Fluorine-Functionalized Covalent Organic Framework Superhydrophobic Modified Melamine Sponge for Efficient oil-water Separation.

Hydrophobic sponges have attracted significant interest in oil spills and water-oil separation as potential absorption materials due to their desirable absorptivity, selectivity, and elasticity. In this paper, a hydrophilic melamine sponge (MS) is transferred into a superhydrophobic sponge via polydimethylsiloxane (PDMS) modification followed by in situ growth of fluorine-functionalized covalent organic framework (denoted as TFA-COF) nanoparticles. Therefore, the PDMS@TFA-COF@MS sponge was successfully prepared for efficient oil-water separation. The resultant PDMS@TFA-COF@MS exhibits superhydrophobic properties with a water contact angle of 156.7°. The superhydrophobic sponge has selectivity adsorption for different organic solvents and oils from water as well as oil-water separation efficiency (96% after 30 cycles) and oil absorption capacity (12 646% after 30 cycles). Meanwhile, the PDMS@TFA-COF@MS sponge exhibits strong thermal stability and flame retardancy in addition to having exceptional resistance to chemical corrosion in acidic, alkaline, and salt solutions. Moreover, the surfactant-stabilized oil-in-water emulsion could be efficiently separated by the sponge. Therefore, the prepared superhydrophobic PDMS@TFA-COF@MS sponge demonstrates possible uses for long-life oil-water separation applications.

CRISPR-Cas12a coupled with universal gold nanoparticle strand-displacement probe for rapid and sensitive visual SARS-CoV-2 detection.

Point of care (POC) diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are particularly significant for preventing transmission of coronavirus disease 2019 (COVID-19) by any user at any given time and place. CRISPR/Cas-assisted SARS-CoV-2 assays are viewed as supplemental to RT-PCR due to simple operation, convenient use and low cost. However, most current CRISPR molecular diagnostics based on fluorescence measurement increased the difficulty of POC test with need of the additional light sources. Some instrument-free visual detection with the naked eye has limitations in probe universality. Herein, we developed a universal, rapid, sensitive and specific SARS-CoV-2 POC test that combines the outstanding DNase activity of Cas12a with universal AuNPs strand-displacement probe. The oligo trigger, which is the switch the AuNPs of the strand-displacement probe, is declined as a result of Cas12a recognition and digestion. The amount of released AuNPs produced color change which can be visual with the naked eye and assessed by UV-Vis spectrometer for quantitative detection. Furthermore, a low-cost hand warmer is used as an incubator for the visual assay, enabling an instrument-free, visual SARS-CoV-2 detection within 20 min. A real coronavirus GX/P2V instead of SARS-CoV-2 were chosen for practical application validation. After rapid virus RNA extraction and RT-PCR amplification, a minimum of 2.7 × 102 copies/mL was obtained successfully. The modular design can be applied to many nucleic acid detection applications, such as viruses, bacteria, species, etc., by simply modifying the crRNA, showing great potential in POC diagnosis.

Understanding Responses of Soil Microbiome to the Nitrogen and Phosphorus Addition in Metasequoia glyptostroboides Plantations of Different Ages.

Nitrogen (N) and phosphorus (P) have significant effects on soil microbial community diversity, composition, and function. Also, trees of different life stages have different fertilization requirements. In this study, we designed three N additions and three P levels (5 years of experimental treatment) at two Metasequoia glyptostroboides plantations of different ages (young, 6 years old; middle mature, 24 years old) to understand how different addition levels of N and P affect the soil microbiome. Here, the N fertilization of M. glyptostroboides plantation land (5 years of experimental treatment) significantly enriched microbes (e.g., Lysobacter, Luteimonas, and Rhodanobacter) involved in nitrification, denitrification, and P-starvation response regulation, which might further lead to the decreasing in alpha diversity (especially in 6YMP soil). The P addition could impact the genes involved in inorganic P-solubilization and organic P-mineralization by increasing soil AP and TP. Moreover, the functional differences in the soil microbiomes were identified between the 6YMP and 24YMP soil. This study provides valuable information that improves our understanding on the effects of N and P input on the belowground soil microbial community and functional characteristics in plantations of different stand ages.

