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Abstract Background Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date. Methods In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice. 16S rDNA sequencing was used to analyze the composition of the gut microbiota of mice at different time points to observe the effect of CPD on these microbial communities. Results In the acute toxicity test, CPD exhibited low toxicity, with a median lethal dose (LD50) > 2000 mg/kg. The sub-chronic toxicity test indicated that CPD administration at doses of 200, 400, and 600 mg/kg did not cause mortality or significant organ damage in mice. Furthermore, analysis of the gut microbiota after gavage administration of CPD at 400 and 600 mg/kg revealed an improved abundance of some beneficial gut bacteria. Conclusions In summary, no acute or sub-chronic toxic effects were observed in mice following the oral administration of CPD. CPD did not affect the structure and diversity of the gut microbiota and may contribute to an increase in the number of beneficial gut bacteria.

Aerobic composting is a key strategy to the sustainable use of livestock manure, which is however constrained by the slow kinetics. Microbe-aided thermophilic composting provides an attractive solution to this problem. In this study, we identified key thermophilic bacteria capable of accelerating manure composting based on the deciphering of manure bacterial community evolution in a thermophilic system. High-throughput sequencing showed a significant evolution of manure bacterial community structure with the increasing heating temperature. Firmicutes were substantially enriched by the heating, particularly some known thermotolerant bacterial species, such as Novibacillus thermophiles, Bacillus thermolactis, and Ammoniibacillus agariperforans. Correspondingly, through function prediction, we found bacterial taxa with cellulolytic and xylanolytic activities were significantly higher in the thermophilic process relative to the initial stage. Subsequently, a total of 47 bacteria were isolated in situ and their phylogenetic affiliation and degradation capacity were determined. Three isolates were back inoculated to the manure, resulting in shortened composting process from 5 to 3 days with Germination Index increased up to 134%, and improved compost quality particularly in wheat growth promoting. Comparing to the mesophilic and thermophilic Bacillus, the genomes of the three isolates manifested some features similar to the thermophiles, including smaller genome size and mutation of specific genes that enhance heat tolerance. This study provide robust evidence that microbe-aided thermophilic composting is capable to accelerate manure composting and improve the quality of compost, which represents a new hope to the sustainable use of manure from the meat industry.

Background and purposeThe underlying basis of the blend sign on brain computed tomography (CT) in patients with intracerebral hemorrhage (ICH) is unclear. Few studies have examined the morphological alterations in the CT blend sign in ICH. Therefore, we assessed changes in the CT blend sign and their association with hematoma expansion (HE) and adverse outcomes in ICH patients.MethodsWe recorded the clinical and radiographic parameters of patients with ICH and blend sign on brain CT. The patients were categorized into two groups, with changes in the relatively hypoattenuating region of the blend sign (CHB group) and with no changes in the relatively hypoattenuating region of the blend sign (NHB groups). We performed univariate and multivariate logistic regression analyses to examine the correlations between CHB and HE and poor outcomes. Furthermore, receiver operating characteristic curve analysis was used to confirm the predictive power of CHB.ResultsIn total, 183 patients were included in the study, of whom 74 (40.4%) demonstrated changes in the hypoattenuating region of the blend sign, whereas 109 (59.6%) did not. Compared with the NHB group, patients in the CHB group exhibited significantly higher levels of HE and adverse outcomes. After adjustment for confounding factors, CHB was independently associated with HE (odds ratio, 19.401 [95% CI, 7.217–52.163]; p

Abstract Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180–365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients’ improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Summary: Neutrophils play an important role in antiviral immunity, but the underlying mechanisms remain unclear. Here, we found that SIRT2 deficiency inhibited the infiltration of neutrophils, as well as the secretion of inflammatory cytokines and the formation of neutrophil extracellular traps (NETs), ameliorating disease symptoms during acute respiratory virus infection. Mechanistically, SIRT2 deficiency upregulates quinolinic acid (QA)-producing enzyme 3-hydroxyanthranilate oxygenase (3-HAO) and leads to expression of quinolinate phosphoribosyltransferase (QPRT), which promotes the synthesis of QA for NAD+ and limits viral infection when de novo NAD+ synthesis is blocked. Tryptophan-2,3-oxygenase expressed in epithelial cells metabolizes tryptophan to produce kynurenine and 3-hydroxyaminobenzoic acid, which is a source of intracellular QA in neutrophils. Thus, our findings reveal a previously unrecognized QPRT-mediated switch in NAD+ metabolism by exploiting neutrophil-derived QA as an alternative source of replenishing intracellular NAD+ pools induced by SIRT2 to regulate neutrophil functions during virus infection, with implications for future immunotherapy approaches.

Summary: Despite the consensus that accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, i.e. ER stress, activates the unfolded protein response (UPR), studies under physiological and pathophysiological conditions suggest that ER stress may not always trigger the UPR, and the UPR can be activated in an ER stress-independent way. To better understand how the UPR is regulated and its relationship with ER stress requires direct detection of unfolded proteins in the ER, a method that is still lacking. Here, we report a strategy of visualizing unfolded protein accumulation in the ER lumen in living cells by employing an engineered ER stress sensor, PERK, which forms fluorescence puncta upon unfolded protein binding, in a fast and reversible way. Our reporter enables us to clarify the involvement of unfolded proteins in UPR activation under several physiological conditions and suggests that persistent unfolded protein accumulation in the ER despite UPR attenuation predicts cell death.

This study investigated the emotional trends of users on social platforms, considering the event of “the Changsha girl jumping off the Lalamove truck” as a case study. It examined the effects of recommendation algorithms and group social comparison attributes on group emotions across three platforms: Zhihu, Weibo, and Bilibili. Through text mining and emotion analysis algorithms, group reviews were analyzed, and an event-based ARIMA robustness detection model was constructed using time series data. Utilizing the theoretical framework of the social comparison process, the study discovered that the “information database” formed by the recommendation algorithms of social platforms fosters the emergence of emotional group polarization among users. Furthermore, the findings revealed that the audience's social comparison attributes play a role in shaping emotional group polarization. High knowledge attributes tend to inhibit emotional group polarization, while low knowledge attributes tend to promote it. Machine learning algorithms were employed to measure user sentiment in social media platform comments, revealing insights into the causes of group polarization through a comparison of social comparison attributes and algorithm techniques. Future studies must focus on measuring technical information entropy.

