Despite the excellent efficacy and low toxicity of photoresponse therapy, which has attracted considerable attention for use in non-small cell lung cancer (NSCLC) therapy, unsatisfactory cellular ...permeability, and instability, both in vitro and in vivo have limited further clinical applications of indole cyanine photosensitizers. Here, we explore the supramolecular self-assembly of a 'hyalurosome' that is mediated by calcium phosphate nanonuclei. Through hyaluronate-mediated CD44 targeting, the constructed hyalurosome specifically delivers ICG into NSCLC cells and then induces severe hyperthermia accompanied by the generation of singlet oxygen upon photoirradiation. In contrast to the action of the native form, indocyanine green encapsulated in a hyalurosome showed significantly increased cellular endocytosis and inhibited cell proliferation both in vitro and in vivo. Our study indicated that this hyalurosome is a promising candidate for the targeted delivery of photosensitizers, which may be useful in NSCLC therapy.
Introduction
There are a number of options for the symptomatic treatment of peripheral neuropathy, but the overall treatment outcomes remain unsatisfactory.
Methods
A total of 60 patients with ...refractory diabetic neuropathy were randomly assigned to two groups. Patients in Group A were treated with computed tomography (CT)-guided sympathetic neurolysis with alcohol, and patients in Group B were treated with a combined therapy of CT-guided catheterization to achieve continuous lumbar block for 4 weeks followed by neurolysis with alcohol administered via the catheter. The outcomes of these two treatment strategies were then analyzed in terms of pain relief, blood flow in the lower limb microcirculation, plasma levels of inflammatory mediators, and complications.
Results
The visual analog scale (VAS) pain scores of all patients after treatment decreased significantly at the different evaluation time points compared with pre-treatment values, with the intergroup analysis revealing that the VAS scores were lower in Group B patients than in Group A patients at all post-treatment time points. Skin temperature, capillary filling time, and blood oxygen saturation level were significantly improved in all patients at the 1- and 7-day post-treatment assessment compared to pre-treatment values, but patients in Group B showed a greater improvement. The plasma levels of inflammatory mediators were lower in all patients at the 7-day post-treatment assessment compared to pre-treatment values, with those of patients in Group B being statistically significantly lower than those of patients in Group A.
Conclusion
Combined treatment with continuous lumbar sympathetic block followed by neurolysis with alcohol provided more benefit in all assessed outcomes than sympathetic alcohol neurolysis alone. The results show that the procedures were associated with satisfactory safety outcomes and sustained analgesic effects, thereby providing clinical evidence supporting the use of this novel treatment for patients with painful diabetic neuropathy.
Lung adenocarcinoma (LUAD) usually contains heterogeneous histological subtypes, among which the micropapillary (MIP) subtype was associated with poor prognosis while the lepidic (LEP) subtype ...possessed the most favorable outcome. However, the genomic features of the MIP subtype responsible for its malignant behaviors are substantially unknown. In this study, eight FFPE samples from LUAD patients were micro-dissected to isolate MIP and LEP components, then sequenced by whole-exome sequencing. More comprehensive analyses involving our samples and public validation cohorts on the two subtypes were performed to better decipher the key biological and evolutionary mechanisms. As expected, the LEP and MIP subtypes exhibited the largest disease-free survival (DFS) differences in our patients.
EGFR
was found with the highest mutation frequency. Additionally, shared mutations were observed between paired LEP and MIP components from single patients, and recurrent mutations were verified in the Lung-Broad, Lung-OncoSG, and TCGA-LUAD cohorts. Distinct biological processes or pathways were involved in the evolution of the two components. Besides, analyses of copy number variation (CNV) and intratumor heterogeneity (ITH) further discovered the possible immunosurveillance escape, the discrepancy between mutation and CNV level, ITH, and the pervasive DNA damage response and WNT pathway gene alternations in the MIP component. Phylogenetic analysis of five pairs of LEP and MIP components further confirmed the presence of ancestral
EGFR
mutations. Through comprehensive analyses combining our samples and public cohorts,
PTP4A3
,
NAPRT
, and
RECQL4
were identified to be co-amplified. Multi-omics data also demonstrated the immunosuppression prevalence in the MIP component. Our results uncovered the evolutionary pattern of the concomitant LEP and MIP components from the same patient that they were derived from the same initiation cells and the pathway-specific mutations acquired after
EGFR
clonal mutation could shape the subtype-specificity. We also confirmed the immunosuppression prevalence in the MIP subtype by multi-omics data analyses, which may have resulted in its unfavorable prognosis.
Although the neuroprotective role of propofol has been identified recently, the regulatory mechanism associated with microRNAs (miRNAs/miRs) in neuronal cells remains to be poorly understood. We ...aimed to explore the regulatory mechanism of propofol in hypoxia-injured rat pheochromocytoma (PC-12) cells.
PC-12 cells were exposed to hypoxia, and cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry assay/Western blot analysis, respectively. Effects of propofol on hypoxia-injured cells were measured, and the expression of miR-153 was determined by stem-loop RT-PCR. After that, whether propofol affected PC-12 cells under hypoxia via miR-153 was verified, and the downstream protein of miR-153 as well as the involved signaling cascade was finally explored.
Hypoxia-induced decrease of cell viability and increase of apoptosis were attenuated by propofol. Then, we found hypoxia exposure up-regulated miR-153 expression, and the level of miR-153 was further elevated by propofol in hypoxia-injured PC-12 cells. Following experiments showed miR-153 inhibition reversed the effects of propofol on hypoxia-treated PC-12 cells. Afterwards, we found BTG3 expression was negatively regulated by miR-153 expression, and BTG3 overexpression inhibited the mTOR pathway and AMPK activation. Besides, hypoxia inhibited the mTOR pathway and AMPK, and these inhibitory effects could be attenuated by propofol.
Propofol protected hypoxia-injured PC-12 cells through miR-153-mediataed down-regulation of BTG3. BTG3 could inhibit the mTOR pathway and AMPK activation.
Background
We aimed to develop a prognostic nomogram based on a new classification of combined micropapillary and solid components in pathological stage IA invasive lung adenocarcinoma (LUAD).
...Methods
According to the total proportion of solid and micropapillary components (TPSM), the X‐tile software was applied to classify patients into the following three groups: TPSM‐low (TPSM‐L), TPSM‐middle (TPSM‐M), and TPSM‐high (TPSM‐H). The postoperative survival was compared among the three groups. The multivariate Cox regression analysis was performed to identify independent prognostic factors for survival. According to these factors, a nomogram model was developed to provide a personalized prognostic evaluation.
Results
A total of 595 patients with pathological stage IA invasive LUAD were included in our study. The 5‐year disease‐free survival and overall survival rates in patients with TPSM‐H and TPSM‐M were significantly lower than those with TPSM‐L. The multivariate Cox regression analysis revealed that the TPSM classification was an independent prognostic factor for survival. According to TPSM classification, we developed a nomogram model which had good calibration and reliable discrimination ability to evaluate survival.
Conclusions
The nomogram based on the combination of micropapillary and solid components has good prognostic value in predicting postoperative recurrence and survival of patients with pathological stage IA invasive LUAD.
Purpose
Maintaining telomeres by recruiting telomerase-to-chromosome ends is essential for cancer cell survival. Inhibiting telomerase recruitment to telomeres represents a novel strategy for ...telomere-based lung cancer therapy. However, approaches for interrupting telomerase recruitment for cancer therapy still need to be explored.
Methods
The telomere-binding protein TPP1 is responsible for recruiting telomerase to telomeres and synthesizing telomeres through the association between the oligosaccharide/oligonucleotide-binding (OB)-fold domain of TPP1 and telomerase reverse transcriptase. We overexpressed the TPP1 OB domain (TPP1-OB) by lentivirus infection in lung cancer cells. Telomere length was examined by Southern blot analysis of terminal restriction fragments. The effects of TPP1-OB on cell proliferation, the cell cycle, apoptosis, chemosensitivity, and tumor growth were evaluated in vitro and in vivo.
Result
TPP1-OB inhibited the recruitment of telomerase to telomeres and shortened telomere length by acting as a dominant-negative mutant of TPP1. TPP1-OB resulted in reduced cell proliferation, G1 cell cycle arrest, and increased cell apoptosis in lung cancer cells. Cell apoptosis occurred mainly through the caspase-3-dependent signaling pathway. TPP1-OB also suppressed anchorage-independent growth and tumor growth in vivo. Moreover, we demonstrated that TPP1-OB enhances the sensitivity of lung cancer cells to the chemotherapeutic drug paclitaxel.
Conclusion
Our results suggest that inhibiting TPP1-mediated telomerase recruitment by expressing the TPP1-OB domain is a potential novel strategy for telomere-targeted lung cancer therapy.
Altered expression of claudin-3 (CLDN3), a key cytoskeletal structural protein of the tight junctions in the epithelium, is associated with the development and metastasis of various human cancers. ...CLDN3 expression has been shown to be significantly associated with the prognosis of lung squamous cell carcinoma (SqCC). This study investigated the role of CLDN3 in inhibiting lung SqCC cell migration and invasion as well as the underlying molecular mechanisms. The CLDN3 levels were assessed between 20 paired lung SqCC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The ectopic CLDN3 overexpression or knockdown was generated by using a plasmid carrying CLDN3 cDNA or shRNA, respectively. CLDN3 expression was significantly reduced in lung SqCC tissues vs. the adjacent normal tissues. The ectopic CLDN3 overexpression markedly inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of lung cancer H520 cells, whereas CLDN3 knockdown had an inverse effect on SK-MES-1 cells. However, cell viability and plate colony formation assays showed that both CLDN3 knockdown and overexpression did not affect SqCC cell proliferation. Both tissue and cell data revealed that CLDN3 expression was significantly associated with the expression of the EMT biomarkers E-cadherin and Vimentin. Furthermore, CLDN3-modulated EMT and expression of the EMT markers were through regulation of the Wnt/β-catenin signaling pathway. In conclusion, this study identified reduced CLDN3 expression in lung SqCC tissues, which was associated with the progression and metastasis of lung SqCC and was attributed to EMT by activation of the Wnt pathway. Thus, CLDN3 could be further evaluated as a novel biomarker for predicting the prognosis of lung SqCC and as a target for the treatment of lung SqCC in the future.
Lead halide perovskites have attracted much attention in photodetector fabrication. Up to now, several strategies have been used to modulate the device performance. Here, P3HT-CsPbBr3 monocrystalline ...microwires based photodetectors are demonstrated by coupling LSPR and piezo-phototronic effects. The photocurrent, response speed and recovery speed under 532 nm laser illumination were increased to nearly 3.5, 70 and 8.4 times when decorated with Au NCs and applied with a compressive strain of −0.29%, respectively. The enhancement of performances can be attributed to the increased light absorption caused by LSPR effect and the enhanced separation of photo-generated holes at the heterojunction interface caused by piezo-phototronic effect. This work suggests that all-inorganic perovskites CsPbBr3 based photodetectors can be significantly enhanced by coupling plasmonic and piezo-phototronic effects. This strategy can be used to modulate the performance of optoelectronic devices based on other piezoelectric materials.
P3HT-CsPbBr3 monocrystalline microwires based photodetectors are demonstrated. The photocurrent, response speed and recovery speed were increased to nearly 3.5, 70 and 8.4 times when decorated with Au NCs and applied with a compressive strain of −0.29%, respectively. The enhancement of performances can be attributed to the increased light absorption caused by LSPR effect and the enhanced separation of photo-generated holes at the heterojunction interface caused by piezo-phototronic effect. Display omitted
•By utilizing LSPR effect, the responsivity and response/recovery speed of photodetectors were obviously enhanced.•The piezo-phototronic effect of CsPbBr3 MWs on devices’ performances with different directions and strains were studied.•High performance photodetectors based on plasmonic and piezo-phototronic coupling effects were developed.
Precipitation is the basic component of the Earth’s water cycle. Obtaining high-resolution and high-precision precipitation data is of great significance. This paper establishes a precipitation ...retrieval model based on a random forest classification and regression model during the day and at night with FY-4B/AGRI Level1 data on China from July to August 2022. To evaluate the retrieval effect of the model, the GPM IMERG product is used as a reference, and the retrieval results are compared against those of the FY-4B/AGRI operational precipitation product. In addition, the retrieval results are analyzed according to different underlying surfaces. The results showed that compared with the FY-4B/AGRI operational precipitation product, the retrieval model can better identify precipitation and capture precipitation areas of light rain, moderate rain, heavy rain and torrential rain. Among them, the probability of detection (POD) of the day model increased from 0.328 to 0.680, and the equitable threat score (ETS) increased from 0.252 to 0.432. The POD of the night model increased from 0.337 to 0.639, and the ETS score increased from 0.239 to 0.369. Meanwhile, the precipitation estimation accuracy of the day model increased by 38.98% and that of the night model increased by 40.85%. Our results also showed that due to the surface uniformity of the ocean, the model can identify precipitation better on the ocean than on the land. Our findings also indicated that for the different underlying surfaces of the land, there is no significant difference in each evaluation index of the model. This is a strong argument for the universal applicability of the model. Notably, the results showed that, especially for more vegetated areas and areas covered by water, the model is capable of estimating precipitation. In conclusion, the precipitation retrieval model that is proposed herein can better determine precipitation regions and estimate precipitation intensities compared with the FY-4B/AGRI operational precipitation product. It can provide some reference value for future precipitation retrieval research on FY-4B/AGRI.
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