Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer.

Purpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.

Recent advances in the applications of DNA frameworks in liquid biopsy: A review.

Cancer is one of the serious threats to public life and health. Early diagnosis, real-time monitoring, and individualized treatment are the keys to improve the survival rate and prolong the survival time of cancer patients. Liquid biopsy is a potential technique for cancer early diagnosis due to its non-invasive and continuous monitoring properties. However, most current liquid biopsy techniques lack the ability to detect cancers at the early stage. Therefore, effective detection of a variety of cancers is expected through the combination of various techniques. Recently, DNA frameworks with tailorable functionality and precise addressability have attracted wide spread attention in biomedical applications, especially in detecting cancer biomarkers such as circulating tumor cells (CTCs), exosomes and circulating tumor nucleic acid (ctNA). Encouragingly, DNA frameworks perform outstanding in detecting these cancer markers, but also face some challenges and opportunities. In this review, we first briefly introduced the development of DNA frameworks and its typical structural characteristics and advantages. Then, we mainly focus on the recent progress of DNA frameworks in detecting commonly used cancer markers in liquid-biopsy. We summarize the advantages and applications of DNA frameworks for detecting CTCs, exosomes and ctNA. Furthermore, we provide an outlook on the possible opportunities and challenges for exploiting the structural advantages of DNA frameworks in the field of cancer diagnosis. Finally, we envision the marriage of DNA frameworks with other emerging materials and technologies to develop the next generation of disease diagnostic biosensors.

Study on the gut symbiotic microbiota in long- and short-winged brown planthopper, Nilaparvata lugens (Stål).

The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most important rice pests in Asia rice regions. BPH has monophagy, migration, rapid reproduction and strong environmental adaptability, and its control is a major problem in pest management. Adult BPH exhibit wing dimorphism, and the symbiotic microbiota enriched in the gut can provide energy for wing flight muscles as a source of nutrition. In order to study the diversity of symbiotic microbiota in different winged BPHs, this paper takes female BPH as the research object. It was found that the number of symbiotic microbiota of different winged BPHs would change at different development stages. Then, based on the 16S rRNA and ITS sequences, a metagenomic library was constructed, combined with fluorescent quantitative PCR and high-throughput sequencing, the dominant symbiotic microbiota flora in the gut of different winged BPHs was found, and the community structure and composition of symbiotic microbiota in different winged BPHs were further determined. Together, our results preliminarily revealed that symbiotic microbiota in the gut of BPHs have certain effects on wing morphology, and understanding the mechanisms underlying wing morph differentiation will clarify how nutritional factors or environmental cues alter or regulate physiological and metabolic pathways. These findings also establish a theoretical basis for subsequent explorations into BPH-symbiont interplay.

CdgB Regulates Morphological Differentiation and Toyocamycin Production in Streptomyces diastatochromogenes 1628.

Bis (3',5')-cyclic diguanylic acid (c-di-GMP) is a ubiquitous second messenger that controls several metabolic pathways in bacteria. In Streptomyces, c-di-GMP is associated with morphological differentiation, which is related to secondary metabolite production. In this study, we identified and characterized a diguanylate cyclase (DGC), CdgB, from Streptomyces diastatochromogenes 1628, which may be involved in c-di-GMP synthesis, through genetic and biochemical analyses. To further investigate the role of CdgB, the cdgB-deleted mutant strain Δ-cdgB and the cdgB-overexpressing mutant strain O-cdgB were constructed by genetic engineering. A phenotypic analysis revealed that the O-cdgB colonies exhibited reduced mycelium formation, whereas the Δ-cdgB colonies displayed wrinkled surfaces and shriveled mycelia. Notably, O-cdgB demonstrated a significant increase in the toyocamycin (TM) yield by 47.3%, from 253 to 374 mg/L, within 10 days. This increase was accompanied by a 6.7% elevation in the intracellular concentration of c-di-GMP and a higher transcriptional level of the toy cluster within four days. Conversely, Δ-cdgB showed a lower c-di-GMP concentration (reduced by 6.2%) in vivo and a reduced toyocamycin production (decreased by 28.9%, from 253 to 180 mg/L) after 10 days. In addition, S. diastatochromogenes 1628 exhibited a slightly higher inhibitory effect against Fusarium oxysporum f. sp. cucumerinum and Rhizoctonia solani compared to Δ-cdgB, but a lower inhibition rate than that of O-cdgB. The results imply that CdgB provides a foundational function for metabolism and the activation of secondary metabolism in S. diastatochromogenes 1628.

