Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus.

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

An FeCl3-catalyzed three-component reaction for the synthesis of ß-(1,2,3-triazolyl)-ketones using DMF as a one-carbon source.

An FeCl3-catalyzed oxidative condensation of NH-1,2,3-triazoles, aryl methyl ketones (or acetophenones) and DMF (N,N-dimethylformamide) for the synthesis of ß-(1,2,3-triazolyl)-ketones was developed. DMF serves as a one-carbon source, and the resulting products display diverse reaction selectivity, highlighting the existence of distinct approaches.

Integrated Untargeted Metabolome, Full-Length Sequencing and Transcriptome Analyses Reveal the Mechanism of Flavonoid Biosynthesis in Blueberry (Vaccinium spp.) Fruit.

As a highly economic berry fruit crop, blueberry is enjoyed by most people and has various potential health benefits, many of which are attributed to the relatively high concentrations of flavonoids. To obtain more accurate and comprehensive transcripts, the full-length transcriptome of half-highbush blueberry (Vaccinium corymbosum/angustifolium cultivar Northland) obtained using single molecule real-time and next-generation sequencing technologies was reported for the first time. Overall, 147,569 consensus transcripts (average length, 2738 bp; N50, 3176 bp) were obtained. After quality control steps, 63,425 high-quality isoforms were obtained and 5030 novel genes, 3002 long non-coding RNAs, 3946 transcription factor genes (TFs), 30,540 alternative splicing events, and 2285 fusion gene pairs were identified. To better explore the molecular mechanism of flavonoid biosynthesis in mature blueberry fruit, an integrative analysis of the metabolome and transcriptome was performed on the exocarp, sarcocarp, and seed. A relatively complete biosynthesis pathway map of phenylpropanoids, flavonoids, and proanthocyanins in blueberry was constructed. The results of the joint analysis showed that the 228 functional genes and 42 TFs regulated 78 differentially expressed metabolites within the biosynthesis pathway of phenylpropanoids/flavonoids. O2PLS analysis results showed that the key metabolites differentially accumulated in blueberry fruit tissues were albireodelphin, delphinidin 3,5-diglucoside, delphinidin 3-O-rutinoside, and delphinidin 3-O-sophoroside, and 10 structural genes (4 Vc4CLs, 3 VcBZ1s, 1 VcUGT75C1, 1 VcAT, and 1 VcUGAT), 4 transporter genes (1 VcGSTF and 3 VcMATEs), and 10 TFs (1 VcMYB, 2 VcbHLHs, 4 VcWD40s, and 3 VcNACs) exhibited strong correlations with 4 delphinidin glycosides. These findings provide insights into the molecular mechanisms of flavonoid biosynthesis and accumulation in blueberry fruit.

Associations of perchlorate, nitrate, and thiocyanate exposure with arthritis and inflammation indicators in young and middle-aged adults, NHANES 2005-2016.

Background: Perchlorates, nitrates, and thiocyanates are prevalent environmental chemicals. Their potential association with arthritis remains unexplored. This study aimed to investigate the link between perchlorate, nitrate, and thiocyanate exposure and arthritis, as well as the potential role of inflammation in this context. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data spanning from 2005 to 2016, the study enrolled 6597 participants aged 20-59 (young and middle-aged), of which 1045 had arthritis. Employing multivariate logistic regression modeling, multiple linear regression models, restricted cubic spline analysis, Bayesian kernel machine regression (BKMR) modeling, and mediation analysis, we assessed these relationships. Results: There was a significant positive association between elevated urinary thiocyanate levels and arthritis risk [1.19 (1.11, 1.28)]. This association held true across subgroups of osteoarthritis (OA) [1.24 (1.10, 1.40)] and rheumatoid arthritis (RA) [1.33 (1.15, 1.55)]. Thiocyanate levels displayed a dose-dependent relationship with arthritis risk, showing a linear trend (nonlinear P > 0.05). Conversely, perchlorate and nitrate did not exhibit associations with arthritis risk. BKMR outcomes highlighted a positive correlation between a mixture of perchlorate, nitrate, and thiocyanate and arthritis risk, with thiocyanate being the predominant predictors. Moreover, BKMR and generalized linear model analyses unveiled no significant synergistic effect of urinary perchlorate, nitrate, and thiocyanate on arthritis risk. Furthermore, thiocyanate exposure has been linked to elevated levels of inflammatory indicators (white blood cell, neutrophils, lymphocytes, and systemic immune-inflammatory index (SII)). Conclusion: Heightened thiocyanate exposure may be linked to elevated arthritis risk, either single or in combined effects. Additionally, thiocyanate exposure is associated with heightened inflammation levels.

