MiR-214_L-1R+4 regulate gossypol-induced immune response through MyD88-dependent signaling pathway in Cyprinus carpio.

MicroRNAs (miRNAs) have been demonstrated to act as crucial modulators with considerable impacts on the immune system. Cottonseed meal is often used as a protein source in aqua feed, cottonseed meal contains gossypol, which is harmful to animals. However, there is a lack of research on the role of miRNAs in fish exposed to gossypol stress. To determine the regulatory effects of miRNAs on gossypol toxicity, Cyprinus carpio were given to oral administration of 20 mg/kg gossypol for 7 days, and the gossypol concentration in the tissues was tested. Then, we detected spleen index, histology, immune enzyme activities of fish induced by gossypol. The results of miRNA sequencing revealed 8 differentially expressed miRNAs in gossypol group, and miR-214_L-1R+4 was found involved in immune response induced by gossypol. The potential targets of miR-214_L-1R+4 were predicted, and found a putative miR-214_L-1R+4 binding site in the 3'UTR of MyD88a. Furthermore, dual-luciferase reporter assays displayed miR-214_L-1R+4 decreased MyD88a expression through binding to the 3'UTR of MyD88a. Moreover, miR-214_L-1R+4 antagomir were intraperitoneally administered to C. carpio, down-regulated miR-214_L-1R+4 could increase MyD88a expression, as well as inflammatory cytokines and anti-inflammatory cytokines expression. These findings revealed that miR-214_L-1R+4 via the MyD88-dependent signaling pathway modulate the immune response to gossypol in C. carpio spleen.

Biodegradable Polyurethane Derived from Hydroxylated Polylactide with Superior Mechanical Properties.

Developing biodegradable polyurethane (PU) materials as an alternative to non-degradable petroleum-based PU is a crucial and challenging task. This study utilized lactide as the starting material to synthesize polylactide polyols (PLA-OH). PLA-based polyurethanes (PLA-PUs) were successfully synthesized by introducing PLA-OH into the PU molecular chain. A higher content of PLA-OH in the soft segments resulted in a substantial improvement in the mechanical attributes of the PLA-PUs. This study found that the addition of PLA-OH content significantly improved the tensile stress of the PU from 5.35 MPa to 37.15 MPa and increased the maximum elongation to 820.8%. Additionally, the modulus and toughness of the resulting PLA-PU were also significantly improved with increasing PLA-OH content. Specifically, the PLA-PU with 40% PLA-OH exhibited a high modulus of 33.45 MPa and a toughness of 147.18 MJ m-3. PLA-PU films can be degraded to carbon dioxide and water after 6 months in the soil. This highlights the potential of synthesizing PLA-PU using biomass-renewable polylactide, which is important in green and sustainable chemistry.

Characteristics of the gut microbiota and serum metabolites in postmenopausal women with reduced bone mineral density.

Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.

Late Holocene relative sea-level records from coral microatolls in Singapore.

Late Holocene relative sea-level (RSL) data are important to understand the drivers of RSL change, but there is a lack of precise RSL records from the Sunda Shelf. Here, we produced a Late Holocene RSL reconstruction from coral microatolls in Singapore, demonstrating for the first time the utility of Diploastrea heliopora microatolls as sea-level indicators. We produced 12 sea-level index points and three marine limiting data with a precision of < ± 0.2 m (2σ) and < ± 26 years uncertainties (95% highest density region). The data show a RSL fall of 0.31 ± 0.18 m between 2.8 and 0.6 thousand years before present (kyr BP), at rates between - 0.1 ± 0.3 and - 0.2 ± 0.7 mm/year. Surface profiles of the fossil coral microatolls suggest fluctuations in the rate of RSL fall: (1) stable between 2.8 and 2.5 kyr BP; (2) rising at ~ 1.8 kyr BP; and (3) stable from 0.8 to 0.6 kyr BP. The microatoll record shows general agreement with published, high-quality RSL data within the Sunda Shelf. Comparison to a suite of glacial isostatic adjustment (GIA) models indicate preference for lower viscosities in the mantle. However, more high quality and precise Late Holocene RSL data are needed to further evaluate the drivers of RSL change in the region and better constrain GIA model parameters.

Topoisomerase I is an evolutionarily conserved key regulator for satellite DNA transcription.

RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

First record of plastiglomerates, pyroplastics and plasticrusts along the beaches of Tamilnadu, Southeast coast of India.

