Chronic PM2.5 exposure disrupts intestinal barrier integrity via microbial dysbiosis-triggered TLR2/5-MyD88-NLRP3 inflammasome activation.

BACKGROUND: PM2.5, a known public health risk, is increasingly linked to intestinal disorders, however, the mechanisms of its impact are not fully understood. PURPOSE: This study aimed to explore the impact of chronic PM2.5 exposure on intestinal barrier integrity and to uncover the underlying molecular mechanisms. METHODS: C57BL/6 J mice were exposed to either concentrated ambient PM2.5 (CPM) or filtered air (FA) for six months to simulate urban pollution conditions. We evaluated intestinal barrier damage, microbial shifts, and metabolic changes through histopathology, metagenomics, and metabolomics. Analysis of the TLR signaling pathway was also conducted. RESULTS: The mean concentration of PM2.5 in the CPM exposure chamber was consistently measured at 70.9 ± 26.8 µg/m³ throughout the study period. Our findings show that chronic CPM exposure significantly compromises intestinal barrier integrity, as indicated by reduced expression of the key tight junction proteins Occludin and Tjp1/Zo-1. Metagenomic sequencing revealed significant shifts in the microbial landscape, identifying 35 differentially abundant species. Notably, there was an increase in pro-inflammatory nongastric Helicobacter species and a decrease in beneficial bacteria, such as Lactobacillus intestinalis, Lactobacillus sp. ASF360, and Eubacterium rectale. Metabolomic analysis further identified 26 significantly altered metabolites commonly associated with intestinal diseases. A strong correlation between altered bacterial species and metabolites was also observed. For example, 4 Helicobacter species all showed positive correlations with 13 metabolites, including Lactate, Bile acids, Pyruvate and Glutamate. Additionally, increased expression levels of TLR2, TLR5, Myd88, and NLRP3 proteins were noted, and their expression patterns showed a strong correlation, suggesting a possible involvement of the TLR2/5-MyD88-NLRP3 signaling pathway. CONCLUSIONS: Chronic CPM exposure induces intestinal barrier dysfunction, microbial dysbiosis, metabolic imbalance, and activation of the TLR2/5-MyD88-NLRP3 inflammasome. These findings highlight the urgent need for intervention strategies to mitigate the detrimental effects of air pollution on intestinal health and identify potential therapeutic targets.

Buck technique supplemented by temporary intersegmental pedicle screw fixation to repair lumbar spondylolysis in youth.

BACKGROUND: Lumbar spondylolysis is a bone defect in the pars interarticularis of the lumbar vertebral, which is a common cause of low back pain in youth. Although non-surgical treatment is a mainstream option, surgery is necessary for patients with persistent symptoms. Buck technique is widely used as a classical direct repair technique, but it cannot achieve reduction of low-grade spondylolisthesis and reconstruction of lumbosacral sagittal balance. We have described a novel surgical procedure based on Buck technique with temporary intersegmental pedicle screw fixation, and report a series of clinical outcomes in 5 patients to provide a reference for the clinical treatment of young lumbar spondylolysis. METHODS: Five young patients with symptomatic lumbar spondylolysis with a mean age of 19.20 ± 5.41 years underwent surgical treatment after an average of 7.60 ± 1.52 months of failure to respond to conservative treatment, using a new surgical procedure based on Buck technique combined with temporary intersegmental pedicle screw fixation. RESULTS: Five patients were successfully operated without serious complications such as nerve and vascular injury. The average operation time was 109.00 ± 7.42 min, the interpretative average blood loss was 148.00 ± 31.14 ml, and the average fusion time was 11.20 ± 1.64 months. All patients were followed up for 2 years after surgery, and the visual analogue score (VAS) of low back pain and Oswestry disability index (ODI) scores were significantly improved compared with those before surgery, and the Henderson's evaluation were rated excellent or good. After the removal of the internal fixation, it was observed that temporary intersegmental fixation could repair the isthmus, reduce lumbar spondylolisthesis, and reconstruct the sagittal balance of the lumbosacral vertebrae while preserving lumbar motion and preventing intervertebral disc degeneration. Postoperative MRI indicated the Pfirrmann classification of the affected discs: 1 case from grade III to grade II, 3 cases from grade II to grade I, and 1 case remained grade II. CONCLUSIONS: Buck technique supplemented by temporary intersegmental pedicle screw fixation is a highly applicable and effective method for the treatment of adolescent lumbar spondylolysis. The isthmic fusion is accurate, and temporary intersegmental fixation can effectively prevent disc degeneration and reconstruct the sagittal balance of lumbosacral vertebra.

