Physical hydrogels from existing polymers consisting of noncovalent interacting networks are highly desired due to their well‐controlled compositions and environmental friendliness; and therefore, ...applied as adhesives, artificial tissues, and soft machines. Nevertheless, these gels have suffered from weak mechanical strength and low water resistance. Current methodologies used to fabricate these hydrogels mainly involve the freezing–thawing process (cryogels), which are complicated in preparation and short in adjustment of polymer conformation. Here, taking the merits of noncovalent bonds in adjustability and reversibility, a solvent‐exchange strategy is developed to construct a class of exogels. Based on the exchange from a good solvent subsequently to a poor one, the intra‐ and interpolymer interactions are initially suppressed and then recovered, resulting in dissolving and cross‐linking to polymers, respectively. Key to this approach is the good solvent, which favors of a stretched polymer conformation to homogenize the network, forming cross‐linked hydrogel networks with remarkable stiffness, toughness, antiswelling properties, and thus underwater adhesive performance. The exogels highlight a facile but highly effective strategy of turning the solvent and consequently the noncovalent interactions to achieve the rational design of enhanced hydrogels and hydrogel‐based soft materials.
A solvent‐exchange strategy is developed to construct a class of stiff and antiswelling hydrogels (named as exogels). Key to this approach is the rational regulation of noncovalent interactions and thus the conformation of polymers and structure of the cross‐linked networks. Moreover, the unique sol–gel progression via solvent exchange makes exogels applicable for robust underwater adhesion.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune ...system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
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•S100A8 is dramatically upregulated in SARS-CoV-2-infected animal models and patients•A group of aberrant immature neutrophils is induced during SARS-CoV-2 infection•Immune disorder is mediated by the S100A8/A9-TLR4 pathway•S100A8/A9 inhibitor, Paquinimod, could prevent COVID-19-associated immune disorder
Guo et al. demonstrate that over-activation of S100A8/A9-TLR4 signaling results in immune imbalance and expansion of aberrant immature neutrophils during SARS-CoV-2 infection. Relevant therapeutic targets were validated in animal infection models.
Au supported on titanium silicalite-1 molecular sieve (Au/TS-1) is commonly used as the catalyst for the direct propylene epoxidation but the carbon deposition is easy to form which deactivates the ...catalyst. To address this issue, silicalite-1 molecular sieves with hollow structure (H-S-1) are synthesized through post-processing silicalite-1 molecular sieves (S-1). TS-1/S-1 and TS-1/H-S-1 composites are successfully prepared using S-1 and H-S-1 as the core, respectively. Compared to Au/TS-1, the performances of the superior Au/TS-1/S-1 and Au/TS-1/H-S-1 catalysts decrease more slowly. The underlying cause of their unique stability is investigated through TGA, NH
3
-TPD, and XPS analysis. Remarkably, the amounts of carbon deposition in Au/TS-1/H-S-1 (2.73 wt%) and Au/TS-1/S-1 (2.88 wt%) are significantly lower than that in Au/TS-1 (6.29 wt%). Moreover, the decrease in silanol groups and the increase in hydrophobicity promote product desorption and enhance PO selectivity. This study presents a promising approach for designing and synthesizing highly efficient Au/TS-1 catalysts.
The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still ...controversial whether Cas13 exhibits collateral activity in mammalian cells.
Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway.
These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.
It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. ...Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
In mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant ...PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete. Here, we demonstrate that E-cadherin (E-cad) plays a crucial role in the maintenance of PFs in mice. E-cad is specifically localized to the cytomembrane of oocytes in PFs. Knockdown of E-cad in neonatal ovaries resulted in significant PF loss owing to oocyte apoptosis. In addition, the expression pattern of NOBOX is similar to that of E-cad. Knockdown of E-cad resulted in a decreased NOBOX level, whereas overexpression of Nobox partially rescued the follicle loss induced by silencing E-cad. Furthermore, E-cad governed NOBOX expression by regulating the shuttle protein, β-catenin, which acts as a transcriptional co-activator. Notably, E-cad, which is a transmembrane protein expressed in the oocytes, was also responsible for maintaining the PF structure by facilitating cell-cell adhesive contacts with surrounding pregranulosa cells. In conclusion, E-cad in oocytes of PFs plays an indispensable role in the maintenance of the PF pool by facilitating follicular structural stability and regulating NOBOX expression. These findings shed light on the physiology of sustaining female reproduction.
In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF ...pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine‐specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time‐specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice.
A diagram showing the function and regulation mechanism of LSD1 during primordial follicle formation. LSD1 regulates the transcription of autophagy adaptor and substate p62 by its H3K4me2 demethylase activity.
As a composite material, the damping energy consumption mechanism of fiber reinforced polymer-confined reinforced concrete (FRP-C RC) structure is very complex. In previous dynamic calculation ...models, the bond-slip effect for steel bars was often ignored, which would lead to a considerable error in the response of the FRP-C RC structures. In this paper, a new numerical model of FRP-C RC columns considering the bond-slip for steel bars is established using a zero-length element and nonlinear beam-column elements in the OpenSees software, and the results of the model are verified by experimental results. Based on the complex damping theory, the loss factor expression and nonlinear damping model of FRP-C RC columns with the bond slip effect are proposed. Finally, the dynamic response of FRP-C RC columns with nonlinear damping under harmonic load is calculated and compared with the results available in literature. The results show that the proposed model considering steel bars’ bond-slip can provide better prediction for dynamic response of FRP-C RC columns and make the future seismic design of FRP-C RC columns safer.
Natriuretic peptides (NPs), brain and C type NPs (BNP and CNP), were involved in the maintenance of porcine oocyte meiotic arrest. The present study investigated the effects of NPs on developmental ...competence of immature porcine oocytes with follicles of different sizes.
Follicular fluid NP levels were examined by radioimmunoassay. The developmental competence of porcine oocytes was evaluated by cleavage and blastocyst developmental rates after in vitro fertilization (IVF) or parthenogenetic activation (PA) of cumulus oocyte complexes (COCs), which were recovered from follicle with different sizes. NP levels were examined and classified according to the cleavage potential after IVF with COCs released from these follicles.
The BNP and CNP concentrations were increased with follicular size in follicular fluid and sustained at the set ranges of 3.0 - 6.0 mm follicles compared to 6.1 - 8.0 mm follicles. The oocytes developed from 3.0 to 6.0 mm follicles demonstrated increased embryo cleavage and blastocyst ratios after IVF, with an increased follicle size (P < 0.05). Moreover, BNP and CNP significantly promoted the blastocyst developmental rates of 3.0 - 6.0 mm follicles, but could not improve the developmental competence of oocytes from 6.1 to 8.0 mm follicles due to low NP levels. The COCs from 3.0 to 4.0 mm follicles were pre-incubated in 100 ng/ml of BNP and CNP media for 20 h before regular in vitro maturation, which demonstrated 2 to 3 folds higher developmental competencies in both PA and IVF groups compared to respective controls (P < 0.01).
The effects of BNP and CNP supplementation in the pre-maturation culture media (PMC) on porcine developmental competence from COCs in follicles of different sizes were different and improved the developmental competence of porcine oocytes from small antral follicle in vitro.
BackgroundRemnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the association between ...RC and unstable carotid plaque remains unclear. Our primary objective is to ascertain whether RC exhibits an independent and significant association with unstable carotid plaque in a neurologically healthy population.MethodsIn the cross-sectional study, we enrolled neurologically healthy participants who visited our centre for health checkups between 2021 and 2022. All eligible participants underwent a standardised questionnaire, physical examinations and laboratory testing. The carotid plaque was evaluated with a standard carotid ultrasound and an advanced ultrasound imaging technique called superb microvascular imaging. The correlation between lipids and unstable carotid plaque was primarily assessed utilising univariate and multivariate logistic regression.ResultsThe study totally enrolled 1100 participants who had an average age of 57.00 years (IQR: 49.00–63.00), with 67.55% being men. Among the participants, 321 (29.18%) had unstable carotid plaque. In the multivariate logistic regression analysis, higher RC had an independent association with an elevated incidence of unstable carotid plaque compared with the lowest concentrations of RC (OR=1.673, 95% CI 1.113 to 2.515, p=0.0134), but not other lipids. In addition, apolipoprotein A1 was negatively related to unstable carotid plaque (OR=0.549, 95% CI 0.364 to 0.830, p=0.0045).ConclusionsElevated concentrations of RC are independently and excellently correlated with unstable carotid plaque within a neurologically healthy population.
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