NIR-II-Absorbing TMB Derivative for 1064 nm-Excited Photothermal Immunoassay.

Materials exhibiting strong absorption in the NIR-II region are appealing for photothermal conversion-based imaging, diagnosis, and therapy, due to better thermal effect and decreased absorption of water in such a region. 3,3',5,5'-Tetramethylbenzidine (TMB), the typical substrate in ELISA, has been explored in photothermal immunoassay, since its oxidation product (oxTMB) is photothermally active in the NIR region. However, its absorption at 1064 nm (the most often used laser wavelength in photothermal studies) is not appreciable, thus limiting the assay sensitivity. Here, we proposed a derivative of TMB (3,3'-dimethoxy-5,5'-dimethylbenzidine, 2-OCH3) bearing higher NIR-II absorption for 1064 nm-excited photothermal immunoassay. Since electron-donating groups can help decrease the energy gap of molecules (here -CH3 → -OCH3), the oxidation product of 2-OCH3 exhibited substantially red-shifted absorption as compared with oxTMB, leading to a more than twofold higher absorption coefficient at 1064 nm. As a result, 2-OCH3 showed enhanced sensitivity over TMB in a photothermal immunoassay (PTIA), yielding a limit of detection (LOD) of 0.1 ng/mL for prostate-specific antigen (PSA). The feasibility of 2-OCH3-based PTIA for diagnosis was further validated by analyzing PSA in 61 serum samples. Considering its superior photothermal performance, 2-OCH3 can be explored for a broad range of photothermal applications.

Integrating Recombinase Polymerase Amplification and Photosensitization Colorimetric Detection in One Tube for Fast Screening of C. sakazakii in Formula Milk Powder.

Cronobacter sakazakii (C. sakazakii) is a widely existing opportunistic pathogen and thus threatens people with low immunity, especially infants. To prevent the outbreak, a rapid and accurate on-site testing method is required. The current standard culture-based method is time-consuming (3-4 days), while the nucleic acid amplification (PCR)-based detection is mostly carried out in central laboratories. Herein, isothermal recombinase polymerase amplification (RPA) coupled with a photosensitization colorimetric assay (PCA) was adopted for the on-site detection of C. sakazakii in powdered infant formulas (PIFs). The lowest visual detection concentration of C. sakazakii is 800 cfu/mL and 2 cfu/g after 8 h bacteria pre-enrichment. Furthermore, to avoid typical cap opening-resulted aerosol pollution, the PCA reagents were lyophilized onto the cap of the RPA tube (containing lyophilized RPA reagents). After amplification, the tube was subjected to simple shaking to mix the PCA reagents with the amplification products for light-driven color development. Such a one-tube assay offered a lowest concentration of 1000 copies of genomic DNA of C. sakazakii within 1 h. After 8 h of bacterial enrichment, the lowest detecting concentration could be pushed down to 5 cfu/g bacteria in PIF. To facilitate on-site monitoring, a portable, battery-powered PCA device was designed to mount the typical RPA 8-tube strip, and a color analysis cellphone APP was further employed for facile readout.

Analysis of the efficacy of upfront brain radiotherapy versus deferred radiotherapy for EGFR/ALK-positive non-small cell lung cancer with brain metastases: a retrospective study.

BACKGROUND: For brain metastases (BMs) from EGFR/ALK-positive non-small cell lung cancer (NSCLC), the best time to administer tyrosine kinase inhibitors (TKIs) and brain radiotherapy (RT) has not been identified. This analysis was an attempt to solve this problem in part. METHODS: A total of 163 patients with EGFR/ALK-positive NSCLC and brain metastasis (BM) who were diagnosed between January 2017 and July 2022 were included in this study. Ninety-one patients underwent upfront RT, and 72 patients received deferred RT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. RESULTS: The average follow-up period was 20.5 months (range 2.0 to 91.9 months). The median overall survival (OS) was 26.5 months, and the median intracranial progression-free survival (iPFS) was 23.6 months. Upfront RT considerably increased the iPFS (26.9 vs. 20.2 months, hazard ratio [HR] = 5.408, P = 0.020) and OS (31.2 vs. 22.3 months, HR = 4.667, P = 0.031) compared to deferred RT. According to multivariate analysis, upfront RT was an independent risk factor for predicting iPFS (HR = 1.670, P = 0.021). Upfront RT (HR = 1.531, P = 0.044), TKI therapy (HR = 0.423, P < 0.001), and oligometastases (HR = 2.052, P = 0.021) were found to be independent risk factors for OS. CONCLUSION: This study showed that upfront RT combined with TKI treatment can significantly improve intracranial disease management and prolong survival in patients with EGFR/ALK mutations in BMs from NSCLC.

