Human-derived bacterial strains mitigate colitis via modulating gut microbiota and repairing intestinal barrier function in mice.

BACKGROUND: Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. RESULTS: In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus, which were positively correlated with gut barrier function, while suppressing Odoribacter, Rikenella, Oscillibacter and Parasutterella, which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. CONCLUSIONS: Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.

Nickel-Catalyzed Enantioselective Carbonyl Addition of Aryl Chlorides and Bromides to Aldehydes.

The Ni-catalyzed enantioselective addition reaction of aryl halides to aldehydes was studied with cyanobis(oxazoline) as chiral ligands and Mn as reductant. Aryl and heteroaryl bromides reacted with phenyl aldehyde at room temperature to produce dibenzyl alcohols in 16-99 % yields with 53-92 % ees. Moreover, the coupling of phenyl chloride with a variety of aryl, heteroaryl and alkyl aldehydes was demonstrated in the presence of cyanobis(oxazoline)/Ni(II) at 60 °C in generally high yields with moderate enantioselectivities.

Insulin Use Is Associated With Improved Outcomes in Critically Ill Patients With Acute Pancreatitis: A Retrospective Matched Cohort Study.

BACKGROUND: Severe acute pancreatitis (SAP) has a mortality of 30% with no current targeted therapy. The potential protective effect of insulin on AP has been reported and needs to be confirmed. Thus, we aim to examine the effect of insulin treatment on the outcome of AP patients. METHODS: A retrospective study was performed using data from the Medical Information Mart for Intensive Care (MIMIC) database. Kruskal-Wallis test, t-tests, and Pearson's chi-squared test were used to compare differences between groups. Propensity score matching and further nearest neighbor matching were used to construct a matched cohort. Cox proportional hazards regression analyses, logistic regression analyses, and the doubly robust estimation method were used to assess the relationship between insulin use and mortality. RESULTS: Nine hundred patients were enrolled in the final analysis. Insulin was associated with better outcomes in AP patients admitted to ICU, and could act as an independent predictor for 30-day mortality (HR = 0.36, 95% CI = 0.24-0.55). Subgroup analysis showed that AP patients with heart failure or without kidney disease or respiratory failure may not benefit from insulin treatment. CONCLUSIONS: Insulin treatment is independently associated with lower 30-day mortality in AP patients, except for those with heart failure or without kidney disease or respiratory failure.

Effects of ambient PM2.5 on non-accidental death: a time-series study in Shenzhen, China during 2014-2019.

This study aims to investigate the impact of PM2.5 on non-accidental death of residents. The single-pollutant model revealed that the influence of PM2.5 on non-accidental death was significant at lag0 and lag4-6, and was greatest at lag5. A 10 µg/m3 increase in PM2.5 was related with a 1.31% increase in non-accidental deaths. The connection between PM2.5 and non-accidental death was stronger in femalesthan males, in people aged ≥ 65 years than people aged < 65 years, and in people below high school education than people with high school education or above. Two-pollutant model revealed that the influence of PM2.5 on non-accidental death was essentially unchanged when CO, SO2, and O3 were included and reduced when NO2 was included. The multiple-pollutant model showed that the effect of ambient PM2.5 on non-accidental death was reduced. An increase in PM2.5 concentrations may cause an increase in non-accidental death.

Spatial epidemiological characteristics and driving factors of myopia among school-age children based on geographical detector: a national study.

The present study aimed to examine the spatial characteristics of myopia and identify the socioeconomic and environmental factors influencing its prevalence. Myopia prevalence among children of school age of Han ethnicity in China was 56.6% in 2019, with the highest and lowest prevalence's in Shandong (66.8%) and Guizhou (47.3%), respectively. There was a spatial aggregation of myopia prevalence in China. Environmental factors (atmospheric PM2.5 concentration and forest coverage) and socioeconomic factors (gross domestic product per capita, per capita disposable income, hospital beds per thousand people, and Engel coefficient) have significant influences on myopia prevalence. The interaction of each factor on myopia showed nonlinear enhancement. Myopia prevalence among children of school age was spatially clustered, and environmental and socioeconomic conditions are associated with myopia prevalence. Our findings provide novel perspectives for the comprehensive prevention and control of myopia.

The effect of Ge doping concentration on the electrochemical performance of silicene anode for lithium-ion batteries: a first-principles study.

