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During its 6,300-km course from the Tibetan Plateau to the ocean, the Yangtze River is joined by two large lakes: Dongting Lake and Poyang Lake. We explain why these lakes exist. Deglaciation forced the ocean adjacent to the Yangtze mouth to rise â¼120 m. This forced a wave of rising water surface elevation and concomitant bed aggradation upstream. While aggradation attenuated upstream, the low bed slope of the Middle-Lower Yangtze River (â¼2 × 10-5 near Wuhan) made it susceptible to sea level rise. The main stem, sourced at 5,054 m above sea level, had a substantial sediment load to "fight" against water surface level rise by means of bed aggradation. The tributaries of the Middle-Lower Yangtze have reliefs of approximately hundreds of meters, and did not have enough sediment supply to fill the tributary accommodation space created by main-stem aggradation. We show that the resulting tributary blockage likely gave rise to the lakes. We justify this using field data and numerical modeling, and derive a dimensionless number capturing the critical rate of water surface rise for blockage versus nonblockage.
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In this study, we use molecular dynamics simulations of liquid water to investigate how shear thinning affects the viscosity of liquid water by structural changes of the hydrogen bond network. The effect of shear on viscosity can be divided into two parts: shear-induced destruction of the hydrogen bond network and the influence of the water structure on shear viscosity. First, strong shear destroys tetrahedral structures and thus reduces the connectivity of the hydrogen bond network. It is mainly because shear deformation, characterized by compression and expansion axes, respectively, triggers the destruction and formation of hydrogen bonds, resulting in anisotropic effects on water structures. At the same time, shear destroys large clusters and enhances the formation of small ones, resulting in a decrease in average cluster sizes. Second, the change of viscosity obeys a power law relationship with the change of hydrogen bond structures, highlighting a one-to-one correspondence between structure and property. Meanwhile, in order to explain why the structure affects viscosity, we define hydrogen-bond viscosity and find that the cooperative motion of the water structures can promote momentum transfer in the form of aggregations. Hydrogen-bond viscosity accounts for 5%-50% of the total viscosity. Our results elucidate that water structures are the important structural units to explain the change of water properties.
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Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are unique archaeal membrane-spanning lipids with 0-8 cyclopentane rings on the biphytanyl chains. The cyclization pattern of GDGTs is affected by many environmental factors, such as temperature and pH, but the underlying molecular mechanism remains elusive. Here, we find that the expression regulation of GDGT ring synthase genes grsA and grsB in thermophilic archaeon Sulfolobus acidocaldarius is temperature- and pH-dependent. Moreover, the presence of functional GrsA protein, or more likely its products cyclic GDGTs rather than the accumulation of GrsA protein itself, is required to induce grsB expression, resulting in temporal regulation of grsA and grsB expression. Our findings establish a molecular model of GDGT cyclization regulated by environment factors in a thermophilic ecosystem, which could be also relevant to that in mesophilic marine archaea. Our study will help better understand the biological basis for GDGT-based paleoclimate proxies. Archaea inhabit a wide range of terrestrial and marine environments. In response to environment fluctuations, archaea modulate their unique membrane GDGTs lipid composition with different strategies, in particular GDGTs cyclization significantly alters membrane permeability. However, the regulation details of archaeal GDGTs cyclization in response to different environmental factor changes remain unknown. We demonstrated, for the first time, thermophilic archaea orchestrate the temporal expression of GDGT ring synthases, leading to delicate control of GDGTs cyclization to respond environmental temperature and acidity stress. Our study provides insight into the regulation of archaea membrane plasticity, and the survival strategy of archaea in fluctuating environments.
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Archaea , Ecossistema , Archaea/metabolismo , Temperatura , Glicerol/metabolismo , Lipídeos de Membrana/metabolismoRESUMO
The production of large-area twisted bilayer graphene (TBG) with controllable angles is a prerequisite for proceeding with its massive applications. However, most of the prevailing strategies to fabricate twisted bilayers face great challenges, where the transfer methods are easily stuck by interfacial contamination, and direct growth methods lack the flexibility in twist-angle design. Here we develop an effective strategy to grow centimetre-scale TBG with arbitrary twist angles (accuracy, <1.0°). The success in accurate angle control is realized by an angle replication from two prerotated single-crystal Cu(111) foils to form a Cu/TBG/Cu sandwich structure, from which the TBG can be isolated by a custom-developed equipotential surface etching process. The accuracy and consistency of the twist angles are unambiguously illustrated by comprehensive characterization techniques, namely, optical spectroscopy, electron microscopy, photoemission spectroscopy and photocurrent spectroscopy. Our work opens an accessible avenue for the designed growth of large-scale two-dimensional twisted bilayers and thus lays the material foundation for the future applications of twistronics at the integration level.
