The BEST (Beerkan Estimation of Soil Transfer parameters) method was used to compare the hydraulic properties of the soils in two Long-term Agroecosystem Experiments (LTAEs) located at the FIELDLAB experimental site of the University of Perugia (central Italy). The LTAE “NewSmoca” consists of a biennial maize-durum wheat crop rotation under integrated low-input cropping systems with (i) inversion soil tillage (INT) or (ii) no-tillage (INT+) and (iii) under an organic cropping system with inversion soil tillage (ORG). ORG and INT+ involve the use of autumn-sown cover crops (before the maize cycle). Pure stand durum wheat was grown in INT and INT+, while a faba bean–wheat temporary intercropping was implemented in ORG. The LTAE “Crop Rotation” consists of different crop rotations and residue management, a continuous soft winter wheat and biennial rotations of soft winter wheat with maize or faba bean. Each rotation is combined with two modes of crop residue management: removal or burial. For INT+, despite the high-bulk density (>1.50 g/cm³), we found that conductivity, sorptivity and available water are comparable to those of INT, probably due to a more structured and efficient micropore system. ORG soils show the highest conductivity, sorptivity and available water content values, probably due to the recent spring tillage occurring in the wheat inter-row with the faba bean incorporation into the soil. For LTAE Rotation, the residue burial seems to influence the capacity-based indicators positively. However, the differences in the removal treatment are minor, and this could be due to the inversion soil tillage, which limits the progressive accumulation of organic matter. Full article

Objectives—The aim of the present study was to characterize the clinical phenotype of patients with primary Sjögren’s syndrome (pSS) with non-identified antinuclear antibodies (ANA) in comparison with that of patients with pSS with negative ANA, positive typical ANA (anti-Ro/SSA and/or La/SSB) and positive atypical ANA. Methods—We conducted an observational, retrospective monocentric study at the Erasme University Hospital (Brussels, Belgium). Two hundred and thirty-three patients fulfilling the 2002 American–European Consensus Group criteria for pSS were included in this study. The patients were subdivided according to their ANA profile and demographics. The clinical and biological data of each subgroup were compared. Moreover, the relationships between these data and the ANA profiles were determined by multiple correspondence analysis. Results—In our cohort, 42 patients (18%) presented a non-identified ANA-positive profile. No statistically significant difference could be observed between non-identified ANA patients and ANA-negative patients in terms of age and/or ESSDAI score at diagnosis. There were significantly more frequent articular manifestations, positive rheumatoid factor (RF), and the use of corticosteroids in anti-Ro/SSA-positive patients compared to ANA-negative (p ≤ 0.0001) and non-identified ANA-positive patients (p ≤ 0.01). However, a significantly higher proportion of RF positivity and corticosteroid treatment was observed in non-identified ANA-positive patients compared to ANA-negative patients (p < 0.05). Conclusions—For the first time to our knowledge, our study has characterized the clinical phenotype of patients with pSS with non-identified ANA at diagnosis. The non-identified ANA-positive patients featured mostly a clinical phenotype similar to that of the ANA-negative patients. On the other hand, the non-identified ANA-positive patients were mainly distinguished from the ANA-negative patients by a greater proportion of RF positivity and the need for corticosteroid use due to articular involvement. Full article

NO₂ is a prevalent environmental pollutant, and its reaction with water produces nitric acid, which is one of the main factors contributing to the degradation of books and paper. Therefore, it is crucial to develop a real-time monitoring system for NO₂ gas content in the air and establish timely response measures to delay book aging and provide effective protection. In this study, TiO₂ nanotubes (NTs) were fabricated using the anodic oxidation method, followed by the preparation of TiO₂ NT/MoS₂ composites through hydrothermal synthesis. It was observed that flaky MoS₂ is attached to the surface of TiO₂ nanotubes, forming aggregated structures resembling flower balls. The TiO₂ NT/MoS₂ nanocomposites were found to exhibit a rapid response with a 5 s response time and an 80 s recovery time towards 367 ppm NO₂ at 260 °C. The gas response to 100 ppm NO₂ vapor was 3.3, which is higher than all the other gases under the same concentration. Our experimental results demonstrate that compared to pure TiO₂ NTs, TiO₂ NT/MoS₂ composites exhibit a larger specific surface area along with higher sensitivity and faster response times towards various concentrations of NO₂ gas. Full article

Formula feeding, obesity and the gut microbiota are closely related. The present investigation explored the profiles of the intestinal microbiota in obese children over 5 years old with formula feeding in early life. We identified functional bacteria with anti-obesity potential through in vitro and in vivo experiments, elucidating their mechanisms. The results indicated that, in the group of children over 5 years old who were fed formula in early life, obese children exhibited distinct gut microbiota, which were characterized by diminished species diversity and reduced Bifidobacterium levels compared to normal-weight children. As a result, Lactobacillus acidophilus H-68 (H-68) was isolated from the feces of the N-FF group and recognized as a promising candidate. H-68 demonstrated the ability to stimulate cholecystokinin (CCK) secretion in STC-1 cells and produce bile salt hydrolase. In vivo, H-68 promoted CCK secretion, suppressing food intake, and regulated bile acid enterohepatic circulation, leading to increased deoxycholic acid and lithocholic acid levels in the ileum and liver. This regulation effectively inhibited the diet-induced body weight and body fat gain, along with the liver fat deposition. In conclusion, H-68 was recognized for its prospective anti-obesity impact, signifying an auspicious pathway for forthcoming interventions targeted at averting pediatric obesity in formula-fed children. Full article

Hinokitiol (HKT) is one of the essential oil components found in the heartwood of Cupressaceae plants, and has been reported to have various bioactive effects, including anti-inflammatory effects. However, the improving effect of HKT on periodontitis, which is characterized by periodontal tissue inflammation and alveolar bone loss, has not been clearly revealed. Therefore, we investigated the periodontitis-alleviating effect of HKT and the related molecular mechanisms in human periodontal ligament cells. According to the study results, HKT downregulated SIRT1 and NOX4, which were increased by Porphyromonas gingivalis Lipopolysaccharide (PG-LPS) stimulation and were found to regulate pro-inflammatory mediators and oxidative stress through SIRT1/NOX4 signals. Additionally, by increasing the expression of osteogenic makers such as alkaline phosphatase, osteogenic induction of human periodontal ligament (HPDL) cells, which had been reduced by PG-LPS, was restored. Furthermore, we confirmed that NOX4 expression was regulated through regulation of SIRT1 expression with HKT. The in vitro effect of HKT on improving periodontitis was proven using the periodontal inflammation model, which induces periodontal inflammation using ligature, a representative in vivo model. According to in vivo results, HKT alleviated periodontal inflammation and restored damaged alveolar bone in a concentration-dependent manner in the periodontal inflammation model. Through this experiment, the positive effects of HKT on relieving periodontal tissue inflammation and recovering damaged alveolar bone, which are important treatment strategies for periodontitis, were confirmed. Therefore, these results suggest that HKT has potential in the treatment of periodontitis. Full article

As the Internet of Things (IoT) continues to expand, wireless communication is increasingly widespread across diverse industries and remote devices. This includes domains such as Operational Technology in the Smart Grid. Notably, there is a surge in resource-constrained devices leveraging wireless communication, especially with the advances of 5G/6G technology. Nevertheless, the transmission of wireless communications demands substantial power and computational resources, presenting a significant challenge to these devices and their operations. In this work, we propose the use of deep learning to improve the Bit Error Rate (BER) performance of Orthogonal Frequency Division Multiplexing (OFDM) wireless receivers. By improving the BER performance of these receivers, devices can transmit with less power, thereby improving IoT devices’ battery life. The architecture presented in this paper utilizes a depthwise Convolutional Neural Network (CNN) for channel estimation and demodulation, whereas a Graph Neural Network (GNN) is utilized for Low-Density Parity Check (LDPC) decoding, tested against a proposed (1998, 1512) LDPC code. Our results show higher performance than traditional receivers in both isolated tests for the CNN and GNN, and a combined end-to-end test with lower computational complexity than other proposed deep learning models. For BER improvement, our proposed approach showed a 1 dB improvement for eliminating BER in QPSK models. Additionally, it improved 16-QAM Rician BER by five decades, 16-QAM LOS model BER by four decades, 64-QAM Rician BER by 2.5 decades, and 64-QAM LOS model BER by three decades. Full article

Low P-containing wastewaters (LPWs) exhibit huge P recovery potential, considering their larger volume. P recovery via CaP crystallization using apatite as seed is documented as being potentially well suited for LPWs. However, its responsible mechanisms remain a subject for debate. Taking hydroxyapatite (HAP) as the seed of LPWs, this paper conducted HAP adsorption/dissolution experiments, titration experiments, and P recovery experiments to distinguish the primary responsible mechanism. Results showed that it was HAP dissolution, not P adsorption, that occurred when the initial P concentration was no higher than 5 mg/L, ruling out adsorption mechanism of P recovery from LPWs using HAP as the seed. Significant OH⁻ consumption and rapid P recovery occurred simultaneously within the first 60 s in titration experiments, suggesting CaP crystallization should be responsible for P recovery. Moreover, the continuous increase in P recovery efficiency with seed dosages observed in P recovery experiments seemed to follow well the mechanism of pre-nucleation ion clusters (PNCs) aggregation. During PNCs aggregation, P aggregates with Ca²⁺ quickly, generating CaP PNCs; then, CaP PNCs aggregate with seed particles, followed by CaP PNCs fusion, and ultimately transform into fines attached to the seed surface. PNCs’ aggregation mechanism was further supported by a comparison of seed SEM images before and after P recovery, since denser and smaller rod-shaped fines were observed on the seed surface after P recovery. This study suggests that PNCs’ aggregation is the dominant mechanism responsible for the recovery of P from LPWs via CaP crystallization using HAP as the seed. Full article

Neurodegenerative disorders entail a progressive loss of neurons in cerebral and peripheral tissues, coupled with the aggregation of proteins exhibiting altered physicochemical properties. Crucial to these conditions is the gradual degradation of the central nervous system, manifesting as impairments in mobility, aberrant behaviors, and cognitive deficits. Mechanisms such as proteotoxic stress, neuroinflammation, oxidative stress, and programmed cell death contribute to the ongoing dysfunction and demise of neurons. Presently, neurodegenerative diseases lack definitive cures, and available therapies primarily offer palliative relief. The integration of nanotechnology into medical practices has significantly augmented both treatment efficacy and diagnostic capabilities. Nanoparticles, capable of traversing the blood–brain barrier, hold considerable potential for diagnosing and treating brain pathologies. By combining gene therapy with nanotechnology, the therapeutic effectiveness against neurodegenerative diseases can be substantially enhanced. Recent advancements in nano-biomaterial-based methodologies have fortified existing approaches to neural stem cell (NSC) differentiation therapies. NSC-targeting technologies offer a promising, potentially safe method for treating neurodegenerative diseases. This review endeavors to summarize current insights and perspectives on nanotechnology-driven therapeutic innovations in neurodegenerative disorders, with a particular emphasis on Alzheimer’s and Parkinson’s disease. Full article

A key goal in current research on industrial curdlan production is the expansion of carbon sources for fermentation. In this study, a recombinant bacterial strain, sp-AmyAXCC, capable of fermenting and synthesizing curdlan using dextrin as a carbon source, was produced via heterologous expression of IPTG-inducible α-amylase from Xanthomonas campestris NRRL B-1459 in Agrobacterium tumefaciens ATCC31749. External expression of the enzyme was confirmed by western blotting, and the expression levels of exogenous proteins during the fermentation process were monitored. Additionally, the properties of the curdlan product were characterized using attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray diffraction. The recombinant strain produced curdlan at a titer of 30.40 ± 0.14 g/L, gel strength of 703.5 ± 34.2 g/cm², and a molecular weight of 3.58 × 10⁶ Da, which is 33% greater than the molecular weight of native curdlan (2.69 × 10⁶ Da). In the batch fermentation of sp-AmyAXCC with 12% dextrin as a carbon source, the titer of curdlan was 66.7 g/L with a yield of 0.56 g/g, and a productivity rate of 0.62 g/L/h at 108 h. The results of this study expand the substrate spectrum for Agrobacterium fermentation in curdlan production and provides guidance for further industrialization of curdlan production. Full article

It is difficult to plug the fracture water channeling of a fractured low-permeability reservoir during water flooding by using the conventional acrylamide polymer gel due to its weak mechanical properties. For this problem, micron graphite powder is added to enhance the comprehensive properties of the acrylamide polymer gel, which can improve the plugging effect of fracture water channeling. The chemical principle of this process is that the hydroxyl and carboxyl groups of the layered micron graphite powder can undergo physicochemical interactions with the amide groups of the polyacrylamide molecule chain. As a rigid structure, the graphite powder can support the flexible skeleton of the original polyacrylamide molecule chain. Through the synergy of the rigid and flexible structures, the viscoelasticity, thermal stability, tensile performance, and plugging ability of the new-type gel can be significantly enhanced. Compared with a single acrylamide gel, after adding 3000 mg/L of micrometer-sized graphite powder, the elastic modulus, the viscous modulus, the phase transition temperature, the breakthrough pressure gradient, the elongation at break, and the tensile stress of the acrylamide gel are all greatly improved. After adding the graphite powder to the polyacrylamide gel, the fracture water channeling can be effectively plugged. The characteristics of the networked water flow channel are obvious during the injected water break through the gel in the fracture. The breakthrough pressure of water flooding is high. The experimental results are an attempt to develop a new gel material for the water plugging of a fractured low-permeability reservoir. Full article

Vaccination arguably remains the only long-term strategy to limit the spread of S. aureus infections and its related antibiotic resistance. To date, however, all staphylococcal vaccines tested in clinical trials have failed. In this review, we propose that the failure of S. aureus vaccines is intricately linked to prior host exposure to S. aureus and the pathogen’s capacity to evade adaptive immune defenses. We suggest that non-protective immune imprints created by previous exposure to S. aureus are preferentially recalled by SA vaccines, and IL-10 induced by S. aureus plays a unique role in shaping these non-protective anti-staphylococcal immune responses. We discuss how S. aureus modifies the host immune landscape, which thereby necessitates alternative approaches to develop successful staphylococcal vaccines. Full article

This research aimed to evaluate the efficacy of a nanoemulgel (NE) containing Cananga odorata (Ylang-Ylang) oil for managing scalp psoriasis and dandruff through various assessments. The study involved phytochemical screening, characterization, stability testing, in vivo performance evaluation, dermatokinetic analysis, central composite rotatable design (CCRD) optimization, in vitro release profiling, and antioxidant and antimicrobial activity assessment of the NE. The NE exhibited excellent stability and maintained physical parameters over a three-month period. In vivo studies showed no skin irritation, maintenance of skin pH (4.55 to 5.08), and improvement in skin hydration (18.09 to 41.28 AU) and sebum content (26.75 to 5.67 mg/cm²). Dermatokinetic analysis revealed higher skin retention of C. odorata in the NE (epidermis: 71.266 µg/cm², dermis: 60.179 µg/cm²) compared to conventional formulations. CCRD optimization yielded NE formulations with the desired particle size (195.64 nm), entrapment efficiency (85.51%), and zeta potential (−20.59 mV). In vitro release studies indicated sustained release behavior, and antioxidant and antimicrobial properties were observed. This study demonstrates the stability, skin-friendliness, therapeutic benefits, and controlled release properties of the NE. The NE presents a promising option for various topical applications in treating bacterial and fungal diseases, potentially enhancing drug delivery and treatment outcomes in pharmaceuticals and cosmetics. Full article

