Extracellular vesicle dynamics in COPD: understanding the role of miR-422a, SPP1 and IL-17 A in smoking-related pathology.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) induced by smoking poses a significant global health challenge. Recent findings highlight the crucial role of extracellular vesicles (EVs) in mediating miRNA regulatory networks across various diseases. This study utilizes the GEO database to uncover distinct expression patterns of miRNAs and mRNAs, offering a comprehensive understanding of the pathogenesis of smoking-induced COPD. This study aims to investigate the mechanisms by which extracellular vesicles (EVs) mediate the molecular network of miR-422a-SPP1 to delay the onset of COPD caused by smoking. METHODS: The smoking-related miRNA chip GSE38974-GPL7723 was obtained from the GEO database, and candidate miRs were retrieved from the Vesiclepedia database. Downstream target genes of the candidate miRs were predicted using mRNA chip GSE38974-GPL4133, TargetScan, miRWalk, and RNA22 databases. This prediction was integrated with COPD-related genes from the GeneCards database, downstream target genes predicted by online databases, and key genes identified in the core module of WGCNA analysis to obtain candidate genes. The candidate genes were subjected to KEGG functional enrichment analysis using the "clusterProfiler" package in R language, and a protein interaction network was constructed. In vitro experiments involved overexpressing miRNA or extracting extracellular vesicles from bronchial epithelial cell-derived exosomes, co-culturing them with myofibroblasts to observe changes in the expression levels of the miR-422a-SPP1-IL-17 A regulatory network, and assessing protein levels of fibroblast differentiation-related factors α-SMA and collagen I using Western blot analysis. RESULTS: The differential gene analysis of chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Subsequently, an intersection was taken among the prediction results from TargetScan, miRWalk, and RNA22 databases, the COPD-related gene retrieval results from GeneCards database, the WGCNA analysis results of chip GSE38974-GPL4133, and the differential gene analysis results. This intersection, combined with KEGG functional enrichment analysis, and protein-protein interaction analysis, led to the final screening of the target gene SPP1 and its upstream regulatory gene miR-422a. KEGG functional enrichment analysis of mRNAs correlated with SPP1 revealed the IL-17 signaling pathway involved. In vitro experiments demonstrated that miR-422a inhibition targets suppressed the expression of SPP1 in myofibroblasts, inhibiting differentiation phenotype. Bronchial epithelial cells, under cigarette smoke extract (CSE) stress, could compensate for myofibroblast differentiation phenotype by altering the content of miR-422a in their Extracellular Vesicles (EVs). CONCLUSION: The differential gene analysis of Chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Further analysis involved the intersection of predictions from TargetScan, miRWalk, and RNA22 databases, gene search on COPD-related genes from the GeneCards database, WGCNA analysis from Chip GSE38974-GPL4133, and differential gene analysis, combined with KEGG functional enrichment analysis and protein interaction analysis. Ultimately, the target gene SPP1 and its upstream regulatory gene miR-422a were selected. KEGG functional enrichment analysis on mRNAs correlated with SPP1 revealed the involvement of the IL-17 signaling pathway. In vitro experiments showed that miR-422a targeted inhibition suppressed the expression of SPP1 in myofibroblast cells, inhibiting differentiation phenotype. Furthermore, bronchial epithelial cells could compensate for myofibroblast differentiation phenotype under cigarette smoke extract (CSE) stress by altering the miR-422a content in their extracellular vesicles (EVs).

Magnetron-Sputtered Lead Titanate Thin Films for Pyroelectric Applications: Part 2-Electrical Characteristics and Characterization Methods.

Pyroelectric materials are naturally electrically polarized and exhibits a built-in spontaneous polarization in their unit cell structure even in the absence of any externally applied electric field. These materials are regarded as one of the ideal detector elements for infrared applications because they have a fast response time and uniform sensitivity at room temperature across all wavelengths. Crystals of the perovskite lead titanate (PbTiO3) family show pyroelectric characteristics and undergo structural phase transitions. They have a high Curie temperature (the temperature at which the material changes from the ferroelectric (polar) to the paraelectric (nonpolar) phase), high pyroelectric coefficient, high spontaneous polarization, low dielectric constant, and constitute important component materials not only useful for infrared detection, but also with vast applications in electronic, optic, and MEMS devices. However, the preparation of large perfect and pure single crystals PbTiO3 is challenging. Additionally, difficulties arise in the application of such bulk crystals in terms of connection to processing circuits, large size, and high voltages required for their operation. In this part of the review paper, we explain the electrical behavior and characterization techniques commonly utilized to unravel the pyroelectric properties of lead titanate and its derivatives. Further, it explains how the material preparation techniques affect the electrical characteristics of resulting thin films. It also provides an in-depth discussion of the measurement of pyroelectric coefficients using different techniques.

