Genomic Insights into the Pathogenicity and Drug-Resistance of a Bacillus cereus Isolated from Human Teeth.

Background: Bacillus cereus is a common bacterium found in the environment. Some strains can cause food poisoning, and very few can cause clinically severe infections, leading to death. Here, we characterized the genome sequence of B. cereus LIN78 isolated from teeth with deep caries and compared it with those of 25 other related species. Methods: Third-generation sequencing technology, bacteriological analyses, biochemistry, and mass spectrometry were applied to characterize the drug-resistance genes and virulence factors of B. cereus LIN78. Results: The complete genome sequence of B. cereus Lin78 consists of 5647 genes distributed on a circular chromosome, a 393 kbp plasmid, and 928 pseudogenes (37.4% of whole-genome DNA). The LIN78 genome contains 14 sets of 16s, 23s, and 5s ribosomal RNA operons; 106 tRNA genes, one tmRNA, 12 genomic islands, six prophases, 64 repeats; 37 antibiotic-resistant genes; and 1119 putative virulence genes, including enterotoxins and cytolysins. The B. cereus LIN78 genome carries multiple copies of non-ribosomal polypeptide synthetase (NRPS) and post-translationally modified peptides (RiPPs). Phylogenetic analysis of the 26 B. cereus strains showed that B. cereus LIN78 is evolutionarily closely related to B. thuringiensis ATCC 10792 and B. cereus ATCC 14579. Conclusion: The newly isolated B. cereus carries many virulence genes, including enterotoxins and hemolysins, similar to B. anthracis, and multiple antibiotic resistance genes. These findings suggest that the strain has a potential risk of causing disease. Our studies are vital for further exploration of the evolution of B. cereus, its pathogenic mechanisms, and the control and treatment of bacterial infections.

Multigenerational Adaptation Can Enhance the Pathogen Resistance of Plants via Changes in Rhizosphere Microbial Community Assembly.

Plants withstand pathogen attacks by recruiting beneficial bacteria to the rhizosphere and passing their legacy on to the next generation. However, the underlying mechanisms involved in this process remain unclear. In our study, we combined microbiomic and transcriptomic analyses to reveal how the rhizosphere microbiome assembled through multiple generations and defense-related genes expressed in Arabidopsis thaliana under pathogen attack stress. Our results showed that continuous exposure to the pathogen Pseudomonas syringae pv tomato DC3000 led to improved growth and increased disease resistance in a third generation of rps2 mutant Arabidopsis thaliana. It could be attributed to the enrichment of specific rhizosphere bacteria, such as Bacillus and Bacteroides. Pathways associated with plant immunity and growth in A. thaliana, such as MAPK signaling pathways, phytohormone signal transduction, ABC transporter proteins, and flavonoid biosynthesis, were activated under the influence of rhizosphere bacterial communities. Our findings provide a scientific basis for explaining the relationship between beneficial microbes and defense-related gene expression. Understanding microbial communities and the mechanisms involved in plant responses to disease can contribute to better plant management and reduction of pesticide use.

Protein Dynamics Mediated by Cardiolipin in Bacteria.

Bacterial proteins targeting the appropriate subcellular sites are the base for their proper function. Several studies have shown that the anionic phospholipid cardiolipin (CL), a conical lipid preferring negative membrane curvature, modulates the lipid bilayers' structure, which impacts the activity of their resident proteins. Due to the favor of negative membrane curvature, CL is not randomly distributed in the bacterial plasma membrane. In contrast, it gathers in particular parts of the cell membrane to form microdomains, in which many functional membrane proteins are accumulated and carry out diverse physiological processes of bacteria, such as cell division, metabolism, infection, and antibiotic residence. In addition, CL has a unique structure that carries two negative charges, which makes it play a pivotal role in protein assembly, interaction, and location. These characteristics of CL make it closely related to many crucial physiological functions of bacteria. Here, we have reviewed the mechanism of protein dynamics mediated by CL initiated on the bacterial membrane. Furthermore, we studied the effect of CL on bacterial infection and antibiotic residence. Finally, the CL-targeting therapeutic agents for antibacterial therapy are also examined.

Experimental Study on Long-Term Mechanical Properties and Durability of Waste Glass Added to OPC Concrete.

This study aims to achieve the sustainable utilization of waste glass resources through an investigation into the influence of three types of admixtures, namely waste glass powder (WGP) (G), waste glass powder-slag (G-S), and waste glass powder-fly ash (G-F), on the mechanical properties and durability performance of waste glass concrete. The experimental results demonstrate that the exclusive use of WGP as an admixture led to the relatively poor early compressive strength of the concrete, which decreased with an increase in dosage. However, at medium to long curing ages, the strength of the waste glass concrete could equal or even surpass that of ordinary concrete. When dual admixtures were employed, the G-S group exhibited higher compressive strength compared to the G-F group. Specifically, within the G-S group, a glass powder dosage of 15% yielded higher compressive strength, and after 180 days, the dual admixture groups exhibited greater strength than ordinary concrete (G0); the compressive strength of the tG1S1 group was 44.57 MPa, and that of the G0 group was 40.07 MPa. The chloride ion diffusion coefficient showed a varying trend with an increase in WGP dosage, initially decreasing and then increasing. The concrete's resistance to erosion was maximized when the glass powder dosage reached 30%. As the WGP dosage increased, the overall frost resistance decreased. For a total dosage of 30%, the optimal glass powder dosage in both G-S and G-F groups was found to be 15%.

Identification of CD147-positive extracellular vesicles as novel non-invasive biomarkers for the diagnosis and prognosis of colorectal cancer.

BACKGROUND: The mortality rate of colorectal cancer (CRC) can be decreased with effective screening and early diagnosis. Exosomes are released from cancer cells into the bloodstream, and circulating exosomes may serve as novel biomarkers. This study aimed to identify a sensitive and rapid method of exosome collection and measurement using specific antibodies. METHODS: ExoCounter, a high-sensitive exosome-counting system, allows the identification of exosomes without enrichment or purification, based on the identification of the transmembrane protein-CD147-on serum exosomes that are associated with CRC. RESULTS: Receiver operating characteristic curves between healthy donors and CRC patients were described and assessed by CD147-specific exosomes (exo-CD147), CEA, and CA19-9. And area under curves for exo-CD147, CEA, and CA19-9 were 0.827 (95%CI: 0.764-0.891), 0.630 (95%CI: 0.536-0.724), and 0.659 (95%CI: 0.559-0.759), respectively. Drawing a clinical decision curve of exo-CD147 for the diagnosis of CRC metastases showed that when the threshold probability of exo-CD147 was between 20% and 92%, the net clinical utilization rate was higher than for all patients with or without metastases. A nomogram was constructed using multivariate COX regression analysis to select significant variables such as the high CD147 group (>34 × 105 particles). Calibration curves for 1-, 3-, and 5-year survival rates of CRC patients showed that the actual 1-, 3-, and 5-year survival rates were in excellent agreement with the survival rates predicted by the nomogram. CONCLUSIONS: The increased CD147 expression in exosomes could serve as a diagnostic and prognostic biomarker for CRC.

The Temporal and Spatial Changes of Autophagy and PI3K Isoforms in Different Neural Cells After Hypoxia/Reoxygenation Injury.

There are limited therapeutic options for patient with traumatic spinal cord injury (SCI). Phosphoinositide 3-kinase family (PI3Ks) are the key molecules for regulating cell autophagy, which is a possible way of treating SCI. As we know, PI3K family are composed of eight isoforms, which are distributed into three classes. While the role of PI3Ks in regulating autophagy is controversial and the effects may be in a cell-specific manner. Different isoforms do not distribute in neural cells consistently and it is not clear how the PI3K isoforms regulate and interact with autophagy. Therefore, we explored the distributions and expression of different PI3K isoforms in two key neural cells (PC12 cells and astrocytes). The results showed that the expression of LC3II/I and p62, which are the markers of autophagy, changed in different patterns in PC12 cells and astrocytes after hypoxia/reoxygenation injury (H/R). Furthermore, the mRNA level of eight PI3K isoforms did not change in the same way, and even for the same isoform the mRNA activities are different between PC12 cells and astrocytes. What is more, the results of western blot of PI3K isoforms after H/R were inconsistent with the relevant mRNA. Based on this study, the therapeutic effects of regulating autophagy on SCI are not confirmed definitely, and its molecular mechanisms may be related with different temporal and spatial patterns of activation and distributions of PI3K isoforms.