Carboxymethyl chitosan-modified UiO-66 for the rapid detection of fenpropathrin in grains.

Fenpropathrin residues in grain are potentially harmful to humans. Therefore, a fluorimetric lateral flow immunoassay using a zirconium-based organic skeleton (UiO-66) as a signal marker was developed for detecting fenpropathrin. Herein, carboxymethyl chitosan (CMCS) was used to modify UiO-66 and improve its water solubility to facilitate stable binding with sodium fluorescein (NaFL). This resulted in formation of a new fluorescent probe that is more suitable for lateral flow immunoassay (LFIA). The materials were characterized via electron microscopy, Fourier-transform infrared spectroscopy, and powder X-ray diffraction. CMCS and NaFL were successfully bound to UiO-66. Under optimized conditions, the constructed NaFL/UiO-66@CMCS-LFIA exhibited a good linear relationship within the range of 0.98-62.5 µg/L, with a detection limit of 3.91 µg/L. This probe was fourfold more sensitive than traditional colloidal gold nanoparticle-based LFIA. Finally, NaFL/UiO-66@CMCS-LFIA was successfully applied to detect fenpropathrin in wheat and maize samples. The detection limit was 1.56 µg/kg and recoveries ranged from 96.58 % to 118.56 %. This study provides a sensitive, stable, and convenient method for the rapid detection of pesticide residues.

The MoLfa1 Protein Regulates Fungal Development and Septin Ring Formation in Magnaporthe oryzae.

Septins play a key regulatory role in cell division, cytokinesis, and cell polar growth of the rice blast fungus (Magnaporthe oryzae). We found that the organization of the septin ring, which is essential for appressorium-mediated infection in M. oryzae, requires long-chain fatty acids (LCFAs), which act as mediators of septin organization at membrane interfaces. However, it is unclear how septin ring formation and LCFAs regulate the pathogenicity of the rice blast fungus. In this study, a novel protein was named MoLfa1 because of its role in LCFAs utilization. MoLfa1 affects the utilization of LCFAs, lipid metabolism, and the formation of the septin ring by binding with phosphatidylinositol phosphates (PIPs), thereby participating in the construction of penetration pegs of M. oryzae. In addition, MoLfa1 is localized in the endoplasmic reticulum (ER) and interacts with the ER-related protein MoMip11 to affect the phosphorylation level of Mps1. (Mps1 is the core protein in the MPS1-MAPK pathway.) In conclusion, MoLfa1 affects conidia morphology, appressorium formation, lipid metabolism, LCFAs utilization, septin ring formation, and the Mps1-MAPK pathway of M. oryzae, influencing pathogenicity.

Traceability of Microplastic Fragments from Waste Plastic Express Packages Using Near-Infrared Spectroscopy Combined with Chemometrics.

The pollution from waste plastic express packages (WPEPs), especially microplastic (MP) fragments, caused by the blowout development of the express delivery industry has attracted widespread attention. On account of the variety of additives, strong complexity, and high diversity of plastic express packages (PEPs), the multi-class classification of WPEPs is a typical large-class-number classification (LCNC). The traceability and identification of microplastic fragments from WPEPs is very challenging. An effective chemometric method for large-class-number classification would be very beneficial for the comprehensive treatment of WPEP pollution through the recycling and reuse of waste plastic express packages, including microplastic fragments and plastic debris. Rather than using the traditional one-against-one (OAO) and one-against-all (OAA) dichotomies, an exhaustive and parallel half-against-half (EPHAH) decomposition, which overcomes the defects of the OAO's classifier learning limitations and the OAA's data proportion imbalance, is proposed for feature selection. EPHAH analysis, combined with partial least squares discriminant analysis (PLS-DA) for large-class-number classification, was performed on 750 microplastic fragments of polyethylene WPEPs from 10 major courier companies using near-infrared (NIR) spectroscopy. After the removal of abnormal samples through robust principal component analysis (RPCA), the root mean square error of cross-validation (RMSECV) value for the model was reduced to 0.01, which was 21.5% lower than that including the abnormal samples. The best models of PLS-DA were obtained using SNV combined with SG-17 smoothing and 2D (SNV+SG-17+2D); the latent variables (LVs), the error rates of Monte Carlo cross-validation (ERMCCVs), and the final classification accuracies were 6.35, 0.155, and 88.67% for OAO-PLSDA; 5.37, 0.103, and 87.33% for OAA-PLSDA; and 3.12, 0.054, and 96.00% for EPHAH-PLSDA. The results showed that the EPHAH strategy can completely learn the complex LCNC decision boundaries for 10 classes, effectively break the tie problem, and greatly improve the voting resolution, thereby demonstrating significant superiority to both the OAO and OAA strategies in terms of classification accuracy. Meanwhile, PLS-DA further maximized the covariance and data interpretation abilities between the potential variables and categories of microplastic debris, thereby establishing an ideal performance identification model with a recognition rate of 96.00%.

Factors Influencing Breast Cancer Awareness in Rural Southwest China: A Cross-Sectional Study.

Background: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition. Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0. Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P<0.001) and decrease with increasing age (P<0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P<0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women's breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women's breast cancer awareness. Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.

CT-based radiomics for differentiating peripherally located pulmonary sclerosing pneumocytoma from carcinoid.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) and pulmonary carcinoid (PC) are difficult to distinguish based on conventional imaging examinations. In recent years, radiomics has been used to discriminate benign from malignant pulmonary lesions. However, the value of radiomics based on computed tomography (CT) images to differentiate PSP from PC has not been well explored. PURPOSE: We aimed to investigate the feasibility of radiomics in the differentiation between PSP and PC. METHODS: Fifty-three PSP and fifty-five PC were retrospectively enrolled and then were randomly divided into the training and test sets. Univariate and multivariable logistic analyses were carried to select clinical predictor related to differential diagnosis of PSP and PC. A total of 1316 radiomics features were extracted from the unenhanced CT (UECT) and contrast-enhanced CT (CECT) images, respectively. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used to select the most significant radiomics features to construct radiomics models. The clinical predictor and radiomics features were integrated to develop combined models. Two senior radiologists independently categorized each patient into PSP or PC group based on traditional CT method. The performances of clinical, radiomics, and combined models in differentiating PSP from PC were investigated by the receiver operating characteristic (ROC) curve. The diagnostic performance was also compared between the combined models and radiologists. RESULTS: In regard to differentiating PSP from PC, the area under the curves (AUCs) of the clinical, radiomics, and combined models were 0.87, 0.96, and 0.99 in the training set UECT, and were 0.87, 0.97, and 0.98 in the training set CECT, respectively. The AUCs of the clinical, radiomics, and combined models were 0.84, 0.92, and 0.97 in the test set UECT, and were 0.84, 0.93, and 0.98 in the test set CECT, respectively. In regard to the differentiation between PSP and PC, the combined model was comparable to the radiomics model, but outperformed the clinical model and the two radiologists, whether in the test set UECT or CECT. CONCLUSIONS: Radiomics approaches show promise in distinguishing between PSP and PC. Moreover, the integration of clinical predictor (gender) has the potential to enhance the diagnostic performance even further.

Comparative analysis of the diversity of symbionts in fat body of long- and short-winged brown planthoppers.

The microbial community structure plays an important role in the internal environment of brown planthopper (BPH), Nilaparvata lugens (Hemiptera: Delphacidae), which is an indispensable part to reflect the internal environment of BPH. Wing dimorphism is a strategy for balancing flight and reproduction of insects. Here, quantitative fluorescence PCR was used to analyse the number and changes of the symbionts in the fat body of long- and short-winged BPHs at different developmental stages. A metagenomic library was constructed based on the 16 S rRNA sequence and internal transcribed spacer sequence for high-throughput sequencing, to analyze the community structure and population number of the symbionts of long- and short-winged BPHs, and to make functional prediction. This study enriches the connotation of BPH symbionts, and laid a theoretical foundation for the subsequent study of BPH-symbionts interaction and the function of symbionts in the host.

Establishment of Indirect Competitive Enzyme-linked Immunosorbent Assay (ic-ELISA) for Copper ion (Cu2+) in Raw Meat Products.

