Temporal variations of bacterial and eukaryotic community in coastal waters-implications for aquaculture.

Despite increased attention to the aquaculture environment, there is still a lack of understanding regarding the significance of water quality. To address this knowledge gap, this study utilized high-throughput sequencing of 16S rRNA and 18S rRNA to examine microbial communities (bacteria and eukaryotes) in coastal water over different months through long-term observations. The goal was to explore interaction patterns in the microbial community and identify potential pathogenic bacteria and red tide organisms. The results revealed significant differences in composition, diversity, and richness of bacterial and eukaryotic operational taxonomic units (OTUs) across various months. Principal coordinate analysis (PCoA) demonstrated distinct temporal variations in bacterial and eukaryotic communities, with significant differences (P = 0.001) among four groups: F (January-April), M (May), S (June-September), and T (October-December). Moreover, a strong association was observed between microbial communities and months, with most OTUs showing a distinct temporal preference. The Kruskal-Wallis test (P < 0.05) indicated significant differences in dominant bacterial and eukaryotic taxa among months, with each group exhibiting unique dominant taxa, including potential pathogenic bacteria and red tide organisms. These findings emphasize the importance of monitoring changes in potentially harmful microorganisms in aquaculture. Network analysis highlighted positive correlations between bacteria and eukaryotes, with bacteria playing a key role in network interactions. The key bacterial genera associated with other microorganisms varied significantly (P < 0.05) across different groups. In summary, this study deepens the understanding of aquaculture water quality and offers valuable insights for maintaining healthy aquaculture practices. KEY POINTS: • Bacterial and eukaryotic communities displayed distinct temporal variations. • Different months exhibited unique potential pathogenic bacteria and red tide organisms. • Bacteria are key taxonomic taxa involved in microbial network interactions.

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.

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.

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.

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.

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.

Retracted: Effects of microRNA-494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c-myc through the p38 MAPK signaling pathway.

Medulloblastoma (MB) is the most prevalent brain tumor that occurs during childhood and originates from cerebellar granule cell precursors. Based on recent studies, the differential expression of several microRNAs is involved in MB, while the role of microRNA-494 (miR-494) in MB remains unclear. Therefore, we conducted this study to investigate the regulative role of miR-494 in MB cells via the p38 mitogen-activated protein kinase (MAPK) signaling pathway by mediating c-myc. In the current study, MB cells were collected and transfected with miR-494 mimic, miR-494 inhibitor, siRNA- c-myc, and miR-494 inhibitor + siRNA-c-myc. The expressions of miR-494, c-myc, p38 MAPK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), interleukin-6 (IL-6), metadherin (MTDH), phosphatase and tensin homolog (PTEN) and survivin were determined. Cell proliferation, cell-cycle distribution, apoptosis, migration, and invasion were evaluated. The results revealed that there was a poor expression of miR-494 and high expression of c-myc in MB tissues. C-myc was determined as the target gene of miR-494. In response to miR-494 mimic, MB cells were found to have increased Bax and PTEN expressions, as well as cell number in G1 phase and cell apoptosis and decreased c-myc, p38 MAPK, Bcl-2, MTDH, IL-6, and survivin expression and cell number count in the S phase, cell proliferation, migration, and invasion. In conclusion, the results demonstrated that the upregulation of miR-494 results in the suppression of cell proliferation, migration, and invasion, while it promotes apoptosis of MB cells through the negative mediation of c-myc, which in turn inactivates the p38 MAPK pathway.

Bacterioplankton Metacommunity Processes across Thermal Gradients: Weaker Species Sorting but Stronger Niche Segregation in Summer than in Winter in a Subtropical Bay.

