Abstract
Chemical fixation of carbon dioxide (CO
2
) may be a pathway to retard the current trend of rapid global warming. However, the current economic cost of chemical fixation remains high because ...the chemical fixation of CO
2
usually requires high temperature or high pressure. The rational design of an efficient catalyst that works at ambient conditions might substantially reduce the economic cost of fixation. Here, we report the rational design of covalent organic frameworks (COFs) as efficient CO
2
fixation catalysts under ambient conditions based on the finding of “pore enrichment”, which is concluded by a detailed investigation of the 10994 COFs. The best predicted COF, Zn-Salen-COF-SDU113, is synthesized, and its efficient catalytic performance for CO
2
cycloaddition to terminal epoxide is confirmed with a yield of 98.2% and turnover number (TON) of 3068.9 under ambient conditions, which is comparable to the reported leading catalysts. Moreover, this COF achieves the cycloaddition of CO
2
to 2,3-epoxybutane under ambient conditions among all porous materials. This work provides a strategy for designing porous catalysts in the economic fixation of carbon dioxide.
Abstract
BACKGROUND
Infertility is a major issue in human reproductive health, affecting an estimated 15% of couples worldwide. Infertility can result from disorders of sex development (DSD) or from ...reproductive endocrine disorders (REDs) with onset in infancy, early childhood or adolescence. Male infertility, accounting for roughly half of all infertility cases, generally manifests as decreased sperm count (azoospermia or oligozoospermia), attenuated sperm motility (asthenozoospermia) or a higher proportion of morphologically abnormal sperm (teratozoospermia). Female infertility can be divided into several classical types, including, but not limited to, oocyte maturation arrest, premature ovarian insufficiency (POI), fertilization failure and early embryonic arrest. An estimated one half of infertility cases have a genetic component; however, most genetic causes of human infertility are currently uncharacterized. The advent of high-throughput sequencing technologies has greatly facilitated the identification of infertility-associated gene mutations in patients over the past 20 years.
OBJECTIVE AND RATIONALE
This review aims to conduct a narrative review of the genetic causes of human infertility. Loss-of-function mutation discoveries related to human infertility are summarized and further illustrated in tables. Corresponding knockout/mutated animal models of causative genes for infertility are also introduced.
SEARCH METHODS
A search of the PubMed database was performed to identify relevant studies published in English. The term ‘mutation’ was combined with a range of search terms related to the core focus of the review: infertility, DSD, REDs, azoospermia or oligozoospermia, asthenozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF), primary ciliary dyskinesia (PCD), acephalic spermatozoa syndrome (ASS), globozoospermia, teratozoospermia, acrosome, oocyte maturation arrest, POI, zona pellucida, fertilization defects and early embryonic arrest.
OUTCOMES
Our search generated ∼2000 records. Overall, 350 articles were included in the final review. For genetic investigation of human infertility, the traditional candidate gene approach is proceeding slowly, whereas high-throughput sequencing technologies in larger cohorts of individuals is identifying an increasing number of causative genes linked to human infertility. This review provides a wide panel of gene mutations in several typical forms of human infertility, including DSD, REDs, male infertility (oligozoospermia, MMAF, PCD, ASS and globozoospermia) and female infertility (oocyte maturation arrest, POI, fertilization failure and early embryonic arrest). The causative genes, their identified mutations, mutation rate, studied population and their corresponding knockout/mutated mice of non-obstructive azoospermia, MMAF, ASS, globozoospermia, oocyte maturation arrest, POI, fertilization failure and early embryonic arrest are further illustrated by tables. In this review, we suggest that (i) our current knowledge of infertility is largely obtained from knockout mouse models; (ii) larger cohorts of clinical cases with distinct clinical characteristics need to be recruited in future studies; (iii) the whole picture of genetic causes of human infertility relies on both the identification of more mutations for distinct types of infertility and the integration of known mutation information; (iv) knockout/mutated animal models are needed to show whether the phenotypes of genetically altered animals are consistent with findings in human infertile patients carrying a deleterious mutation of the homologous gene; and (v) the molecular mechanisms underlying human infertility caused by pathogenic mutations are largely unclear in most current studies.
WILDER IMPLICATIONS
It is important to use our current understanding to identify avenues and priorities for future research in the field of genetic causes of infertility as well as to apply mutation knowledge to risk prediction, genetic diagnosis and potential treatment for human infertility.
