One-Dimensional Chiral Copper Iodide Chain-Like Structure Cu4 I4 (R/S-3-quinuclidinol)3 with Near-Unity Photoluminescence Quantum Yield and Efficient Circularly Polarized Luminescence.

Chiral organic-inorganic hybrid metal halide materials have shown great potential for circularly polarized luminescence (CPL) related applications for their tunable structures and efficient emissions. Here, this work combines the highly emissive Cu4 I4 cubane cluster with chiral organic ligand R/S-3-quinuclidinol, to construct a new type of 1D Cu-I chains, namely Cu4 I4 (R/S-3-quinuclidinol)3 , crystallizing in noncentrosymmetric monoclinic P21 space group. These enantiomorphic hybrids exhibit long-term stability and show bright yellow emission with a photoluminescence quantum yield (PLQY) close to 100%. Due to the successful chirality transfer from the chiral ligands to the inorganic backbone, the enantiomers show intriguing chiroptical properties, such as circular dichroism (CD) and CPL. The CPL dissymmetry factor (glum ) is measured to be ≈4 × 10-3 . Time-resolved photoluminescence (PL) measurements show long averaged decay lifetime up to 10 µs. The structural details within the Cu4 I4 reveal the chiral nature of these basic building units, which are significantly different than in the achiral case. This discovery provides new structural insights for the design of high performance CPL materials and their applications in light emitting devices.

0D Pyramid-intercalated 2D Bimetallic Halides with Tunable Electronic Structures and Enhanced Emission under Pressure.

Hybrid metal halides are emerging semiconductors as promising candidates for optoelectronics. The pursuit of hybridizing various dimensions of metal halides remains a desirable yet highly complex endeavor. By utilizing dimension engineering, a diverse array of new materials with intrinsically different electronic and optical properties has been developed. Here, we report a new family of 2D-0D hybrid bimetallic halides, (C6 N2 H14 )2 SbCdCl9 ⋅ 2H2 O (SbCd) and (C6 N2 H14 )2 SbCuCl9 ⋅ 2H2 O (SbCu). These compounds adopt a new layered structure, consisting of alternating 0D square pyramidal [SbCl5 ] and 2D inorganic layers sandwiched by organic layers. SbCd and SbCu have optical band gaps of 3.3 and 2.3 eV, respectively. These compounds exhibit weak photoluminescence (PL) at room temperature, and the PL gradually enhances with decreasing temperature. Density functional theory (DFT) calculations reveal that SbCd and SbCu are direct gap semiconductors, where first-principles band gaps follow the experimental trend. Moreover, given the different pressure responses of 0D and 2D components, these materials exhibit highly tunable electronic structures during compression, where a remarkable 11 times enhancement in PL emission is observed for SbCd at 19 GPa. This work opens new avenues for designing new layered bimetallic halides and further manipulating their structures and optoelectronic properties via pressure.

Ultrafast Excitonic Response in Two-Dimensional Hybrid Perovskites Driven by Intense Midinfrared Pulses.

Two-dimensional organic-inorganic hybrid perovskites (2DHPs) are natural quantum-well-like materials, in which strong quantum and dielectric confinement effects due to the organic spacers give rise to tightly bound excitons with large binding energy. To examine the mutual interactions between the organic spacer cations and the inorganic charge-residing octahedral framework in 2DHPs, here we perform femtosecond pump-probe spectroscopy by direct vibrational pumping of the organic spacers, followed by a visible-to-ultraviolet probe covering their excitonic resonances. Measurements on prototypical lead-bromide based 2DHP compounds, (BA)_{2}PbBr_{4} and (BA)_{2}(FA)Pb_{2}Br_{7} (BA^{+}=butylammonium; FA^{+}=formamidinium), reveal two distinct regimes of the temporal response. The first regime is dominated by a pump-induced transient expansion of the organic spacer layers that reduces the exciton oscillator strength, whereas the second regime arises from pump-induced lattice heating effects primarily associated with a spectral shift of the exciton energy. In addition, vibrational excitation enhances the biexciton emission, which we attribute to a stronger intralayer exciton confinement as well as vibrationally induced exciton detrapping from defect states. Our study provides fundamental insights regarding the impact of organic spacers on excitons in 2DHPs, as well as the excited-state dynamics and vibrational energy dissipation in these structurally diverse materials.

[Cyberknife stereotactic body radiotherapy for liver metastases from prostate cancer].

