A Conductive Binder Based on Mesoscopic Interpenetration with Polysulfides Capturing Skeleton and Redox Intermediates Network for Lithium Sulfur Batteries.

The practical application of lithium-sulfur batteries with high theoretical energy density and readily available cathode active materials is hampered by problems such as sulfur insulation, dramatic volume changes, and polysulfide shuttling. The targeted development of novel binders is the most industrialized solution to the problem of sulfur cathodes. Herein, an aqueous conductive emulsion binder with the sulfonate-containing hard elastic copolymer core and the conjugate polymer shell, which is capable of forming a bicontinuous mesoscopic interpenetrating polymer network, is synthesized and investigated. Not only can the elastic skeleton formed by the copolymer bind the active substance under drastic volume changes, but also the rich ester and cyanide groups in it can effectively capture lithium polysulfide. Meanwhile, the conducting skeleton consisting of poly(3,4-ethylenedioxythiophene) both provides the additional charge conduction pathways and acts as the redox intermediates, significantly accelerating the kinetic process of lithium polysulfide conversion. Based on the synergistic effect of the above mechanisms, the use of the prepared binder on the sulfur carbon cathode significantly improves the rate performance and cycle stability of lithium sulfur batteries.

Effects of physical activity on infertility in reproductive females.

OBJECTIVES: To explore the relationship between different types of physical activity and female infertility. METHODS: This study analyzed data from 2,796 female participants aged 18-44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors. RESULTS: We found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008). CONCLUSIONS: The relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.

Structural basis for substrate recognition by a S-adenosylhomocysteine hydrolase Lpg2021 from Legionella pneumophila.

S-Adenosyl-l-homocysteine hydrolase (SAHH) is a crucial enzyme that governs S-adenosyl methionine (SAM)-dependent methylation reactions within cells and regulates the intracellular concentration of SAH. Legionella pneumophila, the causative pathogen of Legionnaires' disease, encodes Lpg2021, which is the first identified dimeric SAHH in bacteria and is a promising target for drug development. Here, we report the structure of Lpg2021 in its ligand-free state and in complexes with adenine (ADE), adenosine (ADO), and 3-Deazaneplanocin A (DZNep). X-ray crystallography, isothermal titration calorimetry (ITC), and molecular docking were used to elucidate the binding mechanisms of Lpg2021 to its substrates and inhibitors. Virtual screening was performed to identify potential Lpg2021 inhibitors. This study contributes a novel perspective to the understanding of SAHH evolution and establishes a structural framework for designing specific inhibitors targeting pathogenic Legionella pneumophila SAHH.

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

Effects of culture temperature and light regimes on biomass and lipid accumulation of Chlamydomonas reinhardtii under carbon-rich and nitrogen-limited conditions.

This study investigated the impacts of various culture temperatures and light regimes on growth and biochemical constituents of Chlamydomonas reinhardtii under carbon-supply and nitrogen-limited conditions to improve oil production in algal cells. Results displayed that under a 30 ℃ and 150 µE/m2/s regime, there was a significant increase in biomass, total lipids, and lipid productivity. Specifically, these parameters reached 1.83 g/L, 36.25 %, and 130.73 mg/L/d, respectively. Remarkably, prolonging the photoperiod further enhanced the aforementioned three parameters, reaching peak levels of 1.92 g/L, 41.10 %, and 157.54 mg/L/d, respectively, recorded at a 24/0h photoperiod. Compared with cultures grown under normal conditions, these values displayed increments of 1.21-fold, 74.88 %, and 3.01-fold, respectively. Additionally, under optimal conditions, the soluble sugar content reached 79.72 mg/g, and the biodiesel properties were improved. These findings indicate that moderately increasing temperature, light intensity, and photoperiod could achieve the co-production of biomass, lipids, and sugars in C. reinhardtii.

Crystal structure of an aspartate aminotransferase Lpg0070 from Legionella pneumophila.

