PFMNet: Prototype-based feature mapping network for few-shot domain adaptation in medical image segmentation.

Lack of data is one of the biggest hurdles for rare disease research using deep learning. Due to the lack of rare-disease images and annotations, training a robust network for automatic rare-disease image segmentation is very challenging. To address this challenge, few-shot domain adaptation (FSDA) has emerged as a practical research direction, aiming to leverage a limited number of annotated images from a target domain to facilitate adaptation of models trained on other large datasets in a source domain. In this paper, we present a novel prototype-based feature mapping network (PFMNet) designed for FSDA in medical image segmentation. PFMNet adopts an encoder-decoder structure for segmentation, with the prototype-based feature mapping (PFM) module positioned at the bottom of the encoder-decoder structure. The PFM module transforms high-level features from the target domain into the source domain-like features that are more easily comprehensible by the decoder. By leveraging these source domain-like features, the decoder can effectively perform few-shot segmentation in the target domain and generate accurate segmentation masks. We evaluate the performance of PFMNet through experiments on three typical yet challenging few-shot medical image segmentation tasks: cross-center optic disc/cup segmentation, cross-center polyp segmentation, and cross-modality cardiac structure segmentation. We consider four different settings: 5-shot, 10-shot, 15-shot, and 20-shot. The experimental results substantiate the efficacy of our proposed approach for few-shot domain adaptation in medical image segmentation.

Clinical factors and major pathological response after neoadjuvant chemoimmunotherapy in potentially resectable lung squamous cell carcinoma.

Objective: Major pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC. Methods: This retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups. Results: In total, 91 LUSC patients who met the study's eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001). Conclusion: The MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

BACKGROUND: Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. AIM: To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. METHODS: Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. RESULTS: Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 µmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. CONCLUSION: Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Ultrasmall Gold Nanoparticles Radiolabeled with Iodine-125 as Potential New Radiopharmaceutical.

The relatively high linear energy transfer of Auger electrons, which can cause clustered DNA damage and hence efficient cell death, makes Auger emitters excellent candidates for attacking metastasized tumors. Moreover, gammas or positrons are usually emitted along with the Auger electrons, providing the possibility of theragnostic applications. Despite the promising properties of Auger electrons, only a few radiopharmaceuticals employing Auger emitters have been developed so far. This is most likely explained by the short ranges of these electrons, requiring the delivery of the Auger emitters to crucial cell parts such as the cell nucleus. In this work, we combined the Auger emitter 125I and ultrasmall gold nanoparticles to prepare a novel radiopharmaceutical. The 125I labeled gold nanoparticles were shown to accumulate at the cell nucleus, leading to a high tumor-killing efficiency in both 2D and 3D tumor cell models. The results from this work indicate that ultrasmall nanoparticles, which passively accumulate at the cell nucleus, have the potential to be applied in targeted radionuclide therapy. Even better tumor-killing efficiency can be expected if tumor-targeting moieties are conjugated to the nanoparticles.

Allelic variation of BBX24 is a dominant determinant controlling red coloration and dwarfism in pear.

Variation in anthocyanin biosynthesis in pear fruit provides genetic germplasm resources for breeding, while dwarfing is an important agronomic trait, which is beneficial to reduce the management costs and allow for the implementation of high-density cultivation. Here, we combined bulked segregant analysis (BSA), quantitative trait loci (QTL), and structural variation (SV) analysis to identify a 14-bp deletion which caused a frame shift mutation and resulted in the premature translation termination of a B-box (BBX) family of zinc transcription factor, PyBBX24, and its allelic variation termed PyBBX24ΔN14. PyBBX24ΔN14 overexpression promotes anthocyanin biosynthesis in pear, strawberry, Arabidopsis, tobacco, and tomato, while that of PyBBX24 did not. PyBBX24ΔN14 directly activates the transcription of PyUFGT and PyMYB10 through interaction with PyHY5. Moreover, stable overexpression of PyBBX24ΔN14 exhibits a dwarfing phenotype in Arabidopsis, tobacco, and tomato plants. PyBBX24ΔN14 can activate the expression of PyGA2ox8 via directly binding to its promoter, thereby deactivating bioactive GAs and reducing the plant height. However, the nuclear localization signal (NLS) and Valine-Proline (VP) motifs in the C-terminus of PyBBX24 reverse these effects. Interestingly, mutations leading to premature termination of PyBBX24 were also identified in red sports of un-related European pear varieties. We conclude that mutations in PyBBX24 gene link both an increase in pigmentation and a decrease in plant height.

MAIRNet: weakly supervised anatomy-aware multimodal articulated image registration network.

PURPOSE: Multimodal articulated image registration (MAIR) is a challenging problem because the resulting transformation needs to maintain rigidity for bony structures while allowing elastic deformation for surrounding soft tissues. Existing deep learning-based methods ignore the articulated structures and consider it as a pure deformable registration problem, leading to suboptimal results. METHODS: We propose a novel weakly supervised anatomy-aware multimodal articulated image registration network, referred as MAIRNet, to solve the challenging problem. The architecture of MAIRNet comprises of two branches: a non-learnable polyrigid registration branch to estimate an initial velocity field, and a learnable deformable registration branch to learn an increment. These two branches work together to produce a velocity field that can be integrated to generate the final displacement field. RESULTS: We designed and conducted comprehensive experiments on three datasets to evaluate the performance of the proposed method. Specifically, on the hip dataset, our method achieved, respectively, an average dice of 90.8%, 92.4% and 91.3% for the pelvis, the right femur, and the left femur. On the lumbar spinal dataset, our method obtained, respectively, an average dice of 86.1% and 85.9% for the L4 and the L5 vertebrae. On the thoracic spinal dataset, our method achieved, respectively, an average dice of 76.7%, 79.5%, 82.9%, 85.5% and 85.7% for the five thoracic vertebrae ranging from T6 to T10. CONCLUSION: In summary, we developed a novel approach for multimodal articulated image registration. Comprehensive experiments conducted on three typical yet challenging datasets demonstrated the efficacy of the present approach. Our method achieved better results than the state-of-the-art approaches.

UBC9 stabilizes PFKFB3 to promote aerobic glycolysis and proliferation of glioblastoma cells.

Cancer cells prefer to utilizing aerobic glycolysis to generate energy and anabolic metabolic intermediates for cell growth. However, whether the activities of glycolytic enzymes can be regulated by specific posttranslational modifications, such as SUMOylation, in response to oncogenic signallings, thereby promoting the Warburg effect, remain largely unclear. Here, we demonstrate that phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key glycolytic enzyme, interacts with SUMO-conjugating enzyme UBC9 and is SUMOylated at K302 in glioblastoma cells. Expression of UBC9, which competitively prevents the binding of ubiquitin E3 ligase APC/C to PFKFB3 and subsequent PFKFB3 polyubiquitination, increases PFKFB3 stability and expression. Importantly, EGFR activation increases the interaction between UBC9 and PFKFB3, leading to increased SUMOylation and expression of PFKFB3. This increase is blocked by inhibition of EGFR-induced AKT activation whereas expression of activate AKT by itself was sufficient to recapitulate EGF-induced effect. Knockout of PFKFB3 expression decreases EGF-enhanced lactate production and GBM cell proliferation and this decrease was fully rescued by reconstituted expression of WT PFKFB3 whereas PFKFB3 K302R mutant expression abrogates EGF- and UBC9-regulated lactate production and GBM cell proliferation. These findings reveal a previously unknown mechanism underlying the regulation of the Warburg effect through the EGFR activation-induced and UBC9-mediated SUMOylation and stabilization of PFKFB3.

Molecular mechanisms of tumor resistance to radiotherapy.

BACKGROUND: Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence. MAIN BODY: In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes. CONCLUSIONS: Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.

Neutrophil elastase: From mechanisms to therapeutic potential.

Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Cadmium inhibits powdery mildew colonization and reconstructs microbial community in leaves of the hyperaccumulator plant Sedum alfredii.

Understanding the influence of the heavy metal cadmium (Cd) on the phyllosphere microbiome of hyperaccumulator plants is crucial for enhancing phytoremediation. The characteristics of the phyllosphere of Sedum alfredii Hance, a hyperaccumulator plant, were investigated using 16S rRNA and internal transcribed spacer amplicon sequencing of powdery mildew-infected leaves treated or untreated with Cd. The results showed that the colonization of powdery mildew caused severe chlorosis and necrosis in S. alfredii leaves, and the relative abundance of Leotiomycetes in infected leaves increased dramatically and significantly decreased phyllosphere microbiome diversity. However, S. alfredii preferentially accumulated higher concentrations of Cd in the leaves of infected plants than in uninfected plants by powdery mildew, which in turn significantly inhibited powdery mildew colonization in leaves; the relative abundance of the fungal class Leotiomycetes in infected leaves decreased, and alpha and beta diversities of the phyllosphere microbiome significantly increased with Cd treatment in the infected plants. In addition, the inter-kingdom networks in the microbiota of the infected leaves treated with Cd presented many nodes and edges, and the highest inter-kingdom modularity compared to the untreated infected leaves, indicating a highly connected microbial community. These results suggest that Cd significantly inhibits powdery mildew colonization by altering the composition of the phyllosphere microbiome in S. alfredii leaves, paving the way for efficient heavy metal phytoremediation and providing a new perspective on defense strategies against heavy metals.

