Recent Progress in the Research on RNA-Binding Proteins in Bone Development and Diseases.

RNA-binding proteins (RBPs), which regulate gene expression through post-transcriptional modifications of RNAs, play a role in diverse biological processes that include bone cell development and bone tissue formation. RBP dysregulation may result in aberrant bone homeostasis and contribute to various bone diseases. The function of RBPs in bone physiology and pathophysiology and the underlying molecular mechanisms have been extensively studied in recent years. This article provides a review of such studies, highlighting the potential of RBPs as pivotal targets for therapeutic intervention.

Integrated metabolomics and proteomics analysis to understand muscle atrophy resistance in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus experiences minor muscle atrophy, which is an attractive anti-disuse muscle atrophy model. Integrated metabolomics and proteomics analysis was performed on the hibernating S. dauricus during the pre-hibernation (PRE) stage, torpor (TOR) stage, interbout arousal (IBA) stage, and post-hibernation (POST) stage. Time course stage transition-based (TOR vs. PRE, IBA vs. TOR, POST vs. IBA) differential expression analysis was performed based on the R limma package. A total of 14 co-differential metabolites were detected. Among these, l-cystathionine, l-proline, ketoleucine, serine, and 1-Hydroxy-3,6,7-Trimethoxy-2, 8-Diprenylxanthone demonstrated the highest levels in the TOR stage; Beta-Nicotinamide adenine dinucleotide, Dihydrozeatin, Pannaric acid, and Propionylcarnitine demonstrated the highest levels in the IBA stage; Adrenosterone, PS (18:0/14,15-EpETE), S-Carboxymethylcysteine, TxB2, and 3-Phenoxybenzylalcohol demonstrated the highest levels in the POST stage. Kyoto Encyclopedia of Genes and Genomes pathways annotation analysis indicated that biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism were co-differential metabolism pathways during the different stages of hibernation. The stage-specific metabolism processes and integrated enzyme-centered metabolism networks in the different stages were also deciphered. Overall, our findings suggest that (1) the periodic change of proline, ketoleucine, and serine contributes to the hindlimb lean tissue preservation; and (2) key metabolites related to the biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism may be associated with muscle atrophy resistance. In conclusion, our co-differential metabolites, co-differential metabolism pathways, stage-specific metabolism pathways, and integrated enzyme-centered metabolism networks are informative for biologists to generate hypotheses for functional analyses to perturb disuse-induced muscle atrophy.

Weakened Contractile Performance and Mitochondrial Respiratory Complex Activity in Skeletal Muscle Improve during Interbout Arousal in Hibernating Daurian Ground Squirrel, Spermophilus dauricus.

Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation.

Laboratory Insecticide Efficacy Trials of Lethal Harborages for Control of the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae).

Over the past two decades, there has been a worldwide resurgence in the bed bugs Cimex lectularius L. and Cimex hemipterus (F.). This is primarily due to insecticide resistance, making bed bug management and eradication challenging and expensive. To address the need for more affordable control solutions, "lethal harborages" were explored. Cardboard squares were treated using insecticidal dusts at different dosage levels, including silica dioxide, diatomaceous earth, deltamethrin, permethrin, and fipronil. Two strains of C. lectularius, one susceptible and one resistant, were allowed to enter the treated harborages, and mortality rates were recorded daily. The silica dioxide products proved to be the most efficacious, consistently achieving 100% mortality between 14-17 d at the highest dose. An artificial environment trial using the "new ChinChex®" formulation of silica dioxide resulted in the complete elimination of bed bugs in the treated harborages within 21 d. These findings suggest that lethal harborages, especially those impregnated with silica dioxide, offer a cost-effective solution that could be incorporated into broader integrated bed bug management strategies. This approach may help alleviate the burden of bed bug infestations in economically disadvantaged communities.

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets.

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.

Spatial transcriptomics: recent developments and insights in respiratory research.

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Performance of Pyrethroid-Neonicotinoid Mixture Formulations Against Field-Collected Strains of the Tropical Bed Bug (Hemiptera: Cimicidae) on Different Substrates.

The residual performance of two pyrethroid-neonicotinoid mixture formulations: Temprid SC (10.5% beta-cyfluthrin and 21% imidacloprid) and Tandem (3.5% lambda-cyhalothrin and 11.6% thiamethoxam) on two substrates (glass and filter paper) against eight pyrethroid-resistant strains (BM-MY, BP-MY, CH-MY, GL-MY, KL-MY, SAJ-MY, TT-MY, and QLD-AU) of the tropical bed bug, Cimex hemipterus (F.) (Hemiptera: Cimicidae) collected from Malaysia, and Australia were evaluated. The aging effect of treatment residues on glass was also investigated. A susceptible C. lectularius L. strain (Monheim) was used for comparison. Temprid SC showed varying levels of performance against all C. hemipterus strains: TT-MY (PR50 = 6.5-fold, high performance), BM-MY, GL-MY, SAJ-MY, and QLD-AU (12.8-21.6-fold, moderate performance), BP-MY, and KL-MY (48.2-49-fold, poor performance), CH-MY (128.2-fold, very poor performance). On the other hand, Tandem displayed high performance against all C. hemipterus strains (1.8-8.3-fold). Tandem caused faster mortality than Temprid SC for all strains. Temprid SC and Tandem residues killed C. hemipterus significantly faster on glass than filter paper. Compared with fresh residues, the efficacy of Temprid SC residues significantly declined after one week of aging, while the effectiveness of Tandem residues declined after two weeks of aging. Further investigations using the topical assay method with a diagnostic dose of imidacloprid found two strains (CH-MY and GL-MY) resistant to imidacloprid. The six other strains (BM-MY, BP-MY, KL-MY, SAJ-MY, TT-MY, and QLD-AU) were susceptible.

Transcriptomic and proteomic time-course analyses based on Metascape reveal mechanisms against muscle atrophy in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus is resistant to muscle atrophy. Comprehensive transcriptome and proteome time-course analyses based on Metascape can further reveal the underlying processes (pre-hibernation stage, PRE; torpor stage, TOR; interbout arousal stage, IBA; and post-hibernation stage, POST). Transcriptome analysis showed that the cellular responses to growth factor stimulus and discrete oxygen levels continuously changed during hibernation. Proteomic analysis showed that neutrophil degranulation, sulfur compound metabolic process, and generation of precursor metabolites and energy continuously changed during hibernation. Molecular complex detection (MCODE) analysis in both transcriptome and proteome indicated that smooth muscle contraction was involved in the POST versus IBA stage, and peroxisome proliferator-activated receptor delta (Ppard), Myc proto-oncogene (Myc), Sp1 transcription factor (Sp1), and nuclear factor Kappa B subunit 1 (NFκB1) are the common TFs during the hibernation process. Integrated transcriptome and proteome analyses found 18 molecules in the TOR versus PRE stage, 1 molecule in the IBA versus TOR stage, and 16 molecules in the POST versus IBA stage. Among these molecules, carnitine palmitoyltransferase 1A (Cpt1a), SET and MYND domain containing 2 (Smyd2), four and a half LIM domains 1(Fhl1), reactive oxygen species modulator 1 (Romo1), and translocase of the inner mitochondrial membrane 50 (Timm50) were testified by Western blot. In conclusion, novel muscle atrophy resistance mechanisms can be deciphered by time-course transcriptome and proteome analyses based on Metascape.

Current distribution of distributed all-polar cochlear implant stimulation mode measured in-situ.

Oticon Medical cochlear implants use a stimulation mode called Distributed All-Polar (DAP) that connects all non-stimulating available intracochlear electrodes and an extracochlear reference electrode. It results in a complex distribution of current that is yet undescribed. The present study aims at providing a first characterization of this current distribution. A Neuro Zti was modified to allow the measurement of current returning to each electrode during a DAP stimulation and was implanted in an ex-vivo human head. Maps of distributed current were then created for different stimulation conditions with different charge levels. Results show that, on average, about 20% of current returns to the extracochlear reference electrode, while the remaining 80% is distributed between intracochlear electrodes. The position of the stimulating electrode changed this ratio, and about 10% more current to the extracochlear return in case of the first 3 basal electrodes than for apical and mid position electrodes was observed. Increasing the charge level led to small but significant change in the ratio, and about 4% more current to the extracochlear return was measured when increasing the charge level from 11.7 to 70 nC. Further research is needed to show if DAP yields better speech understanding than other stimulation modes.

Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation.

