A Highly Efficient Fluorescent Turn-Off Nanosensor for Quantitative Detection of Teicoplanin Antibiotic from Humans, Food, and Water Based on the Electron Transfer between Imprinted Quantum Dots and the Five-Membered Cyclic Boronate Esters.

Teicoplanin has been banned in the veterinary field due to the drug resistance of antibiotics. However, teicoplanin residue from the antibiotic abuse of humans and animals poses a threat to people's health. Therefore, it is necessary to develop an efficient way for the highly accurate and reliable detection of teicoplanin from humans, food, and water. In this study, novel imprinted quantum dots of teicoplanin were prepared based on boronate affinity-based precisely controlled surface imprinting. The imprinting factor (IF) for teicoplanin was evaluated and reached a high value of 6.51. The results showed excellent sensitivity and selectivity towards teicoplanin. The relative fluorescence intensity was inversely proportional to the concentration of teicoplanin, in the range of 1.0-17 µM. And its limit of detection (LOD) was obtained as 0.714 µM. The fluorescence quenching process was mainly controlled by a static quenching mechanism via the non-radiative electron-transfer process between QDs and the five-membered cyclic boronate esters. The recoveries for the spiked urine, milk, and water samples ranged from 95.33 to 104.17%, 91.83 to 97.33, and 94.22 to 106.67%, respectively.

Kinesin-1-like protein PSS1 is essential for full-length homologous pairing and synapsis in rice meiosis.

The pairing and synapsis of homologous chromosomes are crucial for their correct segregation during meiosis. The LINC (Linker of Nucleoskeleton and Cytoskeleton) complex can recruit kinesin protein at the nuclear envelope, affecting telomere bouquet formation and homologous pairing. Kinesin-1-like protein Pollen Semi-Sterility1 (PSS1) plays a pivotal role in male meiotic chromosomal behavior and is essential for fertility in rice. However, its exact role in meiosis, especially as kinesin involved in homologous pairing and synapsis, has not been fully elucidated. Here, we generated three pss1 mutants by genome editing technology to dissect PSS1 biological functions in meiosis. The pss1 mutants exhibit alterations in the radial microtubule organization at pachytene and manifest a deficiency in telomere clustering, which is critical for full-length homologous pairing. We reveal that PSS1 serves as a key mediator between chromosomes and cytoskeleton, thereby regulating microtubule organization and transmitting the force to nuclei to facilitate homologous chromosome pairing and synapsis in meiosis.

Therapeutic siRNA targeting PLIN2 ameliorates steatosis, inflammation, and fibrosis in steatotic liver disease models.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. If left untreated, MASLD can progress from simple hepatic steatosis to metabolic dysfunction-associated steatohepatitis, which is characterized by inflammation and fibrosis. Current treatment options for MASLD remain limited, leaving substantial unmet medical needs for innovative therapeutic approaches. Here, we show that PLIN2, a lipid droplet protein inhibiting hepatic lipolysis, serves as a promising therapeutic target for MASLD. Hepatic PLIN2 levels were markedly elevated in multiple MASLD mouse models induced by diverse nutritional and genetic factors. The liver-specific deletion of Plin2 exhibited significant anti-MASLD effects in these models. To translate this discovery into a therapeutic application, we developed a GalNAc-siRNA conjugate with enhanced stabilization chemistry and validated its potent and sustained efficacy in suppressing Plin2 expression in mouse livers. This siRNA therapeutic, named GalNAc-siPlin2, was shown to be biosafe in mice. Treatment with GalNAc-siPlin2 for 6-8 weeks led to a decrease in hepatic triglyceride levels by approximately 60% in high-fat diet- and obesity-induced MASLD mouse models, accompanied with increased hepatic secretion of VLDL-triglyceride and enhanced thermogenesis in brown adipose tissues. Eight-week treatment with GalNAc-siPlin2 significantly improved hepatic steatosis, inflammation, and fibrosis in high-fat/high fructose-induced metabolic dysfunction-associated steatohepatitis models compared to control group. As a proof of concept, we developed a GalNAc-siRNA therapeutic targeting human PLIN2, which effectively suppressed hepatic PLIN2 expression and ameliorated MASLD in humanized PLIN2 knockin mice. Together, our results highlight the potential of GalNAc-siPLIN2 as a candidate MASLD therapeutic for clinical trials.