Exploring the natural diversity of functional genes/proteins from environmental DNA in high throughput remains challenging. In this study, we developed a sequence-based functional metagenomics procedure for mining the diversity of copper (Cu) resistance gene copA in global microbiomes, by combining the metagenomic assembly technology, local BLAST, evolutionary trace analysis (ETA), chemical synthesis, and conventional functional genomics. In total, 87 metagenomes were collected from a public database and subjected to copA detection, resulting in 93,899 hits. Manual curation of 1214 hits of high confidence led to the retrieval of 517 unique CopA candidates, which were further subjected to ETA. Eventually, 175 novel copA sequences of high quality were discovered. Phylogenetic analysis showed that almost all these putative CopA proteins were distantly related to known CopA proteins, with 55 sequences from totally unknown species. Ten novel and three known copA genes were chemically synthesized for further functional genomic tests using the Cu-sensitive Escherichia coli (ΔcopA). The growth test and Cu uptake determination showed that five novel clones had positive effects on host Cu resistance and uptake. One recombinant harboring copA-like 15 (copAL15) successfully restored Cu resistance of the host with a substantially enhanced Cu uptake. Two novel copA genes were fused with the gfp gene and expressed in E. coli for microscopic observation. Imaging results showed that they were successfully expressed and their proteins were localized to the membrane. The results here greatly expand the diversity of known CopA proteins, and the sequence-based procedure developed overcomes biases in length, screening methods, and abundance of conventional functional metagenomics.

Photogrammetry systems are widely used in industrial manufacturing applications as an assistance measurement tool. Not only does it provide high-precision feedback for assembly process inspection and product quality assessment, but also it can improve the flexibility and robustness of manufacturing systems and production lines. However, with growing global competition and demands, companies are forced to enhance production efficiency, shorten production lifecycle and increase product variety by incorporating reconfigurable factory design that can meet challenging timeline and requirements. Although dynamic facility layout is widely investigated, the position selection for the photogrammetry system in dynamic manufacturing environment is usually overlooked. In this paper, dynamic layout of the V-STARS photogrammetry system is investigated and optimised in a digital-twin environment using deep reinforcement learning. The learning objectives are derived from the field of view (FoV) evaluation from point clouds 3D reconstruction, and collision detection from the digital twin simulated in Visual Components. The application feasibility of the proposed dynamic layout optimisation of the V-STARS photogrammetry system is verified with a real world industrial application. [ABSTRACT FROM AUTHOR]

Abstract Background Chromatin-associated phase separation proteins establish various biomolecular condensates via liquid–liquid phase separation (LLPS), which regulates vital biological processes spatially and temporally. However, the widely used methods to characterize phase separation proteins are still based on low-throughput experiments, which consume time and could not be used to explore protein LLPS properties in bulk. Results By combining gradient 1,6-hexanediol (1,6-HD) elution and quantitative proteomics, we developed chromatin enriching hexanediol separation coupled with liquid chromatography-mass spectrometry (CHS-MS) to explore the LLPS properties of different chromatin-associated proteins (CAPs). First, we found that CAPs were enriched more effectively in the 1,6-HD treatment group than in the isotonic solution treatment group. Further analysis showed that the 1,6-HD treatment group could effectively enrich CAPs prone to LLPS. Finally, we compared the representative proteins eluted by different gradients of 1,6-HD and found that the representative proteins of the 2% 1,6-HD treatment group had the highest percentage of IDRs and LCDs, whereas the 10% 1,6-HD treatment group had the opposite trend. Conclusion This study provides a convenient high-throughput experimental method called CHS-MS. This method can efficiently enrich proteins prone to LLPS and can be extended to explore LLPS properties of CAPs in different biological systems.

Objective: To observe the effect of intra-hematoma Rosiglitazone (RSG) infusion therapy in treating intracerebral hemorrhage (ICH). Specifically, to explore the effects of RSG on tight junction associated proteins Occludin and ZO-1 expression within perihematomal brain tissues as well as the blood–brain barrier (BBB) permeability after ICH in rabbits. Methods: A total of 30 rabbits were randomly assigned to three groups including sham control group (NC group, n = 10), hemorrhage model group (HM group, n = 10), and hemorrhage model with RSG treatment group (RSG group, n = 10). ICH was induced in rabbits of HM group and RSG group, involving an injection of autologous non-anticoagulant artery blood (0.3 mL, similar to basal ganglia hematoma 30 mL in humans) into the left basal ganglia of the rabbits’ brains. The NC group was injected with the same amount of saline into the same area. Six hours later after ICH induction or sham surgery, the RSG group received the intra-hematoma RSG (0.5 mg/0.1 mL) infusion, meanwhile the NC group and the HM group were injected with saline (0.1 mL) into the hematoma area. On day seven, the perihematomal brain tissues were obtained to determine the Occludin and ZO-1 expressions by Western Blot and RT-PCR, and the BBB permeability by the Evan’ s Blue (EB) content. Results: Occludin and ZO-1 expressions and mRNA levels were all significantly decreased in the HM group and RSG group compared with the NC group (P

Abstract Cardiac development involves large‐scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR). PERK depletion increases misfolded and/or aggregated protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of human pluripotent stem cells. Mechanistically, it is found that PERK safeguards mesendoderm specification through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation‐induced proteotoxic stress. The results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK‐ATF4‐WARS1 axis.

This paper explores the applicability of cryogenic permanent magnet motor stator materials for LNG pumps. First, this study selected four kinds of silicon steel sheets for motor stators tested at room temperature and ultra-low temperature and obtained the magnetization characteristics and loss characteristics of the four silicon steel sheets at room temperature and ultra-low temperature. Then, through a comparative analysis of experimental data, the applicability of silicon steel sheet material in an ultra-low-temperature environment was verified. Finally, the improved methods of the basic iron loss model of silicon steel sheets and the basic iron loss model of motors were proposed, and the accuracy and feasibility of the improved models were verified.

