Application of exosomes in tumor immunity: recent progresses.

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

Bibliometric analysis of transforaminal lumbar interbody fusion: research status, trends, and future directions.

Purpose: Transforaminal lumbar interbody fusion (TLIF) is a classic surgical procedure for posterior lumbar fusion. This study aims to analyze the TLIF field by bibliometric method and comprehensively summarize the research status and trends. Methods: All TLIF-related articles were retrieved from the Web of Science. The data were analyzed using R software and SPSS to calculate corresponding indicators. Visualizations were drawn using VOSviewer and Scimago Graphica, including country, institution, journal, author, and keywords. Results: A total of 919 articles were included. The annual publication volume of TLIF-related articles presented an exponential growth. North America, Europe, and Asia were the main sources of articles, with the USA and China being the main contributors and the USA being the global research center for TLIF. The level of the national economy was an important factor affecting TLIF-related research. The highest number of contributions in this field was made by Kern Singh among authors and by Rush University among institutions. The European Spine Journal was the most influential journal. The research focus has gradually shifted from perfecting the TLIF technique toward emphasizing the patient level. The improvement of minimally invasive techniques and how to improve clinical outcomes as well as accelerate postoperative rehabilitation of patients may be the hot spot of future research. Conclusions: With the advancement of medical technology and the popularization of minimally invasive concepts in recent years, TLIF and its derivative technologies have attracted increasing attention. Patient-centered minimally invasive surgery is a hot research topic in the field of TLIF currently and will continue to be so into the future.

An oil-absorbing resin with a simple polymerization system with benzyl methacrylate as a functional monomer.

To solve the problem of the low absorbency of oil-absorbing resins, oil-absorbing resins (PAMs) were fabricated in this study by introducing commercially available benzyl methacrylate (BZMA) as a functional monomer copolymerized with stearyl methacrylate (SMA) and butyl acrylate (BA). The internal network structure of the PAMs expanded more easily when absorbing oils or organic solvents after introducing rigid groups of the benzene ring by an uncomplex polymerization process, which provided the oil-absorbing resin with good absorbency. The reagents were all commercially available, and there was no other pretreatment or posttreatment process. Then, the optimum parameters for the monomer feed ratio, water/oil mass ratio, and concentrations of initiator, stabilizer and crosslinker were studied. Simultaneously, the reusability, oil retention and thermal stability of PAMs were investigated in this article. The PAMs swelled in various oils and organic solvents (the values of oil absorbency were 44.52, 56.13, 25.54, 28.21, 32.85, 24.56, 14.17, 15.02 and 29.07 g g-1 for CCl4, CHCl3, CH2Cl2, benzene, toluene, xylene, n-hexane, 0# diesel oil and 93# gasoline, respectively) and displayed good oil absorbency, which met the absorption requirements for common oils or organic solvents.

Generation and enhancement of the sum sideband under double radiation pressure.

A theoretical scheme to enhance the sum sideband generation (SSG) via double radiation pressure is proposed. In this scheme, both sides of the double-cavity system are driven by red and blue detuned pump lasers and frequency components are generated at the sum sideband through optomechanical nonlinear interaction. The results show that the efficiency of SSG can be improved with orders of magnitude. We further investigate the properties of SSG in resolved and unresolved sideband regimes. The efficiencies of upper sum sideband generation (USSG) and lower sum sideband generation (LSSG) are the equivalent in the unresolved sideband regime when the threshold condition is satisfied. It is worth noting that with the increase of the ratio between the dissipation rate of the cavity field and the decay rate of the mechanical resonator (MR), the amplitude of the LSSG can be superior to that of the USSG. Our scheme may provide a potential application in realizing the measurement of high-precision weak forces and quantum-sensitive sensing.

An extracellular electron transfer enhanced electrochemiluminescence aptasensor for Escherichia coli analysis.

As a crucial indicator in food and water safety testing, the detection of Escherichia coli plays a significant role in maintaining environmental sanitation and promoting public health. Herein, based on the electrochemical activity characteristics of E. coli, we established an enhanced electrochemiluminescence aptasensor for E. coli analysis. This study presents a new method for accurate identification by utilizing a double aptamer recognition system. Specifically, a nano-cadmium sulfide (CdS) modified aptamer was used for primary labeling, while a second aptamer was immobilized on a graphene/chitosan composite electrode for re-capture. The use of two aptamers improves the accuracy of the identification process. Furthermore, the application of an electrode potential facilitates continuous electron transfer between the electrode and electrochemically active microorganisms, resulting in an enhanced electroluminescence signal in relation to the metabolic status. This strategy possesses better sensitivity, accuracy, and stability, demonstrating its potential for E. coli analysis.

Rewiring carbon flow in Synechocystis PCC 6803 for a high rate of CO2-to-ethanol under an atmospheric environment.

Cyanobacteria are an excellent microbial photosynthetic platform for sustainable carbon dioxide fixation. One bottleneck to limit its application is that the natural carbon flow pathway almost transfers CO2 to glycogen/biomass other than designed biofuels such as ethanol. Here, we used engineered Synechocystis sp. PCC 6803 to explore CO2-to-ethanol potential under atmospheric environment. First, we investigated the effects of two heterologous genes (pyruvate decarboxylase and alcohol dehydrogenase) on ethanol biosynthesis and optimized their promoter. Furthermore, the main carbon flow of the ethanol pathway was strengthened by blocking glycogen storage and pyruvate-to-phosphoenolpyruvate backflow. To recycle carbon atoms that escaped from the tricarboxylic acid cycle, malate was artificially guided back into pyruvate, which also created NADPH balance and promoted acetaldehyde conversion into ethanol. Impressively, we achieved high-rate ethanol production (248 mg/L/day at early 4 days) by fixing atmospheric CO2. Thus, this study exhibits the proof-of-concept that rewiring carbon flow strategies could provide an efficient cyanobacterial platform for sustainable biofuel production from atmospheric CO2.

The potential of tRF-21-U0EZY9X1B plasmatic level as a biomarker of children with obstructive sleep apnea-hypopnea syndrome.

PURPOSE: We investigated changes in plasma transfer RNA related fragments (tRF) in children with obstructive sleep apnea-hypopnea syndrome (OSAHS) and the potential value as a disease marker. METHODS: Firstly, we randomly selected five plasma samples from the case group and the control group for high-throughput RNA sequencing. Secondly, we screened one tRF with different expression between the two groups, amplified it by quantitative reverse transcription-PCR (qRT-PCR) and sequenced the amplified product. After confirming that the qRT-PCR results were consistent with the sequencing results and the sequence of the amplified product contained the original sequence of the tRF, we performed qRT-PCR on all samples. Then we analyzed the diagnostic value of the tRF and its correlation with some clinical data. RESULTS: A total of 50 OSAHS children and 38 control children were included in this study. There were significant differences in height, serum creatinine (SCR) and total cholesterol (TC) between the two groups. The plasma expression levels of tRF-21-U0EZY9X1B (tRF-21) were significantly different between the two groups. Receiver operating characteristic curve (ROC) showed that it had valuable diagnostic index, with area under the curve (AUC) of 0.773, 86.71% and 63.16% sensitivity and specificity. CONCLUSIONS: The expression levels of tRF-21 in the plasma of OSAHS children decreased significantly which were closely related to hemoglobin, mean corpuscular hemoglobin, triglyceride and creatine kinase-MB, may become novel biomarkers for the diagnosis of pediatric OSAHS.

Ecology, invasion history and biodiversity-driven management of the coconut black-headed caterpillar Opisina arenosella in Asia.

The coconut black-headed caterpillar (BHC), Opisina arenosella Walker (Lepidoptera: Xyloryctidae) is an important herbivore of palm trees that originates in South Asia. Over the past decades, O. arenosella has spread to several countries in Eastern and Southeast Asia. BHC larval feeding can cause severe defoliation and occasional plant death, resulting in direct production losses (e.g., for coconut) while degrading the aesthetic value of urban and rural landscapes. In this review paper, we systematically cover taxonomy, bio-ecology, invasion history and current management of O. arenosella throughout Asia. Given that O. arenosella is routinely controlled with insecticides, we equally explore options for more sustainable management through agroecological and biodiversity-based tactics e.g., cultural control or biological control. Also, recent advances in chemical ecology have unlocked lucrative opportunities for volatile-mediated monitoring, mating disruption and mass-trapping. Substantial progress has been made in augmentation biological control, with scheduled releases of laboratory-reared parasitoids lowering BHC infestation pressure up to 95%. Equally, resident ants provide 75-98% mortality of BHC egg masses within the palm canopy. Biological control has been effectively paired with sanitary measures and good agronomy (i.e., proper fertilization, irrigation), and promoted through participatory farmer training programs. Our comprehensive listing of non-chemical preventative and curative tactics offer bright prospects for a more environmentally-sound, biodiversity-driven mitigation of a palm pest of regional allure.

Pharmacokinetic and Target Engagement Measures of ANX007, an Anti-C1q Antibody Fragment, Following Intravitreal Administration in Nonhuman Primates.

Purpose: C1q and the classical complement cascade are key regulators of synaptic pruning, and their aberrant activation has been implicated in neurodegenerative ophthalmic diseases including geographic atrophy and glaucoma. The antigen-binding fragment antibody ANX007 specifically recognizes globular head groups of C1q to block substrate binding and functionally inhibit classical complement cascade activation. ANX007 was assessed in nonclinical studies of biodistribution and C1q target engagement in the eye following intravitreal (IVT) administration in cynomolgus monkeys. Methods: Female juvenile cynomolgus monkeys (n = 12) received a single bilateral dose of 1 or 5 mg ANX007/eye, with vitreous and non-perfused tissue samples collected approximately 4 weeks later. In a separate study, male (n = 6/5) and female (n = 6/5) animals received repeat bilateral dosing of 1, 2.5, or 5 mg ANX007/eye on days 1 and 29, with aqueous and vitreous collections on day 44 or day 59. Tissues from the 5 mg/eye repeat-dose group were perfused, and retina, choroid, and optic nerve samples were collected approximately 2 and 4 weeks post-last dose. Results: Following a single dose of ANX007, vitreous levels of free drug were measurable through 4 weeks at both the 1 and 5 mg dose levels, with approximately 3-day half-life. With repeat dose of 5 mg/eye, free-ANX007 was measurable 4 weeks post-last dose in perfused retina and choroid and up to approximately 2 weeks post-last dose in optic nerve. There was a strong correlation between C1q target engagement and free drug levels in aqueous and vitreous humors and retinal tissue. Conclusions: Following IVT administration, ANX007 distributes to sites within the retina that are relevant to neurodegenerative ophthalmic disease with clear evidence of C1q target engagement. Based on its mechanism of action inhibiting C1q and its downstream activity, ANX007 is predicted to mitigate tissue damage driven by classical complement activation in the retina. These data support further clinical evaluation of ANX007.

Plasma interleukin-41 serves as a potential diagnostic biomarker for Kawasaki disease.

INTRODUCTION: Kawasaki disease (KD) is a systemic vasculitis that causes abnormalities in the coronary arteries. Interleukin (IL)-41 is a novel immunoregulatory cytokine involved in the pathogenesis of some inflammatory and immune-related diseases. However, the role of IL-41 in KD is unclear. The purpose of this study was to detect the expression of IL-41 in the plasma of children with KD and its relationship with the disease. METHODS: A total of 44 children with KD and 37 healthy controls (HC) were recruited for this study. Plasma concentrations of IL-41 were determined by ELISA. Correlations between plasma IL-41 levels and KD-related clinical parameters were analyzed by Pearson correlation and multivariate linear regression analysis. Receiver operating characteristic curve analysis was used to assess the clinical value of IL-41 in the diagnosis of KD. RESULTS: Our results showed that plasma IL-41 levels were significantly elevated in children with KD compared with HC. Correlation analysis demonstrated that IL-41 levels were positively correlated with D-dimer and N-terminal pro-B-type natriuretic peptide, and negatively correlated with IgM, mean corpuscular hemoglobin concentration, total protein, albumin and pre-albumin. Multivariable linear regression analysis revealed that IgM and mean corpuscular hemoglobin concentrations were associated with IL-41. Receiver operating characteristic curve analysis showed that the area under the curve of IL-41 was 0.7101, with IL-41 providing 88.64 % sensitivity and 54.05 % specificity. CONCLUSION: Our study indicated that plasma IL-41 levels in children with KD were significantly higher than those in HC, and may provide a potential diagnostic biomarker for KD.

Stratified assessment and warning regimen for prevention of acute adverse reactions to iodinated contrast media: results of 150,343 cases in a tertiary hospital.

For contrast-enhanced CT examinations, there is a lack of comprehensive optimal management strategies of risk factors to reduce the risk of iodinated contrast media (ICM)-induced acute adverse reactions (AAR). Here, we determine the relationship between the rate of ICM-AAR and a stratified assessment and warning (SAW) regimen, which integrated risk identification, stratification, early warning, and prevention. A total of 120,822 cases in the conventional assessment period (58 years ± 15, 55.25% men) and 150,343 cases (58 years ± 14, 55.83% men) in the SAW period were enrolled. The results showed that the total AAR incidence in the SAW period (414/150,343, 0.28%) was lower than that in the conventional assessment period (506/120,822, 0.42%, P < 0.001), in which the proportion of AAR patients decreased by one-third. It mainly presented as decreases in mild and moderate reactions (P < 0.001), and a decrease in the proportion of moderate AAR patients (P = 0.001). Subgroup analysis showed lower mild and moderate AAR incidence in patients with different risk levels and with different ICM injection parameters following SAW regimen. We concluded that SAW regimen was associated with lower incidence of mild and moderate AAR, and decreased proportion of moderate AAR patients, which held potential for improved ICM safety.

[Clinical and genetic analysis of a child with Culler-Jones syndrome due to variant of GLI2 gene].

OBJECTIVE: To explore the genetic basis for a child featuring short stature and postaxial polydactyly. METHODS: A child who presented at Ningbo Women & Children's Hospital in May 2021 due to the"discovery of growth retardation for more than two years" was selected as the subject. Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a heterozygous c.3670C>T (p.Q1224) variant of the GLI2 gene, which may lead to premature termination of protein translation. The variant was not detected in either parent. CONCLUSION: The child was diagnosed with Culler-Jones syndrome. The c.3670C>T (p.Q1224*) variant of the GLI2 gene probably underlay the disease in this child.

Hemodynamic effects of intravenous bolus injection of iopromide 370 twice in abdominal contrast-enhanced CT and coronary CTA dual-site sequential examinations.

Little information is available about how intravenous bolus injection of iopromide 370 twice in a short time will affect hemodynamics and whether the changes reach clinically relevant levels. In the present study, 31 healthy adult volunteers received abdominal contrast-enhanced CT and coronary CTA sequential examinations. The same dose and rate of normal saline was injected 30 min in advance as self-control. Hemodynamic data were noninvasively collected at selected time points from 1 min prior to injection to 30 min post-injection. The results showed that after iopromide 370 injection, except for stroke volume, all other indicators changed immediately during the first injection, changed most significantly during the second injection (P < 0.05), and returned to baseline within 10 min. Heart rate and cardiac output exhibited the most pronounced changes, with an increasing rate of 33.5% and 33.8%, respectively. For indicators with a change range of > 15% during the second injection, except for mean arterial pressure and total peripheral resistance, the proportions of subjects for the other indicators between the two groups were statistically different (P < 0.05). In conclusion, intravenous bolus injection of iopromide 370 twice in dual-site sequential examinations induced dose-cumulative and time-dependent hemodynamic effects, which all fluctuated within the normal ranges.

Cuproptosis-associated genes and immune microenvironment characterization in breast cancer.

Excess Cu can cause cell death as a cofactor for essential enzymes. The relationship between cuproptosis-associated genes (CAGs) and breast cancer (BR) is not completely investigated. Here, the transcriptome expression and mutation profile data of BR samples from the Cancer Genome Atlas database were retrieved to identify CAGs. Patients with BR were clustered using consensus clustering. A least absolute shrinkage and selection operator analysis was then performed to construct a CAGs risk signature. As a result, all 13 cuproptosis regulators were significantly differentially expressed between BR and normal samples; among them, 9 cuproptosis genes were correlated with prognoses. Patients with BR were separated into 2 clusters that were associated with patient survival, clinical phenotypes, and immune infiltration, Based on the components of cuproptosis. Subsequently, genes differentially expressed between clusters were obtained, and 11 CAGs were ultimately incorporated into the risk signature. Functional analyses revealed that the risk signature correlated with patient outcomes, ER, PR, HER2 expression, and BR IHC subtypes. Additionally, immune microenvironment analyses showed that CAGs-high-risk patients exhibited lower immune cell infiltration and immune functions. Furthermore, high-risk BR patients had higher TMB, lower immune checkpoint expression, higher m6A gene expression, and higher tumor stemness. Finally, the immunophenoscore analysis revealed that the risk signature could potentially predict the immune response in BR and help guide the application of various immunotherapeutic drugs. Overall, the newly constructed CAGs risk signature presented a predictive value for the prognosis and tumor microenvironment of BR patients and can be further used in the guidance of immunotherapy for BR.

LncRNA CASC9 promotes cell proliferation and invasion in osteosarcoma through targeting miR-874-3p/SOX12 axis.

BACKGROUND: Osteosarcoma (OS) is a common primary malignant bone tumor. This study aimed to explore the biological role of long on-coding RNA (lncRNA) CASC9 and its regulatory mechanism in OC. METHODS: The CASC9 expressions in OS cells and tissues were measured using qRT-PCR. The functional role of CASC9 in OC was studied using MTT assay, colony formation assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function was determined using luciferase reporter assay. Western blot was used to analyze protein expressions in our paper. RESULTS: LncRNA CASC9 was found to be up-regulated in OS. Knockdown of CASC9 inhibited the proliferation and invasion of OS cells. Besides, miR-874-3p was identified as the target of CASC9, and SOX12 acted as a potential target of miR-874-3p. The down-regulation of miR-874-3p recovered the reduction in cell invasion and proliferation in vitro which were induced by CASC9 knockdown and delayed the tumor progression in vivo. CONCLUSION: LncRNA CASC9 promotes cell proliferation and invasion in OS via miR-874-3p/SOX12 axis. Our study might provide novel biomarkers and potential therapeutic targets for OS treatment.

Early-onset diabetes involving three consecutive generations had different clinical features from age-matched type 2 diabetes without a family history in China.

PURPOSE: Early-onset, multigenerational diabetes is a heterogeneous disease, which is often simplistically classified as type 1 diabetes (T1D) or type 2 diabetes(T2D). However, its clinical and genetic characteristics have not been clearly elucidated. The aim of our study is to investigate the clinical features of early-onset diabetes involving three consecutive generations (eDia3) in a Chinese diabetes cohort. METHODS: Of 6470 type 2 diabetic patients, 105 were identified as eDia3 (1.6%). After a case-control match on age, we compared the clinical characteristics of 89 eDia3 patients with 89 early-onset T2D patients without a family history of diabetes (eDia0). WES was carried out in 89 patients with eDia3. We primarily focused on 14 known maturity-onset diabetes of the young (MODY) genes. Variants were predicted by ten tools (SIFT, PolyPhen2_HDIV, PolyPhen2_HVAR, LRT, Mutation Assessor, Mutation Taster, FATHMM, GERP++, PhyloP, and PhastCons). All suspected variants were then validated by Sanger sequencing and further investigated in the proband families. RESULTS: Compared to age-matched eDia0, eDia3 patients had a younger age at diagnosis (26.5 ± 5.8 vs. 29.4 ± 5.3 years, P = 0.001), lower body mass index (25.5 ± 3.9 vs. 27.4 ± 4.6 kg/m2, P = 0.003), lower systolic blood pressure (120 ± 15 vs. 128 ± 18 mmHg, P = 0.003), and better metabolic profiles (including glucose and lipids). Of the 89 eDia3 patients, 10 (11.2%) carried likely pathogenic variants in genes (KLF11, GCK, ABCC8, PAX4, BLK and HNF1A) of MODY. CONCLUSIONS: eDia3 patients had unique clinical features. Known MODY genes were not common causes in these patients.

Serological and molecular characteristics of pathogenic Leptospira in rodent populations in Fujian Province, China, 2018-2020.

BACKGROUND: Leptospirosis is a significant emerging infectious disease worldwide. Rodents are considered to be the most critical hosts of Leptospira spp. Fujian Province is a region highly endemic for leptospirosis in China. However, the genetic diversity of leptospires circulating among rodents in Fujian is limited. RESULTS: The carrier status of rodents for Leptospira spp. was investigated by culture and serological detection in Fujian during 2018-2020. A total of 710 rodents, including 11 species, were trapped, with Rattus losea being the dominant trapped species (50.56%). Fourteen pathogenic Leptospira strains were obtained. Seven L. borgpetersenii serogroup Javanica strains belonging to ST143, 4 L. interrogans serogroup Icterohaemorrhagiae strains belonging to ST1 and ST17, 2 L. interrogans serogroup Bataviae strains belonging to ST96 and ST333, and 1 L. interrogans serogroup Pyrogenes strains belonging to ST332 were identified using 16S rDNA gene sequencing, microscopic agglutination test (MAT) and Multilocus sequence typing (MLST). L. borgpetersenii serogroup Javanica belonging to ST143 was the dominant type (50.00%). A total of 387 rodent serum samples were tested by MAT. Serum were considered positive for seroreactivity at a titer ≥ 1:160 against at least one serovar. A total of 90 (23.26%) serum samples tested positive, and four serogroups were identified, with Javanica being the dominant serogroup (87.78%), which was similar to the dominant serogroup isolated from rodents. This study demonstrates a high prevalence of leptospirosis in rodents and public health education among high-risk workers is highly recommended. CONCLUSIONS: R. losea was the dominant trapped rodent, and L. borgpetersenii serogroup Javanica ST143 was widely distributed among rodents in Fujian from 2018 to 2020. Despite the low number of isolates obtained from rodents, this study suggests that continuous epidemiological surveillance of the aetiological characteristics of pathogenic Leptospira in wild animal reservoirs may help reduce the possible risk of disease transmission.