Social accessibility in queering code/space: Blued-based visibility and social practices of local gay people in mainland China.

As a locative media, Blued articulates physical and digital space in the form of localization, giving a mediated visibility to its users who are not visible in physical space, thus making the city a queering code/space. This can transform social accessibility and the ways that gays come together and interact in local spaces. Taking mainland China, dominated by heteronomativity, as a field, this paper focuses on the visibility negotiation and social accessibility practices in Blued-based queering code/space. Using the digital anthropology method, this study found that Blued-based visibility is essential for non-closeted gay men to gain a sense of local belonging and community inclusion. Offline accessibility is a crucial demand for Blued users, but until then they have negotiated visibility through selective disclosure of social cues. At the same time, Blued users face visibility asymmetries and risks in the pursuit of accessibility. This study then argues that in the Blued-based queering code/space, the gay men constantly reconcile accessibility with others by managing visibility in a heteronormative urban space. In addition, this paper highlights the value of the hybrid of new media and physical space for the public interaction of marginalized groups in the city.

DNA damages in hepatocytes are amended by an inflammation-driven rescue repair mechanism in chronic hepatitis B.

BACKGROUND: Our previous study has shown that intrahepatic necroinflammation favors the eliminations of HBV integration and clonal hepatocytes. Here, the effect of inflammation on host DNA damage eliminations in liver biopsy tissues from patients with chronic hepatitis B (CHB) was further investigated. METHODS: DNA damage markers, histone γ-H2AX and phosphorylated heterochromatin protein 1γ (p-HP1γ), and senescent marker p21 were detected using immunohistochemical and immunofluorescent assays in liver biopsy samples from 69 CHB patients and 12 liver cirrhosis (LC) patients. Twenty paired hepatocellular carcinoma (HCC) surgical samples were used as controls. RESULTS: Both γ-H2AX and p-HP1γ were sensitively detected in nuclear and cytoplasmic/nuclear patterns. Nuclear γ-H2AX was superior as a DNA damage marker in hepatocytes. The level of nuclear γ-H2AX in CHB, comparable to those in LC and HCC, was correlated with liver fibrosis and coexisted with the senescent marker p21. However, hepatocytes carried an alleviated level of DNA damages, which was associated with the level of cytoplasmic γ-H2AX. Cytoplasmic γ-H2AX chiefly occurred in hepatocytes near necroinflammatory foci, was correlated with liver inflammation and usually indicated the decrease or disappearance of nuclear γ-H2AX. The lack of cytoplasmic γ-H2AX together with the high level of nuclear γ-H2AX was associated with the progression from large cell changes/dysplasia to small cell changes/dysplasia. CONCLUSIONS: Hepatocytes in CHB already carry massive DNA damages and undergo cellular senescence. The DNA damages in those senescent hepatocytes are histopathologically demonstrated to be amended by a novel cytoplasmic γ-H2AX-indicated and inflammation-driven rescue repair mechanism, which may be involved in hepatocarcinogenesis if it works improperly.

Study on Explosion Characteristics and Mechanism of Electrostatic Spray Powder.

In order to fully understand the explosion risk of electrostatic spraying powder, corresponding preventive measures are put forward. The explosion characteristics, ignition sensitivity, and flame propagation of three typical electrostatic spraying powders were tested using a 20 L spherical explosion test device, a G-G furnace test device, and a Hartmann tube test device, and the explosion process and mechanism of electrostatic spraying powders were discussed. The results show that the maximum explosion pressure and the maximum explosion pressure rise rate increase first and then decrease with the increase in mass concentration. The maximum explosion pressure and the maximum explosion pressure rise rate of acrylic powder coating are the largest, which are 0.75 and 85.4 MPa/s, respectively. The shortest burning time is 97.5 ms, and the highest explosion danger level is 23.46 MPa·m/s. The flame propagation of electrostatic spraying powder develops slowly; the flame front spreads linearly and the average flame velocity increases first and then decreases. The explosive development process of powder coating particles is concentrated in the three-phase system of solid particles, molten particles, and pyrolytic gasification combustible gas, which goes through the kinetic process of particle heating melting, cross-linking curing, pyrolytic gasification, combustion, and extinction.

Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis.

Background: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition. Methods: Instrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results. Results: Bacteroidia (b = -0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = -0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses. Conclusion: Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Temporal dynamics of Grime's CSR strategies in plant communities during 60 years of succession.

Grime's competitive, stress-tolerant, ruderal (CSR) theory predicts a shift in plant communities from ruderal to stress-tolerant strategies during secondary succession. However, this fundamental tenet lacks empirical validation using long-term continuous successional data. Utilizing a 60-year longitudinal data of old-field succession, we investigated the community-level dynamics of plant strategies over time. Our findings reveal that while plant communities generally transitioned from ruderal to stress-tolerant strategies during succession, initial abandonment conditions crucially shaped early successional strategies, leading to varied strategy trajectories across different fields. Furthermore, we found a notable divergence in the CSR strategies of alien and native species over succession. Initially, alien and native species exhibited similar ruderal strategies, but in later stages, alien species exhibited higher ruderal and lower stress tolerance compared to native species. Overall, our findings underscore the applicability of Grime's predictions regarding temporal shifts in CSR strategies depending on both initial community conditions and species origin.

Tunable templating of photonic microparticles via liquid crystal order-guided adsorption of amphiphilic polymers in emulsions.

Multiple emulsions are usually stabilized by amphiphilic molecules that combine the chemical characteristics of the different phases in contact. When one phase is a liquid crystal (LC), the choice of stabilizer also determines its configuration, but conventional wisdom assumes that the orientational order of the LC has no impact on the stabilizer. Here we show that, for the case of amphiphilic polymer stabilizers, this impact can be considerable. The mode of interaction between stabilizer and LC changes if the latter is heated close to its isotropic state, initiating a feedback loop that reverberates on the LC in form of a complete structural rearrangement. We utilize this phenomenon to dynamically tune the configuration of cholesteric LC shells from one with radial helix and spherically symmetric Bragg diffraction to a focal conic domain configuration with highly complex optics. Moreover, we template photonic microparticles from the LC shells by photopolymerizing them into solids, retaining any selected LC-derived structure. Our study places LC emulsions in a new light, calling for a reevaluation of the behavior of stabilizer molecules in contact with long-range ordered phases, while also enabling highly interesting photonic elements with application opportunities across vast fields.

Research on the Inhibition Effect of NaCl on the Explosion of Mg-Al Alloy Powder.

A study was conducted on the explosion overpressure and flame propagation law of magnesium-aluminum (Mg-Al) alloy powder, and the suppression mechanism of sodium chloride (NaCl) on the explosion of magnesium-aluminum alloy powder was explored. Adding NaCl powder can effectively reduce the explosion pressure, flame front position, and flame propagation speed. The higher the amount of NaCl powder added, the lower the explosion pressure of magnesium-aluminum alloy powder, the slower the flame propagation speed, and the lower the flame brightness. NaCl adsorbed on Mg-Al alloy powder isolated heat transfer and played a cooling role. The Cl- produced by NaCl decomposition will react with the free radicals H+ and OH- in the reaction system, which will reduce the concentration of H+ and OH- in the combustion process and hinder the propagation and expansion of the flame. The research results provide theoretical guidance for the explosion prevention of Mg-Al alloy powder and the preparation of a physical-chemical compound explosion suppressor in the later stage.

TGFß2 mediates oxidative stress-induced epithelial-to-mesenchymal transition of bladder smooth muscle.