Plastic litter affects coastal and marine ecosystems globally. This study represents the first record of pyroplastics and plasticrust in the beaches of Tamil Nadu, India. All samples were FTIR spectroscopically examined to confirm the polymer composition of the suspected plastics. The 16 plastic formations were found in TamilNadu, including six plastiglomerates nine pyroplastics and one plasticrust. Five types of polymers (PET, PP, PVC, PA, and PE) were found on the plastic matrices. The study also revealed that pyroplastics and plasticrust formed by degradation of plastics through weathering in the coastal environment. The present study also found that four types of marine fouling organisms such as oyster larvae, bryozoan, barnacle and polychaete worm were encrusted on the two pyroplastics. The emergence of these new forms of plastic raises concerns about their interactions with the environment and biota.

Breathable Dual-Mode Leather-Like Nanotextile for Efficient Daytime Radiative Cooling and Heating.

Incorporating passive radiative cooling and heating into personal thermal management has attracted tremendous attention. However, most current thermal management materials are usually monofunctional with a narrow temperature regulation range, and lack breathability, softness, and stretchability, resulting in a poor wearer experience and limited application scenarios. Herein, a breathable dual-mode leather-like nanotextile (LNT) with asymmetrical wrinkle photonic microstructures and Janus wettability for highly efficient personal thermal management is developed via a one-step electrospinning technique. The LNT is synthesized by self-bonding a hydrophilic cooling layer with welding fiber networks onto a hydrophobic photothermal layer, constructing bilayer wrinkle structures that offer remarkable optical properties, a wetting gradient, and unique textures. The resultant LNT exhibits efficient cooling capacity (22.0 °C) and heating capacity (22.1 °C) under sunlight, expanding the thermal management zone (28.3 °C wider than typical textiles). Additionally, it possesses favorable breathability, softness, stretchability, and sweat-wicking capability. Actual wearing tests demonstrate that the LNT can provide a comfortable microenvironment for the human body (1.6-8.0 °C cooler and 1.0-7.1 °C warmer than typical textiles) in changing weather conditions. Such a wearable dual-mode LNT presents great potential for personal thermal comfort and opens up new possibilities for all-weather smart clothing.

Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription.

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with Multiple Myeloma.

Multiple myeloma (MM) stands as a prevalent hematological malignancy, primarily incurable, originating from plasma cell clones. MM's progression encompasses genetic abnormalities and disruptions in the bone marrow microenvironment, leading to tumor proliferation, immune dysfunction, and compromised treatment outcomes. Emerging evidence highlights the critical role of regulatory T cells (Tregs) in MM progression, suggesting that targeting Tregs could enhance immune functionality and treatment efficacy. In this study, a notable increase in Treg proportions within MM patients' bone marrow (BM) compared to healthy individuals is observed. Additionally, it is found that the bromodomain and extraterminal domain (BET) inhibitor JQ1 selectively diminishes Treg percentages in MM patients' BM and reduces TGF-ß1-induced Tregs. This reduction occurs via inhibiting cell viability and promoting apoptosis. RNA sequencing further indicates that JQ1's inhibitory impact on Tregs likely involves upregulating STAT3 and suppressing PD-1 expression. Collectively, these findings suggest JQ1's potential to modulate Tregs, bolstering the immune response in MM and introducing a promising avenue for MM immunotherapy.

Integrin subunit alpha 5 maintains mitochondrial function in ox-LDL-induced cardiac microvascular endothelial cells via activating the PI3K/AKT signaling pathway.

Cardiac microvascular endothelial cells (CMECs) assume a pivotal role in the regulation of blood flow, and their impairment precipitates a spectrum of pathological transformations. Our previous study unveiled a notable mitigation of CMECs dysfunction through the intervention of integrin subunit alpha 5 (ITGA5), a member of the integrin protein family. This study delves into the effect of ITGA5 on the mitochondrial function in CMECs and reveals the regulation pathway. CMECs were stimulated with oxidized low-density lipoprotein (ox-LDL) to mimic coronary artery disease (CAD). The effects of ITGA5 on diverse facets of CMEC behavior, encompassing viability, apoptosis, angiogenesis, oxidative stress, and mitochondrial function, was systematically ascertained. Employing the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway as a focal point of investigation, the mediation of this pathway was substantiated utilizing the PI3K inhibitor LY294002. ITGA5 overexpression exerted a mitigating influence upon the ox-LDL-induced detriment to CMECs, manifested as increased viability, angiogenesis, mitochondrial function, and diminished apoptosis and oxidative stress. The counteraction of these salubrious effects by the administration of the PI3K inhibitor attests to the engagement of the PI3K/AKT signaling pathway. Overall, this study has discerned that ITGA5 activates the PI3k/Akt signaling pathway to orchestrate mitochondrial function and diminish ox-LDL-induced CMEC dysfunction. Thus, the targeted amelioration of this cellular injury emerges as a strategically pivotal endeavor for the prevention and amelioration of this ailment.

Superhydrophobic, Highly Conductive, and Trilayered Fabric with Connected Carbon Nanotubes for Energy-Efficient Electrical Heating.

Current electrically heated fabrics provide heat in cold climates, suffer from abundant wasted radiant heat energy to the external environment, and are prone to damage by water. Thus, constructing energy-efficient and superhydrophobic conductive fabrics is in high demand. Therefore, we propose an effective and facile methodology to prepare a superhydrophobic, highly conductive, and trilayered fabric with a connected carbon nanotube (CNT) layer and a titanium dioxide (TiO2) nanoparticle heat-reflecting layer. We construct polyamide/fluorinated polyurethane (PA/FPU) nanofibrous membranes via first electrospinning, then performing blade-coating with the polyurethane (PU) solution with CNTs, and finally fabricating FPU/TiO2 nanoparticles via electrospraying. This strategy causes CNTs to be connected to form a conductive layer and enables TiO2 nanoparticles to be bound together to form a porous, heat-reflecting layer. As a consequence, the as-prepared membranes demonstrate high conductivity with an electrical conductivity of 63 S/m, exhibit rapid electric-heating capacity, and exhibit energy-efficient asymmetrical heating behavior, i.e., the heating temperature of the PA/FPU nanofibrous layer reaches more than 83 °C within 90 s at 24 V, while the heating temperature of the FPU/TiO2 layer only reaches 53 °C, as well as prominent superhydrophobicity with a water contact angle of 156°, indicating promising utility for the next generation of electrical heating textiles.

Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.

Entrapment of atmospheric particle bound heavy metals by ferns as evidenced by lead (Pb) isotope and MixSIAR: Implications for improving air quality.

Plant metal uptake can occur through both soil-root and atmospheric transfer from leaves. The latter holds potential implications for development of biofiltration systems. To explore this potential, it is crucial to understand entrapment capacity and metal sources within plants. As ferns absorb materials from atmosphere, this study focuses on two abundant fern species growing in densely populated and highly polluted regions of Eastern India. Gravimetric quantification, elemental concentration and Pb isotopic analyses were performed by segregating the ferns into distinct components: foliage dusts (loose dust (LD) and wax-bound dust (WD)) and plant tissue (leaves and roots). To understand metal sources, the study analyzes soil, and atmospheric particulates (PM10 and dust fall (DF)). Results indicate that, while LDs have soil dust influence, wax entraps atmospheric particulates and translocates them inside the leaves. Furthermore, roots demonstrate dissimilar isotopic ratios from soil, while displaying close association with atmospheric particulates. Isotopic composition and subsequent mixing model reveal dominant contribution from DF in leaves (53-73%) and roots (33-86%). Apart from DF, leaf Pb is sourced from PM10 (21-38%) with minimal contribution from soil (6-10%). Conversely, in addition to dominance from DF, roots source Pb primarily from soil (12-62%) with a meagre 2-8% contribution from PM10.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Diphylleia Grayi-Inspired Intelligent Temperature-Responsive Transparent Nanofiber Membranes.

Nanofiber membranes (NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent (TRT) membranes, which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 °C, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance (> 90%), and fast response (5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.

TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction.

BACKGROUND: The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment. MATERIALS AND METHODS: Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed. RESULTS: TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs. CONCLUSIONS: This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors. Further studies revealed that these distinct multilayering patterns in the follicular epithelium were determined by epidermal growth factor receptor (EGFR) signaling and its downstream target Pointed, a zinc-finger transcription factor. Additionally, we identified Rho kinase as a Pointed target that regulates formation of distinct multilayering patterns. These findings provide insight into how cell polarity genes and receptor tyrosine kinase signaling interact to govern epithelial cell organization and directional growth that contribute to epithelial tumor formation.

Rapid and sensitive detection of Pseudomonas aeruginosa by isothermal amplification combined with Cas12a-mediated detection.

CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.

Two-Dimensional Nanofibrous Networks by Superspreading-Based Phase Inversion for High-Efficiency Separation.

Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.