgG antibodies and virus in serum and saliva, we demonstrate that the assay can detect the anti-RBD IgG antibodies with a limit of detection (LOD) of 4.0 and 2.0 ng/mL in serum and saliva, respectively. For the virus, we can achieve an LOD of 8.5 × 105 RNA copies/mL and 8.8 × 105 RNA copies/mL in serum and saliva, respectively. Interestingly, this assay can be easily modified to detect myriad analytes of interest.

How it feels in a cell.

Life emerges from thousands of biochemical processes occurring within a shared intracellular environment. We have gained deep insights from in vitro reconstitution of isolated biochemical reactions. However, the reaction medium in test tubes is typically simple and diluted. The cell interior is far more complex: macromolecules occupy more than a third of the space, and energy-consuming processes agitate the cell interior. Here, we review how this crowded, active environment impacts the motion and assembly of macromolecules, with an emphasis on mesoscale particles (10-1000 nm diameter). We describe methods to probe and analyze the biophysical properties of cells and highlight how changes in these properties can impact physiology and signaling, and potentially contribute to aging, and diseases, including cancer and neurodegeneration.

Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Real-world study of bevacizumab treatment in patients with ovarian cancer: a Chinese single-institution study of 155 patients.

OBJECTIVE: The purpose of this study was to retrospectively assess the pattern, compliance, efficacy and safety of bevacizumab in Chinese ovarian cancer patients. METHODS: We reviewed the clinicopathological data of patients with histologically confirmed epithelial ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma, who were diagnosed and treated at the Department of Gynecologic Oncology of Peking University Cancer Hospital between May 2012 and January 2022. RESULTS: A total of 155 patients were eventually enrolled in this study, with 77 as first-line chemotherapy (FL) and 78 as recurrence therapy (RT) among which 37 patients were platinum sensitive and 41 were platinum resistant. Among the 77 patients in the FL group, 35 received bevacizumab during neoadjuvant chemotherapy (NACT) alone (NT), 23 received bevacizumab during both neoadjuvant and first-line chemotherapy (NT + FL) and 19 received bevacizumab during first-line chemotherapy alone (FLA). Among the 43 patients of NT and NT + FL groups undergoing interval debulking surgery (IDS), 38(88.4%) patients achieved optimally debulking and 24 (55.8%) patients had no residual disease after IDS. The patients in the FL group had a median progression free survival (PFS) of 15(95%CI: 9.951-20.049) months, and the 12-month PFS was 61.7%. In the RT group, the overall response rate (ORR) was 53.8%. According to multivariate analysis, the patients' platinum sensitivity had a significant impact on the PFS in the RT group. 13(8.4%) patients discontinued bevacizumab due to toxicity. Seven patients were in the FL group while 4 patients were in the RT group. The most common adverse event associated with bevacizumab therapy was hypertension. CONCLUSION: Bevacizumab is effective and well-tolerated in the real world setting of ovarian cancer treatment. Adding bevacizumab to NACT is feasible and tolerable. Receiving the regimen containing bevacizumab in the last preoperative chemotherapy did not result in increased intraoperative bleeding of IDS. Platinum sensitivity is the most important factor affecting the effectiveness of bevacizumab in recurrent patients.

Prediction of global potential suitable habitats of Nicotiana alata Link et Otto based on MaxEnt model.

Nicotiana alata Link et Otto, widely used in landscaping, is not only of great ornamental value but also of high commercial and medical value. The global potential habitat of N. alata and the environmental factors affecting its distribution are not that clear at present. To provide a reference for the reasonable and extensive planting of N. alata now and in the future, the MaxEnt model was used to predict its global suitable habitats under current and future climate conditions, respectively, based on global geographic distribution data of N. alata and the current and future world bioclimatic variables. The results showed that mean temperature of the driest quarter (bio9), precipitation of driest month (bio14), precipitation seasonality (bio15) and max temperature of warmest month (bio5), were the key bioclimatic variables governing the distribution of N. alata. The global suitable habitats of N. alata were mainly distributed in Europe, the United States, southeastern South America, and China under current climate conditions. Compared with current climate conditions, the future climate decreased suitable habitats of N. alata under SSP1-2.6, and SSP2-4.5 scenario and increased suitable habitats of N. alata under SSP3-7.0, and SSP5-8.5 climatic scenarios. The results provided valuable information and theoretical reference for the reasonable planting of N. alata.

Circulating T-cell receptor diversity as predictive biomarker for PARP inhibitors maintenance therapy in high grade serous ovarian cancer.