Sub-micrometer particles (0.10-1.0 μm) are of great significance to study, e.g., microvesicles and protein aggregates are targets for therapeutic intervention, and sub-micrometer fluorescent ...polystyrene (PS) particles are used as probes for diagnostic imaging. Focusing of sub-micrometer particles - precisely control over the position of sub-micrometer particles in a tightly focused stream - has a wide range of applications in the field of biology, chemistry and environment, by acting as a prerequisite step for downstream detection, manipulation and quantification. Microfluidic devices have been attracting great attention as desirable tools for sub-micrometer particle focusing, due to their small size, low reagent consumption, fast analysis and low cost. Recent advancements in fundamental knowledge and fabrication technologies have enabled microfluidic focusing of particles at sub-micrometer scale in a continuous, label-free and high-throughput manner. Microfluidic methods for the focusing of sub-micrometer particles can be classified into two main groups depending on whether an external field is applied: 1) passive methods, which utilize intrinsic fluidic properties without the need of external actuation, such as inertial, deterministic lateral displacement (DLD), viscoelastic and hydrophoretic focusing; and 2) active methods, where external fields are used, such as dielectrophoretic, thermophoretic, acoustophoretic and optical focusing. This article mainly reviews the studies on the focusing of sub-micrometer particles in microfluidic devices over the past 10 years. It aims to bridge the gap between the focusing of micrometer and nanometer scale (1.0-100 nm) particles and to improve the understanding of development progress, current advances and future prospects in microfluidic focusing techniques.
The ultrafast growth of high‐quality uniform monolayer WSe2 is reported with a growth rate of ≈26 µm s−1 by chemical vapor deposition on reusable Au substrate, which is ≈2–3 orders of magnitude ...faster than those of most 2D transition metal dichalcogenides grown on nonmetal substrates. Such ultrafast growth allows for the fabrication of millimeter‐size single‐crystal WSe2 domains in ≈30 s and large‐area continuous films in ≈60 s. Importantly, the ultrafast grown WSe2 shows excellent crystal quality and extraordinary electrical performance comparable to those of the mechanically exfoliated samples, with a high mobility up to ≈143 cm2 V−1 s−1 and ON/OFF ratio up to 9 × 106 at room temperature. Density functional theory calculations reveal that the ultrafast growth of WSe2 is due to the small energy barriers and exothermic characteristic for the diffusion and attachment of W and Se on the edges of WSe2 on Au substrate.
Ultrafast growth of high‐quality uniform monolayer WSe2 is achieved by chemical vapor deposition using Au as a reusable substrate. The growth rate is ≈2–3 orders of magnitude faster than those reported due to the small energy barriers and exothermic characteristic, and the materials show excellent crystal quality and extraordinary electrical properties comparable to those of exfoliated samples.
Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger ...protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo. In contrast, knockdown of RNF144A promoted malignant phenotypes of breast cancer cells. Quantitative proteomics and biochemical analysis revealed that RNF144A interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. Notably, the ligase activity-defective mutants of RNF144A impaired its ability to induce ubiquitination and degradation of HSPA2, and to suppress breast cancer cell proliferation, migration, and invasion as compared with its wild-type counterpart. Moreover, RNF144A-mediated suppression of breast cancer cell proliferation, migration, and invasion was rescued by ectopic HSPA2 expression. Clinically, low RNF144A and high HSPA2 expression in breast cancer patients was correlated with aggressive clinicopathological characteristics and decreased overall and disease-free survival. Collectively, these findings reveal a previously unappreciated role for RNF144A in suppression of breast cancer growth and metastasis, and identify RNF144A as the first, to our knowledge, E3 ubiquitin ligase for HSPA2 in human cancer.
