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The sensitive detection of cancer-associated exosomal microRNAs shows enormous potential in cancer diagnosis. Herein, a ratiometric fluorescent biosensor based on self-assembled fluorescent gold nanoparticles (Au NPs) and duplex-specific nuclease (DSN)-assisted signal amplification was fabricated for sensitive detection of colorectal cancer (CRC)-associated exosomal miR-92a-3p. In this biosensing system, the hairpin DNA modified with sulfhydryl and fluorescent dye Atto-425 at both ends is conjugated to fluorescent Au NPs through Au-S bonds, resulting in the quenching of Atto-425. The miR-92a-3p can open the hairpin of DNA and forms an miR-92a-3p/DNA heteroduplex, triggering the specific cleavage of DSN for the DNA in the heteroduplex. As a result, Atto-425 leaves the fluorescent Au NPs and recovers the fluorescence emission. The released miR-92a-3p can hybridize with another hairpin DNA and lead to a stronger fluorescence recovery of Atto-425 to form a signal amplification cycle. The stable fluorescence of Au NPs and the changing fluorescence of Atto-425 constitute a ratiometric fluorescent system reflecting the concentration of miR-92a-3p. This biosensor exhibits excellent specificity and can distinguish CRC patients from healthy individuals by detecting miR-92a-3p extracted from clinical exosome samples, showing the potential in CRC diagnosis.

Background The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients’ adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (健脾补肾续贯方, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. Methods A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518)

Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and an important tumor suppressor in human malignancies. Here, we aimed to investigate the expression profile of FBP1 in ovarian cancer, the molecular mechanisms that regulate FBP1 expression and to examine how the FBP1 regulatory axis contributes to tumorigenesis and progression in ovarian cancer. We showed that FBP1 expression was significantly decreased in ovarian cancer tissues compared with normal ovarian tissues, and low-FBP1 expression predicted poor prognosis in patients with ovarian cancer. The enhanced expression of FBP1 in ovarian cancer cell lines suppressed proliferation and 2-D/3-D invasion, reduced aerobic glycolysis, and sensitized cancer cells to cisplatin-induced apoptosis. Moreover, DNA methylation and C-MYC binding at the promoter inhibited FBP1 expression. Furthermore, through physical interactions with signal transducer and activator of transcription 3 (STAT3), FBP1 suppressed nuclear translocation of STAT3 and exerted its non-metabolic enzymatic activity to induce the dysfunction of STAT3. Thus, our study suggests that FBP1 may be a valuable prognostic predictor for ovarian cancer. C-MYC-dependent downregulation of FBP1 acted as a tumor suppressor via modulating STAT3, and the C-MYC/FBP1/STAT3 axis could be a therapeutic target.

Background Although programmed cell death‐ligand 1 (PD‐L1) plays a well‐known function in immune checkpoint response by interacting with programmed cell death‐1 (PD‐1), the cell‐intrinsic role of PD‐L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD‐L1 in the progression and metastasis of ovarian cancer. Methods Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD‐L1‐knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD‐L1 in ovarian cancer. Results Our results showed that PD‐L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD‐L1 was identified to directly interact with vascular endothelial growth factor receptor‐2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD‐L1 was found to be regulated by the oncogenic transcription factor c‐JUN at the transcriptional level, which enhanced the expression of PD‐L1 in ovarian cancer. Furthermore, we demonstrated that PD‐L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti‐angiogenesis and the inhibition of cell migration and invasion. Conclusion Our results demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, suggesting that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients., This manuscript demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, and suggested that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

Artificial skins reproducing properties of human skin are emerging and significant for study in various areas, such as robotics, medicine, and textiles. Perspiration, as one of the most imperative thermoregulation functions of human skin, is gaining increasing attention, but how to realize ideal artificial skin for perspiration simulation remains challenging. Here, an integrated 3D hydrophilicity/hydrophobicity design is proposed for artificial sweating skin (i-TRANS). Based on normal fibrous wicking materials, the selective surface modification with gradient of poly(dimethylsiloxane) (PDMS) creates hydrophilicity/hydrophobicity contrast in both lateral and vertical directions. With the additional help of bottom hydrophilic Nylon 6 nanofibers, the constructed i-TRANS is able to transport "sweat" directionally without trapping undesired excess water and attain uniform "secretion" of sweat droplets on the top surface, decently mimicking human skin perspiration situation. This fairly comparable simulation not only presents new insights for replicating skin properties, but also provides proper in vitro testing platforms for perspiration-relevant research, greatly avoiding unwanted interference from the "skin" layer. In addition, the facile, fast, and cost-effective fabrication approach and versatile usage of i-TRANS can further facilitate its application.

Chemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of the tumor cells, it is difficult to make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) therapy has made significant progress in the treatment of advanced malignant tumors, and patients who benefit from this therapy may obtain a long-lasting response. Unfortunately, immunotherapy is only effective in a limited number of patients with microsatellite instability—high (MSI-H), and segment initial responders can subsequently develop acquired resistance. From September 4, 2014, the first anti-PD-1/PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for mCRC second-line treatment in 2017. Immunotherapy has rapidly developed in the past 7 years. The in-depth research of the ICB treatment indicated that the mechanism of colorectal cancer immune-resistance has become gradually clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies.

Colorectal cancer (CRC) is the third most common malignancy and ranks as the second leading cause of cancer-related deaths worldwide. Despite the improvements in CRC diagnosis and treatment approaches, a considerable proportion of CRC patients still suffers from poor prognosis due to late disease detections and lack of personalized disease managements. Recent evidences have not only provided important molecular insights into their mechanistic behaviors but also indicated that identification of cancer-specific long non-coding RNAs (LncRNAs) could benefit earlier disease detections and improve treatment outcomes in patients suffering from CRC. LncRNAs have raised extensive attentions as they participate in various hallmarks of CRC. The mechanistic evidence gleaned in the recent decade clearly reveals that lncRNAs exert their oncogenic roles by regulating autophagy, epigenetic modifications, enhancing stem phenotype and modifying tumor microenvironment. In view of their pleiotropic functional roles in malignant progression, and their frequently dysregulated expression in CRC patients, they have great potential to be reliable diagnostic and prognostic biomarkers, as well as therapeutic targets for CRC. In the present review, we will focus on the oncogenic roles of lncRNAs and related mechanisms in CRC as well as discuss their clinical potential in the early diagnosis, prognostic prediction and therapeutic translation in patients with this malignancy.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the therapeutic landscape of haematological malignancies. However, resistance and relapse remain prominent limitations, and they are related to the limited persistence and efficacy of CAR T cells, downregulation or loss of tumour antigens, intrinsic resistance of tumours to death signalling, and immune suppressive microenvironment. Rational combined modality treatments are regarded as a promising strategy to further unlock the antitumor potential of CAR T cell therapy, which can be applied before CAR T cell infusion as a conditioning regimen or in ex vivo culture settings as well as concomitant with or after CAR T cell infusion. In this review, we summarize the combinatorial strategies, including chemotherapy, radiotherapy, haematopoietic stem cell transplantation, targeted therapies and other immunotherapies, in an effort to further enhance the effectiveness of this impressive therapy and benefit more patients.

The abnormal expression of long non-coding RNAs (LncRNAs) in platelet-derived microparticles (PMPs) is closely related to immune disorders and may lead to antiphospholipid antibody syndrome and recurrent miscarriage. To understand the association between the LncRNAs in PMPs and RM/APS, the differences in the expression of LncRNAs in RM/APS patients and healthy controls were analyzed. Microarray analysis and RT-qPCR detection proved that RM/APS patient exhibited high levels of LncNR_040117 expression. The lentiviral silent expression transfection of HTR-8/SVneo cells indicated that LncNR_040117 downregulation decreased the activity of HTR-8/SVneo cells and inhibited the MAPK signaling pathway, further confirming the biomarker proficiency of LncNR_040117 for RM/APS. After that, we proposed a β-In2S3@g-C3N4 nanoheterojunction-based photoelectrochemical (PEC) biosensor to achieve the ultrasensitive detection of LncNR_040117. The nanoheterojunction aids in the effective separation of photogenerated carriers and significantly improve the photocurrent response of the biosensor. The conjugation of LncNR_040117 onto the PEC biosensing platform increased the steric hindrance between electrolyte and electrode, subsequently decreasing the photocurrent signal. The PEC biosensor showed a wide detection range of 0.1–106 fM and a low limit of detection of 0.025 fM. For clinical sample testing, the results of the PEC and RT-qPCR were highly consistent. Overall, LncNR_040117 in PMPs was identified as an effective biomarker for RM/APS and could be accurately detected by the proposed PEC biosensor, which is expected to provide a reliable diagnostic platform for RM/APS.

Background: Over half of patients with advanced cancer report appetite loss or anorexia. Previous studies have shown the benefit of acupuncture for cancer-related nausea and vomiting, but limited evidence exists for its role in appetite improvement. Our study aimed to evaluate the feasibility and safety of auricular acupuncture to improve appetite for cancer patients with advanced disease. Methods: We performed a two-arm parallel, pilot randomized controlled trial (RCT) of auricular acupuncture versus usual care control in patients with stage III or IV cancer who experienced appetite loss. The primary outcome was changed in the Simplified Nutritional Appetite Questionnaire (SNAQ; score range, 4–20) between two groups from baseline to weeks 2 and 4, with secondary outcomes including change in weight, as well as an additional evaluation at week 8 for durability of treatment effects. We used independent two-sample t-test for the change in mean score for each outcome during or after treatment. We assessed the interaction between time and treatment from baseline to weeks 2, 4, and 8 using mixed-effects models by ANOVA test. Results: We randomized 55 patients to auricular acupuncture (N=27) or control group (N=28). By week 4, the auricular acupuncture group had a significantly higher escalation in the SNAQ score than the control group compared with baseline [mean difference 3.69; 95% confidential interval (95% CI): 2.5, 4.8; P

Recepteur d’origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the β-catenin expression level through the AKT1/GSK3β signaling pathway. Meanwhile, the binding sites of β-catenin were identified in the promoter region of SIX1 and it was also demonstrated that β-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/β-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer. Electronic supplementary material The online version of this article (10.1007/s10565-020-09525-5) contains supplementary material, which is available to authorized users.

Increasing evidences suggest that insufficient radiofrequency ablation (IRFA) can paradoxically promote tumor invasion and metastatic processes, whereas the effects of moderate hyperthermia on cancer progression are not well illustrated. Our study found that IRFA can increase the in vitro migration, invasion, and epithelial–mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells via induction of Snail, a master regulator of EMT events. Among measured miRNAs, IRFA can decrease the expression of miR-148a-5p in HCC cells. Whereas overexpression of miR-148a-5p can reverse IRFA-induced migration of HCC cells and upregulation of Snail, mechanistically overexpression of miR-148a-5p can directly target and decrease the expression of protein kinase ATM (ataxia telangiectasia mutated), which can increase protein stability of Snail. Collectively, our data suggest that IRFA can regulate the miR-148a-5p/ATM/Snail axis to trigger migration of HCC cells.

Rationale: Cisplatin derivatives are first-line chemotherapeutic agents for epithelial ovarian cancer. However, chemoresistance remains a major hurdle for successful therapy and the underlying molecular mechanisms are poorly understood at present. Methods: RNA sequencing of organoids (PDO) established from cisplatin-sensitive and -resistant ovarian cancer tissue samples was performed. Glucose metabolism, cell senescence, and chemosensitivity properties were subsequently examined. Immunoprecipitation, mass spectrometry, Fӧrster resonance energy transfer-fluorescence lifetime imaging (FRET-FLIM), luciferase reporter assay, ChIP and animal experiments were conducted to gain insights into the specific functions and mechanisms of action of the serine/threonine kinase, Aurora-A, in ovarian cancer. Results: Aurora-A levels were significantly enhanced in cisplatin-resistant PDO. Furthermore, Aurora-A promoted chemoresistance through suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Mechanistically, Aurora-A bound directly to the transcription factor sex determining region Y-box 8 (SOX8) and phosphorylated the Ser327 site, in turn, regulating genes related to cell senescence and glycolysis, including hTERT, P16, LDHA and HK2, through enhancement of forkhead-box k1 (FOXK1) expression. Conclusions: Aurora-A regulates cell senescence and glucose metabolism to induce cisplatin resistance by participating in the SOX8/FOXK1 signaling axis in ovarian cancer. Our collective findings highlight a novel mechanism of cisplatin resistance and present potential therapeutic targets to overcome chemoresistance in ovarian cancer.

Integrative oncology has developed for about 20 years in some countries; however, integrative oncology is still a relative new term for most China’s oncologists. Thus, it is essential to summarize the experience and expertise, share details of differing existing models and discuss future perspectives to help define and guide practice in integrative oncology in China. This study presents a summary of the basic characteristics, status, and challenges of integrative oncology in China, and also reports on China’s integrative physicians’ service delivery, clinical practice and research patterns of integrative oncology by an online national survey, including 405 oncologists. It is easy for cancer patients to access to integrative therapies in China. Public funding is sufficient for integrative oncology in China, and services are often provided through general hospitals and academic hospitals. Most (95.3%) of oncologists showed a positive attitude toward the development of integrative oncology. More than half (55.6%) of the oncologists worried about the influence on integrative oncology of COVID-19, especially for routine treatment, follow-up and holding seminars. We found that integrative oncology in China has swiftly developed in recent years. However, we suggest that standard diagnosis and treatment patterns and national professional guidelines should be set up as soon as possible.

Chemodynamic therapy (CDT) based on Fenton or Fenton-like reactions is an emerging cancer treatment that can both effectively fight cancer and reduce side effects on normal cells and tissues, and it has made important progress in cancer treatment. The catalytic efficiency of Fenton nanocatalysts(F-NCs) directly determines the anticancer effect of CDT. To learn more about this new type of therapy, this review summarizes the recent development of F-NCs that are responsive to tumor microenvironment (TME), and detailedly introduces their material design and action mechanism. Based on the deficiencies of them, some effective strategies to significantly improve the anticancer efficacy of F-NCs are highlighted, which mainly includes increasing the temperature and hydrogen peroxide concentration, reducing the pH, glutathione (GSH) content, and the dependence of F-NCs on acidic environment in the TME. It also discusses the differences between the effect of multi-mode therapy with external energy (light and ultrasound) and the single-mode therapy of CDT. Finally, the challenges encountered in the treatment process, the future development direction of F-NCs, and some suggestions are analyzed to promote CDT to enter the clinical stage in the near future. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12951-022-01278-z.

Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

Drug resistance and potential cardiotoxicity severely limit the DOX-mediated chemotherapy in clinical. Multi-drug combination is conducive to the realization of multi-modal synergy at the molecular level, which is crucial in drug dose optimization and improvement of therapeutic effect. In this work, fluorescent biotinylated Au Nanoclusters as an active targeting carrier was developed to realize real-time biological imaging and dual-drug delivery simultaneously. DNA toxin doxorubicin (DOX) and tyrosinase inhibitor gefitinib (GEF) were selected as dual-drug models for the treatment of human non-small cell lung cancer. The in vitro and in vivo results showed that dual-drug combination suppressed cancer cell growth more efficiently than any single formula at the same concentrations. GEF can block signaling in target cancer cells with mutated and overactive EGFR, thereby inhibiting tumor growth and metastasis and promoting tumor cell apoptosis. Combined with DOX chemotherapy, it will effectively overcome the problem of DOX resistance. In addition, the dual-drug delivery system produced excellent synergistic therapeutic effects without extra adverse toxicities. It provides a reference for the design and clinical application of the dual-drug delivery system.

The prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported.A total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response).Of the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients' prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2).TRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.

Introduction: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. Methods: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale ( n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. Results: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including “I feel loss of appetite,” “I feel abdomen fullness,” “I feel my arms and legs lack strength,” “I feel short of breath when talking,” and “My stool is formless” (Cronbach’s alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related ( P Conclusion: The patient-reported TCM-SDS scale for CRC showed adequate initial reliability and validity. The development of the scale provided an outcome measurement tool, which could facilitate future studies to better evaluate the role of TCM in treating CRC.

Objective: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). Methods: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. Results: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. Conclusion: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.

Intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPCs) are vascular tumors that have a high rate of local recurrence and extracranial metastases. Intradural extramedullary spinal dissemination of intracranial SFT/HPC is extremely rare. There is a paucity of data available to elucidate the molecular mechanisms of intraspinal dissemination of intracranial SFT/HPC. Herein, we presented a case of intracranial SFT/HPC with intraspinal metastasis. The resected tumor specimens were enrolled in a clinical sequencing program, including whole-exome and transcriptome sequencing. By comparing genomic sequencing data of the intracranial tumors with intraspinal metastasis, we established the somatic mutational profiles of these tumors. Clonality analysis revealed a distinct subclonal structure in the intracranial tumor and its intraspinal metastasis, which might reflect the possibility of intratumoral clonal selection and evolution during the process of tumor dissemination. Through bioinformatics analysis and Sanger sequencing validation, a DSTYK mutation (Met296Ile) was identified as a candidate driver of intraspinal metastasis in this SFT/HPC case. Further, an intracranial tumor-derived SFT/HPC cell line, HPC3, was established to explore the mechanisms of the DSTYK mutation in promoting SFT/HPC metastasis. Based on the HPC3 cell model, we found that the DSTYK mutation promoted cell migration and invasion of HPC3 cells via activation of ERK1/2 signaling, which was inhibited by the MEK/ERK inhibitor AZD6244. The DSTYK mutation was also shown to upregulate the expression of two metastasis-related molecules: MMP2 and MMP9 in HPC3 cells; however, this effect was attenuated by AZD6244 treatment. Therefore, the DSTYK mutation may activate ERK1/2/MMP2/9 signaling to promote tumor cell metastasis in SFT/HPC. In conclusion, our study revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease.

