Deciphering the Effects of the PYCR Family on Cell Function, Prognostic Value, Immune Infiltration in ccRCC and Pan-Cancer.

Pyrroline-5-carboxylate reductase (PYCR) is pivotal in converting pyrroline-5-carboxylate (P5C) to proline, the final step in proline synthesis. Three isoforms, PYCR1, PYCR2, and PYCR3, existed and played significant regulatory roles in tumor initiation and progression. In this study, we first assessed the molecular and immune characteristics of PYCRs by a pan-cancer analysis, especially focusing on their prognostic relevance. Then, a kidney renal clear cell carcinoma (KIRC)-specific prognostic model was established, incorporating pathomics features to enhance predictive capabilities. The biological functions and regulatory mechanisms of PYCR1 and PYCR2 were investigated by in vitro experiments in renal cancer cells. The PYCRs' expressions were elevated in diverse tumors, correlating with unfavorable clinical outcomes. PYCRs were enriched in cancer signaling pathways, significantly correlating with immune cell infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI). In KIRC, a prognostic model based on PYCR1 and PYCR2 was independently validated statistically. Leveraging features from H&E-stained images, a pathomics feature model reliably predicted patient prognosis. In vitro experiments demonstrated that PYCR1 and PYCR2 enhanced the proliferation and migration of renal carcinoma cells by activating the mTOR pathway, at least in part. This study underscores PYCRs' pivotal role in various tumors, positioning them as potential prognostic biomarkers and therapeutic targets, particularly in malignancies like KIRC. The findings emphasize the need for a broader exploration of PYCRs' implications in pan-cancer contexts.

OMGMed: Advanced System for Ocular Myasthenia Gravis Diagnosis via Eye Image Segmentation.

This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of "network structure" and "loss function", and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of "nnUNet" network structure and "Cross-Entropy + Iou + Boundary" hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.

Exosomes: potential diagnostic markers and drug carriers for adenomyosis.

Adenomyosis is a common benign gynecological disorder and an important factor leading to infertility in fertile women. Adenomyosis can cause deep lesions and is persistent and refractory in nature due to its tumor-like biological characteristics, such as the ability to implant, adhere, and invade. The pathogenesis of adenomyosis is currently unclear. Therefore, new therapeutic approaches are urgently required. Exosomes are nanoscale vesicles secreted by cells that carry proteins, genetic materials and other biologically active components. Exosomes play an important role in maintaining tissue homeostasis and regulating immune responses and metabolism. A growing body of work has shown that exosomes and their contents are key to the development and progression of adenomyosis. This review discusses the current research progress, future prospects and challenges in this emerging therapeutic tool by providing an overview of the changes in the adenomyosis uterine microenvironment and the biogenesis and functions of exosomes, with particular emphasis on the role of exosomes and their contents in the regulation of cell migration, proliferation, fibrosis formation, neovascularization, and inflammatory responses in adenomyosis.

Weakly Supervised Collaborative Learning for Airborne Pollen Segmentation and Classification from SEM Images.

Existing pollen identification methods heavily rely on the scale and quality of pollen images. However, there are many impurities in real-world SEM images that should be considered. This paper proposes a collaborative learning method to jointly improve the performance of pollen segmentation and classification in a weakly supervised manner. It first locates pollen regions from the raw images based on the detection model. To improve the classification performance, we segmented the pollen grains through a pre-trained U-Net using unsupervised pollen contour features. The segmented pollen regions were fed into a deep convolutional neural network to obtain the activation maps, which were used to further refine the segmentation masks. In this way, both segmentation and classification models can be collaboratively trained, supervised by just pollen contour features and class-specific information. Extensive experiments on real-world datasets were conducted, and the results prove that our method effectively avoids impurity interference and improves pollen identification accuracy (86.6%) under the limited supervision (around 1000 images with image-level labels).

Simulation Palynologists for Pollinosis Prevention: A Progressive Learning of Pollen Localization and Classification for Whole Slide Images.

Existing API approaches usually independently leverage detection or classification models to distinguish allergic pollens from Whole Slide Images (WSIs). However, palynologists tend to identify pollen grains in a progressive learning manner instead of the above one-stage straightforward way. They generally focus on two pivotal problems during pollen identification. (1) Localization: where are the pollen grains located? (2) Classification: which categories do these pollen grains belong to? To perfectly mimic the manual observation process of the palynologists, we propose a progressive method integrating pollen localization and classification to achieve allergic pollen identification from WSIs. Specifically, data preprocessing is first used to cut WSIs into specific patches and filter out blank background patches. Subsequently, we present the multi-scale detection model to locate coarse-grained pollen regions (targeting at "pollen localization problem") and the multi-classifiers combination to determine the fine-grained category of allergic pollens (targeting at "pollen classification problem"). Extensive experimental results have demonstrated the feasibility and effectiveness of our proposed method.

