Optical transmission of microwave control signal towards large-scale superconducting quantum computing.

With the rapid development of superconducting quantum computing and the implementation of surface code, large-scale quantum computing is emerging as an urgent demand. In a superconducting computing system, the qubit is maintained in a cryogenic environment to avoid thermal excitation. Thus, the transmission of control signals, which are generated at room temperature, is needed. Typically, the transmission of these signals to the qubit relies on a coaxial cable wiring approach. However, in a large-scale computing system with hundreds or even thousands of qubits, the coaxial cables will pose great space and heat load to the dilution refrigerator. Here, to tackle this problem, we propose and demonstrate a direct-modulation-based optical transmission line. In our experiment, the average single-qubit XEB error and control error are measured as 0.139% and 0.014% separately, demonstrating the feasibility of the optical wiring approach and paving the way for large-scale superconducting quantum computing.

[Interpretation of the key updates in the 2022 European guideline on the management of neonatal respiratory distress syndrome]. / 2022年欧洲新生儿呼吸窘迫综合征管理指南更新要点解读.

With the deepening of clinical research, the management of neonatal respiratory distress syndrome (RDS) needs to be optimized and improved. This article aims to introduce the 2022 European guideline on the management of neonatal RDS, focusing on its key updates. The guide has optimized the management of risk prediction for preterm birth, maternal referral, application of prenatal corticosteroids, application of lung protective ventilation strategies, and general care for infants with RDS. The guideline is mainly applicable to the management of RDS in neonates with gestational age greater than 24 weeks.

Closing the Locality and Detection Loopholes in Multiparticle Entanglement Self-Testing.

First proposed by Mayers and Yao, self-testing provides a certification method to infer the underlying physics of quantum experiments in a black-box scenario. Numerous demonstrations have been reported to self-test various types of entangled states. However, all the multiparticle self-testing experiments reported so far suffer from both detection and locality loopholes. Here, we report the first experimental realization of multiparticle entanglement self-testing closing the locality loophole in a photonic system, and the detection loophole in a superconducting system, respectively. We certify three-party and four-party GHZ states with at least 0.84(1) and 0.86(3) fidelities in a device-independent way. These results can be viewed as a meaningful advance in multiparticle loophole-free self-testing, and also significant progress on the foundations of quantum entanglement certification.

Neuroprotective effect of resveratrol against radiation after surgically induced brain injury by reducing oxidative stress, inflammation, and apoptosis through NRf2/HO-1/NF-κB signaling pathway.

The impact of resveratrol (RSV) on radiation (RAD)-induced brain injury in rats' brains was investigated. A total of 40 male Wistar Albino rats were randomly divided into four groups (control, RAD, RAD + RSV, and RSV groups, with 10 rats in each group). The results revealed a significant decrease in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, as well as glutathione (GSH) content. Further, a significant elevation in malondialdehyde, nitric oxide, interleukin-1-beta (IL-1ß), IL-6, and transforming growth factor-ß1 levels were observed. Furthermore, decreased B-cell lymphoma 2 (Bcl-2), increased Bcl-2-associated X, and tumor necrosis factor-α genes expression, decreased nuclear factor erythroid-related factor 2, heme oxygenase-1, and increased nuclear factor-κB protein levels were noticed. Also, an apoptosis marker, caspase-3-positive cells, was seen in the hippocampus. Those effects were observed in the RAD group of rats. The treatment of RSV displayed a significant amendment of the studied parameters in the brain tissues of the RAD group of animals. This effect is interrelated to the ability of RSV to scavenge the free radicals, enhance the activity of the antioxidant enzymes, increase GSH contents, and downregulate the inflammatory responses and apoptosis markers in the brain tissues of RAD animals. In conclusion, this study demonstrated that the potent antioxidant, anti-inflammatory, and antiapoptotic activities of RSV can improve the antioxidant status and suppress the inflammatory responses and apoptosis in the brain tissues of RAD animals.

LncRNA RMRP knockdown promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-206/CDK9 axis.