Layer-by-Layer Organic Solar Cells Enabled by 1,3,4-Selenadiazole-Containing Crystalline Small Molecule with Double-Fibril Network Morphology.

A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.

Unveiling hidden interactions: Microorganisms, enzymes, and mangroves at different stages of succession in the Shankou Mangrove Nature Reserve, China.

Understanding the interactions between microorganisms, soil extracellular enzymes, and mangroves is crucial for conserving and restoring mangrove ecosystems. However, the unique environments associated with mangroves have resulted in a lack of pertinent data regarding the interactions between these components. Root, stem, leaf, and soil samples were collected at three distinct stages of mangrove succession. Stoichiometry was employed to analyze the carbon, nitrogen, and phosphorus contents of these samples and to quantify extracellular enzyme activities, microbial biomass, and various physicochemical factors in the soil. The results showed that the trends of C, N, and P in the mangrove plants were consistent. Microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and microbial biomass phosphorus (MBP) were the highest in the Kandelia obovate community. Catalase (CAT) and ß-D-G showed the highest content in K. obovate and Bruguiera gymnorrhiza, whereas cellulase showed the opposite trend. Urease was least abundant in the K. obovate community, whereas neutral protease (NPR) and acid phosphatase (ACP) were most abundant. The overall soil environment in mangroves exhibited a state of N limitation, with varying degrees of limitation observed across different succession stages. The demand for P became more intense in the later stages of succession, particularly in the K. obovate and B. gymnorrhiza communities. In conjunction with correlation analysis, it indicated that the input of mangrove plant litter had a significant regulatory influence on the C, N, and P contents in the soil. There was a significant positive correlation between MBC, MBN, and MBP, indicating synergistic effects of C, N, and P on soil microorganisms. Therefore, evaluating the nutrient ratios and sufficiency of mangroves allowed us to comprehensively understand the present environmental conditions. This study aims to develop sustainable management strategies for the conservation and restoration of mangroves.

Delamination of Plasticized Devices in Dynamic Service Environments.

With the continuous development of advanced packaging technology in heterogeneous semiconductor integration, the delamination failure problem in a dynamic service environment has gradually become a key factor limiting the reliability of packaging devices. In this paper, the delamination failure mechanism of polymer-based packaging devices is clarified by summarizing the relevant literature and the latest research solutions are proposed. The results show that, at the microscopic scale, thermal stress and moisture damage are still the two main mechanisms of two-phase interface failure of encapsulation devices. Additionally, the application of emerging technologies such as RDL structure modification and self-healing polymers can significantly improve the thermal stress state of encapsulation devices and enhance their moisture resistance, which can improve the anti-delamination reliability of polymer-based encapsulation devices. In addition, this paper provides theoretical support for subsequent research and optimization of polymer-based packages by summarizing the microscopic failure mechanism of delamination at the two-phase interface and introducing the latest solutions.

The impact of short-term exposure to meteorological factors on the risk of death from hypertension and its major complications: a time series analysis based on Hefei, China.

OBJECTIVES: This study aimed to reveal the short-term impact of meteorological factors on the mortality risk in hypertensive patients, providing a scientific foundation for formulating pertinent prevention and control policies. METHODS: In this research, meteorological factor data and daily death data of hypertensive patients in Hefei City from 2015 to 2018 were integrated. Time series analysis was performed using distributed lag nonlinear model (DLNM) and generalized additive model (GAM). Furthermore, we conducted stratified analysis based on gender and age. Relative risk (RR) combined with 95% confidence interval (95% CI) was used to represent the mortality risk of single day and cumulative day in hypertensive patients. RESULTS: Single-day lag results indicated that high daily mean temperature (T mean) (75th percentile, 24.9 °C) and low diurnal temperature range (DTR) (25th percentile, 4.20 °C) levels were identified as risk factors for death in hypertensive patients (maximum effective RR values were 1.144 and 1.122, respectively). Extremely high levels of relative humidity (RH) (95th percentile, 94.29%) reduced the risk of death (RR value was 0.893). The stratified results showed that the elderly and female populations are more susceptible to low DTR levels, whereas extremely high levels of RH have a more significant protective effect on both populations. CONCLUSION: Overall, we found that exposure to low DTR and high T mean environments increases the risk of death for hypertensive patients, while exposure to extremely high RH environments significantly reduces the risk of death for hypertensive patients. These findings contribute valuable insights for shaping targeted prevention and control strategies.

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages.

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.

Facile Preparation of a Photo-Cross-Linked Silk Fibroin-Poly Ionic Liquid Hydrogel with Antifreezing and Ion Conductive Properties.

The silk fibroin (SF)/ionic liquid (IL) based hydrogel is a kind of remarkable substrate for flexible devices because of its subzero-temperature elasticity, electrical conductivity, and water retention, although the procedure of the gelation is considered complex and time-consuming. In this work, we introduced an approximate method for the development of novel photo-cross-linked SF/IL hydrogel, that is, SF-IMA/PIL hydrogel via the modification of silk fibroin chain with 2-isocyanatoethyl methacrylate (SF-IMA) in a certain ionic liquid with an unsaturated double bond. The chemical cross-linking between methacrylated SF and IL was triggered by UV light, while the physical cross-linking of the hydrogel was attributed to the ß-sheet formation of SF in SF-IMA/IL mixed solution. In addition to being a UV-induced three-dimensional (3D) printable one, the SF-IMA/PIL hydrogel performed significant ionic conductivity between room temperature and -50 °C and water retention within a wide range of relative humidity, which were the featured advantages as the ionic liquid involved. Moreover, the static and dynamic mechanical tests demonstrated that the hydrogel reserved its great elasticity at -50 °C and displayed its stiffness transition temperatures between -100 and -70 °C.

Global trends and partial forecast of adverse effects of medical treatment from 1990 to 2019: an epidemiological analysis based on the global burden of disease study 2019.

BACKGROUND: The possibility of adverse effects of medical treatment (AEMT) is increasing worldwide, but little is known about AEMT in China. This study analyzed the health burden of AEMT in China in recent years through the Global Burden of Disease Study (GBD) 2019 and compared it with the worldwide average level and those in different sociodemographic index (SDI) regions. METHODS: We calculated the age-standardized rate (ASR) of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), incidence and prevalence attributed to AEMT in China, worldwide and countries with different sociodemographic indices during 1990-2019 using the latest data and methods from the GBD 2019. RESULTS: From 1990 to 2019, the global age-standardized death rate (ASDR), DALYs, and YLLs for AEMT showed a significant downward trend and were negatively associated with the SDI. By 2040, the ASDR is expected to reach approximately 1.58 (95% UI: 1.33-1.80). From 1990 to 2019, there was no significant change in the global incidence of AEMT. The occurrence of AEMT was related to sex, and the incidence of AEMT was greater among females. In addition, the incidence of AEMT-related injuries and burdens, such as ASR of DALYs, ASR of YLLs and ASR of YLDs, was greater among women than among men. Very old and very young people were more likely to be exposed to AEMT. CONCLUSIONS: From 1990 to 2019, progress was made worldwide in reducing the harm caused by AEMT. However, the incidence and prevalence of AEMT did not change significantly overall during this period. Therefore, the health sector should pay more attention to AEMT and take effective measures to reduce AEMT.

Promoting In Vivo NIR-II Fluorescent Imaging for Lipid in Lipid Metabolism Diseases Diagnosis.

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.

Independent and combined associations of polycyclic aromatic hydrocarbons exposure and sleep disorders among adults in the U.S. adult population.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are prevalent organic pollutants in the environment; however, limited research has been conducted to explore their potential effects on sleep disorders. This study aims to investigate the relationship between single and mixed PAHs exposures and sleep disorders. METHODS: This study analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016, involving 7730 adult participants. To examine the relationship between PAHs exposure and sleep disorders, we employed survey-weighted multivariate logistic regression models and restricted cubic spline (RCS) models to evaluate single PAHs exposure. Additionally, we employed three mixed-exposure models to examine the relationship between combined PAHs exposure and sleep disorders. RESULTS: After adjusting for covariates, our analyses revealed positive associations between several urinary PAHs metabolites (1-hydroxynaphthalene (1-NAP), 2-NAP, 3-hydroxyfluorene (3-FLU), 2-FLU, and 1-hydroxypyrene (1-PYR)) and sleep disturbance. Consistency across various analytical methods underscores a discernible positive correlation between simultaneous exposure to PAHs and sleep disorders. This association is predominantly influenced by the presence of NAP and FLU. Remarkably, a positive relationship between combined PAHs exposure and sleep disorders emerged within the younger and middle-aged demographic but did not manifest within the elderly population. CONCLUSION: In conclusion, our study provides new epidemiological evidence suggesting that both single and mixed PAHs exposures may increase the risk of sleep disorders. Further prospective investigations are necessary to validate these findings.

