Nitrogen enrichment ameliorates the stimulatory effects of reduced salinity on photosynthesis and growth of phytoplankton assemblages in the northern South China sea.

Anthropogenic activities and climate change are exacerbating the occurrence of extreme rainfall that normally brings large amounts of nutrient-rich freshwater from the land to the sea, resulting in acute salinity decrease and nutrient increase. To evaluate the effects of such changes in salinity and nutrients, we tracked the changes in photosynthetic efficiency and growth of phytoplankton assemblages from the northern South China Sea at 5 salinity levels and at an intermediate salinity level with 3 or 4 nitrogen concentrations. The results showed that the reduction of salinity reduced the maximum photochemical quantum yield (FV/FM) of photosystem II of phytoplankton within a short-term cultivation (i.e. 24-72 h), followed by a stimulatory effect. The reducing effect of reduced salinity lasted longer in the nearshore area than in the offshore area, so the stimulatory effect occurred later in the former area. Nitrogen enrichment mitigated the negative effect of reduced salinity in short-term cultivation and showed a positive effect on FV/FM in long-term cultivation. Moreover, both reduced salinity and enriched nitrogen stimulated phytoplankton growth after an acclimation period. Our results suggest that the reduced salinity stresses phytoplankton in the short term, which is mitigated by nitrogen enrichment, but benefits them in the long term. This sheds light on how phytoplankton thrive and even flourish in coastal or estuarine environments where salinity and nutrients typically covary strongly after extreme rainfall.

The Wnt/ß-catenin signaling pathway inhibits osteoporosis by regulating the expression of TERT: an in vivo and in vitro study.

Our study was performed to investigate whether the Wingless and int-1 (Wnt) signaling pathway promotes osteogenic differentiation and inhibits apoptosis in bone marrow mesenchymal stem cells (BMSCs) by regulating telomerase reverse transcriptase (TERT) expression. An in vivo model of osteoporosis (OP) in C57BL/6J mice by bilateral ovariectomy (OVX) and an in vitro model of H2O2-induced BMSCs were established separately. Western blotting was used to detect the expression of the pathway-related proteins TERT, ß-catenin, and phosphorylated-glycogen synthase kinase-3beta (p-GSK3ß)/GSK3ß, the osteogenic-related markers osteopontin (OPN), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2), and the apoptosis-related indicators B-cell lymphoma-2 (Bcl-2) and BAX. Osteoblastic phenotypes were also evaluated by alkaline phosphatase (ALP) staining and serum ALP activity assays. Osteogenic differentiation phenotypes in mice were verified by H&E staining, micro-CT, and parameter analysis of the femur. Western blotting results showed that the expression of the pathway-related proteins TERT, ß-catenin, p-GSK3ß/GSK3ß was reduced in OVX mice and H2O2-induced BMSCs, accompanied by downregulated protein expression of osteogenic-related markers and antiapoptotic indicators and upregulated protein expression of apoptotic proteins compared to those in the control group. Mechanistic studies showed that the activation of Wnt signaling pathway in BMSCs promoted ß-catenin translocation to the nucleus, as verified by immunofluorescence and facilitated colocalization between ß-catenin and TERT, as verified by double-labeling immunofluorescence, thereby promoting osteogenic differentiation and reducing apoptosis. In summary, our experiments confirmed that the GSK3ß/ß-catenin/TERT pathway could regulate the osteogenic differentiation and apoptosis of BMSCs and that TERT might be a promising target for the future treatment of osteoporosis.

Circ_0114581 promotes osteogenic differentiation of BMSCs via the MiR-155-5p/HNRNPA3 axis.