Yu-Ping-Feng-San alleviates inflammation in atopic dermatitis mice by TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Yu-Ping-Feng-San (YPF) is a traditional Chinese medicine formula that has therapeutic effects on allergic diseases such as allergic rhinitis and asthma. However, its potential efficacy and mechanism in the treatment of atopic dermatitis (AD) has not been extensively illustrated. AIM OF THE STUDY: The purpose of this study was to investigate the efficacy and possible mechanisms of YPF in AD pathogenesis. METHODS: Network pharmacology and GEO data mining were adopted to firstly identify the potential mechanisms of YPF on AD. Then DNCB induced-AD murine model was established to test the efficacy of YPF and verify its effects on inflammatory cytokines and NF-κB pathway. In addition, molecular docking was performed to detect the binding affinity of YPF's active components with NF-κB pathway related molecules. RESULTS: Network pharmacology and human data mining suggested that YPF may act on the NF-κB pathway in AD pathogenesis. With DNCB mice model, we found that YPF significantly improved AD symptoms, reduced SCORAD scores, and alleviated skin tissue inflammation in mice. At the same time, the expression of inflammatory cytokines, TNF-α, sPLA2-IIA and IL-6, was down-regulated. Moreover, YPF suppressed TLR4/MyD88/NF-κB pathway in situ in a dose-dependent manner. Molecular docking further confirmed that seven compounds in YPF had exceptional binding properties with TNF-α, IL-6 and TLR4. CONCLUSION: YPF may help the recovery of AD by inhibiting the TLR4/MyD88/NF-κB pathway, which provides novel insights for the treatment of AD by YPF.

Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome.

Tripterygium wilfordii Hook. F (TWH) has significant anti-inflammatory and immunosuppressive effects, and is widely used in the inflammatory response mediated by autoimmune diseases. However, the multi-target mechanism of TWH action in Sjögren syndrome (SS) remains unclear. Therefore, the aim of this study was to explore the molecular mechanism of TWH in the treatment of SS using network pharmacology and molecular docking methods. TWH active components and target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. SS-related targets were obtained from the GeneCards database. After overlap, the therapeutic targets of TWH in the treatment of SS were screened. Protein-protein interaction and core target analysis were performed by STRING network platform and Cytoscape software. In addition, the affinity between TWH and the disease target was confirmed by molecular docking. Finally, the DAVID (visualization and integrated) database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of overlapping targets. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database shows that TWH contains 30 active components for the treatment of SS. Protein-protein interaction and core target analysis suggested that TNF, MMP9, TGFB1, AKT1, and BCL2 were the key targets of TWH in the treatment of SS. In addition, the molecular docking method confirmed that the bioactive molecules of TWH had a high affinity with the target of SS. Enrichment analysis showed that TWH active components were involved in multiple signaling pathways. Pathways in cancer, Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications is the main pathway. It is associated with a variety of biological processes such as inflammation, apoptosis, immune injury, and cancer. Based on data mining network pharmacology, and molecular docking method validation, TWH is likely to be a promising candidate for the treatment of SS drug, but still need to be further verified experiment.

Cushing's Syndrome in Pregnancy Secondary to Adrenocortical Adenoma: A Case Series and Review.

PURPOSE: To present a case series of Cushing's syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes. METHODS: We describe five pregnant women with CS, detailing clinical presentations and laboratory findings. RESULTS: Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas. CONCLUSION: Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

A neural m6A pathway regulates behavioral aggregation in migratory locusts.

RNA N6-methyladenosine (m6A), as the most abundant modification of messenger RNA, can modulate insect behaviors, but its specific roles in aggregation behaviors remain unexplored. Here, we conducted a comprehensive molecular and physiological characterization of the individual components of the methyltransferase and demethylase in the migratory locust Locusta migratoria. Our results demonstrated that METTL3, METTL14 and ALKBH5 were dominantly expressed in the brain and exhibited remarkable responses to crowding or isolation. The individual knockdown of methyltransferases (i.e., METTL3 and METTL14) promoted locust movement and conspecific attraction, whereas ALKBH5 knockdown induced a behavioral shift toward the solitary phase. Furthermore, global transcriptome profiles revealed that m6A modification could regulate the orchestration of gene expression to fine tune the behavioral aggregation of locusts. In summary, our in vivo characterization of the m6A functions in migratory locusts clearly demonstrated the crucial roles of the m6A pathway in effectively modulating aggregation behaviors.

Physics-driven structural docking and protein language models accelerate antibody screening and design for broad-spectrum antiviral therapy.

Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. These viruses infect human host cells via the viral spike protein binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2). Using over 1300 IgG sequences derived from convalescent patient B cells that bind with spike's receptor binding domain (RBD), we first established protein structural docking models in assessing the RBD-IgG-ACE2 interaction interfaces and predicting the virus-neutralizing activity of each IgG with a confidence score. Additionally, employing Gaussian process regression (also known as Kriging) in a latent space of an antibody language model, we predicted the landscape of IgGs' activity profiles against individual coronaviral variants of concern. With functional analyses and experimental validations, we efficiently prioritized IgG candidates for neutralizing a broad spectrum of viral variants (wildtype, Delta, and Omicron) to prevent the infection of host cells in vitro and hACE2 transgenic mice in vivo. Furthermore, the computational analyses enabled rational redesigns of selective IgG clones with single amino acid substitutions at the RBD-binding interface to improve the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screening and re-design even in low-data regimes combining protein language models and Kriging for antibody sequence analysis, activity prediction, and efficacy improvement, in synergy with physics-driven protein docking models for antibody-antigen interface structure analyses and functional optimization.

Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis.

Background: Lower extremity motor dysfunction is one of the most severe consequences after stroke, restricting functional mobility and impairing daily activities. Growing evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can improve stroke patients' lower extremity motor function. However, there is still controversy about the optimal rTMS protocol. Therefore, we compared and analyzed the effects of different rTMS protocols on lower extremity motor function in stroke patients using network meta-analysis (NMA). Methods: We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases (from origin to 31 December 2023). Randomized controlled trials (RCTs) or crossover RCTs on rTMS improving lower extremity motor function in stroke patients were included. Two authors independently completed article screening, data extraction, and quality assessment. RevMan (version 5.4) and Stata (version 17.0) were used to analyze the data. Results: A total of 38 studies with 2,022 patients were eligible for the NMA. The interventions included HFrTMS-M1, LFrTMS-M1, iTBS-Cerebellum, iTBS-M1, dTMS-M1, and Placebo. The results of NMA showed that LFrTMS-M1 ranked first in FMA-LE and speed, and HFrTMS-M1 ranked first in BBS, TUGT, and MEP amplitude. The subgroup analysis of FMA-LE showed that HFrTMS-M1 was the best stimulation protocol for post-stroke time > 1 month, and LFrTMS-M1 was the best stimulation protocol for post-stroke time ≤ 1 month. Conclusion: Considering the impact of the stroke phase on the lower extremity motor function, the current research evidence shows that HFrTMS-M1 may be the preferred stimulation protocol to improve the lower extremity motor function of patients for post-stroke time > 1 month, and LFrTMS-M1 for post-stroke time ≤ 1 month. However, the above conclusion needs further analysis and validation by more high-quality RCTs.Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier (CRD42023474215).

Efficient nitrate and Cr(VI) removal by denitrifier: The mechanism of S. oneidensis MR-1 promoting electron production, transportation and consumption.

When Cr(VI) and nitrate coexist, the efficiency of both bio-denitrification and Cr(VI) bio-reduction is poor because chromate hinders bacterial normal functions (i.e., electron production, transportation and consumption). Moreover, under anaerobic condition, the method about efficient nitrate and Cr(VI) removal remained unclear. In this paper, the addition of Shewanella oneidensis MR-1 to promote the electron production, transportation and consumption of denitrifier and cause an increase in the removal of nitrate and Cr(VI). The efficiency of nitrate and Cr(VI) removal accomplished by P. denitrificans as a used model denitrifier increased respectively from 51.3% to 96.1% and 34.3% to 99.8% after S. oneidensis MR-1 addition. The mechanism investigations revealed that P. denitrificans provided S. oneidensis MR-1 with lactate, which was utilized to secreted riboflavin and phenazine by S. oneidensis MR-1. The riboflavin served as coenzymes of cellular reductants (i.e., thioredoxin and glutathione) in P. denitrificans, which created favorable intracellular microenvironment conditions for electron generation. Meanwhile, phenazine promoted biofilm formation, which increased the adsorption of Cr(VI) on the cell surface and accelerated the Cr(VI) reduction by membrane bound chromate reductases thereby reducing damage to other enzymes respectively. Overall, this strategy reduced the negative effect of chromate, thus improved the generation, transportation, and consumption of electrons. SYNOPSIS: The presence of S. oneidensis MR-1 facilitated nitrate and Cr(VI) removal by P. denitrificans through decreasing the negative effect of chromate due to the metabolites' secretion.

An uncommon and easily overlooked case: Delayed intraperitoneal bladder rupture following blunt trauma: A case report and review of the literature.

INTRODUCTION: Delayed intraperitoneal bladder rupture is a rare clinical occurrence, frequently overlooked and misdiagnosed due to its nonspecific clinical manifestations. However, literature provides only a limited number of cases reporting delayed intraperitoneal bladder rupture resulting from blunt abdominal injury. PATIENT CONCERNS: A 72-year-old female pedestrian was struck by a vehicle and experienced sudden, severe abdominal pain on the 8th day following the injury. Abdominal B-ultrasound revealed a significant accumulation of peritoneal effusion. The abdominal puncture retrieved serosanguinous ascites. Then the patient was promptly transferred to our hospital. Upon transfer, the physical examination revealed the patient vital signs to be stable, accompanied by mild abdominal distension, slight tenderness, tension, and an absence of rebound tenderness. Urinalysis detected microscopic hematuria, while contrast-enhanced computed tomography (CT) revealed considerable fluid accumulation in the abdominal cavity, without evidence of solid organ damage, and the bladder was adequately filled. DIAGNOSIS: The diagnosis of delayed intraperitoneal bladder rupture primarily relied on intraoperative observations. INTERVENTIONS: An emergency exploratory laparotomy was performed, revealing a linear rupture at the dome of the bladder. Subsequently, the bladder rupture was repaired. OUTCOMES: Postoperative cystography demonstrated full recovery and the patient was discharged 28 days post-surgery. The postoperative recovery was uneventful without any complications. CONCLUSIONS: A well-distended bladder observed in CT does not definitively rule out the potential for bladder injury. False negatives may occur due to incomplete bladder filling during CT cystography. Retrograde cystography can identify cases missed by CT cystography. In cases of substantial intra-abdominal free fluid, surgical intervention should be actively considered for patients with blunt abdominal trauma without concurrent solid organ damage.

Emergency hybrid surgery for transection of pancreas at the head and neck after blunt abdominal trauma: A case report and review of the literature.

INTRODUCTION: A complete disruption of main pancreatic duct (MPD) presents a significant challenge to the surgeon. Historically, the standard surgical approach for addressing a complete disruption of the MPD involved distal pancreatic resection and pancreaticojejunostomy Roux-en-Y anastomosis. Nevertheless, there have been no reported cases of hybrid surgery being employed for the complete disruption of the MPD. PATIENT CONCERNS: A 63-year-old male patient presented with blunt trauma in the upper abdomen and was transferred to our trauma center 10 hours after injury. Upon arrival at the emergency department, he was conscious, hemodynamically stable, and complained of upper abdominal pain and distention. Physical examination revealed right upper abdominal tenderness and slight abdominal tension. Abdominal contrast-enhanced CT scan revealed a complete transection of pancreatic parenchyma at the junction of the head and neck. DIAGNOSES: Complete transection of pancreatic parenchyma at the junction of the head and neck combined with complete disruption of the MPD, AIS grade IV. INTERVENTIONS: The hybrid surgery was initially utilized for complete MPD disruption, incorporating endoscope-assisted stent placement in the MPD along with primary repair of the pancreatic parenchyma and duct. OUTCOMES: The postoperative period went smoothly, and the patient recovered and was discharged 4 weeks after operation. The MPD stent was removed under endoscope 4 months after operation, and Endoscopic Retrograde Pancreatography examination showed that the MPD was patency and slight MPD stenosis without pancreatic leakage. At the most recent follow-up, the patient had returned to normal life and work without any pancreatic endocrine or exocrine dysfunction. LESSONS: The hybrid surgery, incorporating endoscope-assisted MPD stent placement and primary repair of the pancreatic parenchyma and duct, emerges as a promising alternative for complete MPD disruption in hemodynamically stable patients. The challenge in this hybrid surgery is the precise localization of the distal end of the MPD.

Comparative efficacy of different exercise methods to improve cardiopulmonary function in stroke patients: a network meta-analysis of randomized controlled trials.

Background: Although some studies have shown that exercise has a good effect on improving the cardiopulmonary function of stroke patients, it still needs to be determined which exercise method does this more effectively. We, therefore, aimed to evaluate the effectiveness of different exercise methods in improving cardiovascular function in stroke patients through a network meta-analysis (NMA), providing a basis to select the best treatment plan for stroke patients. Methods: We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and The Cochrane Library databases from establishment to 30 April 2023. Randomized controlled trials (RCTS) on exercise improving cardiopulmonary function in stroke patients were included, and we screened the included articles and extracted the relevant data. RevMan (version 5.4) and Stata (version 17.0) were used for data analysis. Results: We included 35 RCTs and a total of 2,008 subjects. Intervention measures included high-intensity interval training (HIIT), aerobic training (AT), resistance training (RT), combined aerobic and resistance exercise (CE), and conventional therapy (CT). In the network meta-analysis, the surface under the cumulative ranking area (SUCRA) ranking result indicated that HIIT improved peak oxygen uptake (VO2peak) and 6 mins walking distance (6MWD) optimally, with rankings of HIIT (100.0%) > CE (70.5%) > AT (50.2%) > RT (27.7%) > CT (1.6%), and HIIT (90.9%) > RT (60.6%) > AT (48.9%) > RT (48.1%) > CT (1.5%), respectively. The SUCRA ranking result showed that CE improved systolic blood pressure (SBP) and diastolic blood pressure (DBP) optimally, with rankings of CE (82.1%) > HIIT (49.8%) > AT (35.3%) > CT (32.8%), and CE (86.7%) > AT (45.0%) > HIIT (39.5%) > CT (28.8%), respectively. Conclusion: We showed that exercise can effectively improve the cardiopulmonary function of stroke patients. HIIT was the most effective in improving VO2peak and 6MWD in stroke patients. CE was the most effective in improving SBP and DBP in stroke patients. However, due to the limitations of existing clinical studies and evidence, larger sample size, multi-center, and high-quality RCTs are needed to verify the above conclusions in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023436773].

Fe-Zn alloy, a new biodegradable material capable of reducing ROS and inhibiting oxidative stress.

Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cell (EC) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/l. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.

Trappc1 intrinsically prevents ferroptosis of naive T cells to avoid spontaneous autoinflammatory disease in mice.

T lymphocytes are pivotal in adaptive immunity. The role of the trafficking protein particle complex (TRAPPC) in regulating T-cell development and homeostasis is unknown. Using CD4cre -Trappc1flox/flox (Trappc1 cKO) mice, we found that Trappc1 deficiency in T cells significantly decreased cell number of naive T cells in the periphery, whereas thymic T-cell development in Trappc1 cKO mice was identical as WT mice. In the culture assays and mouse models with adoptive transfer of the sorted WT (CD45.1+ CD45.2+ ) and Trappc1 cKO naive T cells (CD45.2+ ) to CD45.1+ syngeneic mice, Trappc1-deficient naive T cells showed significantly reduced survival ability compared with WT cells. RNA-seq and molecular studies showed that Trappc1 deficiency in naive T cells reduced protein transport from the endoplasmic reticulum to the Golgi apparatus, enhanced unfolded protein responses, increased P53 transcription, intracellular Ca2+ , Atf4-CHOP, oxidative phosphorylation, and lipid peroxide accumulation, and subsequently led to ferroptosis. Trappc1 deficiency in naive T cells increased ferroptosis-related damage-associated molecular pattern molecules like high mobility group box 1 or lipid oxidation products like prostaglandin E2, leukotriene B4, leukotriene C4, and leukotriene D4. Functionally, the culture supernatant of Trappc1 cKO naive T cells significantly promoted neutrophils to express inflammatory cytokines like TNFα and IL-6, which was rescued by lipid peroxidation inhibitor Acetylcysteine. Importantly, Trappc1 cKO mice spontaneously developed severe autoinflammatory disease 4 weeks after birth. Thus, intrinsic expression of Trappc1 in naive T cells plays an integral role in maintaining T-cell homeostasis to avoid proinflammatory naive T-cell death-caused autoinflammatory syndrome in mice. This study highlights the importance of the TRAPPC in T-cell biology.

In Situ Copper Coating on Silicon Particles Enables Long Durable Anodes in Lithium-Ion Batteries.

Addressing the significant obstacles of volume expansion and inadequate electronic conductivity in silicon-based anode materials during lithiation is crucial for achieving a long durable life in lithium-ion batteries. Herein, a high-strength copper-based metal shell is coated in situ onto silicon materials through a chemical combination of copper citrate and Si-H bonds and subsequent heat treatment. The formed Cu and Cu3Si shell effectively mitigates the mechanical stress induced by volume expansion during lithiation, strengthens the connection with the copper substrate, and facilitates electron transfer and Li+ diffusion kinetics. Consequently, the composite exhibits a reversible specific capacity of 1359 mA h g-1 at 0.5 A g-1 and maintains a specific capacity of 837 mA h g-1 and an 83.5% capacity retention after 400 cycles at 1 A g-1, surpassing similar reports on electrochemical stability. This facile copper plating technique on silicon surfaces may be used to prepare high-performance silicon-based anodes or functional composites in other fields.

IRG1 restrains M2 macrophage polarization and suppresses intrahepatic cholangiocarcinoma progression via the CCL18/STAT3 pathway.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant and aggressive cancer whose incidence and mortality continue to increase, whereas its prognosis remains dismal. Tumor-associated macrophages (TAMs) promote malignant progression and immune microenvironment remodeling through direct contact and secreted mediators. Targeting TAMs has emerged as a promising strategy for ICC treatment. Here, we revealed the potential regulatory function of immune responsive gene 1 (IRG1) in macrophage polarization. We found that IRG1 expression remained at a low level in M2 macrophages. IRG1 overexpression can restrain macrophages from polarizing to the M2 type, which results in inhibition of the proliferation, invasion, and migration of ICC, whereas IRG1 knockdown exerts the opposite effects. Mechanistically, IRG1 inhibited the tumor-promoting chemokine CCL18 and thus suppressed ICC progression by regulating STAT3 phosphorylation. The intervention of IRG1 expression in TAMs may serve as a potential therapeutic target for delaying ICC progression.

Multimodal Prognostic Model for Predicting Chronic Coronary Artery Disease in Patients Without Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS), with metabolic disorders as a central feature, is closely correlated with coronary artery disease (CAD). Our goal was to develop a prediction nomogram that integrated multimodal data that could accurately predict the prognosis of patients with chronic coronary disease (CCD). METHODS: We evaluated 393 patients with CCD with a low-to-intermediate pretest probability of OSAS based on polysomnography. A nomogram was constructed by means of least absolute shrinkage and selection operator (LASSO) and multiple Cox regression analyses to identify independent risk factors for major adverse cardiovascular events (MACEs). RESULTS: Two hundred seventy-seven patients were randomly assigned to the training set, and 116 to the verification set. The constructed nomogram consisted of seven clinical variables: age, previous CAD, current alcohol consumption, neck circumference, apnea-hypopnea index (AHI), and triglyceride-glucose index (TyG). The nomogram showed good discriminatory power, as evidenced by Harrell's C-index values of 0.79 (95% confidence interval [CI] 0.731-0.849) in the training set and 0.78 (95% CI 0.678-0.882) in the verification set. Moreover, a high correlation was observed between the predicted and actual incidence of MACEs in both the training and verification sets. Decision curve analysis demonstrated excellent clinical utility of the nomogram based on net benefit and threshold probabilities. CONCLUSIONS: We developed an integrated visualized prognostic nomogram that utilizes multi-modal data, including clinical characteristics, AHI, and TyG index, to predict MACEs in patients with CCD. This approach demonstrated excellent performance, highlighting the potential of combining different data sources to enhance prediction accuracy.

Single-cell transcriptomic analysis reveals transcriptional and cell subpopulation differences between human and pig immune cells.

BACKGROUND: The pig is a promising donor candidate for xenotransplantation. Understanding the differences between human and swine immune systems is critical for addressing xenotransplant rejection and hematopoietic reconstitution. The gene transcriptional profile differences between human and pig immune cell subpopulations have not been studied. To assess the similarities and differences between pigs and humans at the levels of gene transcriptional profiles or cell subpopulations are important for better understanding the cross-species similarity of humans and pigs, and it would help establish the fundamental principles necessary to genetically engineer donor pigs and improve xenotransplantation. OBJECTIVE: To assess the gene transcriptional similarities and differences between pigs and humans. METHODS: Two pigs and two healthy humans' PBMCs were sorted for 10 × genomics single-cell sequence. We generated integrated human-pig scRNA-seq data from human and pig PBMCs and defined the overall gene expression landscape of pig peripheral blood immune cell subpopulations by updating the set of human-porcine homologous genes. The subsets of immune cells were detected by flow cytometry. RESULTS: There were significantly less T cells, NK cells and monocytes but more B cells in pig peripheral blood than those in human peripheral blood. High oxidative phosphorylation, HIF-1, glycolysis, and lysosome-related gene expressions in pig CD14+ monocytes were observed, whereas pig CD14+ monocytes exhibited lower levels of cytokine receptors and JAK-STAT-related genes. Pig activated CD4+T cells decreased cell adhesion and inflammation, while enriched for migration and activation processes. Porcine GNLY+CD8+T cells reduced cytotoxicity and increased proliferation compared with human GNLY+CD8+T cells. Pig CD2+CD8+γδT cells were functionally homologous to human CD2+CD4+ γδT cells. Pig CD2-CD8-γδT cells expressed genes with quiescent and precursor characteristics, while CD2-CD8+γδT cells expressed migration and memory-related molecules. Pig CD24+ and CD5+B cells are associated with inflammatory responses. CONCLUSION: Our research with integrated scRNA-seq assays identified the different distribution of pig immune cell subpopulations and the different transcriptional profiles of human and pig immune cells. This study enables a deeper understanding of the development and function of porcine immune cells.

Porcupine quills keratin peptides induces G0/G1 cell cycle arrest and apoptosis via p53/p21 pathway and caspase cascade reaction in MCF-7 breast cancer cells.

BACKGROUND: Porcupine quills, a by-product of porcupine pork, are rich in keratin, which is an excellent source of bioactive peptides. The objective of this study was to investigate the underlying mechanism of anti-proliferation effect of porcupine quills keratin peptides (PQKPs) on MCF-7 cells. RESULTS: Results showed that PQKPs induced MCF-7 cells apoptosis by significantly decreasing the secretion level of anti-apoptosis protein Bcl-2 and increasing the secretion levels of pro-apoptosis proteins Bax, cytochrome c, caspase 9, caspase 3 and PARP. PQKPs also arrested the cell cycle at G0/G1 phase via remarkably reducing the protein levels of CDK4 and enhancing the protein levels of p53 and p21. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis identified nine peptides with molecular weights less than 1000 Da in PQKPs. Molecular docking results showed that TPGPPT and KGPAC identified from PQKPs could bind with p53 mutant and Bcl-2 protein by conventional hydrogen bonds, carbon hydrogen bonds and van der Waals force. Furthermore, the anti-proliferation impact of synthesized peptides (TPGPPT and KGPAC) was shown in MCF-7 cells. CONCLUSION: These findings indicated that PQKPs suppressed the proliferation of MCF-7 breast cancer cells by triggering apoptosis and G0/G1 cell cycle arrest. Moreover, the outcome of this study will bring fresh insights into the production and application of animal byproducts. © 2023 Society of Chemical Industry.