Our phosphoproteomics identified that phosphorylation of EphA2 at serine 897 (pS897-EphA2) was significantly upregulated in the high metastatic nasopharyngeal carcinoma (NPC) cells relative to ...non-metastatic NPC cells. However, the role and underlying mechanism of pS897-EphA2 in cancer metastasis and stem properties maintenance remain poorly understood. In this study, we established NPC cell lines with stable expression of exogenous EphA2 and EphA2-S897A using endogenous EphA2 knockdown cells, and observed that pS897-EphA2 maintained EphA2-dependent NPC cell in vitro migration and invasion, in vivo metastasis and cancer stem properties. Using phospho-kinase antibody array to identify signaling downstream of pS897-EphA2, we found that AKT/Stat3 signaling mediated pS897-EphA2-promoting NPC cell invasion, metastasis and stem properties, and Sox-2 and c-Myc were the effectors of pS897-EphA2. Immunohistochemistry showed that pS897-EphA2 was positively correlated with NPC metastasis and negatively correlated with patient overall survival. Moreover, ERK/RSK signaling controlled serum-induced pS897-EphA2 in NPC cells. Collectively, our results demonstrate that pS897-EphA2 is indispensable for EphA2-dependent NPC cell invasion, metastasis and stem properties by activating AKT/Stat3/Sox-2 and c-Myc signaling pathway, suggesting that pS897-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.
•PS897-EphA2 is indispensable for EphA2-dependent nasopharyngeal carcinoma (NPC) cell invasion, metastasis and stemness.•AKT/Stat3/Sox-2 and c-Myc signaling pathway mediates the actions of pS897-EphA2 in NPC.•PS897-EphA2 is a predictor for patient overall survival.•PS897-EphA2 can serve as an attractive therapeutic target in NPC, opening up opportunities for developing its inhibitors.
At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in ...the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.
The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.
The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.
ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Water resources management, in particular flood control, in the Lancang‐Mekong River Basin (LMRB) faces two key challenges in the 21st century: climate change and dam construction. A large‐scale ...distributed Geomorphology‐Based Hydrological Model coupled with a simple reservoir regulation model (GBHM‐LMK‐SOP) is used to investigate the relative effects of climate change and dam construction on the flood characteristics in the LMRB. Results suggest an increase in both flood magnitude and frequency under climate change, which is more severe in the upstream basin and increases over time. However, stream regulation by dam reduces flood risk consistently throughout this century, with more obvious effects in the upstream basin where larger reservoirs will be located. The flood mitigation effect of dam regulation dominates over the flood intensification effect of climate change before 2060, but the latter emerges more prominently after 2060 and dominates the flood risk especially in the lower basin.
Key Points
The model coupled with reservoir regulation realistically simulated the effects of dams on floods in the Lancang‐Mekong River Basin
Climate change increases flood magnitude and frequency, but reservoir regulation reduces flood risk particularly in the upper basin
Combining climate change and reservoir regulation, flood risk is reduced in the upper basin but still increases in the lower basin
Plain Language Summary
In this study, we present a model‐based projection of flood risk in Lancang‐Mekong River. It is found that the basin will experience more frequent and bigger flood events in the future in response to climate change. Through reservoir regulation, flood risk can be mitigated particularly in the upper basin where large reservoirs are located. Combining climate change and reservoir regulation, flood risk is reduced in the upper basin but the increased flood magnitude and frequency from climate change still dominant in the lower basin.
Annexin A1 (ANXA1) is dysregulated in the various tumors. However, the role and mechanism of ANXA1 in the cancers are poorly understood. In this study, we first showed a clinically positive ...correlation between ANXA1 and autophagy-associated protein SQSTM1 expression in nasopharyngeal carcinoma (NPC) and ANXA1-regulating SQSTM1 expression through autophagy, and further demonstrated that ANXA1 inhibited BECN1 and ATG5-dependent autophagy in the NPC cells. Using phospho-kinase antibody array to identify signaling through which ANXA1 regulated NPC cell autophagy, we found that ANXA1-suppressed autophagy was associated with PI3K/AKT signaling activation. We also showed that ANXA1 expression was significantly increased in the NPCs with metastasis relative to NPCs without metastasis and positively correlated with lymphonode and distant metastasis; high ANXA1 expression in the NPC cells promoted in vitro tumor cell migration and invasion and in vivo metastasis. Lastly, we showed that inhibition of autophagy restored the ability of tumor cell migration and invasion, epithelial-mesenchymal transition (EMT)-like alterations and in vivo metastasis in the ANXA1 knockdown NPC cells with autophagy activation; ANXA1-suppresed autophagy induced EMT-like alterations possibly by inhibiting autophagy-mediated degradation of Snail. Our data suggest that ANXA1-suppressed autophagy promotes NPC cell migration, invasion and metastasis by activating PI3K/AKT signaling pathway, highlighting that the activation of autophagy may inhibit metastasis of NPC with high ANXA1 expression.
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