Development of IFN-Stimulated Gene Expression from Embryogenesis through Adulthood, with and without Constitutive MDA5 Pathway Activation.

Pathogen-associated molecular patterns (e.g., dsRNA) activate expression of IFN-stimulated genes (ISGs), which protect hosts from infection. Although transient ISG upregulation is essential for effective innate immunity, constitutive activation typically causes harmful autoimmunity in mice and humans, often including severe developmental abnormalities. We have shown that transgenic mice expressing a picornavirus RNA-dependent RNA polymerase (RdRP) outside the viral context (RdRP mice) exhibit constitutive, MDA5-dependent, and quantitatively dramatic upregulation of many ISGs, which confers broad viral infection resistance. Remarkably, RdRP mice never develop autoinflammation, interferonopathy, or other discernible abnormalities. In this study, we used RNA sequencing and other methods to analyze ISG expression across five time points from fetal development to adulthood in wild-type and RdRP mice. In RdRP mice, the proportion of upregulated ISGs increased during development, with the most dramatic induction occurring 2 wk postnatally. The amplified ISG profile is then maintained lifelong. Molecular pathways and biological functions associated with innate immune and IFN signaling are only activated postnatally, suggesting constrained fetal responsiveness to innate immune stimuli. Biological functions supporting replication of viruses are only inhibited postnatally. We further determined that the RdRP is expressed at low levels and that blocking Ifnar1 reverses the amplified ISG transcriptome in adults. In conclusion, the upregulated ISG profile of RdRP mice is mostly triggered early postnatally, is maintained through adulthood, and requires ongoing type I IFN signaling to maintain it. The model provides opportunities to study the systems biology of innate immunity and to determine how sustained ISG upregulation can be compatible with robust health.

Systematically investigating the fluorescent signal readout of CRISPR-Cas12a for highly sensitive SARS-CoV-2 detection.

The CRISPR/Cas system is widely used for molecular diagnostics after the discovery of trans-cleavage activity, especially now with the COVID-19 outbreak. However, the majority of contemporary trans-cleavage activity-based CRISPR/Cas biosensors exploited standard single-strand DNA (ssDNA) reporters, which were based on the FRET principle from pioneering research. An in-depth comparison and understanding of various fluorescent readout types are essential to facilitate the outstanding analytical performance of CRISPR probes. We investigated various types of fluorescent reporters of Cas12a comprehensively. Results show that trans-cleavage of Cas12a is not limited to ssDNA and dsDNA reporters, but can be extended to molecular beacons (MB). And MB reporters can achieve superior analytical performance compared with ssDNA and ds DNA reporters at the same conditions. Accordingly, we developed a highly-sensitive SARS-CoV-2 detection with the sensitivity as low as 100 fM were successfully achieved without amplification strategy. The model target of ORF1a could robustly identify the current widespread emerging SARS-CoV-2 variants. A real coronavirus GX/P2V instead of SARS-CoV-2 were chosen for practical application validation. And a minimum of 27 copies/mL was achieved successfully. This inspiration can also be applied to other Cas proteins with trans-cleavage activity, which provides new perspectives for simple, highly-sensitive and universal molecular diagnosis in various applications.

Hyperandrogenism and insulin resistance-induced fetal loss: evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome.