OBJECTIVE: To investigate the effectiveness and adverse effects of Cyberknife stereotactic body radiotherapy (SBRT) on liver metastases from PCa. METHODS: From June 2009 to September 2016, we treated 20 cases of PCa liver metastases by Cyberknife SBRT, at a total dose of 36 (30－50) Gy, on 1－3 liver metastatic lesions, for 3－5 times, with a prescription isodose line of 70－92%. We assessed the therapeutic effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), calculated the survival and disease-control rates using the Kaplan-Meier method, and analyzed the adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events－Version 4.0 (CTCAE 4.0). RESULTS: Of all the cases treated, complete response (CR) was found in 8 (40.0%), partial response (PR) in 9 (45.0%), stable disease (SD) in 2 (10.0%), and progressive disease (PD) in 1 (5.0%), with a local control rate (CR+PR) of 85.0% and a disease-control rate (CR+PR+SD) of 95.0%. Among the 14 patients with elevated PSA, 10 (71.4%) showed a significant decrease after treatment. The median follow-up time was 17 months, the 1- and 2-year survival rates were 85.0% and 15.0%, respectively, and the median survival time of the 20 patients was 16.5 months (95% CI: 12.12－22.88). Cyberknife SBRT was well tolerated in all the patients, with only a few mild adverse events (mainly grades 1 and 2 but no 4 and 5) during the whole course of treatment. CONCLUSIONS: Cyberknife SBRT is safe and effective in the treatment of PCa liver metastases, with a high local control rate, and capable of reducing the PSA level and raising the long-term survival rate of the patients.

Effect of cancer-associated fibroblasts on radiosensitivity of cancer cells.

Solid tumors are composed of tumor epithelial cells and the stroma, which are seemingly separate but actually related through cell-cell and cell-matrix interactions. These interactions can promote tumor evolution. Cancer-associated fibroblasts (CAFs) are the most abundant non-neoplastic cells in the stroma and also among the most important cell types interacting with cancer cells. Particularly, cancer cells promote the formation and maintenance of CAFs by secreting various cytokines. The activated CAFs then synthesize a series of growth factors to promote tumor cell growth, invasion and metastasis. More importantly, the presence of CAFs also interferes with therapeutic efficacy, bringing severe challenges to radiotherapy. This review summarizes the effect of CAFs on the radiosensitivity of tumor cells and underscores the need for further studies on CAFs in order to improve the efficacy of antitumor therapy.

TGF-ß1 rs1982073 polymorphism contributes to radiation pneumonitis in lung cancer patients: a meta-analysis.

Transforming growth factor beta 1(TGF-ß1) polymorphism was associated with radiation pneumonitis (RP) susceptibility, but their results have been inconsistent. The PubMed and CNKI were searched for case-control studies published up to Januray 01, 2016 was Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed eight publications involving 368 radiation pneumonitis cases and 855 controls of the association between TGF-ß1 T869C (rs1982073) and G915C (rs1800471) polymorphism and RP susceptibility. Our analysis suggested that TGF-ß1 T869C rs1982073 polymorphism was associated with lower RP risk for CT combined CC versus TT model (OR = 0.58, 95% CI = 0.43-0.77). However, for the G915C rs1800471 polymorphism, no association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model (OR = 0.82, 95% CI = 0.50-1.35). These results from the meta-analysis suggest that T869C rs1982073 polymorphism of TGF-ß1 may be associated with RP risk, and there may be no association between G915C polymorphism and RP risk.

Development and validation of a prognostic nomogram in patients aged ≥65 years with stage I-II non-small cell lung cancer treated with stereotactic body radiotherapy.

