Hemiprotonic ph-ph+ with two targets inhibits metastatic breast cancer and concurrent candidiasis.

Concurrent infection in breast cancer patients is the direct cause of the high mortality rate of the disease. However, there is no available method to increase the survival rate until now. To address the problem, we propose one drug with two target strategy to treat the refractory disease. A small chemical, ph-ph+, was attempted to be used in the study to explore the feasibility of the approach in anticancer and antifungus at the same time. The results showed that ph-ph+ could prevent the proliferation and metastasis of breast cancer cells, and kill C. albicans simultaneously. The molecular mechanism was associated with the activation of an evolutionarily conserved protease CLpP in the cancer and C. albicans cells. Also, the signaling pathway mediated by PLAGL2 that highly expressed in cancer cells participated in preventing cell metastasis and inducing apoptosis of ph-ph+. The one drug with dual targets inhibited the growth and metastasis of the cancer cells, and meanwhile eliminated C. albicans in tissues in the experimental animals. The results suggested that ph-ph+ with dual targets of CLpP and PLAGL2 would be a feasible approach to prolong the survival rate in patients with metastatic breast cancer and pathogenic infection.

Design and Experiment of an Unoccupied Control System for a Tracked Grain Vehicle.

In order to enhance crop harvesting efficiency, an automatic-driving tracked grain vehicle system was designed. Based on the harvester chassis, we designed the mechanical structure of a tracked grain vehicle with a loading capacity of 4.5 m3 and a grain unloading hydraulic system. Using the BODAS hydraulic controller, we implemented the design of an electronic control system that combines the manual and automatic operation of the chassis walking mechanism and grain unloading mechanism. We utilized a hybrid A* algorithm to plan the traveling path of the tracked grain vehicle, and the path-tracking controller of the tracked grain vehicle was designed by combining fuzzy control and pure pursuit algorithms. Leveraging binocular vision technology and semantic segmentation technology, we designed an automatic grain unloading control system with functions of grain tank recognition and grain unloading regulation control. Finally, we conducted experiments on automatic grain unloading control and automatic navigation control in the field. The results showed that both the precision of the path-tracking control and the automatic unloading system meet the requirements for practical unoccupied operations of the tracked grain vehicle.

Image Feature Detectors in Agricultural Harvesting: An Evaluation.

Image feature detection serves as the cornerstone for numerous vision applications, and it has found extensive use in agricultural harvesting. Nevertheless, determining the optimal feature extraction technique for a specific situation proves challenging, as the Ground Truth correlation between images is exceedingly elusive in harsh agricultural harvesting environments. In this study, we assemble and make publicly available the inaugural agricultural harvesting dataset, encompassing four crops: rice, corn and soybean, wheat, and rape. We develop an innovative Ground Truth-independent feature detector assessment approach that amalgamates efficiency, repeatability, and feature distribution. We examine eight distinct feature detectors and conduct a thorough evaluation using the amassed dataset. The empirical findings indicate that the FAST detector and ASLFeat yield the most exceptional performance in agricultural harvesting contexts. This evaluation establishes a trustworthy bedrock for the astute identification and application of feature extraction techniques in diverse crop reaping situations.

Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer's Disease through NAD+/SIRT1-Mediated Autophagy.

To date, Alzheimer's disease (AD) has grown to be a predominant health challenge that disturbs the elderly population. Studies have shown that mitochondrial dysfunction is one of the most significant features of AD. Transplantation therapy of healthy mitochondria (mitotherapy), as a novel therapeutic strategy to restore mitochondrial function, is proposed to treat the mitochondria-associated disease. Also, the molecular mechanism of mitotherapy remains unclear. Here, we applied the mitotherapy in AD model mice induced by amyloid-ß (Aß) plaque deposition and suggested that autophagy would be an important mechanism of the mitotherapy. After the healthy mitochondria entered the defective neuronal cells damaged by the misfolded Aß protein, autophagy was activated through the NAD+-dependent deacetylase sirtuin 1 (SIRT1) signal. The damaged mitochondria and Aß protein were eliminated by autophagy, which could also decrease the content of radical oxygen species (ROS). Moreover, the levels of brain-derived neurotrophic factor (BDNF) and extracellular-regulated protein kinases (ERK) phosphorylation increased after mitotherapy, which would be beneficial to repair neuronal function. As a result, the cognitive ability of AD animals was ameliorated in a water maze test after the healthy mitochondria were administrated to the mice. The study indicated that mitotherapy would be an effective approach to AD treatment through the mechanism of autophagy activation.