Ribosome Biogenesis Regulator 1 Homolog (RRS1) Promotes Cisplatin Resistance by Regulating AEG-1 Abundance in Breast Cancer Cells.

Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein involved in ribosome biogenesis, also plays a key role in the genesis and development of breast cancer by protecting cancer cells from apoptosis. Given that apoptosis resistance is one of the causes of the cisplatin resistance of tumor cells, our aim was to determine the relationship between RRS1 and cisplatin resistance in breast cancer cells. Here, we report that RRS1 is associated with cisplatin resistance in breast cancer cells. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin and inhibited cancer cell proliferation by blocking cell cycle distribution and enhancing apoptosis. AEG-1 (astrocyte elevated gene-1) promotes drug resistance by interfering with the ubiquitination and proteasomal degradation of MDR1 (multidrug resistance gene 1), thereby enhancing drug efflux. We found that RRS1 binds to and stabilizes AEG-1 by inhibiting ubiquitination and subsequent proteasomal degradation, which then promotes drug efflux by upregulating MDR1. Furthermore, RRS1 also induces apoptosis resistance in breast cancer cells through the ERK/Bcl-2/BAX signaling pathway. Our study is the first to show that RRS1 sensitizes breast cancer cells to cisplatin by binding to AEG-1, and it provides a theoretical basis to improve the efficacy of cisplatin-based chemotherapy.

Improved Zn bioavailability by its enhanced colocalization and speciation with S in wheat grain tissues after N addition.

Zinc bioavailability with the presence of other elements in wheat grains might be affected by fertilizers. A long-term field experiment was conducted to examine effects of N fertilizer on Zn bioavailability in wheat grain tissues, with changes in the concentrations, distribution, and speciation of Zn as well as P and sulfur S via synchrotron-based technology. Results showed that addition of N fertilizer was associated with changes in Zn concentrations and distributions in grain tissues, especially in the crease region and endosperm. Simultaneously, N addition enhanced Zn-S colocalization in the crease region and endosperm and lowered the P/Zn ratio and Zn-P colocalization. Addition of N fertilizer with P increased Zn-cysteine (9.2%) and decreased Zn-phytate (47.3%) in the crease region, leading to potentially higher grain Zn bioavailability. Thus, addition of N fertilizer improved concentrations and bioavailability of Zn, by coordinating the relationships among Zn, P and S within wheat grains.

Thorax radiotherapy using 18F-positron emission tomography/computed tomography-guided precision radiotherapy is a prognostic factor for survival in patients with extracranial oligometastatic non-small cell lung cancer:A two-center propensity score-matched analysis.

Background: This retrospective study compared positron emission tomography (PET)/computed tomography (CT) and CT in the treatment of extracranial oligometastatic non-small-cell lung cancer (NSCLC) and explored the impact of thorax radiotherapy (TRT) on patient survival. Methods: We reviewed the medical records of Chinese patients with stage IV extracranial oligometastatic NSCLC who underwent PET/CT or CT at two centers. Propensity score matching (PSM) was used to control differences in patient characteristics between the maintenance chemotherapy alone and TRT plus maintenance chemotherapy groups. Results: We analyzed 192 eligible patients. The median survival time was better in patients who received PET/CT than in those who only received CT (n = 192, 16 months vs. 6 months, p<0.001). Subgroup analysis showed the median survival time was significantly longer in the TRT plus maintenance group than in the chemotherapy alone group in patients who underwent PET/CT examinations (n = 94, 25 months vs. 11 months, p<0.001). However, there was no statistical difference in survival between both groups in patients who underwent CT examinations (n = 98, 8 months vs. 5 months, p = 0.180). A multifactorial analysis revealed a more favorable prognosis in patients who underwent PET/CT evaluation (HR: 0.343, 95% CI: 0.250-0.471, p <0.001) and TRT (HR: 0.624, 95% CI: 0.464-0.840, p = 0.002), than in those who did not. PSM was consistent with these results. Conclusions: PET/CT-guided TRT is associated with improved clinical outcomes in patients with stage IV extracranial oligometastatic NSCLC.

Synchrotron X-ray Fluorescence Technique Identifies Contribution of Node Iron and Zinc Accumulations to the Grain of Wheat.

Increasing iron (Fe) and zinc (Zn) concentrations in crop grains with high yield is an effective measure to ensure food supply and alleviate mineral malnutrition in humans. Micronutrient concentrations in grains depend on not only their availability in soils but also their uptake in roots and translocation to shoots and grains. In this three-year field study, we investigated genotypic variation in Fe and Zn uptake and translocation within six wheat cultivars and examined in detail Fe and Zn distributions in various tissues of two cultivars with similar high yield but different grain Fe and Zn concentrations using synchrotron micro-X-ray fluorescence. Results revealed that root Fe and Zn concentrations were 11 and 44% greater in high-nutrient (HN) than in low-nutrient (LN) concentration cultivar. Although both cultivars accumulated similar amounts of Fe in shoots, HN cultivar had greater accumulation of Fe in grain and greater accumulation of Zn in both shoots and grain. Grain Zn concentration was positively correlated with shoot Zn accumulation, and grain Fe concentration was positively correlated with the ability to translocate Fe from leaves/stem to grains. In the first nodes of shoots, HN cultivar had 482% greater Fe and 36% greater Zn concentrations in the enlarged vascular bundle (EVB) than LN cultivar. In top nodes, HN cultivar had 225 and 116% greater Fe and Zn concentrations in the transit vascular bundle and 77 and 71% greater in the EVB when compared to LN cultivar. HN cultivar also had a greater ability to allocate Fe and Zn to the grain than LN cultivar. In conclusion, HN cultivar had greater capacity of Fe and Zn acquirement by roots and translocation and partitioning from shoots into grains. Screening wheat cultivars for larger Fe and Zn concentrations in shoot nodes could be a novel strategy for breeding crops with greater grain Fe and Zn concentrations.

Core-shell structured gold nanoparticles as carrier for 166Dy/166Ho in vivo generator.

BACKGROUND: Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. ß- emitters are frequently used in RNT due to the long tissue penetration depth of the ß- particles. The dysprosium-166/holmium-166 (166Dy/166Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide 166Dy and the emission of high energy ß- from the daughter nuclide 166Ho. However, the internal conversion occurring after ß- decay from 166Dy to 166Ho could cause the release of about 72% of 166Ho when 166Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for 166Dy/166Ho in vivo generator such that the loss of the daughter nuclide 166Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core-shell structured gold nanoparticles (AuNPs) with 166Dy and studied the retention of both 166Dy and 166Ho under various conditions. RESULTS: The 166Dy was co-reduced with gold and platinum precursor to form the 166DyAu@AuNPs and 166DyPtAuNPs. The 166Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of 166Dy and 166Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both 166Dy and 166Ho was retained. The results show that the incorporation of 166Dy in AuNPs can prevent the escape of 166Ho released due to internal conversion. CONCLUSION: We developed a chelator-free radiolabelling method for 166Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide 166Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.

Downregulated RRS1 inhibits invasion and metastasis of BT549 through RPL11­c­Myc­SNAIL axis.

Regulator of ribosome synthesis 1 (RRS1) is a key factor in ribosome biosynthesis and other cellular functions. High level of RRS1 in breast cancer cell lines is associated with increased cell proliferation, invasion and migration. RRS1 controls the assembly of the 60s subunit and maturation of 25S rRNA during ribosome biosynthesis. In this study, lentiviral transfection of sh­RNA was used to knock down the level of RRS1, to detect the effect of RRS1 on cell function and to explore the specific mechanism of RRS1 affecting cell invasion and metastasis by COIP and dual­luciferase reporter gene assays. The present study found that RRS1 knockdown reduced the accumulation of ribosome protein L11 (RPL11) in the nucleolus, which then migrated to the nucleoplasm and bound to c­Myc. This inhibited trans­activation of SNAIL by c­Myc and eventually decreased the invasion and metastasis capacity of the human breast cancer cell line BT549. Taken together, RRS1 regulates invasion and metastasis of human breast cancer cells through the RPL11­c­Myc­SNAIL axis. The findings are of great significance for exploring the mechanism of breast cancer invasion and metastasis and the corresponding regulatory factors.

Long non-coding RNA KCNQ1OT1 promotes proliferation, migration and invasion via targeting miR-134 in retinoblastoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) exert a significant role in carcinogenesis. lncRNA KCNQ1OT1 is detected in many tumors and is considered as an oncogene. The expression and mechanism of KCNQ1OT1 in retinoblastoma (Rb) are not clearly elucidated. METHODS: KCNQ1OT1, miR-134 and TRIM44 mRNA expression were examined by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Proliferation, migration and invasion of Weri-Rb1 and Y79 cells were tested by cell counting kit-8, colony formation, scratch and transwell assays. Meanwhile, the regulatory relationships among KCNQ1OT1, miR-134 and TRIM44 were clarified by several biological experiments, including dual-luciferase reporter assay, RNA immunoprecipitation, subcellular distribution, qRT-PCR and western blotting. RESULTS: lncRNA KCNQ1OT1 was up-regulated in Rb tissues and Rb cell lines. In addition, the expression of KCNQ1OT1 was negatively correlated with the disease-free survival rate of RB patients. Silencing KCNQ1OT1 could significantly inhibit the RB progression in vivo and in vitro. The analysis of the mechanism of KCNQ1OT1 showed that KCNQ1OT1 can sponge miR-134, and miR-134 may inhibit TRIM44 expression. Moreover, the rescue assays showed that KCNQ1OT1 promoted RB progression by regulating the miR-134/TRIM44 pathway. CONCLUSIONS: The present study indicates that a new KCNQ1OT1/miR-134/TRIM44 pathway regulates Rb progression. It may be used as a potential prognostic marker for Rb.

Roles of the microRNA­338­3p/NOVA1 axis in retinoblastoma.

Retinoblastoma (RB) is an intraocular malignancy that mainly affects young children. Previous reports have demonstrated that mutations or the inactivation of the RB1 gene were the main cause of RB; however, disruption of the intracellular signaling pathways following deficiency of RB1 requires further investigation. Based on the Gene Expression Omnibus data and bioinformatics prediction, the present study aimed to investigate the microRNA (miR)­338­3p/neuro­oncological ventral antigen 1 (NOVA1) axis in RB. Subsequently, overexpression and knockdown of miR­338­3p and NOVA1, respectively, were performed to study the role of miR­338­3p/NOVA1 in the progression of the RB cells. The results demonstrated that overexpression of miR­338­3p significantly inhibited cell proliferation, migration and invasion, and promoted apoptosis of the RB cells. Moreover, knockdown of NOVA1 showed similar results. A dual­luciferase reporter assay and rescue experiments further confirmed the direct binding between miR­338­3p and NOVA1. Taken together, the results indicated that miR­338­3p acted as tumor suppressor by targeting the oncogene of NOVA1 in RB, which may serve as potential therapeutic targets in RB.

Advances in the Relationship Between Regulator of Ribosome Synthesis 1 (RRS1) and Diseases.

A regulator of ribosome synthesis 1 (RRS1) was discovered in yeast and is mainly localized in the nucleolus and endoplasmic reticulum. It regulates ribosomal protein, RNA biosynthesis, and protein secretion and is closely involved in cellular senescence, cell cycle regulation, transcription, translation, oncogenic transformation etc., Mutations in the RRS1 gene are associated with the occurrence and development of Huntington's disease and cancer, and overexpression of RRS1 promotes tumor growth and metastasis. In this review, the structure, function, and mechanisms of RRS1 in various diseases are discussed.

Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis.

PURPOSE: In this retrospective study, we evaluated the treatment patterns and survival after positron emission tomography-computed tomography (PET/CT)-guided local consolidation therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of Chinese patients with oligometastatic stage IV non-small cell lung cancer (≤ 5 metastases) who had undergone PET/CT and were eligible for systemic therapy at two centers between May 2005 and August 2019. Propensity score matching (1:1) was used to reduce selection bias and imbalanced distribution of confounding factors. RESULTS: We identified 84 eligible patients and used propensity scores to create well-matched groups of 35 patients who did or did not undergo LCT. Among all patients, the 1-year overall survival (OS) rate was 47.6% and the 2-year OS rate was 22.6%. Relative to the group that did not receive LCT, the LCT group had a significantly higher OS rate (13 months vs. 7 months, p = 0.002). The two groups had similar incidences and classifications of LCT-related side effects. In multivariable analysis, LCT was found to be strongly associated with a favorable OS (hazard ratio: 0.508, 95% confidence interval: 0.311-0.828, p = 0.001). CONCLUSION: We concluded that LCT was significantly associated with improved clinical outcomes among the Chinese patients with oligometastatic NSCLC who were eligible for systemic treatment and could undergo PET/CT evaluation.