In recent years, hydroacoustic transducers made of PZT/epoxy composites have been extensively employed in underwater detection, communication, and recognition for their high energy conversion efficiency. Despite the ease with which these transducers can be formed into complex shapes, their lack of mechanical flexibility limits their versatility across various sizes of underwater vehicles. This study introduces a novel flexible piezoelectric composite hydroacoustic transducer (FPCHT) based on a 1-3 PZT-5A/silicone rubber composite and an island–bridge flexible electrode, which can break the limitations of existing hydroacoustic transducers that do not have flexibility. The finite element method is used to optimize the structural parameters of high-performance 1-3 FPC. A large-sized (187 mm × 47 mm × 5.12 mm) FPC is fabricated using an improved cutting–filling method and packaged into the FPCHT. Compared with the planar rigid PZT/epoxy composite hydroacoustic transducer (RPCHT) of the same size, the TVR (186.5 db) of the FPCHT has increased by about 7 dB, indicating that it has better acoustic radiation performance and electroacoustic conversion efficiency. Furthermore, its electroacoustic performance exhibits excellent stability under different bending states. Therefore, the FPCHT with high electroacoustic performance is an ideal substitute for the existing RPCHT and promotes the development of hydroacoustic transducers towards flexibility and portability.

Abstract We explored the association between the serum level of cystatin C (CysC) at admission and short‐term functional outcome in patients with hypertensive intracerebral hemorrhage (HICH) without chronic kidney disease (CKD). A total of 555 patients with HICH were consecutively recruited after admission and were followed‐up for 3 months after admission. The primary outcome was poor functional outcome (modified Rankin Scale [mRS] score ≥ 3). The median serum CysC level in our cohort was 1.03 mg/L (interquartile range, .89–1.20). Patients were categorized into four groups according to the serum CysC quartiles. Multivariate logistic regression analysis revealed a negative association between serum CysC and poor functional outcome at 3‐month follow‐up (quartile [Q]1 vs. Q4: adjusted odds ratio [OR] = .260, 95% confidence interval [CI] = .098, .691, p < .001). The negative association between serum CysC and poor functional outcome at 3 months was more pronounced in subgroups with smaller hematoma volume (≤ 30 mL), and absence of secondary intraventricular hemorrhage (IVH). Addition of serum CysC to a model containing conventional risk factors improved the model performance with net reclassification index (NRI) of .426% (p < .001) and integrated discrimination improvement (IDI) of .043% (p < .001) for poor functional outcome. Serum CysC was found to be a negative predictor of poor short‐term functional outcome in HICH patients independent of renal function.

Low temperature high-speed motors can achieve low temperature and high viscosity fluid media efficient transmission, meanwhile, excessive friction loss and temperature rise issues are addressed. In this paper, a 30kw low-temperature and high-speed permanent magnet motor prototype is implemented as the research object. Three stator axial cooling structures are proposed to effectively control the motor temperature rise. First, the discussion focuses on the friction loss in the air gap and its related influencing factors; at the same time, the effect of different axial cooling structures on the friction loss in the air gap is also considered. Secondly, a calculation method of axial viscous friction loss based on the principle of fluid force equilibrium is proposed in the paper, the variation law of the structure size influence on axial friction loss is also given. Based on the quantitative calculation of axial friction loss, the final structure size is determined by synthesizing the variation of different size structures stator iron loss. Finally, the physical model of the three-dimensional fluid-thermal coupling calculation on the analysis object is established by means of finite element analysis, and the stator temperature rise distribution is calculated.

Abstract Background Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. micra) in the feces of patients with cancer is significantly higher than that in healthy people. Therefore, an important relationship may exist between P. micra and CRC. Methods We first confirmed that P. micra can promote the proliferation of cell lines through cell experiments and mouse models. Then we selected the signaling pathways and content of exosomes to promote the development of CRC by transcriptomics and microRNA sequencing. Finally, we confirmed that P. micra promoted CRC development through miR-218-5p/Ras/ERK/c-Fos pathway through the in vivo and in vitro experiments. Results First, it was confirmed by in vitro and in vivo experiments that P. micra can promote the development of CRC. Transcriptome analysis after the coincubation of bacteria and cells revealed that P. micra promoted cell proliferation by activating the Ras/ERK/c-Fos pathway. Furthermore, microRNA sequencing analysis of the cells and exosomes showed that miR-218-5p and protein tyrosine phosphatase receptor R (PTPRR) were the key factors involved in activating the Ras/ERK/c-Fos pathway, and the miR-218-5p inhibitor was used to confirm the role of microRNA in xenograft mice. Conclusion This experiment confirmed that P. micra promoted the development of CRC by upregulating miR-218-5p expression in cells and exosomes, inhibiting PTPRR expression, and ultimately activating the Ras/ERK/c-Fos signaling pathway.

Objective: The aim of the current study is to evaluate if ETB inhibition following ICH can mitigate the deleterious impact of ET-1, e.g., BBB disruption, and improve neurological function. Methods: A total of 90 male rabbits (2.8–3.4 kg) were randomly assigned to the following groups (n = 10 per group): normal control (NC), pseudo-control (PC), drug control using normal saline (DC), model control (MC + ICH), minimally invasive surgery (MIS + ICH), minimally invasive surgery + ET-1 receptor agonist (MIS + IRL1620 + ICH), IRL1620 + ICH, ET-1 receptor antagonist (BQ788 + ICH), and IS + BQ788 + ICH. ICH was induced in all groups except for NC, DC and PC groups.In MIS, MIS + BQ788, and MIS + IRL1620 groups, at the 6-hour mark following ICH, MIS was used to evacuate the hematoma followed by immediate drug (BQ788 or IRL1620 or saline) injection into the ear vein. On day 3, all rabbits were evaluated by purdy score and then sacrificed. The perihematomal brain tissue was removed to determine the expression of ET-1 and MMP-9 by immunohistochemical procedures. MDA expression was evaluated by ELISA, and BBB permeability was evaluated using Evens Blue (EB) methods. Brain water was determined using a dry-wet weighing method. Results: The purdy score, ET-1, MDA, MMP-9, BWC, and BBB permeability were decreased in groups treated with BQ788 and increased in groups treated with IRL1620. The combination of MIS + BQ788 markedly decreased these deleterious outcomes (purdy score, ET-1, MDA, MMP-9, BWC, and BBB permeability) compared to the MIS group. Conclusions: Using a non-selective antagonist of ETB, deleterious outcomes associated with increased levels of ET-1 following ICH were ameliorated.

Abstract Culturomics employs various cultivating conditions to obtain different types of bacteria and new species. However, current culturomics lacks a highly efficient method for isolating specific pathobionts. Immunomagnetic bead technology, which uses magnetic beads conjugated with antibodies for capturing the antigen to realize enrichment of the targets, has been employed as an alternative method. In this study, we developed a novel method, immunomagnetic bead‐enriched culturomics (IMBEC), in which magnetic bead‐conjugated antibodies purified from the fecal samples of patients with colorectal cancer (CRC) were used to enrich and isolate potential pathobionts. A protocol for enriching potential pathobionts via immunomagnetic capture was developed by optimizing the concentrations of coupling reagents, NaCl, and detergent. The efficacy of pathobiont enrichment was compared between antibody‐coated magnetic beads (antibody group) and nonconjugated blank magnetic beads (blank group). To determine the proinflammatory potential of isolates from both groups, we investigated their ability to induce cytokine production in THP‐1 macrophages. This protocol was employed for isolating bacteria from 10 fecal samples of patients with CRC, which were simultaneously compared with those isolated from the blank group. A total of 209 bacterial species were isolated from both groups, including 173 from the antibody group, 160 from the blank group, and 124 from both groups. Bacteria isolated from the antibody group produced more proinflammatory cytokines than those isolated from the blank group. IMBEC is a promising method for relatively specific isolation of potential pathobionts for a particular disease of interest.

Abstract The peripheral T cell pool is maintained at dynamic homeostasis through fine‐tuning of thymic output and self‐renewal of naïve T cells. Lymphopenia or reduced lymphocyte number is implicated in autoimmune diseases, yet little is known about the homeostatic mechanisms. Here, it is reported that the replication protein A1 (RPA1) plays a critical role in T cell homeostasis. Utilizing T cell‐specific Rpa1‐deficient (Rpa1fl/fl Cd4‐cre) mice, loss of Rpa1 results in lymphopenia through restraining peripheral T cell population and limiting TCR repertoire diversity. Moreover, Rpa1fl/fl Cd4‐cre mice exhibit increased susceptibility to inflammatory diseases, including colitis and hepatitis. Clinical analysis reveals that the expression of RPA1 is reduced in patients with ulcerative colitis or other autoinflammatory diseases. Mechanistically, depletion of RPA1 activates ZBP1‐RIPK3 signaling through triggering the genomic DNA leakage into cytosol, consequently resulting in T cell necroptosis. This necroptotic T cell death induced by RPA1 deficiency allows the release of damage‐associated molecular patterns (DAMPs), which in turn recruits leukocytes and exacerbates inflammatory response. Reciprocally, chemical or genetic inhibition of necroptosis signaling can ameliorate the Rpa1 deficiency‐induced inflammatory damage. The studies thus uncover the importance of RPA1‐ZBP1‐RIPK3 axis in T cell homeostasis and provide a promising strategy for autoinflammatory disease treatment.

Summary: Consisting of three signaling pathways, the unfolded protein response (UPR) can be either protective or detrimental to cells that undergo ER stress. Elaborate regulation of the UPR is key to the cell-fate decision, but how it is achieved remains vague. Here, by studying cells deficient in vacuole membrane protein 1 (VMP1), a UPR regulator, we report a model of UPR regulation in which the three pathways are divergently controlled. Under basal conditions, calcium binding specifically activates PERK. Under ER stress, ER-mitochondria interaction-induced mitochondrial stress cooperates with PERK to suppress IRE1α and ATF6 by decelerating global protein synthesis. Such sophisticated regulation commits limited activation of the UPR yet refrains from UPR hyperactivation, protecting cells from chronic ER stress despite decreasing cell proliferation. Therefore, our study reveals interorganelle-interaction-dependent and calcium-dependent regulation of the UPR that dictates cell fate.

Intracerebral haemorrhage (ICH) is a highly risky cerebrovascular disease with poor prognosis. Lin-28 homolog A (Lin28) has been identified as a crucial regulator in ICH. This study aims to analyse the mechanism of Lin28 in neuronal ferroptosis after ICH and provide theoretical basis for ICH treatment. An ICH mouse model was established via injection of collagenase VII, followed by neurological impairment assessment, and haematoxylin-eosin staining. An in vitro ICH model was established using hemin treatment. Next, cell viability and ferroptosis parameters were detected via cell counting kit-8, assay kits, enzyme-linked immunosorbent assay and western blot. Lin28 expression and tripartite motif-containing 37 (Trim37) mRNA level were detected via western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The binding relationship of Lin28 and Trim37 was verified. ICH mice exhibited neuronal ferroptosis and upregulation of Lin28. Lin28 inhibition alleviated neurological impairment, manifested by decreased hematoma, oedema, neuronal necrosis, glial cell swelling, intracellular vacuoles and inflammatory cell infiltration, reduced Fe2+ concentration and reactive oxygen species content, and increased glutathione and glutathione peroxidase 4 activity. In the hemin-induced HT-22 cells, Lin28 inhibition promoted cell viability and alleviated neuronal ferroptosis. Lin28 bound to Trim37 mRNA to stabilize the mRNA level of Trim37. Overexpression of Trim37 reversed the alleviating role of silencing Lin28 in neuronal ferroptosis after ICH. Overall, Lin28 stabilized the mRNA level of Trim37 to aggravate neuronal ferroptosis after ICH.

This study developed a snowfall detection algorithm over ocean, sea ice, and coast for the advanced technology microwave sounder (ATMS) onboard both NPP and NOAA-20 satellites. The detection algorithm was trained from collocated observations between ATMS-NPP and CloudSat cloud profiling radar (CPR) snowfall product. Both brightness temperature (TB) variables and global forecast system (GFS) output variables are evaluated for snowfall detection in this algorithm. Results show that combining TB variables and GFS variables provide the optimal snowfall detection performance. The Heidke skill score (HSS) values are about 0.56 over all three surface types, and the probability of detection (POD) values are 0.76, 0.70, and 0.72 over ocean, sea ice, and coast, respectively. The importance of the GFS variables differs greatly among these three surface types. The detection algorithm primarily depends on TB variables over ocean and HSS only increased by 0.05 by adding GFS variables. In contrast, GFS variables are critically important to snowfall detection over sea ice and coastal regions. Without GFS variables, the HSS values over both sea ice and coastal regions decrease sharply from about 0.56 to about 0.40. Over ocean, we also developed a regional snowfall detection model in each 10° grid box, which greatly outperform the global detection model over certain regions (e.g., sea of Okhotsk and Labrador Sea). Case studies and validation against NOAA-20 observations showed that the snowfall detection algorithm performs well, which will benefit coastal communities by providing information on snowstorms offshore before they transition to land.

ObjectivesTo develop and validate magnetic resonance imaging (MRI)-based pre-Radiomics and delta-Radiomics models for predicting the treatment response of local advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (NCRT).MethodsBetween October 2017 and August 2022, 105 LARC NCRT-naïve patients were enrolled in this study. After careful evaluation, data for 84 patients that met the inclusion criteria were used to develop and validate the NCRT response models. All patients received NCRT, and the post-treatment response was evaluated by pathological assessment. We manual segmented the volume of tumors and 105 radiomics features were extracted from three-dimensional MRIs. Then, the eXtreme Gradient Boosting algorithm was implemented for evaluating and incorporating important tumor features. The predictive performance of MRI sequences and Synthetic Minority Oversampling Technique (SMOTE) for NCRT response were compared. Finally, the optimal pre-Radiomics and delta-Radiomics models were established respectively. The predictive performance of the radionics model was confirmed using 5-fold cross-validation, 10-fold cross-validation, leave-one-out validation, and independent validation. The predictive accuracy of the model was based on the area under the receiver operator characteristic (ROC) curve (AUC).ResultsThere was no significant difference in clinical factors between patients with good and poor reactions. Integrating different MRI modes and the SMOTE method improved the performance of the radiomics model. The pre-Radiomics model (train AUC: 0.93 ± 0.06; test AUC: 0.79) and delta-Radiomcis model (train AUC: 0.96 ± 0.03; test AUC: 0.83) all have high NCRT response prediction performance by LARC. Overall, the delta-Radiomics model was superior to the pre-Radiomics model.ConclusionMRI-based pre-Radiomics model and delta-Radiomics model all have good potential to predict the post-treatment response of LARC to NCRT. Delta-Radiomics analysis has a huge potential for clinical application in facilitating the provision of personalized therapy.

Background: This study analyzed the phenotypes and genotypes of 41 Chinese families with inherited retinal dystrophy (IRD) and RPGR gene mutations.Methods: This retrospective analysis evaluated a cohort of 41 patients who were subjected to a specific Hereditary Eye Disease Enrichment Panel (HEDEP) analysis. All (likely) pathogenic variants were determined by Sanger sequencing, and co-segregation analyses were performed on the available family members. All cases were subjected to Sanger sequencing for RPGR open reading frame 15 (ORF15) mutations.Results: A total of 41 probands from different families with a clinical diagnosis of retinitis pigmentosa (RP; 34 cases) and cone-rod dystrophy (CORD; 7 cases) were included in this cohort. According to clinical information, 2, 18, and 21 cases were first assigned as autosomal dominant (AD), sporadic, and X-linked (XL) inheritance, respectively. Several cases of affected females who presented with a male phenotype have been described, posing challenges at diagnosis related to the apparent family history of AD. Mutations were located in RPGR exons or introns 1–14 and in ORF15 of 12 of 41 (29.3%) and 29 of 41 (70.7%) subjects, respectively. Thirty-four (likely) pathogenic mutations were identified. Frameshifts were the most frequently observed variants, followed by nonsense, splice, and missense mutations. Herein, a detailed description of four RP patients carrying RPGR intronic mutations is reported, and in vitro splice assays were performed to confirm the pathogenicity of these intronic mutations.Conclusion: Our findings provide useful insights for the genetic and clinical counseling of patients with XL IRD, which will be useful for ongoing and future gene therapy trials.

Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.

Several studies have demonstrated the positive impact of wild pedagogies on the well-being and learning of primary learners. However, wild pedagogies in higher education remain relatively obscure. This study assesses whether wild pedagogies affect the wellness of university students and analyzes the outcomes of the natural learning experiences in a higher education setting. As such, we use the roBERTa model to evaluate the sentiment score and thematic content to analyze 167 reflective essays on conducted natural learning experiences by undergraduate engineering students from a large Canadian public university. Our findings indicate that wild pedagogies benefit the wellness of university students and provide positive learning experiences. Moreover, positive natural learning experiences motivate students to develop environmental consciousness and sentimental connections with nature.

The common negative pressure wave based pipeline leakage detection technology is to locate the leakage based on the time difference of the negative pressure wave reaching the upstream and downstream obtained by calculating the pressure drop point. However, the locating accuracy of leakage is reduced for the pressure drop point is not obvious due to the influence of propagation attenuation of pressure wave, little pressure variation in slow leakage and interference of noises. In order to reduce the locating error of the negative pressure wave based leakage monitoring technology, the propagation time difference of the negative pressure wave transmitting to the upstream and downstream can be obtained by calculating its similarity with Euclidean distance based on its homologous characteristics, which can be further converted into the location of leakage. By field test, the results indicate that: In this way, the abrupt and slow leakage of pipeline can be located accurately, the deficiency of the original negative pressure wave based pipeline leakage monitoring technology for inaccurate locating of slow leakage can be compensated, and the performance can be realized by simply upgrading the original system.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high rates of morbidity, mortality, and disability. It induces cell death that is responsible for the secondary brain injury (SBI). The underlying mechanism of SBI after ICH is still unclear, and whether it is related to iron overload is worthy to be discussed. Ferroptosis is an iron-dependent non-apoptotic modes of cell death and plays a particularly important role in the occurrence and progression of ICH. Many ICH-induced regulators and signalling pathways of ferroptosis have been reported as promising targets for treating ICH. In this article, we review the definition, characteristics, and inhibition methods of neuronal ferroptosis caused by iron deposition after ICH, and review the biomarkers for ferroptosis.

