CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma.

Background: Gliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses. Methods: This investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages. Results: The expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors. Conclusion: CLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury.

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL­1ß, IL­6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-ß, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.

Diagnostic efficacy of tract-specific diffusion tensor imaging in cervical spondylotic myelopathy with electrophysiological examination validation.

PURPOSE: This study aimed to investigate the effectiveness of tract-specific diffusion tensor imaging (DTI) metrics in identifying the responsible segments for neurological dysfunction in cervical spondylotic myelopathy (CSM). METHODS: The study encompassed nineteen participants diagnosed with CSM, including 10 males and 9 females. Additionally, a control group consisting of ten healthy caregivers (5 males and 5 females) were recruited with no symptoms and no compressions on magnetic resonance imaging (MRI). All participants underwent a comprehensive physical examination, MRI assessment, and DTI examination conducted by a senior chief physician. Several parameters were collected from the MR images, including the aspect ratio (defined as the anteroposterior diameter / the transverse diameter of the corresponding segment's spinal cord), transverse ratio (defined as the transverse diameter of the corresponding segment's spinal cord / the transverse diameter of the spinal cord at C2/3), and T2 high signal of the spinal cord. Furthermore, quantitative DTI metrics, such as axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA), were calculated using automatic region-of-interest (ROI) analysis for both whole spinal cord column and dorsal column. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic efficacy of the aspect ratio, transverse ratio, and DTI parameters. The area under the curve (AUC), sensitivity, and specificity were calculated. Intraoperative spinal cord electrophysiological examination was performed as the objective measure of spinal cord function during surgery. RESULTS: As determined by electrophysiological examination, neurological dysfunction was found in 2 patients due to C3/4 compression, in 10 patients due to C4/5 compression, in 6 patients due to C5/6 compression, and in 1 patient due to C6/7 compression. The modified Japanese Orthopedic Association scale (mJOA) was 12.71 ± 1.55 in the CSM group, with 4.87 ± 0.72 for sensory nerve function and 5.05 ± 1.35 for motor nerve function. For the control group, none of the volunteers had neurological dysfunction. T2 high signal was found at the most stenotic segment in 13 patients of the CSM group. Considering all the cervical segments, the aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) was more capable of determining the responsible segment than transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). AD, MD, and RD were significantly higher while FA was significantly lower in the responsible segment than in the irresponsible segment (P < 0.05). The AUC of DTI-Dorsal column parameters (AD, MD, RD, FA) was larger than the corresponding parameters of the DTI (Whole spinal cord). AD of DTI-Dorsal Column possessed the greatest efficacy (AUC = 0.823, sensitivity = 84.21%, specificity = 77.32%) to determine the responsible segment, larger than AD of DTI-Whole spinal cord (AUC = 0.822, P = 0.001, Sensitivity = 89.47%, Specificity = 77.32%), aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) and transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). Subgroup analysis revealed that the diagnostic efficacy of DTI and MRI parameters was influenced by cervical spine segment. CONCLUSIONS: When considering all cervical segments, AD from the DTI-Dorsal Column exhibited the most significant potential in identifying responsible segments. This potential was found to be superior to that of DTI-Whole spinal cord, aspect ratio, the most stenotic segment, T2 high signals, transverse ratio, motor nerve dysfunction, and sensory nerve dysfunction. The diagnostic effectiveness of both DTI and MRI parameters was notably influenced by the specific cervical spine segment.

Spinal cord perfusion is associated with microstructural damage in cervical spondylotic myelopathy patients who underwent cervical laminoplasty.