Two-dimensional materials have been considered as novel anode materials for LIBs because of their large surface area, small volume change, and low Li diffusion barrier. Among them, the two-dimensional material SixGey has many excellent properties as an anode. However, Ge is expensive and not suitable for mass production. Therefore, proper Ge doping is of great significance to improve performance and reduce cost. Herein, we systematically study the effect of Ge doping and its concentration on the structure and electrochemical performance of two-dimensional SixGey by density functional theory (DFT) calculations. The incorporation of low concentration Ge can improve the horizontal and vertical diffusion ability of Li atoms compared to silicene. However, excessive Ge will increase the horizontal diffusion energy barrier of Li and reduce the theoretical capacity, where Si6Ge2 has a relatively high theoretical capacity and a low diffusion energy barrier. In addition, fully lithiated 2D SixGey shows poor electrical conductivity and increasing Ge concentration seems to be effective in improving the electrical conductivity of the material. This study will provide significant theoretical guidance for the design and preparation of two-dimensional silicon-based materials.

Transforming cancer cells for long-term living with cancer: An inspiring new approach.

Cancer is the leading cause of human death and imposes a huge health burden. Currently, no matter what advanced therapeutic modalities or technologies are applied, it is still peculiarly rare for most cancers to be radically cured whereas therapy resistance and tumor recurrence are ever so common. The long-standing cytotoxic therapy is hard to achieve long-term tumor control, and produces side-effects or even promotes cancer progression. With growing understandings of tumor biology, we came to realize that it is possible to transform but not kill cancer cells to achieve long-term living with cancer, and directly altering cancer cells is a promising way. Remarkably, tissue microenvironment is involved in the fate determination of cancer cells. Of note, leveraging cell competition to combat malignant or therapy-resistant cells shows some therapeutic potentials. Furthermore, modulating tumor microenvironment to restore a normal state might help to transform cancer cells. Especially, reprogramming cancer-associated fibroblasts, and tumor-associated macrophages, or normalization of tumor vessel, tumor immune microenvironment, and tumor extracellular matrix or their combinations, et al., revealed some long-term therapeutic benefits. Despite the massive challenges ahead, it would be possible to transform cancer cells for long-term cancer control and living with cancer longevously. The related basic researches and corresponding therapeutic strategies are also ongoing.

Defective graphene/SiGe heterostructures as anodes of Li-ion batteries: a first-principles calculation study.

Two-dimensional silicon-based material siligene (SiGe) has a low diffusion barrier and high theoretical specific capacity, but the conductivity drops sharply after being fully lithiated. To improve their electrical conductivity, the three heterostructures (SV-G/S, DV-G/S, and SW-G/S) formed with defective graphene and SiGe were proposed and the feasibility of them as anode materials was analyzed systematically. Based on density functional theory, the structural properties of defective graphene/SiGe heterostructures (Def-G/S), the adsorption and diffusion behaviours of Li, the voltage and theoretical capacity, and electrical conductivity during the lithiation process were investigated. The results show that defective graphene can form a stable heterostructure with SiGe and the heterostructure with defects can accommodate more Li atoms. The good adsorption and low diffusion energy barrier ensure the capacity, cycling, and safety performance of Def-G/S as anode materials. Moreover, Def-G/S significantly improves the conductivity of pristine 2D SiGe after full lithiation. These excellent properties indicate that Def-G/S has great potential as an anode material for Li-ion batteries.

Reg4 regulates pancreatic regeneration following pancreatitis via modulating the Notch signaling.

Pancreatic regeneration after acute pancreatitis is critical in the normal restoration of pancreatic exocrine function, the inhibition of which can cause severe complications including pancreatic exocrine insufficiency. However, the regulators of pancreatic regeneration and the underlying mechanisms remain uncovered. Here, using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown. Further investigations confirmed that Reg4 exerted its function through regulating Notch activation both in vitro and in vivo. Our study revealed Reg4 as a new regulator and potential therapeutic target for pancreatic regeneration.

Inhibition of nicotinamide phosphoribosyltransferase protects against acute pancreatitis via modulating macrophage polarization and its related metabolites.

