The chloroplast genome of a subtropical tree Sassafras randaiense (Hayata) Rehder, 1920 (Lauraceae).

The complete chloroplast genome sequence of Sassafras randaiense (Hayata) Rehder, 1920, a subtropical tree in the family Lauraceae, was determined. For a better understanding of the differences between S. randaiense and S. tzumu, the complete chloroplast genome of S. randaiense was sequenced and analyzed. The complete chloroplast genome is 151,781 bp in length, consisting of a pair of inverted repeat (IR) regions of 20,114 bp, one large single-copy (LSC) region of 92,740 bp, and one small single-copy (SSC) region of 18,813 bp. The overall GC content of the complete chloroplast genome is 39.2%. Further, maximum-likelihood phylogenetic analysis was conducted using 31 complete plastome sequences, which support that S. randaiense and S. tzumu are nested among the members of Cinnamomum, suggesting that Sassafras belongs to Cinnamomum.

Age-Stage, Two-Sex Life Table of Atractomorpha lata (Orthoptera: Pyrgomorphidae) at Different Temperatures.

Atractomorpha lata Motschoulsky (Orthoptera: Pyrgomorphidae) has recently emerged as an important agricultural pest in China. Understanding the impact of temperature on its developmental period is crucial for predicting its population dynamics. This study systematically observed the biological characteristics of A. lata at five temperatures (16, 20, 24, 28, and 32 °C) using the age-stage, two-sex life table method. The effects of temperature on the developmental period, survival rate, and fecundity of A. lata were studied using fresh bean leaves as host. The results demonstrated that as temperature increased from 16 °C to 32 °C, the developmental period, preadult time, adult longevity, adult preoviposition period (APOP), and total preoviposition period (TPOP) significantly decreased. The developmental threshold temperatures for various stages were calculated, ranging from 10.47 °C to 13.01 °C, using the linear optimal method. As temperature increased, both the intrinsic rate of increase (r) and the finite rate of increase (λ) also increased, while the mean generation time (T) decreased. The optimal values of the net reproductive rate (R0 = 54.26 offspring), gross reproductive rate (GRR = 185.53 ± 16.94 offspring), and fecundity (169.56 ± 9.93 eggs) were observed at 24 °C. Similarly, the population trend index (I) for A. lata peaked at 24 °C (61.64). Our findings indicate that A. lata exhibits its highest population growth rate at 24 °C, providing a scientific basis for predicting its population dynamics in the field.

Patterns and Drivers of Bumblebee Diversity in Gansu.

Understanding the influence of factors responsible for shaping community assemblage is crucial for biodiversity management and conservation. Gansu is one of the richest regions for bumblebee species in the world. We explored the distribution data of 52 bumblebee species collected in Gansu and its surroundings between 2002 and 2022, predicting habitat suitability based on 17 environmental variables using MaxEnt. The factors influencing community assemblage were assessed using canonical correspondence analysis. Net primary productivity, water vapor pressure, temperature seasonality, annual precipitation, and precipitation seasonality were some of the most influential drivers of species distributions. Based on Ward's agglomerative cluster analysis, four biogeographic zones are described: the Southern humid zone, the Western Qilian snow mountain zone, the Eastern Loess plateau zone, and the Western dry mountain zone. In the clusters of grid cells based on beta diversity values, the Southern humid zone comprised 42.5% of the grid cells, followed by the Eastern Loess plateau zone (32.5%), the Western dry mountain zone (20%), and the Western Qilian snow mountain zone (5%). Almost all the environmental factors showed a significant contribution to the assemblages of bumblebees of different groups. Our findings highlight the need for better data to understand species biogeography and diversity patterns, and they provide key baseline data for refining conservation strategies.

miR-9-5p and miR-221-3p Promote Human Mesenchymal Stem Cells to Alleviate Carbon Tetrachloride-Induced Liver Injury by Enhancing Human Mesenchymal Stem Cell Engraftment and Inhibiting Hepatic Stellate Cell Activation.