OBJECTIVES: To investigate the association between spinal cord perfusion and microstructural damage in CSM patients who underwent cervical laminoplasty using MR dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques. METHODS: A follow-up cohort study was conducted with 53 consecutively recruited CSM patients who had undergone cervical laminoplasty 12-14 months after the surgery from April 2016 to December 2016. Twenty-one aged-matched healthy volunteers were recruited as controls. For each patient, decompressed spinal cord levels were imaged on a 3.0-T MRI scanner by diffusion and DSC sequences to quantify the degrees of microstructural damage and perfusion conditions, respectively. The diffusion data were analyzed by DTI and NODDI models to produce diffusion metrics. Classic indicator dilution model was used to quantify the DSC metrics. Mann-Whitney U test was performed for comparison of diffusion metrics between patients and healthy controls. Pearson correlation was used to explore the associations between the metrics of spinal cord perfusion and microstructural damage. RESULTS: DTI metrics, neurite density, and isotropic volume fraction had significant differences between postoperative patients and healthy controls. Pearson correlation test showed that SCBV was significantly positively correlated with RD, MD, and ODI, and negatively correlated with FA and NDI. SCBF was found to be significantly positively correlated with RD and MD, and negatively correlated with FA. CONCLUSIONS: Increased spinal cord perfusion quantified by DSC is associated with microstructural damage assessed by diffusion MRI in CSM patients who underwent cervical laminoplasty. CLINICAL RELEVANCE STATEMENT: This study found that the spinal cord perfusion is associated with microstructural damage in postoperative cervical spondylotic myelopathy patients, indicating that high perfusion may play a role in the pathophysiological process of cervical spondylotic myelopathy and deserves more attention. KEY POINTS: • Spinal cord microstructural damage can be persistent despite the compression had been relieved 12-14 months after the cervical laminoplasty in cervical spondylotic myelopathy (CSM) patients. • Spinal cord perfusion is associated with microstructural damage in CSM patients after the cervical laminoplasty. • Inflammation in the decompressed spinal cord may be a cause of increased perfusion and is associated with microstructural damage during the recovery period of CSM.

Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration.

PURPOSE: Antibody-drug conjugate (ADC) has had a transformative effect on the treatment of many solid tumors, yet it remains unclear how ADCs exert bystander activity in the tumor microenvironment. EXPERIMENTAL DESIGN: Here, we directly visualized and spatiotemporally quantified the intratumor biodistribution and pharmacokinetics of different ADC components by developing dual-labeled fluorescent probes. RESULTS: Mechanistically, we found that tumor penetration of ADCs is distinctly affected by their ability to breach the binding site barrier (BSB) in perivascular regions of tumor vasculature, and bystander activity of ADC can only partially breach BSB. Furthermore, bystander activity of ADCs can work in synergy with coadministration of their parental antibodies, leading to fully bypassing BSBs and enhancing tumor penetration via a two-step process. CONCLUSIONS: These promising preclinical data allowed us to initiate a phase I/II clinical study of coadministration of RC48 and trastuzumab in patients with malignant stomach cancer to further evaluate this treatment strategy in humans.

Role of Cherry Valley duck IRF1 mediated signal pathway in host anti-duck Tembusu virus.

China is the country with the largest amount of duck breeding as well as duck meat and egg production. In recent years, the emergence and spread of duck Tembusu virus (DTMUV) has become one of the important factors in reducing the amount of duck slaughter, which seriously endangers the duck breeding industry in our country. In-depth research on the mechanism of duck innate immunity facilitates the exploration of new models for the treatment of DTMUV infection. IRF1 can induce the expression of many antiviral immune factors in the animal organism and play an important role in the innate immune response. In this study, we used interfering RNA to knock down the IRF1 gene in DEF cells and then the cells were infected with DTMUV. We found that knockdown of IRF1 promoted DTMUV replication at an early stage and caused downregulation of the expression of several major pattern recognition receptors (PRRs), interleukins (IL), interferons (IFN), antiviral proteins, and MHC molecules by assay, showing that the duIRF1-mediated signaling pathway plays an extremely important role in DTMUV-induced host innate immunity. In addition, we constructed the recombinant expression plasmid pET32a(+)-duIRF1-His, and finally prepared the polyclonal antibody of duIRF1 with good specificity, hoping to provide a detection means for research on the mechanism of IRF1 in innate immunity in our laboratory and in this field.

TRIM21 of Micropterus salmoides exerts antiviral roles against largemouth bass ulcer syndrome virus.

Tripartite motif 21 (TRIM21), a member of the TRIM family, plays an important role in apoptosis, autophagy and ubiquitination in human, and has been proven to play antiviral roles in different organisms. In this study, the TRIM21 gene of Micropterus salmoides (MsTRIM21) was cloned, and it encoded 376 amino acids, which showed 89.3% similarity with Micropterus dolomieu and 38.3% with homo sapiens. Bioinformatics analysis revealed MsTRIM21 contained four domains: C4HC3-type RING-variant (RINGv), coiled coil, PRY and SPRY. The high expression level of MsTRIM21 could be detected in liver, stomach and muscle of healthy Micropterus salmoides, and it was significantly upregulated in head kidney, muscle, gill and brain and significantly down-regulated in the stomach of Micropterus salmoides infected with largemouth bass ulcer syndrome virus (LBUSV). The overexpression of MsTRIM21 could significantly inhibit the viral replication in vitro, evidenced by the reduction of CPE severity and the downregulation of the viral gene transcription. In addition, the overexpression of MsTRIM21 could significantly increase the expression level of interferon regulatory factor (IRF) 3, IRF7, myxovirus resistance 1 (Mx1), interferon stimulated gene 15 (ISG15), double-stranded RNA-activated protein kinase (PKR) and tumor necrosis factor α (TNF-α) in vitro, indicating the enhancement of innate immune response and inflammatory response, which may directly affect the replication of LBUSV. Thus, these results provide new lights on the roles of fish TRIM21 in innate immune response against iridovirus.

Automatic identification method of bridge structure damage area based on digital image.

It is of great scientific and practical value to use effective technical means to monitor and warn the structural damage of bridges in real time and for a long time. Traditional image recognition network models are often limited by the lack of on-site images. In order to solve the problem of automatic recognition and parameter acquisition in digital images of bridge structures in the absence of data information, this paper proposes an automatic identification method for bridge structure damage areas based on digital images, which effectively achieves contour carving and quantitative characterization of bridge structure damage areas. Firstly, the digital image features of the bridge structure damage area are defined. By making full use of the feature that the pixel value of the damaged area is obviously different from that of the surrounding image, an image pre-processing method of the structure damaged area that can effectively improve the quality of the field shot image is proposed. Then, an improved Ostu method is proposed to organically fuse the global and local threshold features of the image to achieve the damaged area contour carving of the bridge structure surface image. The scale of damage area, the proportion of damage area and the calculation rule of damage area orientation are constructed. The key inspection and characteristic parameter diagnosis of bridge structure damage area are realized. Finally, test and analysis are carried out in combination with an actual project case. The results show that the method proposed in this paper is feasible and stable, which can improve the damage area measurement accuracy of the current bridge structure. The method can provide more data support for the detection and maintenance of the bridge structure.

Release behavior of fertilizers and heavy metals from iron-loaded sludge biochar in the aqueous environment.

In this study, the release behavior of fertilizers (NH4+-N, PO43- and K) and heavy metals (Mn, Zn, Ni, Cu, Pb and Cr) from iron-loaded sludge biochar (ISBC) was investigated to evaluated the feasibility and risks of ISBC as a slow release fertilizer. Their release capacity was significantly enhanced with decreasing initial pH, increasing solid-liquid ratio (RS-L) and rising temperature (p < 0.05). When the initial pH, RS-L and temperature were separately 5 (fertilizers)/1 (heavy metals), 1:5 and 298 K, the final concentrations of NH4+-N, PO43-, K, Mn, Zn and Ni were 6.60, 14.13, 149.4, 53.69, 72.56, and 1.01 mg L-1, while the maximum concentrations of Cu, Pb and Cr were 0.94, 0.77, and 0.22 mg L-1, respectively. Due to the tiny difference between the R2 values, revised pseudo-first-order and pseudo-second-order kinetics models described their release behavior well, suggesting that physical and chemical interactions played an important role. Activation energies greater than 40 kJ mol-1 indicated that the rate-controlling steps of the release of NH4+-N, PO43- and Ni were chemical reactions, while chemical reactions and diffusion together determined the release rates of K, Mn, Zn, Cu, Pb and Cr because their activation energies were in the range of 20-40 kJ mol-1. The increasingly negative ΔG and positive ΔH and ΔS suggested that their release was a spontaneous (except Cr) and endothermic process with an increase of randomness between the solid-liquid interface. The release efficiency of NH4+-N, PO43- and K were in the ranges of 28.21%-53.97%, 2.09%-18.06% and 39.46%-66.14%, respectively. Meanwhile, the pollution index and evaluation index of heavy metals were in the ranges of 33.31-227.4 and 4.64-29.24, respectively. In summary, ISBC could be used as a slow-release fertilizer with low risk when the RS-L was less than 1:40.

Hourglass-like constriction of the anterior interosseous nerve in the left forearm: A case report.

BACKGROUND: Hourglass-like constriction neuropathy is a rare neurological disorder. The main clinical manifestation is peripheral nerve injury with no apparent cause, and the pathomorphological change is an unexplained narrowing of the diseased nerve. The diagnosis and treatment of the disease are challenging and there is no accepted diagnostic or therapeutic approach. CASE SUMMARY: This report describes a rare hourglass constriction of the anterior interosseous nerve in the left forearm in a 47-year-old healthy male who was treated surgically and gradually recovered function over a 6-mo follow-up period. CONCLUSION: Hourglass-like constriction neuropathy is a rare disorder. With the development of medical technology, more examinations are now available for diagnosis. This case aims to highlight the rare manifestations of Hourglass-like constriction neuropathy and provides a reference for enriching the clinical diagnosis and treatment experience.

Effect of iron-loaded sludge biochar amendments on phytoremediation potential of Cr-contaminated soils by Leersia hexandra swartz.

In this study, the effect of iron-loaded sludge biochar (ISBC) with different amendment dosages (mass ratio of biochar to soil equal to 0, 0.01, 0.025 and 0.05) on the phytoremediation potential of Leersia hexandra swartz (L. hexandra) to Cr-contaminated soil was investigated. With increasing ISBC dosage from 0 to 0.05, plant height, aerial tissue biomass and root biomass increased from 15.70 cm, 0.152 g pot-1 and 0.058 g pot-1 to 24.33 cm, 0.304 g pot-1 and 0.125 g pot-1, respectively. Simultaneously, the Cr contents in aerial tissues and roots increased from 1039.68 mg kg-1 to 2427.87 mg kg-1 to 1526.57 mg kg-1 and 3242.62 mg kg-1, respectively. Thus, the corresponding bioenrichment factor (BCF), bioaccumulation factor (BAF), total phytoextraction (TPE) and translocation factor (TF) values were also increased from 10.52, 6.20, 0.158 mg pot-1 (aerial tissue)/0.140 mg pot-1 (roots) and 0.428 to 15.15, 9.42, 0.464 mg pot-1 (aerial tissue)/0.405 mg pot-1 (roots) and 0.471, respectively. The significant positive effect of ISBC amendment was primarily attributed to the following three aspects: 1) the root resistance index (RRI), tolerance index (TI) and growth toxicity index (GTI) of L. hexandra to Cr were increased from 100%, 100% and 0%-216.88%, 155.02% and 42.18%, respectively; 2) the bio-available Cr content in the soil was decreased from 1.89 mg L-1 to 1.48 mg L-1, while the corresponding TU (toxicity units) value was declined from 0.303 to 0.217; 3) the activities of urease, sucrase and alkaline phosphatase in soil were increased from 0.186 mg g-1, 1.40 mg g-1 and 0.156 mg g-1 to 0.242 mg g-1, 1.86 mg g-1 and 0.287 mg g-1, respectively. In summary, ISBC amendment was able to significantly improve the phytoremediation of Cr-contaminated soils by L. hexandra.

Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas.

Background: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. Methods: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. Results: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. Conclusion: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.

Introduction and comparision of three different fixation methods in the suprahepatic space in laparoscopy-assisted ventriculoperitoneal shunt for hydrocephalus.

Ventriculoperitoneal shunt (VPS) placement is the standard procedure in the management of hydrocephalus. The introduction of laparoscopy allows better visualization during the operation and a more reliable placement of the peritoneal terminal of the catheter, which significantly decreases postoperative obstruction and malposition rates. However, the fixation methods of the peritoneal terminal of the catheter have not been previously discussed. The indications, techniques, and complications were compared between conventional VPS and laparoscopy-guided VPS. Furthermore, same analyses were performed within the laparoscopy-guided VPS group subdivided by three different techniques of the fixation of the peritoneal terminal of catheter, including suture and ligature, titanium clip fixation, and subcutaneous fixation. A total of 137 patients with hydrocephalus who received VPS treatment was retrospectively studied, 85 of which were laparoscopy-guided, and 52 were not. The distal ends of the catheters were all placed in the suprahepatic space. At least one year (mean 28.6 months) follow-up was given postoperatively. The average duration of the whole operation was 45 min for suture and ligature, 40 min for titanium clip fixation, and 30 min for the subcutaneous fixation, respectively. Six patients (4.4%) had obstructive of the ventricular catheter in total. The success rates for the laparoscopy-assisted VPS procedure and the conventional VPS procedure were 87.1% (74/85) and 80.8% (42/52), respectively. Within subgroups of the laparoscopy-assisted VPS divided by fixation methods, the procedures were successful in 85.2% (23/27) of suture and ligation, 82.1% (23/28) of titanium clip fixation, and 93.3% (28/30) of subcutaneous fixation, respectively. Two patients had dislocated shunt tube in peritoneal end in laparoscopy group, all in the titanium clip fixation subgroups. The laparoscopy-assisted VPS insertion is an ideal shunt method for its effectiveness and lesser complication rate after operation. The subcutaneous fixation method of the peritoneal terminal of catheter might be the optimal fixation technique.

The effect of economic growth pressure on green technology innovation: Do environmental regulation, government support, and financial development matter?

Green technology improvement is critical in promoting green development and mitigating negative externalities. Exploring the effect of economic growth pressure (EGP) on green technology innovation (GTI) is important for coordinated economic growth and green transformation. Using the data from 285 cities in China during 2006-2018, this study investigates the influence of EGP on GTI by taking the difference between economic growth target and previous year's actual growth rate to represent the EGP. The results indicate that EGP negatively affects GTI. When there is a 1% increase in EGP, green patent applications will fall by 3.2%. Furthermore, the heterogeneity analysis indicates that the negative effect of EGP is especially significant in western China compared with eastern and central regions. In addition, we find various nonlinear moderating effects between EGP and GTI by using panel threshold model. Specifically, EGP and GTI show an inverted U-shaped relationship with EGP increasing. Meanwhile, only when environmental regulation, government support, and financial development cross the thresholds will EGP have a significant role in promoting GTI. This study provides helpful implications for decision-makers to adopt a more reasonable combination of policy tools to achieve economic growth targets and low-carbon transformation.

Hepatocyte-derived exosomes deliver H2AFJ to hepatic stellate cells and promote liver fibrosis via the MAPK/STMN1 axis activation.

Hepatic stellate cells (HSCs) activate and acquire proliferative features in response to liver injury. However, mechanisms involved in the activation of fibrotic HSCs remain uncharacterized. This study aims at elaborating the mechanistic basis by which exosomal H2AFJ derived from hepatocytes might affect the activation of HSCs and liver fibrosis. Bioinformatics analysis based on transcriptomic RNA-seq data was used to screen out the downstream regulatory genes and pathways of H2AFJ. Mouse hepatocytes AML-12 cells were stimulated with CCl4 to mimic an in vitro microenvironment of liver fibrosis, from which exosomes were isolated. Next, HSCs were co-cultured with hepatocyte-derived exosomes followed by detection of HSC migration and invasion in the presence of manipulated H2AFJ and STMN1 expression and MAPK pathway inhibitor. It was found that H2AFJ was highly expressed in hepatocyte-derived exosomes after CCl4 stimulation. Hepatocyte-derived exosomal H2AFJ promoted HSC migration and invasion. H2AFJ upregulated c-jun-mediated STMN1 by activating the MAPK signaling pathway. Furthermore, in vivo experiments verified that silencing of H2AFJ attenuated liver fibrosis in mice, while restoration of STMN1 negated its effect. Collectively, hepatocyte-derived exosomal H2AFJ aggravated liver fibrosis by activating the MAPK/STMN1 signaling pathway. This study provides a potential therapeutic target for alleviating liver fibrosis.

How ICT development affects manufacturing carbon emissions: theoretical and empirical evidence.

There is a broad consensus that information and communication technology (ICT) development contributes to economic growth, but its environmental benefits have not been thoroughly studied. This paper explores the impact and mechanisms of ICT development on manufacturing carbon emissions. We first conducted empirical tests based on panel data from 18 manufacturing sectors in 42 countries from 2000 to 2014. The results show that domestic ICT development reduces manufacturing carbon emissions, but the effect is only significant in sectors with high ICT embedded. Second, technological progress, industrial internal structure upgrading, energy consumption intensification, and low carbonization are the main channels for ICT development and embedding to reduce manufacturing carbon emissions. Third, the carbon emissions from manufacturing, which are deeply embedded by ICT, will decrease as the position of ICT forward GVCs improves, and increase as the position of backward GVCs increases. In addition, ICT development has a more significant impact on reducing carbon emissions in high-tech manufacturing. This paper has enriched research on the environmental benefits of ICT development and has been informative and insightful for countries in formulating industrial development policies and implementing the Paris Agreement.

Myeloid sarcoma with ulnar nerve entrapment: A case report.

BACKGROUND: Myeloid sarcoma (MS) is relatively rare, occurring mainly in the skin and lymph nodes, and MS invasion of the ulnar nerve is particularly unusual. The main aim of this article is to present a case of MS invading the brachial plexus, causing ulnar nerve entrapment syndrome, and to further clinical understanding of the possibility of MS invasion of peripheral nerves. CASE SUMMARY: We present the case of a 46-year-old man with a 13-year history of well-treated acute nonlymphocytic leukaemia who was admitted to the hospital after presenting with numbness and pain in his left little finger. The initial diagnosis was considered a simple case of nerve entrapment disease, with magnetic resonance imaging showing slightly abnormal left brachial plexus nerve alignment with local thickening, entrapment, and high signal on compression lipid images. Due to the severity of the ulnar nerve compression, we surgically investigated and cleared the entrapment and nerve tissue hyperplasia; however, subsequent pathological biopsy results revealed evidence of MS. The patient had significant relief from his neurological symptoms, with no postoperative complications, and was referred to the haemato-oncology department for further consultation about the primary disease. This is the first report of safe treatment of ulnar nerve entrapment from MS. It is intended to inform hand surgeons that nerve entrapment may be associated with extramedullary MS, as a rare presenting feature of the disease. CONCLUSION: MS invasion of the brachial plexus and surrounding tissues of the upper arm, resulting in ulnar nerve entrapment and degeneration with significant neurological pain and numbness in the little finger, is uncommon. Surgical treatment significantly relieved the patient's nerve entrapment symptoms and prevented further neurological impairment. This case is reported to highlight the rare presenting features of MS.

Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a life-threatening deterioration of mental status in relation to long-term and disabling cognitive dysfunction that is common in intensive care units worldwide. Cortistatin-14 is a neuropeptide structurally resembling somastostatin, which has been proven to play a crucial role in sepsis. The present study aimed to explore the neuroprotective role of cortistatin-14 in sepsis-associated encephalopathy and its underlying mechanisms in a mouse model. A septic mice model was established using the cecal ligation and puncture (CLP) method. The novel object recognition test (NORT), open field test (OFT), elevated plus maze test (EPMT), and tail suspension test (TST) were used to explore the behavioral performance of the mice. Transmission electron microscopy was used to observe the microstructure of the blood-brain barrier (BBB). Evans Blue staining was used to examine the integrity of the BBB. Immunofluorescence was used to examine the morphology and infiltration of microglia. A multiplex cytokine bead array assay was used to determine cytokine and chemokine levels in mouse serum and brain tissues. NORT revealed that cortistatin treatment improved cognitive impairment in septic mice. OFT, EPMT, and TST indicated that cortistatin-14 relieved the anxiety-related behaviors of CLP mice. In addition, cortistatin-14 treatment decreased the levels of various inflammatory cytokines, including interleukin-1ß, interleukin-6, interferon-γ, and tumor necrosis factor-α in both the serum and brain of septic mice. Cortistatin reduced sepsis-induced blood-brain barrier disruption and inhibited microglial activation after the onset of sepsis. Cortistatin exerts neuroprotective effects against SAE and cognitive dysfunction in a CLP-induced mouse model of sepsis.

Zinc-doped calcium silicate additive accelerates early angiogenesis and bone regeneration of calcium phosphate cement by double bioactive ions stimulation and immunoregulation.

Calcium phosphate cement (CPC), a popular injectable bone defect repairing material, has deficiencies in stimulating osteogenesis and angiogenesis. To overcome the weaknesses of CPC, zinc-doped calcium silicate (Zn-CS) which can release bioactive silicon (Si) and zinc (Zn) ions was introduced to CPC. The physicochemical and biological properties of CPC and its composites were evaluated. Firstly, the most effective addition content of calcium silicate (CaSiO3, CS) in promoting the in vitro osteogenesis was first sorted out. On this basis, the most effective Zn doping content in CS for improving osteogenic differentiation of CPC-based composites was screened out. Finally, the immunoregulation of CS/CPC and Zn-CS/CPC in promoting angiogenesis and osteogenesis was studied. The results showed that the most effective incorporation content of CS was 10 wt%. Zn at a doping content of 30 mol% in CS (30Zn-CS) further enhanced the osteogenic capacity of CS/CPC and simultaneously maintained excellent proangiogenic activity. CS/CPC and 30Zn-CS/CPC promoted the recruitment of macrophages and enhanced M2 polarization while inhibiting M1 polarization, which was beneficial to the early vascularization as well as subsequent new bone formation. When implanted into the femoral condylar defects of rabbits, 30Zn-CS/CPC showed high in vivo materials degradation rate, angiogenesis and osteogenesis, due to the synergistic effects of Si and Zn on bio-stimulation and immunoregulation. This study shed light on the synergistic effects of Si and Zn on regulating the angiogenic, osteogenic, and immunoregulatory activity, and 30Zn-CS/CPC is expected to repair the lacunar bone defects effectively.

The complete mitochondrial genome of Crematogaster matsumurai (Forel 1901) (Hymenoptera: Formicidae) and its phylogenetic relationship.

Crematogaster matsumurai (Forel 1901) is an important arboreal ant species commonly found on Phyllostachys heterocycla (Carr.) in Lishui, Zhejiang, China. This study analyzed the mitochondrial genome sequence of C. matsumurai and discussed its phylogenetic relationship in Hymenoptera. The circular mitochondrial genome was 16,028 bp long, including a standard set of 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and 13 protein-coding genes (PCGs), which showed the typical insect mitochondrial genome arrangement. The AT and GC contents of the mitochondrial genome sequence were 76.92% and 23.08%, respectively. The maximum-likelihood (ML) phylogenetic analysis based on whole mitochondrial genome sequences showed that C. matsumurai is closest to Crematogaster teranishii.