Osteoporosis (OP) is a common metabolic bone disease characterized by deterioration of bone tissue structure, reduction of bone mass, and susceptibility to fracture. More and new suitable therapeutic targets need to be discovered. The purpose of this study was to explore the ceRNA mechanisms of circRNAs involved in osteoporosis. In this study, a competing endogenous RNA (ceRNA) regulatory network was obtained through the application of OP-related high throughput data sets. Our results provided evidence that HNRNPA3 was involved in the regulation of osteogenic differentiation in BMSCs. Testing of human bone tissues and ovariectomized mice bones proved that its expression level was negatively correlated with OP. The utilization of miRNA mimic or inhibitor proved that miR-155-5p could negatively regulate the expression of HNRNPA3, while overexpression of hsa_circ_0114581 with a circRNA overexpression vector proved that hsa_circ_0114581 could indirectly promoted HNRNPA3 expression and osteogenic differentiation by sponging hsa-miR-155-5p. A serious of luciferase reporter assay experiments further verified the binding site between miR-155-5p and HNRNPA3 and the binding site between miR-155-5p and hsa_circ_0114581. This study proved that the hsa_circ_0114581/hsa-miR-155-5p/HNRNPA3 axis was related with OP. The results reveal valuable insights into the pathogenesis of OP and noncoding RNA markers that may have a treatment role and will help to provide hypotheses for future studies.

O-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis.

Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. L-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of L-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology.

Biogeographical and Biodiversity Patterns of Marine Planktonic Bacteria Spanning from the South China Sea across the Gulf of Bengal to the Northern Arabian Sea.

Understanding the biogeographical and biodiversity patterns of bacterial communities is essential in unraveling their responses to future environmental changes. However, the relationships between marine planktonic bacterial biodiversity and seawater chlorophyll a are largely understudied. Here, we used high-throughput sequencing to study the biodiversity patterns of marine planktonic bacteria across a broad chlorophyll a gradient spanning from the South China Sea across the Gulf of Bengal to the northern Arabian Sea. We found that the biogeographical patterns of marine planktonic bacteria complied with the scenario of homogeneous selection, with chlorophyll a concentration being the key environmental selecting variable of bacteria taxa. The relative abundance of Prochlorococcus, the SAR11 clade, the SAR116 clade, and the SAR86 clade significantly decreased in habitats with high chlorophyll a concentrations (>0.5 µg/L). Free-living bacteria (FLB) and particle-associated bacteria (PAB) displayed contrasting alpha diversity and chlorophyll a relationships with a positive linear correlation for FLB but a negative correlation for PAB. We further found that PAB had a narrower niche breadth of chlorophyll a than did FLB, with far fewer bacterial taxa being favored at higher chlorophyll a concentrations. Higher chlorophyll a concentrations were linked to the enhanced stochastic drift and reduced beta diversity of PAB but to the weakened homogeneous selection, enhanced dispersal limitation, and increased beta diversity of FLB. Taken together, our findings might broaden our knowledge about the biogeography of marine planktonic bacteria and advance the understanding of bacterial roles in predicting ecosystem functioning under future environmental changes that are derived from eutrophication. IMPORTANCE One of the long-standing interests of biogeography is to explore diversity patterns and uncover their underlying mechanisms. Despite intensive studies on the responses of eukaryotic communities to chlorophyll a concentrations, we know little about how changes in seawater chlorophyll a concentrations affect free-living bacteria (FLB) and particle-associated bacteria (PAB) diversity patterns in natural systems. Our biogeography study demonstrated that marine FLB and PAB displayed contrasting diversity and chlorophyll a relationships and exhibited completely different assembly mechanisms. Our findings broaden our knowledge about the biogeographical and biodiversity patterns of marine planktonic bacteria in nature systems and suggest that PAB and FLB should be considered independently in predicting marine ecosystem functioning under future frequent eutrophication.

Protein kinase C beta relieves autism-like behavior in EN2 knockout mice via upregulation of the FTO/PGC-1α/UCP1 axis.

Increasing evidence suggests that disruption of neuron activity contributes to the autistic phenotype. Thus, we aimed in this study to explore the role of protein kinase C beta (PKCß) in the regulation of neuron activity in an autism model. The expression of PKCß in the microarray data of autism animal models was obtained from the Gene Expression Omnibus database. Then, mice with autism-like behavior were prepared in EN2 knockout (-/- ) mice. The interaction between PKCß on fat mass and obesity-associated protein (FTO) as well as between PGC-1α and uncoupling protein 1 (UCP1) were characterized. The effect of FTO on the N6 -methyladenosine (m6A) modification level of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) was assayed. Following transfection of overexpressed PKCß and/or silenced UCP1, effects of PKCß and UCP1 in autism-like behaviors in EN2-/- mice were analyzed. Results showed that PKCß was downregulated in EN2-/- mouse brain tissues or neurons. PKCß promoted the expression and stability of FTO, which downregulated the m6A modification level of PGC-1α to promote its expression. Moreover, PGC-1α positively targeted the expression of UCP1. PKCß knockdown enhanced sociability and spatial exploration ability, and reduced neuron apoptosis in EN2-/- mouse models of autism, which was reversed by UCP1 overexpression. Collectively, PKCß overexpression leads to activation of the FTO/m6A/PGC-1α/UCP1 axis, thus inhibiting neuron apoptosis and providing neuroprotection in mice with autism-like behavior.