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-ß, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.

A novel nomogram to predict glucocorticoid response in thyroid-associated ophthalmopathy: findings from a pilot study.

PURPOSE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. CONCLUSION: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Yeast ß-glucan-based nanoparticles loading methotrexate promotes osteogenesis of hDPSCs and periodontal bone regeneration under the inflammatory microenvironment.

The regeneration of absorbed alveolar bone and reconstruction of periodontal support tissue are huge challenges in the clinical treatment of periodontitis due to the limited regenerative capacity of alveolar bone. It is essential to regulate inflammatory reaction and periodontal cell differentiation. Based on the anti-inflammatory effect of baker's yeast ß-glucan (BYG) with biosafety by targeting macrophages, the BYG-based nanoparticles loading methotrexate (cBPM) were fabricated from polyethylene glycol-grafted BYG through chemical crosslinking for treatment of periodontitis. In our findings, cBPM promoted osteogenesis of human dental pulp stem cells (hDPSCs) under inflammatory microenvironment, characterized by the enhanced expression of osteogenesis-related Runx2 and activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/Erk) pathway in vitro. Animal experiments further demonstrate that cBPM effectively promoted periodontal bone regeneration and achieved in a better effect of recovery indicated by 19.2 % increase in tissue volume, 7.1 % decrease in trabecular separation, and a significant increase in percent bone volume and trabecular thickness, compared with the model group. Additionally, cBPM inhibited inflammation and repaired alveolar bone by transforming macrophage phenotype from inflammatory M1 to anti-inflammatory M2. This work provides an alternative strategy for the clinical treatment of periodontitis through BYG-based delivery nanoplatform of anti-inflammatory drugs.

SIVA-1 interaction with PCBP1 serves as a predictive biomarker for cisplatin sensitivity in gastric cancer and its inhibitory effect on tumor growth in vivo.

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear. Methods and results: Immunohistochemistry and histoculture drug response assays were used to determine SIVA-1 expression and the inhibition rate (IR) of agents to GC and to further analyze the relationship between these two phenomena. Additionally, cisplatin (DDP)-resistant GC cells were used to elucidate the role and mechanism of SIVA-1 in vivo. The results demonstrated that SIVA-1 expression was positively correlated with the IR of DDP to GC but not with those of 5-fluorouracil (5-FU) or adriamycin (ADM). Furthermore, SIVA-1 overexpression with DDP treatment synergistically inhibited tumor growth in vivo by increasing PCBP1 and decreasing Bcl-2 and Bcl-xL expression. Conclusions: Our study demonstrated that SIVA-1 may serve as an indicator of the GC sensitivity to DDP, and the mechanism of SIVA-1 in GC resistance to DDP was preliminarily revealed.

Inflammatory proteins may mediate the causal relationship between gut microbiota and inflammatory bowel disease: A mediation and multivariable Mendelian randomization study.

This research investigates the causal relationships among gut microbiota, inflammatory proteins, and inflammatory bowel disease (IBD), including crohn disease (CD) and ulcerative colitis (UC), and identifies the role of inflammatory proteins as potential mediators. Our study analyzed gut microbiome data from 13,266 samples collected by the MiBioGen alliance, along with inflammatory protein data from recent research by Zhao et al, and genetic data on CD and UC from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We used Mendelian randomization (MR) to explore the associations, complemented by replication, meta-analysis, and multivariable MR techniques for enhanced accuracy and robustness. Our analysis employed several statistical methods, including inverse-variance weighting, MR-Egger, and the weighted median method, ensuring comprehensive and precise evaluation. After MR analysis, replication and meta-analysis, we revealed significant associations between 11 types of gut microbiota and 17 inflammatory proteins were associated with CD and UC. Mediator MR analysis and multivariable MR analysis showed that in CD, the CD40L receptor mediated the causal effect of Defluviitaleaceae UCG-011 on CD (mediation ratio 8.3%), and the Hepatocyte growth factor mediated the causal effect of Odoribacter on CD (mediation ratio 18%). In UC, the C-C motif chemokine 4 mediated the causal effect of Ruminococcus2 on UC (mediation ratio 4%). This research demonstrates the interactions between specific gut microbiota, inflammatory proteins, and CD and UC. Furthermore, the CD40L receptor may mediate the relationship between Defluviitaleaceae UCG-011 and CD; the Hepatocyte growth factor may mediate the relationship between Odoribacter and CD; and the C-C motif chemokine 4 may mediate the relationship between Ruminococcus2 and UC. The identified associations and mediation effects offer insights into potential therapeutic approaches targeting the gut microbiome for managing CD and UC.

Dixon MRI-based quantitative parameters of extraocular muscles, intraorbital fat, and lacrimal glands for staging thyroid-associated ophthalmopathy.

OBJECTIVE: To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). METHODS: Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. RESULTS: Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p < 0.05). The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were independently associated with active TAO (all p < 0.05). The combination of the EOM-SIRmean, LG-SIRmean, and LG-FFmean values showed better performance than the EOM-SIRmean value alone in staging TAO in both the training (AUC, 0.820 vs 0.793; p = 0.016) and validation (AUC, 0.751 vs 0.733, p = 0.341) cohorts. CONCLUSION: Dixon MRI-based parameters of EOMs, LGs, and IF are useful for differentiating active from inactive TAO. The integration of multiple parameters can further improve staging performance. CRITICAL RELEVANCE STATEMENT: In this study, the authors explored the combined value of quantitative parameters of EOMs, IF, and LGs derived from Dixon MRI in staging TAO patients, which can support the establishment of a proper therapeutic plan. KEY POINTS: The quantitative parameters of EOMs, LGs, and IF are useful for staging TAO. The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were found to independently correlate with active TAO. Joint evaluation of orbital tissue improved the ability to assess TAO activity.

The complete chloroplast genome assembly of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China.

Species in the Amorphophallus genus are important cash crops in many tropical and subtropical Asian countries. Although several molecular markers have been employed to determine relationships and assess genetic variation in the Amorphophallus genus, some conflicts remain in infrageneric classification and evolution. To aid in the phylogenetic research of the Amorphophallus genus, we collected one sample of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China. We assembled the first chloroplast genome of this species using high-throughput sequencing. The assembled genome was 169,341 bp long with a typical quadripartite structure (GenBank accession number: PP234804). The lengths of the large single-copy region, small single-copy region, and two inverted repeats were 90,705 bp, 15,640 bp, 31,498 bp, and 31,498 bp, respectively. We annotated 129 genes across the chloroplast genome of A. tonkinensis. The phylogenetic trees suggested that the Amorphophallus species distributed in continental Asia split into two main clades. The chloroplast genome reported in our study provided valuable genomic resources for the future phylogenetic research of the Amorphophallus genus.

Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability.

As the most prescribed psychotropic drugs in current medical practice, antidepressant drugs (ADs) of the selective serotonin reuptake inhibitor (SSRI) class represent prime candidates for drug repurposing. The mechanisms underlying their mode of action, however, remain unclear. Here, we show that common SSRIs and selected representatives of other AD classes bidirectionally regulate fluid-phase uptake at therapeutic concentrations and below. We further characterize membrane trafficking induced by a canonical SSRI fluvoxamine to show that it involves enhancement of clathrin-mediated endocytosis, endosomal system, and exocytosis. RNA sequencing analysis showed few fluvoxamine-associated differences, consistent with the effect being independent of gene expression. Fluvoxamine-induced increase in membrane trafficking boosted transcytosis in cell-based blood-brain barrier models, while a single injection of fluvoxamine was sufficient to enable brain accumulation of a fluid-phase fluorescent tracer in vivo. These findings reveal modulation of membrane trafficking by ADs as a possible cellular mechanism of action and indicate their clinical repositioning potential for regulating drug delivery to the brain.

Advancements and Practical Considerations for Biophysical Research: Navigating the Challenges and Future of Super-resolution Microscopy.

The introduction of super-resolution microscopy (SRM) has significantly advanced our understanding of cellular and molecular dynamics, offering a detailed view previously beyond our reach. Implementing SRM in biophysical research, however, presents numerous challenges. This review addresses the crucial aspects of utilizing SRM effectively, from selecting appropriate fluorophores and preparing samples to analyzing complex data sets. We explore recent technological advancements and methodological improvements that enhance the capabilities of SRM. Emphasizing the integration of SRM with other analytical methods, we aim to overcome inherent limitations and expand the scope of biological insights achievable. By providing a comprehensive guide for choosing the most suitable SRM methods based on specific research objectives, we aim to empower researchers to explore complex biological processes with enhanced precision and clarity, thereby advancing the frontiers of biophysical research.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

KCTD15 acts as an anti-tumor factor in colorectal cancer cells downstream of the demethylase FTO and the m6A reader YTHDF2.

Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A 'reader' YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15's actions in CRC cells.

Improved Prediction of Epidermal Growth Factor Receptor Status by Combined Radiomics of Primary Nonsmall-Cell Lung Cancer and Distant Metastasis.

OBJECTIVES: This study aimed to investigate radiomics based on primary nonsmall-cell lung cancer (NSCLC) and distant metastases to predict epidermal growth factor receptor (EGFR) mutation status. METHODS: A total of 290 patients (mean age, 58.21 ± 9.28) diagnosed with brain (BM, n = 150) or spinal bone metastasis (SM, n = 140) from primary NSCLC were enrolled as a primary cohort. An external validation cohort, consisting of 69 patients (mean age, 59.87 ± 7.23; BM, n = 36; SM, n = 33), was enrolled from another center. Thoracic computed tomography-based features were extracted from the primary tumor and peritumoral area and selected using the least absolute shrinkage and selection operator regression to build a radiomic signature (RS-primary). Contrast-enhanced magnetic resonance imaging-based features were calculated and selected from the BM and SM to build RS-BM and RS-SM, respectively. The RS-BM-Com and RS-SM-Com were developed by integrating the most important features from the primary tumor, BM, and SM. RESULTS: Six computed tomography-based features showed high association with EGFR mutation status: 3 from intratumoral and 3 from peritumoral areas. By combination of features from primary tumor and metastases, the developed RS-BM-Com and RS-SM-Com performed well with areas under curve in the training (RS-BM-Com vs RS-BM, 0.936 vs 0.885, P = 0.177; RS-SM-Com vs RS-SM, 0.929 vs 0.843, P = 0.003), internal validation (RS-BM-Com vs RS-BM, 0.920 vs 0.858, P = 0.492; RS-SM-Com vs RS-SM, 0.896 vs 0.859, P = 0.379), and external validation (RS-BM-Com vs RS-BM, 0.882 vs 0.805, P = 0.263; RS-SM-Com vs RS-SM, 0.865 vs 0.816, P = 0.312) cohorts. CONCLUSIONS: This study indicates that the accuracy of detecting EGFR mutations significantly enhanced in the presence of metastases in primary NSCLC. The established radiomic signatures from this approach may be useful as new predictors for patients with distant metastases.

Boron Reduced Copper Excess-Induced Oxidative Damage in Citrus sinensis by Modulating Reactive Oxygen Species and Methylglyoxal Formation and Their Detoxification Systems.

Citrus is mainly cultivated in acid soil with low boron (B) and high copper (Cu). In this study, Citrus sinensis seedlings were submitted to 0.5 (control) or 350 µM Cu (Cu excess or Cu exposure) and 2.5, 10, or 25 µM B for 24 weeks. Thereafter, H2O2 production rate (HPR), superoxide production rate (SAPR), malondialdehyde, methylglyoxal, and reactive oxygen species (ROS) and methylglyoxal detoxification systems were measured in leaves and roots in order to test the hypothesis that B addition mitigated Cu excess-induced oxidative damage in leaves and roots by reducing the Cu excess-induced formation and accumulation of ROS and MG and by counteracting the impairments of Cu excess on ROS and methylglyoxal detoxification systems. Cu and B treatments displayed an interactive influence on ROS and methylglyoxal formation and their detoxification systems. Cu excess increased the HPR, SAPR, methylglyoxal level, and malondialdehyde level by 10.9% (54.3%), 38.9% (31.4%), 50.3% (24.9%), and 312.4% (585.4%), respectively, in leaves (roots) of 2.5 µM B-treated seedlings, while it only increased the malondialdehyde level by 48.5% (97.8%) in leaves (roots) of 25 µM B-treated seedlings. Additionally, B addition counteracted the impairments of Cu excess on antioxidant enzymes, ascorbate-glutathione cycle, sulfur metabolism-related enzymes, sulfur-containing compounds, and methylglyoxal detoxification system, thereby protecting the leaves and roots of Cu-exposed seedlings against oxidative damage via the coordinated actions of ROS and methylglyoxal removal systems. Our findings corroborated the hypothesis that B addition alleviated Cu excess-induced oxidative damage in leaves and roots by decreasing the Cu excess-induced formation and accumulation of ROS and MG and by lessening the impairments of Cu excess on their detoxification systems. Further analysis indicated that the pathways involved in the B-induced amelioration of oxidative stress caused by Cu excess differed between leaves and roots.

Portable hydrogel kit driven by bimetallic carbon dots nanozyme for H2O2-self-supplying dual-modal monitoring of atmospheric CH3SH.

Due to the typical volatility of gaseous pollutant methyl mercaptan (CH3SH), the development of a facile, reliable, and accurate onsite environmental surveillance of highly toxic CH3SH faces many challenges, but it is critical to environmental atmosphere assessment and safeguarding public health. Here, we prepared a novel bimetallic carbon dots (Fe&Cu@CDs) nanozyme with high peroxidase-mimicking activity to design a portable hydrogel kit for onsite visual H2O2-self-supplying enzymatic cascade catalytic colorimetric and photothermal signal synergistic amplification dual-modal monitoring of CH3SH in atmospheric environment. Assisted by alcohol oxidase (AOX), CH3SH could be specifically converted into H2O2 for oxidizing chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by Fe&Cu@CDs to produce dark blue ox-TMB with absorption at 652 nm and photothermal characters. Consequently, a CH3SH concentration-dependent change both in naked-eye color and photothermal effect-triggered temperature were observed. By hybridizing AOX-assisted Fe&Cu@CDs + TMB with agarose, a H2O2-self-supplying colorimetric and photothermal signal synergistic amplification sensory hydrogel kit integrated with Color Picker APP-installed smartphone and 660 nm laser-equipped handheld thermal imager for CH3SH was proposed with acceptable results in atmospheric environment around wastepile (e.g., solid waste and food waste piles), which exhibited great potentials to further develop commercial onsite monitoring platforms in warning-early abnormal atmospheric CH3SH for safeguarding environmental health.

DKK1 Activates the PI3K/AKT Pathway via CKAP4 to Balance the Inhibitory Effect on Wnt/ß-Catenin Signaling and Regulates Wnt3a-Induced MSC Migration.

Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.

Altered Static and Dynamic Brain Functional Topological Organization in Patients With Dysthyroid Optic Neuropathy.

CONTEXT: Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. OBJECTIVE: We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional magnetic resonance imaging with the graph theory method. METHODS: A cross-sectional study was conducted at a grade A tertiary hospital with 66 TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). Main outcome measures included topological properties of functional networks. RESULTS: For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. DON and non-DON patients both exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in the orbitofrontal cortex and visual network (VN). For dynamic properties, the DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in the DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. CONCLUSION: Functional network alterations were observed both in DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON.