The role of CELF family in neurodevelopment and neurodevelopmental disorders.

RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1-6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.

Bifunctional molecular probe targeting tumor PD-L1 enhances anti-tumor efficacy by promoting ferroptosis in lung cancer mouse model.

PURPOSE: Immune checkpoint inhibitors (ICIs) targeting tumor-specific PD-1/PD-L1 significantly improve the overall survival rate of patients with advanced cancer by reactivating the immune system to attack cancer cells. To explore their tumor killing effect, we used the radionuclide iodine-131 (131I) to label the anti-PD-L1 antibody Atezolizumab (131I-PD-L1 mAb). METHOD: We prepared the radioimmunoassay molecular probe 131I-PD-L1 mAb by the chloramine-T method and evaluated its affinity using Lewis lung cancer (LLC) cells. The uptake of 131I-PD-L1 mAb by transplanted tumors was examined through SPECT and its in vivo distribution. We then compared the in vitro and in vivo anti-tumor efficacy of groups treated with control, PD-L1 mAb, 131I-PD-L1 mAb, and 131I-PD-L1 mAb + PD-L1 mAb combined treatment. We performed H&E staining to examine the changes in tumor, as well as the damage in major tissues and organs caused by potential side effects. The anti-tumor mechanism of 131I-PD-L1 mAb was analyzed by Western blot, RT-qPCR and immunohistochemistry (IHC). RESULT: 131I-PD-L1 mAb was highly stable and specific, and easily penetrated into tumor. 131I-PD-L1 mAb suppressed cancer cell proliferation in vitro, and inhibited tumor growth in vivo by inducing ferroptosis, thus prolonging the survival of experimental animals while demonstrating biological safety. CONCLUSION: Therefore, our study suggested that 131I-PD-L1 mAb affected the expression of tumor-related factors through ß-rays and thus promoted ferroptosis in tumor. Combined treatment showed better anti-tumor effect compared to single ICI treatment.

Developmental Dopaminergic Signaling Modulates Neural Circuit Formation and Contributes to Autism Spectrum Disorder-Related Phenotypes.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, it remains unclear whether and how disrupted dopaminergic signaling during development contributes to ASD. In this study, human brain RNA sequencing transcriptome analysis revealed a significant correlation between changes in dopaminergic signaling pathways and neural developmental signaling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signaling led to neural circuit abnormalities and behavior reminiscent of autism. Dopaminergic signaling may impact neuronal specification by potentially modulating integrins. These findings shed light on the mechanisms underlying the link between disrupted developmental dopamine signaling and ASD, and they point to the possibility of targeting dopaminergic signaling in early development for ASD treatment.

Delayed sternal Mycobacterium tuberculosis infection after left ventricular assist device implantation: A case report.

The incidence of Mycobacterium tuberculosis (Mtb) infection in patients with mechanical circulatory support devices is extremely rare. We present a case involving a 38-year-old male who experienced a delayed sternal Mtb infection following left ventricular assist device (LVAD) implantation. More than 5 months post-surgery, the patient was readmitted to the hospital presenting a subxiphoid abscess. The incision site displayed an unsatisfactory healing process after the incision and drainage of the abscess. Despite engaging in a rigorous treatment protocol, which included anti-infective therapy, vacuum-assisted closure, and surgical debridement, the patient's wound remained unhealed. Ultimately, after pus gene sequencing confirmed the diagnosis, the patient was administered a regimen combining anti-tuberculosis and anti-infective therapy, which culminated in the successful healing of the wound. This singular case study not only reveals the clinical progression of an unexpected Mtb infection post-implantation but also emphasizes the challenges encountered in diagnosis and management.

Factors that influence the choice of long-acting reversible contraceptive use among adolescents post-abortion in Chongqing, China: a cross-sectional study.