Adding an appropriate amount of copper to feed can promote the growth and development of livestock; however, a large amount of heavy metal copper can accumulate in livestock through the enrichment effect, which poses a serious threat to human health. Traditional Cu2+ detection relies heavily on complex and expensive instruments, such as inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS); thus, convenient and simple rapid detection technologies are urgently needed. In this paper, synthesized copper antigens were used to immunize mice and highly specific anticopper monoclonal antibodies were obtained, which were verified to exhibit high affinity and specificity. Based on the above antibodies, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established for the rapid detection of copper content in pork. The standard inhibition curve of the method was obtained by antigen-antibody working concentration screening, in which the half inhibitory concentration (IC50) was 11.888 ng/mL, the limit of detection (LOD) was 0.841 ng/mL and the correlation coefficient R2 of the curve was 0.998. In the additive recovery experiment, the recovery rate ranged from 90% to 110%, and the coefficient of variation (CV) was less than 10%, indicating that the method achieved high accuracy and precision. Finally, the results of ic-ELISA combined with Bland-Altman analysis showed a high correlation with ICP-MS, and the correlation coefficient (R2) reached 0.990 when the copper concentration was less than 200 ng/mL. Thus, the ic-ELISA method exhibits high reliability.

Silencing NlFAR7 destroyed the pore canals and related structures of the brown planthopper.

Fatty acyl-CoA reductase (FAR) is one of the key enzymes, which catalyses the conversion of fatty acyl-CoA to the corresponding alcohols. Among the FAR family members in the brown planthopper (Nilaparvata lugens), NlFAR7 plays a pivotal role in both the synthesis of cuticular hydrocarbons and the waterproofing of the cuticle. However, the precise mechanism by which NlFAR7 influences the formation of the cuticle structure in N. lugens remains unclear. Therefore, this paper aims to investigate the impact of NlFAR7 through RNA interference, transmission electron microscope, focused ion beam scanning electron microscopy (FIB-SEM) and lipidomics analysis. FIB-SEM is employed to reconstruct the three-dimensional (3D) architecture of the pore canals and related cuticle structures in N. lugens subjected to dsNlFAR7 and dsGFP treatments, enabling a comprehensive assessment of changes in the cuticle structures. The results reveal a reduction in the thickness of the cuticle and disruptions in the spiral structure of pore canals, accompanied by widened base and middle diameters. Furthermore, the lipidomics comparison analysis between dsNlFAR7- and dsGFP-treated N. lugens demonstrated that there were 25 metabolites involved in cuticular lipid layer synthesis, including 7 triacylglycerols (TGs), 5 phosphatidylcholines (PCs), 3 phosphatidylethanolamines (PEs) and 2 diacylglycerols (DGs) decreased, and 4 triacylglycerols (TGs) and 4 PEs increased. In conclusion, silencing NlFAR7 disrupts the synthesis of overall lipids and destroys the cuticular pore canals and related structures, thereby disrupting the secretion of cuticular lipids, thus affecting the cuticular waterproofing of N. lugens. These findings give significant attention with reference to further biochemical researches on the substrate specificity of FAR protein, and the molecular regulation mechanisms during N. lugens life cycle.

The application and development of electron microscopy for three-dimensional reconstruction in life science: a review.

Imaging technologies have played a pivotal role in advancing biological research by enabling visualization of biological structures and processes. While traditional electron microscopy (EM) produces two-dimensional images, emerging techniques now allow high-resolution three-dimensional (3D) characterization of specimens in situ, meeting growing needs in molecular and cellular biology. Combining transmission electron microscopy (TEM) with serial sectioning inaugurated 3D imaging, attracting biologists seeking to explore cell ultrastructure and driving advancement of 3D EM reconstruction. By comprehensively and precisely rendering internal structure and distribution, 3D TEM reconstruction provides unparalleled ultrastructural insights into cells and molecules, holding tremendous value for elucidating structure-function relationships and broadly propelling structural biology. Here, we first introduce the principle of 3D reconstruction of cells and tissues by classical approaches in TEM and then discuss modern technologies utilizing TEM and on new SEM-based as well as cryo-electron microscope (cryo-EM) techniques. 3D reconstruction techniques from serial sections, electron tomography (ET), and the recent single-particle analysis (SPA) are examined; the focused ion beam scanning electron microscopy (FIB-SEM), the serial block-face scanning electron microscopy (SBF-SEM), and automatic tape-collecting lathe ultramicrotome (ATUM-SEM) for 3D reconstruction of large volumes are discussed. Finally, we review the challenges and development prospects of these technologies in life science. It aims to provide an informative reference for biological researchers.

Evolution and expression patterns of the neo-sex chromosomes of the crested ibis.