The etiology of osteoarthritis (OA) has been discussed widely, but the molecular mechanisms beneath OA aggravation have not yet been investigated in detail. This study focused on the role of lncRNA RMRP (RMRP) on OA progression. We found that the expression of RMRP was significantly increased in cartilage tissues of patients with OA. CCK-8 and colony formation assays showed that RMRP knockdown promoted proliferation of chondrocytes treated with IL-1ß. Flow cytometry and caspase-3 activity analysis indicated that RMRP silence inhibited apoptosis of chondrocytes treated with IL-1ß. Moreover, luciferase reporter, RNA pull-down and RIP assays showed that RMRP competing with miR-206. Additionally, CDK9 acted as a direct target of miR-206. Moreover, rescue assays indicated that miR-206 inhibitor or pcDNA-CDK9 reversed the effects of RMRP suppression on the proliferation and apoptosis of chondrocytes. Taken together, our results indicated that RMRP knockdown could promote proliferation and inhibit apoptosis in OA chondrocytes via the miR-206/CDK9 axis.

Genetic variants in IFIH1 and DDX58 influence hepatitis C virus clearance in Chinese Han population.

AIMS: To investigate the association between two RIG-I-like receptor gene polymorphisms and hepatitis C virus (HCV) infection in Chinese Han population. METHODS: The current study genotyped two selected SNPs (IFIH1 rs3747517 and DDX58 rs9695310) using TaqMan allelic discrimination assay to assess their association with the susceptibility and clinical outcome of HCV infection among 3065 participants (1545 non-HCV infection individuals, 568 spontaneous HCV clearance cases, and 952 persistent infection patients). RESULTS: IFIH1 rs3747517 (dominant model: Adjusted odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07-1.68; P = 0.009) and DDX58 rs9695310 (dominant model: Adjusted OR = 1.43, 95% CI = 1.15-1.78; P = 0.001) were associated with chronic hepatitis C (CHC). And the risk of CHC increased when people were carrying more unfavorable rs3747517-GA/AA and rs9695310-GC/CC genotypes from zero to two with the chronic rates of 56.72%, 59.38%, and 69.01%, respectively (Ptrend < 0.001). CONCLUSION: Genetic variations at IFIH1 rs3747517 and DDX58 rs9695310 were independent predictors of chronic hepatitis C in Chinese Han population.

Blockage of AKAP12 accelerates angiotensin II (Ang II)-induced cardiac injury in mice by regulating the transforming growth factor ß1 (TGF-ß1) pathway.

Hypertension is a multifactorial chronic inflammatory disease that leads to cardiac remodeling. A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that has multiple functions in various biological events, including the regulation of vessel integrity and differentiation of neural barriers in blood. However, the role of AKAP12 in angiotensin II (Ang II)-induced cardiac injury remains unclear. In the present study, Ang II infusion reduced AKAP12 expressions in the hearts of wild-type (WT) mice, and AKAP12 knockout (KO) enhanced the infiltration of inflammatory cells. In addition, AKAP12 deletion accelerated Ang II-induced cardiac histologic alterations and dysfunction. Further, AKAP12-/- aggravated heart failure by promoting the inflammation, oxidative stress, cellular apoptosis, and autophagy induced by Ang II. Furthermore, AKAP12 KO elevated Ang II-induced cardiac fibrosis, as indicated by the following: (1) Masson trichrome staining showed that Ang II infusion markedly increased fibrotic areas of the WT mouse heart, which was greatly accelerated in AKAP12-/- mice; (2) immunohistochemistry analysis showed increased expression of transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) in the AKAP12-/- mouse heart; (3) reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed increased expression of fibrosis-related molecules in the AKAP12-deficient mouse heart; and (4) Western blot analysis indicated significantly higher upregulation of p-SMAD2/3 in the AKAP12-/- mouse heart. In vitro, AKAP12 knockdown in HL-1 cells was responsible for TGF-ß1-induced inflammation, the generation of reactive oxygen species (ROS), apoptosis, autophagy, and fibrosis. Furthermore, overexpression of AKAP12 reduced fibrosis triggered by TGF-ß1 in cells. Overall, our study suggests that fibrosis induced by Ang II may be alleviated by AKAP12 expression through inactivation of the TGF-ß1 pathway.