Noncancerous disease-targeting AIEgens.

Noncancerous diseases include a wide plethora of medical conditions beyond cancer and are a major cause of mortality around the world. Despite progresses in clinical research, many puzzles about these diseases remain unanswered, and new therapies are continuously being sought. The evolution of bio-nanomedicine has enabled huge advancements in biosensing, diagnosis, bioimaging, and therapeutics. The recent development of aggregation-induced emission luminogens (AIEgens) has provided an impetus to the field of molecular bionanomaterials. Following aggregation, AIEgens show strong emission, overcoming the problems associated with the aggregation-caused quenching (ACQ) effect. They also have other unique properties, including low background interferences, high signal-to-noise ratios, photostability, and excellent biocompatibility, along with activatable aggregation-enhanced theranostic effects, which help them achieve excellent therapeutic effects as an one-for-all multimodal theranostic platform. This review provides a comprehensive overview of the overall progresses in AIEgen-based nanoplatforms for the detection, diagnosis, bioimaging, and bioimaging-guided treatment of noncancerous diseases. In addition, it details future perspectives and the potential clinical applications of these AIEgens in noncancerous diseases are also proposed. This review hopes to motivate further interest in this topic and promote ideation for the further exploration of more advanced AIEgens in a broad range of biomedical and clinical applications in patients with noncancerous diseases.

Dual-Gene Isothermal Amplification Coupled with Lateral Flow Strip for On-Site Accurate Detection of E. coli O157:H7 in Food Samples.

On-site field detection of E. coli O157:H7 in food samples is of utmost importance, since it causes a series of foodborne diseases due to infections-associated ready-to-eat foods. Due to the instrument-free nature, recombinase polymerase amplification (RPA) coupled with lateral flow assay (LFA) is well-suited for such goal. However, the high genomic similarity of different E. coli serotypes adds difficulty to accurate differentiation of E. coli O157:H7 from others. Dual-gene analysis could significantly improve the serotype selectivity, but will further aggravate the RPA artifacts. To address such issue, here we proposed a protocol of dual-gene RPA-LFA, in which the target amplicons were selectively recognized by peptide nucleic acid (PNA) and T7 exonuclease (TeaPNA), thus eliminating false-positives in LFA readout. Adapting rfbEO157 and fliCH7 genes as the targets, dual-gene RPA-TeaPNA-LFA was demonstrated to be selective for E. coli O157:H7 over other E. coli serotypes and common foodborne bacteria. The minimum detection concentration was 10 copies/µL for the genomic DNA (∼300 cfu/mL E. coli O157:H7), and 0.24 cfu/mL E. coli O157:H7 in food samples after 5 h bacterial preculture. For lettuce samples contaminated with E. coli O157:H7 (single-blind), the sensitivity and specificity of the proposed method were 85% and 100%, respectively. Using DNA releaser for fast genomic DNA extraction, the assay time could be reduced to ∼1 h, which is appealing for on-site food monitoring.

Active Breathing Coordinator reduces radiation dose to the stomach in patients with left breast cancer.

