RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (Mecp2) gene. Here, we found that inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) kinase ameliorated progression of motor dysfunction after onset and prolonged the survival of Mecp2-null mice. Microglia were activated early in myeloid Mecp2-deficient mice, which was inhibited upon inactivation of RIPK1 kinase. RIPK1 inhibition in Mecp2-deficient microglia reduced oxidative stress, cytokines production and induction of SLC7A11, SLC38A1, and GLS, which mediate the release of glutamate. Mecp2-deficient microglia release high levels of glutamate to impair glutamate-mediated excitatory neurotransmission and promote increased levels of GluA1 and GluA2/3 proteins in vivo, which was reduced upon RIPK1 inhibition. Thus, activation of RIPK1 kinase in Mecp2-deficient microglia may be involved both in the onset and progression of RTT.

Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.

Maximum chirality of THz metasurfaces with quasi-bound states in the continuum.

Metasurfaces hold great promise for terahertz (THz) chiral-optical devices. Here, we proposed a chiral THz metasurface with quasi-bound state in the continuum (BIC) for maximum chirality. By exploiting structural perturbations of the dipole displacement and the diverging angle for the THz metasurface, the symmetry-protected BIC transforms into quasi-BIC. The critical coupling condition is satisfied by the introduction of graphene, enabling the theoretical maximum absorption of the quasi-BIC. Subsequently, the perturbations are balanced to obtain maximum chirality. The numerical simulations show that the THz metasurface exhibits strong linear chirality with the circular dichroism (CD) of 0.99 at the quasi-BIC. Additionally, the chiral third harmonic generation (THG) is achieved, characterized by high efficiency up to 19% and strong THG-CD as high as 0.99. It is expected that the THz metasurfaces has great potential for applications in chiral sensing and imaging.

Differential Mechanisms of Microbial As(III) and Sb(III) Oxidation and Their Contribution to Tailings Reclamation.

Mine tailings are extremely oligotrophic environments frequently contaminated with elevated As and Sb, making As(III) and Sb(III) oxidation potentially important energy sources for the tailing microbiome. Although they have been proposed to share similar metabolic pathways, a systemic comparison of the As(III) and Sb(III) oxidation mechanisms and energy utilization efficiencies requires further elucidation. In this study, we employed a combination of physicochemical, molecular, and bioinformatic analyses to compare the kinetic and genetic mechanisms of As(III) and Sb(III) oxidation as well as their respective energy efficiencies for fueling the key nutrient acquisition metabolisms. Thiobacillus and Rhizobium spp. were identified as functional populations for both As(III) and Sb(III) oxidation in mine tailings by DNA-stable isotope probing. However, these microorganisms mediated As(III) and Sb(III) oxidation via different metabolic pathways, resulting in preferential oxidation of Sb(III) over As(III). Notably, both As(III) and Sb(III) oxidation can facilitate nitrogen fixation and phosphate solubilization in mine tailings, with Sb(III) oxidation being more efficient in powering these processes. Thus, this study provided novel insights into the microbial As(III) and Sb(III) oxidation mechanisms and their respective nutrient acquisition efficiencies, which may be critical for the reclamation of mine tailings.

Phototrophic Nitrogen Fixation, a Neglected Biogeochemical Process in Mine Tailings?

Biological nitrogen fixation (BNF) has important ecological significance in mine tailing by contributing to the initial accumulation of nitrogen. In addition to chemolithotrophic and heterotrophic BNF, light may also fuel BNF in oligotrophic mine tailings. However, knowledge regarding the occurrence and ecological significance of this biogeochemical process in mine tailings remains ambiguous. The current study observed phototrophic BNF in enrichment cultures established from three primary successional stages (i.e., original tailings, biological crusts, and pioneer plants) of tailings. Notably, phototrophic BNF in tailings may be more active at vegetation stages (i.e., biological crusts and pioneering plants) than in bare tailings. DNA-stable isotope probing identified Roseomonas species as potential aerobic anoxygenic phototrophs responsible for phototrophic BNF. Furthermore, metagenomic binning as well as genome mining revealed that Roseomonas spp. contained essential genes involved in nitrogen fixation, anoxygenic photosynthesis, and carbon fixation, suggesting their genetic potential to mediate phototrophic BNF. A causal inference framework equipped with the structural causal model suggested that the enrichment of putative phototrophic diazotrophic Roseomonas may contribute to an elevated total nitrogen content during primary succession in these mine tailings. Collectively, our findings suggest that phototrophic diazotrophs may play important roles in nutrient accumulation and hold the potential to facilitate ecological succession in tailings.