Approaching the External Quantum Efficiency Limit in 2D Photovoltaic Devices.

2D transition metal dichalcogenides (TMDs) are promising candidates for realizing ultrathin and high-performance photovoltaic devices. However, the external quantum efficiency (EQE) and power conversion efficiency (PCE) of most 2D photovoltaic devices face great challenges in exceeding 50% and 3%, respectively, due to the low efficiency of photocarrier separation and collection. Here, this study demonstrates photovoltaic devices with defect-free interface and recombination-free channel based on 2D WS2 , showing high EQE of 92% approaching the theoretical limit and high PCE of 5.0%. The high performances are attributed to the van der Waals metal contact without interface defects and Fermi-level pinning, and the fully depleted channel without photocarrier recombination, leading to intrinsic photocarrier separation and collection with high efficiency. Furthermore, this study demonstrates that the strategy can be extended to other TMDs such as MoSe2 and WSe2 with EQE of 92% and 94%, respectively. This work proposes a universal strategy for building high-performance 2D photovoltaic devices. The nearly ideal EQE provides great potential for PCE approaching the Shockley-Queisser limit.

The importance of the compact disordered state in the fuzzy interactions between intrinsically disordered proteins.

The intrinsically disordered C-terminal domain (CTD) of protein 4.1G is able to specifically bind a 26-residue intrinsically disordered region of NuMA, forming a dynamic fuzzy complex. As one of a few cases of extremely fuzzy interactions between two intrinsically disordered proteins/regions (IDPs/IDRs) without induced folding, the principle of the binding is unknown. Here, we combined experimental and computational methods to explore the detailed mechanism of the interaction between 4.1G-CTD and NuMA. MD simulations suggest that the kinetic hub states in the structure ensemble of 4.1G-CTD are favorable in the fuzzy complex. The feature of these hub states is that the binding 'hot spot' motifs ßA and ßB exhibit ß strand propensities and are well packed to each other. The binding between 4.1G-CTD and NuMA is disrupted at low pH, which changes the intramolecular packing of 4.1G-CTD and weakens the packing between ßA and ßB motifs. Low pH conditions also lead to increased hydrodynamic radius and acceleration of backbone dynamics of 4.1G-CTD. All these results underscore the importance of tertiary structural arrangements and overall compactness of 4.1G-CTD in its binding to NuMA, i.e. the compact disordered state of 4.1G-CTD is crucial for binding. Different from the short linear motifs (SLiMs) that are often found to mediate IDP interactions, 4.1G-CTD functions as an intrinsically disordered domain (IDD), which is a functional and structural unit similar to conventional protein domains. This work sheds light on the molecular recognition mechanism of IDPs/IDRs and expands the conventional structure-function paradigm in protein biochemistry.

Why Do We "Like" on WeChat Moments: The Effects of Personality Traits and Content Characteristics.

