E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

Interpretable thoracic pathologic prediction via learning group-disentangled representation.

Deep learning has brought a significant progress in medical image analysis. However, their lack of interpretability might bring high risk for wrong diagnosis with limited clinical knowledge embedding. In other words, we believe it's crucial for humans to interpret how deep learning work for medical analysis, thus appropriately adding knowledge constraints to correct the bias of wrong results. With such purpose, we propose Representation Group-Disentangling Network (RGD-Net) to explain the process of feature extraction and decision making inside deep learning framework, where we completely disentangle feature space of input X-ray images into independent feature groups, and each group would contribute to diagnose of a specific disease. Specifically, we first state problem definition for interpretable prediction with auto-encoder structure. Then, group-disentangled representations are extracted from input X-ray images with the proposed Group-Disentangle Module, which constructs semantic latent space by enforcing semantic consistency of attributes. Afterwards, adversarial constricts on mapping from features to diseases are proposed to prevent model collapse during training. Finally, a novel design of local tuning medical application is proposed based on RGB-Net, which is capable to aid clinicians for reasonable diagnosis. By conducting quantity of experiments on public datasets, RGD-Net have been superior to comparative studies by leveraging potential factors contributing to different diseases. We believe our work could bring interpretability in digging inherent patterns of deep learning on medical image analysis.

A potent new-scaffold androgen receptor antagonist discovered on the basis of a MIEC-SVM model.

Prostate cancer (PCa) is the second most prevalent malignancy among men worldwide. The aberrant activation of androgen receptor (AR) signaling has been recognized as a crucial oncogenic driver for PCa and AR antagonists are widely used in PCa therapy. To develop novel AR antagonist, a machine-learning MIEC-SVM model was established for the virtual screening and 51 candidates were selected and submitted for bioactivity evaluation. To our surprise, a new-scaffold AR antagonist C2 with comparable bioactivity with Enz was identified at the initial round of screening. C2 showed pronounced inhibition on the transcriptional function (IC50 = 0.63 µM) and nuclear translocation of AR and significant antiproliferative and antimetastatic activity on PCa cell line of LNCaP. In addition, C2 exhibited a stronger ability to block the cell cycle of LNCaP than Enz at lower dose and superior AR specificity. Our study highlights the success of MIEC-SVM in discovering AR antagonists, and compound C2 presents a promising new scaffold for the development of AR-targeted therapeutics.

Computationally guided discovery of novel non-steroidal AR-GR dual antagonists demonstrating potency against antiandrogen resistance.

As a major class of medicine for treating the lethal type of castration-resistant prostate cancer (PCa), long-term use of androgen receptor (AR) antagonists commonly leads to antiandrogen resistance. When AR signaling pathway is blocked by AR-targeted therapy, glucocorticoid receptor (GR) could compensate for AR function especially at the late stage of PCa. AR-GR dual antagonist is expected to be a good solution for this situation. Nevertheless, no effective non-steroidal AR-GR dual antagonist has been reported so far. In this study, an AR-GR dual binder H18 was first discovered by combining structure-based virtual screening and biological evaluation. Then with the aid of computationally guided design, the AR-GR dual antagonist HD57 was finally identified with antagonistic activity towards both AR (IC50 = 0.394 µM) and GR (IC50 = 17.81 µM). Moreover, HD57 could effectively antagonize various clinically relevant AR mutants. Further molecular dynamics simulation provided more atomic insights into the mode of action of HD57. Our research presents an efficient and rational strategy for discovering novel AR-GR dual antagonists, and the new scaffold provides important clues for the development of novel therapeutics for castration-resistant PCa.

Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.

HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17.

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 µM to 9.2 µM.

Association between single nucleotide polymorphism rs11057401 of CCDC92 gene and the risk of coronary heart disease (CHD).

BACKGROUND: Given that the CCDC92 (coiled-coil domain containing 92) was important in insulin resistance, we sought to investigate whether the CCDC92 rs825476 SNP is associated with the risk of CHD in Chinese Han population. METHODS: Rs11057401 was genotyped for 817 patients with CHD and 724 age- and sex-matched controls using PCR-based Invader assay with the probe sets designed and synthesized by third wave. RESULTS: Patients were found to have a significantly higher frequency of AA than the controls (23.5% vs. 14.7%, OR = 1.60, p = 0.000), and the frequency of allele A was found to be remarkably higher in the patients than the controls (48.1% vs. 40.3%, OR = 1.19, p = 0.000). Multivariate logistic analysis showed that the incidence of CHD was positively correlated with hyperlipidemia, T2D and rs11057401 AA/AT genotypes. The FPG, TC, and ApoA1 levels in the CHD patients were different among the AA, AT and TT genotypes (P < 0.05), the A allele carriers had higher FPG, TC and lower ApoA1 levels than the A allele non-carriers (P < 0.05). CONCLUSION: The genotypic and allelic frequencies of the rs11057401 SNP were significantly different between the patients with CHD and controls. Subjects with AA genotype or A allele were associated with an increased risk of CHD. The AA/AT genotypes were also associated with increased serum FPG, TC and decreased ApoA1 in CHD.

Rhein induces apoptosis and autophagy in human and rat glioma cells and mediates cell differentiation by ERK inhibition.

In this study, we investigated the anticancer potentials of Rhein, an anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98 glioma cells. The experimental studies revealed that Rhein induced cell cycle arrest, caspase mediated apoptosis. It results in the formation of intracellular acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable cells towards elongation of matured astrocytes was proved by monitoring dramatic changes in morphological characteristics as well as identified from the elevation of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not alter the phosphorylated MAPKs activation including p-38, JNK and NF-κB, transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98 glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein effects on morphology and expressions of GFAP but did not help to induce any apoptosis or autophagy. Collective data exhibited that potentials of rhein in anti-cancer property in ERK-independent apoptosis and autophagy in association with downregulated ERK-dependent differentiation process of glioma cell lines.

Flow diverter treatment of posterior circulation aneurysms. A meta-analysis.

INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option.

[Research on the range of motion measurement system for spine based on LabVIEW image processing technology].

A measurement system based on the image processing technology and developed by LabVIEW was designed to quickly obtain the range of motion (ROM) of spine. NI-Vision module was used to pre-process the original images and calculate the angles of marked needles in order to get ROM data. Six human cadaveric thoracic spine segments T7-T10 were selected to carry out 6 kinds of loads, including left/right lateral bending, flexion, extension, cis/counterclockwise torsion. The system was used to measure the ROM of segment T8-T9 under the loads from 1 Nm to 5 Nm. The experimental results showed that the system is able to measure the ROM of the spine accurately and quickly, which provides a simple and reliable tool for spine biomechanics investigators.

LEO navigation observables extraction using CLOCFC network.

In case of mitigate the reliance of aviation users on the Global Navigation Satellite System (GNSS) in an increasingly interference-prone environment, utilizing opportunistic signals from Low-Earth Orbit (LEO) for navigation and positioning is an alternative approach. However, LEO satellite SOPs are not intended for navigation. Therefore, it is necessary to design methods to extract navigation observables from these signals. In this paper, we proposed a lightweight deep learning model with a two-branch structure called CLOCFC, designed to extract navigation observables. Furthermore, we have established a low Earth orbit satellite signal dataset by using ORBCOMM constellation signals as the input to the model and Doppler frequency as the label for the model. The results show that CLOCFC, as a lightweight model, demonstrates a significantly faster convergence rate and higher accuracy in navigation observables extraction compared to other models (ResNet, Swin Transformer, and Clo Transformer). In CLOCFC, we introduce the CFC module, a kind of Liquid Neural Network, to enhance the information acquisition capability through the spatiotemporal information in the data sequence. Finally, we have also conducted extensive experiments with the Doppler shift extraction of LEO satellites as an example, under various noise and resolution conditions, demonstrating the superiority of the CLOCFC.

Patient satisfaction and follow-up adherence to glaucoma case management clinic in China.

AIM: To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes. METHODS: In this cross-sectional study, a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire. Clinical data was obtained from the case management system. Follow-up adherence was defined as completing each follow-up within ±30d of the scheduled time set by ophthalmologists during the study period. RESULTS: Average satisfaction scored 78.65±7, with an average of 4.39±0.58 across the seven dimensions. Age negatively correlated with satisfaction (P=0.008), whilst patients with follow-up duration of 2 or more years reported higher satisfaction (P=0.045). Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence (OR=0.97, 95%CI, 0.95-1.00, P=0.044). Additionally, patients with suspected glaucoma (OR=2.72, 95%CI, 1.03-7.20, P=0.044) and those with an annual income over 100 000 Chinese yuan demonstrated higher adherence (OR=5.57, 95%CI, 1.00-30.89, P=0.049). CONCLUSION: The case management model proves effective for glaucoma patients, with positive adherence rates. The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.

Effects of biochar on plant growth and hydro-chemical properties of recycled concrete aggregate.