Objective: This study aims to explore the clinical significance of haptoglobin (HP) and protein disulfide-isomerase A3 (PDIA3) in human serum in the screening, diagnosis and staging of colorectal cancer (CRC), and to provide novel screening approaches featuring high specificity, sensitivity, and accuracy for early screening and diagnosis of clinical colorectal cancer.Methods: 88, 77, and 36 blood specimens were respectively harvested from colorectal cancer patients, colorectal polyp patients, and normal subjects (the health examination) who requested medical assistance from our hospital between Oct2019 and February 2022. The serum contents of HP and PDIA3 in each sample were determined through an enzyme linked immunosorbent assay (ELISA). This step was taken to analyze the differences among different specimen groups in terms of the serum contents of HP and PDIA3, to analyze the relationships between the expression levels of HP and PDIA3 and the pathological characteristics of colorectal cancer, and to explore the critical role of HP and PDIA3 in the screening, diagnosis, and staging of colorectal cancer.Results: Serum contents of HP and PDIA3 were higher in colorectal cancer patients, with statistical differences (p < 0.05), than those in the colonic polyp patients and healthy subjects. Receiver operating characteristic (ROC) curve demonstrated that the cut-offs of HP and PDIA3 serum contents indicating colorectal cancer were 149 ug/ml and 66 ng/ml respectively. The individually and jointly tested AUCs of HP (0.802) and PDIA3 (0.727) were higher than those of serum CEA and CA199, the sensitivity and specificity of HP were 64.8 and 91.2%, the sensitivity and specificity of PDIA3 were 65.9 and 71.7%. Moreover, the contents of HP and PDIA3 increased alongside disease progression, with differences (p < 0.05).Conclusion: Our research indicated that joint testing of HP and PDIA3 was of reference value for progressive stage and reliable biological indicators of colorectal cancer screening.

CO2 flooding and burial efficiency can be improved by establishing a standard for screening suitable CO2 flooding reservoirs for the Daqing Oilfield. Moreover, the influencing factors of CO2 flooding can be classified into geological factors, fluid properties, and development factors. An evaluation index system and hierarchical structure are created based on the importance of multiple factors. The subjective analysis error of human beings is quite large when establishing the evaluation index system, especially in the fitting curves that are drawn by different analysts. Based on the geological characteristics of block Bei14 in the Daqing Oilfield, a typical CMG model is presented in this article. A total of 15 factors in the 72 models are used as independent variables, and the recovery factor is used as a dependent variable for multiple linear regression calculations. In addition to sensitivity tests based on how much significance is indicated by the t value in the results, a unique result can be calculated using standard statistical methods when analyzing the calculation results of the multiple linear regression model. The results of the screening standard evaluation system are consistent with the production history of the oilfield based on the mathematical understanding of multiple factors of CO2 flooding. Around the high-score well group, oil saturation decreases significantly, and the cumulative production is generally higher than that of the low-score well group. The calculation results of block Bei 14 show that 74% of well groups have an evaluation value greater than 0.50, and 72% of well groups have an annual oil exchange ratio above 40%, which means that over 70% of well groups can benefit from CO2 flooding. Thus, CO2 flooding can be applied in the Daqing Oilfield, and multiple linear regression can provide effective guidance for the Daqing Oilfield’s development.

Abstract Background The initial CT blend sign is an imaging marker that has been used to predict haematoma expansion and poor outcomes in patients with small-volume intracerebral haemorrhage (ICH). However, the association of the blend sign with the outcomes of patients undergoing surgery remains unclear. The present study aimed to retrospectively evaluate the influence of the initial CT blend sign on short-term outcomes in patients with hypertensive ICH after stereotactic minimally invasive surgery (sMIS). Methods We enrolled 242 patients with spontaneous ICH. The patients were assigned to the blend sign group (91 patients) or non-blend sign (control) group (151 patients) based on the initial CT features. The NIHSS, GCS and mRS were used to assess the effects of sMIS. The rates of severe pulmonary infection and cardiac complications were also compared between the two groups. Results Statistically significant differences in the NIHSS and GCS scores were not observed between the blend sign group and the control group. No significant differences in the proportion of patients with good outcomes during the follow-up period were observed between the two groups. A higher rate of re-haemorrhage was noted in the blend sign group. Significant differences in the rates of severe pulmonary infection and cardiac complications were not observed between the two groups. Conclusions The initial CT blend sign is not associated with poor outcomes in patients with hypertensive ICH after sMIS. ICH patients with the CT blend sign should undergo sMIS if they are suitable candidates for surgery.

Abstract Mass cadmium (Cd) poisoning is a serious health problem in many parts of the world. We propose that dietary intervention can be a practical solution to this problem. This study aimed to identify effective dietary products from traditional Chinese herbs that can detoxify Cd. Five candidate herbal foods with detoxifying potential were selected and subjected to mouse toxicological tests. The chemical composition and dose–response effects of licorice on mouse hepatocytes were determined. Licorice was selected for further tests to examine its effects on growth, tissue Cd accumulation, and gut and liver fitness of mice. The expression of hepatic metallothionein (Mt) genes was quantified in vitro in hepatocytes and in vivo in liver tissues of mice. The results showed that licorice dietary intervention was effective in reducing blood Cd by >50% within 1 month. Cd was also substantially reduced in the heart and lung tissues, but increased 2.1‐fold in the liver. The liver of Cd poisoned mice improved with licorice intervention. Licorice treatment significantly induced Cd accumulation and expression of the Mt1 gene in hepatic cells both in vitro and in vivo. Licorice intake substantially altered gut microbial structure and enriched Parabacteroides distasonis. Omics results showed that licorice improved gut metabolism, particularly the metabolic pathways for glycyrrhizin, bile acids, and amino acids. Dietary licorice effectively reduced mouse blood Cd and had a profound impact on liver and gut fitness. We conclude that herbal licorice can be used as a dietary intervention for mass Cd poisoning.

ObjectiveTo investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.MethodsWe randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.ResultsPurdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.ConclusionsMIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.

Background and PurposeMinimally invasive surgery (MIS) is performed to treat patients with intracerebral hemorrhage (ICH) with favorable results. However, postoperative rehemorrhage is a significant risk. The present study retrospectively analyzed the association of irregular-shaped hematoma with postoperative rehemorrhage following stereotactic MIS (sMIS).MethodsWe enrolled 548 patients with spontaneous ICH who underwent sMIS. Based on the hematoma shape, the patients were assigned to the regular-shaped hematoma group (RSH group; 300 patients) or irregular-shaped hematoma group (ISH group; 248 patients). Logistic regression analysis was performed to identify the predictors of postoperative rehemorrhage after sMIS for ICH evacuation. The functional outcome was assessed using the modified ranking scale (mRS) score at discharge. A receiver operating characteristic (ROC) curve was used to confirm the results.ResultsAmong 548 patients with ICH who underwent sMIS, 116 developed postoperative rehemorrhage. Postoperative rehemorrhage occurred in 30.65% of patients with ISH and 13.30% with RSH (P < 0.01), with a significant difference between the ISH and RSH groups. Among 116 patients with postoperative rehemorrhage, 76 (65.52%) showed ISH on CT scan. In 432 patients without postoperative rehemorrhage, only 39.81% displayed ISH. The logistic regression analysis demonstrated that ISH could independently predict postoperative rehemorrhage. The sensitivity, specificity, positive predictive value, and negative predicative value were 0.655, 0.398, 0.655, and 0.602, respectively. The ROC analysis confirmed the value of ISH in predicting postoperative rehemorrhage with an area under the curve of 0.629.ConclusionsIrregular-shaped hematoma was an independent predictor of postoperative rehemorrhage after sMIS.

Long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes. Knocking out or knocking down some lncRNA genes can lead to death or infertility. These lncRNAs are called essential lncRNAs. Identifying the essential lncRNA is of importance for complex disease diagnosis and treatments. However, experimental methods for identifying essential lncRNAs are always costly and time consuming. Therefore, computational methods can be considered as an alternative approach. We propose a method to identify essential lncRNAs by combining network centrality measures and lncRNA sequence information. By constructing a lncRNA-protein-protein interaction network, we measure the essentiality of lncRNAs from their role in the network and their sequence together. We name our method as the systematic gene importance index (SGII). As far as we can tell, this is the first attempt to identify essential lncRNAs by combining sequence and network information together. The results of our method indicated that essential lncRNAs have similar roles in the LPPI network as the essential coding genes in the PPI network. Another encouraging observation is that the network information can significantly boost the predictive performance of sequence-based method. All source code and dataset of SGII have been deposited in a GitHub repository (https://github.com/ninglolo/SGII).

MicroRNAs (miRNAs) play vital roles in gene expression regulations. Identification of essential miRNAs is of fundamental importance in understanding their cellular functions. Experimental methods for identifying essential miRNAs are always costly and time-consuming. Therefore, computational methods are considered as alternative approaches. Currently, only a handful of studies are focused on predicting essential miRNAs. In this work, we proposed to predict essential miRNAs using the XGBoost framework with CART (Classification and Regression Trees) on various types of sequence-based features. We named this method as XGEM (XGBoost for essential miRNAs). The prediction performance of XGEM is promising. In comparison with other state-of-the-art methods, XGEM performed the best, indicating its potential in identifying essential miRNAs.

For large generators, accurate assessment for the resistance enhancement coefficient (REC) and thermal dissipation is of great significance. With the development of design and manufacturing technology for large generators, the different cross section of the upper and lower strand becomes an effective method to reduce the heat losses. In current electromagnetism design, the eddy current analysis does not take the strand structures into account. In this paper, the REC of strands with special structures of a 150MW turbo-generator is derived by an analytic algorithm. Besides that, a mathematical model of the stator slot is established and the heat losses distribution and REC of strands are calculated by finite element method (FEM). On this basis, the stator REC and thermal dissipation of a 1000MW power turbo-generator are investigated with hollow and solid strands. The calculated results match the experimental data. All of these could provide an important theoretical basis and reference for the design of stator windings in high-power generators.

ObjectiveThis article investigated whether Runt-Related Transcription Factor 3 (RUNX3) and enhancer of zeste homolog 2 (EZH2) can be used to evaluate the clinical efficacy of neoadjuvant therapy and prognosis of locally advanced rectal cancer (LARC). MethodsEighty LARC patients admitted to the Tianjin Medical University Cancer Institute/Hospital and First Affiliated Hospital of Hebei North University from Jan 2015 to Jan 2016 were enrolled. The patients were followed up for 60 months through hospital visits. All patients received neoadjuvant chemoradiotherapy (long range radiotherapy + oral capecitabine) + total mesorecta excision (TME) surgery. The clinical efficacy of the treatments was evaluated through endoscopic, radiography, and tumor regression grade (TRG). In addition, expression level of RUNX3 and EZH2 was quantified via immunohistochemistry. The association of RUNX3 and EZH2 with clinicopathological characteristics of advanced tumors and efficacy of neoadjuvant therapy was explored. Logistic regression analysis was performed to identify predictors of efficacy of neoadjuvant chemoradiotherapy. Survival curve was used to evaluate the impact of RUNX3 and EZH2 on the prognosis of LARC patients.ResultsA total of 80 patients diagnosed with LARC were enrolled in the study. Expression of RUNX3 was elevated in 25 (31.25%) patients, whereas expression of EZH2 was upregulated in 44 (55.00%) patients. Analysis of tumor regression identified 10 cases with TRG grade 0 (pathologic complete response, PCR), 24 cases with TRG grade 1, 35 cases with TRG grade 2, and 11 cases with TRG grade 3. Furthermore, 38 cases had significant down-staging, and 42 cases showed no significant down-staging as revealed by endoscopy and imaging. Patients with high expression of RUNX3 showed better tumor regression response and down-staging compared with those with low expression of RUNX3 (P < 0.001, P < 0.001). Moreover, patients with low EZH2 expression achieved TRG grade 0 and 1 response and down-staging effect compared with those with high expression of EZH2 (P < 0.001, P < 0.001). Logistic regression analysis showed that high expression of RUNX3, low expression of EZH2, and clinical N (cN) stage were good predictors of tumor regression response and down-staging. The 5-year disease free survival (DFS) and overall survival (OS) were 48.75 (39/80) and 58.75% (47/80), respectively. The 5-year DFS and OS of patients with high RUNX3 expression were significantly higher than low RUNX3 expression, whereas the 5-year DFS and OS of patients with high EZH2 expression were significantly lower than low EZH2 expression (P < 0.001). Univariate survival analysis showed that RUNX3 expression, EZH2 expression, cN, clinical T (cT), pathological T (pT) and pathological N (pN) were significantly correlated with the 5-year DFS and 5-year OS. Multivariate survival analysis showed that EZH2 expression and PN were good predictors of 5-year DFS and 5-year OS, whereas RUNX3 was a good predictor of 5-year DFS but not 5-year OS.ConclusionsExpression level of RUNX3 and EZH2 accurately predicts clinical efficacy of neoadjuvant chemoradiotherapy and the prognosis of LARC patients, suggesting that RUNX3 and EZH2 can be used as pivotal clinical predictors for LARC.