To probe the motivational roles of hedonic gratification and social gratification in giving "Like" feedback on social media, we developed a set of novel pictures to simulate WeChat Moments. We subsequently examined how the personality trait of extraversion and stimulus content characteristics (e.g., emotional valence, personal relevance) influenced "Liking" behavior. A 2 (extraversion: extrovert group vs. introvert group) × 3 (emotional valence: positive vs. neutral vs. negative) × 2 (personal relevance: personally relevant vs. personally irrelevant)-mixed experimental design was applied to data obtained from 56 WeChat Moments users. These participants included 28 individuals with the highest extraversion scale scores (the extrovert group), and 28 individuals with the lowest extraversion scale scores (the introvert group), according to the NEO Five-Factor Inventory. Briefly, participants observed pictures on an interface similar to that of WeChat Moments and were given the option to "Like" each picture. "Like" rates and response time were then compared across groups and conditions by applying a mixed-design analysis of variance. Pearson's correlation coefficients were calculated to explore relationships between the "Like" rates under each condition and the scores for each personality trait. Compared with the neutral pictures, the positive and negative pictures were "Liked" more and less frequently, respectively (F 2, 108 = 46.22, p < 0.001). Compared with the poster-unrelated pictures, the personally related pictures were "Liked" more frequently (F 1, 54 = 19.54, p < 0.001). In the extrovert group, the frequency of "Likes" given to unrelated negative content positively associated with neuroticism (r = 0.42, p = 0.025) and negatively associated with conscientiousness (r = -0.46, p = 0.014). No correlations were observed in the introvert group. Compared with not giving "Like" feedback, participants gave "Likes" to positive and negative pictures more quickly (p = 0.035) and slowly (p < 0.001), respectively.These results support the hypothesis that hedonic gratification and social gratification motivate "Like" feedback for positive content and personally related content, respectively. "Liking" behavior was not affected by extraversion, but was related to neuroticism and conscientiousness. Content-related differences in time intervals for giving "Like" feedback in this study suggest that people do not hesitate to give "Like" feedback to positive content on WeChat Moments, yet linger in deciding to give "Like" feedback to negative content.

Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation.

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the ALPL mutations showed a significant difference between the control, mild and severe HPP phenotypes. Molecular dynamics simulations coupled with protein structure network analysis were employed to analyze the effect of single-residue variation on conformational dynamics of TNSALP dimers, and the developed machine learning model suggested that the topological network parameters could serve as a robust indicator of severe mutations. The results indicated that the severity of disease-associated mutations is often linked with mutation-induced modulation of allosteric communications in the protein. This study suggested that ALPL mutations associated with mild and more severe HPPs can exert markedly distinct effects on the protein stability and long-range network communications. By linking the disease phenotypes with dynamic and allosteric molecular signatures, the proposed integrative computational approach enabled to characterize and quantify the allosteric effects of ALPL mutations and role of allostery in the pathogenesis of HPPs.

Metagenomics reveals bacterioplankton community adaptation to long-term thermal pollution through the strategy of functional regulation in a subtropical bay.

Thermal effluents from coastal nuclear power plants have led to undesirable pollution and subsequent ecological impacts on local marine ecosystems. However, despite the ecological importance, we know little about the impacts on functionality of bacterioplankton subjected in systems with long-term thermal pollution. We used metagenomic sequencing to study of the effect of thermal pollution on bacterioplankton community metagenomics in summer in a subtropical bay located on the northern coast of the South China Sea. Thermal pollution (>15 y), which resulted in an increase in the summer seawater temperature around 8°C and caused seawater temperature up to approximate 39°C, significantly decreased bacterioplankton metabolic potentials in photosynthesis, organic carbon synthesis, and energy production. The bacterioplankton community metagenomics underwent a significant change in its structure from Synechococcus-dominant autotrophy to Alteromonas, Vibrio, and Pseudoalteromonas-dominated heterotrophy, and significantly up-regulated genes involved in organic compound degradation and dissimilatory nitrate reduction for the matter and energy acquisition under thermal pollution. Moreover, the bacterioplankton community metagenomics showed an up-regulation with heating of genes involved in DNA repair systems, heat shock responsive chaperones and proteins, and proteins involved in other biological processes, such as biofilm formation and the biosynthesis of unsaturated fatty acids and glycan, to adapt to the thermal environment. Collectively, it indicates a functional regulation of bacterioplankton adaptation to high-temperature stress, which might advance the understanding of the molecular mechanisms of community adaptation to global extreme warming in aquatic ecosystems.

Using AI chatbots to provide self-help depression interventions for university students: A randomized trial of effectiveness.

BACKGROUND: Depression impacts the lives of a large number of university students. Mobile-based therapy chatbots are increasingly being used to help young adults who suffer from depression. However, previous trials have short follow-up periods. Evidence of effectiveness in pragmatic conditions are still in lack. OBJECTIVE: This study aimed to compare chatbot therapy to bibliotherapy, which is a widely accepted and proven-useful self-help psychological intervention. The main objective of this study is to add to the evidence of effectiveness for chatbot therapy as a convenient, affordable, interactive self-help intervention for depression. METHODS: An unblinded randomized controlled trial with 83 university students was conducted. The participants were randomly assigned to either a chatbot test group (n = 41) to receive a newly developed chatbot-delivered intervention, or a bibliotherapy control group (n = 42) to receive a minimal level of bibliotherapy. A set of questionnaires was implemented as measurements of clinical variables at baseline and every 4 weeks for a period of 16 weeks, which included the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder scale (GAD-7), the Positive and Negative Affect Scale (PANAS). The Client Satisfaction Questionnaire-8 (CSQ-8) and the Working Alliance Inventory-Short Revised (WAI-SR) were used to measure satisfaction and therapeutic alliance after the intervention. Participants' self-reported adherence and feedback on the therapy chatbot were also collected. RESULTS: Participants were all university students (undergraduate students (n = 31), postgraduate students (n = 52)). They were between 19 and 28 years old (mean = 23.08, standard deviation (SD) = 1.76) and 55.42% (46/83) female. 24.07% (20/83) participants were lost to follow-up. No significant group difference was found at baseline. In the intention-to-treat analysis, individuals in the chatbot test group showed a significant reduction in the PHQ-9 scores (F = 22.89; P < 0.01) and the GAD-7 scores (F = 5.37; P = 0.02). Follow-up analysis of completers suggested that the reduction of anxiety was significant only in the first 4 weeks. The WAI-SR scores in the chatbot group were higher compared to the bibliotherapy group (t = 7.29; P < 0.01). User feedback showed that process factors were more influential than the content factors. CONCLUSIONS: The chatbot-delivered self-help depression intervention was proven to be superior to the minimal level of bibliotherapy in terms of reduction on depression, anxiety, and therapeutic alliance achieved with participants.

Microzooplankton grazing and its key group composition in subtropical eutrophic coast of Southern China: in relation to environmental changes.

Microzooplanton play a crucial role in marine ecosystems, as they transfer matter and energy from pico- and nano-phytoplankton to mesozooplankton. In this study, we explored the seasonal variations of microzooplankton grazing derived from dilution experiments in a typical eutrophic coast of Southern China, as well as the abundance and biodiversity of its key group (ciliate), to further understand its function in the subtropical coastal food web associated with potential regulation factors. A total of 29 ciliate species belonging to 18 genera were identified, with the dominating species of Mesodinium rubrum, Strombidium globosaneum and Strombidium conicum. The spatial difference of ciliates abundance was attributed by the changes of temperature and salinity. Phytoplankton growth rate (µ) and microzooplankton grazing rate (m) ranged from 0.03 to 1.36 d-1 and 0.10 to 1.57 d-1, respectively, and both µ and m showed the highest values in summer and the lowest in winter. Moreover, microzooplankton grazing pressure on the phytoplankton standing stocks and potential primary production ranged from 10% to 79% and 58% to 471%, respectively. Our results indicated that temperature is the main environmental driving force for the seasonal changes of µ and m, and that the impacts of run-offs from the Pearl River and offshore seawater intrusion from the South China Sea are responsible for the spatial-temporal variations of phytoplankton growth and microzooplankton grazing.

Human urine-derived stem cell-derived exosomal miR-21-5p promotes neurogenesis to attenuate Rett syndrome via the EPha4/TEK axis.

Rett syndrome (RTT) is a rare neurodevelopmental disorder that results in multiple disabilities. Exosomal microRNA (miRs) from urine-derived stem cells (USCs) have been shown to induce neurogenesis and aid in functional recovery from brain ischemia. In the present study, we sought to determine whether that exosomal miR-21-5p from USCs could promote early neural formation in a model of RTT. USCs were isolated and evaluated by flow cytometry. Exosomes were analyzed by transmission electron microscopy, tunable resistive pulse sensing (TRPS), and western blotting. PKH26 fluorescent dyes were used to observe intake of exosomes in vivo and in vitro. An RTT mouse model was treated with exosomes for behavioral studies. Dual-luciferase report gene assays were conducted to evaluate the relationship between miR-21-5p and Eph receptor A4 (EphA4). In vitro, treatment with exosomes from human urine-derived stem cells (USC-Exos) increased the percentage of neuron-specific class III beta-tubulin (Tuj1)+ nerve cells as well as the transcription levels of ß-III tubulin and doublecortin (DCX). A higher level of miR-21-5p was observed in USC-Exos, which promoted differentiation in NSCs by targeting the EPha4/TEK axis. In vivo, exosomal miR-21-5p improved the behavior, motor coordination, and cognitive ability of mice, facilitated the differentiation of NSCs in the subventricular zone of the lateral ventricle and promoted a marked rise in the number of DCX+ cells. Our data provide evidence that exosomal miR-21-5p from human USCs facilitate early nerve formation by regulating the EPha4/TEK axis.

miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models.

We investigated the role of microRNA (miR)-485 and its downstream signaling molecules on mediating epilepsy in cellular and rat models. We established a cellular epilepsy model by exposing hippocampal neurons to magnesium and a rat model by treating ICR mice with lithium chloride (127 mg/kg) and pilocarpine (30 mg/kg). We confirmed that miR-485 could bind and inhibit histone deacetylase 5 (HDAC5) and then measured expression of miR-485 and in mice and cells. Cells were transfected with overexpression or knockdown of miR-485, HDAC5, hypoxia-inducible factor-1alpha (HIF1α), or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme (PFKFB3) to verify their roles in apoptosis, oxidative stress, and inflammation in epileptic hippocampal neurons. Binding relationship between miR-485, HDAC5, HIF1α, and PFKFB3 was verified. Oxidative stress and inflammation marker levels in epilepsy model mice were assessed. miR-485 was downregulated and HDAC5 was upregulated in cell and animal model of epilepsy. Seizure, neuronal apoptosis, oxidative stress (increased SOD and GSH-Px expression and decreased MDA and 8-OHdG expression) and inflammation (reduced IL-1ß, TNF-α, and IL-6 expression) were reduced by miR-485 in epileptic cells. HIF1α and PFKFB3 expression was reduced by HDAC5 knockdown in cells, which was recapitulated in vivo. Thus, miR-485 alleviates neuronal damage and epilepsy by inhibiting HDAC5, HIF1α, and PFKFB3.

Photosynthetic Characteristics of Smaller and Larger Cell Size-Fractioned Phytoplankton Assemblies in the Daya Bay, Northern South China Sea.

Cell size of phytoplankton is known to influence their physiologies and, consequently, marine primary production. To characterize the cell size-dependent photophysiology of phytoplankton, we comparably explored the photosynthetic characteristics of piconano- (<20 µm) and micro-phytoplankton cell assemblies (>20 µm) in the Daya Bay, northern South China Sea, using a 36-h in situ high-temporal-resolution experiment. During the experimental periods, the phytoplankton biomass (Chl a) in the surface water ranged from 0.92 to 5.13 µg L-1, which was lower than that in bottom layer (i.e., 1.83-6.84 µg L-1). Piconano-Chl a accounted for 72% (mean value) of the total Chl a, with no significant difference between the surface and bottom layers. The maximum photochemical quantum yield (FV/FM) of Photosystem II (PS II) and functional absorption cross-section of PS II photochemistry (σPS II) of both piconano- and micro-cells assemblies varied inversely with solar radiation, but this occurred to a lesser extent in the former than in the latter ones. The σPS II of piconano- and micro-cell assemblies showed a similar change pattern to the FV/FM in daytime, but not in nighttime. Moreover, the fluorescence light curve (FLC)-derived light utilization efficiency (α) displayed the same daily change pattern as the FV/FM, and the saturation irradiance (EK) and maximal rETR (rETRmax) mirrored the change in the solar radiation. The FV/FM and σPS II of the piconano-cells were higher than their micro-counterparts under high solar light; while the EK and rETRmax were lower, no matter in what light regimes. In addition, our results indicate that the FV/FM of the micro-cell assembly varied quicker in regard to Chl a change than that of the piconano-cell assembly, indicating the larger phytoplankton cells are more suitable to grow than the smaller ones in the Daya Bay through timely modulating the PS II activity.

Signal value difference between white matter and tumor parenchyma in T1- and T2- weighted images may help differentiating solitary fibrous tumor/ hemangiopericytoma and angiomatous meningioma.

