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The family Apiaceae, distributed throughout the Northern Hemisphere, is the largest family of angiosperms. However, little is known about the conservation status, diversity, and distribution of Apiaceae species in Mongolia. This study had two main aims: (1) to assess the national status of Apiaceae species under IUCN Red List Criterion B; (2) to evaluate the species diversity and richness of Apiaceae across Mongolia. We utilized ConR packages to assess the national Red List status of all known Mongolian Apiaceae species by analyzing their most comprehensive occurrence records. The results indicated that 27 species were classified as threatened, including 4 Critically Endangered (CR), 9 Endangered (EN), and 14 Vulnerable (VU) species. Meanwhile, 39 species were assessed as non-threatened, with 2 Near Threatened (NT) species and 37 species of Least Concern (LC). Furthermore, detailed distribution maps for 66 Apiaceae species in Mongolia were presented. We assessed the species diversity and Shannon and Simpson diversity indices of Apiaceae by analyzing all occurrence records using the iNext package. Overall, the Hill diversity estimates indicate that the sampling conducted in Mongolia adequately captured species occurrences. For species pattern analysis, we examined the species richness, weighted endemism, and the corrected weighted endemism index using Biodiverse v.4.1 software. Mongolia was portioned into 715 grid cells based on 0.5° × 0.5° grid sizes (equivalent to approximately 50 × 50 km2). There was a total of 3062 unique occurrences of all Apiaceae species across Mongolia. In the species richness analysis, we identified 10 grids that exhibited high species richness (18–29 species) and 36 grids with 11–17 species. For genus richness, we observed seven grids that exhibited a high genus richness of 16–22 genera. Furthermore, we analyzed species richness with a specific focus on threatened species, encompassing CR, EN, and VU species throughout Mongolia. A total of 92 grids contained at least one threatened species. There were six grids that had two to five threatened species, which were adequately covered by protected areas in western Mongolia. Overall, our results on species richness and conservation status will serve as important foundational research for future conservation and land management efforts in Mongolia. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a widely prevalent malignancy strongly linked to inflammation, remains a significant public health concern. Triggering receptor expressed on myeloid cells 1 (TREM1), a modulator of inflammatory responses identified in recent years, has emerged as a crucial facilitator in cancer progression. Despite its significance, the precise regulatory mechanism of TREM1 in HCC metastasis remains unanswered. In the present investigation, we observed aberrant upregulation of TREM1 in HCC tissues, which was significantly linked to poorer overall survival. Inhibition of TREM1 expression resulted in a significant reduction in HCC Huh-7 and MHCC-97H cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) process. Furthermore, inhibiting TREM1 decreased protein expressions of toll-like receptor 2/4 (TLR2/4) and major myeloid differentiation response gene 88 (MyD88), leading to the inactivation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in HCC cells. Notably, these effects were reversed by treatment with TLR2-specific agonist (CU-T12-9), indicating a potential crosstalk between TREM1 and TLR2/4. Mechanistic studies revealed a direct interaction between TREM1 and both TLR2 and TLR4. In vivo studies demonstrated that inhibition of TREM1 suppressed the growth of HCC cells in the orthotopic implant model and its metastatic potential in the experimental lung metastasis model. Overall, our findings underscore the role of TREM1 inhibition in regulating EMT and metastasis of HCC cells by inactivating the TLR/PI3K/AKT signaling pathway, thereby providing deeper mechanistic insights into how TREM1 regulates metastasis during HCC progression. [ABSTRACT FROM AUTHOR]

Wind power has emerged as a successful component within power systems. The ability to reliably and accurately forecast wind speed is of great importance in maintaining the security and stability of the power grid. However, the significance of explaining prediction models has often been overlooked by researchers. To address this gap, this study introduces a novel approach to wind speed forecasting that incorporates a significant decomposition method, attention‐based machine learning, and local explanation techniques. The proposed model utilizes grid search variational mode decomposition to decompose the wind speed sequence into different modes while employing gate recurrent unit with an attention mechanism to achieve superior forecasting performance. Experimental evaluations conducted on eight real‐world wind speed datasets demonstrate that the proposed approach outperforms other popular models across multiple performance criteria. In two specific experiments, the proposed approach achieved a minimal mean absolute percentage error of 2.74% and 1.70%, respectively. Furthermore, local interpretable model‐agnostic explanations (LIME) were employed to assess the influence of factors, highlighting whether they positively or negatively affected the predicted values. [ABSTRACT FROM AUTHOR]

To address the issues of insufficient receptive fields for extracting low-level features and the lack of reinforcement for local key features in lightweight networks, this paper proposed a multistage feature distillation-weighted lightweight image super-resolution network LMSWN. Firstly, a pyramid- like module is employed to expand the receptive field during shallow feature extraction, integrate feature information of different scales, and enrich the information flow of the network. Secondly, a multi-stage residual distillation-weighted module is designed to enhance the ability of square convolution to extract local key features, recover more detailed information, and improve reconstruction performance. At the same time, the combination of channel separation and 1x1 convolution realizes gradual distillation of features, reducing the number of network parameters. Finally, two adaptive parameters are introduced to jointly learn the features of the two branches of the multi-stage residual distillationweighted module, enhancing the attention to different levels of feature information and further enhancing the representation ability of the network. Experimental results show that the proposed network is fully validated on five benchmark datasets: Set 5, Set 14, BSDS 100, Urban 100, and Manga 109, and its performance exceeds the current mainstream lightweight network [ABSTRACT FROM AUTHOR]

The acyltransferase from Pseudomonas protegens (PpATase) catalyzes in nature the reversible transformation of monoacetylphloroglucinol to diacetylphloroglucinol and phloroglucinol. Interestingly, this enzyme has been shown to catalyze the promiscuous transformation of 3‐hydroxyphenyl acetate to 2′,4′‐dihydroxyacetophenone, representing a biological version of the Fries rearrangement. In the present study, we report a mechanistic investigation of this activity of PpATase using quantum chemical calculations. A detailed mechanism is proposed, and the energy profile for the reaction is presented. The calculations show that the acylation of the enzyme is highly exothermic, while the acetyl transfer back to the substrate is only slightly exothermic. The deprotonation of the C6−H of the substrate is rate‐limiting, and a remote aspartate residue (Asp137) is proposed to be the general base group in this step. Analysis of the binding energies of various acetyl acceptors shows that PpATase can promote both intramolecular and intermolecular Fries rearrangement towards diverse compounds. [ABSTRACT FROM AUTHOR]