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To understand the relation between the macroscopic properties and microscopic structure of hydrogen bond networks in solutions, we introduced a hierarchical clustering method to analyze the typical configurations of water clusters in this type of network. Regarding hydrogen bonds as frames, the rings, fragments and clusters are defined and analyzed to provide a comprehensive perspective for the distributional and dynamic characteristics of the hydrogen-bonding network in NaCl solution at different concentrations. The properties of the radial distribution function and hydrogen bonds are first analyzed. Destruction and shorter lifetimes of hydrogen bonds are observed in solutions. In further analysis of the two-dimensional configuration, i.e., ring, and three-dimensional configuration, i.e., fragment, the average number, size and lifetime of these structures consistently decrease as the concentration increases. Ionic effects on disrupting rings and fragments are significant in the first hydration shell, especially with sodium cations, and these effects weaken beyond the first hydration shell. Regarding the clusters obtained using the Louvain algorithm, our results indicate that clusters break and become smaller as the NaCl concentration increases. The presence of ions also leads to the isolation of clusters and therefore the inhibition of changes. The lifetime of clusters increases with NaCl concentration, indicating the slowed breakage and reformation of clusters in NaCl solutions. This method can be further applied to quantitatively characterize hydrogen bond networks to elucidate more properties of aqueous solutions.
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Our previous study showed that dizocilpine (MK-801) induced schizophrenia-like behavior in rats, enhanced GFAP expression, and activated primary cultured hippocampal astrocytes. Astrocytes play an essential role in neuroinflammation and contribute to the crosstalk that generates chronic neuro-inflammation in neurological diseases. However, the effects of MK-801 treatment on astrocytic neuroinflammatory responses and its mechanism of action have not been studied in detail. To address this issue, IL1ß, IL6, TNFα and IL10 expression and secretion levels were evaluated in hippocampal astrocytes in response to MK-801 for 24 h by ELISA and real-time PCR, with and without pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. Cell apoptosis, viability, and proliferation were also examined. MK-801 treatment did not induce hippocampal astrocytes apoptosis or proliferation, however, MK-801 enhanced astrocytes viability. Additionally, the expression and secretion levels of IL1ß, IL6 and TNFα were elevated, but that of IL10 was decreased, in which ERK1/2 and PI3K signals were involved. These findings suggest that hippocampal astrocytes may regulate the expressions of inflammatory cytokines through ERK1/2 and PI3K signaling pathway to participate in the pathogenesis of schizophrenia.
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Astrócitos/metabolismo , Citocinas/biossíntese , Maleato de Dizocilpina/farmacologia , Hipocampo/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Astrócitos/efeitos dos fármacos , Proliferação de Células , Cromonas/farmacologia , Citocinas/metabolismo , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Inflamação , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Sistema de Sinalização das MAP Quinases , Morfolinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Background Microcirculation is an important factor frequently overlooked when studying the survival of prefabricated flaps. In the current study, we use different prefabrication techniques for characterizing microcirculation within the flap, with the goal of finding an effective way to improve its survival area. Methods An abdominal prefabricated flap rodent model was created using a two-stage operation. All rats were randomly divided into six groups (n = 10/group): group A, prefabricated femoral vessels; group B, prefabricated femoral artery with a connected superficial inferior epigastric vein (SIEV); group C, connected superficial inferior epigastric artery (SIEA) with a prefabricated femoral vein; group D was similar to group A along with a prefabricated SIEA, and group E was similar to group A along with a prefabricated SIEV; and group F acted as a control group and consisted of an axial flap nourished by superficial inferior epigastric vessels. Flaps were assessed for survival area, blood perfusion area, and capillary density using macroscopic analysis, near-infrared fluorescence imaging (NIFI), and histology. Results The survival area was not significantly different when comparing groups B to C, and D to E. The survival area of groups D and E was larger than that of groups B and C. Groups B through E had a smaller survival area in comparison to group F and a larger survival area than group A. NIFI were consistent with the macroscopic outcomes. The capillary density was not significantly different between groups A to C and groups D to F. Conclusion Both arterial and venous supercharging could potentially improve the survival area of prefabricated flaps.