A Modified Unilateral Extrapedicular Approach Applied to Percutaneous Kyphoplasty to Treat Lumbar Osteoporotic Vertebral Compression Fracture: A Retrospective Analysis.

BACKGROUND: In recent years, many extrapedicular puncture methods have been applied to percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs). However, these techniques were generally complex and had the risk of some puncture-related complications, which greatly limited the wide applications in PKP. Finding a safer and more feasible extrapedicular puncture method was rather important. OBJECTIVES: To evaluate the treatment effect of modified unilateral extrapedicular PKP in patients with lumbar OVCFs clinically and radiologically. STUDY DESIGN: Retrospective study. SETTING: Department of Orthopedic Surgery, an affiliated hospital of a medical university. METHODS: Patients who were treated by modified unilateral extrapedicular PKP in our institution, from January 2020 to March 2021, were retrospectively enrolled. The degree of pain relief and functional recovery were evaluated by the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI), respectively. Radiologic results were assessed including anterior vertebral height (AVH) and kyphotic angle. In addition, volumetric analysis was performed to evaluate bone cement distribution. And the intraoperative data and complications were also recorded. RESULTS: A total of 48 patients with lumbar OVCFs were successfully treated by modified unilateral extrapedicular PKP. All patients experienced a significant decrease in VAS and ODI scores after surgery (P < 0.01) and maintained the statistical significance until the last follow-up (P < 0.01), as well as significant AVH restoration (P < 0.01) and kyphotic angle correction (P < 0.01) compared with preoperative corresponding values. Volumetric analysis showed that all cases of bone cement diffused across the midline of the vertebral body (VB), in which 43 patients (89.6%) presented optimal contralateral distribution with good or excellent bone cement spread. In addition, 8 patients (16.7%) experienced asymptomatic cement leakage, and no other severe complications, such as injuries to segmental lumbar arteries and nerve roots, were found. LIMITATIONS: A noncontrol study with a small patient population and short follow-up duration. CONCLUSIONS: Modified unilateral extrapedicular PKP, in which the puncture trajectory was advanced through the bottom of Kambin's triangle to or across the midline of VB for proper bilateral cement distribution, greatly alleviated back pain and restored the morphology of fractured vertebrae. It seemed to be a safe and effective alternative applied to treat lumbar OVCFs with appropriate patient selection.

Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer.

BACKGROUND AND AIMS: This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk. MATERIALS AND METHODS: There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis. RESULTS: Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis. CONCLUSION: Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk.

Imaging diagnostic features of intracranial primary extranodal Rosai-Dorfman disease: Two case reports and literature review.

In this report, we describe 2 cases of rare intracranial extranodal Rosai-Dorfman disease. The occurrence of this type of non-Langerhans cell histiocytosis in the central nervous system is infrequent, with less than 5% of cases. The first patient was a 35-year-old male who presented with recurring headaches, and the second patient was a 50-year-old male who reported sudden onset of dizziness and vomiting. Computed tomography scans were performed in both cases, but magnetic resonance imaging played a crucial role in the characterization of the lesions and their locations in the thalamus, third ventricle, lateral ventricles, and cerebellopontine angle area. The final diagnosis was confirmed through pathological examination and immunohistochemistry following brain tumor resection. These cases underscore the significance of magnetic resonance imaging in the early diagnosis of intracranial extranodal Rosai-Dorfman disease.

Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m6A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m6A levels and m6A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m6A, but the relevant profile in LUAD remains unclear. RESULTS: The m6A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m6A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m6A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m6A-modified and manifested a negative correlation between expression levels and m6A modification levels. More than half of the differentially m6A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m6A-induced pathogenicity in LUAD. CONCLUSIONS: These data have demonstrated that differential RNA m6A modification and m6A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m6A-modified lncRNAs in LUAD.

Understanding the ecological effects of the fungicide difenoconazole on soil and Enchytraeus crypticus gut microbiome.

Increasing knowledge of the impacts of pesticides on soil ecological communities is fundamental to a comprehensive understanding of the functional changes in the global agroecosystem industry. In this study, we examined microbial community shifts in the gut of the soil-dwelling organism Enchytraeus crypticus and functional shifts in the soil microbiome (bacteria and viruses) after 21 d of exposure to difenoconazole, one of the main fungicides in intensified agriculture. Our results demonstrated reduced body weight and increased oxidative stress levels of E. crypticus under difenoconazole treatment. Meanwhile, difenoconazole not only altered the composition and structure of the gut microbial community, but also interfered with the soil-soil fauna microecology stability by impairing the abundance of beneficial bacteria. Using soil metagenomics, we revealed that bacterial genes encoding detoxification and viruses encoding carbon cycle genes exhibited a dependent enrichment in the toxicity of pesticides via metabolism. Taken together, these findings advance the understanding of the ecotoxicological impact of residual difenoconazole on the soil-soil fauna micro-ecology, and the ecological importance of virus-encoded auxiliary metabolic genes under pesticide stress.

Evaluation of Adjacent Segment With Pre-Existing Degeneration Using the Cerebrospinal Fluid Occlusion Sign on MRI Before Posterior Lumbar Fusion: A Multi-Center Observational Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether pre-existing adjacent spinal canal stenosis (SCS) is associated with short-term outcomes after lumbar fusion surgery. METHODS: We included patients with lumbar spinal stenosis treated surgically between July 2015 and December 2017 at 4 centers. All patients had the same pathology, with L4-S1 as the culprit sections. Patients were divided into 2 groups based on the cerebrospinal fluid occlusion sign on MRI at the adjacent L3/4 level. Patients without SCS (grade 0) and with mild SCS (grade 1) were classified into the non-stenosis (NS) and mild stenosis (MS) groups, respectively. All patients underwent PLIF and completed at least 1-year follow-up. The incidence of adjacent segment degeneration (ASDeg) and clinical outcomes were compared between the 2 groups. RESULTS: A total of 308 patients (NS, 156; MS, 152) met the inclusion criteria. The incidence of ASDeg in the NS group (n = 40, 25.6%) was significantly lower than that in the MS group (n = 74, 48.7%; P < .001). The most frequent type of ASDeg in the 2 groups was the SCS-aggravated type. No significant difference was observed in adjacent segment disease incidence between the 2 groups (P = .243). The NS group had better outcomes according to the clinical function scores (P < .05). CONCLUSIONS: The cerebrospinal fluid occlusion sign on MRI is valuable for evaluating the adjacent segment with pre-existing degeneration. Patients with mild SCS in adjacent segments were more likely to have ASDeg, and the most frequent type of ASDeg was the SCS-aggravated type at early follow-up.

Study on the Relationship between Unexplained Recurrent Abortion and HLA-DQ Gene Polymorphism.

Objective: The study aimed to investigate the relationship between human leukocyte antigen (HLA-DQB1) gene variants and recurrent miscarriage. Methods: HLA-DQ gene polymorphisms (PCR-SSP) were detected in 50 couples with recurrent miscarriage (URSA group) and 30 couples with normal births (control group) using sequence-specific primer-guided polymerase chain reaction. Results: The frequency of the DQB1 ∗ 0303 allele in the URSA group (21.50%) was substantially higher than that of the control group (11.67%) (P=0.0260 0.05, RR = 1.754); however, the frequency of the DQB1 ∗ 0302 allele in the URSA group (4.00%) was substantially lower than that of the control pair (10.00%) (P=0.0318 0.05, RR = 0.400); the frequency of sharing one allele was 46.00% (23/50) in the URSA group and 0.00% (0/30) in the normal control group; the frequency of sharing two alleles was 40.00% (2/50) in the URSA group and 43.33% (13/30) in the normal control group, with no significant difference between the two groups. Conclusion: For the Zhejiang population, HLA-DQB1 ∗ 0303 may be a susceptibility gene for recurrent miscarriage, while HLA-DQB1 ∗ 0302 may be protective against recurrent miscarriage, especially for women.

Investigation of Utilizing Industrial Waste Residue Proportion on Concrete Structure: Computer Finite Element Analysis.

To study the influence of different proportions and amounts of admixtures on the structural performance of concrete, increase the utilization rate of waste material, and finally reduce the cost and environmental pollution, a computer-based finite element analysis method is proposed to investigate the structural performance of concrete composing of waste residue. Firstly, the available types of industrial waste residue and their application in concrete cementitious materials are researched. Secondly, the fly ash in the industrial waste residue is utilized as an example to design an experiment composed of material selection and mixed design set up to determine factors. Finally, the finite element analysis method is proposed and conducted. This model is employed to calculate early shrinkage stress and temperature deformation of concrete with varying contents of fly ash. The results suggest that when the content of fly ash reaches more than 40%, the compressive strength of concrete decreases gradually with the increase of the content, and the decrease is consistent with the increase of the content. Besides, different amounts of fly ash have a certain effect on the hydrated reaction and stress reduction of concrete. The effect becomes more obvious when an increase in dosage is observed.

A Comparison Between Modified Unilateral Extrapedicular and Bilateral Transpedicular Percutaneous Kyphoplasty in the Treatment of Lumbar Osteoporotic Vertebral Compression Fracture.

BACKGROUND: Few researchers have verified the clinical efficacy and safety of the modified unilateral extrapedicular approach (mUEP) applied to the percutaneous kyphoplasty (PKP) in comparative studies with other puncture techniques. Compared with the bilateral transpedicular approach (BTP), whether mUEP PKP is a preferred treatment for lumbar osteoporotic vertebral compression fracture (OVCF) remains unclear. METHODS: Patients treated by PKP for single-level lumbar OVCF in our institution from September 2019 to December 2020 were retrospectively enrolled. Patients were grouped according to the puncture techniques. Clinical and radiologic outcomes were evaluated preoperatively, postoperatively, and at follow-up. The clinical evaluation was performed by using visual analog scale for pain relief and Oswestry Disability Index for health status. Radiologic measurements contained anterior vertebral height, kyphotic angle, and bone cement distribution. RESULTS: In total, 76 patients with a mean follow-up duration of 16.6 months were enrolled, including 34 patients in the mUEP PK group and 42 patients in the BTP PKP group. In the mUEP group, operation time, fluoroscopy times, and injected cement volume were significantly less than that in the BTP group (P < 0.01). Both visual analog scale and Oswestry Disability Index scores of all patients decreased significantly after surgery (P < 0.01), with no significant differences between the 2 groups at each follow-up. Both mUEP PKP and BTP PKP showed significant anterior height restoration and kyphotic angle correction (P < 0.01), with no significant differences between the 2 groups at each follow-up. Meanwhile, the mUEP PKP reduced the incidence of intraspinal cement leakage (P < 0.05), and no facet joint violation was found in mUEP PKP. CONCLUSIONS: mUEP PKP could be clinically and radiographically equivalent to BTP PKP. However, it has advantages in reducing operation time and fluoroscopy times, lowering the risk of intraspinal cement leakage, and preventing the presence of facet joint violation. Compared with BTP PKP, the mUEP PKP seems to be an effective and alternative puncture technique for the treatment of lumbar OVCF after appropriate patient selection.

Adsorption and photocatalytic conversion of ethyl mercaptan to diethyl disulfide on Fe2O3-loaded HNbMoO6 nanosheet.

Ethyl mercaptans which commonly exist in natural gas need to be removed due to their toxic, odorous, and corrosive properties. Herein, a novel Fe2O3-modified HNbMoO6 nanosheet catalyst (Fe2O3@e-HNbMoO6) was prepared by an exfoliation-impregnation method for the ethyl mercaptans removal. In the heterojunction catalyst, e-HNbMoO6 can be excited by visible light to generate the photogenic charge and has certain adsorption property for ethyl mercaptan with hydrogen bonding (Nb-OH or Mo-OH as the hydrogen bonding donor); Fe2O3 plays the role of accelerating photogenerated electrons and holes, and enhancing the adsorption of ethyl mercaptan with another hydrogen bonding (Fe-OH as the hydrogen bonding donor and receptor). Results showed that the adsorption capacity of Fe2O3@e-HNbMoO6 is 69.9 µmol/g for ethyl mercaptan. In addition, the photocatalytic conversion efficiency of ethyl mercaptan to diethyl disulfide is nearly 100% and it is higher than that of the other Nb-Mo based photocatalysts, such as LiNbMoO6, Fe1/3NbMoO6, Ce1/3NbMoO6, TiO2-HNbMoO6, e-HNbMoO6, CeO2@e-HNbMoO6, and Ag2O@e-HNbMoO6. Under the experimental conditions, the photocatalytic conversion efficiency is greater than the adsorption efficiency over Fe2O3@e-HNbMoO6, and there is no ethyl mercaptan output in the process of adsorption and photocatalytic conversion. Fe2O3@e-HNbMoO6 heterojunction catalyst has practical value and reference significance for purifying methane gas and enhancing photocatalytic conversion of ethyl mercaptan.

Histone Methyltransferase SETDB1 Promotes Immune Evasion in Colorectal Cancer via FOSB-Mediated Downregulation of MicroRNA-22 through BATF3/PD-L1 Pathway.

Tumors may develop a variety of immune evasion mechanisms during the progression of colorectal cancer (CRC). Here, we intended to explore the mechanism of histone methyltransferase SETDB1 in immune evasion in CRC. The expression of SETDB1, microRNA-22 (miR-22), BATF3, PD-L1, and FOSB in CRC tissues and cells was determined with their interactions analyzed also. Gain-of-function and loss-of-function approaches were employed to evaluate the effects of the SETDB1/FOSB/miR-22/BATF3/PD-L1 axis on T cell function, immune cell infiltration, and tumorigenesis. Aberrant high SETDB1 expression in CRC was positively associated with PD-L1 expression. SETDB1 negatively regulated miR-22 expression by downregulating FOSB expression, while miR-22 downregulated PD-L1 expression via targeting BATF3. Furthermore, SETDB1 silencing promoted the T cell-mediated cytotoxicity to tumor cells via the FOSB/miR-22/BATF3/PD-L1 axis and hindered CRC tumor growth in mice while leading to decreased immune cell infiltration. Taken together, SETDB1 could activate the BATF3/PD-L1 axis by inhibiting FOSB-mediated miR-22 and promote immune evasion in CRC, which provides a better understanding of the mechanisms underlying immune evasion in CRC.

Insulin-like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway.

Spinal cord injury (SCI) is a serious trauma; however, the mechanisms underlying the role of insulin-like growth factor 1 (IGF-1) in autophagy following SCI remain to be elucidated. The present study aimed to investigate the therapeutic effect of IGF-1 on SCI and to determine whether IGF-1 regulates autophagy via the PI3K/Akt/mTOR signaling pathway. SH-SY5Y neuroblastoma cells were assigned to the H2O2, IGF-1 and control groups to investigate subsequent neuron injury in vitro. An MTT assay was performed to evaluate cell survival. In addition, Sprague-Dawley rats were randomly assigned to SCI, SCI + IGF-1 and sham groups, and Basso-Beatlie-Bresnahan scores were assessed to determine rat neurological function. Western blotting was used to analyze the autophagy level and the activation of the PI3K/Akt/mTOR signaling pathway. Cell survival was increased significantly in the IGF-1 group compared with the control group in vitro (P<0.05). Furthermore, neurological function was improved in the SCI + IGF-1 group compared with the control group in vivo (P<0.05). The western blotting results further demonstrated that LC3II/LC3I expression was increased in the IGF-1 group compared with the sham group in vivo and compared with the control group in vitro (both P<0.05). In the SCI + IGF-1 group, the expression levels of PI3K, phosphorylated (p)-Akt and p-mTOR were higher compared with those in the sham and SCI groups in vivo (P<0.05). Moreover, in the IGF-1 group, the expression levels of p-Akt and p-mTOR were higher compared with the control and the H2O2 groups in vitro (P<0.05). Collectively, the results of the present study suggested that IGF-1 promoted functional recovery in rats following SCI through neuroprotective effects. Furthermore, the underlying mechanism may involve activation of the PI3K/Akt/mTOR signaling pathway, followed by inhibition of autophagy. However, further investigation into the association between IGF-1-regulated autophagy and the activation of different subtypes of PI3K is required.

The Applicability of ADA, AFU, and LAC in the Early Diagnosis and Disease Risk Assessment of Hepatitis B-Associated Liver Cirrhosis and Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the applicability of adenosine deaminase (ADA), α-l-fucosidase (AFU), lactic acid (LAC), and their combined detection in the early diagnosis of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: A retrospective analysis of hepatitis B-positive liver disease patients admitted between 2015 and 2020 was conducted. The receiver operating characteristic (ROC) curve was used to determine the diagnostic value of each indicator in LC and HCC, and binary logistic regression analysis was performed to determine the factors and risks related to the occurrence of the two conditions. Results: The levels of ADA, AFU, and LAC were significantly increased in patients with CHB, LC, and HCC (p < 0.05). The ROC curve showed that the sensitivity and specificity of ADA, AFU, LAC, and their combined detection in the CHB and LC groups as well as in the LC and HCC groups reflected different degrees of clinical value. In the CHB and LC groups, the adjusted odds ratio (OR) values of ADA, AFU, and LAC among patients in the high-level group were 3.218, 1.859, and 11.474, respectively, when the median was considered the cutoff point. When quartiles were considered the cutoff point, the OR risk values of the adjusted levels of ADA, AFU, and LAC were higher than those of the lowest-level group (Q1) (p < 0.05). In the LC and HCC groups, the adjusted OR values of ADA, AFU, and LAC among patients in the high-level group were 0.967, 2.365, and 38.368, respectively. When quartiles were considered the cutoff point, the OR risk values of AFU and LAC levels were higher than those of the lowest-level group (Q1) (p < 0.05). Conclusion: ADA, AFU, and LAC demonstrated good value in the early diagnosis of LC and HCC. The combined detection of ADA+AFU+LAC is more effective than single detection for the early diagnosis of the two conditions. ADA, AFU, and LAC can serve as risk predictors of LC, while AFU and LAC can be considered early risk predictors of HCC.

Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons.

OBJECTIVE: An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury, and that regulating autophagy can enhance recovery from spinal cord injury. However, the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear. Therefore, in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison, in an effort to provide a basis for further research. DATA SOURCE: Relevant literature published from inception to February 1, 2018 were included by searching Wanfang, CNKI, Web of Science, MEDLINE (OvidSP), PubMed and Google Scholar in English and Chinese. The keywords included "autophagy", "spinal cord injury", and "rat". DATA SELECTION: The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury (including intervention pre- and post-spinal cord injury). Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy, and subgroup analyses were also conducted. OUTCOME MEASURE: Basso, Beattie, and Bresnahan scores. RESULTS: Of the 622 studies, 33 studies of median quality were included in the analyses. Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 1.80, 95% CI: 0.81-2.79, P = 0.0004), 3 days (MD = 0.92, 95% CI: 0.72-1.13, P < 0.00001), 1 week (MD = 2.39, 95% CI: 1.85-2.92, P < 0.00001), 2 weeks (MD = 3.26, 95% CI: 2.40-4.13, P < 0.00001), 3 weeks (MD = 3.13, 95% CI: 2.51-3.75, P < 0.00001) and 4 weeks (MD = 3.18, 95% CI: 2.43-3.92, P < 0.00001) after spinal cord injury with upregulation of autophagy compared with the control group (drug solvent control, such as saline group). Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 6.48, 95% CI: 5.83-7.13, P < 0.00001), 2 weeks (MD = 2.43, 95% CI: 0.79-4.07, P = 0.004), 3 weeks (MD = 2.96, 95% CI: 0.09-5.84, P = 0.04) and 4 weeks (MD = 4.41, 95% CI: 1.08-7.75, P = 0.01) after spinal cord injury with downregulation of autophagy compared with the control group. Indirect comparison of upregulation and downregulation of autophagy showed no differences in Basso, Beattie, and Bresnahan scores at 1 day (MD = -4.68, 95% CI: -5.840 to -3.496, P = 0.94644), 3 days (MD = -0.28, 95% CI: -2.231-1.671, P = 0.99448), 1 week (MD = 1.83, 95% CI: 0.0076-3.584, P = 0.94588), 2 weeks (MD = 0.81, 95% CI: -0.850-2.470, P = 0.93055), 3 weeks (MD = 0.17, 95% CI: -2.771-3.111, P = 0.99546) or 4 weeks (MD = -1.23, 95% CI: -4.647-2.187, P = 0.98264) compared with the control group. CONCLUSION: Regulation of autophagy improves neurological function, whether it is upregulated or downregulated. There was no difference between upregulation and downregulation of autophagy in the treatment of spinal cord injury. The variability in results among the studies may be associated with differences in research methods, the lack of clearly defined autophagy characteristics after spinal cord injury, and the limited autophagy monitoring techniques. Thus, methods should be standardized, and the dynamic regulation of autophagy should be examined in future studies.