KEY POINTS: Women with polycystic ovary syndrome (PCOS) commonly suffer from miscarriage, but the underlying mechanisms remain unknown. Herein, pregnant rats chronically treated with 5α-dihydrotestosterone (DHT) and insulin exhibited hyperandrogenism and insulin resistance, as well as increased fetal loss, and these features are strikingly similar to those observed in pregnant PCOS patients. Fetal loss in our DHT+insulin-treated pregnant rats was associated with mitochondrial dysfunction, disturbed superoxide dismutase 1 and Keap1/Nrf2 antioxidant responses, over-production of reactive oxygen species (ROS) and impaired formation of the placenta. Chronic treatment of pregnant rats with DHT or insulin alone indicated that DHT triggered many of the molecular pathways leading to placental abnormalities and fetal loss, whereas insulin often exerted distinct effects on placental gene expression compared to co-treatment with DHT and insulin. Treatment of DHT+insulin-treated pregnant rats with the antioxidant N-acetylcysteine improved fetal survival but was deleterious in normal pregnant rats. Our results provide insight into the fetal loss associated with hyperandrogenism and insulin resistance in women and suggest that physiological levels of ROS are required for normal placental formation and fetal survival during pregnancy. ABSTRACT: Women with polycystic ovary syndrome (PCOS) commonly suffer from miscarriage, but the underlying mechanism of PCOS-induced fetal loss during pregnancy remains obscure and specific therapies are lacking. We used pregnant rats treated with 5α-dihydrotestosterone (DHT) and insulin to investigate the impact of hyperandrogenism and insulin resistance on fetal survival and to determine the molecular link between PCOS conditions and placental dysfunction during pregnancy. Our study shows that pregnant rats chronically treated with a combination of DHT and insulin exhibited endocrine aberrations such as hyperandrogenism and insulin resistance that are strikingly similar to those in pregnant PCOS patients. Of pathophysiological significance, DHT+insulin-treated pregnant rats had greater fetal loss and subsequently decreased litter sizes compared to normal pregnant rats. This negative effect was accompanied by impaired trophoblast differentiation, increased glycogen accumulation, and decreased angiogenesis in the placenta. Mechanistically, we report that over-production of reactive oxygen species (ROS) in the placenta, mitochondrial dysfunction, and disturbed superoxide dismutase 1 (SOD1) and Keap1/Nrf2 antioxidant responses constitute important contributors to fetal loss in DHT+insulin-treated pregnant rats. Many of the molecular pathways leading to placental abnormalities and fetal loss in DHT+insulin treatment were also seen in pregnant rats treated with DHT alone, whereas pregnant rats treated with insulin alone often exerted distinct effects on placental gene expression compared to insulin treatment in combination with DHT. We also found that treatment with the antioxidant N-acetylcysteine (NAC) improved fetal survival in DHT+insulin-treated pregnant rats, an effect related to changes in Keap1/Nrf2 and nuclear factor-κB signalling. However, NAC administration resulted in fetal loss in normal pregnant rats, most likely due to PCOS-like endocrine abnormality induced by the treatment. Our results suggest that the deleterious effects of hyperandrogenism and insulin resistance on fetal survival are related to a constellation of mitochondria-ROS-SOD1/Nrf2 changes in the placenta. Our findings also suggest that physiological levels of ROS are required for normal placental formation and fetal survival during pregnancy.

Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR-384.

It was reported that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR-384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR-384 exhibited the functions of tumor-suppressive. The expression of miR-384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR-384 expression, whereas inhibition of miR-384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR-384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA-binding protein immunoprecipitation assays. Overexpression of miR-384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR-384.

LncRNA CRNDE promotes the epithelial-mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/ß-catenin signaling pathway.

Colorectal neoplasia differentially expressed (CRNDE) is a significantly upregulated long noncoding RNA in hepatocellular carcinoma (HCC). CRNDE could promote cell proliferation, migration, and invasion, while its molecular mechanisms were still largely unclear. In this study, we investigated the expression and function of CRNDE. CRNDE was significantly upregulated in tumor tissues compared with adjacent normal tissues. In vitro, we revealed that knockdown of CRNDE inhibited cell proliferation, migration, and cell invasion capacities in HCC. Animal studies indicated that CRNDE knockdown represses both growth and metastasis of HCC tumors in vivo. Moreover, knockdown of CRNDE suppressed the cell epithelial-mesenchymal transition (EMT) process by increasing the expression of E-cadherin and ZO-1, whereas, decreasing the expression of N-cadherin, slug, twist, and vimentin in HCC cells. We also revealed that knockdown of CRNDE suppressed the Wnt/ß-catenin signaling in HCC. Thus, CRNDE could modulate EMT of HCC cells and knockdown of CRNDE impaired the mesenchymal properties. CRNDE increased invasion of HCC cells might be through activating the Wnt/ß-catenin signaling pathway.

Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant reactive oxygen species production.

Women with polycystic ovary syndrome (PCOS) are at increased risk of miscarriage, which often accompanies the hyperandrogenism and insulin resistance seen in these patients. However, neither the combinatorial interaction between these two PCOS-related etiological factors nor the mechanisms of their actions in the uterus during pregnancy are well understood. We hypothesized that hyperandrogensim and insulin resistance exert a causative role in miscarriage by inducing defects in uterine function that are accompanied by mitochondrial-mediated oxidative stress, inflammation, and perturbed gene expression. Here, we tested this hypothesis by studying the metabolic, endocrine, and uterine abnormalities in pregnant rats after exposure to daily injection of 5α-dihydrotestosterone (DHT; 1.66 mg·kg body wt-1·day-1) and/or insulin (6.0 IU/day) from gestational day 7.5 to 13.5. We showed that whereas DHT-exposed and insulin-exposed pregnant rats presented impaired insulin sensitivity, DHT + insulin-exposed pregnant rats exhibited hyperandrogenism and peripheral insulin resistance, which mirrors pregnant PCOS patients. Compared with controls, hyperandrogenism and insulin resistance in the dam were associated with alterations in uterine morphology and aberrant expression of genes responsible for decidualization (Prl8a2, Fxyd2, and Mt1g), placentation (Fcgr3 and Tpbpa), angiogenesis (Flt1, Angpt1, Angpt2, Ho1, Ccl2, Ccl5, Cxcl9, and Cxcl10) and insulin signaling (Akt, Gsk3, and Gluts). Moreover, we observed changes in uterine mitochondrial function and homeostasis (i.e., mitochondrial DNA copy number and the expression of genes responsible for mitochondrial fusion, fission, biogenesis, and mitophagy) and suppression of both oxidative and antioxidative defenses (i.e., reactive oxygen species, Nrf2 signaling, and interactive networks of antioxidative stress responses) in response to the hyperandrogenism and insulin resistance. These findings demonstrate that hyperandrogenism and insulin resistance induce mitochondria-mediated damage and a resulting imbalance between oxidative and antioxidative stress responses in the gravid uterus.

Activation of a human chromosomal replication origin by protein tethering.

The specification of mammalian chromosomal replication origins is incompletely understood. To analyze the assembly and activation of prereplicative complexes (pre-RCs), we tested the effects of tethered binding of chromatin acetyltransferases and replication proteins on chromosomal c-myc origin deletion mutants containing a GAL4-binding cassette. GAL4(DBD) (DNA binding domain) fusions with Orc2, Cdt1, E2F1 or HBO1 coordinated the recruitment of the Mcm7 helicase subunit, the DNA unwinding element (DUE)-binding protein DUE-B and the minichromosome maintenance (MCM) helicase activator Cdc45 to the replicator, and restored origin activity. In contrast, replication protein binding and origin activity were not stimulated by fusion protein binding in the absence of flanking c-myc DNA. Substitution of the GAL4-binding site for the c-myc replicator DUE allowed Orc2 and Mcm7 binding, but eliminated origin activity, indicating that the DUE is essential for pre-RC activation. Additionally, tethering of DUE-B was not sufficient to recruit Cdc45 or activate pre-RCs formed in the absence of a DUE. These results show directly in a chromosomal background that chromatin acetylation, Orc2 or Cdt1 suffice to recruit all downstream replication initiation activities to a prospective origin, and that chromosomal origin activity requires singular DNA sequences.

Behavior identification based on geotagged photo data set.