Neochlorogenic Acid Combined with Bone Marrow Mesenchymal Stem Cells Encapsulated into GelMA Hydrogel for Transplantation to Repair Intervertebral Disk Degeneration.

Intervertebral disk degeneration is a common disease with an unknown etiology. Currently, tissue engineering is considered to be an important method for intervertebral disk repair. Although transplanted stem cells may disrupt the repair process because of apoptosis caused by the oxidative microenvironment. Herein, bone marrow mesenchymal stem cell (BMSC) and Neochlorogenic acid (Ncg) were encapsulated into a GelMA hydrogel as a carrier to protect transplanted stem cells. Ncg effectively inhibited the oxidative stress process and reduced the apoptosis rate. A 5% GelMA hydrogel had a large pore size and porosity that provided an enhanced survival space for cells. An in vivo assessment showed that treatment with GelMA + BMSC + Ncg produced greater repair of degenerated intervertebral disks than that found in other model groups. Thus, this study may help contribute to improving stem cell transplantation for treating intervertebral disk degeneration.

Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling.

BACKGROUND & AIMS: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti-hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency. METHODS: HBV-infected cells were used to screened the anti-HBV potency of interleukin-6 family cytokines. The concentration of oncostatin M (OSM) in patients with chronic HBV infection was examined by enzyme-linked immunosorbent assay. The underlying mechanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo. RESULTS: OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%). Hepatitis B e antigen-positive CHB patients with high OSM levels had lower hepatitis B surface antigen and hepatitis B e antigen than those with low levels. OSM activated JAK-STAT signaling pathway promoting the formation of STAT1-IRF9 transcription factor complex. Following this, OSM increased the expression of various genes with known functions in innate and adaptive immunity, which was higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (data from GEO: GSE65359). Interferon-induced transmembrane protein 1, one of the most differentially expressed genes, was identified as an HBV restriction factor involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited HBV replication and induced expression of antiviral effector interferon-induced transmembrane protein 1. CONCLUSIONS: Our study shows that OSM remodels the immune response against HBV and exerts potent anti-HBV activity, supporting its further development as a potential therapy for treating CHB.

Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection.

OBJECTIVE: Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism. DESIGN: In total, 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, were recruited for this study. MOTS-c levels were measured by ELISA and its diagnostic value was evaluated by receiving operating characteristic curve analysis. The therapeutic effect of MOTS-c was observed in multiple HBV-infected mice and cells through various techniques, including transcriptomic sequencing, flow cytometry, immunofluorescence and electron microscopy. Additionally, MOTS-c's potential interaction with myosin-9 (MYH9) and actin was predicted using immunoprecipitation, proteomics and target prediction software. RESULTS: MOTS-c negatively correlates with HBV DNA expression (R=-0.71), and its AUC (the area under the curve) for distinguishing CHB from healthy controls is 0.9530, and IA (immune reactive) from IC (inactive HBV carrier) is 0.8689. Inhibition of HBV replication (with a 50-70% inhibition rate) was observed alongside improved liver function without notable toxicity in vitro or in vivo. MOTS-c was found to promote mitochondrial biogenesis and enhance the MAVS (mitochondrial antiviral signalling protein) signalling pathway. The impact is dependent on MOTS-c's ability to regulate MYH9-actin-mediated mitochondrial homeostasis. CONCLUSION: MOTS-c has the potential to serve as a biomarker for the progression of HBV infection while also enhancing antiviral efficacy. These findings present a promising innovative approach for effectively treating patients with CHB. Furthermore, our research uncovers a novel role for MOTS-c in regulating MYH9-actin-mediated mitochondrial dynamics and contributing to mitochondrial biogenesis.

Active Learning the High-Dimensional Transferable Hubbard U and V Parameters in the DFT + U + V Scheme.

