TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Compact and cost-effective laser-powered speckle contrast optical spectroscopy fiber-free device for measuring cerebral blood flow.

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution. Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz. Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head. Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies.

Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis: A case report.

BACKGROUND: Gastric wall necrosis is a rare complication of endoscopic treatment for bleeding gastric ulcer, which may exacerbate the patient's condition once it occurs and may even require surgical intervention for treatment. CASE SUMMARY: A 59-year-old man was admitted to our department with melena. Endoscopy revealed a giant ulcer in the gastric antrum with a visible vessel in its center, which was treated with sclerosants and tissue glue injection and resulted in necrosis of the gastric wall. CONCLUSION: Injection of sclerosants and tissue glue may lead to gastric wall necrosis, which is a serious complication. Therefore, before administering this treatment to patients, we should consider other more effective methods of hemostasis to avoid gastric wall necrosis.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Omaveloxolone Prevents Polystyrene Microplastic-Induced Ovarian Granulosa Cell Apoptosis via the Keap1/Nrf2/HO-1 Pathway in Rats.

Microplastics (MPs) are persistent environmental pollutants that enter the circulatory system and subsequently reduce sperm quantity and quality. However, the influence of polystyrene MPs (PS-MPs) on the ovary and relevant mechanisms remain elusive. Herein, we aimed to examine the impact of PS-MPs on oxidative disorders in ovarian tissues and elucidate the underlying mechanisms. Healthy female rats were treated with different concentrations of 0.5 µm PS-MPs (diluted in deionized H2O) for 90 days. Upon examination of hematoxylin-eosin-stained ovarian tissue sections, the number of growing follicles was reduced in PS-MP-treated rats when compared with that in control rats. Enzyme-linked immunosorbent assays revealed that PS-MP exposure markedly reduced anti-Müllerian hormone (AMH) levels. Treatment with PS-MPs downregulated superoxide dismutase, glutathione, and catalase activities in ovarian tissues while upregulating malondialdehyde levels. Furthermore, exposure to PS-MP blocked the Keap1/Nrf2/HO-1 signal transduction pathway. PS-MPs also triggered apoptosis in the ovarian tissue, as evidenced by increased TUNEL staining and expression levels of cleaved caspase-9, Bax, and Bcl-2. To reactivate the Keap1/Nrf2/HO-1 pathway, rats were co-administered PS-MPs and omaveloxolone (Oma), an Nrf2 activator, for 1 week. We found that Oma could counteract the PS-MP-mediated effects on oxidative disorder, apoptosis, AMH production, and follicle number in rat ovarian tissues. To develop an in vitro model, granulosa cells (GCs) were treated with 10 µM H2O2 for 12 h to induce oxidative stress. H2O2-stimulated GCs exhibited attenuated cell growth and upregulated apoptosis and oxidative stress. Oma administration could ameliorate the H2O2-induced effects in terms of regulating cell viability, apoptosis, and oxidative stress in GCs. In summary, PS-MPs could induce apoptosis and oxidative stress via the Keap1/Nrf2/HO-1 signaling pathway in both rats and GCs.

Response of bacterial ecological and functional properties to anthropogenic interventions during maturation of mine sand soil.

Soil formation is a complex process that starts from the biological development. The ecological principles and biological function in soil are of great importance, whereas their response to anthropogenic intervention has been poorly understood. In this study, a 150-day microcosmic experiment was conducted with the addition of sludge and/or fermented wood chips (FWC) to promote the soil maturation. The results showed that, compared to the control (natural development without anthropogenic intervention), sludge, FWC, and their combination increased the availability of carbon, nitrogen, and potassium, and promoted the soil aggregation. They also enhanced the cellulase activity, microbial biomass carbon (MBC) and bacterial diversity, indicating that anthropogenic interventions promoted the maturation of sand soil. Molecular ecology network and functional analyses indicated that soil maturation was accomplished with the enhancement of ecosystem functionality and stability. Specifically, sludge promoted a transition in bacterial community function from denitrification to nitrification, facilitated the degradation of easily degradable organic matter, and enhanced the autotrophic nutritional mode. FWC facilitated the transition of bacterial function from denitrification to ammonification, promoted the degradation of recalcitrant organic matter, and simultaneously enhanced both autotrophic and heterotrophic nutritional modes. Although both sludge and FWC promoted the soil functionality, they showed distinct mechanistic actions, with sludge enhancing the physical structure, and FWC altering chemical composition. It is also worth emphasizing that sludge and FWC exhibited a synergistic effect in promoting biological development and ecosystem stability, thereby providing an effective avenue for soil maturation.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Bowel Habits, Obesity, Intestinal Microbiota and Their Influence on Hemorrhoidal Disease: a Mendelian Randomization Study.

Purpose: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease. Patients and Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane's Q value, to detect and correct the effects of horizontal pleiotropy. Results: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis. Conclusion: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.

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

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

Theoretical Perspective on the Design of Surface Frustrated Lewis Pairs for Small-Molecule Activation.

The excellent reactivity of frustrated Lewis pairs (FLP) to activate small molecules has gained increasing attention in recent decades. Though the development of surface FLP (SFLP) is prompting the application of FLP in the chemical industry, the design of SFLP with superior activity, high density, and excellent stability for small-molecule activation is still challenging. Herein, we review the progress of designing SFLP by surface engineering, screening natural SFLP, and the dynamic formation of SFLP from theoretical perspectives. We highlight the breakthrough in fine-tuning the activity, density, and stability of the designed SFLP studied by using computational methods. We also discuss future challenges and directions in designing SFLP with outstanding capabilities for small-molecule activation.

CSF2 Impairs Nrf2 Signaling through the Akt/Mtor Pathway in the Development of Bladder Cancer.

Bladder Cancer (BCa) is one of the most common cancers of the urinary system. Colony-stimulating factor 2 (CSF2) is involved in many cancers, but not BCa. We investigated the effect of CSF2 on BCa in this study and the underlying molecular mechanisms. CSF2 mRNA levels in BCa were analyzed using the Cancer Genome Atlas (TCGA) database. Western blot was conducted to verify CSF2 expression in BCa tissue samples and cell lines. The effect of CSF2 on the growth of BCa cells was assessed by CCK8 and colony formation. To determine the migration and invasion capabilities of BCa cells, transwell analysis and wound healing assays were conducted. Next, western blot was used to explore the underlying mechanism. In the end, a xenografted BCa mouse model was established to examine the effects of CSF2 on tumorigenesis in vivo. Results showed that CSF2 mRNA was upregulated in BCa samples. Knocking down CSF2 significantly inhibited the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Mechanism analysis revealed that CSF2 knockdown inhibited the proliferation and invasion of BCa cells via AKT/mTOR signaling. Based on these results, CSF2 promotes the proliferation and tumorigenesis of BCa.

GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.

Accumulating evidence suggests that prenatal stress (PNS) increases offspring susceptibility to depression, but the underlying mechanisms remain unclear. We constructed a mouse model of prenatal stress by spatially restraining pregnant mice from 09:00-11:00 daily on Days 5-20 of gestation. In this study, western blot analysis, quantitative real-time PCR (qRT‒PCR), immunofluorescence, immunoprecipitation, chromatin immunoprecipitation (ChIP), and mifepristone rescue assays were used to investigate alterations in the GR/P300-MKP1 and downstream ERK/CREB/TRKB pathways in the brains of prenatally stressed offspring to determine the pathogenesis of the reduced neurogenesis and depression-like behaviors in offspring induced by PNS. We found that prenatal stress leads to reduced hippocampal neurogenesis and depression-like behavior in offspring. Prenatal stress causes high levels of glucocorticoids to enter the fetus and activate the hypothalamic‒pituitary‒adrenal (HPA) axis, resulting in decreased hippocampal glucocorticoid receptor (GR) levels in offspring. Furthermore, the nuclear translocation of GR and P300 (an acetylation modifying enzyme) complex in the hippocampus of PNS offspring increased significantly. This GR/P300 complex upregulates MKP1, which is a negative regulator of the ERK/CREB/TRKB signaling pathway associated with depression. Interestingly, treatment with a GR antagonist (mifepristone, RU486) increased hippocampal GR levels and decreased MKP1 expression, thereby ameliorating abnormal neurogenesis and depression-like behavior in PNS offspring. In conclusion, our study suggested that the regulation of the MKP1 signaling pathway by GR/P300 is involved in depression-like behavior in prenatal stress-exposed offspring and provides new insights and ideas for the fetal hypothesis of mental health.