Bird sex chromosomes play a unique role in sex-determination, and affect the sexual morphology and behavior of bird species. Core waterbirds, a major clade of birds, share the common characteristics of being sexually monomorphic and having lower levels of inter-sexual conflict, yet their sex chromosome evolution remains poorly understood. Here, by we analyse of a chromosome-level assembly of a female crested ibis (Nipponia nippon), a typical core waterbird. We identify neo-sex chromosomes resulting from fusion of microchromosomes with ancient sex chromosomes. These fusion events likely occurred following the divergence of Threskiornithidae and Ardeidae. The neo-W chromosome of the crested ibis exhibits the characteristics of slow degradation, which is reflected in its retention of abundant gametologous genes. Neo-W chromosome genes display an apparent ovary-biased gene expression, which is largely driven by genes that are retained on the crested ibis W chromosome but lost in other bird species. These results provide new insights into the evolutionary history and expression patterns for the sex chromosomes of bird species.

Comparative Mitogenome Analyses of Fifteen Ramshorn Snails and Insights into the Phylogeny of Planorbidae (Gastropoda: Hygrophila).

Ramshorn snails from the family Planorbidae are important freshwater snails due to their low trophic level, and some of them act as intermediate hosts for zoonotic trematodes. There are about 250 species from 40 genera of Planorbidae, but only 14 species from 5 genera (Anisus, Biomphalaria, Bulinus, Gyraulus, and Planorbella) have sequenced complete mitochondrial genomes (mitogenomes). In this study, we sequenced and assembled a high-quality mitogenome of a ramshorn snail, Polypylis sp. TS-2018, which represented the first mitogenome of the genus. The mitogenome of Polypylis sp. TS-2018 is 13,749 bp in length, which is shorter than that of most gastropods. It contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and 2 ribosomal RNA (rRNA). We compared mitogenome characteristics, selection pressure, and gene rearrangement among all of the available mitogenomes of ramshorn snails. We found that the nonsynonymous and synonymous substitution rates (Ka/Ks) of most PCGs indicated purifying and negative selection, except for atp8 of Anisus, Biomphalaria, and Gyraulus, which indicated positive selection. We observed that transpositions and reverse transpositions occurred on 10 tRNAs and rrnS, which resulted in six gene arrangement types. We reconstructed the phylogenetic trees using the sequences of PCGs and rRNAs and strongly supported the monophyly of each genus, as well as three tribes in Planorbidae. Both the gene rearrangement and phylogenetic results suggested that Polypylis had a close relationship with Anisus and Gyraulus, while Bulinus was the sister group to all of the other genera. Our results provide useful data for further investigation of species identification, population genetics, and phylogenetics among ramshorn snails.

NT5DC2 knockdown suppresses progression, glycolysis, and neuropathic pain in triple-negative breast cancer by blocking the EGFR pathway.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive breast cancer subtype associated with neuropathic pain. This study explores the effects of 5'-nucleotidase domain-containing protein 2 (NT5DC2) on the progression of TNBC and neuropathic pain. Microarray analysis was conducted to identify differentially expressed genes in TNBC and the pathways involved. Gain- and loss-of-function assays of NT5DC2 were performed in TNBC cells, followed by detection of the extracellular acidification rate, adenosine triphosphate (ATP) levels, lactic acid production, glucose uptake, proliferation, migration, and invasion in TNBC cells. Macrophages were co-cultured with TNBC cells to examine the release of polarization-related factors and cytokines. A xenograft tumor model was established for in vivo validation. In addition, a mouse model of neuropathic pain was established through subepineural injection of TNBC cells, followed by measurement of the sciatic functional index and behavioral analysis to assess neuropathic pain. NT5DC2 was upregulated in TNBC and was positively correlated with epidermal growth factor receptor (EGFR). NT5DC2 interacted with EGFR to promote downstream signal transduction in TNBC cells. NT5DC2 knockdown diminished proliferation, migration, invasion, the extracellular acidification rate, ATP levels, lactic acid production, and glucose uptake in TNBC cells. Co-culture with NT5DC2-knockdown TNBC cells alleviated the M2 polarization of macrophages. Furthermore, NT5DC2 knockdown reduced tumor growth and neuropathic pain in mice. Importantly, activation of the EGFR pathway counteracted the effects of NT5DC2 knockdown. NT5DC2 knockdown protected against TNBC progression and neuropathic pain by inactivating the EGFR pathway.

Evolution of radiation-induced temporal lobe injury after intensity-modulated radiation therapy in nasopharyngeal carcinoma: a large cohort retrospective study.

