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"Bian, Qian"
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Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment
During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes.
During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.
Journal Article
Continuous Wavelet Transform-Based Method for High-Sensitivity Detection of Image Signals of Fluorescence Lateral Flow Assay
Fluorescence lateral flow assays (FLFA) based on quantum dot probes have attracted significant attention in recent years due to their high sensitivity and quantitative detection capabilities. FLFA requires the use of a straightforward fluorescence reader for quantitative detection. Most fluorescence readers employ narrowband filters for auxiliary imaging, which facilitates the acquisition of high-contrast signals. However, during trace detection, the weak signal from FLFA can be easily lost due to optical flux loss associated with narrowband filters, thereby indirectly diminishing detection sensitivity. To address this issue, we developed a fluorescence signal reader that employs CMOS imaging without optical filters and proposed a highly sensitive signal detection algorithm based on continuous wavelet transform (CWT) to identify weak fluorescence signals with low contrast. Experimental results demonstrate that the method achieves a fluorescence detection sensitivity for quantum dots of 10−10 mol/L, with a relative standard deviation (RSD) of < 1.45%. The designed filter-free detection system and CWT analysis algorithm were applied to various FLFA systems (including the sandwich method and the competition method), with the correlation coefficient (R2) between all detection results and sample concentration exceeding 0.997. The findings of this study offer a highly sensitive signal detection method for the precise quantification of FLFA.
Journal Article
6-PPD Quinone Inhibits Phosphatidic Acid Synthesis Associated with an Increase in Intestinal Barrier Permeability in C. elegans
6-PPD quinine (6-PPDQ) affects intestinal barrier function; however, its underlying mechanisms remain largely unknown. In the current study, we examined the role of reduction in phosphatidic acid synthesis in mediating the toxicity of 6-PPDQ in affecting intestinal barrier function. In Caenorhabditis elegans, 6-PPDQ exposure reduced the phosphatidic acid content, which was accompanied by the decreased expression of acl-5 and acl-6 encoding glycerol-3-phosphate acyltransferase. The RNAi of acl-5 and acl-6 lowered the phosphatidic acid content, enhanced intestinal permeability, and resulted in the increased accumulation of 6-PPDQ. Meanwhile, acl-5 and acl-6 RNAi caused susceptibility to 6-PPDQ toxicity by upregulating the expressions of insulin ligands and receptor genes and downregulating the expressions of daf-16 and its target genes. Moreover, the RNAi of acl-5 and acl-6 elevated the expression of let-363, and the RNAi of let-363 could reduce the expressions of insulin ligand genes and confer resistance to 6-PPDQ toxicity. The double RNAi of acl-5 and acl-6 caused more severe enhanced intestinal permeability and 6-PPDQ toxicity. Therefore, 6-PPDQ exposure potentially disrupts phosphatidic acid synthesis to affect intestinal barrier function by downregulating acl-5 and acl-6 expressions.
Journal Article
The SUN1-SPDYA interaction plays an essential role in meiosis prophase I
Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Association of telomeres with the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex composed of SUN1 and KASH5 enables telomere-led chromosome movements and telomere bouquet formation, facilitating precise pairwise alignment of homologs. Here, we identify a direct interaction between SUN1 and Speedy A (SPDYA) and determine the crystal structure of human SUN1-SPDYA-CDK2 ternary complex. Analysis of meiosis prophase I process in SPDYA-binding-deficient SUN1 mutant mice reveals that the SUN1-SPDYA interaction is required for the telomere-LINC complex connection and the assembly of a ring-shaped telomere supramolecular architecture at the nuclear envelope, which is critical for efficient homologous pairing and synapsis. Overall, our results provide structural insights into meiotic telomere structure that is essential for meiotic prophase I progression.
Telomeres attach to the nuclear envelope to facilitate homolog pairing during meiosis prophase I. Here, the authors show that SUN1 and SPDYA interact, and demonstrate that this interaction is important for telomere structure and function, and essential to mice gametogenesis.
Journal Article
Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response
Cells rapidly and extensively remodel their transcriptome in response to stress to restore homeostasis, but the underlying mechanisms are not fully understood. Here, we characterize the dynamic changes in transcriptome, epigenetics, and 3D genome organization during the integrated stress response (ISR). ISR induction triggers widespread transcriptional changes within 6 h, coinciding with increased binding of ATF4, a key transcriptional effector. Notably, ATF4 binds to hundreds of genes even under non-stress conditions, priming them for stronger activation upon stress. The transcriptional changes at ATF4-bound sites during ISR do not rely on increased H3K27 acetylation, chromatin accessibility, or rewired enhancer-promoter looping. Instead, ATF4-mediated gene activation is linked to the redistribution of CEBPγ from non-ATF4 sites to a subset of ATF4-bound regions, likely by forming an ATF4/CEBPγ heterodimer. CEBPγ preferentially targets the sites pre-occupied by ATF4, as well as genomic regions exhibiting a unique higher-order chromatin structure signature. Thus, the transcriptional responses during ISR are largely pre-wired by intrinsic chromatin properties. These findings provide critical insights into transcriptional remodeling during ISR with broader implications for other stress responses.
Cells reprogram gene expression to adapt to stress, but the mechanisms remain unclear. Here, the authors show that transcriptional responses during the integrated stress response are pre-wired by ATF4 binding and chromatin features, enabling rapid stress adaptation.
Journal Article
Systematic Review of Anastomotic Leakage Rate According to an International Grading System Following Anterior Resection for Rectal Cancer
A generally acceptable definition and a severity grading system for anastomotic leakages (ALs) following rectal resection were not available until 2010, when the International Study Group of Rectal Cancer (ISGRC) proposed a definition and a grading system for AL.
A search for published data was performed using the MEDLINE database (2000 to December 5, 2012) to perform a systematic review of the studies that described AL, grade AL according to the grading system, pool data, and determine the average rate of AL for each grade after anterior resection (AR) for rectal cancer.
A total of 930 abstracts were retrieved; 40 articles on AR, 25 articles on low AR (LAR), and 5 articles on ultralow AR (ULAR) were included in the review and analysis. The pooled overall AL rate of AR was 8.58% (2,085/24,288); the rate of the asymptomatic leakage (Grade A) was 2.57%, that of AL that required active intervention without relaparotomy (Grade B) was 2.37%, and that of AL that required relaparotomy (Grade C) was 5.40%. The pooled rate of AL that required relaparotomy was higher in AR (5.40%) than in LAR (4.70%) and in ULAR (1.81%), which could be attributed to the higher rate of protective defunctioning stoma in LAR (40.72%) and ULAR (63.44%) compared with that in AR (30.11%).
The new grading system is simple that the ALs of each grade can be easily extracted from past publications, therefore likely to be accepted and applied in future studies.
Journal Article
Cu(I)-catalysed chemo-, regio-, and stereoselective radical 1,2-carboalkynylation with two different terminal alkynes
Transition-metal-catalysed asymmetric multicomponent reactions with two similar substrates often suffer from the lack of strategies to control the chemo-, regio-, and stereoselectivity of these substrates due to the close similarity in the chemical structures and properties of each reagent. Here, we describe a Cu(I)-catalysed asymmetric radical 1,2-carboalkynylation of two different terminal alkynes and alkyl halides with high chemo-, regio-, and stereoselectivity by using sterically bulky chiral tridentate anionic
N,N,P
-ligands and modulating alkynes with different electronic properties to circumvent above-mentioned challenges. This method features good substrate scope, high functional group tolerance of two different terminal alkynes, and diverse alkyl halides, providing universal access to a series of useful axially chiral 1,3-enyne building blocks.
Transition-metal-catalyzed asymmetric multicomponent reactions with two similar substrates often suffer from the lack of strategies to control the chemo-, regio-, and stereoselectivity. Here, the authors report a Cu(I)-catalyzed asymmetric radical 1,2-carboalkynylation of two different terminal alkynes and alkyl halides with chemo-, regio-, and stereoselectivity.
Journal Article
Chinese version of the Perceived Stress Scale-10: A psychometric study in Chinese university students
Chinese university students often suffer from acute stress, which can affect their mental health. We measured and evaluated perceived stress in this population using the Simplified Chinese version of the 10-item Perceived Stress Scale (SCPSS-10). The SCPSS-10, Patient Health Questionnaire (PHQ), and Generalized Anxiety Disorder 7-item scale (GAD-7) were conducted in 1096 university students. Two weeks later, 129 participants were re-tested using the SCPSS-10. Exploratory factor analysis yielded two factors with Eigen values of 4.76 and 1.48, accounting for 62.41% of the variance. Confirmatory factor analysis demonstrated good fit of this two-factor model. The internal consistency reliability, as measured by Cronbach's α, was 0.85. The test-retest reliability coefficient was 0.7. The SCPSS-10 exhibited high correlation with the PHQ-9 and GAD-7, indicating an acceptable concurrent validity. The SCPSS-10 exhibited satisfactory psychometric properties in Chinese university students.
Journal Article
Subacute Inhalation Exposure of Mice to Ozone Induces Damage to Various Organs
Ambient ozone (O3) pollution, which has become a global problem, is associated with damage to various biological systems, as determined by many studies. However, there is limited experimental evidence regarding the systemic damage induced by O3 exposure, and there are few associated studies on mice. In the present investigation, we constructed a subacute C57BL/6J female mouse model involving exposure to 0, 0.5, 1, or 2 ppm O3 for 28 days (3 h/day). Body weights, pulmonary function, hematology, serum biochemistry, inflammatory factors, and injuries to various organs were assessed for O3-exposed mice. After O3 exposure, especially to 2 ppm O3, mice showed a loss of body weight, abnormal glucose and lipid metabolism, respiratory and nervous system injuries, an inflammatory response, and pathological changes, which supported the data reported for epidemiology studies. In addition, the IL-6 levels in bronchoalveolar lavage fluid (BALF), the lungs, the livers, the kidneys, and the brains were increased, which indicated that IL-6 was associated with the damage to various organs induced by O3 exposure. The present report highlights the pathological injury to various organs and provides a basis for further studies of the molecular mechanisms associated with O3 exposure.
Journal Article