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Anastomose Cirúrgica/métodos , Microcirculação , Procedimentos de Cirurgia Plástica/métodos , Reto do Abdome/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Modelos Animais de Doenças , Artéria Femoral , Sobrevivência de Enxerto , Masculino , Ratos , Ratos Sprague-Dawley , Reto do Abdome/transplanteRESUMO
In general, adjusting the composition of a fluorescent material is an effective way to tune its luminescent properties such as peak energy and bandwidth. In most solid-solutions, the emission peak shifts linearly with the materials' composition, which is referred to as Vegard's Law. However, we found extraordinary variations in our samples Ba2xSr2-2xV2O7, that is, both the excitation and emission peaks show nonlinear dependence on the composition x, and the same is true for the spectral bandwidths. The nonlinearities are not due to structural anomaly, as all the samples are confirmed to be solid-solutions by X-ray diffraction measurements. To explain these phenomena, we proposed a model by considering the disorder of Ba(2+) and Sr(2+) distributions in solid-solutions and the changes of configurations between the ground and excited electronic states. This novel phenomenon could be applied to further exploit new fluorescent materials.
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Gastric cancer, a high-risk malignancy, is a genetic disease developing from a cooperation of multiple gene mutations and a multistep process. Gene therapy is a novel treatment method for treating gastric cancer. Here, we developed a novel Arg-Gly-Asp (RGD) peptides conjugated copolymers nanoparticles-based gene delivery system in order to actively targeting inhibit the growth of gastric cancer cells. These transcription factor (AP-2α) expression plasmids were also encapsulated into pluronic triblock copolymers nanoparticles which was constituted of poly(ethylene glycol)-block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO-block-PPO-block-PEO, P123). The size, morphology and composition of prepared nanocomposites were further characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) analysis, these nanocomposites have minor effects on the proliferation of GES-1 cells but significantly decreased the viability of MGC-803, suggesting they own low cytotoxicity but good antitumor activity. The following in vivo evaluation experiments confirmed that these nanocomposites could prevent the growth of gastric cancer cells in the tumor xenograft mice model. In conclusion, these unique RGD peptides conjugated P123 encapsulated AP-2α nanocomposites could selectively and continually kill gastric cancer cells by over-expression of AP-2α in vitro and in vivo; this exhibits huge promising applications in clinical gastric cancer therapy.
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Terapia de Alvo Molecular , Oligopeptídeos/química , Plasmídeos/metabolismo , Poloxâmero/química , Polímeros/química , Neoplasias Gástricas/terapia , Fator de Transcrição AP-2/metabolismo , Animais , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanocompostos/química , Nanocompostos/ultraestrutura , Tamanho da Partícula , Neoplasias Gástricas/patologia , Carga Tumoral/efeitos dos fármacosRESUMO
Algal blooms have been increasingly prevalent in recent years, especially in lakes and reservoirs; their accurate prediction is essential for preserving water quality. In this study, the observed chlorophyll a (chl-a) levels were assimilated into the Environmental Fluid Dynamics Code (EFDC) of algal bloom dynamics by using a particle filter (PF), and the state variables of water quality and model parameters were simultaneously updated to achieve enhanced algal bloom predictive performance. The developed data assimilation system for algal blooms was applied to Xiangxi Bay (XXB) in the Three Gorges Reservoir (TGR). The results show that the ensemble mean accuracy and reliability of the confidence intervals of the predicted state variables, including chl-a and indirectly updated phosphate (PO4), ammonium (NH4), and nitrate (NO3) levels, were considerably improved after PF assimilation. Thus, PF assimilation is an effective tool for the dynamic correction of parameters to represent their inherent variations. Increased assimilation frequency can effectively suppress the accumulation of model errors; therefore, the use of high-frequency water quality data for assimilation is recommended to ensure more accurate and reliable algal bloom prediction.