[Clinicopathological features and management of penile verrucous carcinoma].

OBJECTIVE: To explore the clinicopathological characteristics, diagnosis and treatment of penile verrucous carcinoma (VC). METHODS: We retrospectively analyzed the clinical data about 18 penile VC patients at the mean age of 52 (35－66) years. The tumors were cauliflower-like, measuring 2.5－8.7 cm in diameter, all with mucopurulentive discharge. A giant tumor invaded the perineum in 1 case, which had a history of surgical excision of penile condyloma acuminatum. The lesions invaded the glans penis in 2 cases, the shafts in 4 (all with a history of phimosis or redundant prepuce), and the whole penis in 11. Partial penectomy was performed for 2 cases with the proximal coronary sulcus involved and another 2 with the condylomata located in the glans penis and measuring <3.5 cm in diameter. Radical surgery was done for 2 cases of glans VC >3.5 cm in diameter, 11 cases with the whole penis involved, and 1 case with the perineum invaded. RESULTS: Postoperative pathology showed well-differentiated tumor cells, negative surgical margins, papillary epithelia with hyperkeratosis and hyperplasia, and lymphocyte infiltration in the surrounding interstitial tissue in all the cases. Neither recurrence nor metastasis was found during the 1 to 8 years of follow-up. CONCLUSIONS: Penile VC is a special type of squamous cell carcinoma with little invasiveness and rare regional lymph node or distant metastasis, for the treatment of which partial penectomy or radical surgery confers good prognosis.

[Low-intensity extracorporeal shockwave therapy for Peyronie's disease: A preliminary study of 32 cases].

OBJECTIVE: To investigate the clinical effect of low-intensity extracorporeal shockwave therapy (LI-ESWT) on Peyronie's disease. METHODS: From October 2016 to December 2017, we treated 32 cases of Peyronie's disease by LI-ESWT, with the therapeutic index of 0.09 mJ/mm2 and a pulse frequency of 120 beats/min. Each plaque was approached from two angles, each angle with a shockwave output of 900 times, and the larger ones from three points, each with an output of 600 times in addition to 300 times from the distal and proximal ends of the plaque, respectively. All the patients received 12 courses of treatment (2 courses a week) with a break of 3 weeks between the 1st and 2nd 6 courses. Then we observed the plague size and penile curvature of the patients, obtained their scores on the Visual Analogue Scale (VAS) and International Index of Erectile Function 5 (IIEF-5), and recorded their adverse reactions. RESULTS: The plagues were softened or diminished in different degrees in 9 of the 32 cases and erectile pain was alleviated in 15 cases after treatment. Penile curvature at erection, however, showed no significant improvement. The IIEF-5 scores were increased in 18 of the patients complicated with varied degrees of erectile dysfunction after LI-ESWT. No obvious complications were observed in any of the patients. CONCLUSIONS: Low-intensity extracorporeal shockwave therapy has a certain effect on Peyronie's disease by relieving plague-induced pain and improving the patient's penile erection and quality of life.

[Focused low-intensity extracorporeal shock wave therapy for erectile dysfunction: Preliminary observation of 32 cases].

OBJECTIVE: To make a preliminary investigation on the safety and efficacy of focused low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). METHODS: We treated 32 ED patients by focused LI-ESWT with the device of Medispec's ED1000. Before and at 4 and 12 weeks after treatment, we evaluated the erectile function of the patients using the International Index of Erectile Function-erectile function domain (IIEF-EF), Erection Hardness Score (EHS), Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), and Global Assessment Questionnaire questions 1 and 2 (GAQ1 and GAQ2), and recorded the incidence rate of adverse events. RESULTS: The patients averaged 30.69 years of age. Compared with the baseline, the mean IIEF-EF score of the patients was significantly increased at 4 and 12 weeks after LI-ESWT (14.94 vs 20.97 and 21.47, P <0.01), and so were the EHS (1.75 vs 2.66 and 2.56, P <0.01) and the "Yes" answers to SEP2 (21.88% vs 68.75% and 71.88%), SEP3 (0 vs 43.75% and 56.25%), GAQ1 (NA vs 81.25% and 71.88%) and GAQ2 (NA vs 65.63% and 68.75%). The total effectiveness rates at 4 weeks and 12 weeks were 75% and 71.88% respectively. One of the patients felt penile shaft pain with mild ecchymosis after LI-ESWT but was recovered without special treatment a week later. CONCLUSIONS: LI-ESWT can significantly improve the erectile function of ED patients with no obvious adverse effects within 12 weeks after treatment.