Biochar has been used as a sustainable amendment to mitigate environmental risks, improve plant growth and soil properties. This study conducted laboratory column tests to investigate the effects of plant-biochar interactions on shrub growth, hydraulic properties and nutrient contents of recycled concrete aggregates (RCAs). In total, three test conditions, namely, vegetated RCA without biochar (R), with 5 % biochar (R5) and 10 % biochar (R10) were subject to drying. With biochar application, total N, P and K of RCA increased by >100 %, 200 % and 31 %, respectively, while pH reduced to 8.3. With shrub growth, the lowest RCA pH was reduced to 7.8. The leaf area index (LAI) of shrub increased by 51 % due to biochar amendment, while the differences in shoot height were insignificant. The water retention capacity of RCA was enhanced by improving the saturated water content and air-entry value by 27 % and 100 %. The slope of the soil suction-LAI correlation for biochar amend cases was 1.6 times lower than R. This indicates that biochar may limit the increase of matric suction and prevent excessive water loss during drying. However, the differences between R5 and R10 were not significant. Therefore, 5 % biochar amendment is highly suggested as it can substantially improve plant growth and soil hydraulic properties during drying.

Two Path Gland Segmentation Algorithm of Colon Pathological Image Based on Local Semantic Guidance.

Colonic adenocarcinoma is a disease severely endangering human life caused by mucosal epidermal carcinogenesis. The segmentation of potentially cancerous glands is the key in the detection and diagnosis of colonic adenocarcinoma. The appearance of cancerous tissue is different in gland segmentation in colon pathological images, and it is impossible to accurately segment the changes of glands from benign to malignant using a single network. Given these issues, a two-path gland segmentation algorithm of colon pathological image based on local semantic guidance is proposed in this paper. The improved candidate region search algorithm is adopted to expand the original image data set and generate sub-datasets sensitive to specific features. Then, the semantic feature-guided model is employed to extract the local adenocarcinoma features and acts on the backbone network together with context feature extraction based on the attention mechanism. In this way, a larger receptive field and more local feature information are obtained, the learning ability of the network to the morphological features of glands is enhanced, and the performance of automatic gland segmentation is finally improved. The algorithm is verified on Warwick Qu-Dataset. Compared with the current popular segmentation algorithms, our algorithm has good performance in Dice coefficient, F1 score, and Hausdorff distance on different types of test sets.

Effects of different storage containers on the flavor characteristics of Jiangxiangxing baijiu.

Storage is a key factor controlling the quality of Jiangxiangxing baijiu, and storage time and the type of storage container play crucial roles in shaping the baijiu's distinct flavor. To investigate the influence of storage containers on the flavor characteristics of Jiangxiangxing baijiu, the sensory qualities, flavor components, and metal ions of Jiangxiangxing baijiu were measured during 24 months of storage in a pottery jar or a stainless steel tank. The results showed that Jiangxiangxing baijiu preserved in a pottery jar was superior to that stored in a stainless steel tank. A total of 96 flavor substances were detected, and 17 key flavor characteristic substances were screened by combining the results of odor activity values (OAV) and orthogonal partial least squares-discriminant analysis (OPLS-DA). A correlation heat map and redundancy analysis (RDA) showed that aluminum, cadmium, iron, cobalt, magnesium, potassium, and copper ions promoted the formation of key characteristic substances including diethoxymethane, lactic acid, 2,3-dimethyl-5-ethylpyrazine, 1-hexanol, and 2-methyl-1-propanol. Overall, the results show that 24-month pottery jar storage can promote the flavor quality of Jiangxiangxing baijiu. This study established a theoretical foundation to select the appropriate storage conditions and control the flavor quality of Jiangxiangxing baijiu.

Case report: Clinical characteristics of two cases of pneumonia caused with different strains of Chlamydia psittaci.

Background: With the development of metagenomic sequencing technologies, more and more cases of pneumonia caused with Chlamydia psittaci (C. psittaci) have been reported. However, it remains unknown about the characteristics of patients with pneumonia caused by different strains of C. psittaci. Here, we shared the clinical characteristics of two cases of pneumonia caused with C. psittaci strains SZ18-2 and SZ15 which were rarely identified in humans. Case presentation: Case 1: A 69-year-old male farmer who fed ducks presented to hospital for cough, diarrhea and lethargy with the temperature of 39.8°C. Case 2: A 48-year-old male worker who slaughtered ducks was transferred to hospital for high fever, cough, myalgia, diarrhea and loss of appetite. Both patients did not take any protective measures (wearing face masks or gloves) while processing ducks. C. psittaci pneumonia was diagnosed by metagenomic next-generation sequencing and polymerase chain reaction. After treatment with doxycycline and azithromycin individually, they recovered well and discharged from hospital. Through OmpA sequencing, two different strains of SZ18-2 and SZ15 were identified in case 1 and case 2, respectively. Conclusions: Patients infected with different strains of C. psittaci may own different clinical manifestations. C. psittaci infection should be suspected when pneumonia appears, accompanied by digestive symptoms and multiple organ dysfunction, especially under the exposure of specific birds.