Thermal effluents from nuclear power plants greatly change the environmental and ecological conditions of the receiving marine water body, but knowledge about their impact on microbial ecology is limited. Here we used high-throughput sequencing of the 16S rRNA gene to examine marine bacterioplankton metacommunity assembly across thermal gradients in two representative seasons (i.e., winter and summer) in a subtropical bay located on the northern coast of the South China Sea. We found high heterogeneity in bacterioplankton community compositions (BCCs) across thermal gradients and between seasons. The spatially structured temperature gradient created by thermal effluents was the key determinant of BCCs, but its influence differed by season. Using a metacommunity approach, we found that in the thermal discharge area, i.e., where water is frequently exchanged with surrounding seawater and thermal effluent water, the BCC spatial patterns were shaped by species sorting rather than by mass effects from surrounding seawater or by dilution of thermal effluent water by surrounding seawater. However, this effect of species sorting was weaker in summer than in winter seawater. In both seasons, the bacterioplankton community structure was predominately determined by niche sharing; however, the relative importance of niche segregation was enhanced in summer seawater. Our findings suggest that for the seasonal differences in metacommunity processes, the BCCs of subtropical summer seawater were more sensitive to temperature and were more difficult to predict than those of winter seawater in the face of different intensities of thermal impacts.IMPORTANCE Understanding the mechanisms of bacterial community assembly across environmental gradients is one of the major goals of marine microbial ecology. Thermal effluents from two nuclear power plants have been present in the subtropical Daya Bay for more than 20 years and have generated a comparatively stable and long thermal gradient (a temperature increase from 0 to 10°C). The environmental patches across thermal gradients are heterogeneous and very strongly interconnected on a microbial scale; thus, this is a useful model for the study of the metacommunity processes (i.e., patch dynamics, species sorting, mass effects, and neutral processes) that underlie marine bacterioplankton assembly. The significance of our research is to reveal how environmental conditions and dispersal-related processes interact to influence bacterioplankton metacommunity processes and their seasonal differences across thermal gradients. Our results may advance the understanding of marine microbial ecology under future conditions of global warming.

Is phosphorus a limiting factor to regulate the growth of phytoplankton in Daya Bay, northern South China Sea: a mesocosm experiment.

Previous field investigations implied a potential phosphorus (P)-limitation on the growth of phytoplankton in Daya Bay, a mesotrophic bay in the northern South China Sea. Using a total of 15 mesocosms (3 × 3 × 1.5 m, with ~10.8 m3 natural seawater containing phytoplankton assemblages for each), we found P-enrichment caused no obvious effect on phytoplankton (Chl a) growth across 8-day's cultivation in neither winter nor summer, while nitrogen (N)-enrichment greatly increased Chl a in both seasons. N plus P-enrichment further increased Chl a content. The N- or N plus P-enrichments increased the allocation of nano-Chl a but decreased micro-Chl a in most cases, with no obvious effect by P-alone. Coincided with nutrients effect on Chl a content, N- or N plus P-enrichments significantly enhanced the maximum photochemical quantum yield of Photosystem II (FV/FM) and maximum relative electron transport rate (rETRmax), but declined the non-photochemical quenching (NPQ), as well as the threshold for light saturation of electron transport (EK); again, P-enrichment had no significant effect. Moreover, the absorption cross section for PSII photochemistry (σPSII) and electron transport efficiency (α) increased due to N- or N plus P-enrichments, indicating the increased nutrients enhance the light utilization efficiency through promoting PSII light harvesting ability, and thus to enhance phytoplankton growth. Our findings indicate that N- or N plus P-enrichments rigorously fuel phytoplankton blooms regardless of N:P ratios, making a note of caution on the expected P-deficiency or P-limitation on the basis of Redfield N:P ratios in Daya Bay.

Bacterial growth efficiency in a partly eutrophicated bay of South China Sea: Implication for anthropogenic impacts and potential hypoxia events.

Bacterial metabolism plays a dual role [bacterial production (BP) and bacterial respiration (BR)] in the aquatic ecosystem and potentially leads to hypoxia in the coastal eutrophic area. Bacterial growth efficiency (BGE) is an important index showing the contribution of bacterial metabolism to marine biological production and carbon budget in the pelagic ecosystem. In this study, the spatial and seasonal variety as well as diurnal variation dynamics of BGE and associated ecological characteristics were investigated in a partly eutrophicated subtropical bay (the Daya Bay) located in the northern South China Sea. Furthermore, the relationship between bacterial metabolism and potential hypoxia event was analyzed. The average BGE was 0.14 and 0.22 in summer and winter, respectively, which was lower than the mean value ever reported in other coastal and estuarine waters. The diurnal variations of BGE and BP were widely fluctuated in the Daya Bay, with approximately 3-8 fold variation of BP and 2-3 fold variation of BR in different seasons, suggesting the importance of short-term ecological dynamics on evaluating the long-term ecological processes in the coastal waters. BR was the predominant contributor to the bacterial carbon demand; however, the variation of BGE was controlled by BP in both seasons. BGE was always high in the near-shore waters with higher eutrophic level and more active BP and BR. The bacterial metabolism could deplete dissolved oxygen (DO) in the Daya bay within about 9 days when the water body was enclosed and photosynthesis was prohibited. Therefore, low DO concentration and potential hypoxia was more likely to be found in the near-shore waters of the Daya Bay in summer, since the water was stratified and enclosed with poor water exchange capacity in this area. While in winter, hypoxia seldom occurred due to vertical mixing throughout the water column. Further biological-physical coupling research is recommended to find out the detailed formation mechanism of hypoxia in the bay, and to predict the potential hypoxia events and their environmental impacts in the future.

