Spermatogenesis is a highly coordinated and complex process, and is pivotal for transmitting genetic information between mammalian generations. In this study, we investigated the conservation, ...differences, and biological functions of homologous genes during spermatogenesis in Mongolia sheep, humans, cynomolgus monkey, and mice using single‐cell RNA sequencing technology. We compared X chromosome meiotic inactivation events in Mongolia sheep, humans, cynomolgus monkey, and mice to uncover the concerted activity of X chromosome genes. Subsequently, we focused on the dynamics of gene expression, key biological functions, and signaling pathways at various stages of spermatogenesis in Mongolia sheep and humans. Additionally, the ligand‐receptor networks of Mongolia sheep and humans in testicular somatic and germ cells at different developmental stages were mapped to reveal conserved germ cell‐soma communication using single‐cell resolution. These datasets provided novel information and insights to unravel the molecular regulatory mechanisms of Mongolia sheep spermatogenesis and highlight conservation in gene expression during spermatogenesis between Mongolia sheep and humans, providing a foundation for the establishment of a large mammalian disease model of male infertility.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This ...study aimed to screen patients with PE to identify the high-risk population with persistent PHTN.
Methods
This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN.
Results
The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92–8.27) and three times (OR, 2.931; 95% CI, 1.91–4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups.
Conclusion
Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study’s findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bufalin, the major active component of the traditional Chinese medicine ChanSu obtained from the skin and parotid venom glands of toads, has long been known as an anticancer agent. Recent studies ...show that microRNAs (miRs) are involved in the anticancer activities of bufalin, while long non-coding RNAs (lncRNAs) are known to interact with miRNAs to regulate various biological functions. In this paper, we investigated the possible network related to the antimetastatic effect of bufalin in prostate cancer (PCa) cells. We demonstrated that bufalin (0.05-10 µM) dose-dependently suppressed the proliferation of prostate cancer DU145 and PC3 cells with IC
values of 0.89 and 1.28 µM, respectively. Furthermore, bufalin treatment significantly suppressed the cell migration and invasion. To explore the role of lncRNAs in the antimetastatic activity of bufalin, we used an lncRNA microarray and found that HOX transcript antisense RNA (HOTAIR) was the most markedly downregulated lncRNA in bufalin-treated PCa cells. Overexpression of HOTAIR counteracted the suppressing effects of bufalin on DU145 and PC3 cells. We then predicted and verified that HOTAIR upregulated FGFR1 expression by sponging miR-520b in PCa cells. In 40 patients with PCa bone metastasis, we used in situ hybridization or immunohistochemical assay to assess the HOTAIR and FGFR1 expression, which revealed that both HOTAIR and FGFR1 expression were significantly higher in bone metastasis tissues than in the primary PCa tissues. In addition, the level of serum HOTAIR was positively associated with the levels of serum bone metabolic markers (CTx, OST, B-ALP and PINP) and may serve as a reasonable biomarker for PCa bone metastasis. Taken together, this is the first study revealing that HOTAIR promotes PCa bone metastasis, and bufalin may be a promising candidate for the treatment of this disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims The responses of functional structures in plant communities to global change drivers is predicted to be driven by both species turnover and intraspecific trait variability (ITV). However, the ...relative importance of those two drivers is not well-known, which retards our ability to predict the functional changes of plant community under global change scenarios. We hypothesized that ITV rather than species turnover would drive the nutritional responses of plant community at the initial stage after nitrogen and water enrichment. Methods We measured community weighted means (CWM) and non-weighted means (CM) of foliar N and P concentrations and N:P ratio in a temperate steppe after two years factorial N and water addition. Species composition and nutrition traits of each species were recorded in each plot. Results The impacts of N addition on community level nutrition traits were highly dependent on water conditions, as indicated by significant interactive effects between N and water addition. Nitrogen addition significantly increased CWM of foliar N, but only under ambient water condition. Water addition decreased CWM of foliar P and increased that of N:P. Consistent with our hypothesis, communities responded to both N and water addition after two years treatments mainly through ITV. Conclusions Our results highlight the importance of ITV in driving short-term responses of community functional composition to the increases of nitrogen and water availability in the temperate steppe. The existence of interactive effects of N and water addition would make it more difficult to predict the impacts of N deposition on plant-mediated biogeochemical cycling under the scenarios of precipitation regime changes than previously assumed.
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BFBNIB, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•The effect of oxytetracycline on anammox performance and microbial communities was investigated.•The changes in properties of anammox granules under oxytetracycline stress were observed.
The effect ...of oxytetracycline (OTC) on anaerobic ammonium oxidation (anammox) performance and the evolution of anammox consortia under OTC stress were analyzed in this study. Meanwhile, the level of resistance genes under OTC stress was monitored for the first time in the anammox system. The nitrogen removal capacity of anammox reactor was almost deprived within three weeks under the stress of 2mgL−1 OTC, accompanied by a significant reduction of specific anammox activity of 81.3% and heme c content of 50.1%. However, the abundance of hydrazine synthase gene was adversely affected, with a loss of 29.7%. The efflux pump antibiotic resistance genes tetA, tetB, and tetC and the enzymatic modification gene tetX were first detected in anammox mixed culture. The abundance of tetA was increased from 1.03 to 2.51%. The ratios of tetB and tetC doubled, while there was no obvious change in the ratios of tetX. Therefore, it can be inferred that anammox microorganisms resisted the biotoxicity of OTC via efflux pumping mechanism. After the withdrawal of OTC from the influent, the nitrogen removal capacity of anammox reactor recovered, and the abundance of resistance genes declined gradually.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing ...to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (
CEBPG
), a gene implicated in myeloid differentiation and AML progression.
Methods
shRNA mediated gene interference was used to down-regulate the expression of
CEBPG
in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of
CEBPG
were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of
CEBPG
was Eukaryotic translation initiation factor 4E binding protein 1 (
EIF4EBP1
), a known repressor of translation. Knockdown of
EIF4EBP1
was used to assess its potential role in AML progression downstream of
CEBPG
.
Results
We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found
CEBPG
was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found
CEBPG
was overexpressed in AML. Moreover, we observed that
CEBPG
promotes AML cell proliferation by activating
EIF4EBP1
, thus contributing to the progression of AML. These findings indicate that
CEBPG
could act as a potential therapeutic target for AML patients.
Conclusion
In summary, we systematically explored the molecular characteristics of
CEBPG
in AML and identified
CEBPG
as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for
CEBPG
in promoting AML progression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•The impact of NZVI on anammox biomass was investigated for the first time.•1–200mgL−1 NZVI did not show short-term toxicity to anammox biomass.•The presence of 20 or 50mgL−1 NZVI disturbed the ...performance of anammox reactor.•“Ca. Kuenenia” dominated the community in the presence of 1–200mgL−1 NZVI.•Genes related to iron assimilation were down-regulated at 200mgL−1 NZVI.
Given the increasing use of nanoscale zero-valent iron (NZVI) particles for environmental remediation and wastewater treatment, their potential impact on anaerobic ammonium oxidation (anammox) bacteria was investigated in this study using anammox sludge. Batch assays showed that NZVI concentrations up to 200mgL−1 did not affect anammox activity, reactive oxygen species production, and cell membrane integrity. The nitrogen removal efficiency of the continuous-flow reactor fluctuated in the presence of 20 or 50mgL−1 NZVI, but it could return to normal over time, even at 200mgL−1 NZVI. 16S rDNA-based high-throughput sequencing indicated that although the presence of 10, 20, 50, and 200mgL−1 NZVI to some extent affected microbial composition, the anammox bacteria (Candidatus Kuenenia) never lost its dominance. The abundance of gene families that are related to the assimilation and utilization of iron was down-regulated in response to the stress of high-level NZVI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The interaction of paeoniflorin with human serum albumin (HSA) was investigated using fluorescence, UV–vis absorption, circular dichroism (CD) spectra and molecular docking techniques under ...simulative physiological conditions. The results clarified that the fluorescence quenching of HSA by paeoniflorin was a static quenching process and energy transfer as a result of a newly formed complex (1:1). Paeoniflorin spontaneously bound to HSA in site I (subdomain IIA), which was primarily driven by hydrophobic forces and hydrogen bonds (ΔH° = − 9.98 kJ mol
−1
, ΔS° = 28.18 J mol
−1
K
−1
). The binding constant was calculated to be 1.909 × 10
3
L mol
−1
at 288 K and it decreased with the increase of the temperature. The binding distance was estimated to be 1.74 nm at 288 K, showing the occurrence of fluorescence energy transfer. The results of CD and three-dimensional fluorescence spectra showed that paeoniflorin induced the conformational changes of HSA. Meanwhile, the study of molecular docking also indicated that paeoniflorin could bind to the site I of HSA mainly by hydrophobic and hydrogen bond interactions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
20(S)‐protopanaxadiol (PPD)‐type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer ...cells, which suggests that they have anti‐cancer activity. Anti‐angiogenesis is a promising therapeutic approach for controlling angiogenesis‐related diseases such as malignant tumors, age‐related macular degeneration, and atherosclerosis. Studies showed that 20(S)‐PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)‐PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)‐PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)‐PPD induces apoptosis in HUVECs for the first time. We found that caspase‐9 and its downstream caspase, caspase‐3, were cleaved into their active forms after 20(S)‐PPD treatment. Treatment with 20(S)‐PPD decreased the level of Bcl‐2 expression but did not change the level of Bax expression. 20(S)‐PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R‐like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP‐homologous protein (CHOP) expression increased after treatment with 20(S)‐PPD. Furthermore, siRNA‐mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)‐PPD‐induced apoptosis. Collectively, our findings show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)‐PPD could be used to treat angiogenesis‐related diseases.
In this study, we show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Soil nematodes play a fundamental role in regulating ecosystem carbon and nutrient cycling. It is widely recognized that soil nematode community composition is sensitive to nutrient ...enrichment, but the linkage between community assembly processes and functional changes under nutrient enrichment condition remains poorly understood.
Methods
We examined the compositional and functional responses and quantified the role of main community assembly processes (genus losses, genus gains, and context-dependent variations of abundance) in driving the carbon budget of soil nematode communities in response to nitrogen (N) and phosphorus (P) addition in a temperate grassland.
Results
Nitrogen and P addition significantly interacted to affect nematodes abundance, biomass, and functional variables of C cycling, in that P addition increased all the variables under ambient N condition but not under N enriched condition. Soil pH, ammonium concentration, and total phosphorus concentration played important roles in driving the variations of nematode C budgets, indicating the minor role of plant community characteristics. The enhancement of all variables following P addition was caused by the increases in the abundance of common genera (e.g.
Acrobeles
,
Scutylenchus
, and
Tylencholaimus
). The variation of genus richness contributed to the P-induced increases of nematode abundance but not to the increases of carbon budgets.
Conclusions
Our results uncover the linkages between community assembly processes and the abundance and C cycling function of soil nematode community under nutrient enrichment conditions. The significant interactive effects between N and P addition highlight the complexity in predicting the compositional and functional changes in soil nematode community under a scenario of multiple-nutrient enrichment.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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