Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis: A Decision Tree Approach.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers. MATERIALS AND METHODS: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 µg/g. The outcomes were then confirmed in a validation cohort of 26 patients. RESULTS: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort. CONCLUSIONS: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI.

Low-Intensity Pulsed Ultrasound Maintains Bone Mass After Withdrawal of Human Parathyroid Hormone in Ovariectomized Mice.

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.

Intrinsic Properties Affecting the Catalytic Activity toward Oxygen Reduction Reaction of Nanostructured Transition Metal Nitrides as Catalysts for Hybrid Na-Air Batteries.

Nanostructured transition metal nitrides (TMNs) have been considered as a promising substitute for precious metal catalysts toward ORR due to their multi-electron orbitals, metallic properties, and low cost. To design TMN catalysts with high catalytic activity toward ORR, the intrinsic features of the influencing factor on the catalytic activity toward ORR of nanostructured TMNs need to be investigated. In this paper, titanium nitride (TiN), zirconium nitride (ZrN), and hafnium nitride (HfN) nanoparticles (NPs) are highly efficient and synthesized in one step by the direct current arc plasma. TiN, ZrN, and HfN NPs with an oxidation layer are applied as the catalysts of hybrid sodium-air batteries (HSABs). The effect of the composition and structural attributes of TMNs on ORR catalysis is defined as follows: (i) composition effect. With the increase in the oxygen content, the catalytic ORR capability of TMNs decreases progressively due to the reduction in oxygen adsorption capacity; (ii) structure effect. The redistribution of the density of states (DOS) of ZrN indicates higher ORR activity than TiN and HfN. HSABs with ZrN exhibit an excellent cyclic stability up to 137 cycles (about 140 h), an outstanding rate performance, and a specific capacity of 2817 mAh·g-1 at 1.0 mA·cm-2.

Low-intensity pulsed ultrasound irradiation attenuates collagen degradation of articular cartilage in early osteoarthritis-like model mice.

PURPOSE: Osteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA. METHODS: After 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR). RESULTS: We observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4. CONCLUSIONS: These results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.

oskar acts with the transcription factor Creb to regulate long-term memory in crickets.

Novel genes have the potential to drive the evolution of new biological mechanisms, or to integrate into preexisting regulatory circuits and contribute to the regulation of older, conserved biological functions. One such gene, the novel insect-specific gene oskar, was first identified based on its role in establishing the Drosophila melanogaster germ line. We previously showed that this gene likely arose through an unusual domain transfer event involving bacterial endosymbionts and played a somatic role before evolving its well-known germ line function. Here, we provide empirical support for this hypothesis in the form of evidence for a neural role for oskar. We show that oskar is expressed in the adult neural stem cells of a hemimetabolous insect, the cricket Gryllus bimaculatus. In these stem cells, called neuroblasts, oskar is required together with the ancient animal transcription factor Creb to regulate long-term (but not short-term) olfactory memory. We provide evidence that oskar positively regulates Creb, which plays a conserved role in long-term memory across animals, and that oskar in turn may be a direct target of Creb. Together with previous reports of a role for oskar in nervous system development and function in crickets and flies, our results are consistent with the hypothesis that oskar's original somatic role may have been in the insect nervous system. Moreover, its colocalization and functional cooperation with the conserved pluripotency gene piwi in the nervous system may have facilitated oskar's later co-option to the germ line in holometabolous insects.

Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS.

In eukaryotes, CREB-binding protein (CBP), a coactivator of CREB, functions both as a platform for recruiting other components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. We previously showed that the transcriptional activity of cAMP-responsive element binding protein (CREB) plays a crucial role in neuronal plasticity in the pond snail Lymnaea stagnalis. However, there is no information on the molecular structure and HAT activity of CBP in the Lymnaea central nervous system (CNS), hindering an investigation of its postulated role in long-term memory (LTM). Here, we characterize the Lymnaea CBP (LymCBP) gene and identify a conserved domain of LymCBP as a functional HAT. Like CBPs of other species, LymCBP possesses functional domains, such as the KIX domain, which is essential for interaction with CREB and was shown to regulate LTM. In-situ hybridization showed that the staining patterns of LymCBP mRNA in CNS are very similar to those of Lymnaea CREB1. A particularly strong LymCBP mRNA signal was observed in the cerebral giant cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, the key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of the LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors. Preincubation of the CNS with such inhibitors blocked cAMP-induced synaptic facilitation between the CGC and an identified follower motoneuron of the feeding system. Taken together, our findings suggest a role for the HAT activity of LymCBP in synaptic plasticity in the feeding circuitry.