BACKGROUND: Previous studies have shown that microtubule actin crosslinking factor 1 (MACF1) can regulate osteoblast proliferation and differentiation through non-coding RNA (ncRNA) in bone-forming osteoblasts. However, the role of MACF1 in targeting the competing endogenous RNA (ceRNA) network to regulate osteoblast differentiation remains poorly understood. Here, we profiled messenger RNA (mRNA), microRNA (miRNA), and long ncRNA (lncRNA) expression in MACF1 knockdown MC3TC­E1 pre­osteoblast cells. RESULTS: In total, 547 lncRNAs, 107 miRNAs, and 376 mRNAs were differentially expressed. Significantly altered lncRNAs, miRNAs, and mRNAs were primarily found on chromosome 2. A lncRNA-miRNA-mRNA network was constructed using a bioinformatics computational approach. The network indicated that mir-7063 and mir-7646 were the most potent ncRNA regulators and mef2c was the most potent target gene. Pathway enrichment analysis showed that the fluid shear stress and atherosclerosis, p53 signaling, and focal adhesion pathways were highly enriched and contributed to osteoblast proliferation. Importantly, the fluid shear stress and atherosclerosis pathway was co-regulated by lncRNAs and miRNAs. In this pathway, Dusp1 was regulated by AK079370, while Arhgef2 was regulated by mir-5101. Furthermore, Map3k5 was regulated by AK154638 and mir-466q simultaneously. AK003142 and mir-3082-5p as well as Ak141402 and mir-446 m-3p were identified as interacting pairs that regulate target genes. CONCLUSION: This study revealed the global expression profile of ceRNAs involved in the differentiation of MC3TC­E1 osteoblasts induced by MACF1 deletion. These results indicate that loss of MACF1 activates a comprehensive ceRNA network to regulate osteoblast proliferation.

Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models.

1,2,4-triazole derivatives exhibit various biological activities, including antibacterial and antifungal properties. On the other hand, these chemicals may have unique cumulative and harmful effects on living organisms. The goal of this work is to use quantitative structure-toxicity relationship (QSTR) and interspecies quantitative toxicity-toxicity relationship (iQSTTR) models to predict the acute toxicity of 1,2,4-triazole derivatives. The QSTR models were generated by multiple linear regression (MLR) following the OECD recommendations for QSAR model development and validation. The iQSTTR models were constructed using data on acute oral toxicity in rats and mice, as well as the 2D descriptor. The application domain (AD) analysis was used to identify model outliers and determine if the forecast was credible. Six QSTR models were successfully constructed in rats and mice using various delivery methods, and the scatter plots demonstrated excellent consistency across training and test sets. According to external and internal validation criteria, all six QSTR models may be broadly accepted; however, the orally administered mice model was the optimum one among the six species. Several chemicals with leverage values above the requirements were identified as response or structural outliers in the training sets for six QSTR and two iQSTTR models. All outliers, however, fell slightly outside the threshold or had low prediction errors, which may have had little impact on the capacity to forecast and were therefore preserved in the final models. In fact, neither the QSTR nor the iQSTTR test sets contained any response outliers. Additionally, all external and internal validation results for the iQSTTR models were approved, with the iQSTTR models outperforming the comparable QSTR models, which are deemed more dependable. The QSTR and iQSTTR models performed well in predicting toxicity using test sets, which would be beneficial in evaluating and synthesizing newly discovered 1,2,4-triazoles derivatives with low toxicity and environmental hazard.

The role of protein glycosylation in muscle diseases.

INTRODUCTION: As a post-translational modification, glycosylation plays vital role in regulating the folding and function of proteins necessary for many biological processes. Unlike glycation, glycosylation is an enzymatic process; glycosyltransferases transfer sugars to proteins, forming glycosidic bonds with amino acid residues on proteins. Changes that interfere with the enzymatic reaction and result in abnormal glycosylation can spatio-temporally affect the balance of glycosylation, leading to disease states. Muscle diseases have been associated with dysfunctional protein glycosylation, and many studies have focused on the pathophysiology underlying this association. This review aims to summarize the research progress on protein glycosylation in the pathogenesis of muscle diseases and provides new insight into the muscle research field. METHODS: Literatures were reviewed comparatively and data were organized to find information about protein glycosylation and its role in muscle disease. RESULTS: Protein glycosylation modification is closely related to the occurrence of muscle diseases. α-DG is a key protein in the study of inherited muscle diseases and has a wide range of glycosylation, including O-linked glycosylation and N-linked glycosylation. Besides, O-GlcNAc glycosylation is an important mechanism of protein glycosylation, helping maintaining the structure and function of skeletal muscle and participating in multiple biological processes. Protein glycosylation is also connected to muscle disease and neurodegenerative diseases, especially Alzheimer's disease. CONCLUSIONS: Taken together, better understanding of protein glycosylation and its implication in muscle disease would help provide new perspectives in the prevention and treatment measures for human muscle diseases.

Multiple Mechanisms Conferring Broad-Spectrum Insecticide Resistance in the Tropical Bed Bug (Hemiptera: Cimicidae).

The modern resurgence of the common (Cimex lectularius L.) and tropical bed bugs (C. hemipterus [F.]) is thought to be primarily due to insecticide resistance. While there are many reports on insecticide resistance mechanisms in C. lectularius, such information in C. hemipterus is limited. We examined dichloro-diphenyl-trichloroethane (DDT), malathion, deltamethrin, permethrin, lambda-cyhalothrin resistance, and the underlying mechanisms in several C. hemipterus strains (Australia: Queensland [QLD-AU]; Malaysia: Kuala Lumpur [KL-MY], Tanjung Tokong [TT-MY], Christian [CH-MY], and Green Lane [GL-MY]). We used a surface contact method, synergism studies (utilizing piperonyl butoxide [PBO], S,S,S-tributyl phosphorotrithioate [DEF], and diethyl maleate [DEM]), and molecular detection of kdr mutations. Results demonstrated that all C. hemipterus strains possessed high resistance to DDT and the pyrethroids and moderate to high resistance to malathion. Synergism studies showed that deltamethrin resistance in all strains was significantly (P < 0.05) inhibited by PBO. In contrast, deltamethrin resistance was not affected in DEF or DEM. Similar findings were found with lambda-cyhalothrin resistance. Malathion resistance was significantly (P < 0.05) reduced by DEF in all strains. Resistance to DDT was not affected by DEM in all strains. Multiple kdr mutations (M918I, D953G, and L1014F) were detected by molecular analyses. TT-MY strain was found with individuals possessing three kdr mutation combinations; D953G + L1014F (homozygous susceptible: M918), M918I + D953G + L1014F (heterozygous resistant: I918), and M918I + D953G + L1014F (homozygous resistant: I918). Individuals with M918I + D953G + L1014F (homozygous resistant: I918) survived longer on deltamethrin (>12 h) than those (≤1 h) with other combinations. M918I + L1014F mutations most likely conferred super-kdr characteristic toward pyrethroids and DDT in C. hemipterus.

Different fuel regulation in two types of myofiber results in different antioxidant strategies in Daurian ground squirrels (Spermophilus dauricus) during hibernation.

We previously showed that different skeletal muscles in Daurian ground squirrels (Spermophilus dauricus) possess different antioxidant strategies during hibernation; however, the reason for these varied strategies remains unclear. To clarify this issue, we studied REDD1, FOXO4, PGC-1α, FOXO1 and atrogin-1 proteins to determine the potential cause of the different antioxidant strategies in Daurian ground squirrels during hibernation, and to clarify whether different strategies affect atrophy-related signals. Results showed that the soleus (SOL) muscle experienced intracellular hypoxia during interbout arousal, but no oxidative stress. This may be due to increased PGC-1α expression enhancing antioxidant capacity in the SOL under hypoxic conditions. Extensor digitorum longus (EDL) muscle showed no change in oxidative stress, hypoxia or antioxidant capacity during hibernation. The FOXO1 and PGC-1α results strongly suggested differentially regulated fuel metabolism in the SOL and EDL muscles during hibernation, i.e. enhanced lipid oxidation and maintained anaerobic glycolysis, respectively. Atrogin-1 expression did not increase during hibernation in either the SOL or EDL, indicating that protein synthesis was not inhibited by atrogin-1. Thus, our results suggest that different fuel regulation may be one mechanism related to antioxidant defense strategy formation in different kinds of skeletal muscle fibers of Daurian ground squirrels during hibernation.

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Role of LncRNAs and CircRNAs in Bone Metabolism and Osteoporosis.

Bone is a mechanosensitive organ that provides strength and support. Many bone cells, various pathways, and signaling molecules coordinate bone metabolism and also determine the course of bone diseases, such as osteoporosis, osteonecrosis, osteopenia, etc. Osteoporosis is caused by increased bone resorption and reduced bone formation due to the changes in the level of different proteins and RNAs in osteoclast or/and osteoblasts. The available therapeutic interventions can significantly reduce bone resorption or enhance bone formation, but their prolonged use has deleterious side effects. Therefore, the use of non-coding RNAs as therapeutics has emerged as an interesting field of research. Despite advancements in the molecular field, not much is known about the role of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in bone homeostasis and osteoporosis. Therefore, in this article, we summarize the role of lncRNAs and circRNAs in different bone cells and osteoporosis so that it might help in the development of osteoporotic therapeutics.

A Comprehensive Analysis of MicroRNAs in Human Osteoporosis.

MicroRNAs (miRNAs) are single-stranded RNA molecules that control gene expression in various processes, such as cancers, Alzheimer's disease, and bone metabolic diseases. However, the regulatory roles of miRNAs in osteoporosis have not been systematically analyzed. Here, we performed a comprehensive analysis to identify the differentially expressed miRNAs involved in osteoporosis. MiRNAs associated with osteoporosis were collected through literature retrieval and further screened based on specific inclusion and exclusion criteria. The osteoporosis therapeutic targets of miRNAs were obtained by the integration of miRWalk 3.0 database and five human disease therapeutic target databases. Then, the network analysis and functional enrichment analysis of miRNAs and their targets were performed. As a result, 11 eligible miRNAs were identified highly associated with osteoporosis. MiRNA-mRNA network demonstrated there were the complex mutual interactions between miRNAs and their targets. Besides, ADRB2, AR, ESR1, FGFR1, TRAF6, etc., were identified as the top hub genes in protein-protein interaction (PPI) network. Functional enrichment analysis revealed that miRNAs and their targets were mainly mapped on processes associated with bone and immune system, such as bone remolding, bone mineralization, PI3K/AKt, TNF signaling pathways and Th17 cell differentiation. RT-PCR results showed that the expression of miR-335-3p was significantly down-regulated in hind limb unloading (HLU) mice tibia samples compared with controls, the remaining 10 miRNAs were significantly up-regulated after HLU (P < 0.01). In summary, we identified 11 differentially expressed miRNAs and their hub target genes in osteoporosis, which may be novel diagnostic biomarkers for osteoporosis.

Isolation and identification of a novel bacterium, Pseudomonas sp. ZyL-01, involved in the biodegradation of CL-20.

Hexanitrohexaazaisowurtzitane (CL-20) is a compound with a polycyclic cage and an N-nitro group that has been shown to play an unfavorable role in environmental fate, biosafety, and physical health. The aim of this study was to isolate the microbial community and to identify a single microbial strain that can degrade CL-20 with desirable efficiency. Metagenomic sequencing methods were performed to investigate the dynamic changes in the composition of the community diversity. The most varied genus among the microbial community was Pseudomonas, which increased from 1.46% to 44.63% during the period of incubation (MC0-MC4). Furthermore, the new strain was isolated and identified from the activated sludge by bacterial morphological and 16s rRNA sequencing analyses. The CL-20 concentrations decreased by 75.21 µg/mL and 74.02 µg/mL in 48 h by MC4 and Pseudomonas sp. ZyL-01, respectively. Moreover, ZyL-01 could decompose 98% CL-20 of the real effluent in 14 day's incubation with the glucose as carbon source. Finally, a draft genome sequence was obtained to predict possible degrading enzymes involved in the biodegradation of CL-20. Specifically, 330 genes that are involved in energy production and conversion were annotated by Gene Ontology functional enrichment analysis, and some of these candidates may encode enzymes that are responsible for CL-20 degradation. In summary, our studies indicate that microbes might be a valuable biological resource for the treatment of environmental contamination caused by CL-20 and that Pseudomonas sp. ZyL-01 might be a promising candidate for eradicating CL-20 to achieve a more biosafe environment and improve public health.

Leveraging maximum entropy and correlation on latent factors for learning representations.

Many tasks involve learning representations from matrices, and Non-negative Matrix Factorization (NMF) has been widely used due to its excellent interpretability. Through factorization, sample vectors are reconstructed as additive combinations of latent factors, which are represented as non-negative distributions over the raw input features. NMF models are significantly affected by latent factors' distribution characteristics and the correlations among them. And NMF models are faced with the challenge of learning robust latent factor. To this end, we propose to learn representations with an awareness of the semantic quality evaluated from the aspects of intra- and inter-factors. On the one hand, a Maximum Entropy-based function is devised for the intra-factor semantic quality. On the other hand, the semantic uniqueness is evaluated via inter-factor correlation, which reinforces the aim of semantic compactness. Moreover, we present a novel non-linear NMF framework. The learning algorithm is presented and the convergence is theoretically analyzed and proved. Extensive experimental results on multiple datasets demonstrate that our method can be successfully applied to representative NMF models and boost performances over state-of-the-art models.