Microbial Sulfur and Arsenic Oxidation Facilitate the Establishment of Biocrusts during Reclamation of Degraded Mine Tailings.

Degraded tailings generated by the mining of metal ores are major environmental threats to the surrounding ecosystems. Tailing reclamation, however, is often impeded due to adverse environmental conditions, with depleted key nutrients (i.e., nitrogen (N) and phosphorus (P)) and elevated sulfur and metal(loid) concentrations. Formation of biocrusts may significantly accelerate nutrient accumulation and is therefore an essential stage for tailing reclamation. Although suggested to play an important role, the microbial community composition and key metabolisms in biocrusts remain largely unknown and are therefore investigated in the current study. The results suggested that sulfur and arsenic oxidation are potential energy sources utilized by members of predominant biocrust bacterial families, including Beijerinckiaceae, Burkholderiaceae, Hyphomicrobiaceae, and Rhizobiaceae. Accordingly, the S and As oxidation potentials are elevated in biocrusts compared to those in their adjacent tailings. Biocrust growth, as proxied by chlorophyll concentrations, is enhanced in treatments supplemented with S and As. The elevated biocrust growth might benefit from nutrient acquisition services (i.e., nitrogen fixation and phosphorus solubilization) fueled by microbial sulfur and arsenic oxidation. The current study suggests that sulfur- and arsenic-oxidizing microorganisms may play important ecological roles in promoting biocrust formation and facilitating tailing reclamation.

Mechanisms of low cadmium accumulation in crops: A comprehensive overview from rhizosphere soil to edible parts.

Cadmium (Cd) is a toxic heavy metal often found in soil and agricultural products. Due to its high mobility, Cd poses a significant health risk when absorbed by crops, a crucial component of the human diet. This absorption primarily occurs through roots and leaves, leading to Cd accumulation in edible parts of the plant. Our research aimed to understand the mechanisms behind the reduced Cd accumulation in certain crop cultivars through an extensive review of the literature. Crops employ various strategies to limit Cd influx from the soil, including rhizosphere microbial fixation and altering root cell metabolism. Additional mechanisms include membrane efflux, specific transport, chelation, and detoxification, facilitated by metalloproteins such as the natural resistance-associated macrophage protein (Nramp) family, heavy metal P-type ATPases (HMA), zinc-iron permease (ZIP), and ATP-binding cassette (ABC) transporters. This paper synthesizes differences in Cd accumulation among plant varieties, presents methods for identifying cultivars with low Cd accumulation, and explores the unique molecular biology of Cd accumulation. Overall, this review provides a comprehensive resource for managing agricultural lands with lower contamination levels and supports the development of crops engineered to accumulate minimal amounts of Cd.

Highly-sensitive temperature sensor based on photopolymerized-waveguide embedded Mach-Zehnder interferometer.

Biology, medicine, and chemistry all rely heavily on highly sensitive optical fiber temperature sensors. To the best of our knowledge, this research introduces a unique design framework for high-performance fiber temperature sensors that helps eliminate the all-fiber interferometers' sensitivity bottleneck. A section of photopolymerized waveguide is embedded in a typical Mach-Zehnder interferomenter framework with multimode fiber-single mode fiber-multimode fiber (MSM) structure. The thermal-optical coefficient (TOC) of the photopolymerized waveguide core, which is created via the fiber-end lithography technique, differs dramatically from that of the resin cladding. Due to the considerable TOC difference, the phase difference between the interfering beams significantly increases as the temperature changes. The fundamental variables affecting temperature sensitivity are conceptually explored and experimentally verified. The suggested device achieves a typical temperature sensitivity of 1.15 nm/ ∘C in the range of 30-100 ∘C, which is about 10 times as high as that of the all-fiber MSM sensors. The suggested designing framework offers a fresh thought for creating high-performing fiber optic temperature sensors.

Lab-on-fiber: laser-induced micro-cavity for a relative humidity measurement.

The lab-on-fiber design philosophy is the foundation for creating high-performance integrated fiber sensors. Hence, this Letter proposes an ultra-compact Fabry-Perot interferometer (FPI) based on a laser-induced micro-cavity (LIMC-FPI) on a fiber end for measuring relative humidity. To our knowledge, this novel approach, named the fiber-end photopolymerization (FEP) technique, is applied to create a micro-cavity. Specifically, a pair of humidity-sensitive polymer pillars and a resin end cap obtained by FEP are integrated to generate the cavity. As the ambient humidity changes, the pillars lengthen or shorten, resulting in the spectral evolution of the LIMC-FPI. A typical humidity sensitivity of 0.18 nm/%RH is obtained experimentally. For monitoring the human breathing process, the LIMC-FPI is responsive in the breathing frequency range of 0.2 to 0.5 Hz, allowing a response and recovery time of less than 0.388 s and 1.171 s, respectively. This work introduces a fresh and cost-effective approach for developing lab-on-fiber concept-based sensors.