Toward real-time and accurate dense 3D mapping of crop fields for combine harvesters using a stereo camera.

Fast and accurate 3D scene perception is a crucial prerequisite for the autonomous navigation and harvesting of combine harvesters. However, crop field scenarios pose severe challenges for vision-based perception systems due to repetitive scenes, illumination changes and real-time constraints on embedded computing platforms. In this paper, we propose a feature-based, two-stage approach for real-time dense 3D mapping for combine harvesters. In the first stage, our approach constructs a sparse 3D map using reliable feature matching, which provides prior knowledge about the environment. In the second stage, our method formulates per-pixel disparity calculation as probabilistic inference. The key to our approach is the ability to compute dense 3D maps by combining Bayesian estimation with efficient and discriminative point cues from images, exhibiting tolerance against visual measurement uncertainties due to repetitive textures and uneven lighting in crop fields. We validate the performance of the proposed method using real crop field data, and the results demonstrate that our dense 3D maps provide detailed spatial metric information while maintaining a balance between accuracy and efficiency. This makes our approach highly valuable for online perception in combine harvesters operating with resource-limited systems.

Papillary thyroid carcinoma with desmoid-type fibromatosis: the clinicopathological features with characteristic imaging and molecular correlation requiring comprehensive treatment.

The pathogenesis and treatment of papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF), a rare subtype of papillary thyroid carcinoma characterized by a mixed epithelial-mesenchymal structure, are still ill-defined. Previous reports on PTC-DTF have had limited follow-up and recurrence has been rarely reported. To better understand this condition, we conducted a thorough analysis of five cases of PTC-DTF from our institute, including clinical and pathological examinations, imaging, immunohistochemistry, and molecular analysis. We also reviewed relevant literature. The mean age of the patients was 51.8 years, with three women and two men included in the group. Ultrasound often showed a hypoechogenic and well-defined nodule in the thyroid gland, except for one individual who had distant lung metastases detected by PET-CT. The nodules ranged in width from 0.5 to 5.0 cm and were excised in each case. Following surgery, 131I therapy was used in two cases. The overall number of PTC-DTF cases has risen from the previously reported 55 to 60, with females being the most commonly affected and ranging in age from 19 to 82. Most masses underwent a thyroidectomy, and approximately half of the patients had lymph node metastases. Histologically, PTC-DTFs were composed of a predominant stromal component (65%-90%) and an intervening epithelial component. These spindle cells were arranged in parallel with abundant cytoplasm and vacuole-like nucleus but there wasn't evident atypia. The carcinoma cells were positively stained for CK and TTF-1 by immunohistochemistry, whereas mesenchymal cells were positive for SMA and displayed nuclear immunoreactivity for ß-catenin. BRAF, NRAS, and CTNNB1 mutations were identified in the epithelial and mesenchymal components through molecular testing, respectively. Perhaps because the mesenchyme harbors aberrant nuclear ß-catenin expression, PTC-DTF is more aggressive and prone to invasion and distant recurrence, as shown by our case 2, which is the first case to be reported thus far. PTC-DTF is typically treated with surgery, but clinicians may occasionally consider more holistic treatment plans that involve radioactive iodine and endocrine therapy.

Energy Storage Mechanism of C12-3-3 with High-Capacity and High-Rate Performance for Li/Mg Batteries.