INSURE: An Information Theory iNspired diSentanglement and pURification modEl for Domain Generalization.

Domain Generalization (DG) aims to learn a generalizable model on the unseen target domain by only training on the multiple observed source domains. Although a variety of DG methods have focused on extracting domain-invariant features, the domain-specific class-relevant features have attracted attention and been argued to benefit generalization to the unseen target domain. To take into account the class-relevant domain-specific information, in this paper we propose an Information theory iNspired diSentanglement and pURification modEl (INSURE) to explicitly disentangle the latent features to obtain sufficient and compact (necessary) class-relevant feature for generalization to the unseen domain. Specifically, we first propose an information theory inspired loss function to ensure the disentangled class-relevant features contain sufficient class label information and the other disentangled auxiliary feature has sufficient domain information. We further propose a paired purification loss function to let the auxiliary feature discard all the class-relevant information and thus the class-relevant feature will contain sufficient and compact (necessary) class-relevant information. Moreover, instead of using multiple encoders, we propose to use a learnable binary mask as our disentangler to make the disentanglement more efficient and make the disentangled features complementary to each other. We conduct extensive experiments on five widely used DG benchmark datasets including PACS, VLCS, OfficeHome, TerraIncognita, and DomainNet. The proposed INSURE achieves state-of-the-art performance. We also empirically show that domain-specific class-relevant features are beneficial for domain generalization. The code is available at https://github.com/yuxi120407/INSURE.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Elucidating the intricacies of the H2S signaling pathway in gasotransmitters: Highlighting the regulation of plant thiocyanate detoxification pathways.

In recent decades, there has been increasing interest in elucidating the role of sulfur-containing compounds in plant metabolism, particularly emphasizing their function as signaling molecules. Among these, thiocyanate (SCN-), a compound imbued with sulfur and nitrogen, has emerged as a significant environmental contaminant frequently detected in irrigation water. This compound is known for its potential to adversely impact plant growth and agricultural yield. Although adopting exogenous SCN- as a nitrogen source in plant cells has been the subject of thorough investigation, the fate of sulfur resulting from the assimilation of exogenous SCN- has not been fully explored. There is burgeoning curiosity in probing the fate of SCN- within plant systems, especially considering the possible generation of the gaseous signaling molecule, hydrogen sulfide (H2S) during the metabolism of SCN-. Notably, the endogenous synthesis of H2S occurs predominantly within chloroplasts, the cytosol, and mitochondria. In contrast, the production of H2S following the assimilation of exogenous SCN- is explicitly confined to chloroplasts and mitochondria. This phenomenon indicates complex interplay and communication among various subcellular organelles, influencing signal transduction and other vital physiological processes. This review, augmented by a small-scale experimental study, endeavors to provide insights into the functional characteristics of H2S signaling in plants subjected to SCN--stress. Furthermore, a comparative analysis of the occurrence and trajectory of endogenous H2S and H2S derived from SCN--assimilation within plant organisms was performed, providing a focused lens for a comprehensive examination of the multifaceted roles of H2S in rice plants. By delving into these dimensions, our objective is to enhance the understanding of the regulatory mechanisms employed by the gasotransmitter H2S in plant adaptations and responses to SCN--stress, yielding invaluable insights into strategies for plant resilience and adaptive capabilities.

Finding Natural, Dense, and Stable Frustrated Lewis Pairs on Wurtzite Crystal Surfaces for Small-Molecule Activation.

The surface frustrated Lewis pairs (SFLPs) open up new opportunities for substituting noble metals in the activation and conversion of stable molecules. However, the applications of SFLPs on a larger scale are impeded by the complex construction process, low surface density, and sensitivity to the reaction environment. Herein, wurtzite-structured crystals such as GaN, ZnO, and AlP are found for developing natural, dense, and stable SFLPs. It is revealed that the SFLPs can naturally exist on the (100) and (110) surfaces of wurtzite-structured crystals. All the surface cations and anions serve as the Lewis acid and Lewis base in SFLPs, respectively, contributing to the surface density of SFLPs as high as 7.26×1014 cm-2. Ab initio molecular dynamics simulations indicate that the SFLPs can keep stable under high temperatures and the reaction atmospheres of CO and H2O. Moreover, outstanding performance for activating the given small molecules is achieved on these natural SFLPs, which originates from the optimal orbital overlap between SFLPs and small molecules. Overall, these findings not only provide a simple method to obtain dense and stable SFLPs but also unfold the nature of SFLPs toward the facile activation of small molecules.

Influences of Heat Stress on Glutamate Transmission-Dependent Expression Levels of IL-1ß and IL-18 in BV-2 Microglial Cells.

OBJECTIVE: This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1ß (IL-1ß) and IL-18 in BV-2 microglial cells. METHODS: BV-2 microglial cells were cultured in vitro , with cells maintained at 37 °C serving as the control. The HS group experienced incubation at 40 °C for 1 h, followed by further culturing at 37 °C for 6 or 12 h. The experimental group was pre-incubated with glutamate, the glutamate antagonist riluzole, or the mGluR5 agonist, 2-Chloro-5-hydroxyphenylglycine (CHPG), before HS. Glutamate content in BV-2 culture supernatant was assessed using colorimetric assay. Moreover, mRNA expression levels of EAAT3 and/or mGluR5 in BV-2 cells were determined via quantitative polymerase chain reaction. Interleukins (IL-1ß and IL-18) in cell culture supernatant were measured using enzyme-linked immunosorbent assay. Western blot analysis was employed to assess protein levels of IL-1ß and IL-18 in BV-2 cells. RESULTS: HS induced a significant release of glutamate and increased the expression levels of mGluR5 and EAAT3 in BV-2 cells. It also triggered the expression levels and release of pro-inflammatory factors, such as IL-1ß and IL-18, synergizing with the effects of glutamate treatment. Preincubation with both riluzole and CHPG significantly reduced HS-induced glutamate release and mitigated the increased expression levels and release of IL-1ß and IL-18 induced by HS. CONCLUSION: The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1ß and IL-18.

Isoglutaminyl Cyclase Overexpression Enhances KYSE30 Cancer Cell Proliferation and Migration via the MAPK Signaling Pathway.

To understand how upregulated isoglutaminyl cyclase (isoQC) is involved in the initiation of diseases such as cancer, we developed a human KYSE30 carcinoma cell model in which isoQC was stably overexpressed. GO and KEGG analysis of the DEGs (228) and DEPs (254) respectively implicated isoQC on the proliferation invasion and metastasis of cells and suggested that isoQC might participate in the regulation of MAPK, RAS, circadian rhythm, and related pathways. At the functional level, isoQC-overexpressing KYSE30 cells showed enhanced proliferation, migration, and invasion capacity. Next, we decided to study the precise effect of isoQC overexpression on JNK, p-JNK, AKT, p-AKT, ERK, p-ERK, and PER2, as RNA levels of these proteins are significantly correlated with signal levels indicated in RNA-Seq analysis, and these candidates are the top correlated DEPs enriched in RT-qPCR analysis. We saw that only p-ERK expression was inhibited, while PER2 was increased. These phenotypes were inhibited upon exposure to PER2 inhibitor KL044, which allowed for the restoration of p-ERK levels. These data support upregulated isoQC being able to promote cancer cell proliferation and migration in vitro, likely by helping to regulate the MAPK and RAS signaling pathways, and the circadian protein PER2 might be a potential mediator.