Exoskeleton type long-period fiber grating for cross-talk-resistance single-parameter measurement.

This paper proposes a new, to the best of our knowledge, design framework of long-period fiber grating (LPFG) sensors resistant to multi-parameter cross talk. A section of hollow quartz capillary (HQC), which acts as an exoskeleton, is periodically merged with a single-mode fiber (SMF) by the arc-discharge method. The mechanical stress in the SMF is released while the thermal stress is enhanced after a high-temperature fusion process. Under the influence of the elastic-optical effect, the refractive index of the core is periodically modulated along the axial direction to form an exoskeleton long-period fiber grating (Es-LPFG). The unique exoskeleton structure not only induces mode coupling but also enables the proposed device to resist cross talk among the strain, ambient refractive index, and vector bending. The temperature is able to be measured independently with a sensitivity of 74 pm/ ∘C. The novel Es-LPFG is promising in single-parameter sensing, mode-locked lasers, and frequency-locked gain flattening.

Microglia-neuron interactions promote chronic itch via the NLRP3-IL-1ß-GRPR axis.

BACKGROUND: Spinal astrocytes contribute to chronic itch via sensitization of itch-specific neurons expressing gastrin-releasing peptide receptor (GRPR). However, whether microglia-neuron interactions contribute to itch remains unclear. In this study, we aimed to explore how microglia interact with GRPR+ neurons and promote chronic itch. METHODS: RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin-containing domain 3) inflammasome activation and IL-1ß-IL1R1 signaling in chronic itch. Grpr-eGFP and Grpr KO mice were used to investigate microglia-GRPR+ neuron interactions. RESULTS: We observed NLRP3 inflammasome activation and IL-1ß production in spinal microglia under chronic itch conditions. Blockade of microglial activation and the NLRP3/caspase-1/IL-1ß axis attenuated chronic itch and neuronal activation. Type 1 IL-1 receptor (IL-1R1) was expressed in GRPR+ neurons, which are essential for the development of chronic itch. Our studies also find that IL-1ß+ microglia are localized in close proximity to GRPR+ neurons. Consistently, intrathecal injection of IL1R1 antagonist or exogenous IL-1ß indicate that the IL-1ß-IL-1R1 signaling pathway enhanced the activation of GRPR+ neurons. Furthermore, our results demonstrate that the microglial NLRP3/caspase-1/IL-1ß axis contributes to several different chronic itches triggered by small molecules and protein allergens from the environment and drugs. CONCLUSION: Our findings reveal a previously unknown mechanism in which microglia enhances the activation of GRPR+ neurons through the NLRP3/caspase-1/IL-1ß/IL1R1 axis. These results will provide new insights into the pathophysiology of pruritus and novel therapeutic strategies for patients with chronic itch.

Aerobic Denitrification Enhanced by Immobilized Slow-Released Iron/Activated Carbon Aquagel Treatment of Low C/N Micropolluted Water: Denitrification Performance, Denitrifying Bacterial Community Co-occurrence, and Implications.

The key limiting factors in the treatment of low C/N micropolluted water bodies are deficient essential electron donors for nitrogen removal processes. An iron/activated carbon aquagel (IACA) was synthesized as a slowly released inorganic electron donor to enhance aerobic denitrification performance in low C/N micropolluted water treatment. The denitrification efficiency in IACA reactors was enhanced by more than 56.72% and the highest of 94.12% was accomplished compared with those of the control reactors. Moreover, the CODMn removal efficiency improved by more than 34.32% in IACA reactors. The Illumina MiSeq sequencing consequence explained that the denitrifying bacteria with facultative denitrification, iron oxidation, and iron reduction function were located in the dominant species niches in the IACA reactors (e.g., Pseudomonas, Leptothrix, and Comamonas). The diversity and richness of the denitrifying bacterial communities were enhanced in the IACA reactors. Network analysis indicated that aerobic denitrifying bacterial consortia in IACA reactors presented a more complicated co-occurrence structure. The IACA reactors presented the potential for long-term denitrification operation. This study affords a pathway to utilize IACA, promoting aerobic denitrification during low C/N micropolluted water body treatment.

Chemolithotrophic Biological Nitrogen Fixation Fueled by Antimonite Oxidation May Be Widespread in Sb-Contaminated Habitats.

Nitrogen (N) deficiency in mining-contaminated habitats usually hinders plant growth and thus hampers tailing revegetation. Biological N fixation (BNF) is an essential biogeochemical process that contributes to the initial accumulation of N in oligotrophic mining-contaminated regions. Previous studies reported that chemolithotrophic rather than heterotrophic diazotrophs frequently dominated in the mining-contaminated regions. Chemolithotrophic diazotrophs may utilize elements abundant in such habitats (e.g., sulfur (S), arsenic (As), and antimony (Sb)) as electron donors to fix N2. BNF fueled by the oxidation of S and As has been detected in previous studies. However, BNF fueled by Sb(III) oxidation (Sb-dependent BNF) has never been reported. The current study observed the presence of Sb-dependent BNF in slurries inoculated from Sb-contaminated habitats across the South China Sb belt, suggesting that Sb-dependent BNF may be widespread in this region. DNA-stable isotope probing identified bacteria associated with Rhodocyclaceae and Rhizobiaceae as putative microorganisms responsible for Sb-dependent BNF. Furthermore, metagenomic-binning demonstrated that Rhodocyclaceae and Rhizobiaceae contained essential genes involved in Sb(III) oxidation, N2 fixation, and carbon fixation, suggesting their genetic potential for Sb-dependent BNF. In addition, meta-analysis indicated that these bacteria are widespread among Sb-contaminated habitats with different niche preferences: Rhodocyclaceae was enriched in river sediments and tailings, while Rhizobiaceae was enriched only in soils. This study may broaden our fundamental understanding of N fixation in Sb-mining regions.

H2S-activated fluorescent probe enables dual-channel fluorescence tracking of drug release in tumor cells.

Nowadays, the selective release of therapeutic drugs into tumor cells has become an important way of tumor treatment due to the high side effects of chemotherapy drugs. As one of the gas mediators, hydrogen sulfide (H2S) is closely related to cancer. Due to the high content of H2S in tumor cells, it can be used as a signaling molecule that triggers the release of drugs to achieve the selective release of therapeutic drugs. In addition, dual-channel fluorescence imaging technology can be better applied to monitor the drug delivery process and distinguish the state before and after drug release, so as to better track the effect of drug therapy. Based on this, we used NBD amines (NBD-NHR) as the recognition group of H2S and connected the tyrosine kinase inhibitor crizotinib to construct an activated dual-channel fluorescent probe CZ-NBD. After the probe enters the tumor cells, it consumes H2S and releases crizotinib, which is highly toxic to the tumor cells. Importantly, the probe displays significant fluorescence changes in different cells, enabling not only the screening of tumor cells, but also tracking and monitoring drug release and tumor cell activity. Therefore, the construction of probe CZ-NBD provides a new strategy for drug release monitoring in tumor cells.

Temporal patterns of algae in different urban lakes and their correlations with environmental variables in Xi'an, China.

Urban lakes were critical in aquatic ecology environments, but how environmental factors affected the distribution and change characteristics of algal communities in urban lakes of Xi'an city was not clearly. Here, we investigated the algal community structure of six urban lakes in Xi'an and evaluated the effects of water quality parameters on algae. The results indicated that the significant differences on physicochemical parameters existed in different urban lakes. The maximum concentration of total phosphorus in urban lakes was (0.18 ± 0.01) mg/L and there was a phenomenon of phosphorus limitation. In addition, 51 genera of algae were identified and Chlorella sp. was the dominant algal species, which was affiliated with Chlorophyta. Network analysis elucidated that each lake had a unique algal community network and the positive correlation was dominant in the interaction between algae species, illustrating that mature microbial communities existed or occupied similar niches. Redundancy analysis illustrated that environmental factors explained 47.35% variance of algal species-water quality correlation collectively, indicating that water quality conditions had a significant influence on the temporal variations of algae. Structural equation model further verified that algal community structure was directly or indirectly regulated by different water quality conditions. Our study shows that temporal patterns of algal communities can reveal the dynamics and interactions of different urban ecosystem types, providing a theoretical basis for assessing eutrophication levels and for water quality management.

Metabolic potentials of members of the class Acidobacteriia in metal-contaminated soils revealed by metagenomic analysis.

The relative abundance of Acidobacteriia correlated positively with the concentrations of arsenic (As), mercury (Hg), chromium (Cr), copper (Cu) and other metals, suggesting their adaptation of the metal-rich environments. Metagenomic binning reconstructed 29 high-quality metagenome-assembled genomes (MAGs) associated with Acidobacteriia, providing an opportunity to study their metabolic potentials. These MAGs contained genes to transform As, Hg and Cr through oxidation, reduction, efflux and demethylation, suggesting the potential of Acidobacteriia to transform such metal(loid)s. Additionally, genes associated with alleviation of acidic and metal stress were also detected in these MAGs. Acidobacteriia may have the capabilities to resist or transform metal(loid)s in acidic metal-contaminated sites. Moreover, these genes encoding metal transformation could be also identified in the Acidobacteriia-associated MAGs from five additional metal-contaminated sites across Southwest China, as well as Acidobacteriia-associated reference genomes from the NCBI database, suggesting that the capability of metal transformation may be widespread among Acidobacteriia members. This discovery provides an understanding of metabolic potentials of the Acidobacteriia in acidic metal-rich sites.

Concise Biothiol-Activatable HPQ-NBD Conjugate as a Targeted Theranostic Probe for Tumor Cells.

Cancer, as a malignant tumor, seriously endangers human health. The study of cancer diagnosis and therapy has great practical significance. The development of theranostic agents has become a very important research topic. Nevertheless, some existing agents still have imperfections, such as complex structures and difficult syntheses. Therefore, it is urgent for researchers to develop simple novel theranostic agents. In this study, the precipitated fluorophore HAPQ was used as a simple drug molecule for the first time and combined with NBD-Cl to construct a simple and efficient theranostic probe (HAPQ-NBD). The theranostic probe can distinguish between tumor cells and normal cells based on the higher levels of biothiol in tumor cells. In addition, the probe can use biothiol as a control switch to release higher levels of precipitated fluorophore HAPQ in tumor cells, leading to selective high toxicity to tumor cells, thus achieving the goal of selectively killing tumor cells. The construction of probe HAPQ-NBD provides a practical tool for the diagnosis and therapy of cancer. It is expected that the development and utilization of precipitated fluorophore will provide a new method and strategy for cancer diagnosis and therapy.

Multi-parameter sensor with high sensitivity based on a long-period fiber grating prepared by a polarization-maintaining fiber.

We propose what we believe to be a novel long-period fiber grating (LPFG) based on a polarization-maintaining fiber (PMF) and single-mode fiber. Due to the principal axis of stress, the resonance peak is strongly dependent on the polarization state of the input light. Under different polarization states, the response of the resonance peak to the change of the external environment is different. A single resonance peak can measure several physical quantities without wavelength overlap using polarization multiplexing. The experimental results show that the PMF-LPFG realizes a high sensitivity torsion and bending measurement under different polarization states (-3.27 nm/rad*m and -13.38 nm/m) and can also measure the ambient temperature (84.10 pm/°C). The PMF-LPFG unit has the advantages of small size, high sensitivity, and multi-parameter measurement. The design scheme of the sensor provides a new idea for a multi-parameter sensor.

Ultra-low sample consumption consecutive-detection method for biochemical molecules based on a whispering gallery mode with a liquid crystal microdroplet.

Ultra-low sample consumption detection has many applications in molecular biology, bioanalytical chemistry, and medical science. In this Letter, a novel, to the best of our knowledge, simple type of ultra-low sample consumption detection method based on a whispering gallery mode is proposed as a means to realize consecutive detection with a liquid crystal (LC) microdroplet for biochemical molecule detection, using deoxyribonucleic acid (DNA) as a model biomarker. The sensor consists of a 105-µm-core multimode fiber fused with a hollow capillary tube, with the LC microdroplet suspended stably in the testing solution. Its application to the detection of salmon sperm DNA yielded an adjustable measurement range of 3.75-11.25 µg/ml and a sensitivity of 0.33 nm/µg/ml. The test solution required as little as 3 nl of the sample, and the limit of detection was 1.32 µg/ml, which corresponds to the effective detection of as little as 3.96 pg of DNA. This method has great potential for application in the ultra-low sample consumption detection of biochemical molecules.

High-sensitivity strain sensor based on a helical-core long-period fiber grating.

A highly sensitive strain sensor based on a helical-core long-period fiber grating (HC-LPFG) is proposed and experimentally investigated. The helical core is fabricated in the common single-mode fiber by using a high-frequency CO2 laser and hydrogen-oxygen flame. This helical shape core of the structure experienced the highly centralized refractive index modulation, which enhances the strain sensitivity and shortens the length of the sensing area to 2 mm. Experimental results indicate that the maximum strain sensitivity of the HC-LPFG reaches -97 pm/µÉ› within the measuring range of 0-400 µÉ›.