High-Q lasing in Nd3+-doped phosphate glass microsphere resonators.

Nd3+-doped glasses are the most widely used laser gain media. However, Nd3+-doped non-silica microsphere lasers generally have lower quality (Q) factors due to the presence of non-radiative energy-loss impurities in traditional glass systems. In this work, we report the first, to the best of our knowledge, Nd3+-doped phosphate glass microsphere laser with the highest Q-factor of 1.54 × 106 among all Nd3+-doped non-silica glass microsphere lasers. Whispering gallery modes in the 1020-1120-nm band can be obtained for a typical microsphere with a diameter of 82.57 µm. When the pump power exceeds the threshold of 0.17 mW, single- and multi-mode microsphere lasing can be generated under 808-nm laser diode (LD) pumping. Typical Q-factors of the phosphate glass microspheres can reach 106, which is at least an order of magnitude higher than those of other Nd3+-doped non-silica glass microsphere lasers. The Nd3+-doped phosphate glass microsphere laser reported in this work can be considered as an active optical/photonic device with low pump thresholds.

Cu2+ -Anchored Carbon Nano-Photocatalysts for Visible Water Splitting to Boost Hydrogen Cuproptosis.

Both hydrogen (H2 ) and copper ions (Cu+ ) can be used as anti-cancer treatments. However, the continuous generation of H2 molecules and Cu+ in specific sites of tumors is challenging. Here we anchored Cu2+ on carbon photocatalyst (Cu@CDCN) to allow the continuous generation of H2 and hydrogen peroxide (H2 O2 ) in tumors using the two-electron process of visible water splitting. The photocatalytic process also generated redox-active Cu-carbon centers. Meanwhile, the Cu2+ residues reacted with H2 O2 (the obstacle to the photocatalytic process) to accelerate the two-electron process of water splitting and cuprous ion (Cu+ ) generation, in which the Cu2+ residue promoted a pro-oxidant effect with glutathione through metal-reducing actions. Both H2 and Cu+ induced mitochondrial dysfunction and intracellular redox homeostasis destruction, which enabled hydrogen therapy and cuproptosis to inhibit cancer cell growth and suppress tumor growth. Our research is the first attempt to integrate hydrogen therapy and cuproptosis using metal-enhanced visible solar water splitting in nanomedicine, which may provide a safe and effective cancer treatment.

Carbon Dots Derived from Tea Polyphenols as Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) has become an emerging cancer treatment method. Choosing the photosensitizer (PS) compounds is one of the essential factors that can influence the PDT effect and action. Carbon dots (CDs) have shown great potential as photosensitizers in PDT of cancers due to their excellent biocompatibility and high generation of reactive oxygen species (ROS). Here, we used tea polyphenol as raw material for synthesized tea polyphenol carbon dots (T-CDs) that show dual emission bands of red and blue fluorescence and can efficiently generate hydroxyl radicals (OH) under mildly visible irradiation with a LED light (400-500 nm, 15 mW cm-2). The extremely low cytotoxicity and excellent biocompatibility of T-CDs without light irradiation were tested using MTT and hemolytic assay. Further, T-CDs have been shown by in vivo experiments, using a mouse breast cancer cell line (4T1) subcutaneously injected in the back of the mouse buttock as a model, to effectively inhibit the tumor cell proliferation in solid tumors and show an excellent PDT effect. In addition, pathological sections of the mice tissues after further treatment showed that the T-CDs had no apparent impact on the major organs of the mice and did not produce any side effect lesions. This work demonstrates that the as-synthesized T-CDs has the potential to be used as a PS in cancer treatment.

Fluorescent carbon dots with excellent moisture retention capability for moisturizing lipstick.

Long-lasting moisture retention is a huge challenge to humectants, and effective methods or additives for promote these functions are limited, especially nano-additives. Carbon dots (CDs) have attracted increasing research interest due to its ultra-small size, excellent optical properties and low toxicity, etc. However, most of researches have been focused on the photoexcited CDs and its subsequent photophysical and chemical processes, such as photoluminescence, photodynamic, photothermal and photocatalytic behavior. The intrinsic chemo-physical properties of the pristine CDs are not fully explored. Here, we report an excellent moisture retention capability of a new carmine cochineal-derived CDs (Car-CDs) for the first time. The relationship between the structure of Car-CDs and its moisture retention capability is revealed. More interestingly, the effective applications of Car-CDs in moisturizing lipstick are demonstrated. This work expands the research and application of CDs into a broad, new area, potentially in skin care.