BACKGROUND: Solitary fibrous tumor / hemangiopericytoma (SFT/HPC) has a similar radiographic appearance to angiomatous meningioma (AM). However, not like angiomatous meningioma with benign outcome, SFT/HPC tend to exhibit aggressive behavior. Distinguishing them preoperatively is important for determining the treatment and follow-up plan.The aim of this study was to determine the clinical and radiographic factors that can be used to differentiate SFT/HPC from AM. METHODS: The analysis included 57 cases of SFT/ HPC and 64 cases of angiomatous meningioma. Clinical characteristics and conventional magnetic resonance imaging were evaluated via multivariate logistic regression analysis using IBM SPSS to identify the factors that distinguish SFT/HPC from angiomatous meningioma. RERULTS: Patients with SFT/HPC were younger than those with angiomatous meningioma (mean age: 47.4 years VS 54.8 years, P = 0.001). The mean maximum diameter of SFTs/ HPCs was larger than that of angiomatous meningiomas (4.9 cm VS 3.5 cm, p < 0.001). Angiomatous meningiomas were more likely with dural tail sign (p < 0.001) and serious peritumoral edema (p < 0.001) compared with SFTs/HPCs. Tumor with signal value difference between white matter and tumor parenchyma in T1- weighted images between -20 to 100 or in T2- weighted images between -220 to 20 may be, with high probability, a SFT/ HPC instead of a AM. CONCLUSION: Age, tumor size, dural tail sign, peritumoral edema, signal value difference between white matter and tumor parenchyma in T1- and T2- weighted images may help distinguishing SFT/HPC from angiomatous meningioma preoperatively.

The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach.

SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.

Comparative Dynamics and Functional Mechanisms of the CYP17A1 Tunnels Regulated by Ligand Binding.

As an important member of cytochrome P450 (CYP) enzymes, CYP17A1 is a dual-function monooxygenase with a critical role in the synthesis of many human steroid hormones, making it an attractive therapeutic target. The emerging structural information about CYP17A1 and the growing number of inhibitors for these enzymes call for a systematic strategy to delineate and classify mechanisms of ligand transport through tunnels that control catalytic activity. In this work, we applied an integrated computational strategy to different CYP17A1 systems with a panel of ligands to systematically study at the atomic level the mechanism of ligand-binding and tunneling dynamics. Atomistic simulations and binding free energy computations identify the dynamics of dominant tunnels and characterize energetic properties of critical residues responsible for ligand binding. The common transporting pathways including S, 3, and 2c tunnels were identified in CYP17A1 binding systems, while the 2c tunnel is a newly formed pathway upon ligand binding. We employed and integrated several computational approaches including the analysis of functional motions and sequence conservation, atomistic modeling of dynamic residue interaction networks, and perturbation response scanning analysis to dissect ligand tunneling mechanisms. The results revealed the hinge-binding and sliding motions as main functional modes of the tunnel dynamic, and a group of mediating residues as key regulators of tunnel conformational dynamics and allosteric communications. We have also examined and quantified the mutational effects on the tunnel composition, conformational dynamics, and long-range allosteric behavior. The results of this investigation are fully consistent with the experimental data, providing novel rationale to the experiments and offering valuable insights into the relationships between the structure and function of the channel networks and a robust atomistic model of activation mechanisms and allosteric interactions in CYP enzymes.

Interleukin-35 reduces inflammation in acute lung injury through inhibiting TLR4/NF-κB signaling pathways.

Acute lung injury (ALI) in children is a complex disease that is accompanied by an inflammatory response. The pathogenesis of ALI in children is not yet well understood. Mice with ALI exhibit inflammation of the lungs and decreased expression of interleukin (IL)-35. To investigate whether the function of IL-35 affects lipopolysaccharide (LPS)-induced ALI, IL-35 was overexpressed in cells. Enzyme-linked immunosorbent assays indicated decreased levels of IL-6 and tumor necrosis factor-α in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. Finally, toll-like receptor 4 (TLR4)/NF-κB signaling pathways were analyzed. The expression of TLR4, NF-κB p65 and NF-κB p50 were decreased, as was the degradation of NF-κB inhibitor-α, in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. The results of the present study demonstrated that IL-35 may exhibit a protective role in ALI by modulating the TLR4/NF-κB signaling pathways.