Density functional theory (DFT) is a powerful quantum mechanical computational tool to perform electronic structure calculations for materials. Few DFT methods can ensure accuracy and efficiency simultaneously. DFT + U + V is an alternative effective approach to overcome this drawback. However, the accuracy sensitively depends on the self-consistent estimation of the high-dimensional onsite and intersite Hubbard interaction U and V terms. We propose Bayesian optimization using a dropout (BOD) algorithm, one type of active learning method, to optimize U and V terms. The DFT + U + V with U/V obtained by BOD can produce improved electronic properties for diverse bulk materials of comparable quality to the hybrid functionals with lower computational cost compared to the linear response approach. Note that the band gaps calculated by BOD are somewhat different from that of hybrid functionals by simply applying the same U/V parameters as in the case of surface slabs and interfaces, which suggests that the transferability of U/V from the bulk models to slabs and interfaces is not as well as expected. BOD is extended to calculate the U/V parameters for slabs and interfaces and reach similar results as bulk solids. Moreover, we find that the U/V are reasonably transferable between surface slabs and interfaces with different thicknesses under various effects of quantum confinement, which contributes to fast access to the electronic properties of large-scale systems with higher accuracy.

Be Careful When Using Peer-Influence on Nudging Solicitation: Evidence of Potential Negative Effect from a Sample of Chinese University Students.

Purpose: Peer information is now commonly used in solicitation. However, scholars have long focused on testing its effectiveness on increasing the donation amount without paying attention to its potential negative effects on donors. Thus, the current study employs high vs low peer donation amount (HPDA vs LPDA) information to explore its effect on "how-much-to-donate" decisions and the corresponding neural and psychological reactions at the same time. Participants and Methods: Student samples from a Chinese university and behavioral experiments with the event-related potential (ERP) method were used in this study. Results: The behavioral results are consistent with previous research in which HPDA was positively associated with higher donation levels. ERP results show the mechanisms behind decision-making can be summarized into a cognitive approach represented by cost-benefit analysis and an affective approach represented by reward perception. More surprisingly, in contrast to the behavioral results, LPDA elicits higher level of reward perception than HPDA. Conclusion: The results indicate that although HPDA leads to higher levels of donation, donors do not show higher levels of reward anticipation at the neurological level, indicating the increment of donation may come at the cost of donors. Theoretical and practical implications are also discussed.

Study on Kinetics of Carbonization Reaction of Hardened Cement Paste Powder Based on Carbonization Degree.

The hardened cement paste powder (HCP) powder, devoid of the hydration cementing property, can be regenerated and cemented into a test block with practical strength of almost 60 MPa via CO2 carbonization using appropriate means. This study established a kinetic model of CO2 curing of an HCP powder test block based on the degree of carbonization to study the carbonization reaction kinetic characteristics of the test block. The model was modified according to the characteristics of the evident temperature differences in the reaction kettle in the early, middle, and late stages of the carbonization process. The proposed model can be used to formulate and control the carbonization and cementation processes of HCP powder and can also be applied to describe the kinetics of the reaction processes of other similar systems.

Biomechanical evaluation of lumbar spondylolysis repair with various fixation options: A finite element analysis.

Objective: This study was designed to compare the biomechanical properties of lumbar spondylolysis repairs using different fixation methods by using three-dimensional finite element analysis. Methods: Five finite element models (A, B, C, D, and E) of L4-S1 vertebral body were reconstructed by CT images of a male patient (A: intact model; B: spondylolysis model; C: spondylolysis model with intrasegmental direct fixation by Buck screw; D: spondylolysis model with intersegmental indirect fixation by pedicle screw system; E: spondylolysis model with hybrid internal fixation). L5-S1 level was defined as the operative level. After the intact model was verified, six physiological motion states were simulated by applying 500 N concentrated force and 10 Nm torque on the upper surface of L4. The biomechanical properties of the three different internal fixation methods were evaluated by comparing the range of motion (ROM), maximum stress, and maximum displacement. Results: Compared with Model B, the ROM and maximum displacement of Model C, D, and E decreased. The maximum stress on L5/S1 disc in models A, B, and C was much higher than that in Model D and E under extension and lateral bending conditions. Under axial rotation and lateral bending conditions, the maximum stress of interarticular muscle and internal fixation system in Model B and Model C was significantly higher than that in Model D and Model E. In contrast to Model D, the stress in Model E was distributed in two internal fixation systems. Conclusion: In several mechanical comparisons, hybrid fixation had better biomechanical properties than other fixation methods. The experimental results show that hybrid fixation can stabilize the isthmus and reduce intervertebral disc stress, which making it the preferred treatment for lumbar spondylolysis.

Salvianolic acid B combined with bone marrow mesenchymal stem cells piggybacked on HAMA hydrogel re-transplantation improves intervertebral disc degeneration.