OBJECTIVE: T-cell receptor (TCR) repertoire diversity is getting increasing attention as a predictive biomarker in cancer patients. However, the characteristics of the TCR together with its predictive significance for high grade serous ovarian cancer (HGSOC) patients receiving poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy remain unknown. METHODS: Twenty-seven patients with HGSOC were analyzed including 22 patients receiving PARPi maintenance therapy and 5 untreated patients as control. Peripheral blood samples were collected for TCR sequencing at baseline as well as one month and three months after the exposure to PARPi. To determine whether TCR diversity was related to PARPi efficacy, we compared the TCR repertoire between patients who had received PARPi and those who had not. RESULTS: For patients receiving PARPi treatment or not, we evaluated changes in clone abundance during PARPi maintenance and the similarity of the TCR repertoire before and after the treatment. The results revealed that patients receiving PARPi had TCR repertoires that were more stable than those of untreated cases. We next correlated TCR diversity with the efficacy of PARPi in the treatment group. The rising trend of TCR diversity after three months with PARPi treatment was associated with a longer PFS (21.7 vs 7.4 months, hazard ratio = 0.19, p < 0.001) and a better response to PARPi (91.7% vs 25.0%, p = 0.004). Furthermore, we discovered that the primary characteristic with predictive value for the effectiveness of PARPi is the considerable reduction of the high-frequency T cell clones. CONCLUSION: We suggested that the circulating TCR diversity could be a potential predictive biomarker for PARPi maintenance therapy in HGSOC.

Using bimetallic Au/Cu nanoplatelets for construction of facile and label-free inner filter effect-based photoluminescence sensing platform for sarcosine detection.

Herein, we report a facile and label-free method for sensitive and specific determination of prostate cancer biomarker sarcosine via using photoluminescent bimetallic Au/Cu nanoplatelets (AuCu NPs) to construct an inner filter effect (IFE)-based photoluminescence (PL) sensing platform. The AuCu NPs were formed by the cysteine-induced co-reduction reaction, which displayed bright PL with an emission peak at 560 nm. Meanwhile, the Cu(I) doping caused a maximum 25-fold enhancement of quantum yield (QY), compared with the native Au(I) complexes, i.e., from 0.85 to 21.5%. By integrating the AuCu NPs with p-phenylenediamine (PPD) oxidation reaction, an IFE-based sensor for sarcosine detection was constructed. In this method, sarcosine is oxidized under the catalysis of sarcosine oxidase (SOx) to yield H2O2. The latter further oxidizes PPD to form 2,5-diamino-N,N'-bis(p-aminophenyl)-l,4-benzoquinone di-imine (PPDox) in the presence of horseradish peroxidase (HRP). The UV-vis absorption spectrum of the PPDox can overlap well with the excitation and emission spectra of the AuCu NPs, resulting in the efficient quenching of the AuCu NPs via the IFE effect. Therefore, this IFE-based AuCu NPs/SOx/PPD/HRP sensing platform can be used for highly sensitive and specific sensing of sarcosine. The sensing platform showed two linear regions of the PL intensity of the AuCu NPs versus the concentration of sarcosine in the range of 0.5-5 µM and 5-100 µM with a detection limit (LOD) of 0.12 µM (S/N = 3). Furthermore, this IFE-based sensing platform could be developed into a paper-based biosensor for simple, instrument-free, and visual detection of sarcosine.

Luminescent Covalent Organic Frameworks for Biosensing and Bioimaging Applications.

Luminescent covalent organic frameworks (LCOFs) have attracted significant attention due to their tunability of structures and photophysical properties at molecular level. LCOFs are built to highly ordered and periodic 2D or 3D framework structures through covalently assembling with various luminophore building blocks. Recently, the advantages of LCOFs including predesigned properties of structure, unique photoluminescence, hypotoxicity and good biocompatibility and tumor penetration, broaden their applications in biorelated fields, such as biosensing, bioimaging, and drug delivery. A specific review that analyses the advances of LCOFs in the field of biosensing and bioimaging is thus urged to emerge. Here the construction of LCOFs is reviewed first. The synthetic chemistry of LCOFs highlights the key role of chemical linkages, which not only concrete the building blocks but also affect the optical properties and even can act as the responsive sites for potential sensing applications. How to brighten LCOFs are clarified through description of structure managements. The ability to utilize the luminescence of LCOFs for applications in biosensing and bioimaging is discussed using state-of-the-art examples of varied practical goals. A prospect finally addresses opportunities and challenges the development of LCOFs facing from chemistry, physics to the applications, according to their current progress.