BACKGROUND & OBJECTIVES: Acute pancreatitis is a common inflammatory disorder of the exocrine pancreas with no specific therapy. Intracellular nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) salvage pathway, is involved in many inflammatory disorders. In this study, we investigated the role of NAMPT in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in mice using three disparate models: (1) caerulein hyperstimulation, (2) ethanol plus palmitoleic acid, and (3) retrograde biliopancreatic ductal infusion of sodium taurocholate. The NAMPT inhibitor FK866 and NAMPT downstream product nicotinamide mononucleotide (NMN) was administered. Serum and pancreas were collected and analyzed biochemically and histologically. Bone marrow derived macrophages were isolated, cultured with cytokines or pancreatic acini, then analyzed by quantitative PCR and non-targeted metabolomics. RESULTS: The levels of pancreatic NAMPT and NAD were down-regulated upon acute pancreatitis. NAMPT inhibitor FK866 suppressed M1 macrophage polarization while NMN boosted it. In co-culture of macrophages with acinar cells, inhibition of NAMPT prevented M1-like macrophage differentiation induced by injured pancreatic acini. The injured pancreatic acinar milieu induced a unique metabolic signature linked to macrophage polarization, and inhibition of NAMPT reversed these metabolites changes. Furthermore, NMN supplementation aggravated caerulein hyperstimulation pancreatitis and alcoholic pancreatitis, and inhibition of NAMPT protected against caerulein hyperstimulation, alcoholic and biliary acute pancreatitis and reducing pancreatic macrophage infiltration in vivo. CONCLUSIONS: NAMPT inhibition protects against acute pancreatitis via preventing M1 macrophage polarization and restoring the metabolites related to macrophage polarization and that NAMPT could be a promising therapeutic target for acute pancreatitis.

Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer.

BACKGROUND: Tumor repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying tumor cells played vital roles in tumor repopulation through promoting proliferation of the residual tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate tumor repopulation after radiotherapy. METHODS: Tumor repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells. RESULTS: Exosomes derived from dying tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer repopulation upon radiation via inhibiting secretion of exosomes and PGE2. CONCLUSION: Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate tumor repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.

Aspirin in pancreatic cancer: chemopreventive effects and therapeutic potentials.

Pancreatic cancer is one of the most aggressive malignancies with dismal prognosis. Recently, aspirin has been found to be an effective chemopreventive agent for many solid tumors. However, the function of aspirin use in pancreatic cancer largely remains unknown. We herein argued that aspirin could also lower the risk of pancreatic cancer. Importantly, aspirin assumes pleiotropic effects by targeting multiple molecules. It could further target the unique tumor biology of pancreatic cancer and modify the cancer microenvironment, thus showing remarkable therapeutic potentials. Besides, aspirin could reverse the chemoradiation resistance by repressing tumor repopulation and exert synergistic potentials with metformin on pancreatic cancer chemoprevention. Moreover, aspirin secondarily benefits pancreatic cancer patients through modestly reducing cancer pain and the risk of venous thromboembolism. Furthermore, new aspirin derivatives and delivery systems might help to improve risk-to-benefit ratio. In brief, aspirin is a promising chemopreventive agent and exerts significant therapeutic potentials in pancreatic cancer.

MicroRNA-7 inhibits cell proliferation of chronic myeloid leukemia and sensitizes it to imatinib in vitro.

MicroRNA is a large class of non-coding small RNA that exerts critical roles in many physiological processes including cell proliferation. MicroRNA-7 (miR-7) has been considered as a tumor suppressor in most malignant tumors versus a tumor promoter in some other ones. However, its role in chronic myeloid leukemia remains unknown. Herein, we found that K562 cell proliferation was largely suppressed when it was stably transfected with miR-7. In accordance with that, apoptosis was also significantly upregulated in miR-7 stably-transfected K562 cells. Moreover, we found that miR-7-overexpressed K562 cells were far more sensitive to imatinib than controls. Further investigations showed that the ABL1 was a direct target of miR-7. Expression level of BCR-ABL and the activity of its downstream PI3K/AKT pathway were significantly reduced in miR-7-transfected cells. Taken together, our results showed that miR-7 inhibited proliferation and promoted apoptosis in K562 cells, and miR-7 might help to sensitize them to imatinib through BCR-ABL/PI3K/AKT signaling in chronic myeloid leukemia.

Unsupervised shape-and-texture-based generative adversarial tuning of pre-trained networks for carotid segmentation from 3D ultrasound images.

BACKGROUND: Vessel-wall volume and localized three-dimensional ultrasound (3DUS) metrics are sensitive to the change of carotid atherosclerosis in response to medical/dietary interventions. Manual segmentation of the media-adventitia boundary (MAB) and lumen-intima boundary (LIB) required to obtain these metrics is time-consuming and prone to observer variability. Although supervised deep-learning segmentation models have been proposed, training of these models requires a sizeable manually segmented training set, making larger clinical studies prohibitive. PURPOSE: We aim to develop a method to optimize pre-trained segmentation models without requiring manual segmentation to supervise the fine-tuning process. METHODS: We developed an adversarial framework called the unsupervised shape-and-texture generative adversarial network (USTGAN) to fine-tune a convolutional neural network (CNN) pre-trained on a source dataset for accurate segmentation of a target dataset. The network integrates a novel texture-based discriminator with a shape-based discriminator, which together provide feedback for the CNN to segment the target images in a similar way as the source images. The texture-based discriminator increases the accuracy of the CNN in locating the artery, thereby lowering the number of failed segmentations. Failed segmentation was further reduced by a self-checking mechanism to flag longitudinal discontinuity of the artery and by self-correction strategies involving surface interpolation followed by a case-specific tuning of the CNN. The U-Net was pre-trained by the source dataset involving 224 3DUS volumes with 136, 44, and 44 volumes in the training, validation and testing sets. The training of USTGAN involved the same training group of 136 volumes in the source dataset and 533 volumes in the target dataset. No segmented boundaries for the target cohort were available for training USTGAN. The validation and testing of USTGAN involved 118 and 104 volumes from the target cohort, respectively. The segmentation accuracy was quantified by Dice Similarity Coefficient (DSC), and incorrect localization rate (ILR). Tukey's Honestly Significant Difference multiple comparison test was employed to quantify the difference of DSCs between models and settings, where p ≤ 0.05 $p\,\le \,0.05$ was considered statistically significant. RESULTS: USTGAN attained a DSC of 85.7 ± 13.0 $85.7\,\pm \,13.0$ % in LIB and 86.2 ± 10.6 ${86.2}\,\pm \,{10.6}$ % in MAB, improving from the baseline performance of 74.6 ± 30.7 ${74.6}\,\pm \,{30.7}$ % in LIB (p < 10 - 12 $<10^{-12}$ ) and 75.7 ± 28.9 ${75.7}\,\pm \,{28.9}$ % in MAB (p < 10 - 12 $<10^{-12}$ ). Our approach outperformed six state-of-the-art domain-adaptation models (MAB: p ≤ 3.63 × 10 - 7 $p \le 3.63\,\times \,10^{-7}$ , LIB: p ≤ 9.34 × 10 - 8 $p\,\le \,9.34\,\times \,10^{-8}$ ). The proposed USTGAN also had the lowest ILR among the methods compared (LIB: 2.5%, MAB: 1.7%). CONCLUSION: Our framework improves segmentation generalizability, thereby facilitating efficient carotid disease monitoring in multicenter trials and in clinics with less expertise in 3DUS imaging.

Epidemiological characteristics of myopia among school-age children before, during, and after the COVID-19 pandemic: a cohort study in Shenzhen, China.

Objectives: To evaluate the epidemiological characteristics of myopia among school-aged children before, during, and after the coronavirus disease (COVID-19) pandemic. Methods: A total of 848,697 students aged 6-15 years from 786 primary and secondary schools in Shenzhen, China, were randomly selected as research subjects. We conducted annual myopia screenings from 2019 to 2022. 2019 was considered before the COVID-19 pandemic, 2020 as during the pandemic, and 2021 and 2022 as after the pandemic. Demographic characteristics, visual acuity, and spherical equivalent refraction (SE) were collected. Results: During the 4-year follow-up period, the uncorrected visual acuity (UCVA) of the study subjects progressed following a trend of -0.18 ± 0.30D (-0.17 ± 0.29D for boys, -0.21 ± 0.32Dfor girls) (p < 0.001). Those students who were in grade 4 aged 9-10 years at the baseline examination showed the greatest decline in visual acuity (0.23). The SE of the study subjects progressed following a trend of -1.00 ± 1.27D (-0.96 ± 1.25D for boys, -1.05 ± 1.31D for girls) (p < 0.001). The students who were in grade 5 aged 10-11 years at the baseline examination showed the greatest decline in SE (1.15D ± 1.22, p < 0.001). The prevalence of myopia (UCVA<5.0 and SE < -0.50D of any eye) increased by 28.2% (27.0% for boys and 29.8% for girls). Those students who were in grade 2 aged 7-8 years at the baseline examination showed the greatest increase in myopia prevalence (37.6%, p < 0.001). During the COVID-19 pandemic, the subjects' visual acuity and SE measurements decreased by -0.05 ± 0.19 (p < 0.001) and - 0.36 ± 0.89D (p < 0.001) respectively, and the prevalence of myopia increased by 11.3% (10.6% for boys and 12.2% for girls) (p < 0.001). The 3-year cumulative incidence of myopia for non-myopic grade 1 aged 6-7 years students with baseline SE of ≥1.00D, ≥ 0.50D and < 1.00D, ≥0D and < 0.50D, and ≥ -0.50D and < 0D were 6.8, 24.8, 39.0, and 48.1%, respectively. Conclusion: During the COVID-19 pandemic, the SE of school-aged children showed myopic drift and decreased visual acuity. Myopia progressed faster among girls than among boys in the same grades. The risk of myopia among school-aged children persisted even after the home quarantine of the COVID-19 pandemic was lifted.

5-aminosalicylic acid alleviates colitis and protects intestinal barrier function by modulating gut microbiota in mice.

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

Development of a nomogram for predicting myopia risk among school-age children: a case-control study.

OBJECTIVES: To analyze the factors influencing myopia and construct a nomogram to forecast the risk of myopia among school-age children, providing a reference for identifying high-risk groups to aid prevention and control. METHODS: This case-control study enrolled 3512 students from three primary schools in Shenzhen using random cluster sampling for a questionnaire survey, myopia screening and ocular biometric parameter measurement. Logistic regression was used to analyze the influencing factors of myopia, and a nomogram was constructed to forecast myopia risk. Bootstrap resampling was used to verify the practicability of the nomogram. RESULTS: Older age (odds ratio[OR] = 1.164; 95% confidence interval [CI]: 1.111-1.219), female sex (OR = 2.405; 95% CI: 2.003-2.887), maternal myopia (OR = 1.331; 95% CI: 1.114-1.589), incorrect posture during reading and writing (OR = 1.283; 95% CI: 1.078-1.528) and axial length (OR = 7.708; 95% CI: 6.044-8.288) are risk factors for myopia, whereas an increase in corneal radius (OR = 0.036; 95% CI: 0.025-0.052) is a protective factor against myopia. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.857, and the net benefit was high when the risk threshold of the decision curve analyses (DCA) ranged from 0.20 to 1.00. The measured values were consistent with the prediction. CONCLUSION: The nomogram was accurate in predicting the risk of myopia among schoolchildren. This study provides a reference for screening high-risk students and for individualized myopia prevention and control.

Older age, female sex, maternal myopia, incorrect posture during reading and writing, and prolonged axial length are risk factors for myopia among primary school students.The nomogram constructed based on age, sex, maternal myopia, incorrect posture during reading and writing, axial length and corneal radius showed good predictive accuracy and practicability.The nomogram constructed in this study can be used for individualized myopia risk assessment.

Pancreatic cancer cells hijack tumor suppressive microRNA-26a to promote radioresistance and potentiate tumor repopulation.

Pancreatic cancer is one of the most lethal cancers with significant radioresistance and tumor repopulation after radiotherapy. As a type of short non-coding RNA that regulate various biological and pathological processes, miRNAs might play vital role in radioresistance. We found by miRNA sequencing that microRNA-26a (miR-26a) was upregulated in pancreatic cancer cells after radiation, and returned to normal state after a certain time. miR-26a was defined as a tumor suppressive miRNA by conventional tumor biology experiments. However, transient upregulation of miR-26a after radiation significantly promoted radioresistance, while stable overexpression inhibited radioresistance, highlighting the importance of molecular dynamic changes after treatment. Mechanically, transient upregulation of miR-26a promoted cell cycle arrest and DNA damage repair to promote radioresistance. Further experiments confirmed HMGA2 as the direct functional target, which is an oncogene but enhances radiosensitivity. Moreover, PTGS2 was also the target of miR-26a, which might potentiate tumor repopulation via delaying the synthesis of PGE2. Overall, this study revealed that transient upregulation of miR-26a after radiation promoted radioresistance and potentiated tumor repopulation, highlighting the importance of dynamic changes of molecules upon radiotherapy.

Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis.

Background: Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules. Methods: Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis. Results: Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes. Conclusion: High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy.

Effectiveness of prognostic nutritional index in predicting overall survival and evaluating immunotherapy response in anaplastic thyroid carcinoma.

BACKGROUND: The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS: We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS: A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION: PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.