BACKGROUND: Induced abortion can seriously harm the physical and mental health of adolescent women. Long-acting reversible contraception (LARC) can effectively reduce unplanned pregnancies and prevent repeated abortions among adolescents. This study aimed to analyse the factors affecting the choice of LARC among adolescents in Chongqing of China. METHODS: A total of 555 adolescents who underwent induced abortions for unplanned pregnancies between January 2019 and October 2021 were selected as study subjects. Logistic regression analysis was used to determine the factors affecting adolescent LARC choices following induced abortions. RESULTS: The factors that affected adolescent LARC choices included an average monthly income ≥ ¥3000 (OR = 3.432, 95% CI: 1.429∼8.244), history of previous abortions (OR = 3.141, 95% CI: 1.632∼6.045), worrying about unplanned pregnancy (OR = 0.365, 95% CI: 0.180∼0.740), parental support for using LARC (OR = 3.549, 95% CI: 1.607∼7.839), sexual partners' support for using LARC (OR = 2.349, 95% CI: 1.068∼5.167), concerns about using LARC (OR = 0.362, 95% CI: 0.176∼0.745), and willingness to use free IUDs (OR = 13.582, 95% CI: 7.173∼25.717). CONCLUSION: Cost is one of the factors affecting LARC choices. Parents and sexual partners may play important role in the choice of LARC.

The study analysed the choice of contraceptive methods and the factors affecting the choice of long-acting reversible contraception methods after induced abortion among adolescents in Chongqing, China. The results showed that the income level, history of previous abortions, extent of worrying about unplanned pregnancy, parents' and sexual partners' attitude towards to use long-acting reversible contraception methods, concerns about using long-acting reversible contraception methods, and willingness to use free intrauterine devices were the factors affecting the choice of long-acting reversible contraception methods after induced abortion among adolescents.

Impact factors of benefiting from initial 131 I ablation in patients with intermediate-risk differentiated thyroid carcinoma: a study based on a re-evaluation of therapeutic response.

OBJECTIVE: This study was carried out to confirm whether patients with intermediate-risk differentiated thyroid cancer (DTC) could benefit from initial 131 I ablation and to identify the factors that impacted the benefit. METHODS: We retrospectively assessed a cohort of 548 patients with intermediate-risk DTC who were classified into structural incomplete response (SIR), biochemical incomplete response (BIR), indeterminate response (IDR), and excellent response (ER) groups according to the ATA guidelines (version 2015). A downgrade in the classification, such as from initial SIR to final BIR, IDR, or ER, from BIR to IDR or ER, and from initial IDR to final ER, was defined as benefiting from initial 131 I ablation (benefit group). Non-downgraded classification meant non-benefit. RESULTS: 64.78% of patients benefited from the initial 131 I ablation in the final re-evaluation. Gender (OR = 0.038, P  = 0.002), interval time (OR = 0.038, P  = 0.002) and serum ps-Tg (OR = 0.961, P  = 0.001) were independent prognostic factors for benefiting from initial 131 I ablation, with the cutoff value were 5 months and 19.08 ng/ml. CONCLUSION: Patients with intermediate-risk DTC could benefit from initial 131 I ablation. Female patients with intermediate-risk DTC whose interval time <5 months and ps-Tg <19.08 ng/ml were more likely to benefit. Early 131 I ablation for such patients is beneficial for achieving a complete therapeutic response.

Emergence of a novel ISS1N-optrA-carrying transposon within an integrative and conjugative element from Streptococcus parasuis.

OBJECTIVES: To investigate the genetic context and transferability of the oxazolidinone resistance gene optrA in a Streptococcus parasuis isolate. METHODS: The optrA-carrying S. parasuis isolate SFJ45 was characterized by PCR, antimicrobial susceptibility testing, complete genome sequencing and bioinformatic analysis. The transferability of optrA was verified by conjugation, followed by SmaI-PFGE and Southern blotting. RESULTS: The S. parasuis isolate SFJ45 was positive for optrA, mef(A), msr(D), erm(B), tetAB(P)', tet(M), aadE, aphA3, catQ, dfrG and mdt(A), conferring an MDR phenotype. The optrA gene was flanked by ISS1N at both termini in the same orientation, representing a novel 8750 bp pseudo-compound transposon, organized as the ISS1N-hth-clb-4hp-optrA-2hp-ISS1N structure. The ISS1N-optrA-carrying transposon was further inserted within an integrative and conjugative element, ICESpsuSFJ45, at 3' end of the fda gene. Conjugative transfer of the ISS1N-optrA-carrying transposon with ICESpsuSFJ45 was observed from S. parasuis to Streptococcus suis at a frequency of (1.01 ± 3.12) × 10-7. CONCLUSIONS: ISS1N was found to be associated with optrA spreading for the first time. Integration of the ISS1N-optrA transposon within ICESpsuSFJ45 may lead to the co-selection of optrA with other antimicrobial resistance genes, contributing to its horizontal transfer from S. parasuis to clinically more important bacterial pathogens.

Development and validation of a clinical model to predict preconception risk of gestational diabetes mellitus in nulliparous women: A retrospective cohort study.

OBJECTIVE: To develop and validate a model to predict the preconception risk of gestational diabetes mellitus (GDM) in nulliparous women. METHODS: This was a retrospective cohort study. A total of 1565 women in early pregnancy who underwent preconception health examinations in the Women and Children's Hospital of Chongqing Medical University between January 2020 and June 2021 were invited to participate in a questionnaire survey. Logistic regression analysis was performed to determine the preconception risk factors for GDM. These factors were used to construct a model to predict GDM risk in nulliparous women. Then, the model was used to assess the preconception risk of GDM in 1060 nulliparous women. RESULTS: Independent preconception risk factors for GDM included the following: age 35 years or greater, diastolic blood pressure 80 mm Hg or greater, fasting plasma glucose 5.1 mmol/L or greater, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) 24 or greater, weight gain 10 kg or greater in the year before pregnancy, age of menarche 15 years or greater, three or more previous pregnancies, daily staple food intake 300 g or greater, fondness for sweets, and family history of diabetes. BMI less than 18.5, daily physical activity duration 1 h or greater, and high-intensity physical activity were protective factors. These factors were used to construct a model to predict GDM risk in nulliparous women, and the incidence of GDM significantly increased as the risk score increased. The area under the curve of the prediction model was 0.82 (95% confidence interval 0.80-0.85). CONCLUSION: The preconception GDM risk prediction model demonstrated good predictive efficacy and can be used to identify populations at high risk of GDM before pregnancy, which provides the possibility for preconception intervention.

An extranodal Richter's syndrome presenting with cardiac diffuse large B-cell lymphoma: a case report.

BACKGROUND: Richter's syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves lymph nodes and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose. CASE PRESENTATION: A 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm × 37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma. CONCLUSIONS: We present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

Altered m6A RNA methylation governs denervation-induced muscle atrophy by regulating ubiquitin proteasome pathway.

BACKGROUND: Denervation-induced muscle atrophy is complex disease involving multiple biological processes with unknown mechanisms. N6-methyladenosine (m6A) participates in skeletal muscle physiology by regulating multiple levels of RNA metabolism, but its impact on denervation-induced muscle atrophy is still unclear. Here, we aimed to explore the changes, functions, and molecular mechanisms of m6A RNA methylation during denervation-induced muscle atrophy. METHODS: During denervation-induced muscle atrophy, the m6A immunoprecipitation sequencing (MeRIP-seq) as well as enzyme-linked immunosorbent assay analysis were used to detect the changes of m6A modified RNAs and the involved biological processes. 3-deazidenosine (Daa) and R-2-hydroxyglutarate (R-2HG) were used to verify the roles of m6A RNA methylation. Through bioinformatics analysis combined with experimental verification, the regulatory roles and mechanisms of m6A RNA methylation had been explored. RESULTS: There were many m6A modified RNAs with differences during denervation-induced muscle atrophy, and overall, they were mainly downregulated. After 72 h of denervation, the biological processes involved in the altered mRNA with m6A modification were mainly related to zinc ion binding, ubiquitin protein ligase activity, ATP binding and sequence-specific DNA binding and transcription coactivator activity. Daa reduced overall m6A levels in healthy skeletal muscles, which reduced skeletal muscle mass. On the contrary, the increase in m6A levels mediated by R-2HG alleviated denervation induced muscle atrophy. The m6A RNA methylation regulated skeletal muscle mass through ubiquitin-proteasome pathway. CONCLUSION: This study indicated that decrease in m6A RNA methylation was a new symptom of denervation-induced muscle atrophy, and confirmed that targeting m6A alleviated denervation-induced muscle atrophy.

Erratum: [Corrigendum] MicroRNA­23a inhibits endometrial cancer cell development by targeting SIX1.

[This corrects the article DOI: 10.3892/ol.2019.10694.].

A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Long-term, single-center study comparing open and laparoscopic procedures for congenital midureteral obstruction in children.

PURPOSE: To compare the safety and outcomes of open and laparoscopic procedures in the management of congenital midureteral obstruction in children (CMO). METHODS: Between February 2008 and February 2022, a total of 18 patients underwent open ureteroureterostomy (OU group), and 26 underwent laparoscopic ureteroureterostomy (LU group). The operative time, postoperative hospital stay, hospital costs, postoperative complications, and success rates of the two groups were compared. RESULTS: The median age of the patients was 59 months, with 29 patients presenting with asymptomatic hydronephrosis, 12 with intermittent abdominal pain, and 3 with flank mass. The median follow-up time was 42 months, and all patients were successfully treated surgically. The operative time and postoperative hospital stay in the LU group were shorter than those in the OU group (106.3 ± 21.4 vs. 85.8 ± 16.5 min, 11.6 ± 1.9 vs. 8.3 ± 1.7 days, respectively; p < 0.05). The OU group had two postoperative complications, both of which were classified as Clavien-Dindo grade II based on the Clavien-Dindo classification. One case of postoperative complication occurred in the LU group, which was classified as Clavien-Dindo Grade II. There was no significant statistical difference in complications between the two groups (P > 0.05). CONCLUSIONS: Our data showed that laparoscopic ureteroureterostomy is a safe and effective treatment for congenital midureteral obstruction in children, and provides several advantages, including fewer postoperative complications, shorter postoperative hospital stay, and a shorter operative time. Laparoscopic procedures should be the first choice for treating children with congenital midureteral obstructions.

ICESpsuAH0906, a novel optrA-carrying element conferring resistance to phenicols and oxazolidinones from Streptococcus parasuis, is transferable to Streptococcus suis.

Streptococcus parasuis is a potential opportunistic zoonotic pathogen which is a close relative to Streptococcus suis, which exhibit extensive genetic exchange. The occurrence and dissemination of oxazolidinone resistance poses a severe threat to public health. However, such knowledge about the optrA gene in S. parasuis is limited. Herein, we characterized an optrA-positive multi-resistant S. parasuis isolate AH0906, in which the capsular polysaccharide locus exhibited a hybrid structure of S. suis serotype 11 and S. parasuis serotype 26. The optrA and erm(B) genes were co-located on a novel ICE of the ICESsuYZDH1 family, designated ICESpsuAH0906. IS1216E-optrA-carrying translocatable unit could be formed when excised from ICESpsuAH0906. ICESpsuAH0906 was found to be transferable from isolate AH0906 to Streptococcus suis P1/7RF at a relative high frequency of ∼ 10-5. Nonconservative integrations of ICESpsuAH0906 into the primary site SSU0877 and secondary site SSU1797 with 2-/4-nt imperfect direct repeats in recipient P1/7RF were observed. Upon transfer, the transconjugant displayed elevated MICs of the corresponding antimicrobial agents and performed a weak fitness cost when compared with the recipient strain. To our knowledge, it is the first description of the transfer of optrA in S. prarasuis and the first report of interspecies transfer of ICE with triplet serine integrases (of the ICESsuYZDH1 family). Considering the high transmission frequency of the ICEs and the extensive genetic exchange potential of S. parasuis with other streptococci, attention should be paid to the dissemination of the optrA gene from S. parasuis to clinically more important bacterial pathogens.

Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes.

Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.

A regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins to access indanone-fused 2D/3D skeletons.

The regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins was established with DABCO as a base under mild conditions. Using this approach, a series of diversely substituted indanone-fused cyclopentane polycycles with highly crowded multiple substituents were synthesized in high yields.

Defect-engineered Sulfur Vacancy Modified NiCo2 S4-x Nanosheet Anchoring Polysulfide for Improved Lithium Sulfur Batteries.

The low conductivity of sulfur and the shuttle effect of lithium polysulfides (LiPSs) are the two intrinsic obstacles that limit the application of lithium-sulfur batteries (LSBs). Herein, a sulfur vacancy introduced NiCo2 S4 nanosheet array grown on carbon nanofiber (CNF) membrane (NiCo2 S4-x /CNF) is proposed to serve as a self-supporting and binder-free interlayer in LSBs. The conductive CNF skeleton with a non-woven structure can effectively reduce the resistance of the cathode and accommodate volume expansion during charge-discharge process. The bonding between CNF matrix and NiCo2 S4 nanosheet is enhanced by in situ growth, ensuring fast electron transfer. Besides, the sulfur vacancies in NiCo2 S4 enhance the chemisorption of LiPSs, and the highly active sites at vacancies can accelerate the LiPSs conversion kinetics. LSB paired with NiCo2 S4-x /CNF interlayer achieved improved stability in 500 cycles at 0.2 C and long life of 3000 cycles at 3 C. More importantly, a high areal capacity of 9.69 mAh cm-2 is achieved with a sulfur loading of 10.8 mg cm-2 and a low electrolyte to sulfur (E/S) ratio of 4.8. This work provides insight into the sulfur vacancy in catalysis design for LiPSs conversion and demonstrates a promising direction for electronic defect engineering in material design for LSBs.

The circRNA-0001361/miR-491/FGFR4 axis is associated with axillary response evaluated by ultrasound following NAC in subjects with breast cancer.

Background: miR-491-5p has been reported to regulate the expression of FGFR4 and promote gastric cancer metastasis. Hsa_circ_0001361 was demonstrated to play an oncogenic role in bladder cancer invasion and metastasis by sponging the expression of miR-491-5p. This work aimed to study the molecular mechanism of the effect of hsa_circ_0001361 on axillary response in the treatment of breast cancer. Methods: Ultrasound examinations was performed to evaluate the response of breast cancer patients receiving NAC treatment. Quantitative real-time PCR, IHC assay, luciferase assay and Western blot were performed to analyze the molecular interaction between miR-491, circRNA_0001631 and FGFR4. Results: Patients with low circRNA_0001631 expression had a better outcome after NAC treatment. The expression of miR-491 was remarkably higher in the tissue sample and serum collected from patients with lower circRNA_0001631 expression. On the contrary, the FGFR4 expression was notably suppressed in the tissue sample and serum collected from patients with lower circRNA_0001631 expression when compared with patients with high circRNA_0001631 expression. The luciferase activities of circRNA_0001631 and FGFR4 were effectively suppressed by miR-491 in MCF-7 and MDA-MB-231 cells. Moreover, inhibition of circRNA_0001631 expression using circRNA_0001361 shRNA effectively suppressed the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Up-regulation of circRNA_0001631 expression remarkably enhanced the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Conclusion: Our study suggested that the up-regulation of hsa_circRNA-0001361 could up-regulate the expression of FGFR4 via sponging the expression of miR-491-5p, resulting in the alleviated axillary response after neoadjuvant chemotherapy (NAC) in breast cancer.

Various Mobile Genetic Elements Involved in the Dissemination of the Phenicol-Oxazolidinone Resistance Gene optrA in the Zoonotic Pathogen Streptococcus suis: a Nonignorable Risk to Public Health.