microRNA-375 inhibits the malignant behaviors of hepatic carcinoma cells by targeting NCAPG2.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Emerging evidence has revealed the vital functions of microRNAs (miRNAs) in cancer malignant progressions. miR-375 has been verified to serve as an antioncogene in tumorigenesis and a potential therapeutic target in various types of cancer. In this study, we aimed to determine the role of miR-375 in the regulation of chemoresistance and metastasis of HCC. Differentially expressed miR-375 and NCAPG2 were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-375 in HCC tissues and cell lines. miR-375 mimics and NCAPG2-overexpression were transfected into HepG2 and Huh7 cells to establish miR-375 overexpression models. Cell Counting Kit-8, Transwell, and flow cytometry experiments were conducted to monitor cell proliferation, migration, and apoptosis. The targeting relationship between miR-375 and non-SMC condensin II complex subunit G 2 (NCAPG2) was determined by qRT-PCR, western blot, and luciferase reporter gene assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using Gene Set Enrichment Analysis (GSEA). The pathway enrichment analysis was used to predict the potential pathways for further study. miR-375 was significantly downregulated in HCC tissues and cells compared to adjacent tissue and normal hepatocyte cell line respectively while NCAPG2 was upregulated. The targeting relationship was verified by luciferase reporting assay, and miR-375 could target the 3'UTR of NCAPG2 mRNA and effectively suppress NCAPG2 protein expression. Replenishing of miR-375 significantly repressed HCC cell proliferation and migration, and induced cell apoptosis. Overexpression of NCAPG2 recovered those biological abilities in miR-375 overexpressed cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating NCAPG2. Replenishing of miR-375 or knockout of NCAPG2 could be therapeutically exploited for HCC.

Chemical Characterization and Immunomodulatory Activity of Fucoidan from Sargassum hemiphyllum.

Fucoidan is a sulfated algal polyanionic polysaccharide that possesses many biological activities. In this paper, a fucoidan (SHF) polysaccharide was extracted from Sargassum hemiphyllum collected in the South China Sea. The SHF, with a molecular weight of 1166.48 kDa (44.06%, w/w), consisted of glucose (32.68%, w/w), galactose (24.81%, w/w), fucose (20.75%, w/w), xylose (6.98%, w/w), mannose (2.76%, w/w), other neutral monosaccharides, and three uronic acids, including glucuronic acid (5.39%, w/w), mannuronic acid (1.76%, w/w), and guronuronic acid (1.76%, w/w). The SHF exhibited excellent immunostimulatory activity. An immunostimulating assay showed that SHF could significantly increase NO secretion in macrophage RAW 264.7 cells via upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) levels based on both gene expression and protein abundance. These results suggest that SHF isolated from Sargassum hemiphyllum has great potential to act as a health-boosting ingredient in the pharmaceutical and functional-food fields.

[Application of Magnetization-prepared True Fast Imaging with Steady-state Precession Sequence in Brain Tumor Enhancement].

Objective To evaluate the application of two-dimensional magnetization-prepared true fast imaging with steady-state precession(2D-MP-TrueFISP)sequence in brain tumor enhancement.Methods In this study,60 cases of brain tumor patients who underwent enhanced magnetic resonance imaging of brain were scanned with 2D-MP-TrueFISP/two-dimensional spoiled gradient-recalled echo(2D-SPGR)before and after enhancement.The scores of lesions on the images of 2D-MP-TrueFISP/2D-SPGR were compared.At the same level of 2D-SPGE and 2D-MP-TrueFISP,the signal intensities(SIs)of lesions,white matter,and cerebrospinal fluid were measured before and after enhancement,and the contrast ratios(CRs)of lesions were calculated.The CRs before and after 2D-SPGR/2D-MP-TrueFISP enhancement and those between 2D-SPGR and 2D-MP-TrueFISP after enhancement were compared.Results The scores of lesions after 2D-MP-TrueFISP/2D-SPGR T1WI enhancement were 9.0(9.0,9.0)and 7.0(6.0,7.0),respectively,with significant difference(Z=-6.86,P=0.00).CRs showed significant difference before and after enhancement with 2D-SPGR and 2D-MP-TrueFISP(all P<0.01).The CRs of lesion compared with white matter and cerebrospinal fluid(1.58±0.46 and 8.50±2.47,respectively)after 2D-MP-TrueFISP enhancement were significantly higher than those[0.57±0.29(t=-17.38,P=0.00)and 2.64±0.85(t=-19.71,P=0.00),respectively]after 2D-SPGR enhancement.Conclusion Compared with 2D-SPGR,2D-MP-TrueFISP demonstrated improved enhancement and uniformity as well as clear boundary and display of edema around the lesion.