[Embedding sutures of single inner- and outer-prepuce flap for the treatment of concealed penis: A report of 37 cases].

OBJECTIVE: To evaluate the clinical effect of embedding sutures of single inner- and outer-prepuce flap in the treatment of concealed penis. METHODS: This retrospective analysis included 37 cases of concealed penis treated by embedding sutures of single inner- and outer-prepuce flap between July 2011 and May 2015. Catheters were pulled out from the patients within 24 hours and the dressing removed about 1 week after surgery. All the patients were followed up for 12－24 months postoperatively for evaluation of the long-term outcomes of surgery. RESULTS: One-stage wound healing was achieved in all the patients. No foreskin flap necrosis, inflammation, edema, voiding dysfunction, or painful erection was found during the follow-up. The penises were extended by 2－4 cm. No complications were observed axcept 8 cases of mild prepuce edema, which all subsided with 6 months postoperatively. CONCLUSIONS: Embedding sutures of single inner- and outer-prepuce flap, with the advantages of simple operation, rapid recovery and few complications, is a desirable surgical option for the treatment of concealed penis.

[Microsurgical bypass for varicocele with nutcracker syndrome].

OBJECTIVE: To investigate the clinical effect and feasibility of internal spermatic vein-inferior epigastric vein (ISV-IEV) bypass surgery in the treatment of varicocele complicated by left renal vein nutcracker syndrome (NCS). METHODS: We retrospectively analyzed the clinical data about 30 cases of varicocele with left renal vein NCS treated by ISV-IEV bypass surgery in our hospital from June 2014 to February 2017. We reviewed the follow-up data and results of ultrasonography, routine urianlysis and semen routine examination. RESULTS: All the operations were successfully accomplished and postoperative color Doppler ultrasonography showed that varicocele was cured in all the cases. At 6 months after surgery, sperm concentration and the percentage of grade a+b sperm were significantly improved (ï¼»34.47 ± 8.60ï¼½ ×106/ml and ï¼»63.54% ± 9.58ï¼½ %) as compared with the baseline (ï¼»19.90 ± 8.97ï¼½ ×106/ml and ï¼»37.93 ± 8.73ï¼½ %) (P <0.05). Hematuria was cured in 23 and alleviated in 1 of the 24 cases. Proteinuria disappeared in all the 14 cases, with neither scrotal pain symptoms nor obvious complications. CONCLUSIONS: ISV-IEV bypass surgery, with its advantages of safety, effectiveness, minimal invasiveness, and simple operation, deserves wide clinical application in the treatment of varicocele with left renal vein NCS.

[8.5/11.5F transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory hematospermia].

OBJECTIVE: To investigate the clinical application value of 8.5/11.5 F transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory hematospermia. METHODS: We retrospectively analyzed 78 cases of refractory hematospermia diagnosed and treated by 8.5/11.5 F transurethral seminal vesiculoscopy from June 2012 to June 2014. The patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography, and pelvis CT or MRI before surgery, and all received transurethral seminal vesiculoscopy under the 8.5/11.5 F rigid ureteroscope. RESULTS: Operations were all successfully accomplished, which revealed abnormal opening of the ejaculatory duct in 5 cases, mucosal inflammatory hyperemia in the prostatic utricle and seminal vesicle in 78, dark red mucilage substance in the seminal vesicle in 34, seminal vesicle stones in 19, small polyp in the seminal vesicle in 2, and ejaculatory duct or seminal vesicle cyst in 4. All the patients received symptomatic treatment during the surgery. After surgery, hematouria was found in 13 cases, which disappeared within 2 weeks, pelvic hematoma in 1 case, which was cured by conservative treatment within 3 months, and epididymitis in 2 cases, which was controlled by anti-infection treatment. Hematospermia recurred in 3 cases during the 1-year postoperative follow-up. CONCLUSION: 8.5/11.5 F transurethral seminal vesiculoscopy, with its advantages of easy operation, wide field of vision, large channel for operation, and few complications, deserves general clinical application in the diagnosis and treatment of refractory hematospermia.

[Construction of Eukaryotic Expression Vector Containing ROP18-ROP12 of Toxoplasma gondii RH Strain].

OBJECTIVE: To construct a recombinant eukaryotic expression plasmid containing ROP18-ROP12 (encoding rhoptry protein 18 and 12) complex gene of Toxoplasma gondii, and examine its expression in eukaryotic cells. METHODS: Recombinant plasmids pVAX1-ROP18 and pVAX1-ROP12 were digested by restriction enzymes BamH I and Xba I . ROP12 gene was cloned into pVAX1-ROP18 to construct the eukaryotic expression plasmid pVAX1-ROP18- ROP12. After colony PCR, enzyme digestion and sequencing, the correct recombinant plasmid pVAX1-ROP18-ROP12 was transfected into HeLa cells. Along with it were groups of empty plasmid, pVAX1-ROP18 and pVAX1-ROP12. Total RNA was extracted from HeLa cells and reverse-transcribed to cDNA. RT-PCR was performed to evaluate mRNA expression of the housekeeping gene ß-actin and ROP18-ROP12 complex gene. Immunofluorescence assay and Western blotting were performed to determine the protein levels of ROP18-ROP12 fusion protein. RESULTS: Colony PCR in recombinant plasmid pVAX1-ROP18-ROP12 showed a specific band at about 2 373 bp, consistent with expectation. The extracted recombinant plasmids were confirmed by Hind III, BamH I and Xba I digestion. Sequencing results showed that the sequence of pVAX1-ROP18-ROP12 was 100% identical to that of T. gondii RH strain ROP18 gene (Accession No. AM075204.1) and 99% identical to that of T. gondii RH strain ROP12 gene (Accession No. DQ096559.1). Further, RT-PCR showed amplification products at 613 bp for ß-actin in all the groups, while only the pVAX1-ROP18-ROP12 transfection group showed amplification products for the ROP18-ROP12 complex at 2,373 bp. In addition, the indirect immunofluorescence assay showed yellow-green fluorescence in HeLa cells transfected with pVAX1-ROP18-ROP12, but not in control cells. Western blotting showed that the ROP18-ROP12 fusion protein was expressed in HeLa cells transfected with recombinant plasmid pVAX1-ROP18-ROP12. CONCLUSIONS: The recombinant eukaryotic plasmid pVAX1-ROP18-ROP-2 is constructed and can be expressed in eukaryotic system.

Impulse control behaviors and apathy commonly co-occur in de novo Parkinson's disease and predict the incidence of levodopa-induced dyskinesia.

OBJECTIVE: Impulse control behaviors (ICBs) and apathy are believed to represent opposite motivational expressions of the same behavioral spectrum involving hypo- and hyperdopaminergic status, but this has been recently debated. Our study aims to estimate the co-occurrence of ICBs and apathy in early Parkinson's disease (PD) and to determine whether this complex neuropsychiatric condition is an important marker of PD prognoses. METHODS: Neuropsychiatric symptoms, clinical data, neuroimaging results, and demographic data from de novo PD patients were obtained from the Parkinson's Progression Markers Initiative, a prospective, multicenter, observational cohort. The clinical characteristics of ICBs co-occurring with apathy and their prevalence were analyzed. We compared the prognoses of the different groups during the 8-year follow-up. Multivariate Cox regression analysis was conducted to predict the development of levodopa-induced dyskinesia (LID) using baseline neuropsychiatric symptoms. RESULTS: A total of 422 PD patients and 195 healthy controls (HCs) were included. In brief, 87 (20.6 %) de novo PD patients and 37 (19.0 %) HCs had ICBs at baseline. Among them, 23 (26.4 %) de novo PD patients and 3 (8.1 %) HCs had clinical symptoms of both ICBs and apathy. The ICBs and apathy group had more severe non-motor symptoms than the isolated ICBs group. Cox regression analysis demonstrated that the co-occurrence of ICBs and apathy was a risk factor for LID development (HR 2.229, 95 % CI 1.209 to 4.110, p = 0.010). CONCLUSIONS: Co-occurrence of ICBs and apathy is common in patients with early PD and may help to identify the risk of LID development.

Development of the near-infrared fluorescence probe for detection of ONOO- and its application in vitro and vivo.

Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO- level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO- level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO- response site, which can detect ONOO- with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO- level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO- level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO- was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO-.

Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease: A randomized double-blind placebo-controlled trial.

BACKGROUND: Patients with Parkinson's disease (PD) undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia (LID). Amantadine is the main drug recommended for the treatment of LID by current guidelines, but it is far from meeting clinical needs. Tianqi Pingchan Granule (TPG), a compound Chinese herbal medicine, has been developed to relieve symptom of LID. OBJECTIVE: This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a randomized double-blind placebo-controlled trial, conducted from January 2020 to August 2021 at 6 sites in Jiangsu, Zhejiang and Shanghai, China. One hundred PD patients with ≥ 0.5 h of LID were randomly assigned to either the TPG plus amantadine group (TPG group) or the placebo plus amantadine group (placebo group), and treated for a period of 12 weeks. To ensure unbiased results, all study participants, investigators and sponsors were unaware of group allocations. Additionally, the data analysts remained blinded until the analysis was finalized. MAIN OUTCOME MEASURES: The primary outcome was assessed using the Unified Dyskinesia Rating Scale (UDysRS) (Range 0-104). The key secondary end point was improvement of motor and non-motor symptoms. Safety analyses included all enrolled patients. RESULTS: One hundred patients were enrolled and randomized into the two treatment groups. The changes in UDysRS at week 12 were -11.02 for the TPG group and -4.19 for the placebo group (treatment difference -6.83 [-10.53 to -3.12]; P = 0.0004). Adverse events were reported for 2 of 50 patients (4.0%) in each of the groups. CONCLUSION: This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated, demonstrating the efficacy and safety of TPG for the treatment of LID in PD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04173832. PLEASE CITE THIS ARTICLE AS: Zhang Y, Zhu XB, Zhao Y, Cui GY, Li WT, Yuan CX, Huang JP, Wan Y, Wu N, Song L, Zhao JH, Liang Y, Xu CY, Liu MJ, Gao C, Chen XX, Liu ZG. Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease: A randomized double-blind placebo-controlled trial. J Integr Med. 2024; 22(5): 545-551.

Icariin represses the inflammatory responses and survival of rheumatoid arthritis fibroblast-like synoviocytes by regulating the TRIB1/TLR2/NF-kB pathway.

BACKGROUND: Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. METHODS: qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. RESULTS: Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. CONCLUSIONS: Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.

Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL), which is abnormally increased in the serum of colorectal cancer (CRC) patients consuming a high-fat diet (HFD), may be one of the risk factors for the development of CRC. Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment. The role of ox-LDL in CRC remains unclear. AIM: To investigate the role of ox-LDL through macrophages in HFD associated CRC. METHODS: The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence. We stimulated the macrophages with 20 µg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction. We further knocked down LOX-1, the surface receptor of ox-LDL, to confirm the function of ox-LDL in macrophages. Then, LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot. RESULTS: The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia, and also upregulated in the HFD-fed mice. Moreover, an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation. Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages. Ox-LDL could induce CD206+ macrophages, which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells. CONCLUSION: Ox-LDL stimulates CD206+ macrophages to upregulate CD44 and CD133 expression in HFD related CRC.

Identifying and Exploring the Candidate Susceptibility Genes of Cirrhosis Using the Multi-Tissue Transcriptome-Wide Association Study.

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism. Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA). Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268). Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.