The low specific capacity and Mg non-affinity of graphite limit the energy density of ion rechargeable batteries. Here, we first identify that the monolayer C12-3-3 in sp2-sp3 carbon hybridization with high Li/Mg affinity is an appropriate anode material for Li-ion batteries and Mg-ion batteries via the first-principles simulations. The monolayer C12-3-3 can achieve high specific capacities of 1181 mAh/g for Li and 739 mAh/g for Mg, higher than those of most previous anodes. The Li storage reaction is an "adsorption-conversion-intercalation mechanism", while the Mg storage reaction is an "adsorption mechanism". The 2D carbon material of C12-3-3 displays fast diffusion kinetics with low diffusion barriers of 0.41 eV for Li and 0.21 eV for Mg. As a new carbon-based anode material, the monolayer C12-3-3 will promote the practical application of batteries with high-capacity and high-rate performance.

Stereovision-Based Ego-Motion Estimation for Combine Harvesters.

Ego-motion estimation is a foundational capability for autonomous combine harvesters, supporting high-level functions such as navigation and harvesting. This paper presents a novel approach for estimating the motion of a combine harvester from a sequence of stereo images. The proposed method starts with tracking a set of 3D landmarks which are triangulated from stereo-matched features. Six Degree of Freedom (DoF) ego motion is obtained by minimizing the reprojection error of those landmarks on the current frame. Then, local bundle adjustment is performed to refine structure (i.e., landmark positions) and motion (i.e., keyframe poses) jointly in a sliding window. Both processes are encapsulated into a two-threaded architecture to achieve real-time performance. Our method utilizes a stereo camera, which enables estimation at true scale and easy startup of the system. Quantitative tests were performed on real agricultural scene data, comprising several different working paths, in terms of estimating accuracy and real-time performance. The experimental results demonstrated that our proposed perception system achieved favorable accuracy, outputting the pose at 10 Hz, which is sufficient for online ego-motion estimation for combine harvesters.

Synthesis of Hemiprotonic Phenanthroline-Phenanthroline+ Compounds with both Antitumor and Antimicrobial Activity.

Currently, cancer patients with microbial infection are a severe challenge in clinical treatment. To address the problem, we synthesized hemiprotonic compounds based on the unique structure of hemiprotonic nucleotide base pairs in a DNA i-motif. These compounds were produced from phenanthroline (ph) dimerization with phenanthroline as a proton receptor and ammonium as a donor. The biological activity shows that the compounds have a selective antitumor effect through inducing cell apoptosis. The molecular mechanism could be related to specific inhibition of transcription factor PLAGL2 of tumor cells, assessed by transcriptomic analysis. Moreover, results show that the hemiprotonic ph-ph+ has broad-spectrum antibacterial and antifungal activities, and drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus, are sensitive to the compound. In animal models of liver cancer with fungal infection, the ph-ph+ retards proliferation of hepatoma cells in tumor-bearing mice and remedies pneumonia and encephalitis caused by Cryptococcus neoformans. The study provides a novel therapeutic candidate for cancer patients accompanied by infection.

Pornography Use Could Lead to Addiction and Was Associated With Reproductive Hormone Levels and Semen Quality: A Report From the MARHCS Study in China.

This study aimed to investigate the situations of pornography use among male college students of China, to explore the addiction possibility for pornography use, and to study the associations between pornography use and reproductive hormone levels and semen quality. Five hundred sixty-eight participants met the inclusion criteria and finished all of the questionnaires and hormone level and semen parameter examinations. A majority of participants (except one) had pornography use experience, 94.2% participants started pornography use before college, and 95.9% participants reported they had masturbation experience when using pornography. Early contact to pornography, frequent pornography use, high amount of time spending on pornography use, and frequent masturbation during pornography use were correlated with addiction trends. Earlier pornography use was found to be associated with lower serum prolactin (PRL), follicle-stimulating hormone (FSH), and progesterone (Prog), as well as lower sperm concentration and total sperm count. Higher frequency of pornography use was associated with lower serum estrogen (E2). In conclusion, pornography use was common among male college students in China. Early contact, high frequent use, and high frequency of masturbation during pornography use could lead to addiction trends and aberrant reproductive hormone levels and semen quality.

An exposomic approach with 138 chemical and non-chemical exposures to predict 32 biomarkers of male reproductive damages: A case study of college students in Chongqing, China.

Male reproductive damage in the general population comprises different disorders in various biomarkers, which could be respectively caused by a number of exposure factors. However, researchers considering the environmental/behavioral/psychological exposures together to evaluate their contribution to male reproductive damage are still lacking. The present study investigated the comprehensive association between 138 environmental/behavioral/psychological exposures and 32 male reproductive biomarkers in 796 young Chinese men using graph-guided fused lasso (GFLASSO) and hierarchical clustering methods. All biomarkers were found to be associated with various exposures. A combination of these exposures not only predicted the levels of single biomarkers in another test dataset, but also identified the comprehensive reproductive features by clustering the men into five subgroups with distinct damages representing disrupted spermatogenesis with abnormal sperm morphology, low sperm motility with DNA fragmentation, chromatin immaturity, aberrant endocrine, or DNA strand breakage. The findings can be used to suggest a novel way to identify the males with a high risk of reproductive damage and develop personalized preventive strategies.

Unusual subcutaneous dedifferentiated liposarcoma exhibiting coexistence of meningothelial-like whorls and inflammatory myofibroblastic tumor-like structures.

To explore the clinicopathological features of a rare dedifferentiated liposarcoma (DDLPS) with meningothelial-like whorls, we retrospectively analyzed 46 reported cases and 1 case that we encountered. Fluorescence in situ hybridization (FISH) analysis of the MDM2 amplification status of our case was also performed. Our case involved a 73-year-old male patient who had a mass in the upper part of his left arm for 10 years and was treated by surgical ablation of the tumor because of the mass' recent rapid enlargement. Microscopically, the tumor tissues showed coexistence of well-differentiated and dedifferentiated components, the latter of which included meningothelial-like whorls and inflammatory myofibroblastic tumor-like structures. The dedifferentiated components diffusely expressed vimentin, MDM2, CDK4, p16, and smooth muscle actin. They were also focally positive for desmin but negative for S-100, CD117, CD34, ALK, EMA, SOX-10, p53, and ß-catenin. FISH detection showed MDM2 amplification. In conclusion, subcutaneous DDLPS with meningothelial-like whorls and inflammatory myofibroblastic tumor-like features is rare. This case broadens the histopathological lineage of DDLPS, and confirms DDLPS with myogenic differentiation. The use of the combination of MDM2, CDK4, p16, and FISH to detect MDM2 amplification is a reliable basis for the diagnosis of DDLPS with meningothelial-like whorls.

Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients. This hyper-methylation at promoter of SOX30 directly causes its silencing of expression in NOA. The reduced levels of SOX30 expression are correlated with severity of NOA disease. Deletion of Sox30 in mice uniquely impairs testis development and spermatogenesis with complete absence of spermatozoa in testes leading to male infertility, but does not influence ovary development and female fertility. The pathology and testicular size of Sox30 null mice highly simulate those of NOA patients. Re-expression of Sox30 in Sox30 null mice at adult age reverses the pathological damage of testis and restores the spermatogenesis. The re-presented spermatozoa after re-expression of Sox30 in Sox30 null mice have the ability to start a pregnancy. Moreover, the male offspring of Sox30 re-expression Sox30 null mice still can father children, and these male offspring and their children can live normally more than 1 year without significant difference of physical appearance compared with wild-type mice. In summary, methylated inactivation of SOX30 uniquely impairs spermatogenesis, probably causing NOA disease, and re-expression of SOX30 can successfully restore the spermatogenesis and actual fertility. This study advances our understanding of the pathogenesis of NOA, offering a promising therapy target for NOA disease.

Author Correction: Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.

After publication of this article, it came to the attention of the authors that their names had been reordered. Professor. Jia Cao and Prof. Jin-yi Liu are the co-corresponding authors, and Prof. Jin-yi Liu should be the last author.

Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.

Although TC2N has proven to be an oncogene in lung cancer, its biological function and molecular mechanisms in other cancer still remains unclear. Here, we investigate in breast cancer that TC2N expression is sharply overexpressed in breast cancer specimens compared with normal breast specimens, and the low TC2N expression was associated with advanced stage, lymphatic metastasis, larger tumors and shorter survival time. Upregulation of TC2N significantly restrains breast cancer cell proliferation in vitro and tumor growth in vivo. Mechanistically, TC2N blocks AKT signaling in a PI3K dependent and independent way through weakening the interaction between ALK and p55γ or inhibiting the binding of EBP1 and AKT. To sum up, these results unmask an ambivalent role of TC2N in cancer, providing a promising inhibitor for PI3K-AKT signaling.