Cell-based tissue engineering approaches have emerged as a realistic alternative for regenerative disc tissue repair. The multidirectional differentiation potential of bone marrow mesenchymal stem cells (BMSCs) to treat disc degeneration intervertebral disc degeneration has also become a viable option. We used 1% HAMA hydrogel as a carrier and co-encapsulated BMSCs and Salvianolic acid B (SalB) into the hydrogel to reduce the apoptosis of the transplanted cells. The protective effect of SalB on BMSCs was first verified in vitro using the CCK8 method, flow cytometry, and Western-Blotting, and the physical properties and biocompatibility of HAMA hydrogels were verified in vitro. The rat model was then established using the pinprick method and taken at 4 and 8 W, to examine the extent of disc degeneration by histology and immunohistochemistry, respectively. It was found that SalB could effectively reduce the apoptosis of BMSCs in vitro by activating the JAK2-STAT3 pathway. 1% HAMA hydrogels had larger pore size and better water retention, and the percentage of cell survival within the hydrogels was significantly higher after the addition of SalB to the HAMA hydrogels. In the in vivo setting, the HAMA + SalB + BMSCs group had a more pronounced delaying effect on the progression of disc degeneration compared to the other treatment groups. The method used in this study to encapsulate protective drugs with stem cells in a hydrogel for injection into the lesion has potential research value in the field of regenerative medicine.

Aberrant expression of SPAG6 and NM23 predicts poor prognosis of human osteosarcoma.

Objective: To investigate the expression and clinical significance of sperm-associated antigen 6 and NM23 proteins in human osteosarcoma. Methods: The specimens of conventional osteosarcoma with follow-up from 42 Chinese patients were analyzed in this study, and 12 cases of osteochondroma were considered controls. The expression of SPAG6 and NM23 was inspected using immunohistochemical staining, qRT-PCR, and Western blotting methods. Results: The positive expression rate of SPAG6 protein (71.43%) in 42 cases of osteosarcoma tissue was significantly higher than that (33.33%) in 12 cases of osteochondroma tissues (p < 0.05), while the positive rate of NM23 protein (35.71%) in osteosarcoma tissue was lower than that (58.33%) in osteochondroma tissue (p < 0.05). The mRNA and protein levels of SPAG6 were significantly higher than those of the adjacent normal tissues, while the expression of NM23 was lower in osteosarcoma tissues than that in the controls (p < 0.05 for all). There was a positive relationship between the expression of SPAG6 and pathological grade, metastasis, and Enneking stage (p < 0.05 for all). The overall survival rate of osteosarcoma patients with SPAG6 positive expression was significantly lower than that with SPAG6 negative expression. The relationship between the expression of NM23 and pathological grade, metastasis, and Enneking stage was negative (p < 0.05 for all). The overall survival rate of the osteosarcoma patients with NM23 positive expression was higher than that of the patients with NM23 negative expression (p < 0.05). Conclusion: Overexpression of SPAG6 and low expression of NM23 are negatively related to pathological grade, metastasis, and Enneking stage and prognosis of osteosarcoma patients. This suggested that SPAG6 and NM23 should be considered candidate prognostic biomarkers for patients with osteosarcoma.

Correction to "Solution and Analysis of Wellbore Temperature and Pressure Field Coupling Model under Lost Circulation".

[This corrects the article DOI: 10.1021/acsomega.2c04185.].

Strength Characteristics and Microstructure Analysis of Alkali-Activated Slag-Fly Ash Cementitious Material.

Modifying the admixture of alkali-activated cementitious materials using components such as fly ash and fine sand may reduce CO2 emissions and conserve natural resources and energy. This study adopted strength testing, scanning electron microscopy, and mercury intrusion porosimetry to investigate the influence of different admixtures on the compressive strength and flexural strength of alkali slag cementing materials and the microstructure characteristics of hardened slurry under the action of load. The flexural strength of alkali slag cement slurry and mortar was reduced by replacing slag powder with fly ash. Content of fine sand less than 20% had little effect on the strength of alkali slag cement mortar; however, when the content of fine sand exceeded 30%, the strength decreased significantly. The hydration degree at 3 d was large, and the density of slurry increased with the extension of age. Increased fly ash or fine sand content decreased the density of the slurry, and increased fly ash resulted in a large number of unhydrated fly ash particles in the cementitious materials. Addition of fine sand resulted in a large number of microcracks in the slurry, which gradually decreased with the extension of hydration age.

Solution and Analysis of Wellbore Temperature and Pressure Field Coupling Model under Lost Circulation.

The fluid in the annulus is in a variable mass flow state under the lost circulation condition, significantly affecting wellbore pressure distribution and the heat transfer efficiency between wellbore and formation. Therefore, based on the hydrodynamics and energy conservation law, a coupling model of transient wellbore temperature and pressure field under lost circulation conditions is established, which fully considers the casing program, bottom hole assembly, and heat source generated in drilling, as well as the influence of the temperature and pressure coupling in wellbore on the physical parameters of drilling fluid. The calculation results of the model in this paper are in good agreement with the field measured data and the previous research results, which verifies the rationality and accuracy of the model in this paper. The effects of the loss rate and the lost circulation zone location on the wellbore temperature and pressure distribution are analyzed, and the variation rule of the physical parameters of drilling fluid under the lost circulation condition is studied. The numerical simulation results show that the density and viscosity of drilling fluid in the annulus and bottom hole pressure increase with the increase in the circulation time; the annulus temperature decreases gradually with the increase in cycle time and tends to become stable after 8 h of the cycle. The annulus temperature and bottom hole pressure decrease with the increase in loss rate and closeness of the loss zone to the well bottom. When the loss zone is in the upper open-hole section, an inflection point consistent with the location of the loss zone appears on the annular temperature difference curve between the loss circulation and the nonloss circulation, and the position of the loss zone can be judged according to the inflection point.

TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance.

Glioblastoma (GBM) is the most common type of primary adult brain tumor. Glioma stem cell (GSC) residence and temozolomide (TMZ) resistance in GBM both contribute to poor patient outcome. TRAF4 is a scaffold protein with E3 ubiquitin ligase activity that has recently been discovered to promote invasion and metastasis in several malignancies, but the effects and functions of TRAF4 in GBM remain to be determined. Here, we report that TRAF4 is preferentially overexpressed in GSCs and is required for stem-like properties as well as TMZ sensitivity in GBM cells. TRAF4 specifically interacted with the N-terminal tail of Caveolin-1 (CAV1), an important contributor to the tumorigenicity of GBM cells. TRAF4 regulated CAV1 stability by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination independently of its E3 ubiquitin ligase catalytic activity. TRAF4-mediated stabilization of CAV1 activated protumorigenic AKT/ERK1/2 signaling, and disruption of this axis resulted in defects in stemness maintenance. In addition, expression of TRAF4 and CAV1 was positively correlated and predicted poor prognosis in human GBM samples. Screening of common nervous system drugs identified risperidone interaction with TRAF4, and risperidone treatment resulted in the dissociation of TRAF4 and CAV1. Importantly, pharmacologic inhibition of TRAF4 with risperidone potently inhibited self-renewal, abrogated tumorigenicity, and reversed TMZ resistance in GBM. Overall, TRAF4-mediated stabilization of CAV1 promotes stemness and TMZ resistance in GBM, providing a therapeutic strategy that could improve patient outcomes. SIGNIFICANCE: The identification of a TRAF4/Caveolin-1 axis that plays a crucial role in malignant progression of glioblastoma provides new insights into the function of TRAF4 in ubiquitin signaling and suggests TRAF4 as a potential therapeutic target.

A novel method for extracting circulating cell-free DNA from whole blood samples and its utility in the non-invasive prenatal test.

OBJECTIVE: We verified a magnetic bead-based, simple, and fast method for circulating cell-free DNA (cfDNA) extraction from whole blood samples(CEWB) and characterised its utility in non-invasive prenatal testing (NIPT). METHOD: We extracted cfDNA from both plasma and whole blood of the patients using CEWB and compared it to that extracted using a Qiagen extraction kit; droplet digital polymerase chain reaction test was used to calculate the fragment size bias. In all, 304 samples were used for NIPT. RESULTS: The CEWB group (mean ± standard deviation [SD]: 4.34 ± 0.41 ng/ml plasma) reported less DNA weight yield than the Qiagen group (4.90 ± 0.50 ng/ml plasma). There was no significant difference between the CEWB group and the Qiagen group in the gene fragments (136 bp: p = 0.064 and 420 bp: p = 0.534). In a parallel cohort study to characterise the utility of the CEWB method in NIPT, the treatment group extracted by CEWB showed a sensitivity of 100%, a specificity of 99.65%, and a positive predictive value of 95%. CONCLUSIONS: This study demonstrated that CEWB achieves an acceptable yield of DNA without contamination from genomic DNA. Subsequent clinical experiments in a parallel cohort indicated its utility for NIPT.

Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach.

Currently, determining when to start antiviral therapy in patients with chronic HBV infection is a controversial issue. One crucial reason is that biomarkers for distinguishing the natural history of chronic HBV infection are unmet needs. In this study, we aimed to explore novel biomarkers and therapeutic targets for the diagnosis and treatment of chronic HBV infection by using tandem mass tag (TMT)-based quantitative proteomics approach. Here, we firstly revealed the serum proteomic characterization of the natural history of chronic HBV infection using multiplex TMT labeling coupled with liquid chromatography-mass spectrometry. Then, we verified the levels of differentially expressed proteins (DEPs) across a large number of clinical samples by enzyme-linked immunosorbent assay (ELISA). We found that DEPs over the different phases of chronic HBV infection were primarily involved in the biological process of leukocyte-mediated immunity. Patients with chronic hepatitis were characterized as having an up-regulated proteasome pathway, including upregulation of proteasome activator subunit 1 (PSME1) and proteasome subunit alpha type 7 (PSMA7) levels. In addition, immune tolerant phase patients were characterized by having the lowest ephrin-B2 (EFNB2) levels and highest heat responsive protein 12 (HRSP12) levels. Moreover, inactive HBV carrier state patients were characterized by having a down-regulated glycolysis/gluconeogenesis pathway, with especially low expression of related enzymes alpha-enolase (ENO1) and fructose-1,6-bisphosphatase 1 (FBP1). What's more, HBeAg-negative chronic hepatitis patients were characterized as having the highest interleukin 18 binding protein (IL-18BP) levels. Thus, our results provide several potential diagnostic biomarkers for distinguishing the natural history of chronic HBV infection, such as PSME1, PSMA7, EFNB2, ENO1, and IL-18BP, and also present potential therapeutic interventions for chronic hepatitis B patients, such as targeting the proteasome or glycolysis/gluconeogenesis pathways. Our findings shed new light on the development of novel diagnostic biomarkers and therapeutic targets for the diagnosis and treatment of chronic HBV infection.

The Neural and Psychological Processes of Peer-Influenced Online Donation Decision: An Event-Related Potential Study.

With the rapid development of information and communication technology (ICT), social media-based donation platforms emerged. These platforms innovatively demonstrate peer information (e.g., number of donated peers) on the donation page, which inevitably brings the peer influence into donors' donation decision process. However, how the peer influence will affect the psychological process of donation decisions are remained unknown. This study used the number of donated peers to examine the effects of peer influence on donors' donation decisions and extracted event-related potential (ERP) from electroencephalographic data to explore the underlying psychological process. The behavioral results indicated that the number of donated peers positively influenced donors' willingness to donate. The ERP results suggested that a larger number of donated peers might indicate a higher level of conformity and greater perceived emotional rewards, as a larger P2 amplitude was observed. Following the early processing of emotional stimuli, cognitive detection of decisional risk took place, and the donors reckoned a smaller number of donated peers as a high potential risk, which was reflected by a larger N2 amplitude. In the later stage, the larger number of donated peers, which represented a higher magnitude of prospective emotional rewards, led to a higher incentive to donate, and reflected in a larger amplitude of P3. Additionally, implications and future directions were discussed.

Notch-mediated lactate metabolism regulates MDSC development through the Hes1/MCT2/c-Jun axis.

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) play critical roles in tumorigenesis. However, the mechanisms underlying MDSC and TAM development and function remain unclear. In this study, we find that myeloid-specific activation of Notch/RBP-J signaling downregulates lactate transporter MCT2 transcription via its downstream molecule Hes1, leading to reduced intracellular lactate levels, blunted granulocytic MDSC (G-MDSC) differentiation, and enhanced TAM maturation. We identify c-Jun as a novel intracellular sensor of lactate in myeloid cells using liquid-chromatography-mass spectrometry (LC-MS) followed by CRISPR-Cas9-mediated gene disruption. Meanwhile, lactate interacts with c-Jun to protect from FBW7 ubiquitin-ligase-mediated degradation. Activation of Notch signaling and blockade of lactate import repress tumor progression by remodeling myeloid development. Consistently, the relationship between the Notch-MCT2/lactate-c-Jun axis in myeloid cells and tumorigenesis is also confirmed in clinical lung cancer biopsies. Taken together, our current study shows that lactate metabolism regulated by activated Notch signaling might participate in MDSC differentiation and TAM maturation.