Biphasic activation of nuclear factor-kappa B in experimental models of subarachnoid hemorrhage in vivo and in vitro.

It has been proven that nuclear factor-kappa B (NF-κB) is activated as a well-known transcription factor after subarachnoid hemorrhage (SAH). However, the panoramic view of NF-κB activity after SAH remained obscure. Cultured neurons were signed into control group and six hemoglobin- (Hb-) incubated groups. One-hemorrhage rabbit SAH model was produced, and the rabbits were divided randomly into one control group and five SAH groups. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. Real-time polymerase chain reaction (PCR) was performed to assess the downstream genes of NF-κB. NeuN immunofluorescence and lactate dehydrogenase (LDH) quantification were used to estimate the neuron injury. Double drastically elevated NF-κB activity peaks were detected in rabbit brains and cultured neurons. The downstream gene expressions showed an accordant phase peaks. NeuN-positive cells decreased significantly in day 3 and day 10 groups. LDH leakage exhibited a significant increase in Hb-incubated groups, but no significant difference was found between the Hb incubated groups. These results suggested that biphasic increasing of NF-κB activity was induced after SAH, and the early NF-κB activity peak indicated the injury role on neurons; however, the late peak might not be involved in the deteriorated effect on neurons.

[Study of process optimization on freeze drying of human amniotic membrane].

The study was aimed to investigate the optimum conditions of freeze drying preservation of amniotic membrane (AM). The AM from the health puerperal woman was preserved by freeze drying at optimized way. The key factors of freeze drying process, including abstersion aqua, conservation liquor, the curve of freezing temperature, and the ingredient of protective agent, were optimized. All their morphologic structure was observed by light microscope and scanning electron microscope. The degradation rates by collagenase IV and the characterization of biomechanics were analyzed. The radio-immunologic method was used to investigate the cytokines quantity. All properties of freeze dried AM were compared with those of fresh AM. Light micrographs showed that the five structure-layers exist both in the fresh AM and in those preserved by freeze drying, while the fibro-material was tight-structured in the fresh AM, but loose slightly; the thickness of fibro-material was larger slightly in freeze dried AM. Scanning electron micrographs show that the micro-hairs of epithelial cells in fresh AM were decreased slightly in optimized drying AM, the collagen fibre of fresh AM and of optimized drying AM were well in morphological structures and arranged tightly. The degradation rate by collagenase IV was faster in optimized drying AM,compared with that of the fresh AM. There were insignificant diversity in biomechanical characters (tensile strength, elongation at break and elastic modulus) of the optimized drying AM compared with fresh AM. The cytokines quantity in optimized drying AM decreased significantly compared with fresh AM. The improved freeze drying process has better advantage in keeping the morphological structure, preferable biomechanics and biological vitality of AM, compared with the early research.

Experimental Investigation on the Influencing Factors of Compressive Strength of Foamed Lightweight Material Utilizing Completely Decomposed Granite.

The utilization of construction waste soil to produce foamed concrete together with cement and a foaming agent is a promising method for waste recycling. Completely decomposed granite (CDG), which is widely available in southern China, was selected as a typical construction waste soil in foamed material production. The Taguchi method was applied to study the influence of various parameters on compressive strength, including cement dosage, CDG dosage, water to solid materials ratio (W/M), fine particles content, and gravel particles content. Analysis of variance (ANOVA) on a CDG-based sample showed that all factors have significant effects on compressive strength and the most effective parameter was cement dosage, followed in sequence by CDG dosage, W/M, gravel particles content, and fine particles content. However, only cement dosage and W/M influence the internal structure significantly during water/vacuum-immersion tests. The relationship between micro-pore structure and compressive strength suggested that with the decrease of open porosity, the compressive strength showed an increasing trend. This study reveals the possibility of CDG as a raw material for foamed lightweight soil and provides a technical reference of production procedure.

[Design of absorbable Bondi of dura].

A sort of absorbable Bondi of dura, whose main body is glue capsule, to compensate the deficiency of previous craniotomy, which easily causes delayed epidural hematoma. This device will help conglutinate dura to skull plate tightly, to stop bleeding and other purposes.