Bladder outlet obstruction (BOO) is the primary clinical manifestation of benign prostatic hyperplasia, the most common urinary system disease in elderly men, and leads to associated lower urinary tract symptoms. Although BOO is reportedly associated with increased systemic oxidative stress (OS), the underlying mechanism remains unclear. The elucidation of this mechanism is the primary aim of this study. A Sprague-Dawley rat model of BOO was constructed and used for urodynamic monitoring. The bladder tissue of rats was collected and subjected to real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), histological examination, and immunohistochemical staining. Through bioinformatics prediction, we found that transforming growth factor ß2 (TGFß2) expression was upregulated in rats with BOO compared with normal bladder tissue. In vitro analyses using primary bladder smooth muscle cells (BSMCs) revealed that hydrogen peroxide (H2O2) induced TGFß2 expression. Moreover, H2O2 induced epithelial-to-mesenchymal transition (EMT) by reducing E-cadherin, an endothelial marker and CK-18, a cytokeratin maker, and increasing mesenchymal markers, including N-cadherin, vimentin, and α-smooth muscle actin (α-SMA) levels. The downregulation of TGFß2 expression in BSMCs using siRNA technology alleviated H2O2-induced changes in EMT marker expression. The findings of the study indicate that TGFß2 plays a crucial role in BOO by participating in OS-induced EMT in BSMCs.

Engineering Entropy-Driven Nanomachine-Mediated Morphological Evolution of Anisotropic Silver Triangular Nanoplates for Colorimetric and Photothermal Biosensing.

A DNA/RNA biosensor capable of single nucleotide variation (SNV) resolution is highly desirable for drug design and disease diagnosis. To meet the point-of-care demand, rapid, cost-effective, and accurate SNV detection is of great significance but still suffers from a challenge. In this work, a unique nonenzymatic dual-modal (multicolorimetric and photothermal) visualization DNA biosensor is first proposed for SNV identification on the basis of an entropy-driven nanomachine with double output DNAs and coordination etching of anisotropic silver triangular nanoplates (Ag TNPs). When the target initiates the DNA nanomachine, the liberated multiple output DNAs can be utilized as a bridge to produce a superparamagnetic sandwich complex. The incoming poly-C DNA can coordinate and etch highly active Ag+ ions at the tips of Ag TNPs, causing a shift in the plasmon peak of Ag TNPs from 808 to 613 nm. The more target DNAs are introduced, the more output DNAs are released and thus the more Ag+ ions are etched. The noticeable color changes of anisotropic Ag TNPs can be differentiated by "naked eye" and accurate temperature reading. The programmable DNA nanotechnology and magnetic extraction grant the high specificity. Also, the SNV detection results can be self-verified by the two-signal readouts. Moreover, the dual-modal biosensor has the advantages of portability, cost-effectiveness, and simplicity. Particularly, the exclusive entropy-driven amplifier liberates double output DNAs to bridge more poly-C DNAs, enabling the dual-modal visualization DNA biosensor with improved sensitivity.

Exploring the micromorphological characteristics of adult lower cervical vertebrae based on micro-computed tomography.

We will use micro-computed tomography to scan 31 sets of the adult lower cervical vertebrae (155 vertebrae) to observe the morphological characteristics and direction of trabeculae in the lower cervical vertebrae by outlining and reconstructing the regions of interest and to calculate the variation laws of the microstructure in the regions of interest to reveal their structural characteristics and weak areas. As a result, the images showed that the trabeculae in the lower cervical pedicle near the medial and lateral cortices were relatively dense, and their bone plates were lamellar. There were cavities between the superior and inferior articular processes where the ossification centers had not been absorbed after ossified. The lamellar trabeculae in the vertebral plates near the cortical bones were only 1-2 layers, extended and transformed into rod-shaped trabeculae in a radial shape toward the medullary space. The lamellar trabeculae of the vertebral plate extend over the spinous process near the cortical bone. The statistical results of the trabeculae's morphological parameters showed significant differences in bone volume fraction values among the four parts (P < 0.05). There were substantial differences in BS/BV, except for no differences between the pedicle and the vertebral plate (P < 0.05). There was a significant difference in trabecular pattern factor values between the articular process, the spinous process, and the vertebral plate (P < 0.05) and a significant difference between the pedicle, the spinous process, and the vertebral plate (P < 0.05). There were no significant differences in trabecular bone thickness and trabecular space values among the four parts (P < 0.05). The anatomical microstructural perspective confirms that the optimal choice is internal fixation via the pedicle. If using pedicle screws, the nail tract needs to be placed into the spinous process to increase its holding power and resistance to extraction.

Highly conductive and tough polyacrylamide/sodium alginate hydrogel with uniformly distributed polypyrrole nanospheres for wearable strain sensors.

Conductive hydrogels have attracted widespread attention because of their integrated characteristics of being stretchable, deformable, adhesive, self-healable, and conductive. Herein, we report a highly conductive and tough double-network hydrogel based on a double cross-linked polyacrylamide (PAAM) and sodium alginate (SA) network with conducting polypyrrole nanospheres (PPy NSs) uniformly distributed in the network (PAAM-SA-PPy NSs). SA was employed as a soft template for synthesis of PPy NSs and distribution of PPy NSs uniformly in the hydrogel matrix to construct SA-PPy conductive network. The PAAM-SA-PPy NS hydrogel exhibited both high electrical conductivity (6.44 S/m) and excellent mechanical properties (tensile strength of 560 kPa at 870 %), as along as high toughness, high biocompatibility, good self-healing and adhesion properties. The assembled strain sensors showed high sensitivity and a wide sensing range (a gauge factor of 1.89 for 0-400 % strain and 4.53 for 400-800 % strain, respectively), as well as fast responsiveness and reliable stability. When used as a wearable strain sensor, it was able to monitor a series of physical signals from human large-scale joint motions and subtle muscle movements. This work provides a new strategy for the development of electronic skins and flexible strain sensors.

miR-199a-5p from bone marrow mesenchymal stem cell exosomes promotes the proliferation of neural stem cells by targeting GSK-3ß.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes are a promising therapeutic agent for human disease, but their effects on neural stem cells (NSCs) subject to spinal cord ischaemia-reperfusion injury (SCIRI) remain unknown. Here, we examine the impact of miR-199a-5p-enriched exosomes derived from BMSCs on NSC proliferation. We establish a rat model of aortic cross-clamping to induce SCIRI in vivo and a primary NSC model of oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate SCIRI in vitro. CCK8, EdU, and BrdU assays are performed to evaluate the proliferation of NSCs. Hematoxylin and eosin (H&E) staining is used to determine the number of surviving neurons. The Basso, Beattie, and Bresnahan (BBB) scale and inclined plane test (IPT) are used to evaluate hind limb motor function. DiO-labelled exosomes are efficiently internalized by NSCs and increase ectopic amounts of miR-199a-5p, which promotes the proliferation of NSCs. In contrast, exosomes derived from miR-199a-5p-depleted BMSCs exert fewer beneficial effects. MiR-199a-5p targets and negatively regulates glycogen synthase kinase 3ß (GSK-3ß) and increases nuclear ß-catenin and cyclin D1 levels. miR-199a-5p inhibition reduces the total number of EdU-positive NSCs after OGD/R, but the GSK-3ß inhibitor CHIR-99021 reverses this effect. In vivo, intrathecal injection of BMSC-derived exosomes increases the proliferation of endogenous spinal cord NSCs after SCIRI. In addition, more proliferating NSCs are found in rats intrathecally injected with exosomes overexpressing miR-199a-5p. In summary, miR-199a-5p in BMSC-derived exosomes promotes NSC proliferation via GSK-3ß/ß-catenin signaling.

Branched polyethylenimine-assisted boronic acid functionalized magnetic nanoparticles for highly efficient capture of lincomycin and clindamycin.

As lincosamide antibiotics, lincomycin and clindamycin are widely used in the drug manufacturing industry for the health of human beings and animals. Thus, the quantitative detection of them in real samples is of great significance. Due to the presence of complex interfering components in actual samples, the separation and enrichment of lincomycin and clindamycin prior to analysis are key. Therefore, it is necessary to develop a non-complex, cost-effective enrichment method for them. A five- or six-membered boronic cyclic ester is formed through boronate affinity materials binding a cis-diol-containing compound in aqueous media, which is a reversible reaction. However, low binding capacity and affinity, and high binding pH of boronate affinity materials are key concerns. In this study, polyethylenimine-assisted 3-fluoro-4-formylphenylboronic acid functionalized magnetic nanoparticles were developed to capture efficiently cis-diol-containing lincomycin and clindamycin under neutral conditions. Thereinto, polyethylenimine (PEI) was applied as a scaffold to amplify the number of boronic acid moieties. And 3-fluoro-4-formylphenylboronic acid was used as an affinity ligand due to its excellent water solubility and low pKa value toward lincomycin and clindamycin. The results indicated that the prepared branched boronic acid-functionalized MNPs provided high binding capacity and fast binding kinetics under neutral conditions. Furthermore, the obtained MNPs exhibited relatively high binding affinity (Kd ≈ 10-4 M) and low binding pH (pH ≥ 6.0).

The Extended Pterional Approach Allows Satisfactory Results for the Resection of Huge Medial Sphenoid Ridge Meningioma.

OBJECTIVE: To investigate the surgical method and efficacy of the extended pterional approach in the resection of huge medial sphenoid ridge meningiomas (MSRMs). METHODS: Retrospective analysis of clinical data from 41 patients diagnosed with MSRMs (diameter ≥4.0 cm) from Nanjing Brain Hospital between January 2012 and February 2022 was conducted. Within 24 hours after surgery, head computed tomography and magnetic resonance imagingwere reviewed to evaluate the extent of tumor resection based on Simpson grading. Cranial magnetic resonance imagingwas repeated 3 to 60 months after surgery to assess tumor recurrence or progression. Preoperative, discharge, and follow-up Karnofsky functional status scores (KPS) were assessed to determine patients' functional status. Repeated-measures analysis of variance was utilized to compare KPS at preoperative, hospital discharge, and final follow-up. RESULTS: The 41 selected cases included 38 cases (92.7%) of Simpson I-III resection and 3 cases (7.3%) of Simpson IV resection. All the cases had typical pathological features and definite pathological diagnoses. There were 2 recurrent tumors and 4 progressed tumors when the patients were followed up from 3 months to 60 months after operations. The results demonstrated that the KPS score at the final follow-up (91.4 ± 9.6) was higher than at hospital discharge (85.3 ± 8.9) and preoperation (78.2 ± 8.5) (F = 69.46, P = 0.033). CONCLUSIONS: The use of the extended pterional approach in the resection of huge MSRMs appears to be an effective surgical method. Careful dissection and preservation of vascular and neural structures, as well as meticulous microsurgical techniques in managing cavernous sinus tumors, can lead to reduced surgical complications and improved treatment outcomes.

Identification of Ubr1 as an amino acid sensor of steatosis in liver and muscle.

BACKGROUND: Malnutrition is implicated in human metabolic disorders, including hepatic steatosis and myosteatosis. The corresponding nutrient signals and sensors as well as signalling pathways have not yet been well studied. This study aimed to unravel the nutrient-sensing mechanisms in the pathogenesis of steatosis. METHODS: Plin2, a lipid droplet (LD) protein-inhibiting lipolysis, is associated with steatosis in liver and muscle. Taking advantage of the Gal4-UAS system, we used the Drosophila melanogaster wing imaginal disc as an in vivo model to study the regulation of Plin2 proteostasis and LD homeostasis. Drosophila Schneider 2 (S2) cells were used for western blotting, immunoprecipitation assays, amino acid-binding assays and ubiquitination assays to further investigate the regulatory mechanisms of Plin2 in response to nutrient signals. Mouse AML12 hepatocytes, human JHH-7 and SNU-475 hepatoma cells were used for immunofluorescence, western blotting and immunoprecipitation to demonstrate that the mode of Plin2 regulation is evolutionarily conserved. In addition, we purified proteins from HEK293 cells and reconstituted in vitro cell-free systems in amino acid-binding assays, pulldown assays and ubiquitination assays to directly demonstrate the molecular mechanism by which Ubr1 senses amino acids to regulate Plin2 proteostasis. RESULTS: As a lipolysis inhibitor, Plin2 was significantly elevated in liver (P < 0.05) and muscle (P < 0.05) in patients with steatosis. Consistently, we found that the ubiquitin moiety can be conjugated to any Lys residue in Plin2, ensuring robust clearance of Plin2 by protein degradation. We further demonstrated that the E3 ubiquitin ligase Ubr1 targets Plin2 for degradation in an amino acid-dependent manner. Ubr1 uses two canonical substrate-binding pockets, independent of each other, to bind basic and bulky hydrophobic amino acids, respectively. Mechanistically, amino acid binding allosterically activates Ubr1 by alleviating Ubr1's auto-inhibition. In the absence of amino acids, or when the amino acid-binding capacity of Ubr1 is diminished, Ubr1-mediated Plin2 degradation is inactivated, leading to steatosis. CONCLUSIONS: We identified Ubr1 as an amino acid sensor regulating Plin2 proteostasis, bridging the knowledge gap between steatosis and nutrient sensing. Our work may provide new strategies for the prevention and treatment of steatosis.

Development and Experimental Validation of a Novel Prognostic Signature for Gastric Cancer.

BACKGROUND: Gastric cancer is a malignant tumor with high morbidity and mortality. Therefore, the accurate recognition of prognostic molecular markers is the key to improving treatment efficacy and prognosis. METHODS: In this study, we developed a stable and robust signature through a series of processes using machine-learning approaches. This PRGS was further experimentally validated in clinical samples and a gastric cancer cell line. RESULTS: The PRGS is an independent risk factor for overall survival that performs reliably and has a robust utility. Notably, PRGS proteins promote cancer cell proliferation by regulating the cell cycle. Besides, the high-risk group displayed a lower tumor purity, higher immune cell infiltration, and lower oncogenic mutation than the low-PRGS group. CONCLUSIONS: This PRGS could be a powerful and robust tool to improve clinical outcomes for individual gastric cancer patients.

Explosive Characteristics and Kinetic Mechanism of Methane-Air Mixtures under High-Temperature Conditions.

In the gas extraction and utilization process of coal mines, gas (mainly containing methane) explosion accidents happen occasionally under high-temperature conditions, causing serious casualties and economic losses. To reveal the mechanism and risk evolution of methane explosion under high-temperature conditions and control such accidents, the explosive characteristics of methane at 25∼200 °C were experimentally investigated by establishing a test platform for gas explosion under high-temperature conditions. In the experiments, three conditions were considered: the concentration near the upper explosion limit (CNUEL) (15.47 vol %), stoichiometric concentration (SC), and concentration near the lower explosion limit (4.68 vol %). Furthermore, the explosion pressure of methane-air mixtures and sensitivity characteristics of key free radicals at different high temperatures were determined based on the GRI-Mech 3.0 reaction mechanism of methane and using software CHEMKIN-PRO. The results show that at SC, P max decreases, while (DP/DT)max remains unchanged as the temperature increases, indicating a gradual decrease in the explosion risk. Near the explosion limits, P max and (DP/DT)max both grow as an exponential function, which implies that the explosion risk gradually increases. The temperature rise exerts a greater effect in improving the risk of explosion overpressure of methane at CNUEL (15.47 vol %), and compared with P max, the temperature rise has a greater improvement effect on (DP/DT)max. In the early stage of consuming methane, methane at SC mainly has two chemical reaction paths: CH4 → CH3 → CH3O → CH2O → HCO → CO and CH4 → CH3 → HCO → CO. The former and the latter to some extent separately promote and inhibit the explosive reactions. As the temperature increases, the proportion of methane consumed by the former reduces, while that by the latter slightly increases. The temperature rise inhibits the increase in the explosion risk of methane at SC, which is consistent with the experimental results.