Indole monooxygenases (IMOs) are enzymes from the family of Group E monooxygenases, requiring flavin adenine dinucleotide (FAD) for their activities. IMOs play important roles in both sulfoxidation and epoxidation reactions. The broad substrate range and high selectivity of IMOs make them promising biocatalytic tools for synthesizing chiral compounds. In the present study, quantum chemical calculations using the cluster approach were performed to investigate the reaction mechanism and the enantioselectivity of the IMO from Variovorax paradoxus EPS (VpIndA1). The sulfoxidation of methyl phenyl sulfide (MPS) and the epoxidation of indene were chosen as the representative reactions. The calculations confirmed that the FADOOH intermediate is the catalytic species in the VpIndA1 reactions. The oxidation of MPS adopts a one-step mechanism involving the direct oxygen-transfer from FADOOH to the substrate and the proton transfer from the –OH group back to FAD, while the oxidation of indene follows a stepwise mechanism involving a carbocation intermediate. It was computationally predicted that VpIndA1 prefers the formation of (S)-product for the MPS sulfoxidation and (1S,2R)-product for the indene epoxidation, consistent with the experimental observations. Importantly, the factors controlling the stereo-preference of the two reactions are identified. The findings in the present study provide valuable insights into the VpIndA1-catalyzed reactions, which are essential for the rational design of this enzyme and other IMOs for industrial applications. It is also worth emphasizing that the quantum chemical cluster approach is again demonstrated to be powerful in studying the enantioselectivity of enzymatic reactions. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time–kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin. [ABSTRACT FROM AUTHOR]

Aiming at the inaccurate phoneme segmentation problem caused by the lack of consideration of Lao language tone changes and audio diversity in existing methods, this paper proposes an unsupervised phoneme segmentation method for Lao language with multi-feature interaction fusion. Firstly, self-supervised features, spectral features and pitch features are independently coded to avoid the insufficiency of a single feature. Secondly, multiple independent features are gradually fused based on the attention mechanism, so that the model can more comprehensively capture the information of Lao language tone changes and phoneme boundaries. Finally, a learnable framework is adopted to optimize the phoneme segmentation model. The experimental results show that the proposed method improves the R-value by 27.88% on the Lao phoneme segmentation task compared with the baseline methods. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to develop a Transformer‐based deep learning (DL) network for prognostic stratification in hepatocellular carcinoma (HCC) patients undergoing RFA. Methods: A Swin Transformer DL network was trained to establish associations between magnetic resonance imaging (MRI) datasets and the ground truth of microvascular invasion (MVI) based on 696 surgical resection (SR) patients with solitary HCC ≤3 cm, and was validated in an external cohort (n = 180). The multiphase MRI‐based DL risk outputs using an optimal threshold of.5 was employed as a MVI classifier for prognosis stratification in the RFA cohort (n = 180). Results: Over 90% of all enrolled patients exhibited hepatitis B virus infection. Liver cirrhosis was significantly more prevalent in the RFA cohort compared to the SR cohort (72.2% vs. 44.1%, p <.001). The MVI risk outputs exhibited good performance (area under the curve values =.938 and.883) for predicting MVI in the training and validation cohort, respectively. The RFA patients at high risk of MVI classified by the MVI classifier demonstrated significantly lower recurrence‐free survival (RFS) and overall survival rates at 1, 3 and 5 years compared to those classified as low risk (p <.001). Multivariate cox regression modelling of a‐fetoprotein > 20 ng/mL [hazard ratio (HR) = 1.53; 95% confidence interval (95% CI): 1.02–2.33, p =.047], high risk of MVI (HR = 3.76; 95% CI: 2.40–5.88, p <.001) and unfavourable tumour location (HR = 2.15; 95% CI: 1.40–3.29, p =.001) yielded a c‐index of.731 (bootstrapped 95% CI:.667–.778) for evaluating RFS after RFA. Among the three risk factors, MVI was the most powerful predictor for intrahepatic distance recurrence. Conclusions: The proposed MVI classifier can serve as a valuable imaging biomarker for prognostic stratification in early‐stage HCC patients undergoing RFA. [ABSTRACT FROM AUTHOR]

Norcoclaurine synthase from Thalictrum flavum (TfNCS) demonstrated high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, achieving kinetic resolution of aldehydes. However, the mechanism and the factors contributing to the stereoselectivity remain unclear. Herein, by using quantum chemical calculations, the mechanisms of TfNCS-catalyzed reactions of dopamine with both enantiomers of α-methyl-phenylacetaldehyde are studied. The calculations reveal a mechanism mirroring the reaction of natural substrates, for which the deprotonation of the C5−H of the cyclized intermediate is rate-limiting. The calculated overall barriers are 20.1 kcal mol-1 and 21.6 kcal mol-1 for the reactions of (R)- and (S)-α-methyl-phenylacetaldehyde, respectively. The M97 and L72 residues are proposed to be the key residues contributing to the stereospecificity. The obtained detailed information is helpful for designing new variants of TfNCS with extended substrate scope, and also advancing our understanding of TfNCS reactions for potential applications. Norcoclaurine synthase from Thalictrum flavum (TfNCS) has been demonstrated to display high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, however, the mechanism and factors related to this high stereospecificity remain unclear. Here, the authors conduct quantum chemical calculations and reveal the rate-limiting step and differential energy barriers for the reactions of two enantiomers of α-methylphenylacetaldehyde, as well as key residues related to stereospecificity. [ABSTRACT FROM AUTHOR]