An immune gene signature to predict prognosis and immunotherapeutic response in lung adenocarcinoma.

Lung adenocarcinoma is one of the most common malignant tumors worldwide. The purpose of this study was to construct a stable immune gene signature for prediction of prognosis (IGSPP) and response to immune checkpoint inhibitors (ICIs) therapy in LUAD patients. Five genes were screened by weighted gene coexpression network analysis, Cox regression and LASSO regression analyses and were used to construct the IGSPP. The survival rate of the IGSPP low-risk group was higher than that of the IGSPP high-risk group. Multivariate Cox regression analysis showed that IGSPP could be used as an independent prognostic factor for the overall survival of LUAD patients. IGSPP genes were enriched in cell cycle pathways. IGSPP gene mutation rates were higher in the high-risk group. CD4 memory-activated T cells, M0 and M1 macrophages had higher infiltration abundance in the high-risk group, which was associated with poor overall survival. In contrast, the abundance of resting CD4 memory T cells, monocytes, resting dendritic cells and resting mast cells associated with a better prognosis was higher in the low-risk group. TIDE scores and the expressions of different immune checkpoints showed that patients in the high-risk IGSPP group benefited more from ICIs treatment. In short, an IGSPP of LUAD was constructed and characterized. It could be used to predict the prognosis and benefits of ICIs treatment in LUAD patients.

Vitamin C protects early mouse embryos against juglone toxicity.

Juglone, a naphthoquinone isolated from many species of the Juglandaceae (walnut) family, has been used in traditional Chinese medicine for centuries for its various pharmacological effects. Our previous research found its toxic effects on oocytes maturation. But we still know a little about its toxic effects on embryo development. Here, we used mouse embryo as a model to explore the effects of juglone on early mammalian embryo development. Exposure to juglone significantly decreased the development rate in early mouse embryos in vitro. Moreover, juglone exposure led to developmental arrest by disturbing mitochondrial function, producing abnormal epigenetic modifications, inducing high levels of oxidative stress and DNA damage, and increasing the rate of embryonic cell apoptosis. However, vitamin C (VC) ameliorated the toxic effects of juglone to a certain extent. Overall, juglone has a toxic effect on early embryo development through the generation of ROS and apoptosis. But VC was able to protect against these juglone-induced defects. These results not only give a new perspective on juglone's pharmacological effects on early mammalian embryo development, but also provide ideas for the better application of this agent in traditional Chinese medicine.

The Effect of L-Carnitine Additive During In Vitro Maturation on the Vitrification of Pig Oocytes.

Cryopreservation of oocytes/embryos is an important technique for genetic resources; however, the success of vitrification in pig oocytes remained at a relatively lower level due to the high content of lipid droplets (LDs). Considering the positive effect of L-carnitine on the function of LDs, the present study was designed to investigate the effect of the addition of L-carnitine on the vitrification of porcine cumulus cells of complexes (cumulus/oocyte complexes [COCs]). First, COCs were randomly divided into two groups: one group of COCs were commonly in vitro maturation (IVM) for 42-46 hours (nonvitrification [NV]), while another group of COCs were IVM with 10 mM L-carnitine (NVL [nonvitrification with L-carnitine addition in IVM]). In addition, random parts of COCs with L-carnitine addition were vitrified (VL [vitrification with L-carnitine addition in IVM]), while vitrification was performed on COCs without L-carnitine used as control group (V). Results showed that the maturation rate of pig oocytes reduced significantly when the vitrification was performed at 16 hours during IVM (VL vs. NVL, 40.09 ± 2.85 vs. 90.76 ± 1.16; V vs. NV, 34.41 ± 2.55 vs. 89.71 ± 1.33, p < 0.01). With the addition of L-carnitine, intracellular LDs were decreased significantly (p < 0.01). However, no difference was observed on the efficiency of vitrification in pig oocytes (VL vs. V, 40.09 ± 2.85 vs. 34.41 ± 2.55, p > 0.05). In addition, not only the reactive oxygen species (ROS) level in pig oocytes with the L-carnitine addition group reduced significantly (p < 0.01), but also the expression of SOD1 gene was improved (p < 0.05). In conclusion, results demonstrated that although no difference could be observed on pig COC vitrification, the LDs and ROS level in pig oocytes could be modified by the addition of L-carnitine, which might be helpful for further development.

[Analysis of adverse reactions risk signal of Xinyuan Capsules based on national ADR monitoring spontaneous reporting system].

In recent years, the safety problems and events of traditional Chinese medicine represented by liver injury have occurred frequently. In particular, Polygonum multiflorum has been widely used and considered as a "non-toxic" tonic traditional Chinese medicine for thousands of years. However, in recent years, frequent reports of liver injury events have attracted widespread attention at home and abroad, which has made unfavorable impacts on traditional Chinese medicine and its international development. Some scho-lars have found that susceptible genes of P. multiflorum on liver injury lay a scientific foundation for formulating rational comprehensive prevention and control measures for liver injury risk of P. multiflorum and its relevant preparations. But what are the risk signals of adverse reactions of P. multiflorum in clinical application? Spontaneous reporting system is an important way to monitor and find adverse drug reaction(ADR) signals after the drug is launched in the market. It can find the ADR signals in time and effectively, and then effectively prevent and avoid the occurrence of adverse drug events. At present, the data mining technique has gradually become the main method of ADR/adverse event(AE) report analysis and evaluation at home and abroad. Specifically, Bayesian confidence propagation neural network in Bayesian method is a commonly used risk signal early warning analysis method. In this paper, BCPNN method was used to excavate the risk signals of adverse reactions of Xinyuan Capsules, a traditional Chinese medicine preparation containing P. multiflorum, such as nausea, diarrhea, rash, dizziness, vomiting, abdominal pain, headache, liver cell damage, so as to provide evidence-based evidence for clinical safe and rational use of drugs.

[Clinical characteristics and prognoses of 167 acute erythroleukemia patients].

OBJECTIVE: To observe the biological characteristic and the prognoses in patients with acute erythroleukemia (AEL). METHODS: The results of 167 patients with newly diagnosed AEL, from January 2003 and June 2013 in the First Affiliated Hospital of Soochow University, were reviewed by MICM. RESULTS: Flow cytometry analysis indicated that CD13(96.1%), CD33(95.1%), CD117(87.4%) and CD34 (79.4%) were highly expressed in AEL. 56 of 148 (37.8%) AEL patients had a variety of cytogenetic abnormalities, 27 of 148(18.2%) patients were complex karyotype (abnormalities involving 3 or more chromosomes), the abnormalities of chromosomes 3, 5, 7 and 8 were more frequently involved and the most common one was ＋8, accounting for 35.7% of all abnormal karyotype, followed by 5q- (17.9%). Mutation analysis showed CEBPA mutation ratio of AEL patients was 44.0% (11/25), that of NPM1 as 15.4% (4/26). Initial induced remission rate of AEL was 56.6% (30/53), compared by 33.3% (4/12) of MDSM6. Survival analysis showed that the overall survival in female was better than that in male (P=0.047). The overall survival time of transplantation group is significantly longer than chemotherapy group (P=0.000). The OS of 13-39 years old group was the best, 40-49 years old group took second place, >50 years old group appeared to be the worst. CONCLUSION: AEL had its own unique biological features, and allogeneic hematopoietic stem cell transplantation could significantly improve its poor prognosis.

Enlarging photovoltaic effect: combination of classic photoelectric and ferroelectric photovoltaic effects.

Converting light energy to electrical energy in photovoltaic devices relies on the photogenerated electrons and holes separated by the built-in potential in semiconductors. Photo-excited electrons in metal electrodes are usually not considered in this process. Here, we report an enhanced photovoltaic effect in the ferroelectric lanthanum-modified lead zirconate titanate (PLZT) by using low work function metals as the electrodes. We believe that electrons in the metal with low work function could be photo-emitted into PLZT and form the dominant photocurrent in our devices. Under AM1.5 (100 mW/cm²) illumination, the short-circuit current and open-circuit voltage of Mg/PLZT/ITO are about 150 and 2 times of those of Pt/PLZT/ITO, respectively. The photovoltaic response of PLZT capacitor was expanded from ultraviolet to visible spectra, and it may have important impact on design and fabrication of high performance photovoltaic devices based on ferroelectric materials.