INTRODUCTION: This study aims to discern the efficacy and toxicity of stereotactic body radiotherapy (SBRT) in older adults with stage I-II non-small cell lung cancer (NSCLC) and establish a prognostic nomogram for these patients. MATERIALS AND METHODS: One hundred forty-two patients (aged ≥65 years) with clinically-confirmed stage I-II NSCLC treated with SBRT from 2009 to 2020 were enrolled in the study. Primary end points included overall survival (OS), progression free survival (PFS), cumulative incidences of local failure (LF), regional failure (RF), distant failure (DF), and toxicity. A nomogram for OS was developed and validated internally using one thousand bootstrap resamplings. RESULTS: The median times to LF, RF, and DF were 22.1 months, 26.9 months and 24.1 months, respectively. The 1-, 3-, and 5-year PFS rates from the start of SBRT were 79.4 %, 53.1 %, and 38.9 %, respectively. Performance status, pre-SBRT platelet to lymphocyte ratio (PLR), and planning tumor volume (PTV) were predictive of PFS. The 1-, 3-, and 5-year OS rates from the start of SBRT were 90.8 %, 67.9 % and 47.6 %, respectively. In multivariate analysis, good performance status, a low level of pre-SBRT PLR, and small tumor size were associated with better prognosis, all of which were included in the nomogram. The model showed optimal discrimination, with a C-index of 0.651 and good calibration. The most common adverse reactions were grade 1-2, such as anemia, cough, and fatigue. DISCUSSION: SBRT is a reasonable treatment modality for early-stage NSCLC in older adults. It achieved good survival outcomes and low toxicity. The proposed nomogram may be able to estimate individual outcomes for these patients.

Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer.

Background: Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution. Methods: From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP). Results: Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47-42.53 months). The median OS of all patients was 69 months (95% CI, 33.8-104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2-23.23%), 42.99% (95%CI, 27.56-57.53%), and 65.94% (95%CI, 45.76-80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84-11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15-12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up. Conclusion: This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.

Application of intraoperative radiotherapy for malignant glioma.

Malignant glioma is characterized by rapid tumor cell proliferation and high recurrence risk. In terms of its treatment, the therapeutic effects of maximum resection and postoperative radiotherapy with adjuvant chemotherapy as well as many other new therapeutic techniques such as antiangiogenic therapy and immunotherapy remain poor. Glioma recurrence, especially local recurrence, is an important reason of glioma treatment failure. Intraoperative radiotherapy (IORT) enables exclusion of radiation-sensitive normal tissue from the radiation field in operation and then the application of a single high-dose precision irradiation to the residual tumor or tumor bed. IORT has great application potential in the control of local recurrence of malignant tumors. This paper thus aims to review the current status and prospects of IORT's application in malignant glioma treatment.

Effect of chemical and biological factors on the densification of filamentous sludge.

Densification may be an alternative method for controlling sludge bulking; however, little information is available on the method. Various methods including different oxygen concentrations, surface velocities of aeration, calcium concentrations and extended starvation period were employed for triggering densification of filamentous sludge in this study. It was found that high surface velocity of aeration could effectively improve the settleability of filamentous sludge in the short term, which resulted in filamentous granulation, but could not avoid filamentous bulking even after granulation. Increase of calcium concentration could also improve the settleability by forming pigtail filaments colony in the short term, but could not trigger granulation. Extension of starvation period seems effective neither for further densification nor for granulation. Additionally, increased ovality of meshes formed by filaments was frequently associated with a dense structure of filamentous sludge. It was suggested that pigtail type of filamentous colony that thus increased the resistance to elevated shear force may encourage the densification of sludge, and two kind of densification growth patterns, i.e., granular or cluster growth pattern of filamentous sludge, were identified.

Efficacy of stereotactic body radiation therapy for locoregional recurrent pancreatic cancer after radical resection.

Objective: This study aimed to analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for locoregional recurrent pancreatic cancer after radical resection. Methods: Patients with locoregional recurrent pancreatic cancer after surgery treated with SBRT in our institution were retrospectively investigated from January 2010 to January 2020. Absolute neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS) and cumulative incidences of local failure (LF) and metastatic failure (MF). Results: A total of 22 patients received SBRT with a median prescribed dose of 40 Gy (range of 30-50 Gy)/4 to 7 fractions. The median OS of all patients was 13.6 months (95% CI, 9.6-17.5 months). 0-1 performance status (HR 12.10, 95% CI 2.04-71.81, P=0.006) and ≤2.1 pre-SBRT NLR (HR 4.05, 95% CI 1.21-13.59, P=0.023) were significant predictors of higher OS on multivariable analysis. The median progression-free survival (PFS) of the cohort was 7.5 months (95% CI, 6.5-8.5 months). The median time to LF and MF were 15.6 months and 6.4 months, respectively. The rate of MF as a first event was higher than that of first event LF. Pain relief was observed in all patients (100%) 6 weeks after SBRT. In terms of acute toxicity, grade 1 including fatigue (6, 27.3%), anorexia (6, 27.3%), nausea (4, 18.2%) and leukopenia (4, 18.2%) was often observed. No acute toxicity of grade 4 or 5 was observed. In terms of late toxicity, no treatment-related toxicity was found during follow-up. Conclusion: This study showed that SBRT can significantly reduce pain, effectively control local tumor progression, and have acceptable toxicity for patients with locoregional recurrence after radical resection of primary pancreatic cancer. Good performance status and lower pre-SBRT NLR were associated with improved overall survival.