The popularity of mobile devices has produced a set of image data with geographic information, time information, and text description information, which is called geotagged photo data set. The division of this kind of data by its behavior and the location not only can identify the user's important location and daily behavior, but also helps users to sort the huge image data. This paper proposes a method to build an index based on multiple classification result, which can divide the data set multiple times and distribute labels to the data to build index according to the estimated probability of classification results in order to accomplish the identification of users' important location and daily behaviors. This paper collects 1400 discrete sets of data as experimental data to verify the method proposed in this paper. The result of the experiment shows that the index and actual tagging results have a high inosculation.

A core-shell structured AuNPs@ZnCo-MOF SERS substrate for sensitive and selective detection of thiram.

Surface-enhanced Raman scattering (SERS) enables pesticide residue monitoring to become facile and efficient. In this study, a core-shell structured gold nanoparticles@ZnCo metal-organic framework (AuNPs@ZnCo-MOF) SERS substrate was designed and successfully synthesized for efficient and selective detection of thiram. The bimetallic ZnCo-MOF shell can not only enrich the targeted molecules in the electromagnetic field because of its excellent absorptive capacity, but also act as a stabilized matrix for protecting the AuNPs from aggregation. The AuNPs@ZnCo-MOFs exhibited a high enhancement factor (EF) of 3.51 × 106 and a low detection limit of 1 × 10-7 mol L-1. Besides, the substrate material showed exceptional stability for up to 28 days at room temperature. The AuNPs@ZnCo-MOFs were used to detect thiram which displayed wide linearity (1 × 10-7 to 1 × 10-4 mol L-1) and high recoveries (83.45-99.61%). Moreover, the AuNPs@ZnCo-MOF SERS substrate exhibited excellent anti-interference ability and size selectivity for the target molecules. These indicate that the AuNPs@ZnCo-MOF substrate has great potential for the detection of thiram residues in practical applications.

Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations.

Calcium homeostasis imbalance in the body can lead to a variety of chronic diseases. Supplement efficiency is essential. Peptide calcium chelate, a fourth-generation calcium supplement, offers easy absorption and minimal side effects. Its effectiveness relies on peptide's calcium binding capacity. However, research on amino acid sequences in peptides with high calcium binding capacity (HCBC) is limited, affecting the efficient identification of such peptides. This study used soybean peptides (SP), separated and purified by gel chromatography, to obtain HCBC peptide (137.45 µg mg-1) and normal peptide (≤95.78 µg mg-1). Mass spectrometry identified the sequences of these peptides, and an analysis of the positional distribution of characteristic amino acids followed. Two HCBC peptides with sequences GGDLVS (271.55 µg mg-1) and YEGVIL (272.54 µg mg-1) were discovered. Molecular dynamics showed that when either aspartic acid is located near the N-terminal's middle, or glutamic acid is near the end, or in cases of continuous Asp or Glu, the binding speed, probability, and strength between the peptide and calcium ions are superior compared to those at other locations. The study's goal was to clarify how the positions of characteristic amino acids in peptides affect calcium binding, aiding in developing peptide calcium chelates as a novel calcium supplement.

Replication fork stalling and checkpoint activation by a PKD1 locus mirror repeat polypurine-polypyrimidine (Pu-Py) tract.

DNA sequences prone to forming noncanonical structures (hairpins, triplexes, G-quadruplexes) cause DNA replication fork stalling, activate DNA damage responses, and represent hotspots of genomic instability associated with human disease. The 88-bp asymmetric polypurine-polypyrimidine (Pu-Py) mirror repeat tract from the human polycystic kidney disease (PKD1) intron 21 forms non-B DNA secondary structures in vitro. We show that the PKD1 mirror repeat also causes orientation-dependent fork stalling during replication in vitro and in vivo. When integrated alongside the c-myc replicator at an ectopic chromosomal site in the HeLa genome, the Pu-Py mirror repeat tract elicits a polar replication fork barrier. Increased replication protein A (RPA), Rad9, and ataxia telangiectasia- and Rad3-related (ATR) checkpoint protein binding near the mirror repeat sequence suggests that the DNA damage response is activated upon replication fork stalling. Moreover, the proximal c-myc origin of replication was not required to cause orientation-dependent checkpoint activation. Cells expressing the replication fork barrier display constitutive Chk1 phosphorylation and continued growth, i.e. checkpoint adaptation. Excision of the Pu-Py mirror repeat tract abrogates the DNA damage response. Adaptation to Chk1 phosphorylation in cells expressing the replication fork barrier may allow the accumulation of mutations that would otherwise be remediated by the DNA damage response.

The putative maintaining mechanism of gut bacterial ecosystem in giant pandas and its potential application in conservation.

Animals living in captivity and the wild show differences in the internal structure of their gut microbiomes. Here, we performed a meta-analysis of the microbial data of about 494 fecal samples obtained from giant pandas (captive and wild giant pandas). Our results show that the modular structures and topological features of the captive giant panda gut microbiome differ from those of the wild populations. The co-occurrence network of wild giant pandas also contained more nodes and edges, indicating a higher complexity and stability compared to that of captive giant pandas. Keystone species analysis revealed the differences between geographically different wild populations, indicating the potential effect of geography on the internal modular structure. When combining all the giant panda samples for module analysis, we found that the abundant taxa (e.g., belonged to Flavobacterium, Herbaspirillum, and Escherichia-Shigella) usually acted as module hubs to stabilize the modular structure, while the rare taxa usually acted as connectors of different modules. We conclude that abundant and rare taxa play different roles in the gut bacterial ecosystem. The conservation of some key bacterial species is essential for promoting the development of the gut microbiome in pandas. The living environment of the giant pandas can influence the internal structure, topological features, and strength of interrelationships in the gut microbiome. This study provides new insights into the conservation and management of giant panda populations.

Food provisioning results in functional, but not compositional, convergence of the gut microbiomes of two wild Rhinopithecus species: Evidence of functional redundancy in the gut microbiome.

The consumption of similar diets has led to the convergence of gut microbial compositions and functions across phylogenetically distinct animals. However, given the functional redundancy in gut microbiomes, it remains unclear whether synchrony occurs in their functions only and not in their composition, even within phylogenetically close animals consuming a similar diet. In this study, we collected fresh fecal samples from a Rhinopithecus roxellana population in April 2021 (before food provisioning) and June and December 2021 (after food provisioning) and used high-throughput sequencing methods (full-length 16S rRNA gene sequencing and metagenomes) to investigate changes in the gut microbiome due to food provisioning. Combining the results from our previous studies on a wild Rhinopithecus bieti population, we found that the artificial food provisions (e.g., apples, carrots, and peanuts) affected the gut microbiome, and synchrony occurred only in its functions and antibiotic resistance gene community in both Rhinopithecus species, reflecting its ecological functional redundancy. Given the current findings (e.g., depletion in probiotic microbes, dysbiosis in the gut microbial community, and changes in the antibiotic resistance gene profile), anthropogenic disturbances (e.g., food provisioning) would have potential negative effects on host health. Therefore, human activity in animal conservation should be rethought from the standpoint of gut microbial diversity.

Modulation of the vitamin D/vitamin D receptor system in osteoporosis pathogenesis: insights and therapeutic approaches.

Osteoporosis is a prevalent bone disorder characterized by low bone mineral density (BMD) and deteriorated bone microarchitecture, leading to an increased risk of fractures. Vitamin D (VD), an essential nutrient for skeletal health, plays a vital role in maintaining bone homeostasis. The biological effects of VD are primarily mediated through the vitamin D receptor (VDR), a nuclear receptor that regulates the transcription of target genes involved in calcium and phosphate metabolism, bone mineralization, and bone remodeling. In this review article, we conduct a thorough literature search of the PubMed and EMBASE databases, spanning from January 2000 to September 2023. Utilizing the keywords "vitamin D," "vitamin D receptor," "osteoporosis," and "therapy," we aim to provide an exhaustive overview of the role of the VD/VDR system in osteoporosis pathogenesis, highlighting the most recent findings in this field. We explore the molecular mechanisms underlying VDR's effects on bone cells, including osteoblasts and osteoclasts, and discuss the impact of VDR polymorphisms on BMD and fracture risk. Additionally, we examine the interplay between VDR and other factors, such as hormonal regulation, genetic variants, and epigenetic modifications, that contribute to osteoporosis susceptibility. The therapeutic implications of targeting the VDR pathway for osteoporosis management are also discussed. By bringing together these diverse aspects, this review enhances our understanding of the VD/VDR system's critical role in the pathogenesis of osteoporosis and highlights its significance as a potential therapeutic target.

Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human cells.

Instability of (CTG) x (CAG) microsatellite trinucleotide repeat (TNR) sequences is responsible for more than a dozen neurological or neuromuscular diseases. TNR instability during DNA synthesis is thought to involve slipped-strand or hairpin structures in template or nascent DNA strands, although direct evidence for hairpin formation in human cells is lacking. We have used targeted recombination to create a series of isogenic HeLa cell lines in which (CTG) x (CAG) repeats are replicated from an ectopic copy of the Myc (also known as c-myc) replication origin. In this system, the tendency of chromosomal (CTG) x (CAG) tracts to expand or contract was affected by origin location and the leading or lagging strand replication orientation of the repeats, and instability was enhanced by prolonged cell culture, increased TNR length and replication inhibition. Hairpin cleavage by synthetic zinc finger nucleases in these cells has provided the first direct evidence for the formation of hairpin structures during replication in vivo.

Invasion and defense of the basic social unit in a nonhuman primate society leads to sexual differences in the gut microbiome.

Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates. Given the potential connection between social behavior and gut microbiome composition, the multilevel social system could affect the primate gut microbiome. Here, based on long-term observation (e.g. social unit dynamics, transfer, and behavior), we investigated this potential integrating 16S rRNA gene amplicon sequencing and behavior data in Yunnan snub-nosed monkeys (Rhinopithecus bieti), which possess a multilevel social group based on one male units (OMUs, each unit with several breeding females and their offspring) and all-male unit (AMU, several bachelor males residing together). We found that the mean unweighted Unifrac distance between adult males from different OMUs was significantly lower than that between adult females from different OMUs (paired Wilcoxon test, P = 0.007). There was no significant difference in the mean unweighted Unifrac distance between females within the same OMU or between females from different OMUs. These findings indicated the potential connection between the defense and invasion of social units and the gut microbiome community in wild Yunnan snub-nosed monkeys. We speculated that the resident males of OMUs displaying a significantly higher similarity in the gut microbial community than that of adult females in separate OMUs might be associated with the sexual differences in their interactions and from previously having cohabitated together in the AMU. Therefore, this study suggested that multilevel societies might have an effect on the gut microbial community in this wild nonhuman primate species.

Biological Properties and Clinical Significance of Lipoprotein-Associated Phospholipase A2 in Ischemic Stroke.

Ischemic stroke, which occurs following blockage of the blood supply to the brain, is a leading cause of death worldwide. Its main cause is atherosclerosis, a disease of the arteries characterized by the deposition of plaques of fatty material on the inner artery walls. Multiple proteins involved in the inflammation response have been identified as diagnosing biomarkers of ischemic stroke. One of these is lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme that can hydrolyze circulating oxidized phospholipids, generating proinflammatory lysophosphatidylcholine and promoting the development of atherosclerosis. In the last two decades, a number of studies have revealed that both the concentration and the activity of Lp-PLA2 are independent biomarkers of ischemic stroke. The US Food and Drug Administration (FDA) has approved two tests to determine Lp-PLA2 mass and activity for predicting stroke. In this review, we summarize the biological properties of Lp-PLA2, the detection sensitivity and limitations of Lp-PLA2 measurement, the clinical significance and association of Lp-PLA2 in ischemic stroke, and the prospects of therapeutic inhibition of Lp-PLA2 as an intervention and treatment.