In Vivo Imaging of γ-Glutamyl Transferase in Cardiovascular Diseases with a Photoacoustic Probe.

In this work, a photoacoustic (PA) probe, HDS-GGT, was developed for the in vivo imaging of cardiovascular diseases by monitoring the γ-glutamyl transferase (GGT) dynamics. HDS-GGT exhibited a stable PA signal with auxiliary absorbance and NIRF variation after the trigger by GGT. In all three modalities of absorbance, NIRF, and PA, HDS-GGT could quantitatively reflect the GGT level. In PA modality, HDS-GGT indicated the practical advantages including high sensitivity, high stability, and high specificity. In living oxidized low-density lipoprotein-induced RAW264.7 cells, HDS-GGT indicated proper capability for imaging the plaques by visualizing the GGT dynamics. Moreover, during imaging in living model mice, HDS-GGT was achieved to distinguish the plaques from healthy blood vessels via a multiview PA presentation. HDS-GGT could also suggest the severity of plaques in the extracted aorta from the model mice, which was consistent with the histological staining results. The information herein might be useful for future investigations on cardiovascular diseases.

GK921, a transglutaminase inhibitor, strengthens the antitumor effect of cisplatin on pancreatic cancer cells by inhibiting epithelial-to-mesenchymal transition.

Pancreatic adenocarcinoma (PAAD), a common digestive malignant tumor, presents high mortality rates and limited treatment methods. Currently, chemotherapy remains the main therapy method for patients with PAAD. As a classical chemotherapy drug, cisplatin (DDP) is limited by dose-related toxicity in patients with PAAD. In this study, we demonstrated that TGM2 may be a treatment and prognosis marker in pancreatic cancer patients. Co-treatment of low dose of DDP and GK921, a transglutaminase (TGM2) inhibitor, is capable of synergistically inhibiting the PAAD cell viability and proliferation in vitro and in vivo. Based on in vitro study, GK921 inhibited the epithelial-to-mesenchymal transition (EMT) induced by TGM2 as well as aggravated cell cycle arrest and apoptosis resulted from DDP, making pancreatic cancer cells more sensible to DDP. Our results showed that GK921 increased the protein levels regarding E-cadherin as well as decreased the protein level regarding Snail2, N-cadherin, which indicated that GK921 inhibited EMT in pancreatic cancer cells. Snail2 overexpression inhibited GK921/DDP-induced cell apoptosis, as well as mitigated the GK921/DDP-caused cell death and the EMT inhibition. In vivo studies also found GK921/DDP combination can further inhibit the growth of PAAD without significantly side effects. To sum up, we showed that GK921 increased PAAD cells sensitivity to DDP via inhibiting EMT. As revealed, DDP/GK921 co-treatment could promisingly serve for treating PAAD patients.

Discovery of a novel potential polyphosphate accumulating organism without denitrifying phosphorus uptake function in an enhanced biological phosphorus removal process.

Enhanced biological phosphorus removal (EBPR) is an effective process for phosphorus removal from wastewater. In this study, two lab-scale sequencing batch reactors (SBR) were used to perform EBPR process, in which genus Propioniciclava was unexpectedly accumulated and its relative abundance was over 70 %. A series of tests were conducted to explore the role of Propioniciclava in the two EBPR systems. The two systems performed steadily throughout the study, and the phosphorus removal efficiencies were 96.6 % and 93.5 % for SBR1 and SBR2, respectively. The stoichiometric analysis related to polyphosphate accumulating organisms (PAOs) indicated that polyphosphate accumulating metabolism (PAM) was achieved in the anaerobic phase. It appeared that the Propioniciclava-dominated systems could not perform denitrifying phosphorus removal. Instead, phosphorus was released under anoxic conditions without carbon sources. According to the genomic information from Integrated Microbial Genomes (IMG) database, Propioniciclava owns ppk1, ppk2 and ppx genes that are associated with phosphorus release and uptake functions. By phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) analysis, the abundance of genes related to phosphorus metabolism was much higher than that of genes related to denitrification. Therefore, Propioniciclava was presumed to be a potential PAO without denitrifying phosphorus uptake function. In addition to Propioniciclava, Tessaracoccus and Thiothrix were also enriched in both systems. Overall, this study proposes a novel potential PAO and broadens the understanding of EBPR microbial communities.

Metal-organic framework-modulated Fe3O4 composite au nanoparticles for antibacterial wound healing via synergistic peroxidase-like nanozymatic catalysis.

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Near-infrared imaging of hepatocellular carcinoma and its medicinal treatment with a γ-glutamyl transpeptidase-monitoring fluorescence probe.

Herein, the Near-infrared imaging of hepatocellular carcinoma (HCC) and its medicinal treatment was achieved with a γ-glutamyl transpeptidase (GGT)-monitoring fluorescence probe KYZ-GGT which consisted of the typical recognition group γ-glutamyl and the structurally modified signal reporting group hemicyanine-thioxanthene. Compared with the recently reported probes, KYZ-GGT suggested practical and steady capability for monitoring the GGT level in the cellular, xenograft, induced as well as medicinal treatment HCC models. It realized the mitochondrial targeting intracellular imaging to reflect the GGT dynamics in the induction or medicinal treatment of HCC. In the xenograft and induced model mice with multiple factors, KYZ-GGT showed stable performance for visualizing the HCC status. In the medicinal treatment of the long-period-induced HCC model mice verified by the serum indexes and histopathological analysis, KYZ-GGT successfully imaged the medicinal treatment process of HCC with two marketed drugs (Sorafenib and Lenvatinib) respectively, with an applicative penetration depth. The information here was meaningful for investigating effective medicinal strategies for overcoming HCC.

Optimization Landscape of Policy Gradient Methods for Discrete-Time Static Output Feedback.

In recent times, significant advancements have been made in delving into the optimization landscape of policy gradient methods for achieving optimal control in linear time-invariant (LTI) systems. Compared with state-feedback control, output-feedback control is more prevalent since the underlying state of the system may not be fully observed in many practical settings. This article analyzes the optimization landscape inherent to policy gradient methods when applied to static output feedback (SOF) control in discrete-time LTI systems subject to quadratic cost. We begin by establishing crucial properties of the SOF cost, encompassing coercivity, L -smoothness, and M -Lipschitz continuous Hessian. Despite the absence of convexity, we leverage these properties to derive novel findings regarding convergence (and nearly dimension-free rate) to stationary points for three policy gradient methods, including the vanilla policy gradient method, the natural policy gradient method, and the Gauss-Newton method. Moreover, we provide proof that the vanilla policy gradient method exhibits linear convergence toward local minima when initialized near such minima. This article concludes by presenting numerical examples that validate our theoretical findings. These results not only characterize the performance of gradient descent for optimizing the SOF problem but also provide insights into the effectiveness of general policy gradient methods within the realm of reinforcement learning.

Integration of transcriptomic and metabolomic analyses reveal the molecular responses of the mud crab Scylla paramamosain to infection by an undescribed endoparasite Portunion sp.

Portunion is a rare endoparasitic isopod genus, recently observed inhabiting the hemocoel of the commercially important mud crab, Scylla paramamosain. For better understanding of the host-parasite interaction between S. paramamosain and Portunion sp., the metabolomic and transcriptomic changes in the hemolymph of the S. paramamosain were analyzed. We detected a total of 143 and 126 differentially accumulated metabolites in the positive and negative modes, respectively. Pathways related to amino acids and vitamin synthesis, such as Aminoacyl-tRNA biosynthesis, Tyrosine metabolism, Cysteine and methionine metabolism, Vitamin B6 metabolism, and Biotin metabolism were significantly enriched. Based on the transcriptomic data, a total of 942 differentially expressed genes were identified, of which 25 and 36 were significantly related to the immune system and metabolic pathways, respectively. Based on the metabolomic and transcriptomic data, 90 correlated metabolite-gene pairs were selected to build a regulatory network. Common significantly enriched pathways, including Starch and sucrose metabolism, Metabolism of xenobiotics by cytochrome P450, Aminoacyl-tRNA biosynthesis, Nitrogen metabolism, and Galactose metabolism were detected. On the basis of our analysis, the endoparasite Portunion sp. places a heavy metabolic burden on the host, particularly with respect to fundamental resources, such as amino acids, vitamins, carbohydrates, and lipids. In summary, these data provide an overview of the global metabolic and transcriptomic changes of the S. paramamosain resulting from Portunion sp. infection.