UV-Vis-NIR Full-Range Responsive Carbon Dots with Large Multiphoton Absorption Cross Sections and Deep-Red Fluorescence at Nucleoli and In Vivo.

Carbon dots (CDs), with excellent optical property and cytocompatibility, are an ideal class of nanomaterials applied in the field of biomedicine. However, the weak response of CDs in the near-infrared (NIR) region impedes their practical applications. Here, UV-vis-NIR full-range responsive fluorine and nitrogen doped CDs (N-CDs-F) are designed and synthesized that own a favorable donor-π-acceptor (D-π-A) configuration and exhibit excellent two-photon (λex = 1060 nm), three-photon (λex = 1600 nm), and four-photon (λex = 2000 nm) excitation upconversion fluorescence. D-π-A-conjugated CDs prepared by solvothermal synthesis under the assistance of ammonia fluoride are reported and are endowed with larger multiphoton absorption (MPA) cross sections (3PA: 9.55 × 10-80 cm6 s2 photon-2 , 4PA: 6.32 × 10-80 cm8 s3 photon-3 ) than conventional organic compounds. Furthermore, the N-CDs-F show bright deep-red to NIR fluorescence both in vitro and in vivo, and can even stain the nucleoli of tumor cells. A plausible mechanism is proposed on the basis of the strong inter-dot and intra-dot hydrogen bonds through NH···F that can facilitate the expanding of conjugated sp2 domains, and thus not only result in lower highest occupied molecular orbital-lowest unoccupied molecular orbital energy level but also larger MPA cross sections than those of undoped CDs.

Photoactivated Fluorescence Enhancement in F,N-Doped Carbon Dots with Piezochromic Behavior.

Photoactivation in CdSe/ZnS quantum dots (QDs) on UV/Vis light exposure improves photoluminescence (PL) and photostability. However, it was not observed in fluorescent carbon quantum dots (CDs). Now, photoactivated fluorescence enhancement in fluorine and nitrogen co-doped carbon dots (F,N-doped CDs) is presented. At 1.0 atm, the fluorescence intensity of F,N-doped CDs increases with UV light irradiation (5 s-30 min), accompanied with a blue-shift of the fluorescence emission from 586 nm to 550 nm. F,N-doped CDs exhibit photoactivated fluorescence enhancement when exposed to UV under high pressure (0.1 GPa). F,N-doped CDs show reversible piezochromic behavior while applying increasing pressure (1.0 atm to 9.98 GPa), showing a pressure-triggered aggregation-induced emission in the range 1.0 atm-0.65 GPa. The photoactivated CDs with piezochromic fluorescence enhancement broadens the versatility of CDs from ambient to high-pressure conditions and enhances their anti-photobleaching.

Evolution of insect arylalkylamine N-acetyltransferases: structural evidence from the yellow fever mosquito, Aedes aegypti.

Arylalkylamine N-acetyltransferase (aaNAT) catalyzes the transacetylation from acetyl-CoA to arylalkylamines. aaNATs are involved in sclerotization and neurotransmitter inactivation in insects. Phyletic distribution analysis confirms three clusters of aaNAT-like sequences in insects: typical insect aaNAT, polyamine NAT-like aaNAT, and mosquito unique putative aaNAT (paaNAT). Here we studied three proteins: aaNAT2, aaNAT5b, and paaNAT7, each from a different cluster. aaNAT2, a protein from the typical insect aaNAT cluster, uses histamine as a substrate as well as the previously identified arylalkylamines. aaNAT5b, a protein from polyamine NAT -like aaNAT cluster, uses hydrazine and histamine as substrates. The crystal structure of aaNAT2 was determined using single-wavelength anomalous dispersion methods, and that of native aaNAT2, aaNAT5b and paaNAT7 was detected using molecular replacement techniques. All three aaNAT structures have a common fold core of GCN5-related N-acetyltransferase superfamily proteins, along with a unique structural feature: helix/helices between ß3 and ß4 strands. Our data provide a start toward a more comprehensive understanding of the structure-function relationship and physiology of aaNATs from the mosquito Aedes aegypti and serve as a reference for studying the aaNAT family of proteins from other insect species. The structures of three different types of aaNATs may provide targets for designing insecticides for use in mosquito control.

Biochemical evaluation of the decarboxylation and decarboxylation-deamination activities of plant aromatic amino acid decarboxylases.

Plant aromatic amino acid decarboxylase (AAAD) enzymes are capable of catalyzing either decarboxylation or decarboxylation-deamination on various combinations of aromatic amino acid substrates. These two different activities result in the production of arylalkylamines and the formation of aromatic acetaldehydes, respectively. Variations in product formation enable individual enzymes to play different physiological functions. Despite these catalytic variations, arylalkylamine and aldehyde synthesizing AAADs are indistinguishable without protein expression and characterization. In this study, extensive biochemical characterization of plant AAADs was performed to identify residues responsible for differentiating decarboxylation AAADs from aldehyde synthase AAADs. Results demonstrated that a tyrosine residue located on a catalytic loop proximal to the active site of plant AAADs is primarily responsible for dictating typical decarboxylase activity, whereas a phenylalanine at the same position is primarily liable for aldehyde synthase activity. Mutagenesis of the active site phenylalanine to tyrosine in Arabidopsis thaliana and Petroselinum crispum aromatic acetaldehyde synthases primarily converts the enzymes activity from decarboxylation-deamination to decarboxylation. The mutation of the active site tyrosine to phenylalanine in the Catharanthus roseus and Papaver somniferum aromatic amino acid decarboxylases changes the enzymes decarboxylation activity to a primarily decarboxylation-deamination activity. Generation of these mutant enzymes enables the production of unusual AAAD enzyme products including indole-3-acetaldehyde, 4-hydroxyphenylacetaldehyde, and phenylethylamine. Our data indicates that the tyrosine and phenylalanine in the catalytic loop region could serve as a signature residue to reliably distinguish plant arylalkylamine and aldehyde synthesizing AAADs. Additionally, the resulting data enables further insights into the mechanistic roles of active site residues.

Diverse functional evolution of serine decarboxylases: identification of two novel acetaldehyde synthases that uses hydrophobic amino acids as substrates.

BACKGROUND: Type II pyridoxal 5'-phosphate decarboxylases are an important group of phylogenetically diverse enzymes involved in amino acid metabolism. Within plants, this group of enzymes is represented by aromatic amino acid decarboxylases, glutamate decarboxylases and serine decarboxylases. Additional evolutionary divergence of plant aromatic amino acid decarboxylases has resulted in further subcategories with distinct substrate specificities and enzymatic activities. Despite shared homology, no such evolutionary divergence has been characterized within glutamate decarboxylases or serine decarboxylases (SDC). RESULTS: Comparative analysis of two previously characterized serine decarboxylase-like (SDC-like) enzymes demonstrates distinct substrate specificities despite their highly conserved primary sequence. The alternate substrate preference of these homologous SDC-like proteins indicated that functional divergence might have occurred with in SDC-like proteins. In an effort to identify additional SDC-like functional divergence, two uncharacterized SDC-like enzymes were recombinantly expressed and characterized. CONCLUSIONS: An extensive biochemical analysis of two serine decarboxylases-like recombinant proteins led to an interesting discovery; both proteins catalyze the formation of acetaldehyde derivatives from select hydrophobic amino acids substrates. Specifically, Medicago truncatula [GenBank: XP_003592128] and Cicer arietinum [GenBank: XP_004496485] catalyze the decarboxylation and oxidative deamination of phenylalanine, methionine, leucine and tryptophan to generate their corresponding acetaldehydes. The promiscuous aldehyde synthase activity of these proteins yields novel products of 4-(methylthio) butanal, 3-methylbutanal (isovaleraldehyde) and indole-3-acetaldehyde from methionine, leucine and tryptophan respectively. A comparative biochemical analysis of the Medicago truncatula and Cicer arietinum enzymes against two previously characterized SDC-like enzymes further emphasizes the unusual substrate specificity and activity of these novel aldehyde synthases. Due to the strong substrate preference towards phenylalanine, it is likely that both enzymes function as phenylacetaldehyde synthesis in vivo. However, due to their significant sequence divergence and unusual substrate promiscuity these enzymes are functionally and evolutionary divergent from canonical phenylacetaldehyde synthesis enzymes. This work further elaborates on the functional complexity of plant type II PLP decarboxylases and their roles in secondary metabolite biosynthesis.

Cuproptosis and Cuproptosis-Based Synergistic Therapy for Cancer Treatment.

Copper, as an essential trace nutrient for human, plays a crucial role in numerous cellular activities, and is vital for maintaining homeostasis in organisms. Deviations from normal intracellular copper concentration range can disrupt the cellular homeostasis and lead to cell death. Cell death is the process in which cells lose their vitality and cannot sustain normal metabolism, which has various forms. The recently discovered cuproptosis mechanism differs from the previously recognized forms, which is triggered by intracellular copper accumulation. The discovery of cuproptosis has sparked interest among researchers, and this mechanism has been applied in the treatment of various intractable diseases, including different types of cancer. However, the developed cuproptosis-based therapies have revealed certain limitations, such as low immunostimulatory efficiency, poor tumor targeting, and inhibition by the tumor microenvironment. Therefore, researchers are devoted to combining cuproptosis with existing cancer therapies to develop more effective synergistic cancer therapies. This review summarizes the latest research advancements in the cuproptosis-based therapies for various types of cancer, with a focus on the synergistic cancer therapies. Finally, it provides an outlook on the future development of cuproptosis in anti-tumor therapy.

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system.

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6.37), which preferentially selected cancerous cells with a favorable dose reduction (dose reduction index (DRI) of HCFU was 4.09). Moreover, the growth of CRC in tumor-bearing mice was effectively suppressed, with tumor suppression rates up to 94.74%, and a combination index (CI) value of less than one (CI = 0.41 for CT26 cell lines), indicating a significant synergistic therapeutic effect. Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-ß levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC.

Risk assessment and source tracing of heavy metals in major rice-producing provinces of Yangtze River Basin.

Heavy metal contamination in rice constitutes a global concern, its migration is influenced by environmental factors as well as socioeconomic activities. However, tracing its origins within complex context remains a significant challenge. The concentrations of five heavy metals (HMs) in 1754 samples from major rice-producing provinces were analyzed, and their pollution characteristics, associated health risks and temporal-spatial variations were discussed. Potential sources were classified by positive matrix factorization (PMF) models, considering correlations with human activities, climatic conditions, and interaction within ecosystems. The results showed that cadmium (Cd) and arsenic (As) were the primary contributors to pollution risk, with the borders between Hunan and central Jiangxi, as well as northeast Jiangxi and northwest Anhui, identified as critical areas for risk management. PMF serves as an effective methodology for identifying the sources of HMs in rice. Industrial activities, particularly mining and transportation, represent the predominant sources of Cd and lead (Pb), accounting for 75.6 % of the total pollution. Conversely, agricultural practices and natural factors constitute the primary sources of As, contributing to the remaining 24.4 %. It is noteworthy that the rapid industrial development has facilitated the expansion of the freight industry, consequently increasing the risk associated with Pb. Furthermore, effective governmental policy management can mitigate the risks related to HMs. Our research highlights the influence of industrial development on HMs risk in various regions and the moderating role of policy formulation. SYNOPSIS: Minimal research exists on the impact of regional economic development on heavy metals in rice. This study reports mining and transportation activities increase carcinogenic risks caused by Cd and Pb in rice during industrialization.

An acid-activatable fluorouracil prodrug for colorectal cancer synergistic therapy.

5-Fluorouracil has demonstrated certain efficiency in patients with colorectal cancer. However, significant side effects of use by injection are common. To address this issue defects, a reengineered 5'-deoxy-5-fluorocytidine (DFCR) based drug delivery system (POACa) is developed as a prominent tumor-selective nano-activator. Investigations demonstrate that the constructed nano-activator exhibits good biocompatibility and high therapeutic efficiency in mice with subcutaneous and orthotopic SW-480 colorectal tumors, as its activity is strictly dependent on the tumor-associated acid environment and thymidine phosphorylase. These strategies diminish the off-target toxicity and improve the specificity and sensitivity of human colorectal cancer cells to 5-Fu, obtaining potent efficiency by the combination of H2O2 mediated oxidative stress, calcium overload and 5-Fu-induced chemotherapy (the combination index is 0.11). Overall, the engineered nano-activator exhibits a high therapeutic index in vitro and in vivo. STATEMENT OF SIGNIFICANCE: In this study, we designed and prepared a pH-responsive polymer to synchronously deliver DFCR (5'-deoxy-5-fluorocytidine, a prodrug of 5-Fu), Ca2+ and H2O2. The constructed nano-activator was denoted as POACa. (1) To address the problem of premature leakage of cargo by physical embedding, our research modified the inactive prodrug DFCR through chemical bonding. (2) The activation of the prepared nano-activator was strictly dependent on the tumor-associated acid environment and thymidine phosphorylase, providing the drug delivery system with inherent safety. (3) A distinctly low combination index value (0.11) of CaO2 and DFCR indicated that POACa has a prominent tumor suppression effect by tumor calcium overload sensitized chemotherapy and H2O2 mediated cytotoxicity.

Biodegradable copper-iodide clusters modulate mitochondrial function and suppress tumor growth under ultralow-dose X-ray irradiation.

Both copper (Cu2+/+) and iodine (I-) are essential elements in all living organisms. Increasing the intracellular concentrations of Cu or I ions may efficiently inhibit tumor growth. However, efficient delivery of Cu and I ions into tumor cells is still a challenge, as Cu chelation and iodide salts are highly water-soluble and can release in untargeted tissue. Here we report mitochondria-targeted Cu-I cluster nanoparticles using the reaction of Cu+ and I- to form stable bovine serum albumin (BSA) radiation-induced phosphors (Cu-I@BSA). These solve the stability issues of Cu+ and I- ions. Cu-I@BSA exhibit bright radioluminescence, and easily conjugate with the emission-matched photosensitizer and targeting molecule using functional groups on the surface of BSA. Investigations in vitro and in vivo demonstrate that radioluminescence under low-dose X-ray irradiation excites the conjugated photosensitizer to generate singlet oxygen, and combines with the radiosensitization mechanism of the heavy atom of iodine, resulting in efficient tumor inhibition in female mice. Furthermore, our study reveals that BSA protection causes the biodegradable Cu-I clusters to release free Cu and I ions and induce cell death by modulating mitochondrial function, damaging DNA, disrupting the tricarboxylic acid cycle, decreasing ATP generation, amplifying oxidative stress, and boosting the Bcl-2 pathway.

Development of Machine Learning Model for Predicting Prolonged Operation Time in Lumbar Stenosis undergoing Posterior Lumbar Interbody Fusion: A Multi-center study.

BACKGROUND CONTEXT: Longer posterior lumbar interbody fusion (PLIF) surgeries for individuals with lumbar spinal stenosis are linked to more complications and negatively affect recovery after the operation. Therefore, there is a critical need for a method to accurately predict patients who are at risk for prolonged operation times. PURPOSE: This research aimed to develop a clinical model to predict prolonged operation time for patients undergoing PLIF procedures. STUDY DESIGN/SETTING: This study employs a machine-learning approach to analyze data retrospectively collected. PATIENT SAMPLE: 3233 patients diagnosed with lumbar spinal stenosis (LSS) had posterior lumbar interbody fusion (PLIF) at 22 hospitals in China from January 2015 to December 2022. OUTCOME MEASURES: The primary outcome was operation time. Prolonged operation time defined as exceeded 75% of the overall surgical duration, which mean exceeding 240 minutes. METHODS: A total of 3233 patients who underwent PLIF surgery with lumbar spinal stenosis (LSS) were divided into one training group and four test groups based on different district areas. The training group included 1569 patients, while Test1 had 541, Test2 had 403, Test3 had 351, and Test4 had 369 patients. Variables consisted of demographics, perioperative details, preoperative laboratory examinations and other Additional factors. Six algorithms were employed for variable screening, and variables identified by more than two screening methods were incorporated into the final model. In the training cohort, a 10-fold cross-validation (CV) and Bayesian hyperparameter optimization techniques were utilized to construct a model using eleven machine learning algorithms. Following this, the model was evaluated using four separate external test sets, and the mean Area Under the Curve (AUC) was computed to determine the best-performing model. Further performance metrics of the best model were evaluated, and SHapley Additive exPlanations(SHAP) were used for interpretability analysis to enhance decision-making transparency. Ultimately, an online calculator was created. RESULTS: Among the various machine learning models, the Random Forest achieved the highest performance in the validation set, with AUROC scores of 0.832 in Test1, 0.834 in Test2, 0.816 inTest3, 0.822 in Test4) compared with other machine learning models. The top contributing variables were number of levels fusion, pre-APTT, weight and age. The predictive model was further refined by developing a web-based calculator for clinical application. (https://wenle.shinyapps.io/PPOT_LSS/) CONCLUSIONS: This predictive model can facilitate identification of risk for prolonged operation time following PLIF surgery. Predictive calculators are expected to improve preoperative planning, identify patients with high risk factors, and help clinicians facilitating the improvement of treatment plans and the implementation of clinical intervention.

Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis.

This manuscript concerns the tissue-specific transcription of mouse and cattle glutamate decarboxylase-like protein 1 (GADL1) and the biochemical activities of human GADL1 recombinant protein. Bioinformatic analysis suggested that GADL1 appears late in evolution, only being found in reptiles, birds, and mammals. RT-PCR determined that GADL1 mRNA is transcribed at high levels in mouse and cattle skeletal muscles and also in mouse kidneys. Substrate screening determined that GADL1, unlike its name implies, has no detectable GAD activity, but it is able to efficiently catalyze decarboxylation of aspartate, cysteine sulfinic acid, and cysteic acid to ß-alanine, hypotaurine, and taurine, respectively. Western blot analysis verified the presence of GADL1 in mouse muscles, kidneys, C2C12 myoblasts, and C2C12 myotubes. Incubation of the supernatant of fresh muscle or kidney extracts with cysteine sulfinic acid resulted in the detection of hypotaurine or taurine in the reaction mixtures, suggesting the possible involvement of GADL1 in taurine biosynthesis. However, when the tissue samples were incubated with aspartate, no ß-alanine production was observed. We proposed several possibilities that might explain the inactivation of ADC activity of GADL1 in tissue protein extracts. Although ß-alanine-producing activity was not detected in the supernatant of tissue protein extracts, its potential role in ß-alanine synthesis cannot be excluded. There are several inhibitors of the ADC activity of GADL1 identified. The discovery of GADL1 biochemical activities, in conjunction with its expression and activities in muscles and kidneys, provides some tangible insight toward establishing its physiological function(s).

Mechanism of cysteine-dependent inactivation of aspartate/glutamate/cysteine sulfinic acid α-decarboxylases.

Animal aspartate decarboxylase (ADC), glutamate decarboxylase (GDC) and cysteine sulfinic acid decarboxylase (CSADC) catalyze the decarboxylation of aspartate, glutamate and cysteine sulfinic acid to ß-alanine, γ-aminobutyric acid and hypotaurine, respectively. Each enzymatic product has been implicated in different physiological functions. These decarboxylases use pyridoxal 5-phosphate (PLP) as cofactor and share high sequence homology. Analysis of the activity of ADC in the presence of different amino determined that beta-alanine production from aspartate was diminished in the presence of cysteine. Comparative analysis established that cysteine also inhibited GDC and CSADC in a concentration-dependent manner. Spectral comparisons of free PLP and cysteine, together with ADC and cysteine, result in comparable spectral shifts. Such spectral shifts indicate that cysteine is able to enter the active site of the enzyme, interact with the PLP-lysine internal aldimine, form a cysteine-PLP aldimine and undergo intramolecular nucleophilic cyclization through its sulfhydryl group, leading to irreversible ADC inactivation. Cysteine is the building block for protein synthesis and a precursor of cysteine sulfinic acid that is the substrate of CSADC and therefore is present in many cells, but the presence of cysteine (at comparable concentrations to their natural substrates) apparently could severely inhibit ADC, CSADC and GDC activity. This raises an essential question as to how animal species prevent these enzymes from cysteine-mediated inactivation. Disorders of cysteine metabolism have been implicated in several neurodegenerative diseases. The results of our study should promote research in terms of mechanism by which animals maintain their cysteine homeostasis and possible relationship of cysteine-mediated GDC and CSADC inhibition in neurodegenerative disease development.

Biochemical characterization and crystal structure of a GH10 xylanase from termite gut bacteria reveal a novel structural feature and significance of its bacterial Ig-like domain.

Bacterial Ig-like (Big) domains are commonly distributed in glycoside hydrolases (GH), but their structure and function remains undefined. Xylanase is a GH, and catalyzes the hydrolysis of the internal ß-xylosidic linkages of xylan. In this study, we report the molecular cloning, biochemical and biophysical characterization, and crystal structure of a termite gut bacterial xylanase, Xyl-ORF19, which was derived from gut bacteria of a wood-feeding termite (Globitermes brachycerastes). The protein architecture of Xyl-ORF19 reveals that it has two domains, a C-terminal GH10 catalytic domain and an N-terminal Big_2 non-catalytic domain. The catalytic domain folds in an (α/ß)8 barrel as most GH10 xylanases do, but it has two extra ß-strands. The non-catalytic domain is structurally similar to an immunoglobulin-like domain of intimins. The recombinant enzyme without the non-catalytic domain has fairly low catalytic activity, and is different from the full-length enzyme in kinetic parameters, pH and temperature profiles, which suggests the non-catalytic domain could affect the enzyme biochemical and biophysical properties as well as the role for enzyme localization. This study provides a molecular basis for future efforts in xylanase bioengineering.

Synthesis and NO2 Sensing Properties of In2O3 Micro-Flowers Composed of Nanorods.

Semiconductor oxide gas sensors have important applications in environmental protection, domestic health, and other fields. Research has shown that designing the morphology of sensitive materials can effectively improve the sensing characteristics of sensors. In this paper, by controlling the solvothermal reaction time, a unique hexagonal flower-like structure of In2O3 materials consisting of cuboid nanorods with a side length of 100-300 nm was prepared. The characterization results indicated that with the increase in reaction time, the materials exhibited significant morphological evolution. When the solvent heating time is 5 h, the flower-like structure is basically composed of hexagonal nanosheets with a thickness of several hundred nanometers and a side length of several micrometers. With the increase in reaction time, the apex angles of the nano sheets gradually become obtuse, and, finally, with the Ostwald ripening process, they become cuboid nanorods with side lengths of 100-300 nanometers, forming unique micro-flowers. Among them, the material prepared with a reaction time of 20 h has good sensing performance for NO2, exhibiting low operating temperature and detection limit, good selectivity, repeatability, and long-term stability, thus suggesting a good application prospect.

Single-Atom Gadolinium Anchored on Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier.

A single-atom metal doped on carbonaceous nanomaterials has attracted increasing attention due to its potential applications as high-performance catalysts. However, few studies focus on the applications of such nanomaterials as nanotheranostics for simultaneous bioimaging and cancer therapy. Herein, it is pioneeringly demonstrated that the single-atom Gd anchored onto graphene quantum dots (SAGd-GQDs), with dendrite-like morphology, was successfully prepared. More importantly, the as-fabricated SAGd-GQDs exhibits a robustly enhanced longitudinal relaxivity (r1 = 86.08 mM-1 s-1) at a low Gd3+ concentration of 2 µmol kg-1, which is 25 times higher than the commercial Gd-DTPA (r1 = 3.44 mM-1 s-1). In vitro and in vivo studies suggest that the obtained SAGd-GQDs is a highly potent and contrast agent to obtain high-definition MRI, thereby opening up more opportunities for future precise clinical theranostics.