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs. Full article

Syndemics, the adverse interaction of two or more coterminous diseases or other negative health conditions, have probably existed since human settlement, plant and animal domestication, urbanization, and the growth of social inequality beginning about 10–12,000 years ago. These dramatic changes in human social evolution significantly increased opportunities for the spread of zoonotic infectious diseases in denser human communities with increased sanitation challenges. In light of a growing body of research that indicates that anthropogenic air pollution causes numerous threats to health and is taking a far greater toll on human life and wellbeing than had been reported, this paper proposes the possibility that air pollution is now the primary driver of infectious disease syndemics. In support of this assertion, this paper reviews the growth and health impacts of air pollution, the relationship of air pollution to the development and spread of infectious diseases, and reported cases of air pollution-driven infectious disease syndemics, and presents public health recommendations for leveraging the biosocial insight of syndemic theory in responding to infectious disease. Full article

Membrane emulsification technology has garnered increasing interest in emulsion preparation due to controllable droplet size, narrower droplet size distribution, low energy consumption, simple process design and excellent reproducibility. Nevertheless, the pore structure and surface engineering in membrane materials design play a crucial role in achieving high-quality emulsions with high throughput simultaneously. In this work, an oriented interpenetrating capillary network composed of highly aligned and interconnected wood cell lumens has been utilized to fabricate an emulsion membrane. A novel honeycomb porous ZnO layer obtained by a seed prefabrication–hydrothermal growth method was designed to reconstruct wood channel surfaces for enhanced microfluid mixing. The results show that through the unique capillary mesh microstructure of wood, the emulsion droplets were smaller in size, had narrower pore-size distribution, and were easy to obtain under high throughput conditions. Meanwhile, a well-designed ZnO layer could further improve the emulsion quality of a wood membrane, while the emulsifying throughput is still maintained at a higher level. This demonstrates that the convection process of the microfluid in these wood capillary channels was intensified markedly. This study not only develops advanced membrane materials in emulsion preparation, but also introduces a brand-new field for functional applications of wood. Full article

The protection of ecological systems is currently a trending topic. Numerous countries have implemented various measures to safeguard ecosystems. Evaluating the effectiveness of regional ecological protection and cooperative conservation is of paramount importance. In this paper, Hainan Island, China, was taken as an example to construct an evaluation framework of the ecosystem change characteristics and conservation effects of different types of protected areas. In this way, the study evaluated the ecological status of important protected areas and the effects of collaborative management and control, and it discussed the changes in ecological status and protection effects. The results revealed the following. (1) Important protected areas occupy a large proportion of natural ecological space, reaching 76.33%, more than twice the proportion of ecological space on Hainan Island. In the past 20 years, the ecological space retention rate has increased by 0.57%. (2) The contribution of excellent-quality and good-quality ecosystems is the greatest, accounting for 82.65% of the whole island. In the past 20 years, the ec7osystem quality has improved in more than 80% of the areas. The proportion of excellent-quality and good-quality ecosystems is as high as 96.75% in these conservation areas, and their contribution to Hainan Island is 44.29%, while conservation areas only account for about 38%. (3) The ecosystem services of Hainan Island have improved and become stable in the past 20 years. The contribution of all types of protected areas to the ecosystem services of Hainan Island is more than 53.22%. In general, the ecological quality and service function has increased in Hainan Island, and the ecological space tends to be stable. Different types of protected areas have effectively protected various ecosystems on Hainan Island with different protection and management mechanisms. Full article

In 1862, the German naturalist Carl Semper traveled through the Palau Islands, a Spanish colony in the Southwestern Pacific. He published an account of his travels in 1873 and claimed that the people of Palau possessed Jewish facial features. Although his book was rejected by professional anthropologists in Imperial Germany, popular anthropologists widely circulated his observation that Palauans shared physical characteristics with Jewish people. This article demonstrates that the racialization of Pacific Islanders, specifically those inhabiting the Palau Islands, was rooted in antisemitic notions about Jewish people as a race built on stereotypes about particular traits. This topic has been thus far overlooked by scholars of German colonialism, German anthropology, and German discourses on the Pacific Islands, particularly the Palau Islands. Full article

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA–ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38β MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38β MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF–EGFR pathway for novel therapeutic approaches. Full article