The rapid increase of phenicol-oxazolidinone (PhO) resistance in Streptococcus suis due to transferable resistance gene optrA is a matter of concern. However, genetic mechanisms for the dissemination of the optrA gene remain to be discovered. Here, we selected 33 optrA-positive S. suis isolates for whole-genome sequencing and analysis. The IS1216E element was present in 85% of the optrA-carrying contigs despite genetic variation observed in the flanking region. IS1216E-optrA-carrying segments could be inserted into larger mobile genetic elements (MGEs), including integrative and conjugative elements, plasmids, prophages, and antibiotic resistance-associated genomic islands. IS1216E-mediated circularization occurred to form the IS1216E-optrA-carrying translocatable units, suggesting a crucial role of IS1216E in optrA spreading. Three optrA-carrying MGEs (ICESsuAKJ47_SSU1797, plasmid pSH0918, and prophage ΦSsuFJSM5_rum) were successfully transferred via conjugation at different transfer frequencies. Interestingly, two types of transconjugants were observed due to the multilocus integration of ICESsuAKJ47 into an alternative SSU1943 attachment site along with the primary SSU1797 attachment site (type 1) or into the single SSU1797 attachment site (type 2). In addition, conjugative transfer of an optrA-carrying plasmid and prophage in streptococci was validated for the first time. Considering the abundance of MGEs in S. suis and the mobility of IS1216E-optrA-carrying translocatable units, attention should be paid to the potential risks to public health from the emergence and spread of PhO-resistant S. suis. IMPORTANCE Antimicrobial resistance to phenicols and oxazolidinones by the dissemination of the optrA gene leads to treatment failure in both veterinary and human medicine. However, information about the profile of these MGEs (mobilome) that carry optrA and their transferability in streptococci was limited, especially for the zoonotic pathogen S. suis. This study showed that the optrA-carrying mobilome in S. suis includes integrative and conjugative elements (ICEs), plasmids, prophages, and antibiotic resistance-associated genomic islands. IS1216E-mediated formation of optrA-carrying translocatable units played important roles in optrA spreading between types of MGEs, and conjugative transfer of various optrA-carrying MGEs (ICEs, plasmids, and prophages) further facilitated the transfer of optrA across strains, highlighting a nonignorable risk to public health of optrA dissemination to other streptococci and even to bacteria of other genera.

SAA1 Has Potential as a Prognostic Biomarker Correlated with Cell Proliferation, Migration, and an Indicator for Immune Infiltration of Tumor Microenvironment in Clear Cell Renal Cell Carcinoma.

The tumor microenvironment (TME) plays an important part in the initiation and development of clear cell renal cell carcinoma (ccRCC). However, an understanding of the immune infiltration in TME is still unknown. Our study aims to explore the correlation between the TME and the clinical features, as well as the prognosis of ccRCC. In the present study, ESTIMATE and CIBERSORT computational methods were applied to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal fractions in the ccRCC form The Cancer Genome Atlas (TCGA) database. Then, we sought to find out those immune cell types and genes which may play a significant role and validated them in the GEO database. Furthermore, an immunohistochemical analysis of our external validation dataset was used to detect SAA1 and PDL1 expression in the ccRCC cancer tissues and corresponding normal tissues. Statistical analysis was performed to study the relationship between SAA1 and clinical characteristics, as well as PDL1 expression. Furthermore, a ccRCC cell model with SAA1 knockdown was constructed, which was used for cell proliferation and the migration test. The intersection analysis of the univariate COX and PPI analysis were performed to imply Serum Amyloid A1 (SAA1) as a predictive factor. The expression of SAA1 was significantly negatively correlated to OS and positively correlated to the clinical TMN stage system. The genes in the high-expression SAA1 group were basically enriched in immune-related activities. The proportion of mast cells resting was negatively correlated with SAA1 expression, indicating that SAA1 may be involved in the maintenance of the immune status for the TME. Moreover, the PDL1 expression was positively related to the SAA1 expression and negatively correlated with the patients' prognosis. Further experiments revealed that the knockdown of SAA1 inhibited ccRCC development through suppressing cell proliferation and migration. SAA1 may be a novel marker for the prognosis prediction of ccRCC patients and may play a vital role in the TME by mast cell resting and PDL1 expression. SAA1 has the potential to become a therapeutic target and indicator for immune target therapy in ccRCC treatment.