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Background & Aims: The immunological mechanisms underpinning the pathogenesis of alcoholic-associated liver disease (ALD) remain incompletely elucidated. This study aims to explore the transcriptomic profiles of hepatic immune cells in ALD compared with healthy individuals and those with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We utilized single-cell RNA sequencing to analyze liver samples from healthy subjects and patients with MASLD and ALD, focusing on the immune cell landscapes within the liver. Key alterations in immune cell subsets were further validated using liver biopsy samples from additional patient cohorts. Results: We observed a significant accumulation of CD4+ T cells in livers of patients with ALD, surpassing the prevalence of CD8+ T cells, in contrast to patients with MASLD and healthy counterparts, whereas natural killer (NK) cells and γδT cells exhibited reduced intrahepatic infiltration. In-depth transcriptional and developmental trajectory analyses unveiled that a distinct CD4+ subset characterized by granzyme K (GZMK) expression, displaying a tissue-resident signature and terminal effector state, prominently enriched among CD4+ T cells infiltrating the livers of patients with ALD. Subsequent examination of an independent ALD patient cohort corroborated the substantial enrichment of GZMK+CD4+ T lymphocytes, primarily within liver fibrotic zones, suggesting their potential involvement in disease progression. Additionally, we noted shifts in myeloid populations, with expanded APOE+ macrophage and FCGR3B+ monocyte subsets in ALD samples relative to MASLD and healthy tissues. Conclusions: In summary, this study unravels the intricate cellular diversity within hepatic immune cell populations, highlighting the pivotal immune pathogenic role of the GZMK+CD4+ T lymphocyte subset in ALD pathogenesis.

Abstract Spatial heterogeneity and plasticity of the mammalian liver are critical for systemic metabolic homeostasis in response to fluctuating nutritional conditions. Here, a spatially resolved transcriptomic landscape of mouse livers across fed, fasted and refed states using spatial transcriptomics is generated. This approach elucidated dynamic temporal‐spatial gene cascades and how liver zonation—both expression levels and patterns—adapts to shifts in nutritional status. Importantly, the pericentral nuclear receptor Nr1i3 (CAR) as a pivotal regulator of triglyceride metabolism is pinpointed. It is showed that the activation of CAR in the pericentral region is transcriptionally governed by Pparα. During fasting, CAR activation enhances lipolysis by upregulating carboxylesterase 2a, playing a crucial role in maintaining triglyceride homeostasis. These findings lay the foundation for future mechanistic studies of liver metabolic heterogeneity and plasticity in response to nutritional status changes, offering insights into the zonated pathology that emerge during liver disease progression linked to nutritional imbalances.

The development of shale gas reservoirs often involves the utilization of horizontal well segmental multi-stage fracturing techniques. However, these reservoirs face challenges, such as rapid initial wellhead pressure and production decline, leading to extended periods of low-pressure production. To address these issues and enhance the production during the low-pressure stage, pressurized mining is considered as an effective measure. Determining the appropriate pressurization target and method for the shale gas wells is of great practical significance for ensuring stable production in shale gas fields. This study takes into account the current development status of shale gas fields and proposes a three-stage pressurization process. The process involves primary supercharging at the center station of the block, secondary supercharging at the gas collecting station, and the introduction of a small booster device located behind the platform separator and in front of the outbound valve group. By incorporating a compressor, the wellhead pressure can be reduced to 0.4 MPa, resulting in a daily output of 12,000 to 14,000 cubic meters from the platform. Using a critical liquid-carrying model for shale gas horizontal wells, this study demonstrates that reducing the wellhead pressure decreases the critical flow of liquid, thereby facilitating the discharge of the accumulated fluid from the gas well. Additionally, the formation pressure of shale gas wells is estimated using the mass balance method. This study calculates the cumulative production of different IPR curves based on the formation pressure. It develops a dynamic production decline model for gas outlet wells and establishes a relationship between the pressure depletion of gas reservoirs and the cumulative gas production before and after pressurization of H10 −2 and H10 −3 wells. The final estimated ultimate recovery of two wells is calculated. In conclusion, the implementation of multi-stage pressurization, as proposed in this study, effectively enhances the production of, and holds practical significance for, stable development of shale gas fields.

Erythritol, sorbitol, maltitol, fructooligosaccharide or isomaltulose instead of sucrose was used in lotus paste filling. The effects of different sweeteners on the eating quality of lotus paste filling were investigated by gas chromatography-ion mobility spectrometry (GC-IMS), an electronic tongue, a texture analyzer and sensory evaluation. The results showed that sugar alcohol sweeteners significantly increased the brightness of lotus paste filling, and fructooligosaccharide and isomaltulose deepened the color of lotus paste filling. In addition, the water content of lotus paste filling was negatively correlated with the hardness (r = −0.882, P < 0.01), but positively correlated with the adhesiveness (r = 0.620, P < 0.01) and cohesiveness (r = 0.622, P < 0.01). All functional sweeteners except erythritol increased the water content and improved the texture quality of lotus paste filling. The results of electronic tongue test showed that the functional sweeteners reduced the sweetness of lotus paste filling and helped to mask undesirable tastes such as bitterness. A total of 32 volatile substances were detected in lotus paste filling by GC-IMS, including aldehydes (53.94%–70.60%), ketones (10.36%–18.63%), alcohols (5.25%–14.25%), acids (1.62%–2.81%), esters (0.22%–0.57%), furans (0.29%–0.72%) and alkanes (0.47%–0.71%). Oligofructose and isomaltose increased the types and contents of aldehydes and ketones and enriched the flavor of lotus paste filling. The flavor of lotus paste filling with sugar alcohols was bland. Isomaltulose and fructooligosaccharide improved the quality of lotus paste filling, and therefore could be used as a substitute for sucrose in the production of low-sugar lotus paste filling.