Green tea accounts for approximately 20% of the world's total tea yield. (-)-Epigallocatechin gallate (EGCG) is an active catechin in green tea, which suppresses tumor growth and enhances drug sensitivity in various cancers, but the molecular mechanism is still unclear. Chemotherapy drugs, such as 5-fluorouracil (5-FU), are a common strategy for clinical treatment of cancer patients; however, the lower response rate caused by prolonged use becomes the main reason for tumor recurrence. Therefore, discovering a safe and effective chemo-sensitizer is an urgent task required to be solved. Here, we report that EGCG reinforces the sensitivity of colon cancer cells to 5-FU, and the IC50 values of 5-FU is decreased from 40 ± 4.2 μM to 5 ± 0.36 μM in one human colon carcinoma cell line-HCT-116, and from 150 ± 6.4 μM to 11 ± 0.96 μM in the other human colon carcinoma cell line-DLD1 when these cells are cotreated with 50 μM EGCG. Consistently, compared to 5-FU or EGCG treatment alone, the combination of both significantly promotes cancer cell apoptosis and DNA damage. Further mechanism research reveals that treatment of colorectal cancer (CRC) with 50 μM EGCG inhibits GRP78 expression, activates the NF-κB (2.55 ± 0.05-fold for HCT-116 and 2.27 ± 0.08-fold for DLD1) pathway, and enhances miR-155-5p (2.12 ± 0.02-fold for HCT-116 and 2.01 ± 0.01-fold for DLD1) level. The elevated miR-155-5p strongly suppresses target gene MDR1 expression, which blocks the efflux of 5-FU. The accumulation of 5-FU resulted in caspase-3 and PARP activation, Bcl-2 reduction, and Bad increase, which ultimately lead to cancer cell apoptosis. Overall, our data show that EGCG may be act as a novel chemo-sensitizer, and the GRP78/NF-κB/miR-155-5p/MDR1 pathway plays a vital role in EGCG enhancing the sensitivity of colorectal cancer to 5-FU.

Barasertib is a highly selective Aurora kinase B (AURKB) inhibitor and has been widely applied in a variety of cancer cells to investigate the regulatory function of AURKB. However, the effect of barasertib on glucose metabolism in gastric cancer (GC) remains illustrated. Here, barasertib was identified to effectively reduce glucose uptake and lactate production in GC cells in a dose-dependent and time-dependent manner. The expression levels of GLUT1, LDHA and HK2 were decreased by barasertib treatment of GC cells. Furthermore, we found that barasertib induced the expression of ribosomal protein S7 (RPS7), as a tumor suppressor, to regulate glucose metabolism. Silencing of RPS7 rescued the effects of barasertib on glucose metabolism in GC cells. Overexpression of RPS7 suppressed the promoter activity of C-Myc, which has been identified as an important regulator of glucose metabolism in cancer cells. The clinical data showed that the expression level of AURKB in GC patients' sera and tissues were positively correlated with those of C-Myc, GLUT1 and LDHA, but negatively with that of RPS7. Therefore, these findings provide new evidence that barasertib regulates GC cell glucose metabolism by inducing the RPS7/C-Myc signal pathway, and have important implications for the development of therapeutic approaches using AURKB as a target protein to prevent tumor recurrence.

Glucose-regulated protein 78 (GRP78) often highly expresses in a wide range of tumors, which plays promotive functions due to its diversity of location in the development of tumor. Particularly, GRP78 can be secreted into microenvironment by tumor cells through the pathway of exosome, which promotes proliferation, angiogenesis, and drug resistance in cancer cells. Hence, we discovered a potential inhibitor to block GRP78 secretion. We screened five small molecules that may interact with the GRP78 from 51 traditional Chinese medicine molecules by molecular docking. By using western blot, we found that one of the molecules can inhibit the secretion of GRP78, which is salvianolic acid A (SAA). Further, SAA could interact with the lysine residue 633 (K633) of GRP78, which inhibited GRP78 secretion. Moreover, SAA-GRP78 interaction can facilitate GRP78 of cytosol sorted into lysosome for degradation rather than exosome. In conclusion, our research revealed that SAA has the novel function of anti-angiogenesis via the tumor environment.

Aim: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. Method: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. Results: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_9 (coef. −0.64, P = .01). Conclusion: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC).It was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1-20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018.Median follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9-28.5] vs. 14.3 months in the control group (95% CI 11.3-21.4, P;0.05). Hazard ratio (95% CI) was 0.55 (0.31-0.95, P=0.040). There were no significant differences between the two groups in PFS (P0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P;0.05 or P;0.01), respectively.Quxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).

Background: Traditional Chinese medicine (TCM) is widely used among Chinese cancer patients. However, little is known about Chinese patients’ expectations and barriers toward using TCM for cancer. Methods: We conducted a cross-sectional survey within a patient-support group, the Beijing Anti-Cancer Association. We measured the outcome, Chinese cancer survivors’ expectations and barriers toward TCM utilization, using a modified version of ABCAM (Attitudes and Beliefs towards Complementary and Alternative Medicine), the ABTCM (Attitudes and Beliefs towards Traditional Chinese Medicine). We used multivariate models to evaluate the impact of socioeconomic status and clinical factors on their expectations and barriers (including treatment concerns and logistical challenges domain) toward TCM. Results: Among 590 participants, most patients expected TCM to boost their immune system (96%), improve their physical health (96%), and reduce symptoms (94%). Many had logistical challenges (difficulty decocting herbs (58%) and finding a good TCM physician (55%)). A few were concerned that TCM might interfere with conventional treatments (7.6%), and that many TCM treatments are not based on scientific research (9.1%). In the multivariable regression model, age ≤60 years was independently associated with higher expectation score ( P = .031). Age ≤60 years (coefficient 5.0, P = .003) and localized disease (coefficient 9.5, P = .001) were both associated with higher treatment concerns. Active employment status (coefficient 9.0, P = .008) and localized disease (coefficient 7.5, P = .030) were related to more logistical challenges. Conclusion: Age and cancer stage were related to Chinese cancer patients’ perceived expectations and barriers toward TCM use. Understanding these attitudes is important for reshaping the role that TCM plays in China’s patient-centered comprehensive cancer care model.

Purpose We aimed to quantify Chinese cancer survivors’ perceived needs for survivorship care and to evaluate whether these needs could impact their willingness to use traditional Chinese medicine (TCM). Methods We conducted a cross-sectional survey with members of the Beijing Anti-Cancer Association in China. We measured perceived needs with the seven-item Brief Chinese Cancer Survivorship Needs Scale that assesses psychological, functional, nutritional, social, body image, pain, and symptom needs. The outcome variable was willingness to use TCM for survivorship care. We performed multivariable logistic regression analyses to evaluate whether perceived needs are associated with willingness. Results A total of 600 patients were invited, with a response rate of 81%. The mean (standard deviation) score of the perceived needs scale (0 to 10) was 4.4 (2.2), with the majority of participants endorsing nutritional (72%), symptom (65%), and psychological (54%) needs. Among survivors, 387 (80%; 95% CI, 76% to 83%) were willing to use TCM for survivorship care. In multivariable analysis, a higher perceived needs score (adjusted odds ratio [OR], 1.33; 95% CI, 1.14 to 1.56; P < .001) was associated with greater willingness to use TCM. Specifically, nutritional (OR, 3.17; 95% CI, 1.79 to 5.62; P < .001) and symptom needs (OR, 3.15; 95% CI, 1.79 to 5.55; P < .001) had the strongest relationship. Conclusion A higher level of perceived needs, especially in the areas of nutrition and symptoms, was associated with greater willingness to use TCM for survivorship care.

A total of 47 passive air samples and 25 soil samples were collected to study the temporal trend, distribution, and air–soil exchange of polychlorinated naphthalenes (PCNs) in Shanghai, China. Atmospheric PCNs ranged from 3.44 to 44.1 pg/m3 (average of 21.9 pg/m3) in summer and 13.6 to 153 pg/m3 (average of 40.0 pg/m3) in winter. In the soil samples, PCN concentrations were 54.7–1382 pg/g dry weight (average of 319 pg/g). Tri-CNs and tetra-CNs were two dominant homolog groups in air samples, while di-CNs were also found at comparable proportions to tri-CNs and tetra-CNs in soil samples. Most air and soil samples from the industrial and urban areas showed higher PCN concentrations than those from suburban areas. However, some soil samples in urban centers presented higher PCN concentrations than industrial areas. Analysis of PCN sources indicated that both industrial thermal process and historical usage of commercial PCN mixtures contributed to the PCN burden in most areas. The fugacity fraction results indicated a strong tendency of volatilization for lighter PCNs (tri- to hexa-CNs) in both seasons, and air–soil deposition for octa-CNs. Moreover, air–soil exchange fluxes indicate that soil was an important source of atmospheric PCNs in some areas. The results of this study provide information for use in the evaluation of the potential impact and human health risk of PCNs around the study areas.

The correlation between right hepatic vein (RHV) diameter and inferior RHV (IRHV) incidence and that between IRHV incidence and other clinical features remain unclear. We investigated factors correlated with IRHV incidence as well as provide a simple and reliable method for predicting IRHV presence preoperatively.We obtained computed tomography (CT) imaging data of 1980 patients from the Department of Radiology, Qingdao Municipal Hospital, from July 1, 2016, to July 1, 2017. We excluded patients with heart disease, inferior vena cava (IVC) disease, history of liver surgery or trauma, space-occupying lesions in the liver, and other diseases, which can cause hepatic hemodynamic changes. CT images of patients were three-dimensionally reconstructed. We measured RHV and IRHV diameter as well as the angle between the RHV and the IVC.Data on 299 patients were included in this study; the incidence of IRHV was 34.44%. Sex, age, and the angle between the RHV and IVC did not correlate with IRHV incidence. RHV diameter negatively correlated with IRHV incidence (P 0.05). The area under the receiver-operating characteristic curve for IRHV incidence was 0.878. The diagnostic threshold value of RHV diameter was 8.86 mm.A negative correlation was found between RHV diameter and IRHV incidence, suggesting that IRHV is absent with RHV diameter 8.86 mm, but is present with RHV diameter 8.86 mm. This suggests that measuring only RHV diameter can predict the presence of an IRHV when IRHV-related hepatectomy and IRHV preserved living donor liver transplantation are needed.

Apatinib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR2), and has shown encouraging therapeutic effects in various malignant tumors. As yet, however, the role of apatinib in ovarian cancer has remained unknown. Here, we sought to elucidate the role of apatinib in the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as in glucose metabolism in these cells. The effects of apatinib on ovarian cancer cell viability and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, respectively. The expression of VEGFR2/AKT1/SOX5/GLUT4 pathway proteins was assessed using Western blotting, and glucose uptake and lactate production assays were used to detect glycolysis in ovarian cancer cells. SOX5 was exogenously over-expressed and silenced in ovarian cancer cells using expression vector and shRNA-based methods, respectively. RNA expression analyses were performed using RNA-seq and gene-chip-based methods. GLUT4 promoter activity was assessed using a dual-luciferase reporter assay. The expression of p-VEGFR2 (Tyr1175), p-AKT1 (Ser473), p-GSK3β (Ser9), SOX5 and GLUT4 in xenograft tissues was assessed using immunohistochemistry (IHC). We found that apatinib inhibited the in vitro and in vivo viability and proliferation in Hey and OVCA433 ovarian cancer cells in a dose-dependent and time-dependent manner. We also found that apatinib effectively suppressed glucose uptake and lactate production by blocking the expression of GLUT4 in these cells. In addition, we found that SOX5 predominantly rescued the inhibitory effect of apatinib on GLUT4 expression by activating its promoter. Finally, we found that apatinib regulated the expression of SOX5 by suppressing the VEGFR2/AKT1/GSK3β signaling pathway. From our results, we conclude that apatinib suppresses the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as glycolysis by inhibiting the VEGFR2/AKT1/GSK3β/SOX5/GLUT4 signaling pathway. Apatinib may serve as a promising drug for the treatment of ovarian cancer.

Quxie capsule (QX), a herbal remedy used in traditional Chinese medicine, is routinely used in advanced colorectal cancer treatment in Xiyuan Hospital in Beijing, China. However, the mechanism(s) underlying the effect of QX in colorectal cancer remain unclear, which hampers the optimal use of QX for the treatment of the disease. The transcription factor forkhead box O1 (Foxo1) plays important roles in regulation of cell cycle, apoptosis, and immune response in various cancers. In this study, we examined the antitumor efficacy of QX in a mouse model of colorectal cancer and further investigated the mechanism by which QX regulated Foxo1 protein-mediated pathways. QX administered via gavage daily for 2 weeks in mice carrying CT26 mouse colon tumors resulted in significantly lower mean tumor weight (0.93 ± 0.32 g) compared with that in vehicle control-treated mice (1.57 ± 0.57 g, P

Women with aggressive triple-negative breast cancer (TNBC) are at high risk of brain metastasis, which has no effective therapeutic option partially due to the poor penetration of drugs across the blood−brain barrier. Trifluoperazine (TFP) is an approved antipsychotic drug with good bioavailability in brain and had shown anticancer effect in several types of cancer. It drives us to investigate its activities to suppress TNBC, especially the brain metastasis. In this study, we chose three TNBC cell lines MDA-MB-468, MDA-MB-231, and 4T1 to assess its anticancer activities along with the possible mechanisms. In vitro, it induced G0/G1 cell cycle arrest via decreasing the expression of both cyclinD1/CDK4 and cyclinE/CDK2, and stimulated mitochondria-mediated apoptosis. In vivo, TFP suppressed the growth of subcutaneous xenograft tumor and brain metastasis without causing detectable side effects. Importantly, it prolonged the survival of mice bearing brain metastasis. Immunohistochemical analysis of Ki67 and cleaved caspase-3 indicated TFP could suppress the growth and induce apoptosis of cancer cells in vivo. Taken together, TFP might be a potential available drug for treating TNBC with brain metastasis, which urgently needs novel treatment options.

Radioresistance resulted from the intrinsic features of tumors often gives rise to unsatisfied therapeutic outcome. In particular, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H2O2) and hypoxia has been believed as a tremendous obstacle for radiotherapy. Therefore, developing an effective radiosensitizer in response to both X-ray and the TME is highly imperative but remains a challenge so far. Here, we for the first time explore bismuth heteropolytungstate (BiP5W30) nanoclusters as radiosensitizers for the TME-manipulated enhancement of radiotherapy. On the one hand, BiP5W30 nanoclusters can increase radiation dose deposition within tumors by high-Z elements like Bi and W. On the other hand, in virtue of the unique electron structure and multi-electron property, they have the capability of depleting glutathione (GSH) via redox reaction and catalyzing the decomposition of H2O2 to HO to enhance ROS generation upon X-ray radiation. Moreover, reduced graphene oxide (rGO) coupled with BiP5W30 can further improve radiocatalytic activity through promoting electron-hole separation. Simultaneously, due to the considerable near-infrared absorption of rGO, photothermal therapy can overcome the tumor hypoxia microenvironment and thus synergize with radiotherapy. In addition to providing a promising radiosensitizer, this finding is expected to extend the application of polyoxometalates used in the biomedical field.

In this work, the concentrations of polybrominated diphenyl ethers (PBDEs) were determined in air, dust and fly ash samples from three legal waste electrical and electronic equipment dismantling plants with strict pollution controls. The risks posed by PBDEs to workers at the plants were assessed. The atmospheric concentrations of PBDEs in the different e-waste recycling workshops were 0.58–2.89 × 103 ng/m3, and predominantly distributed in the particle phase (90.7%–99.9%). The concentrations of the PBDEs in the floor dust and fly ash samples from bag-type dust collectors in different workshops were 2.39–125 μg/g, 5.84–128 μg/g, respectively. The contributions of BDE-209 in air, floor dust and fly ash samples were 84.0%–97.9%, 11.2%–95.3% and 74.0%–94.9%, respectively, indicating that deca-BDE commercial formulations were their major sources. Daily exposure to PBDEs was also lower than has been found for workers in other recycling workshops. Human exposures to BDE-47, BDE-99, BDE-153, and BDE-209 were all below the levels considered to pose appreciable risks. Dust ingestion was the main exposure route for manual recyclers, and inhalation was the main exposure route for waste transportation workers. The results of this study indicate that PBDEs emissions and risks are lower in modern, legal e-waste recycling facilities with effective pollution controls. However, the effectiveness of the pollution controls need to be further researched in plastic crushing areas.

Ovarian cancer is the most malignant gynecologic cancer among women worldwide. Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been identified as a potential therapeutic agent in treating several malignant tumors, but the molecular mechanism of CT in ovarian cancer still remains illustrated. Here, we sought to elucidate the regulatory function of CT on cell glucose metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells effectively inhibited glucose uptake and lactate production in ovarian cancer cells. The expression levels of glycolysis‐related proteins, such as GLUT1, LDHA, and HK2, were decreased by the treatment of CT detected by qRT‐PCR and immunoblotting. Mechanistically, CT exerted its anti‐tumor effect by targeting STAT3/SIRT3/HIF‐1α signaling pathway in vitro and in vivo, which could be rescued by the introduction of SIRT3 shRNA in ovarian cancer cells. The clinical data showed that the expression level of STAT3 in ovarian cancer patients’ sera and tissues was positively correlated with those of GLUT1, LDHA, HK2 and HIF‐1α, but negatively with that of SIRT3These findings provide evidence that CT inhibited cellular glycolysis‐induced cell growth and proliferation through repression of STAT3/SIRT3/HIF‐1α signaling pathway, indicating that CT may be developed as a chemotherapeutic agent to treat ovarian cancer.

Glucose-regulated protein 78 (GRP78), an important molecular chaperone in the endoplasmic reticulum, is often over-expressed in the central region of advanced tumor and acts as a promoter of tumor progression. As main immune cells in the tumor microenvironment, infiltration of abundant macrophages into advanced tumor further facilitates growth of tumor. Although the potential association between GRP78 and infiltration of macrophages, its underlying mechanisms are poorly understood. Here, we reported that the level of secreted GRP78 was positively correlated with the malignant degree of tumor; and enhanced secretion of GRP78 facilitated recruitment of macrophages into tumors both in vitro and in vivo. Further studies revealed that secreted GRP78 was able to transport into macrophages and bound to intracellular Ca2 , which led to uneven distribution of Ca2 and subsequent polarization of macrophages. Furthermore, macrophages polarization promoted pro-adhesion by activating Fibronectin−integrin-β1−FAK pathway and accelerated MMP2/9 mediated extracellular matrix degradation that contributed to migration of macrophages. Polarization of macrophages also led to the distribution of GTP-Rac1 and GTP-Cdc42 in front protrusion and GTP-RhoA in rear contraction by activating RhoGTPase family members, which further resulted in migration of macrophages in a certain direction. Mechanistically, GRP78-mediated polarization of macrophages activated expression of microRNA-200b-3p. By directly targeting RhoGDI, miR-200b-3p stimulated the activity of RhoGTPase that facilitated cytoskeleton remodeling and subsequently polarization of macrophages. Together, our results reveal a novel function of GRP78 to promote the recruitment of macrophages to tumor and provide a potential therapeutic target for malignancies. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 31770382 and No. 81803791), “1331 project” Collaborative Innovation Center and team (1331 CIC). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All animal experiments conducted in this study were approved by the Institutional Animal Care and Use Committee of Shanxi University (Taiyuan, China). All of the experimental procedures were performed in accordance with the protocols and ethical regulations approved by the Institutional Animal Care and Use Committee of Shanxi University (Taiyuan, China).

Road dusts were collected from an area where intense mechanical recycling of plastic wastes occurs in Wen'an, north China. These dusts were investigated for polybrominated diphenyl ethers (PBDEs) and heavy metals contamination to assess the health risk related to these components. Decabromodiphenyl ether (BDE-209) and Σ21PBDE concentrations in these dusts ranged from 2.67 to 10,424 ng g(-1) and from 3.23 to 10,640 ng g(-1), respectively. These PBDE concentrations were comparable to those observed in road dust from e-waste recycling areas but were 1-2 orders of magnitude higher than concentrations in outdoor or road dusts from other areas. This indicates that road dusts in the study area have high levels of PBDE pollution. BDE-209 was the predominant congener, accounting for 86.3% of the total PBDE content in dusts. Thus, commercial deca-BDE products were the dominant source. The average concentrations of As, Cd, Cr, Cu, Hg, Pb, Sb, and Zn in these same dust samples were 10.1, 0.495, 112, 54.7, 0.150, 71.8, 10.6, and 186 mg kg(-1), respectively. The geoaccumulation index suggests that road dusts in this area are moderately to heavily polluted with Cd, Hg, and Sb. This study shows that plastic waste processing is a major source of toxic pollutants in road dusts in this area. Although the health risk from exposure to dust PBDEs was low, levels of some heavy metals in this dust exceeded acceptable risk levels for children and are of great concern.

We performed a proteomic survey of Salmonella enterica serovar Typhimurium during infection of host epithelial cells. Our data reveal substantial metabolic reshuffling of Salmonella in the host in addition to severe degeneration of bacterial flagella and chemotaxis systems. The large-scale quantitative data allowed us to chart an overview of intracellular Salmonella carbon metabolism. Notably, we found preferential utilization of glycolysis, the pentose phosphate pathway, mixed acid fermentation, and nucleotide metabolism. In contrast, the tricarboxylic acid (TCA) cycle and aerobic and anaerobic respiration pathways were largely repressed. Furthermore, inactivation of glycolysis and purine biosynthesis led to severe growth defects, indicating important roles in intracellular Salmonella replication. In summary, we exploited quantitative proteomics for rational design of follow-up genetic studies and identified pathways important for bacterial fitness within host cells.

We collected street dust from Huainan, a typical coal-mining city in China, to investigate the contamination features and health risks of heavy metals. Concentrations of Co, Cr, Cu, Pb, As, and Sb were generally low to moderate, while pollution levels of Cd and Hg were moderate to high. Concentrations of Cd and Hg were associated with considerable health risks at 64.3% and 58.6% of sites, respectively. In particular, about a fifth of samples had associated high risks as a result of Hg contamination levels. Relative to other urban areas, the street dust from the mining area had no more severe metal pollution, which might be partly attributed to the deposition of coal dust onto street dusts. A source assessment indicated that metals in dust form Huainan were mainly derived from vehicular-related activities, industrial emissions, weathering of coal dust and natural soils, and coal combustion. Although the health risk levels from exposure to individual metals in dusts were low, the non-carcinogenic risks from multiple metals to local children exceeded the acceptable level (1.0), suggesting that the overall risk from exposure to multiple metals in dust is concerning.

Concentrations of heavy metals (As, Cd, Co, Cr, Cu, Hg, Pb and Sb) in vegetables, meat and fish purchased from traditional agri-product markets in Huainan, China, were measured. Concentrations of the eight metals in most of the measured samples were lower than their respective maximum allowable concentrations (MACs), except for Pb, Cd, Cr and Cu in some of the samples exceeded safe limits. Based on local food consumption, the intake of individual metals was estimated to be less than their respective recommended limits. However, the overall target hazard quotient (THQ) for the eight metals was 1.07 based on the digestion of leafy vegetables and 2.12 based on the consumption of all of the investigated foods. The results of this study suggest that the overall risk from exposure to multiple metals in foods should be of concern, even though low-to-moderate heavy metal pollution is present in foods from Huainan markets.

As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control.

Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

We reported a simple and reusable fluorescent sensor for heme proteins based on the electrospun nanofibrous membrane doped with a fluorescent conjugated polymer P. The sensor showed favorable fluorescence sensing performance towards the heme proteins, including hemoglobin (Hb), myoglobin (Mb) and cytochrome c (Cyt c). The surface wettability and sensing performance of the electrospun nanofibrous membrane were investigated in detail using Hb as the model. The nanofibrous sensor showed satisfactory reversibility with less than 10% signal loss after nine quenching–regeneration cycles, and good batch-to-batch reproducibility with a relative standard deviation of 3.4% (n = 3). The linear range of the sensor for Hb determination was 2.0 × 10−8 to 3.0 × 10−6 M with a detection limit of 1.2 × 10−8 M. The quenching process is mainly based on the fluorescence resonance energy transfer mechanism between the fluorescent conjugated polymer P and the heme prosthetic groups, therefore the sensor was selective against most of the common interferents. As an example to evaluate the feasibility of the sensor in practical application, Hb in human blood samples was determined and the results were in good agreement with the data provided by the hospital. To the best of our knowledge, this is the first work using fluorescent electrospun nanofibrous sensor for protein analysis in real biological sample.

Plastic wastes are increasingly being recycled in many countries. However, available information on the metals released into the environment during recycling processes is rare. In this study, the contamination features and risks of eight heavy metals in soils and sediments were investigated in Wen'an, a typical plastic recycling area in North China. The surface soils and sediments have suffered from moderate to high metal pollution and in particular, high Cd and Hg pollution. The mean concentrations of Cd and Hg were 0.355 and 0.408 mg kg(-1), respectively, in the soils and 1.53 and 2.10 mg kg(-1), respectively, in the sediments. The findings suggested that there is considerable to high potential ecological risks in more than half of the soils and high potential ecological risk in almost all sediments. Although the health risk levels from exposure to soil metals were acceptable for adults, the non-carcinogenic risks to local children exceeded the acceptable level. Source assessment indicated that heavy metals in soils and sediments were mainly derived from inputs from poorly controlled plastic waste recycling operations in this area. The results suggested that the risks associated with heavy metal pollution from plastic waste recycling should be of great concern.

The seasonal and spatial variations, compositional profiles, and possible sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in ambient air samples in Shanghai of China were investigated by passive air samplers, and the potential inhalation risks posed by these chemicals were evaluated. The following results were obtained: (1) The World Health Organization (WHO) toxic equivalency (TEQ) values for PCDD/Fs were in the range of 10.8-259 fg m(-3) (mean 63.4 fg m(-3)) in summer and 24.1-154 fg m(-3) (mean 83.4 fg m(-3)) in winter. Atmospheric PCDD/F levels were in the following order: industrial areas commercial and residential areas rural areas. (2) 2,3,4,7,8-PeCDF (24 %), 2,3,7,8-TeCDD (16 %), 1,2,3,7,8-PeCDD (13 %), and 2,3,7,8-TeCDF (12 %) were the predominant contributors to the TEQ of PCDD/Fs. (3) There was a slight seasonal trend with higher TEQ values in winter than in summer, which could be related to seasonal variations in the dispersion of PCDD/Fs in ambient air. (4) The children's daily intake was at the lower end of the range for the tolerable daily intake of PCDD/Fs recommended by WHO, which indicates that the inhalation risk of PCDD/Fs for local residents in Shanghai is relatively low.

The release of pollutants during the recycling of contaminated plastics is a problem which has drawn worldwide attention; however, little information on the transfer of polybrominated diphenyl ethers (PBDEs) in these processes is available. We conducted a survey of PBDEs in soils, sediments, and human hair in a typical plastic waste recycling area in northern China. The total concentrations (ng/g) of 21 PBDEs were 1.25-5504 (average 600), 18.2-9889 (average 1619), and 1.50-861 (average 112) in soils, sediments, and hair, respectively. The PBDE concentrations were comparable to concentrations observed in e-waste recycling areas; however, the concentrations in soils and sediments were 1-3 orders of magnitude higher than in other areas, and the concentrations in hair were much higher than in other areas. This indicates that this area is highly polluted with PBDEs. BDE-209 was the dominant congener (representing 91.23%, 92.3%, and 91.5% of the total PBDEs observed in soils, sediments, and hair, respectively), indicating that the commercial deca-BDE product was dominant. The commercial penta- and octa-BDE products made small contributions to the total PBDE concentrations, unlike what has been found in some e-waste recycling areas. Our results show that crude plastic waste processing is a major contributor of PBDEs to the environment and humans, which should be of great concern.