General synthesis of ionic-electronic coupled two-dimensional materials.

Two-dimensional (2D) AMX2 compounds are a family of mixed ionic and electronic conductors (where A is a monovalent metal ion, M is a trivalent metal, and X is a chalcogen) that offer a fascinating platform to explore intrinsic coupled ionic-electronic properties. However, the synthesis of 2D AMX2 compounds remains challenging due to their multielement characteristics and various by-products. Here, we report a separated-precursor-supply chemical vapor deposition strategy to manipulate the chemical reactions and evaporation of precursors, facilitating the successful fabrication of 20 types of 2D AMX2 flakes. Notably, a 10.4 nm-thick AgCrS2 flake shows superionic behavior at room temperature, with an ionic conductivity of 192.8 mS/cm. Room temperature ferroelectricity and reconfigurable positive/negative photovoltaic currents have been observed in CuScS2 flakes. This study not only provides an effective approach for the synthesis of multielement 2D materials with unique properties, but also lays the foundation for the exploration of 2D AMX2 compounds in electronic, optoelectronic, and neuromorphic devices.

In-Sublattice Carrier Transition Enabled Polarimetric Photodetectors with Reconfigurable Polarity Transition.

Miniaturized polarimetric photodetectors based on anisotropic two-dimensional materials attract potential applications in ultra-compact polarimeters. However, these photodetectors are hindered by the small polarization ratio values and complicated artificial structures. Here, a novel polarization photodetector based on in-sublattice carrier transition in the CdSb2Se3Br2/WSe2 heterostructure, with a giant and reconfigurable PR value, is demonstrated. The unique periodic sublattice structure of CdSb2Se3Br2 features an in-sublattice carrier transition preferred along Sb2Se3 chains. Leveraging on the in-sublattice carrier transition in the CdSb2Se3Br2/WSe2 heterostructure, gate voltage has an anisotropic modulation effect on the band alignment of heterostructure along sublattice. Consequently, the heterostructure exhibits a polarization-tunable photo-induced threshold voltage shift, which provides reconfigurable PR values from positive (unipolar regime) to negative (bipolar regime), covering all possible numbers (1→+∞/-∞→-1). Using this anisotropic photovoltaic effect, gate-tunable polarimetric imaging is successfully implemented. This work provides a new platform for developing next-generation highly polarimetric optoelectronics.

Ionic Photovoltaics-in-Memory in van der Waals Material.

The photovoltaic effect is gaining growing attention in the optoelectronics field due to its low power consumption, sustainable nature, and high efficiency. However, the photovoltaic effects hitherto reported are hindered by the stringent band-alignment requirement or inversion symmetry-breaking, and are challenging for achieving multifunctional photovoltaic properties (such as reconfiguration, nonvolatility, and so on). Here, a novel ionic photovoltaic effect in centrosymmetric CdSb2Se3Br2 that can overcome these limitations is demonstrated. The photovoltaic effect displays significant anisotropy, with the photocurrent being most apparent along the CdBr2 chains while absent perpendicular to them. Additionally, the device shows electrically-induced nonvolatile photocurrent switching characteristics. The photovoltaic effect is attributed to the modulation of the built-in electric field through the migration of Br ions. Using these unique photovoltaic properties, a highly secure circuit with electrical and optical keys is successfully implemented. The findings not only broaden the understanding of the photovoltaic mechanism, but also provide a new material platform for the development of in-memory sensing and computing devices.

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.

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.

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.

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.

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.