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Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide. Recent advances in immunotherapies, targeted therapies, and combination treatments have significantly improved outcomes for many patients with HCC. This review summarizes key findings from the 2024 ASCO Annual Meeting, focusing on emerging therapies, including immune checkpoint inhibitors (ICIs), CAR-T cell therapies, oncolytic viruses, and locoregional treatments like transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC). ICIs, particularly when combined with other agents, have shown promising efficacy, though challenges such as immune-related adverse events and resistance mechanisms remain. CAR-T cell therapies and oncolytic viruses offer novel therapeutic avenues for advanced HCC, but their long-term efficacy in solid tumors is still under investigation. Locoregional therapies, especially in combination with systemic treatments, continue to play a critical role in managing unresectable HCC and improving conversion rates to surgical resection. Additionally, the potential of biomarkers, such as hypoxia scores and CTNNB1 mutations, is being explored to better personalize treatment and predict patient responses. These biomarkers could pave the way for more targeted and effective therapeutic strategies. Overall, the recent studies presented at the ASCO meeting highlight progress in HCC treatment, underscoring the importance of continued innovation. Future research should focus on overcoming resistance mechanisms, optimizing combination therapies, and integrating biomarker-driven approaches to improve patient outcomes and enhance personalized treatment strategies.

Liver cancer is a major global health concern, ranking among the top causes of cancer-related deaths worldwide. Despite advances in medical research, the prognosis for liver cancer remains poor, largely due to the inherent limitations of current therapies. Traditional treatments like surgery, radiation, and chemotherapy often fail to provide long-term remission and are associated with significant side effects. Immunotherapy has emerged as a promising avenue for cancer treatment, leveraging the body’s immune system to target and destroy cancer cells. However, its application in liver cancer has been limited. One of the primary challenges is the liver’s unique immune microenvironment, which can inhibit the effectiveness of immunotherapeutic agents. This immune microenvironment creates a barrier, leading to drug resistance and reducing the overall efficacy of treatment. Recent studies have focused on understanding the immunological landscape of liver cancer to develop strategies that can overcome these obstacles. By identifying the specific factors within the liver that contribute to immune suppression and drug resistance, researchers aim to enhance the effectiveness of immunotherapy. Prospective strategies include combining immunotherapy with other treatments, using targeted therapies to modulate the immune microenvironment, and developing new agents that can bypass or counteract the inhibitory mechanisms in the liver. These advancements hold promise for improving outcomes in liver cancer treatment.

Total oxidisable precursor (TOP) assay can oxidise some per- and polyfluoroalkyl substances (PFASs) and their precursors, most of which cannot be quantitatively detected so far, and convert them to detectable PFASs, such as perfluoroalkyl acids (PFAAs). However, the conversion is constrained by the complexity of the target samples, including co-existent organics, unknown PFAS precursors, and background. In this study, the TOP assay is modified to increase the oxidation and conversion efficiency by changing the initial concentration of target sample, increasing oxidising doses, time, temperature, etc. The modified TOP assay is applied to test several aqueous film-forming foams (AFFF) and a PFAS-contaminated soil extract. The sum concentrations of the detectable PFASs are increased by up to ∼534× in the AFFF samples and ∼7× in the PFAS-contaminated soil extract. The detectable fluorotelomer sulfonate (FTS, such as 6:2/8:2 FTS) is accounted as an oxidation indicator to monitor the oxidation and conversion progress of the oxidisable PFASs precursors to the detectable PFASs. Overall, the modified TOP assay could be an appropriate method for identifying missing PFASs mass in complex matrices by detecting the PFASs precursors effectively.

Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies < -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI.

Northwest China is a typical arid and semi-arid region that is part of Central Asia. However, during the past 60 years, the climate in Northwest China has shown a warm and humid trend, with both average and extreme precipitation continuing to increase. Humidification in Northwest China is mainly caused by anomalous westward water vapor transport. Change in the water vapor transport path is directly related to the Mongolian anticyclone anomaly and weakening of the Asian summer monsoon. Our research shows that interdecadal changes in sea surface temperature (SST) in the North Atlantic, North Pacific, and Indian oceans, play an important role in interdecadal adjustment of atmospheric circulation and the wetting climate over Northwest China. Since the 1980s, the Indian Ocean has been warming continuously, and the land–sea thermal gradient has weakened, resulting in a significant reduction in water vapor transport of the Asian summer monsoon. In contrast, anomalous northerly water vapor transport from the polar region increased. Concurrently, SST over the North Atlantic is also warming, and the Atlantic multidecadal oscillation (AMO) changes from the negative to positive phase, triggering anomalous anticyclones over Mongolia, which also leads to weakening of the Asian summer monsoon. Therefore, eastern China is affected by abnormal northeast winds. These northeast winds can continuously transport water vapor to the western region of China, leading to the prevalence of easterly winds in Northwest China. Moreover, Pacific decadal oscillation (PDO) changed from the positive to negative phase after the 1990s, which promoted the East Asian westerly jet to move to the Arctic and produce easterly anomalies in East Asia and Northwest China. Interdecadal changes in SST over the Indian, North Atlantic, and North Pacific Oceans all have reduced summer water vapor from the Indian Ocean. However, water vapor from the North Pacific and high latitudes (including the polar region) can be transported to Northwest China through easterly anomalies, resulting in increased precipitation and climate humidification.

Background: Liver fibrosis is a pathological outcome of a variety of liver diseases, and it can also progress into liver cirrhosis and liver cancer. Specific liver antifibrotic drugs have not been clinically approved yet. Studies have demonstrated the protective effects of Ganfule capsule (GFL) on the liver and its therapeutic potential in hepatic cancer. However, the mechanism of GFL is not clear in the treatment of liver fibrosis.Objective: This article aims to study the protective effect of GFL on liver fibrosis and its possible mechanism.Methods: The cholestatic liver fibrosis model was prepared by subjecting C57BL/6 mice to bile duct ligation (BDL). The GFL groups were treated with different concentrations of GFL for 14 days. Pathological analysis, serum biochemical index detection, metabonomic analysis, immunohistochemistry, Western blot, and real-time PCR were carried out.Results: GFL could alleviate liver injury and liver fibrosis caused by BDL in mice. Metabonomic analysis of mice serum showed postoperative metabolic disorder, which could be alleviated by GFL through glutamine metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-tRNA biosynthesis; and other metabolic pathways. GFL affected glutamine metabolism by inhibiting the activity of glutaminase 1 (GLS1). The activation of GLS1 is regulated by the NF-κB pathway, and experiments showed that GFL could inhibit IκB-α and NF-κB p65 phosphorylation.Conclusion: This study confirms the protective effect of GFL on liver injury and shows that GFL inhibits glutamine metabolism, which was correlated with the NF-κB pathway, and eventually alleviates liver fibrosis. These results are conducive to the development of new therapeutic drugs for liver fibrosis.

As an interesting and important trait of some drought-tolerant species, heteromorphic leaves are distributed differentially along plant vertical heights. However, the underpinning mechanism for the formation of heteromorphic leaves remains unclear. We hypothesize that heteromorphic leaves are caused by the hydraulic constraints possibly due to the compensation of the changes in functional traits in response to water transport capacity or the reduction of ineffective water loss. In this study, differences in water transport capacity, morphological traits, anatomical structures, and cellular water relations among three typical types of heteromorphic leaves (i.e., lanceolate, ovate, and broad-ovate) of Populus euphratica Oliv. (a dominant species of desert riparian forest in Central and West Asia) and their relationships were analyzed in order to explore the forming mechanism of heteromorphic leaves. The results showed that the lanceolate, ovate, and broad-ovate leaves were growing in the lower, intermediate, and higher positions from the ground, respectively. Morphological traits, anatomical structures, cellular water relations, and water transport capacity significantly varied among the three types of heteromorphic leaves (P< 0.01). Drought stress in broad-ovate leaves was significantly higher than that in ovate and lanceolate leaves (P< 0.01). Water transport capacity has significant correlations with morphological traits, anatomical structures, and cellular water relations (R2 ≥ 0.30; P< 0.01). Our results indicated that heteromorphic leaves were used as an important adaptive strategy for P. euphratica to alleviate the increase of hydraulic constraints along vertical heights.

In this study, the interdecadal variability of Eurasian spring snowmelt and its relationship with Eastern China summer precipitation (ECSP) are investigated based on observations and reanalysis data. Results show that the second mode of the empirical orthogonal function (EOF) analysis of the spring snowmelt, featured as a west-east dipole pattern, displays two interdecadal changes near the late-1970s and in the mid-2000s. The increased spring snowmelt over the Western Siberia (WSI) and the opposite situation over the Eastern Europe (EEU) are significantly linked to a meridional quadrupole summertime rainfall pattern on interdecadal time scales, with excessive rainfall over the regions of southern China (SC) and the Huang-Huai River (HHR) and deficient rainfall over the middle and lower reaches of Yangtze River Valley (YRV) and Inner Mongolia-northeastern China (IMNC). Besides, the possible mechanisms are discussed from the perspective of the hydrological effect related to snowmelt-induced soil moisture. Increased spring snowmelt can produce more water inflowing into the soil, leading to anomalous soil moisture, which can persist into summer. Excessive (deficient) snowmelt-related soil moisture anomalies over the WSI (EEU) in summer will change local land thermal conditions and thus generate cyclonic (anticyclonic) circulations with a quasi-barotropic structure. Therefore, the eastward-propagating wave-activity flux (WAF) could be strengthened over the WSI and EEU in the mid- and upper-troposphere and further propagate downstream. Combining the local response of atmospheric circulations to summer surface heating induced by local snowmelt-related SM anomalies over Mongolia, an anomalous anticyclonic (cyclonic) circulation near the Lake Baikal (SC) and the related strong descending (ascending) motion over the IMNC (SC) are founded. Besides, strong positive (negative) upper-level divergence appears over the YRV (HHR), which is the right (left) side of the exit region of upper-level jet. The upper-level divergence could be attributed to the convergence (divergence) of meridional winds on the right side of the anticyclonic circulation, thus the uniform descending (ascending) motion also appears over the YRV (HHR) through the collocation of upper-level convergence (divergence) and the compensatory lower-level circulations. Consequently, a quadrupole pattern of secondary circulation over Eastern China is founded, thereby causing the anomalously distributed ECSP under favorable water vapor conditions.

As opposed to macro-expressions, micro-expressions are subtle and not easily detectable emotional expressions, often containing rich information about mental activities. The practical recognition of micro-expressions is essential in interrogation and healthcare. Neural networks are currently one of the most common approaches to micro-expression recognition. Still, neural networks often increase their complexity when improving accuracy, and overly large neural networks require extremely high hardware requirements for running equipment. In recent years, vision transformers based on self-attentive mechanisms have achieved accuracy in image recognition and classification that is no less than that of neural networks. Still, the drawback is that without the image-specific biases inherent to neural networks, the cost of improving accuracy is an exponential increase in the number of parameters. This approach describes training a facial expression feature extractor by transfer learning and then fine-tuning and optimizing the MobileViT model to perform the micro-expression recognition task. First, the CASME II, SAMM, and SMIC datasets are combined into a compound dataset, and macro-expression samples are extracted from the three macro-expression datasets. Each macro-expression sample and micro-expression sample are pre-processed identically to make them similar. Second, the macro-expression samples were used to train the MobileNetV2 block in MobileViT as a facial expression feature extractor and to save the weights when the accuracy was highest. Finally, some of the hyperparameters of the MobileViT model are determined by grid search and then fed into the micro-expression samples for training. The samples are classified using an SVM classifier. In the experiments, the proposed method obtained an accuracy of 84.27%, and the time to process individual samples was only 35.4 ms. Comparative experiments show that the proposed method is comparable to state-of-the-art methods in terms of accuracy while improving recognition efficiency.

This study aimed to elucidate the mechanism of Bletilla striata oligosaccharides (BO) in the treatment of ulcerative colitis (UC). A UC mouse model was induced by 3% Dextran sodium sulfate (DSS), and BO (200 mg/kg/d) were administered for intervention. The results show that BO effectively inhibited the release of intestinal inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Also, BO profoundly elevated the secretion of mucins and the expression of tight junction (TJ) proteins to attenuate dysfunction of the intestinal barrier. The 16S rDNA sequencing and liquid chromatography/gas chromatography-mass spectrometer (LC/GC-MS) analysis of mouse feces revealed that BO regulated the disturbance of gut microbiota and intestinal metabolites. By using the in vitro fermentation broth of BO and gut microbiota-depleted mice treated with antibiotics, we confirmed the protection of BO against UC. In conclusion, BO played a role in improving UC by modulating gut microbial composition and intestinal metabolites, which provided new therapeutic strategies for UC treatment.

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent organic contaminants of concern to human and environmental health. Several literature reviews and laboratory column experiments have been conducted to determine the transport parameters and to describe the fate of PFAS as they migrate in subsurface environments. However, there are very few case studies focusing on contaminated sites with high-resolution field data. Such studies are crucial for the validation of transport simulation models that have been developed from experimental studies, prior to their broader applications. The key purpose of this research was to evaluate lithological separations of PFAS fractions as they are transported in the vadose zone of a historically (1979) contaminated site where Aqueous Film Forming Foam (AFFF) formulations (3M Lightwater™ and Ansulite™) have been used for fire training exercises. Surface and subsurface soils, and groundwater samples were collected across the site and a total of 29 PFAS compounds were selected as target analytes. The results indicated a distinct profile of PFAS concentration with depth at most of the test bores, exhibiting separation of PFAS as transported in vadose zone soils. Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonic acid (PFOS), and Perfluorohexane sulfonic acid (PFHxS) were the predominant compounds detected in the site samples and they have been found in near-surface soils (

Atractylodes lancea (Thunb.) DC. (AL) is used in traditional Chinese medicine for the treatment of spleen-deficiency syndrome (SDS). Bran-processed Atractylodes lancea (BAL) has been found to be more effective than unprocessed AL. However, the compound in BAL active against SDS remains unclear. The pharmacological efficacy of BAL and its mechanism of action against SDS were investigated by HPLC-ELSD. Candidate compound AA (atractyloside A) in AL and BAL extracts was identified by HPLC-MS analysis. AA was tested in a rat model of SDS in which body weight, gastric residual rate, and intestinal propulsion were measured, and motilin (MTL), gastrin (GAS), and c-Kit were quantified by enzyme-linked immunosorbent assay. Potential targets and associated pathways were identified based on network pharmacology analysis. mRNA expression levels were measured by qRT-PCR and protein expression levels were measured by Western blot analysis and immunohistochemistry. AA increased body weight, intestinal propulsion, MTL, GAS, and c-Kit levels, while decreasing gastric residual volume and intestinal tissue damage, as same as Epidermal Growth Factor Receptor and Proliferating Cell Nuclear Antigen levels. Seventy-one potential pharmacologic targets were identified. Analysis of protein interaction, Gene Ontology (GO) functional analysis, pathway enrichment analysis, and docking and molecular interactions highlighted MAPK signaling as the potential signal transduction pathway. Validation experiments indicated that treatment with AA increased MTL, GAS, ZO-1, and OCLN levels, while reducing AQP1, AQP3, and FGF2 levels. In addition, phosphorylation of p38 and myosin light-chain kinase (MLCK) expression were inhibited. AA improved gastrointestinal function by protecting the intestinal mucosal barrier via inhibition of the p38 MAPK pathway. The results have clinical implications for the therapy of SDS.