Our current knowledge on bacterial cadmium (Cd) resistance is mainly based on the functional exploration of specific Cd-resistance genes. In this study, we carried out a genomic study on Cd resistance of a newly isolated Cellulomonas strain with a MIC of 5 mM Cd. Full genome of the strain, with a genome size of 4.47 M bp and GC-content of 75.35%, was obtained through high-quality sequencing. Genome-wide annotations identified 54 heavy metal-related genes. Four potential Cd-resistance genes, namely zntAY8, copAY8, HMTY8, and czcDY8, were subjected to functional exploration. Quantitative PCR determination of in vivo expression showed that zntAY8, copAY8, and HMTY8 were strongly Cd-inducible. Expression of the three inducible genes against time and Cd concentrations were further quantified. It is found that zntAY8 responded more strongly to higher Cd concentrations, while expression of copAY8 and HMTY8 increased over time at lower Cd concentrations. Heterologous expression of the four genes in Cd-sensitive Escherichia coli led to different impacts on hosts’ Cd sorption, with an 87% reduction by zntAY8 and a 3.7-fold increase by HMTY8. In conclusion, a Cd-resistant Cellulomonas sp. strain was isolated, whose genome harbors a diverse panel of metal-resistance genes. Cd resistance in the strain is not controlled by a dedicated gene alone, but by several gene systems collectively whose roles are probably time- and dose-dependent. The plasmid-free, high-GC strain Y8 may provide a platform for exploring heavy metal genomics of the Cellulomonas genus.

The objective of this study was to investigate the mechanism underlying miR-21-associated apoptosis in HB. In this study, HB and adjacent tissues were collected from patients with HB. RT-PCR, FISH, western blot, apoptosis assay, migration, invasion and wound healing assays, caspase activity assay, luciferase reporter assays, and xenografts mouse model were used to determine the effects of miR-21 on HB cell apoptosis. The results revealed that miR-21 was up-regulated in both HB cell and tissue and was associated with progression of HB. MiR-21 inhibitor enhanced the apoptosis level in HB cells. MiR-21 inhibitor showed reduced abilities of migration and invasion. ASPP2 was a target gene of miR-21. Inhibition of ASPP2 increased abilities of migration and invasion in HB cells. Furthermore, miR-21 inhibitor caused increased activity p-38 signaling. In a xenografts mouse model, miR-21 inhibitor could significantly suppress tumor growth in nude mice along with enhanced expressions of ASPP2 and p38. Taken together, the results suggest that upregulation of miR-21 is related to HB progression and miR-21-associated apoptosis in HB is mediated through ASPP2/p38 signaling pathway in vitro and in vivo. This study provides novel insight into the effects of miR-21 on HB apoptosis and clue to develop new therapies.

ABSTRACT It is known that organisms have developed various mechanisms to cope with cadmium (Cd) stress, while we still lack a system-level understanding of the functional isomorphy among them. In the present study, a cross-kingdom comparison was conducted among Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii, through toxicological tests, comparative transcriptomics, as well as conventional functional genomics. An equivalent level of Cd stress was determined via inhibition tests. Through transcriptome comparison, the three organisms exhibited differential gene expression under the same Cd stress relative to the corresponding no-treatment control. Results from functional enrichment analysis of differentially expressed genes (DEGs) showed that four metabolic pathways responsible for combating Cd stress were commonly regulated in the three organisms, including antioxidant reactions, sulfur metabolism, cell wall remodeling, and metal transport. In vivo expression patterns of 43 DEGs from the four pathways were further examined using quantitative PCR and resulted in a relatively comparable dynamic of gene expression patterns with transcriptome sequencing (RNA-seq). Cross-kingdom comparison of typical Cd stress-responding proteins resulted in the detection of 12 groups of homologous proteins in the three species. A class of potential metal transporters were subjected to cross-transformation to test their functional complementation. An ABC transporter gene in E. coli, possibly homologous to the yeast ycf1, was heterologously expressed in S. cerevisiae, resulting in enhanced Cd tolerance. Overall, our findings indicated that conserved genetic modules against Cd toxicity were commonly regulated among distantly related microbial species, which will be helpful for utilizing them in modifying microbial traits for bioremediation. IMPORTANCE Research is establishing a systems biology view of biological response to Cd stress. It is meaningful to explore whether there is regulatory isomorphy among distantly related organisms. A transcriptomic comparison was done among model microbes, leading to the identification of a conserved cellular model pinpointing the generic strategies utilized by microbes for combating Cd stress. A novel E. coli transporter gene substantially increased yeast’s Cd tolerance. Knowledge on systems understanding of the cellular response to metals provides the basis for developing bioengineering remediation technology.

Rectangular double-laminated piezoelectric elements are widely used in low frequency transducers. At present, most of these piezoelectric elements use a piezoelectric ceramic laminated structure. In this work, the bending vibration properties of double-laminated piezoelectric ceramic elements with different transverse dimensions were analyzed by the finite element method. It was found that there was a strong transverse mechanical coupling, and the transverse dimensions had a great effect on the bending vibration. To suppress the transverse mechanical coupling effect, a double-laminated piezoelectric element based on a 2-2 piezoelectric composite was designed. The simulation results show that the bending vibration performance of the double-laminated composite element is not affected by the transverse size. The 2-2 piezoelectric composite double-laminated and ceramic elements were prepared. In addition, simulation and experimental results indicate that the transverse mechanical coupling of the bending vibration of the piezoelectric composite double-laminated element is effectively suppressed, the vibration frequency is reduced by about 100 Hz, and the vibration displacement is increased by 2.2 times, in comparison with the piezoelectric ceramic double-laminated element.