Enhanced decomposition of caffeine by water plasma combined with mist generator: Effect of operational parameter and decomposition pathway.

Water plasma coupled with mist generator was introduced to perform the decomposition of caffeine (CAF) wastewater. The mist-shaped water molecule was directly used for plasma-forming gas with no additional gas. The influence of arc current on the decomposition of CAF was elucidated in detail. With the increase of input power from 0.8 to 1.1 kW according to arc current, the removal efficiency of total organic carbon (TOC) and CAF increased, reaching 91.1 and 99.8% at 9.5 A, respectively. H2, CO, CO2, and N2 were major effluent gaseous species, of which the H2 generation was more than 40% for all conditions. The concentration of nitrate in the effluent liquids was the highest at 9.5 A due to a higher oxidation environment. The H, O, and OH as reactive species formed via the dissociation of water molecules were demonstrated, and the plasma temperatures were at over 5000 K. The detailed decomposition pathway was deduced based on eleven intermediate products identified in this process. Electron impact and hydroxyl radical were found to take leading roles in the decomposition of CAF.

The effects of compression load to the trunk on lipid metabolism in an inactive phase.

The effects of compression load to a specific body part, e.g. leg, arm, or trunk, evoke many functions and are applied in various fields including clinical medicine, sports, and general health care. Nevertheless, little is known about the functional mechanism of compression load, especially regarding its effects on metabolic function. We investigated the effects of compression load to the trunk on the metabolism. We designed adjustable compression clothes for mice and attached them to ten-week-old C57BL/6N male mice in a controlled environment. The mice were divided into compression and no-compression groups, the latter only wearing the clothes without added compression. The evoked metabolic changes were evaluated using indirect calorimetry and transcriptomics with liver tissue to investigate the mechanism of the metabolic changes induced by the compression load. The results indicated decreases in body weight gain, food intake, and respiratory exchange ratio in the compression group compared to the no-compression group, but these effects were limited in the "light period" which was an inactive phase for mice. As a result of the transcriptome analysis after eight hours of compression load to the trunk, several DEGs, e.g., Cpt1A, Hmgcr, were classified into functional categories relating to carbohydrate metabolism, lipid metabolism, or immune response. Lipid metabolism impacts included suppression of fatty acid synthesis and activation of lipolysis and cholesterol synthesis in the compression group. Taken together, our results showed that activation of lipid metabolism processes in an inactive phase was induced by the compression load to the trunk.

The levels of IL-1ß and soluble IL-1 receptors in patients with IgG4-related periaortitis/periarteritis.

PURPOSE: IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory and an immune-mediated disease characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system, and its pathogenesis and characteristics remain unclear. The inflammatory cytokine IL-1ß is involved in a variety of cellular activities including inflammation, fibrosis, and angiogenesis. The present study compared the levels of the inflammatory cytokine IL-1ß and two soluble IL-1 receptors, IL-1R1 and IL-1R2, between IgG4-RD patients with and without IgG4-related periaortitis/periarteritis. METHODS: The patients with IgG4-related periaortitis/periarteritis (n â€‹= â€‹38), those without (n â€‹= â€‹66) and healthy (n â€‹= â€‹33) were recruited to measure cytokines of IL-1ß and soluble receptors (sIL-1R1 and sIL-1R2) in sera by ELISA assay. RESULTS: Serum IgG4 was significantly higher in patients with periaortitis/periarteritis compared to non-periaortitis/periarteritis (p â€‹= â€‹0.0074), while serum IL-1ß was significantly lower in patients with periaortitis/periarteritis (p â€‹= â€‹0.00037). The three groups did not show significant difference in sIL1-R1, while sIL-1R2 in the periaortitis/periarteritis and healthy group was higher than in the group without periaortitis/periarteritis (p â€‹= â€‹0.00001). CONCLUSIONS: The characteristic changes in IL-1ß, sIL-1R1, and sIL-1R2 levels in IgG4-RD patients with and without IgG4-related periaortitis/periarteritis may indicate an active phase of the inflammatory process in these diseases.

As(iii) removal through catalytic oxidation and Fe(iii) precipitation.

To remove arsenite (As(iii)) from wastewater effectively, the catalytic oxidation of As(iii) to arsenate (As(v)) and As(v) precipitation with iron ions (Fe(iii)) was investigated. The Pt/SiO2 catalyst functioned as a reaction site for As(iii) with oxygen in the atmosphere. The combination of the Pt/SiO2 catalyst and Fe(iii) precipitant improved the removal of As(iii) in the precipitate; Pt/SiO2 worked as both an As(iii) oxidation site and precipitation site with Fe(iii) precipitant.

Silencing the odorant receptor co-receptor impairs olfactory reception in a sensillum-specific manner in the cockroach.

Insects detect odors via a large variety of odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). The insect OR is a heteromeric complex composed of a ligand-specific receptor and the co-receptor (ORco). In this study, we identified the ORco gene of the cockroach, Periplaneta americana (PameORco), and performed RNAi-based functional analysis of PameORco. All OSNs in the basiconic sensilla expressed PameORco and received a large variety of odors including sex pheromones. In trichoid sensilla, a PameORco-positive OSN was consistently paired with a PameORco-negative OSN tuned to acids. In adult cockroaches injected with PameORco dsRNA at the nymphal stage, the expression of PameORco, odor receptions via ORs, and its central processing were strongly suppressed. These results provide new insights into the molecular basis of olfactory reception in the cockroach. The long-lasting and irreversible effects of PameORco RNAi would be an effective method for controlling the household pest.

Clinical Characteristics Associated with the Development of Diabetic Ketoacidosis in Patients with Type 2 Diabetes.

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated. Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated. Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p<0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (<65 years old) (p<0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity. Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.

The differential diagnosis of IgG4-related disease based on machine learning.

INTRODUCTION: To eliminate the disparity and maldistribution of physicians and medical specialty services, the development of diagnostic support for rare diseases using artificial intelligence is being promoted. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare disorder often requiring special knowledge and experience to diagnose. In this study, we investigated the possibility of differential diagnosis of IgG4-RD based on basic patient characteristics and blood test findings using machine learning. METHODS: Six hundred and two patients with IgG4-RD and 204 patients with non-IgG4-RD that needed to be differentiated who visited the participating institutions were included in the study. Ten percent of the subjects were randomly excluded as a validation sample. Among the remaining cases, 80% were used as training samples, and the remaining 20% were used as test samples. Finally, validation was performed on the validation sample. The analysis was performed using a decision tree and a random forest model. Furthermore, a comparison was made between conditions with and without the serum IgG4 concentration. Accuracy was evaluated using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: In diagnosing IgG4-RD, the AUROC curve values of the decision tree and the random forest method were 0.906 and 0.974, respectively, when serum IgG4 levels were included in the analysis. Excluding serum IgG4 levels, the AUROC curve value of the analysis by the random forest method was 0.925. CONCLUSION: Based on machine learning in a multicenter collaboration, with or without serum IgG4 data, basic patient characteristics and blood test findings alone were sufficient to differentiate IgG4-RD from non-IgG4-RD.

Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020.

In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.

Treatment of pyridine in industrial liquid waste by atmospheric DC water plasma.

Pyridine is a basic heterocyclic compound with high toxicity, widely found in liquid waste from industrial processes. The treatment of highly-concentrated pyridine was demonstrated using a novel mist-type water thermal plasma torch. Decomposition rate and TOC removal rate were more than 94% in all conditions, while the max energy efficiency reached about 23 g/kWh. With a high temperature of 5500-7500 K, more than 95% of carbon content in pyridine was converted into valuable gas products, while a little amount of formic acid and acetic acid were observed as liquid by-products. The production of hydrogen cyanide (HCN) during the thermal decomposition of pyridine was observed, which can be inhibited by increasing the input power. Based on the experimental results, detailed decomposition mechanisms in the high-temperature and the downstream region were discussed respectively. Water plasma shows significant potential in the treatment of non-biodegradable industrial liquid waste.

IL1R1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system. Since the genetic factors related to disease onset are unclear, we examined the genetic associations with IgG4-related periaortitis/periarteritis susceptibility. METHODS: A small scale of genome-wide association analysis identified that interleukin 1 receptor type 1 (IL1R1) gene variants were correlated with the development of IgG4-related periaortitis/periarteritis in 75 patients with IgG4-RD. Accordingly, 8 single nucleotide polymorphisms (SNPs) in the IL1R1 gene were selected and genotyped in 124 patients with IgG4-RD (43 with periaortitis/periarteritis and 81 without periaortitis/periarteritis) and 344 healthy subjects. RESULTS: The minor allele frequencies of 6 SNPs (rs2287049, rs3917273, rs2160227, rs951192, rs3917318, rs7582198) were significantly increased in IgG4-related periaortitis/periarteritis patients compared with those without periaortitis/periarteritis (corrected P < 0.05). In addition, the frequency of the AGAAA haplotype, comprised of 5 SNPs (rs3917273, rs2160227, rs951192, rs3917318, rs7582198), was significantly higher in patients with periaortitis/periarteritis (OR = 2.41, 95% CI:1.42-4.10). CONCLUSION: Our findings indicated that IL1R1 genetic polymorphisms contributed to IgG4-related periaortitis/periarteritis and the possibility of certain genetic factors influencing the risk of specific IgG4-RD manifestations.

Comprehensive Characterization of Structural, Electrical, and Mechanical Properties of Carbon Nanotube Yarns Produced by Various Spinning Methods.

A comprehensive characterization of various carbon nanotube (CNT) yarns provides insight for producing high-performance CNT yarns as well as a useful guide to select the proper yarn for a specific application. Herein we systematically investigate the correlations between the physical properties of six CNT yarns produced by three spinning methods, and their structures and the properties of the constituent CNTs. The electrical conductivity increases in all yarns regardless of the spinning method as the effective length of the constituent CNTs and the density of the yarns increase. On the other hand, the tensile strength shows a much stronger dependence on the packing density of the yarns than the CNT effective length, indicating the relative importance of the interfacial interaction. The contribution of each physical parameter to the yarn properties are quantitatively analyzed by partial least square regression.

Validation of Self-Monitoring Devices Supporting Sodium Intake Reduction: An Experimental Feeding Study Using Standardized Low-Salt and High-Salt Meals among Healthy Japanese Volunteers.

INTRODUCTION: Although several approaches for approximating daily Na intake and the Na/K ratio using casual urine are available, the most useful method remains unclear during daily practice and at home. METHODS: Twenty-seven participants measured their casual urinary Na/K ratio repeatedly using a Na/K ratio monitor and also measured overnight urine once daily using a monitoring device which delivers on-site feedback to estimate their salt intake under unrestricted, low-salt (LS) (6 g/day), and high-salt (HS) (12 g/day) diets. RESULTS: The monitoring method utilizing overnight urine to estimate daily Na remained insensitive, resulting in significant overestimation during the LS diet and underestimation during the HS diet periods; estimated salt intake during the LS and HS diet periods plateaued at 7-8 g/day and 9-10 g/day within 3 day; mean estimated salt intake was 11.3 g/day, 7.9 g/day, and 9.8 g/day on the last day of the unrestricted, LS, and HS diets; the coefficient of variation (CV) of the estimated Na intake was 0.23 and 0.17 in the latter half of the low- and high-salt diet periods, respectively. The mean urinary Na/K molar ratio was 5.6, 2.5, and 5.3 on the last day of the unrestricted, LS, and HS diets; the CV of the daily mean Na/K ratio was 0.41 and 0.36 in the latter half of the LS and HS diet periods, respectively. The urinary Na/K ratio during the LS and HS diet periods plateaued within 2 days. The monitoring method based on the daily mean of the casual urinary Na/K ratio reflected the actual change in Na intake, and the estimated value tracked the actual changes in salt intake with smaller difference than the overnight urine estimates when using the estimation coefficient set at 2; estimated salt intake during the LS and HS diet periods plateaued at 5-6 g/day and 10-12 g/day within 2-3 day; mean estimated salt intake was 11.0 g/day, 5.7 g/day, and 10.7 g/day on the last day of the unrestricted, LS, and HS diets, respectively. DISCUSSION/CONCLUSION: Estimates of daily Na intake derived from overnight urine may remain insensitive during dietary interventions. The urinary Na/K ratio reflects the actual change in Na intake during dietary modification and may serve as a practical marker, particularly during short-term interventions. Conversion from the urinary Na/K ratio to estimated salt intake may be useful, if the coefficient was set appropriate by further investigations.

Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice.

The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.