BACKGROUND: Previous studies have demonstrated conflicting findings regarding the initial MRI patterns of radiotherapy-induced temporal lobe injury (RTLI) and the evolution of different RTLI patterns. The aim of this study was to evaluate the initial MRI pattern and evolution of RTLI in patients with nasopharyngeal carcinoma (NPC) by means of a large cohort study. METHODS: Data of patients with RTLI were retrospectively collected from two hospitals between January 2011 and December 2021. The injured lobes were categorized into three patterns based on initial MRI patterns: isolated white matter lesions (WMLs), isolated contrast-enhanced lesions (CELs), and combined WMLs and CELs. The latency period, MRI appearances, and temporal changes in WMLs and CELs were evaluated. RESULTS: A total of 913 RTLI patients with 1092 injured lobes were included in this study. The numbers of isolated WMLs, isolated CELs, and combined WMLs and CELs identified at the first MRI detection were 7 (0.6%), 172 (15.8%), and 913 (83.6%), respectively. The evolution of bilateral RTLI was different in the same patient, and that of unilateral RTLI combined with WMLs and CELs also may occur asynchronously. The time intervals from the initial MRI detection of isolated WMLs, isolated CELs, combined WMLs and CELs to the last negative MRI scan were 8.6, 8.9 and 11.0 months, respectively. A significant difference was observed in the time intervals between the three patterns (H = 14.287, P = 0.001). And the time interval was identified as an independent factor influencing the initial MRI pattern of RTLI after Poisson regression (P = 0.002). CONCLUSION: Both WMLs and CELs could be the initial and only MRI abnormalities in patients with RTLI. This study is of great significance in accurately diagnosing RTLI early and providing timely treatment options. Additionally, it provides clinical evidence for guidelines on NPC, emphasizing the importance of regular follow-up of NPC patients.

CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling.

PERK/eIF2α/ATF4/CHOP signaling pathway is one of three major branches of unfolded protein response (UPR) and has been implicated in tumor progression. CCT020312 is a selective PERK activator and may have a potential anti-tumor effect. Here we investigated the anti-prostate cancer effect and its underlying mechanism of CCT020312. Our results showed that CCT020312 inhibited prostate cancer cell viability by inducing cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling. CCT020312 treatment caused cell cycle arrest at G1 phase and increased the levels of cleaved-Caspase3, cleaved-PARP and Bax in prostate cancer C4-2 and LNCaP cells. Moreover, CCT020312 increased LC3II/I, Atg12-Atg5 and Beclin1 levels and induced autophagosome formation. Furthermore, knockdown of CHOP reversed CCT020312-induced cell viability decrease, apoptosis and autophagy. Bafilomycin A1 reversed CCT020312-induced cell viability decrease but had no effect on CCT020312-induced CHOP activation in C4-2 and LNCaP cells. In vivo, CCT020312 suppressed tumor growth in C4-2 cells-derived xenograft mouse model, activated PERK pathway, and induced autophagy and apoptosis. Our study illustrates that CCT020312 exerts an anti-tumor effect in prostate cancer via activating the PERK pathway, thus indicating that CCT020312 may be a potential drug for prostate cancer.

Targeting autophagy drug discovery: Targets, indications and development trends.

Autophagy plays a vital role in sustaining cellular homeostasis and its alterations have been implicated in the etiology of many diseases. Drugs development targeting autophagy began decades ago and hundreds of agents were developed, some of which are licensed for the clinical usage. However, no existing intervention specifically aimed at modulating autophagy is available. The obstacles that prevent drug developments come from the complexity of the actual impact of autophagy regulators in disease scenarios. With the development and application of new technologies, several promising categories of compounds for autophagy-based therapy have emerged in recent years. In this paper, the autophagy-targeted drugs based on their targets at various hierarchical sites of the autophagic signaling network, e.g., the upstream and downstream of the autophagosome and the autophagic components with enzyme activities are reviewed and analyzed respectively, with special attention paid to those at preclinical or clinical trials. The drugs tailored to specific autophagy alone and combination with drugs/adjuvant therapies widely used in clinical for various diseases treatments are also emphasized. The emerging drug design and development targeting selective autophagy receptors (SARs) and their related proteins, which would be expected to arrest or reverse the progression of disease in various cancers, inflammation, neurodegeneration, and metabolic disorders, are critically reviewed. And the challenges and perspective in clinically developing autophagy-targeted drugs and possible combinations with other medicine are considered in the review.