Many traditional Chinese medicines (TCMs) have been confirmed to have antibacterial activities. However, very few substances have been found to be active against Gram-negative bacteria. This study aimed to identify antimicrobial activity substances against Gram-negative bacteria from fourteen TCMs. Fourteen TCMs with antibacterial potential were chosen for quantitative extraction and antibacterial activity assay, and the plant with the highest activity against Escherichia coli was selected to construct the component-target network. The following virtual screening and enzyme inhibition experiments were performed to analyse the antibacterial mechanisms of the compounds from Galla chinensis. The chemical constituents of Galla chinensis were identified by chemical fingerprinting. 1, 2, 3, 4, 6-Penta-O-galloyl-β-D-glucose (PGG) from Galla chinensis exhibited significant inhibition activity against adenylyl transferase (ATase) of E. coli and antibacterial activity against E. coli. Meanwhile, PGG was identified in the Galla chinensis ethanol extract as the abundant ingredient with a high content of 1.95% (w/w). PGG enriched in Galla chinensis is a promising natural antibiotic with the mode of action inhibiting ATase activity. To our knowledge, this is the first study attributing the antibacterial activity of PGG to its affinity with ATase. [ABSTRACT FROM AUTHOR]

Invasive alien plants (IAPs) have serious environmental and economic impacts, especially in vulnerable areas of China. However, IAP richness distribution patterns, their driving factors, and the dynamic shifts in potential distribution areas remain elusive. We assessed IAP richness distribution patterns and drivers using 402 IAPs recorded in China at 88 926 occurrence points, and then predicted their potential distribution areas. The results show that IAP hotspots were mainly located in southeastern China, especially coastal areas of the South and East and large inland cities. Population density, gross domestic product (GDP), and four climate variables associated with precipitation and temperature jointly influenced the richness distribution pattern of all IAPs. Specifically, population density and GDP impacted the richness distribution pattern of narrow‐range IAPs, and population density, GDP, distance to the nearest national highway, and five climate variables affected the richness distribution pattern of widespread IAPs. Only GDP contributed significantly to the richness distribution pattern of the top 5% hotspot grid cells, whereas population density, GDP, and precipitation in the driest month (BIO14) significantly influenced the richness distribution patterns of hotspots for both the top 10% and top 20%. Prediction analysis demonstrated that southeastern China would have particularly high invasion risk under both current and future climate scenarios. Regions with increases in predicted species richness are more common (44.83–64.97%) than those with decreases, except under the Representative Concentration Pathway (RCP) 4.5 scenario. Climate change will contribute greatly to the expansion of potential IAP distribution areas under both optimistic (RCP 2.5) and pessimistic scenarios (RCP 8.5). The results of this study provide insights into the priority management of IAPs by developing promising strategies for the control and prevention of IAP invasion. [ABSTRACT FROM AUTHOR]

Bioactive peptides derived from proteins found in various foods provide significant health benefits, including regulating blood sugar levels by inhibiting carbohydrate-hydrolyzing enzymes. Hydrolysates of peanut protein were prepared using alcalase (AH) or trypsin (TH) to generate antidiabetic peptides with high activity against α-amylase (IC50 of 6.46 and 5.71 mg/mL) and α-glucosidase (IC50 of 6.30 and 5.57 mg/mL), as well as antiradical activity to scavenge DPPH• (IC50 of 4.18 and 3.12 mg/mL) and ABTS•+ (IC50 of 2.87 and 2.56 mg/mL), respectively. The bioactivities of hydrolysates were greatest in the ultrafiltration-generated F3 fraction (< 3 kDa). The most active fraction was TH-F3, which was purified by gel filtration chromatography to generate sub-fractions (SF). With IC50 values of 1.05 and 0.69 mg/mL, the F3-SF8 fraction was the most effective at inhibiting the activity of α-amylase and α-glucosidase, respectively. This fraction was further purified using RP-HPLC to generate sub-subfractions (SSF), the most active of which were F3-SF8-SSF9 and SSF10. The peptide sequences F3-SF8-SSF9 and SSF10 were determined using LC-MS/MS. Two novel antidiabetic peptides with the potential to inhibit α-amylase and α-glucosidase were identified, with the sequences Asp-Trp-Arg (476.22 Da, IC50 of 0.78, and 0.35 mg/mL) and Phe-Tyr (329.15 Da, IC50 of 0.91, and 0.41 mg/mL). These results suggest that peptides derived from peanut protein are attractive natural ingredients for diabetes management applications. [ABSTRACT FROM AUTHOR]

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C−C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ‐tertiary alcohols from readily available materials, such as L‐aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single‐step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment. [ABSTRACT FROM AUTHOR]

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C−C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ‐tertiary alcohols from readily available materials, such as L‐aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single‐step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment. [ABSTRACT FROM AUTHOR]

Background: C2H2-zinc finger transcription factors comprise one of the largest and most diverse gene superfamilies and are involved in the transcriptional regulation of flowering. Although a large number of C2H2 zinc-finger proteins (C2H2-ZFPs) have been well characterized in a number of model plant species, little is known about their expression and function in Coptis teeta. C. teeta displays two floral phenotypes (herkogamy phenotypes). It has been proposed that the C2H2-zinc finger transcription factor family may play a crucial role in the formation of floral development and herkogamy observed in C. teeta. As such, we performed a genome-wide analysis of the C2H2-ZFP gene family in C. teeta. Results: The complexity and diversity of C. teeta C2H2 zinc finger proteins were established by evaluation of their physicochemical properties, phylogenetic relationships, exon-intron structure, and conserved motifs. Chromosome localization showed that 95 members of the C2H2 zinc-finger genes were unevenly distributed across the nine chromosomes of C. teeta, and that these genes were replicated in tandem and segmentally and had undergone purifying selection. Analysis of cis-acting regulatory elements revealed a possible involvement of C2H2 zinc-finger proteins in the regulation of phytohormones. Transcriptome data was then used to compare the expression levels of these genes during the growth and development of the two floral phenotypes (F-type and M-type). These data demonstrate that in groups A and B, the expression levels of 23 genes were higher in F-type flowers, while 15 genes showed higher expressions in M-type flowers. qRT-PCR analysis further revealed that the relative expression was highly consistent with the transcriptome data. Conclusion: These data provide a solid basis for further in-depth studies of the C2H2 zinc finger transcription factor gene family in this species and provide preliminary information on which to base further research into the role of the C2H2 ZFPs gene family in floral development in C. teeta. [ABSTRACT FROM AUTHOR]

Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring- closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies. [ABSTRACT FROM AUTHOR]

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as FHJ / exp(-0:20 ± 0:06 ± t Gyr). In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar agemetallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as FHJ / 101:6+0:3 -0:3-[Fe=H] and FWJ=CJ / 101:1+0:2 -0:3-[Fe=H], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits. [ABSTRACT FROM AUTHOR]

Little research has been done for artificial intelligence applications of semiconductor backend. This study aims to develop a deep learning based fault diagnosis framework as prognostics and health management (PHM) solutions with a comprehensive analytics process. A linear encoder sensor is employed to measure position, while data preparation is conducted to convert position information into a signal. Then, signal processing is used to extract the features, in which high pass filter is applied to normalize the signal and emphasize the features. High-dimensional features including time domain statistical features, time-frequency domain features obtained by continuous wavelet transform (CWT), and frequency domain features converted by fast Fourier transform (FFT) are extracted to prepare the dataset. An ensemble neural network model that integrates deep neural network (DNN) and convolutional neural network (CNN) is employed to recognize the pattern and diagnose the positioning errors. The accuracy and false alarm rate are considered to support maintenance decisions. An empirical study was conducted in a world leading IC assembly and testing company for validation. The results have shown that the proposed approach can effectively detect inappropriate installation of the bond head in wire bonding equipment for predictive maintenance and cost reduction. [ABSTRACT FROM AUTHOR]

National key protected wild plants (NKPWPs) are species with important conservation value based on genetics, ecology, culture, and/or scientific research, which are also confronted with serious threats. However, their geographical distribution patterns and conservation status remain unclear. In this study, we compiled 1032 species of NKPWPs. We measured the diversity to identify hotspots of NKPWPs based on species richness, weighted range size rarity and a complementarity‐based analysis. Comparing the distribution and hotspots of NKPWPs with the coverage of Chinese nature reserves (NRs), we assessed conservation effectiveness and identified conservation gaps. The results identified 13 diversity hotspots; only 9.5% of them were covered by NRs with >30% of the grid cell area, and even 19.5% were not covered at all by NRs. Overall, 44.7% of NKPWPs were effectively protected by national NRs. Despite this success, 571 species in Yunnan, Guizhou, Sichuan, Chongqing, Guangxi, Guangdong, southern Hainan, Taiwan, and northern Xinjiang remain unprotected by NRs. The protected proportion of plants with first‐level protection was lower than that of plants with second‐level protection. The low overall proportion of protected hotspots indicates that the conservation outlook for NKPWPs is not optimistic. This study identifies priority conservation areas and conservation gaps and provides a scientific reference for the conservation of wild plants in China. [ABSTRACT FROM AUTHOR]

Background: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time. Purpose: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients. Material and Methods: Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared. Results: Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06–0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05). Conclusion: A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients. [ABSTRACT FROM AUTHOR]

The canonical glycolysis pathway is responsible for converting glucose into 2 molecules of acetyl-coenzyme A (acetyl-CoA) through a cascade of 11 biochemical reactions. Here, we have designed and constructed an artificial phosphoketolase (APK) pathway, which consists of only 3 types of biochemical reactions. The core enzyme in this pathway is phosphoketolase, while phosphatase and isomerase act as auxiliary enzymes. The APK pathway has the potential to achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating a one-carbon condensation reaction. We tested the APK pathway in vitro, demonstrating that it could efficiently catabolize typical C1-C6 carbohydrates to acetyl-CoA with yields ranging from 83% to 95%. Furthermore, we engineered Escherichia coli stain capable of growth utilizing APK pathway when glycerol act as a carbon source. This novel catabolic pathway holds promising route for future biomanufacturing and offering a stoichiometric production platform using multiple carbon sources. The canonical glycolysis pathway converts glucose into two molecules of acetyl-CoA via a cascade of eleven biochemical reactions. This study repurposes phosphoketolase to construct an artificial pathway which comprises only three reactions and could theoretically achieve a 100% carbon yield of acetyl-CoA from any sugar. [ABSTRACT FROM AUTHOR]

Background: A number of patients with Crohn's disease (CD) suffer from loss of response to infliximab (IFX) therapy. Splenic volume is reported to be enlarged in patients with CD compared to normal individuals. The association between splenic volume and IFX efficacy in CD remains unclear. Methods: We performed a retrospective study of patients with CD who received regular IFX treatment at Zhongshan Hospital, Fudan University, between August 2015 and December 2021. We collected baseline characteristics and clinical features from medical records in the CD database of Zhongshan Hospital. We accurately measured the splenic volume using semi-auto spleen segmentation software, followed by the analysis of splenic volume and IFX efficacy. Results: We included 49 patients with CD receiving IFX treatment, of whom 41 responded to IFX and 8 failed to respond to IFX. Splenic volume, as well as volume adjusted for body mass index (SV/BMI) and body weight (SV/W), was significantly decreased after IFX treatment in responders but increased in non-responders compared to the volume before the treatment. Accordingly, the levels of leukocyte count, platelet count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were decreased after IFX treatment in responders. Contrarily, the levels of hemoglobin, albumin, and tumor necrosis factor (TNF)- α were elevated in responders. Moreover, both CRP and TNF-α levels were significantly positively correlated with SV/BMI in all patients. Conclusion: Splenic volume, especially SV/BMI and SV/W, was reduced after IFX treatment in CD patients responsive to IFX. SV/BMI was positively correlated with disease activity. Splenic volume is a promising indicator to evaluate IFX efficacy in CD. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 exploits the homotrimer transmembrane Spike glycoproteins (S protein) during host cell invasion. The Omicron XBB subvariant, delta, and prototype SARS-CoV-2 receptor-binding domain show similar binding strength to hACE2 (human Angiotensin-Converting Enzyme 2). Here we utilized multiligand virtual screening to identify small molecule inhibitors for their efficacy against SARS-CoV-2 virus using QPLD, pseudovirus ACE2 Inhibition -Time Resolved Forster/Fluorescence energy transfer (TR-FRET) Assay Screening, and Molecular Dynamics simulations (MDS). Three hundred and fifty thousand compounds were screened against the macrodomain of the nonstructural protein 3 of SARS-CoV-2. Using TR-FRET Assay, we filtered out two of 10 compounds that had no reported activity in in vitro screen against Spike S1: ACE2 binding assay. The percentage inhibition at 30 µM was found to be 79% for "Compound F1877-0839" and 69% for "Compound F0470-0003". This first of its kind study identified "FILLY" pocket in macrodomains. Our 200 ns MDS revealed stable binding poses of both leads. They can be used for further development of preclinical candidates. [ABSTRACT FROM AUTHOR]

Text normalization (TN) is an indispensable work in the front-end analysis task of speech synthesis text. Lao text normalization is to convert non-standard words (NSW) in Lao text into spoken-form words (SFW). At present, the task of text normalization has not yet been carried out in Lao, which mainly faces the problems of difficult acquisition of training data, diversified language expression and text regularization with ambiguity. A text normalization task in Lao is carried out. This ask is completed as a sequence tagging task, and neural networks are used to predict NSW with ambiguity in combination with context. The corpus of the Lao text normalization task is constructed, the model results is predicted through the neural network, the self-attention mechanism is increased to deepen the relationship between the sequence characters, and different strategies are explored to introduce the pre-trained language model. An accuracy of 67.59% is achieved on the test set. [ABSTRACT FROM AUTHOR]

A significant fraction of higher plants in China are threatened due to dramatic landscape transformation and increasing climate change. However, the conservation effectiveness of threatened higher plants (THPs) and their response to climate change are still underexplored to date. Based on the latest list of THPs in China, we obtained 102 593 occurrence records with latitude and longitude for 3858 THPs. By integrating the distribution patterns of three biodiversity indexes (i.e., species richness, species complementarity, and weighted endemism) and 10 plant categories, we identified hotspots for THPs and calculated the conservation effectiveness of nature reserves. We then selected 1959 THPs to project the shift of species richness and range sizes under climate change (representative concentration pathway [RCP] 2.6 and RCP 8.5). In total, 16 hotspot areas covering 7.38% of Chinese land area and containing 91.73% of THPs were identified. Current nature reserves protected 35.05% of hotspots, 73.07% of all THPs, and 56.64% of narrow‐ranged species. By the 2070s, the species richness of THPs were predicted to decrease in Southeast and Central China, and 42.42% (RCP 2.6) and 51.40% (RCP 8.5) of the 1959 THPs would confront habitat contraction. Future conservation efforts should focus on the conservation gaps and carry out targeted conservation for THPs with narrow distribution range. In order to cope with climate change, the hotspots with relatively low species loss can serve as important areas to contain current species diversity and the areas with high species gain offer opportunities for ex‐situ conservation of THPs. [ABSTRACT FROM AUTHOR]

Background: Limited data regarding the effects of school-based obesity prevention programs focusing on the changes in obesity-related knowledge and behaviors in China are available. The objective of this paper was to evaluate the effects of a school-based comprehensive lifestyle intervention among Chinese kids against obesity (CLICK-Obesity) in primary schools in Nanjing. Methods: We designed a cluster randomized controlled trial in eight randomly selected urban primary schools among 4th graders between May 2011 to April 2012 in Jianye, an urban district of Nanjing. Each school was randomly assigned to either the intervention or control group (four schools in each group). Mixed regression models and generalized estimating equations (GEE) were used to adjust for individual-level covariates under cluster randomization. Results: In this study, 1178 students (96.2%; 665 boys and 513 girls, 544 in control and 634 in intervention) participated in the baseline survey with mean age 10.2 ± 0.5 years. At the end of one-year intervention, 1125 students (91.8%; 628 boys and 497 girls, 513 in control and 612 in intervention) were reassessed. Notably, we found that the intervention group improved the knowledge and awareness of obesity-related risk factors, presented a lower increase of consumption of red/white meat (with a mean difference of −180.9 g/week, 95% CI: −350.6 to −11.2, p = 0.040), a larger increase in the time spent playing ball (with a mean difference of 24.2 min/week, 95% CI: −5.3 to 53.7, p = 0.090), and a significant reduction in screen time (with a mean difference of −71.0 min/week, 95% CI: −125.3 to −16.6, p = 0.020) compared to the control group after cluster (school) adjustment. Conclusion: The school-based integrated intervention was successful to modify unhealthy lifestyle behaviors and had a potential effect on childhood obesity prevention in urban China. However, the long-term effects and cost-effectiveness need to be evaluated in through further study. [ABSTRACT FROM AUTHOR]

Advanced hepatocellular carcinoma (HCC) is a formidable public health problem with limited curable treatment options. Axitinib, an oral tyrosine kinase inhibitor, is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. This anti-angiogenic drug was found to have promising activity in various solid tumors, including advanced HCC. At present, however, there is no relevant review article that summarizes the exact roles of axitinib in advanced HCC. In this review, 24 eligible studies (seven studies in the ClinicalTrials, eight experimental studies, and nine clinical trials) were included for further evaluation. The included randomized or single-arm phase II trials indicated that axitinib could not prolong the overall survival compared to the placebo for the treatment of advanced HCC, but improvements in progression free survival and time to tumor progression were observed. Experimental studies showed that the biochemical effects of axitinib in HCC might be regulated by its associated genes and affected signaling cascades (e.g. VEGFR2/PAK1, CYP1A2, CaMKII/ERK, Akt/mTor, and miR-509-3p/PDGFRA). FDA approved sorafenib combined with nivolumab (an inhibitor of PD-1/PD-L1) as the first line regimen for the treatment of advanced HCC. Since both axitinib and sorafenib are tyrosine kinase inhibitors as well as the VEGFR inhibitors, axitinib combined with anti-PDL-1/PD-1 antibodies may also exhibit tremendous potential in anti-tumoral effects for advanced HCC. The present review highlights the current clinical applications and the molecular mechanisms of axitinib in advanced HCC. To move toward clinical applications by combining axitinib and other treatments in advanced HCC, more studies are still warranted in the near future. [ABSTRACT FROM AUTHOR]

Strictosidine synthase (STR) catalyzes the Pictet–Spengler (PS) reaction of tryptamine and secologanin to produce strictosidine. Recent studies demonstrated that the enzyme can also catalyze the reaction of non‐natural substrates to form new alkaloid skeletons. For example, the PS condensation of 1H‐indole‐4‐ethanamine with secologanin could be promoted by the STR from Rauvolfia serpentina (RsSTR) to generate a rare class of skeletons with a seven‐membered ring, namely azepino‐[3,4,5‐cd]‐indoles, which are precursors for the synthesis of new compounds displaying antimalarial activity. In the present study, the detailed reaction mechanism of RsSTR‐catalyzed formation of the rare seven‐membered azepino‐indole skeleton through the PS reaction was revealed at the atomic level by quantum chemical calculations. The structures of the transition states and intermediates involved in the reaction pathway were optimized, and the energetics of the complete reaction were analyzed. Based on our calculation results, the most likely pathway of the enzyme‐catalyzed reaction was determined, and the rate‐determining step of the reaction was clarified. The mechanistic details obtained in the present study are important in understanding the promiscuous activity of RsSTR in the formation of the rare azepino‐indole skeleton molecule and are also helpful in designing STR enzymes for the synthesis of other new alkaloid skeleton molecules. [ABSTRACT FROM AUTHOR]

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Rubus (Rosaceae), one of the most complicated angiosperm genera, contains about 863 species, and is notorious for its taxonomic difficulty. The most recent (1910–1914) global taxonomic treatment of the genus was conducted by Focke, who defined 12 subgenera. Phylogenetic results over the past 25 years suggest that Focke's subdivisions of Rubus are not monophyletic, and large‐scale taxonomic revisions are necessary. Our objective was to provide a comprehensive phylogenetic analysis of the genus based on an integrative evidence approach. Morphological characters, obtained from our own investigation of living plants and examination of herbarium specimens are combined with chloroplast genomic data. Our dataset comprised 196 accessions representing 145 Rubus species (including cultivars and hybrids) and all of Focke's subgenera, including 60 endemic Chinese species. Maximum likelihood analyses inferred phylogenetic relationships. Our analyses concur with previous molecular studies, but with modifications. Our data strongly support the reclassification of several subgenera within Rubus. Our molecular analyses agree with others that only R. subg. Anoplobatus forms a monophyletic group. Other subgenera are para‐ or polyphyletic. We suggest a revised subgeneric framework to accommodate monophyletic groups. Character evolution is reconstructed, and diagnostic morphological characters for different clades are identified and discussed. Based on morphological and molecular evidence, we propose a new classification system with 10 subgenera: R. subg. Anoplobatus, R. subg. Batothamnus, R. subg. Chamaerubus, R. subg. Cylactis, R. subg. Dalibarda, R. subg. Idaeobatus, R. subg. Lineati, R. subg. Malachobatus, R. subg. Melanobatus, and R. subg. Rubus. The revised infrageneric nomenclature inferred from our analyses is provided along with synonymy and type citations. Our new taxonomic backbone is the first systematic and complete global revision of Rubus since Focke's treatment. It offers new insights into deep phylogenetic relationships of Rubus and has important theoretical and practical significance for the development and utilization of these important agronomic crops. [ABSTRACT FROM AUTHOR]

Endophytic fungi from desert plants belong to a unique microbial community that has been scarcely investigated chemically and could be a new resource for bioactive natural products. In this study, 13 secondary metabolites (1-13) with diverse carbon skeletons, including a novel polyketide (1) with a unique 5,6-dihydro-4H,7H-2,6-methanopyrano[4,3-d][1,3]dioxocin-7-one ring system and three undescribed polyketides (2, 7, and 11), were obtained from the endophytic fungus Neocamarosporium betae isolated from two desert plant species. Different approaches, including HR-ESI-MS, UV spectroscopy, IR spectroscopy, NMR, and CD, were used to determine the planar and absolute configurations of the compounds. The possible biosynthetic pathways were proposed based on the structural characteristics of compounds 1-13. Compounds 1, 3, 4, and 9 exhibited strong cytotoxicity toward HepG2 cells compared with the positive control. Several metabolites (2, 4-5, 7-9, and 11-13) were phytotoxic to foxtail leaves. The results support the hypothesis that endophytic fungi from special environments, such as desert areas, produce novel bioactive secondary metabolites. [ABSTRACT FROM AUTHOR]

Accurate prediction of oil consumption plays a dominant role in oil supply chain management. However, because of the effects of the coronavirus disease 2019 (COVID-19) pandemic, oil consumption has exhibited an uncertain and volatile trend, which leads to a huge challenge to accurate predictions. The rapid development of the Internet provides countless online information (e.g., online news) that can benefit predict oil consumption. This study adopts a novel news-based oil consumption prediction methodology–convolutional neural network (CNN) to fetch online news information automatically, thereby illustrating the contribution of text features for oil consumption prediction. This study also proposes a new approach called attention-based JADE-IndRNN that combines adaptive differential evolution (adaptive differential evolution with optional external archive, JADE) with an attention-based independent recurrent neural network (IndRNN) to forecast monthly oil consumption. Experimental results further indicate that the proposed news-based oil consumption prediction methodology improves on the traditional techniques without online oil news significantly, as the news might contain some explanations of the relevant confinement or reopen policies during the COVID-19 period. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL), an AMP mimics, has gained attention due to its broad-spectrum antibacterial activities, but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid, e.g., alanine (A), tryptophan (W) or phenylalanine (F), to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The G. mellonella infection model demonstrates that the copolymers are effective against the S. aureus infection in vivo. The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers. [ABSTRACT FROM AUTHOR]

Autophagy contributes to bone homeostasis and development under physiological conditions. Although previous studies have demonstrated the induction of the autophagy machinery by endogenous glucocorticoids (GCs), the precise mechanisms involved have not yet been clarified. The current study aimed to explore the effect of a low dose of GC (10−8 M dexamethasone, Dex) on autophagy in mouse embryonic osteoblastic precursor cells (MC3T3‐E1 cells) and the potential mechanisms. The results showed that 10−8 M Dex induced significant time‐dependent increases in the expression and activation of serum‐ and glucocorticoid‐induced kinase‐1 (SGK1) in MC3T3‐E1 cells and that these effects were accompanied by increased cell viability and decreased apoptosis. The autophagy inhibitor 3‐MA significantly inhibited Dex‐mediated promotion of viability. Moreover, Dex increased LC3II and Beclin‐1 levels and decreased SQSTM/p62 levels in a time‐dependent manner, and these effects were attenuated by pretreatment with 3‐MA. Transfection of Dex‐treated MC3T3‐E1 cells with shRNA‐SGK1 resulted in a significant reduction in cell viability and an increase in apoptosis. 3‐MA further exacerbated these effects of SGK1 inhibition. Knocking down SGK1 before Dex exposure significantly reduced the phosphorylated forkhead box O3a (p‐FOXO3a)/FOXO3 ratio, suppressed LC3II and Beclin‐1 levels, and increased SQSTM/p62 levels in MC3T3‐E1 cells, and these effects were amplified by 3‐MA. In conclusion, the results revealed that low‐dose GC treatment increased osteoblast viability by activating autophagy via the SGK1/FOXO3a pathway. [ABSTRACT FROM AUTHOR]

The polymerase chain reaction (PCR) is essential in nucleic acid amplification tests and is widely used in many applications such as infectious disease detection, tumor screening, and food safety testing; however, most PCR devices have inefficient heating and cooling ramp rates for the solution, which significantly limit their application in special scenarios such as hospital emergencies, airports, and customs. Here, we propose a temperature control strategy to significantly increase the ramp rates for the solution temperature by switching microfluidic chips between multiple temperature zones and excessively increasing the temperature difference between temperature zones and the solution; accordingly, we have designed an ultrafast thermocycler. The results showed that the ramp rates of the solution temperature are a linear function of temperature differences within a range, and a larger temperature difference would result in faster ramp rates. The maximum heating and cooling ramp rates of the 25 μL solution reached 24.12 °C/s and 25.28 °C/s, respectively, and the average ramp rate was 13.33 °C/s, 6–8 times higher than that of conventional commercial PCR devices. The thermocycler achieved 9 min (1 min pre-denaturation + 45 PCR cycles) ultrafast nucleic acid amplification, shortening the time by 92% compared to the conventional 120 min nucleic acid amplification, and has the potential to be used for rapid nucleic acid detection. [ABSTRACT FROM AUTHOR]

PURPOSE We aimed to assess the performance of quantitative 3D shape analysis in the differential diagno- sis of pancreatic serous oligocystic adenoma (SOA) and mucinous cystic neoplasm (MCN). METHODS Four hundred thirty-two patients diagnosed with serous cystic neoplasms (SCNs) or MCNs were retrospectively reviewed from August 2014 to July 2019 and finally 87 patients with MCNs (n = 45) and SOAs (n = 42) were included. Clinical data and magnetic resonance morphologic fea- tures with 3D shape analysis of lesions (shape sphericity, compacity, and volume) were recorded and compared between MCNs and SOAs according to the pathology. Univariable and multivari- able regression analyses were used to identify independent impact factors for differentiating MCN from SOA. RESULTS The age of MCN patients was younger than SOAs (43.02 ± 10.83 years vs. 52.78 ± 12.31 years; OR = 0.275; 95% CI: 0.098-0.768; P = .014). MCN has a higher female/male ratio than SOA (43/2 vs. 27/15; OR = 40.418; 95% CI: 2.704-604.171; P = .007) and was more often located in the distal of pancreas (OR = 31.403; 95% CI: 2.985-330.342; P = .004). Shape_Sphericity derived from 3D shape analysis was a significant independent factor in the multivariable analysis and the value of MCN was closer to 1 than SOA (OR = 35.153; 95% CI: 5.301-237.585; P < .001). Area under the receiver operating characteristic curve (AUC) of Shape_Sphericity was 0.923 (optimal cutoff value was 0.964876). CONCLUSION Shape_Sphericity in combination with age, sex, and location could help to distinguish MCN from SOA. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. Methods: 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. Results: Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P<0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II<600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II>600 mAU/mL) and PIMEThigh group (with metastasis and PIVKA-II>600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. Conclusion: The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients. [ABSTRACT FROM AUTHOR]

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulationevoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of j opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itchrelated scratching behaviors. [ABSTRACT FROM AUTHOR]

Instant dark teas (IDTs) were individually liquid-state fermented using the fungi Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis. To understand how the chemical constituents of IDTs were affected by the fungi, samples were collected and measured by liquid chromatography-tandem mass-tandem mass spectrometry (LC-MS/MS). Untargeted metabolomics analysis revealed that 1,380 chemical constituents were identified in positive and negative ion modes, and 858 kinds of chemical components were differential metabolites. Through cluster analysis, IDTs were different from the blank control, and their chemical constituents mostly included carboxylic acids and their derivatives, flavonoids, organooxygen compounds, and fatty acyls. And the metabolites of IDTs fermented by A. niger and A. tubingensis had a high degree of similarity and were classified into one category, which showed that the fungus used to ferment is critical to the formation of certain qualities of IDTs. The biosynthesis of flavonoids and phenylpropanoid, which involved nine different metabolites such as p-coumarate, p-coumaroyl-CoA, caffeate, ferulate, naringenin, kaempferol, leucocyanidin, cyanidin, and (-)-epicatechin, were significant pathways influencing the quality formation of IDTs. Quantification analysis indicated that the A. tubingensis fermented-IDT had the highest content of theaflavin, theabrownin, and caffeine, while the A. cristatus fermented-IDT had the lowest content of theabrownin, and caffeine. Overall, the results provided new insights into the relationship between the quality formation of IDTs and the microorganisms used in liquid-state fermentation. [ABSTRACT FROM AUTHOR]

Purpose: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs. Methods: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed. We used a certain CT attenuation of 30 HU to extract the enhancing tissue component from the tumor. Enhancing tissue volume and other CT features were assessed on venous-phase images. We evaluated the value of preoperative CT features for predicting the DFS after surgery. Univariate and multivariate Cox regression analyses were performed to find the independent risk factor for predicting the DFS. Results: Of the 132 patients, 68 were males and 64 were females, with a mean age of 61 years. The median follow-up duration was 60 months, and 28 patients experienced disease recurrence and distant metastasis during the follow-up period. Serosal invasion (p < 0.001; HR = 5.277) and enhancing tissue volume (p = 0.005; HR = 1.447) were the independent risk factors for predicting the DFS after curative resection for patients with primary gastric GISTs. Conclusion: Preoperative contrast-enhanced CT could be useful for predicting the DFS after the surgery of gastric GISTs, and serosal invasion and enhancing tissue volume were the independent risk factors. [ABSTRACT FROM AUTHOR]

The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking and a protease activity assay, we found four novel inhibitors targeting Mpro with the half maximal inhibitory concentration (IC50) and their binding affinities shown by the dissociation constants (KDs). Our new inhibitors CB-21, CB-25, CP-1 and LC24-20 have IC50s at 14.88 µM (95% Confidence Interval (95% CI): 10.35 µM to 20.48 µM), 22.74 µM (95% CI: 13.01 µM to 38.16 µM), 18.54µM (95% CI: 6.54 µM to 36.30 µM) and 32.87µM (95% CI: 18.37 µM to 54.80 µM)), respectively. The evaluation of interactions suggested that each inhibitor has a hydrogen bond or hydrophobic interactions with important residues, including the most essential catalytic residues: His41 and Cys145. All the four inhibitors have a much higher 50% lethal dose (LD50) compared with the well-known Mpro inhibitor GC376, demonstrating its low toxicity. These four inhibitors can be potential drug candidates for further in vitro and in vivo studies against COVID-19. [ABSTRACT FROM AUTHOR]

Spiraea hypericifolia L. is affiliated with the section Chamaedryon Ser. of the genus Spiraea L. (Rosaceae). Similar to many other Spiraea species, S. hypericifolia most often accumulates flavonols among other flavonoids, in particular quercetin and its derivatives. An ethanol–water extract from the aerial part of S. hypericifolia collected in the vicinity of the Ilyichovo settlement (Krasnoyarsk Krai, Russia) was analyzed by liquid chromatography with high-resolution mass spectrometry. Primary and secondary metabolites were found in the extract; structural interpretation consistent with quercetin and its derivatives was proposed for 10 of them. Major compounds were various glycosides of quercetin containing glucose (four compounds), galactose (one compound), xylose (two compounds), arabinose (one compound), or rutinose (one compound) as a carbohydrate residue. Isorhamnetin and 3-O-methylquercetin-3′-O-β-D-glucopyranoside were identified among methyl-containing compounds. The latter compound and reynoutrin, rhamnetin-3-O-β-D-xylopyranosyl-β-D-glucopyranoside, and quercetin-3-O-(6″-O-malonyl)-β-D-glucoside have not been previously found in S. hypericifolia. Data on the presence of quercetin and its derivatives in the extract of S. hypericifolia expand the understanding of the possible practical use of this plant. In addition, the microscopic features of S. hypericifolia leaves were studied. The diagnostic features of the leaf blade necessary for the authentication of raw materials were revealed: straight-walled epidermis cells, stomata located on both sides of the leaf blade (amphistomatic type), two types of trichomes, and wrinkled cuticula with nodi. The main anatomical diagnostic features of the leaves of S. hypericifolia were determined, which makes it possible to assess the authenticity of the raw material. [ABSTRACT FROM AUTHOR]

Salicylic acid decarboxylase (SDC) from the amidohydrolase superfamily (AHS) catalyzes the reversible decarboxylation of salicylic acid to form phenol. In this study, the substrate binding mode and reaction mechanism of SDC were investigated using computational and crystallographic methods. Quantum chemical calculations show that the enzyme follows the general mechanism of AHS decarboxylases. Namely, the reaction begins with proton transfer from a metal-coordinated aspartic acid residue (Asp298 in SDC) to the C1 of salicylic acid, which is followed by the C–C bond cleavage, to generate the phenol product and release CO2. Interestingly, the calculations show that SDC is a Mg-dependent enzyme rather than the previously proposed Zn-dependent, and the substrate is shown to be bidentately coordinated to the metal center in the catalysis, which is also different from the previous proposal. These predictions are corroborated by the crystal structure of SDC solved in complex with the substrate analogue 2-nitrophenol. The mechanistic insights into SDC in the present study provide important information for the rational design of the enzyme. [ABSTRACT FROM AUTHOR]

Impatiens yunlingensis S.X. Yu, Chang Y. Xia & J.H. Yu (Balsaminaceae), a species new to science discovered in Yunnan, China, is described and illustrated here, along with its phylogenetic position among other Impatiens species. Morphological, micro-morphological and molecular evidence is presented as an attestation of its novelty. Impatiens yunlingensis is similar to I. delavayi in having coarsely crenate leave margins, bracts in the upper part, ca. 4/5 length of the pedicels, saccate lower sepal with shallowly bifid spur, linear capsules, and elliptic-oblong, tuberculate seeds, but differs from I. delavayi with lateral sepals 4 (vs. 2), lateral united petal basal lobes subtriangular (vs. dolabriform), and seeds' surface equipped with tubercular ornamentation mostly covered with grain shaped appendages (vs. glabrous and without grain shaped appendages on the top). [ABSTRACT FROM AUTHOR]