BACKGROUND/PURPOSE: Gastric dose parameters comparison for deep inspiration breath-hold (DIBH) or free breathing (FB) mode during radiotherapy (RT) for left-sided breast cancer patients (LSBCPs) has not been investigated before. This study aimed to analyze the impact of Active Breath Coordinator (ABC)-DIBH technique on the dose received by the stomach during RT for LSBCPs and to provide organ-specific dosimetric parameters. MATERIALS AND METHODS: The study included 73 LSBCPs. The dosimetric parameters of the stomach were compared between FB and DIBH mode. The correlation between the stomach volume and dosimetric parameters was analyzed. RESULTS: Compared to FB mode, statistically significant reductions were observed in gastric dose parameters in ABC-DIBH mode, including Dmax (46.60 vs 17.25, p < 0.001), D1cc (38.42 vs 9.60, p < 0.001), Dmean (4.10 vs 0.80, p < 0.001), V40Gy (0.50 vs 0.00, p < 0.001), V30Gy (6.30 vs 0.00, p < 0.001), V20Gy (20.80 vs 0.00, p < 0.001), V10Gy (51.10 vs 0.77, p < 0.001), and V5Gy (93.20 vs 9.60, p < 0.001). ABC-DIBH increased the distance between the stomach and the breast PTV when compared to FB, from 1.3 cm to 2.8 cm (p < 0.001). Physiologic decrease in stomach volume was not found from FB to ABC-DIBH (415.54 cm3 vs 411.61 cm3, p = 0.260). The stomach volume showed a positive correlation with V40Gy (r2 = 0.289; p < 0.05), V30Gy (r2 = 0.287; p < 0.05), V20Gy (r2 = 0.343; p < 0.05), V10Gy (r2 = 0.039; p < 0.001), V5Gy (r2 = 0.439; p < 0.001), Dmax (r2 = 0.269; p < 0.05) and D1cc (r2 = 0.278; p < 0.05) in FB mode. While in ABC-DIBH mode, most stomach dosimetric parameters were not correlated with gastric volume. CONCLUSIONS: The implementation of ABC-DIBH in LSBCPs radiotherapy resulted in lower irradiation of the stomach. Larger stomach volume was associated with statistically significantly higher dose irradiation in FB mode. To reduce radiotherapy related side effects in FB mode, patients should be fast for at least 2 hours before the CT simulation and treatment.

Transcriptional factor CCAAT enhancer binding protein beta inhibits epithelial-mesenchymal transition in cervical cancer via regulating attractin-like 1.

Cervical cancer (CC) is a malignancy seriously endangering women's life and health worldwide. GEPIA demonstrated that attractin-like 1 (ATRNL1) presents downregulation in CC tissue. Transcription factor CCAAT enhancer binding protein beta (CEBPB) was previously revealed to present depletion in CC tissue. We attempted to clarify molecular mechanism between ATRNL1 and CEBPB underlying CC progression. Bioinformatics, RT-qPCR and western blotting revealed expression characteristics of ATRNL1 in CC. RT-qPCR measured ATRNL1 and CEBPB levels in CC cell lines. Gain-of-function assays clarified role of ATRNL1 in CC cell behaviors. Bioinformatics, Pearson correlation, ChIP and luciferase reporter experiments assessed association of ATRNL1 and CEBPB in CC cells. Rescue assays assessed regulatory function of CEBPB-ATRNL1 in CC cellular processes. ATRNL1 showed depletion in CC tissue and cells at mRNA and protein levels. ATRNL1 upregulation repressed CC cell viability, migration and EMT. CEBPB bound to ATRNL1 promoter to transcriptionally upregulate ATRNL1 in CC cells. The impact of CEBPB elevation on CC cell viability, migration and EMT were countervailed by ATRNL1 depletion. ATRNL1 and CEBPB present depletion and serve as tumor suppressors in CC cells. ATRNL1 suppresses CC cell malignancy through CEBPB activation, which may provide a potential new direction for seeking therapeutic plans for CC.

Low-Cost Naked-Eye UVB and UVC Dosimetry Based on 3,3',5,5'-Tetramethylbenzidine.

Ultraviolet radiation (UVR) is both useful to human beings and can cause irreversible harm of varying degrees (UVA, UVB, and UVC). Especially, in areas with excessive sunlight, the appearance of UVB results in an increased risk of skin cancer. On the other hand, UV lamps (254 nm, UVC) are widely used in disinfection (air, water, and factory food) and hospital sterilization; the leakage of UVC is thus sometimes inevitable, which may cause fatal injuries to the related staff. Therefore, low-cost UV dosimetry-based personal protective equipment (PPE) and industrial monitoring devices are of great importance. Here, for the first time, we found that 3,3',5,5'-tetramethylbenzidine (TMB) could be rapidly oxidized upon UVB and UVC irradiation in a dose-dependent manner, in which TMB acts as a self-photosensitizer. Since TMB is a typical and widely used chromogenic substrate in enzyme-linked immunosorbent assay (ELISA), it is well-commercialized with low cost and vast availability worldwide, which permitted the development of low-cost naked-eye UVB and UVC dosimetry. A wearable bracelet mounted with TMB-loaded paper was developed for successful indication of whether the UVB exposure in the sunlight exceeded the minimum erythema dose (MED). In addition, we also developed a clock dial equipped with a TMB solution for unattended detection of UVC leakage from UVC disinfection lamps. The UVB- and UVC-selective coloration and low cost of TMB offered remarkable potential in facile detection of UVR in our daily life.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Recombinase Polymerase Amplification Coupled with a Photosensitization Colorimetric Assay for Fast Salmonella spp. Testing.

Salmonella spp. is one of the most serious foodborne pathogens causing millions of infection cases annually, especially in resource-limited areas. The standard culture method (2-3 days) and current nucleic acid amplification-based testing are not suitable for on-site testing in rural areas with heavy Salmonella spp. burden. Here, we developed a colorimetric recombinase polymerase amplification (RPA) method for fast and sensitive Salmonella spp. testing in 1 h. Specifically, the invA gene from the genomic DNA of Salmonella spp. was amplified isothermally to produce double-stranded DNA (dsDNA) amplicons, which were directly quantified by a photosensitization colorimetric assay. The proposed method offered the lowest detectable concentration of 5 × 103 colony-forming units/mL (cfu/mL), which is much lower than that of ELISA (105-107 cfu/mL). The detectable limit could be further pushed down to 3 cfu/mL upon coupling with bacteria pre-enrichment for 6 h. Analysis of synthetic milk samples confirmed the high precision (90%) and specificity (95%) of the method for Salmonella spp. testing. Moreover, use of a DNA releaser could further simplify the whole testing operation. Because RPA features low-temperature amplification (25-42 °C) without the need for specific instruments and the dsDNA-based photosensitization colorimetric assay served as a simple and facile readout for RPA, our method thus allows fast and low-cost Salmonella spp. testing in food samples.

Photothermal and Enhanced Photocatalytic Therapies Conduce to Synergistic Anticancer Phototherapy with Biodegradable Titanium Diselenide Nanosheets.

Nanomaterial-based photothermal and photocatalytic therapies are effective against various types of cancers. However, combining two or more materials is considered necessary to achieve the synergistic anticancer effects of photothermal and photocatalytic therapy, which made the preparation process complicated. Herein, the authors describe simple 2D titanium diselenide (TiSe2 ) nanosheets (NSs) that can couple photothermal therapy with photocatalytic therapy. The TiSe2 NSs are prepared using a liquid exfoliation method. They show a layered structure and possess high photothermal conversion efficiency (65.58%) and good biocompatibility. Notably, upon near-infrared irradiation, these NSs exhibit good photocatalytic properties with enhanced reactive oxygen species generation and H2 O2 decomposition in vitro. They can also achieve high temperatures, with heat improving their catalytic ability to further amplify oxidative stress and glutathione depletion in cancer cells. Furthermore, molecular mechanism studies reveal that the synergistic effects of photothermal and enhanced photocatalytic therapy can simultaneously lead to apoptosis and necrosis in cancer cells via the HSP90/JAK3/NF-κB/IKB-α/Caspase-3 pathway. Systemic exploration reveals that the TiSe2 NSs has an appreciable degradation rate and accumulates passively in tumor tissue, where they facilitate photothermal and photocatalytic effects without obvious toxicity. Their study thus indicates the high potential of biodegradable TiSe2 NSs in synergistic phototherapy for cancer treatment.

Can Prognostic Nutritional Index be a Prediction Factor in Esophageal Cancer?: A Meta-Analysis.

Objective: Prognostic nutritional index (PNI) can be used for survival predication in patients with esophageal cancer (EC). However, the prognostic value of PNI in EC is inconclusive in accordance to the literature. This meta-analysis aimed to evaluate the prediction value of PNI in EC.Methods: Studies focus on the association of PNI and EC were retrieved from the electronic databases. Standard meta-analysis methods were used for data evaluation.Results: Our search yield 12 studies, involving 3118 patients with EC for data analysis. The pooled data suggested that low PNI was correlated with worse overall survival (hazard ratio (HR) = 1.29, 95% confidence interval (CI):1.11-1.50, P = 0.001) and cancer-specific survival (HR = 2.18, 95% CI: 1.68-2.83, P < 0.0001). Moreover, lower PNI was associated with unfavorable prognostic factors (the presence of lymph node metastasis, deeper tumor invasion and advanced TNM stages).Conclusion: The lower PNI was correlated with unfavorable prognostic factor and poor prognosis in patients with EC.

Effect of HIF-1αsiRNA-linked AuNRs on radiotherapy of nasopharyngeal carcinoma.

The radiation sensitivity of tumor cells is closely related to tumor cell hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is considered a key transcription factor which regulates the sensitivity of hypoxic tumor cells to radiotherapy. On the other hand, some studies have shown that gold nanomaterials improve radiation sensitivity. However, studies on the effect of gold nanomaterials carrying HIF-1αsiRNA on tumor radiotherapy, and the underlying mechanisms are limited. Thus, the present study was aimed at investigating the effect of gold nanocomposites (AuNRs) carrying HIF-1αsiRNA (AuNRs-HIF-1αsiRNA) on the radiation sensitivity of nasopharyngeal carcinoma (NPC) hypoxia cells. The effect of AuNRs-HIF-1αsiRNA on radiation sensitivity of hypoxic NPC cells was determined under X-ray irradiation. The results showed that Au-HIF-1αsiRNA improved the radio-sensitivity of NPC tumor. Thus, this study has demonstrated that gold nanomaterials carrying HIF-1αsiRNA effectively increased the radio-sensitivity of hypoxic tumor, thereby improving the effect of radiotherapy on NPC cells.

Identification of miRNA signatures in serum exosomes as a potential biomarker after radiotherapy treatment in glioma patients.

Despite development in therapies, the high recurrence and low positivity of biomarkers for diagnosis still result in glioma with high mortality. In this study, we aimed to identify a potential miRNA signature to evaluate the effect of radiotherapy in glioma patients. MicroRNA (miRNA) sequencing was performed on miRNAs isolated from serum exosomes in a cohort of glioma patients before and after radiotherapy. A total of 18 up-regulated differentially expressed (DE) miRNAs and 16 down-regulated DE miRNAs were identified. Subsequently, the target genes of DE miRNAs were predicted based on multiple miRNA-target databases. Further, it was indicated that these targets were primarily involved in metabolic process, p53 signaling pathway and cancer pathways, suggesting that these miRNAs play a crucial role in glioma by regulating targets and affect the occurrence and development of the disease. In general, this study presented the variation of miRNAs in blood exosomes before and after radiotherapy. It can not only be helpful for the diagnosis of glioma, but also find new candidate biomarkers for monitoring the condition and evaluating the efficacy of radiotherapy in glioma. It provides a new idea for the diagnosis, treatment and prognosis evaluation of glioma.

MicroRNA-450b-3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma.

Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR-450b-3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression level of miR-450b-3p and the patient's prognosis. Cell functional analyses and tumor xenograft model were used to assess the role of miR-450b-3p in HCC. Bioinformatics was used to predict the downstream target gene of miR-450b-3p, which was verified by dual-luciferase reporter assay. MiR-450b-3p was found to be downregulated in HCC cell lines and tissues, compared with nontransformed immortal hepatic cells and adjacent normal liver tissues, respectively. Lower expression of miR-450b-3p was associated with poor overall survival and disease-free survival in patients with HCC. Ectopic expression of miR-450b-3p inhibited HCC cell viability, colony formation, and cell-cycle progression in vitro, and suppressed the growth of HCC xenograft tumors in vivo. Interestingly, a negative correlation between miR-450b-3p and phosphoglycerate kinase 1 (PGK1) protein was observed among HCC specimens. Additionally, miR-450b-3p inhibited PGK1 expression and phosphorylation of protein kinase B in HCC cell lines. Further experiments confirmed that PGK1 was a direct target of miR-450b-3p. Moreover, restoration of PGK1 abrogated the inhibitory effect of miR-450b-3p on HCC proliferation and cell division. In conclusion, miR-450b-3p is downregulated in human HCC and exerts tumor suppressive effects at least in part by inhibiting PGK1.

Comparative analysis of robotic gastrectomy and laparoscopic gastrectomy for gastric cancer in terms of their long-term oncological outcomes: a meta-analysis of 3410 gastric cancer patients.

BACKGROUND: Data regarding the long-term oncological outcomes of robotic gastrectomy (RG) are limited despite the increased commonality of this method as an alternative for gastric cancer treatment. Here, we conducted a meta-analysis to evaluate the long-term oncological outcomes of RG in comparison to that of laparoscopic gastrectomy (LG). METHODS: The PubMed, ISI Web of Science, EMBASE, and Cochrane Library databases were comprehensively searched for studies that compared RG and LG in terms of their long-term survival outcomes. The hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) were obtained, while the odds ratio (OR) was recorded for the recurrence rate. A sensitivity analysis was performed. Egger's test and Begg's test were applied to evaluate publication bias. RESULTS: Eight studies were identified and involved 3410 gastric cancer patients (RG, 1009; LG, 2401). The two groups had no significant differences in OS (HR, 0.98; 95% CI, 0.80-1.20; P = 0.81), DFS (HR, 1.36; 95% CI, 0.33-5.59; P = 0.67), RFS (HR, 0.92; 95% CI, 0.72-1.19; P = 0.53), or recurrence rate (OR, 0.92; 95% CI, 0.71-1.19; P = 0.53). Moreover, the two techniques were comparable in length of hospital stay (LOS), postoperative complication rate, 30-day mortality rate, and rate of conversion to open surgery. CONCLUSIONS: The long-term oncological outcomes, expressed as OS, DFS, RFS, and recurrence rate, were similar between RG and LG. However, more randomized controlled trials with rigorous study designs and patient cohorts are needed to evaluate the oncologic outcomes of RG in patients with gastric cancer.

MiR-216a-3p inhibits colorectal cancer cell proliferation through direct targeting COX-2 and ALOX5.

Colorectal Cancer (CRC) is a most common digestive system malignant tumor. Despite recent advance in CRC treatment, searching for efficient biomarker and individual treatment therapy remains an urgent need. Cyclooxygenase-2 (COX-2) plays a critical role in the development and progression of CRC. In addition, shunting of arachidonic acid metabolism to the 5-lipoxygenase (ALOX5, 5-LO) pathway has also been reported to be implicated in the CRC pathogenesis. Cancer cell viability is promoted by ALOX5 through several mechanisms that are similar to those of COX-2. In recent years, it has been widely recognized that through inhibition of target genes, miRNAs can exert both oncogenic and tumor suppressive functions, depending on circumstances. In the present study, we screened for candidate microRNAs (miRNAs) which were predicted to regulate COX-2 and ALOX5 by online tools. Among the candidate miRNAs, miR-216a-3p expression was down-regulated in CRC tissues and cell lines; a higher miR-216a-3p expression was correlated with longer overall survival in patients with CRC. Moreover, ectopic miR-216a-3p expression significantly suppressed CRC cell proliferation. Using luciferase reporter gene, real-time PCR, and western blot assays, we confirmed the miR-216a-3p regulation of COX-2 and ALOX5 through direct targeting; further verified that miR-216a-3p could inhibit COX-2 and ALOX5 expression in CRC cells, thus to affect CRC cell proliferation. Taken together, miR-216a-3p presents a novel target of CRC treatment; rescuing miR-216a-3p expression in CRC might be a promising strategy for CRC treatment.

In Situ Generation and Consumption of H2O2 by Bienzyme-Quantum Dots Bioconjugates for Improved Chemiluminescence Resonance Energy Transfer.

Exploration of quantum dots (QDs) as energy acceptors revolutionizes the current chemiluminescence resonance energy transfer (CRET), since QDs possess large Stokes shifts and high luminescence efficiency. However, the strong and high concentration of oxidant (typically H2O2) needed for luminol chemiluminescence (CL) reaction could cause oxidative quenching to QDs, thereby decreasing the CRET performance. Here we proposed the use of bienzyme-QDs bioconjugate as the energy acceptor for improved CRET sensing. Two enzymes, one for H2O2 generation (oxidase) and another for H2O2 consumption (horseradish peroxidase, HRP), were bioconjugated onto the surface of QDs. The bienzyme allowed fast in situ cascaded H2O2 generation and consumption, thus alleviating fluorescence quenching of QDs. The nanosized QDs accommodate the two enzymes in a nanometric range, and the CL reaction was confined on the surface of QDs accordingly, thereby amplifying the CL reaction rate and improving CRET efficiency. As a result, CRET efficiency of 30-38% was obtained; the highest CRET efficiency by far was obtained using QDs as the energy acceptor. The proposed CRET system could be explored for ultrasensitive sensing of various oxidase substrates (here exemplified with cholesterol, glucose, and benzylamine), allowing for quantitative measurement of a spectrum of metabolites with high sensitivity and specificity. Limits of detection (LOD, 3σ) for cholesterol, glucose, and benzylamine were found to be 0.8, 3.4, and 10 nM, respectively. Furthermore, multiparametric blood analysis (glucose and cholesterol) is demonstrated.

Norcantharidin inhibits lymphangiogenesis by downregulating the expression of VEGF-C and VEGF-D in human dermal lymphatic endothelial cells in vitro.

AIMS: To investigate the effects of norcantharidin on the growth and migration of human dermal lymphatic endothelial cells (HDLECs) and further characterize its effect on lymphangiogenesis. METHODS: A 3-dimensional fibrin gel lymphangiogenesis model was built. Flow cytometry was used to analyze the rate of apoptosis and necrosis. RT-PCR, immunohistochemistry and immunoblotting assays were used to examine the effect of norcantharidin on vascular endothelial growth factor C (VEGF-C), VEGF-D and VEGF receptor 3 during in vitro lymphangiogenesis. RESULTS: Norcantharidin caused a marked dose and time-dependent inhibition of the growth of HDLECs with an IC50 of 40 nmol/l. The apoptotic rate of HDLECs was 13.21 ± 1.60% 24 h after treatment with 7.5 nmol/l norcantharidin and 42.34 ± 3.80% with 90 nmol/l norcantharidin (p < 0.01 vs. controls in both). Fibrin gel assays showed that norcantharidin (15 nmol/l) reduced the number of tubular structures from 68.4 ± 5.2 in untreated controls to 10.9 ± 2.3 (p = 0.000). RT-PCR, immunohistochemistry and immunoblotting assays showed norcantharidin markedly reduced the expression of VEGF-C and VEGF-D. CONCLUSION: Norcantharidin inhibits lymphangiogenesis by downregulating the expression of VEGF-C and VEGF-D, suggesting that norcantharidin could be an effective agent for targeting neolymphangiogenesis.

Neutral pH photoenzymatic activity of Au-doped g-C3N4 nanosheet for colorimetric detection of total antioxidant capacity in food samples.

Total antioxidant capacity (TAC) is vital for food quality evaluation. The emergence of various nanozymes with TMB as substrate offered a new avenue for TAC detection due to simple operation and fast response, but a long-standing challenge is its low activity at physiological pH, which may account for the discrepancy between the measured TAC and the actual antioxidant capacity in vivo. Herein, Au doping was explored to break the pH limitation of g-C3N4 nanosheets (CNNS) photozyme. The catalytic activities of Au@CNNS at pH 4.0 and 7.4 were 14.9- and 6.2-fold higher than that of CNNS at pH 4. The neutral pH photozymatic activity (photosensitized oxidation of TMB, oxidase mimic) of Au@CNNS was explored for sensitivity TAC detection (LOD: 1.0 µM TE), which featured more convenient operations and higher sensitivity over the DPPH assay. The proposed Au@CNNS-based photozymatic colorimetric method was explored for accurate detection of TAC in drinks and juices.