Legionella pneumophila aspartate aminotransferase (Lpg0070) is a member of the transaminase and belongs to the pyridoxal 5'-phosphate (PLP)-dependent superfamily. It is responsible for the transfer of α-amino between aspartate and α-ketoglutarate to form glutamate and oxaloacetate. Here, we report the crystal structure of Lpg0070 at the resolution of 2.14 Å and 1.7 Å, in apo-form and PLP-bound, respectively. Our structural analysis revealed the specific residues involved in the PLP binding and free form against PLP-bound supported conformational changes before substrate recognition. In vitro enzyme activity proves that the absence of the N-terminal arm reduces the enzyme activity of Lpg0070. These data provide further evidence to support the N-terminal arm plays a crucial role in catalytic activity.

CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway.

The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute to airway inflammation and mucus hypersecretion. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. CTNNAL1-silenced female mice exhibit a decreased level of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated and ATP-gated Cl - channel that correlates with mucus hypersecretion. Our previous study demonstrated that ROCK1 expression decreases but ROCK2 expression increases in the lungs of a CTNNAL1-silenced mouse model. Inhibition of ROCK1 leads to a reduction in CFTR expression in CTNNAL1-overexpressing and CTNNAL1-silenced human bronchial epithelial (HBE) cells. It has been reported that ROCK1 is a downstream target of RhoA and that activation of RhoA increases CFTR expression after CTNNAL1 deficiency in vitro and in vivo. The above results indicate that CTNNAL1 regulates CFTR expression through the ROCK1 pathway. In addition, the expression of CFTR-associated ligand (CAL) is increased after CTNNAL1 silencing, and immunoprecipitation results confirm the interaction between ROCK1 and CAL. Inhibition of CAL does not influence ROCK1 expression but increases CFTR expression in CTNNAL1-silenced HBE cells. These data suggest that CTNNAL1 deficiency decreases CFTR expression in the HDM-induced asthma mouse model through the ROCK1-CAL signaling pathway.

Recombinant-luteinzing hormone supplementation in women during IVF/ICSI cycles with GNRH-antagonist protocol: A systematic review and meta-analysis.

The objective of this meta-analysis is to determine the beneficial effect of recombinant-luteinizing Hormone (r-LH) addition in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with gonadotropin-releasing hormone (GnRH) antagonist protocol and whether an optimal time of Recombinant-Luteinizing Hormone (r-LH) supplementation exist during the controlled of stimulation (COS). The primary outcomes are clinical Pregnancy rate and the number of oocytes retrieved. Secondary outcomes are the number of metaphase II oocytes, miscarriage rate and live birth rate. Results show that supplementation of LH generated a greater number of oocytes retrieved than patients who did not receive LH supplementation, but it did not help with other pregnancy outcomes. Furthermore, the result of the subgroup analysis revealed no significant difference in the outcomes with different LH addition times.

Current Status and Correlation of Physical Activity and Tendency to Problematic Mobile Phone Use in College Students.

OBJECTIVE: To explore the effect of problematic mobile phone use on college students' physical activity and their relationships. METHODS: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students' physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students' physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS). RESULTS: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use (r = -0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001). CONCLUSIONS: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students' physical activity level was one of the important constraints of problematic mobile phone use tendency.

[Speciation and Pollution Assessment of Heavy Metals in Mangrove Surface Sediments in Jiulong River Estuary].

The speciation of heavy metals was analyzed using modified BCR four-step extraction methods to analyze the pollution of heavy metals in surface sediments collected from the mangrove wetland in Jiulong River Estuary. Subsequently, the pollution degree and the ecological risk of heavy metals were evaluated by using the ratio of secondary phase to primary phase (RSP), risk assessment code (RAC), and modified potential ecological risk index (MRI) assessment methods. The results of BCR four-step extraction showed that Cd (52.55%) and Mn (47.71%) mainly existed in weak-acid extractable fractions. Pb, Y, and Cu mainly existed in reducible and oxidizable fractions. Ba, Tl, V, Th, Cr, As, U, Hg, Ni, Zn, and Co mainly existed in residue fractions. The results of RSP showed that the sediments were heavily polluted by Cd and Mn and moderately polluted by Pb. Cu, Y, and Co were slightly polluted, whereas Zn, Hg, As, U, Ni, Cr, Th, V, Ba, and Tl were not polluted. The results of RAC showed that Cd and Mn were high risk, whereas Co and Zn were moderate risk. Ni, Cu, Hg, and Y were slight risk, and the other elements (U, As, Pb, Cr, V, Tl, Ba, and Th) presented no risk. The MRI results showed that the comprehensive potential ecological risk of heavy metals was serious in the surface sediments, whereas Hg and Cd were the main contribution factors. Hg was a serious potential hazard, followed by Cd. Tl was a medium potential hazard, and the other elements were low potential hazards. These results demonstrated that the mangroves were polluted by heavy metals in Jiulong River Estuary, and effective strategies should be employed to remediate the mangrove sediment in the future.

Maternal Hypercholesterolemia May Involve in Preterm Birth.

Maternal hypercholesterolemia during pregnancy is associated with an increased risk of preterm birth which is defined as <37 weeks of complete gestation. However, the underlying mechanism for the association between hypercholesterolemia and preterm birth is not fully understood. Macrophage, as one of the largest cell types in the placenta, plays a very critical role in mediating inflammation and triggers labor initiation. Here, we hypothesize that macrophages can uptake maternal excessive cholesterol leading to its accumulation, resulting in a breach of the immune tolerance and precipitating labor.

Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity.

The decline of nicotinamide adenine dinucleotide (NAD) occurs in a variety of human pathologies including neurodegeneration. NAD-boosting agents can provide neuroprotective benefits. Here, we report the discovery and development of a class of potent activators (NATs) of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. We obtained the crystal structure of NAMPT in complex with the NAT, which defined the allosteric action of NAT near the enzyme active site. The optimization of NAT further revealed the critical role of K189 residue in boosting NAMPT activity. NATs effectively increased intracellular levels of NAD and induced subsequent metabolic and transcriptional reprogramming. Importantly, NATs exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity. These findings demonstrate the potential of NATs in the treatment of neurodegenerative diseases or conditions associated with NAD level decline.

Optimization of NAMPT activators to achieve in vivo neuroprotective efficacy.

NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the treatment of many diseases associated with NAD exhaustion such as neurodegenerative diseases. Herein, we present the systematic optimization of NAT, an initial hit of NAMPT activator discovered by us through high-throughput screening, based on the co-crystal structure of the NAMPT-NAT complex. Over 80 NAT derivatives have been designed and synthesized, among which compound 72 showed notably improved potency as NAMPT activator and effectively protected cultured cells from FK866-mediated toxicity. Moreover, compound 72 exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity, which renders it a promising candidate for the development of novel neuroprotective agents.

Molecular Mediators of Estrogen Reduction-induced Otolith Shedding.

OBJECTIVE: Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith. METHODS: The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression. RESULTS: The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90. CONCLUSION: Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.

Efficacy of probiotic adjuvant therapy for irritable bowel syndrome in children: A systematic review and meta-analysis.