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors.

Radiotherapy is one of the mainstays of cancer treatment. More than half of cancer patients receive radiation therapy. In addition to the well-known direct tumoricidal effect, radiotherapy has immunomodulatory properties. When combined with immunotherapy, radiotherapy, especially high-dose radiotherapy (HDRT), exert superior systemic effects on distal and unirradiated tumors, which is called abscopal effect. However, these effects are not always effective for cancer patients. Therefore, many studies have focused on exploring the optimized radiotherapy regimens to further enhance the antitumor immunity of HDRT and reduce its immunosuppressive effect. Several studies have shown that low-dose radiotherapy (LDRT) can effectively reprogram the tumor microenvironment, thereby potentially overcoming the immunosuppressive stroma induced by HDRT. However, bridging the gap between preclinical commitment and effective clinical delivery is challenging. In this review, we summarized the existing studies supporting the combined use of HDRT and LDRT to synergistically enhance antitumor immunity, and provided ideas for the individualized clinical application of multimodal radiotherapy (HDRT+LDRT) combined with immunotherapy.

Study on Motion Management of Pancreatic Cancer Treated by CyberKnife.

PURPOSE: We investigated the movement characteristics of pancreas and the clinical accuracy of tracking pancreas with the Synchrony Respiratory Tracking System (SRTS) during the CyberKnife treatment. These data provide a clinical data basis for the expansion margins of pancreatic tumor target. METHODS AND MATERIALS: Forty-two patients with pancreatic cancer treated by CyberKnife were retrospectively studied. The pancreatic displacement calculated from the x-ray images collected during the time interval between two consecutive movements constituted a data set. RESULTS: The total mean motion amplitudes and standard deviations of pancreatic tumors in SI, LR, AP, and radial directions were 3.66 ± 1.71 mm, 0.97 ± 0.62 mm, 1.52 ± 1.02 mm, and 1.36 ± 0.49 mm, respectively. The overall mean correlation errors and standard deviations were 0.82 ± 0.46 mm, 0.47 ± 0.33 mm, 0.41 ± 0.24 mm, and 0.98 ± 0.37 mm, respectively. The overall mean prediction errors and standard deviations were 0.57 ± 0.14 mm, 0.62 ± 0.28 mm, 0.39 ± 0.17 mm, and 1.58 ± 0.36 mm, respectively. The correlation errors and prediction errors of pancreatic tumors at different anatomical positions in SI, LR, and AP directions were statistically significant (p < 0.05). CONCLUSIONS: The tumor motion amplitude, the tumor location, and the treatment time are the main factors affecting the tracking accuracy. The pancreatic tumors at different anatomical locations should be treated differently to ensure sufficient dose coverage of the pancreatic target area.

Combined inhibition of AURKA and HSF1 suppresses proliferation and promotes apoptosis in hepatocellular carcinoma by activating endoplasmic reticulum stress.

PURPOSE: In this study we aimed to assess the anti-tumor effect of co-inhibition of Aurora kinase A (AURKA) and heat shock transcription factor 1 (HSF1) on hepatocellular carcinoma (HCC), as well as to explore the mechanism involved. METHODS: Expression of AURKA and HSF1 in primary HCC tissues and cell lines was detected by immunohistochemistry (IHC), qRT-PCR and Western blotting. AURKA was knocked down in HepG2 and BEL-7402 HCC cells using lentivirus-mediated RNA interference. Next, CCK-8, clone formation, transwell and flow cytometry assays were used to assess their viability, migration, invasion and apoptosis, respectively. The expression of proteins related to cell cycle progression, apoptosis and endoplasmic reticulum stress (ERS) was analyzed using Western blotting. In addition, in vivo tumor growth of HCC cells was assessed using a nude mouse xenograft model, and the resulting tumors were evaluated using HE staining and IHC. RESULTS: Both AURKA and HSF1 were highly expressed in HCC tissues and cells, while being negatively related to HCC prognosis. Knockdown of AURKA significantly inhibited the colony forming and migrating capacities of HCC cells. In addition, we found that treatment with an AURKA inhibitor (Danusertib) led to marked reductions in the proliferation and migration capacities of the HCC cells, and promoted their apoptosis. Notably, combined inhibition of AURKA and HSF1 induced HCC cell apoptosis, while increasing the expression of ERS-associated proteins, including p-eIF2α, ATF4 and CHOP. Finally, we found that co-inhibition of AURKA and HSF1 elicited an excellent in vivo antitumor effect in a HCC mouse model with a relatively low cytotoxicity. CONCLUSIONS: Combined inhibition of AURKA and HSF1 shows an excellent anti-tumor effect on HCC cells in vitro and in vivo, which may be mediated by ERS. These findings suggest that both AURKA and HSF1 may serve as targets for HCC treatment.

Enhancing the magnetic performance of pyrazine-N-oxide bridged dysprosium chains through controlled variation of ligand coordination modes.

While assembling superparamagnetic units in a controlled manner is crucial for future applications of molecular nanomagnets, optimizing their magnetic properties while achieving directional assembly of these units still remains a formidable challenge. Herein, we demonstrate how the assembly of two dysprosium chain complexes, namely, [Dy2(L)2Cl2(CH3OH)3]n·nCH3OH (1) and [Dy(L)Cl(DMF)]n (2) (H2L = N'-(5-bromo-2-hydroxybenzylidene)pyrazine-N-oxide-carbohydrazide), can be successfully manipulated using an appropriate bridging ligand design. Both complexes contain similar dimeric units bridged by two alkoxido oxygens from an L2- ligand, but extended by its pyrazine-N-oxide group exhibiting two distinct coordination modes, namely, single and double pyrazine-N-oxide bridges, respectively. Magnetic studies reveal that both complexes display typical slow magnetic relaxation under zero direct-current field; however, the anisotropy barrier and the coercive field at 2 K for complex 2 are twice as much as that of 1. A further theoretical study indicates that switching the coordination mode from a single pyrazine-N-oxide bridge to double bridges can enhance both the magnetic anisotropy of dysprosium ions and magnetic coupling within the dimeric cores. The synergistic effect between the magnetic anisotropy of dysprosium ions and magnetic interactions among them directly contributes to the overall better performance of complex 2.

Clinical Effects of Stereotactic Body Radiation Therapy Targeting the Primary Tumor of Liver-Only Oligometastatic Pancreatic Cancer.

AIM: To investigate the efficacy and safety of stereotactic body radiotherapy (SBRT) targeting the primary tumor for liver-only oligometastatic pancreatic cancer. METHODS: We compared the efficacy and safety of SBRT plus chemotherapy with chemotherapy alone in patients with liver-only oligometastatic pancreatic cancer. The populations were balanced by propensity score-weighted and propensity score-matched analyses based on baseline variables. The primary outcome was overall survival (OS). The secondary outcomes included progression free survival (PFS), local progression, metastatic progression and symptomatic local control. RESULTS: This is a retrospective study of 89 pancreatic cancer patients with liver-only oligometastasis. Overall, 34 (38.2%) and 55 (61.8%) patients received SBRT plus chemotherapy and chemotherapy alone, respectively. After propensity score matching, 1-year OS rate was 34.0% (95%CI, 17.8-65.1%) in the SBRT plus chemotherapy group and 16.5% (95%CI, 5.9-46.1%) in chemotherapy alone group (P=0.115). The 6-month PFS rate was 29.4% (95%CI, 15.4-56.1) in SBRT plus chemotherapy and 20.6% (95%CI, 8.8-48.6) in chemotherapy alone group (P=0.468), respectively. Further subgroup analysis indicated that the addition of SBRT improved OS in patients with primary tumor located in the head of pancreas (stratified HR, 0.28; 95% CI, 0.09 to 0.90) or good performance status (stratified HR, 0.24; 95% CI, 0.07 to 0.86). In terms of disease control, SBRT delayed local progression of pancreas (P=0.008), but not distant metastatic progression (P=0.56). Besides, SBRT offered significant abdominal/back pain relief (P=0.016) with acceptable toxicities. CONCLUSIONS: The addition of SBRT to chemotherapy in patients with liver-only oligometastatic pancreatic cancer improves the OS of those with primary tumor located in the head of pancreas or good performance status. In addition, it is a safe and effective method for local progression control and local symptomatic palliation in patients with metastatic pancreatic cancer.

Metformin inhibits hepatocellular carcinoma development by inducing apoptosis and pyroptosis through regulating FOXO3.

This study aimed to expand our understanding of metformin (Met) in inhibiting hepatocellular carcinoma (HCC) progression and to investigate its underlying mechanism. Met was administrated to HCC cells at 5, 10, and 20 µM, after which the cell phenotype was evaluated. RNA-seq cluster analysis was used to screen for target genes modulated by Met. Luciferase activity and ChIP assays were performed to detect the effect of FOXO3 on the transcriptional activation of NLRP3. We evaluated the effect of Met and FOXO3 and on the growth of HCC cells in vivo. Met inhibited HCC cell proliferation and promoted apoptosis. Met also induced pyroptosis of HCC cells. FOXO3 was significantly upregulated by Met treatment, and FOXO3 activated transcription of NLRP3. Cells after Met treatment together with FOXO3 knockdown have a stronger colony formation and migration ability but a lower apoptosis rate compared to the Met treatment alone group. In vivo, Met inhibited HCC tumor growth. The tumors in Met treatment and FOXO3 knockdown group grew faster than in Met treatment group. Thus, Met attenuates HCC cell development by inducing apoptosis and pyroptosis. This effect of metformin is partially dependent on FOXO3 which can activate the transcription of NLRP3.

Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes.

Background: Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells. Methods: In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation. Results: The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells in vitro, and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. In vivo imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues. Conclusion: Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.

Role of thoracic radiotherapy in extensive stage small cell lung cancer: a systemic review and meta-analysis.

BACKGROUND: The role of thoracic consolidation radiotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) remains controversial. This study aimed to evaluate the efficacy of thoracic radiotherapy (TRT) in these patients. METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane library to identify qualified clinical studies. The hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were extracted, and toxicity of the TRT group versus non-TRT group was analyzed. RESULTS: A total of 12 studies were included in this meta-analysis, including 936 patients in the TRT group and 1,059 patients in the non-TRT group. The combined results showed that TRT significantly improved OS (HR =0.65; 95% CI: 0.55-0.77, P<0.00001), PFS (HR =0.64; 95% CI: 0.56-0.72, P<0.00001) and LRFS (HR =0.38, 95% CI: 0.26-0.53, P<0.00001). Subgroup analysis showed that OS benefits were observed in patients receiving sequential TRT (HR =0.67; 95% CI: 0.54-0.84, P=0.0006). The addition of TRT significantly improved OS in patients over 65 years of age (HR =0.55; 95% CI: 0.40-0.74, P=0.0001). For patients with only one organ metastasis, there was no significant difference in OS between the two groups (HR =0.61; 95% CI: 0.36-1.01, P=0.06). There was no statistical difference in hematologic toxicity (leukopenia, thrombocytopenia, anemia) and non-hematologic toxicity (nausea or vomiting) between the two groups. The incidence of grade ≥3 esophageal toxicity was 4.6% in the TRT group and 0% in the non-TRT group (P=0.0001). Grade ≥3 bronchopulmonary toxicity was 2.9% in the TRT group and 0.8% in the non-TRT group (P=0.02). CONCLUSIONS: TRT improves OS, PFS and LRFS in patients with ES-SCLC, with a low increase in esophageal and bronchopulmonary toxicity. More randomized controlled trials (RCTs) are expected to confirm our conclusions. PROSPERO REGISTRATION NUMBER: CRD42020190575.

Transparent Cellulose Nanofibrils Composites with Two-layer Delignified Rotary-cutting Poplar Veneers (0°-layer and 90°-layer) for Light Acquisition of Solar Cell.

Our transparent cellulose nanofibrils composites (TCNC) directly from rotary-cutting poplar veneer (RPV) whose lignin can be easily stripped by our treatment. This TCNC is prepared by stripping lignin of original RPV and infiltrating epoxy resin (ER) into delignified RPV. This TCNC with two-layer delignified RPVs whose grains perpendicular (0/90°) to each other, which were solidified on solar cell while infiltrating ER. This TCNC with high transmittance (~90%), high haze (~90%), and equal refractive index fluctuation. Comparing with epoxy resin (ER), this TCNC can enhance open circuit voltage (VOC) from 1.16 to ~1.36 and short circuit density (JSC) from 30 to ~34 for the solar cell, and can enhance test fore from 0.155 kN to ~0.185 kN and displacement from 43.6 mm to ~52.5 mm.