Objective: There is a scarcity of data on hospital length of stay (LOS) in the osteoarthritis population. Therefore, this study aimed to investigate hospital LOS and associated factors in patients with osteoarthritis from Germany. Methods: The present cross-sectional study included patients hospitalized for osteoarthritis in one of fourteen hospitals in Germany between 2018 and 2023 (hospital database; IQVIA). The study outcome was the duration of hospital stay in days. Study covariables included age, sex, hospital department, osteoarthritis type, co-diagnosis, and hospitalization-related procedure. Associations between covariables and hospital LOS were analyzed using hierarchical linear regression models. Results: There were 8770 patients included in the study (mean [standard deviation] age 68.7 [10.8] years; 60.2% women). The mean (standard deviation) hospital LOS was 8.5 (5.0) days. Factors positively and significantly associated with hospital LOS were older age, female sex, orthopedic surgery and other medical specialty departments (compared with other surgery departments), knee and other and unspecified osteoarthritis (compared with hip osteoarthritis), multiple co-diagnoses (e.g., acute posthemorrhagic anemia, other disorders of fluid, electrolyte, and acid–base balance, and disorders of purine and pyrimidine metabolism), and several hospitalization-related procedures (i.e., geriatric rehabilitation, hip arthroplasty, and knee arthroplasty). Conclusions: The mean hospital LOS was higher than eight days in this osteoarthritis population from Germany, with a spectrum of demographic, clinical, and hospitalization-related factors associated with this hospital LOS. In this context, interventions are needed to reduce the LOS of hospitalizations for osteoarthritis in Germany. Full article

This research investigates the suitability of printed polyamide 12 (PA12) and its dyed version to support cells in bioengineering applications. For this purpose, human gingival fibroblasts (hGF06) were cultured on PA-12 scaffolds that were 3D-printed by Multi Jet Fusion (MJF). The study examined the direct cultivation of cells on MJF-printed cell culture scaffolds and the effect of leachate of PA-12 printed by MJF on the cultured cells. The article presents research on the surface treatment of PA12 material used in 3D printing and the effect of automatic staining on cell vitality and proliferation in vitro. The study presents a unique device designed exclusively for staining prints made of the biocompatible material PA12 and demonstrates the compatibility of 3D-printed polyamide 12 parts stained in the novel device with a nutrient culture medium and cells. This novel PA12 surface treatment for biomedical purposes does not affect the compatibility with the culture medium, which is essential for cell viability and proliferation. Fluorescence microscopy revealed that mitochondrial fitness and cell survival were not affected by prolonged incubation with clear or dyed PA12 3D-printed parts. Full article

Liver fibrosis, characterized by excessive extracellular matrix (ECM) deposition, can progress to cirrhosis and increases the risk of liver cancer. Hepatic stellate cells (HSCs) play a pivotal role in fibrosis progression, transitioning from a quiescent to activated state upon liver injury, wherein they proliferate, migrate, and produce ECM. Calcium signaling, involving the inositol 1,4,5-trisphosphate receptor (IP3R), regulates HSC activation. This study investigated the efficacy of a novel IP3R inhibitor, desmethylxestospongin B (dmXeB), in preventing HSC activation. Freshly isolated rat HSCs were activated in vitro in the presence of varying dmXeB concentrations. The dmXeB effectively inhibited HSC proliferation, migration, and expression of fibrosis markers without toxicity to the primary rat hepatocytes or human liver organoids. Furthermore, dmXeB preserved the quiescent phenotype of HSCs marked by retained vitamin A storage. Mechanistically, dmXeB suppressed mitochondrial respiration in activated HSCs while enhancing glycolytic activity. Notably, methyl pyruvate, dimethyl α-ketoglutarate, and nucleoside supplementation all individually restored HSC proliferation despite dmXeB treatment. Overall, dmXeB demonstrates promising anti-fibrotic effects by inhibiting HSC activation via IP3R antagonism without adverse effects on other liver cells. These findings highlight dmXeB as a potential therapeutic agent for liver fibrosis treatment, offering a targeted approach to mitigate liver fibrosis progression and its associated complications. Full article