OBJECTIVE: Irritable bowel syndrome (IBS) affects children's quality of life and learning. The purpose of this research was to systematically evaluate the efficacy of probiotic adjuvant therapy for IBS in children. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE and Clinical Trials databases were electronically searched for randomized controlled trials (RCTs) published prior to January 2021 exploring the use of probiotic adjuvant therapy for IBS in children. Strict screening and quality evaluations of the eligible articles were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using RevMan 5.4.1 and STATA 16 software. Finally, the risk of bias in the included studies was assessed with the RCT bias risk assessment tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (5.1.0). RESULTS: A total of nine RCTs were included. In children, probiotics significantly reduced the abdominal pain score (I2 = 95%, SMD = -1.15, 95% (-2.05, -0.24), P = 0.01) and Subject's Global Assessment of Relief (SGARC) score (I2 = 95%, MD = -3.84, 95% (-6.49, -1.20), P = 0.004), increased the rate of abdominal pain treatment success (I2 = 0%, RR = 3.44, 95% (1.73, 6.87), P = 0.0005) and abdominal pain relief (I2 = 40%, RR = 1.48, 95% (0.96, 2.28), P = 0.08), and reduced the frequency of abdominal pain (I2 = 2%, MD = -0.82, 95% (-1.57, -0.07), P = 0.03). However, we found that it might not be possible to relieve abdominal pain by increasing the daily intake of probiotics. CONCLUSIONS: Probiotics are effective at treating abdominal pain caused by IBS in children, however, there was no significant correlation between abdominal pain and the amount of probiotics ingested. More attention should be given to IBS in children, and a standardized evaluation should be adopted.

Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) remains the deadliest pathogenic bacteria worldwide. The search for new antibiotics to treat drug-sensitive as well as drug-resistant tuberculosis has become a priority. The essential enzyme phenylalanyl-tRNA synthetase (PheRS) is an antibacterial drug target because of the large differences between bacterial and human PheRS counterparts. In a high-throughput screening of 2148 bioactive compounds, PF-3845, which is a known inhibitor of human fatty acid amide hydrolase, was identified inhibiting Mtb PheRS at Ki ∼ 0.73 ± 0.06 µM. The inhibition mechanism was studied with enzyme kinetics, protein structural modeling, and crystallography, in comparison to a PheRS inhibitor of the noted phenyl-thiazolylurea-sulfonamide class. The 2.3-Å crystal structure of Mtb PheRS in complex with PF-3845 revealed its novel binding mode, in which a trifluoromethyl-pyridinylphenyl group occupies the phenylalanine pocket, whereas a piperidine-piperazine urea group binds into the ATP pocket through an interaction network enforced by a sulfate ion. It represents the first non-nucleoside bisubstrate competitive inhibitor of bacterial PheRS. PF-3845 inhibits the in vitro growth of Mtb H37Rv at ∼24 µM, and the potency of PF-3845 increased against an engineered strain Mtb pheS-FDAS, suggesting on target activity in mycobacterial whole cells. PF-3845 does not inhibit human cytoplasmic or mitochondrial PheRS in biochemical assay, which can be explained from the crystal structures. Further medicinal chemistry efforts focused on the piperidine-piperazine urea moiety may result in the identification of a selective antibacterial lead compound.

[VOCs Removal and Emission Monitoring of Beijing Bulk Gasoline Terminals in 2012-2019].

Bulk gasoline terminals are an important emission source of volatile organic compounds (VOCs) in cities. Beijing started to promote the installation of oil and gas recovery devices at oil storage terminals in 2006 to reduce VOCs emissions, since then VOCs emissions from the terminals have been monitored by the municipal government every year. This paper analyzes the VOCs emission characteristics of oil storage terminals in Beijing from 2012 to 2019. We found that the VOCs import concentration was 165.3 g·m-3 in 2019 and had experienced a decline-rise-decline pattern during 2012-2019. The emission concentration was 7.3 g·m-3 in 2019 and had declined continuously during the preceding eight years. The removal efficiency of VOCs of the gas recovery devices tended to be stable and ranged from 45.5% to 100%. Although the emission concentration had decreased significantly, the removal efficiency of the recovery unit at the oil storage terminals had decreased. Therefore, this paper proposed to strengthen process management, the inspection of the service life of the oil and gas recovery units, and check and maintain records. In addition, the removal efficiency index should be included in the scope of law enforcement and "double index" requirements should be implemented This paper will provide a scientific basis for the future development of atmospheric improvement measures.