Kisspeptin Protein in Seminal Plasma Is Positively Associated with Semen Quality: Results from the MARHCS Study in Chongqing, China.

OBJECTIVES: To study the associations between kisspeptin levels in seminal plasma and blood plasma and semen quality. MATERIALS AND METHODS: We conducted a male reproductive health survey in June 2014. A total of 666 volunteers were recruited from colleges in Chongqing, China. All volunteers completed a questionnaire including information on domestic characteristics and some potential confounders. We tested the kisspeptin levels in both blood and seminal plasma. Total seminal kisspeptin was calculated as the concentration of kisspeptin in seminal plasma multiplied by semen volume. Semen samples were tested according to the 2010 World Health Organization's (WHO) guidelines. Spearman correlation and multivariate linear regression were used to explore the association between kisspeptin concentrations in seminal plasma and blood plasma and semen quality. Potential confounders that were adjusted for included age, abstinence time, body mass index (BMI), grade, and smoking. RESULTS: The median of kisspeptin levels in seminal plasma was 60,000 times higher than kisspeptin in blood plasma (28.0 × 106 pg/ml versus 448.9 pg/ml). Each interquartile range (IQR) of kisspeptin in seminal plasma was associated with a 4.6% (95% confidence interval [CI]: 1.6%-7.6%) increase in sperm concentration. Each IQR of total kisspeptin was associated with a 7.7% (95% CI: 4.4%-11.0%) increase in total sperm number and a 7.8% (95% CI: 4.0%-11.7%) increase in total motile sperm count. Kisspeptin levels were further classified into quartiles and Q1 was set as the reference level. Subjects in the high total kisspeptin group had 57.5% (95% CI: 33.2%-86.2%) higher total sperm number than the reference group. CONCLUSION: The positive association between kisspeptin levels in seminal plasma and semen quality supported an important role for the KISS1/GPR54 system in male reproductive health. Kisspeptin may be a potential marker of male reproductive health and an alternative strategy for treating infertility.

Proteomic analysis reveals dysregulated cell signaling in ejaculated spermatozoa from infertile men.

Dysfunctional sperm maturation is the primary reason for the poor sperm motility and morphology in infertile men. Spermatozoa from infertile men were fractioned on three-layer density gradient (80%, 60%, and 40%). Fraction 1 (F1) refers to the least mature stage having the lowest density, whereas the fraction 4 (F4) includes the most dense and morphologically mature motile spermatozoa. Fraction 2 (F2) and fraction 3 (F3) represent the intermediate stages. Proteins were extracted and separated by 1-dimensional gel. Bands were digested with trypsin and analyzed on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Functional annotations of proteins were obtained using bioinformatics tools and pathway databases. A total of 1585 proteins were detected in the four fractions of spermatozoa. A dysregulated protein turnover and protein folding may lead to accumulation of defective proteins or proteins that otherwise would have been eliminated during the process of maturation, resulting in the impairment of sperm function. Aberrant chaperone expression may be a major contributing factor to the defective sperm function. Androgen receptor was predicted as a transcription regulator in one of the networks and the affected pathways were chaperone-mediated stress response, proteosomal pathway, and sperm function. The downregulation of key pathways and proteins which compromises the fertilizing potential of spermatozoa may provide insight into the mechanisms that lead to male infertility.

Spindle cell lipoma: clinicopathologic characterization of 40 cases.

OBJECTIVE: In view of the existence of multifarious pathologic subtypes of spindle cell lipoma (SCL), which is easily misdiagnosed as other benign and malignant soft tissue tumors, we performed this study and aimed to better define the category of SCL. METHODS: We collected and analyzed 40 cases of SCL with complete clinical and pathologic information from January 2010 to December 2018. Clinical and histopathologic analyses of SCL were performed, as well as immunohistochemical staining and fluorescence in situ hybridization (FISH) using probes for RB1 and MDM2, and the related literature was reviewed. RESULTS: In 40 cases, the male to female ratio was 3.4:1, and the mean age was 54 years old. SCL of our study included six pathologic subtypes: classic (25/40), fibrous (4/40), myxoid (4/40), low-fat (3/40), pseudoangiomatous (2/40), and fat-rich (2/40) changes. Microscopically, SCL showed distinctive morphology, with uniform spindle cells and a variably adipocytic component. The spindle cells were bland in morphology, without prominent atypia or pleomorphism, set in a myxoid or fibrous matrix. Immunohistochemically, CD34 and vimentin were positive in spindle cells, and spindle cells of 6 cases also expressed S-100 protein. FISH analysis of 10 cases revealed that heterozygous deletion of RB1 was in six samples with chromosome 13 aberrations and MDM2 gene amplification was not detected in any cases. Surgical resection is considered as the primary treatment for SCL, as there was no any recurrence or metastasis in our cases after 2-105 months of follow-up. CONCLUSIONS: SCL is a rare benign lipoma, and the proportion of spindle cells and adipocytic component varies, which may form various pathologic changes. The diagnosis needs to be combined with clinicopathologic features, immunophenotypes, and genetics. It has to be differentiated from mammary-type myofibroblastoma, cellular angiolipoma, solitary fibrous tumor, and myxoid liposarcoma.

TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer.

The protein containing the C2 domain has been well documented for its essential roles in endocytosis, cellular metabolism and cancer. Tac2-N (TC2N) is a tandem C2 domain-containing protein, but its function, including its role in tumorigenesis, remains unknown. Here, we first identified TC2N as a novel oncogene in lung cancer. TC2N was preferentially upregulated in lung cancer tissues compared with adjacent normal lung tissues. High TC2N expression was significantly associated with poor outcome of lung cancer patients. Knockdown of TC2N markedly induces cell apoptosis and cell cycle arrest with repressing proliferation in vitro, and suppresses tumorigenicity in vivo, whereas overexpression of TC2N has the opposite effects both in vitro and in vivo. Using a combination of TCGA database and bioinformatics, we demonstrate that TC2N is involved in regulation of the p53 signaling pathway. Mechanistically, TC2N attenuates p53 signaling pathway through inhibiting Cdk5-induced phosphorylation of p53 via inducing Cdk5 degradation or disrupting the interaction between Cdk5 and p53. Moreover, the blockade of p53 attenuates the function of TC2N knockdown in the regulation of cell proliferation and apoptosis. In addition, downregulated TC2N is involved in the apoptosis of lung cancer cells induced by doxorubicin, leading to p53 pathway activation. Overall, these findings uncover a role for the p53 inactivator TC2N in regulating the proliferation and apoptosis of lung cancer cells. Our present study provides novel insights into the mechanism of tumorigenesis in lung cancer.

Early pubertal timing is associated with lower sperm concentration in college students.

To study the associations between pubertal timing and semen quality and reproductive hormones, 680 volunteers were recruited from universities in Chongqing, China. Pubertal timing was obtained using a questionnaire. The main measurements were five routine semen parameters and six reproductive hormones. After adjusting for potential confounders, we found that early pubertal timing was associated with lower sperm concentration. An one-year increase in age of peak height velocity was associated with a 4.7% (95% confidence interval [CI] = 1.0 to 8.6) increase in sperm concentration. An one-year increase in age of first spermatorrhea was associated with a 6.4% increase in sperm concentration and a 2.9% decrease in semen volume (95% CI = 1.7 to 11.3, -5.5 to -0.3; respectively). Regarding reproductive hormones, an one-year increase in age of height spurt and peak height velocity was associated with a 6.5% and a 6.7% decrease in estrogen (95% CI = -9.8 to -3.0, -10.4 to -2.8; respectively). While an one-year increase in age of height spurt was associated with higher follicle-stimulating hormone (% change = 2.6, 95% CI = 0.2 to 4.7). This was the first report that has suggested that early pubertal timing is associated with lower sperm concentration. However, further study is still needed to validate this association and fully elucidate the mechanism behind it.