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Eutrofização , Rios , Clorofila A , Reprodutibilidade dos Testes , Qualidade da Água , China , Monitoramento AmbientalRESUMO
Carbon storage plays a pivotal role in addressing climate change, maintaining ecological equilibrium, and fostering sustainable development. Gansu Province, situated in the arid to semi-arid region of Northwestern China, is confronted with substantial carbon storage losses as a result of ongoing ecological land desertification processes. However, studies on carbon storage loss under various scenarios in desertified regions are seldom reported. In this study, we delineated the ecological red line using quantified indicators encompassing multiple ecosystem service functions and ecological vulnerability sensitivity. Furthermore, we projected future land use and carbon storage transformations under multiple policy scenarios employing the patch-generating land use simulation (PLUS) model. Lastly, we unveiled spatial disparities in the driving factors behind alterations in carbon storage by geographically weighted regression model. Our findings suggest that: (1) The delineated ecological red line covers an area of 11.8 × 104 km2, approximately 27 % of the total land area of Gansu Province. (2) Quantitative findings reveal that the overall accuracy of the PLUS model reached an impressive 0.975, accompanied by a Kappa coefficient of 0.964, thus affirming the model's exceptional applicability. (3) Under the base line scenario, Gansu Province's carbon storage witnesses a consistent decline from 2000 to 2050, with a substantial total loss of 1.62 × 107 t over the ensuing three decades. The ecological red line scenario, by controlling 27 % of the land area in Gansu Province, achieves a 61.7 % effect of the global ecological scenario by 2050, thus reversing the declining trend in carbon storage. (4) Natural factors primarily influence carbon storage in the southeastern region, while human activity factors are distributed in the central region. This study offers scientifically robust policy recommendations to facilitate the attainment of carbon neutrality objective.
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Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.
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The seismic or static undrained slip line field theory and Cauchy, Riemann, mixed boundary value problems for undrained soil slopes are derived. A new failure mechanism is proposed to determine the undrained bearing capacity adjacent to slopes. The effects of geometric or strength parameters and seismic forces on static and seismic undrained bearing capacity are investigated. The convergence of the proposed method is proved. The static and seismic undrained bearing capacities predicted by the proposed method are close to those of the currently existing methods. The proposed method does not need to assume or search the failure modes, and a new limit state evaluation index is given.
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A new failure mechanism is proposed for calculating the ultimate inclined load adjacent to the slope, i.e., the slope is in the limit state when the critical slope contour and the slope surface are at the critical position where two intersections will occur. The conventional view is that the critical slope contour calculated by the method of characteristics has only a concave shape. This study found that the critical slope contour changes from concave to convex when the inclined load imposed on the slope top surface increases. The feasibility of the proposed method is verified by the finite element limit analysis (FELA) and the definition of the ultimate load. The parametric analysis showed that the current method of characteristics (CMOC) overestimated the ultimate inclined load and gave an incorrect conclusion since it assumed larger failure models at a low strength ratio or large friction angle. The proposed method does not require assumption or search of the failure models, and it can solve the shortcomings of CMOC.
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Análise de Elementos Finitos , FricçãoRESUMO
Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain-white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.
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Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Neoplasias Vulvares , Feminino , Humanos , Líquen Escleroso Vulvar/diagnóstico por imagem , Líquen Escleroso Vulvar/patologia , População do Leste Asiático , Líquen Escleroso e Atrófico/diagnóstico por imagem , Líquen Escleroso e Atrófico/patologia , Vulva/diagnóstico por imagem , Vulva/patologia , Microscopia ConfocalRESUMO
Background: Idiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood. Methods: In this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF. Results: We identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment. Conclusion: Our findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.
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Fibrose Pulmonar Idiopática , Camundongos , Animais , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Bleomicina , Cromatina , Biologia Computacional , Histona Desmetilases com o Domínio Jumonji/genética , Histona-Lisina N-Metiltransferase/genéticaRESUMO
The management of sediment-water interfaces, especially bed stability, is essential for controlling accumulated contaminants in the sediment. In this study, the relationship between sediment erosion and phosphorus (P) release under the remediation strategy of contaminated sediment backfilling (CSBT) was explored through a flume experiment, i.e. the dredged sediment was calcined into ceramsite after dewatering and detoxification and then backfilled to the dredged area for sediment capping, thus avoiding the introduction of foreign materials via in-situ remediation and the large-scale land occupation associated with ex-situ remediation. Acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) were used to measure the vertical distributions of flow velocity and sediment concentration in the overlying water, respectively, and diffusive gradients in thin films (DGT) was used to measure the P distribution in the sediment. The results revealed that improving bed stability from CSBT can considerably improve the robustness of sediment-water interface and reduce sediment erosion by more than 70%. The corresponding P release from the contaminated sediment could be inhibited with an inhibition efficiency as high as 80%. CSBT is a potent strategy for managing contaminated sediment. This study provides a theoretical reference for controlling sediment pollution, further supporting river and lake ecological management and environmental restoration.
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Recuperação e Remediação Ambiental , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Fósforo , Sedimentos Geológicos , Lagos , ÁguaRESUMO
Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks. Methods: We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS. Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes. Conclusion: Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions.