Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice.

Tanshinone I (Tan I) has been proven to exert an anti-inflammatory effect, but the complete mechanism remains unclear. In this study, Tan I was described to have no effect on Syk expression in resting or LPS-stimulated macrophages ex vivo, but dramatically suppressed Syk phosphorylation and CD80, CD86, and IL-1ß expression of macrophages. The inflammatory activity of macrophages in ApoC3-transgenic (ApoC3TG) mice is upregulated by Syk activation. Tan I was determined to downregulate Syk phosphorylation and inflammatory activity of macrophages in ApoC3TG mice, both ex vivo and in vivo. Intraperitoneal injection of Tan I (4 mg/kg) effectively alleviated DSS-induced colitis in mice, accompanying with suppressing the activation of intestinal macrophages. Mechanistically, Tan I-treated macrophages exhibited a decrease in cytoplasmic ROS, NLRP3, GSDMD, and IL-1ß, which suggested that the alternative pathway of inflammasome activation in macrophages was suppressed. The SPR assay demonstrated that Tan I bound to Syk protein with a dissociation constant (KD) of 2.473 × 10-6 M. When Syk expression was knocked down by its shRNA, the inhibitory effects of Tan I on macrophages were blocked. Collectively, Tanshinone I effectively alleviated DSS-induced colitis in mice by inhibiting Syk-stimulated inflammasome activation, hence suppressing the inflammatory activity of macrophages.

A cross-sectional study on the impact of hemodialysis duration on retinal nerve fiber layer thinning in hemodialysis patients.

This study aimed to investigate the relationship between hemodialysis duration (HDD) and retinal nerve fiber layer (RNFL) thickness. A total of 60 patients receiving maintenance hemodialysis and 67 healthy controls were analyzed. Spectral domain optical coherence tomography (SD-OCT) was employed to measure annular RNFL thicknesses. The hemodialysis group exhibited reduced temporal and inferior RNFL thicknesses relative to the control group. In hemodialysis patients, the inferior RNFL thickness was negatively correlated with HDD and positively correlated with intraocular pressure (IOP). Moreover, IOP was positively correlated with HDD. Mediation analysis showed that the negative correlation between HDD and inferior RNFL thickness was mediated by IOP. In conclusion, hemodialysis leads to temporal and inferior RNFL thinning, and the thickness reduction is proportional to hemodialysis duration. However, such changes are not induced by an increase in IOP.

Optimized nitrogen management improves grain yield of rice by regulating panicle architecture in South China.

Optimized nitrogen (N) management (OPT), with reduced total N input and more N applied during panicle development, has been proved to increase grain yield of rice through panicle enlargement. However, the changes in panicle architecture and source of variation are not well understood. A hybrid rice variety named Tianyou 3618 was subjected to OPT and farmer's fertilizer practice (FFP) in early cropping seasons of 2016 and 2017. With 16.7 % less N input, OPT increased panicle size by 8.6 % and 27.4 %, and grain yield by 13.8 % and 12.3 % for 2016 and 2017, respectively. OPT had greater dry matter accumulation and N uptake from panicle initiation to heading, which bolstered panicle enlargement. The number of surviving florets per branch was quite constant under different N treatments for all primary, secondary, and tertiary branches, implying that panicle size was mainly determined by the number of branches rather than the number of florets per branch. Little change was observed between OPT and FFP in differentiation, degeneration and survival of primary branches and their florets. Surviving secondary and tertiary branches and their florets were significantly more under OPT than those under FFP. The increase in surviving secondary branches under OPT resulted from both enhanced differentiation and reduced degeneration. While the increase in surviving tertiary branches under OPT was merely from enhanced differentiation though their degeneration was also dramatically increased. Among the increased differentiated florets under OPT, 32.4%-36.3 % and 61.6%-67.7 % came from secondary and tertiary branches, respectively. Among the increased surviving florets under OPT, 62.2%-65.2 % and 32.5%-37.8 % came from secondary and tertiary branches, respectively. Both secondary branches and tertiary branches were principal contributors to the increase in panicle size of OPT. To our knowledge, this is the first report on the detailed changes in panicle architecture and their involvement in panicle enlargement and yield gain under OPT.

Decrease in UCP1 by sustained high lipid promotes NK cell necroptosis to exacerbate nonalcoholic liver fibrosis.

Uncoupling protein 1 (UCP1) catalyzes the leak of protons across the mitochondrial inner membrane for thermogenesis. Compromised NK cell activity is involved in the occurrence of nonalcoholic liver fibrosis. Here, decreased UCP1 in NK cells was identified in patients with advanced nonalcoholic fatty liver disease. Although no obvious changes were observed in the NK cells of physiologic UCP1-/- mice (8-10 weeks old), impaired NK cell bioactivity was shown in methionine-choline-diet (MCD)-fed UCP1-/- mice and involved in the acerbation of nonalcoholic steatohepatitis (NASH) progress to liver fibrosis. Moreover, UCP1-deficient NK cells were responsible for the aggravation of liver fibrosis, as confirmed in MCD-fed UCP1flox/flox-NCR1cre mice. Acerbation of liver fibrosis was also seen in wild-type mice when their endogenous NK cells were replaced with UCP1-/- NK cells. Transcriptions of mitophagy-associated molecules in UCP1-/- NK cells were enhanced according to RNA-seq. Electron microscopic results showed mitochondrial injuries and autophagic vesicles in MCD-fed NKWT cells, PA-treated NKWT cells, or physiologic NKKO cells. However, the co-existence of UCP1 deficiency and high lipid can synergistically induce NK cell necroptosis via DRP1S616 accompanied with reduced mitophagy. Finally, The UCP1 in NK cells was downregulated when treated by sustained high PA (600 µM) via the PPARγ/ATF2 axis. Thus, persistent high-lipid treatment not only decreases UCP1 expression but also combines with reduced UCP1 to promote NK cell necroptosis, and it is involved in NASH progression to fibrosis.

Increase in GPIHBP1 expression in advanced stage colorectal cancer indicates poor immune surveillance.

Background: Glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a crucial role in fatty acid metabolism, which is involved in the progression of colorectal cancer (CRC). The aim of this study was to determine the expressional variations of GPIHBP1 in CRC at different stages and to verify whether this protein affects the shaping of the immune microenvironment of cancer cells. Methods: Variations of GPIHBP1 messenger RNA (mRNA) levels were first analysed using The Cancer Genome Atlas (TCGA) database. Protein levels of GPIHBP1 in cancer nest cells, stromal cells or surrounding normal tissues from 68 patients with CRC were checked by immunohistochemistry. Infiltration of immune cells such as macrophages, myeloid-derived suppressor cells (MDSCs), CD8+ and CD56+ cells was parallelly stained in the same tissues. Ectopic GPIHBP1 expressed colonic tumour cells were transplanted into the back of mice. Tumour growth and immune cell infiltrations were also observed. Results: Compared with those in healthy tissues, GPIHBP1 mRNA and protein levels decreased in the patients with CRC at Dukes A-B stage but gradually increased in the patients at Dukes C-D stage. GPIHBP1 in foci or stroma was positively correlated with recruited macrophages or MDSCs and negatively correlated with recruited CD8+, CD56+ or granzyme+ cells. The mice injected with GPIHBP1 overexpression cells bore large tumours. Histological analysis confirmed the infiltration of many macrophages and MDSCs but less CD8+ T or CD56+ cells. Conclusions: The increased expression of GPIHBP1 is involved in the progression of CRC. High GPIHBP1 level of advanced CRC indicates efficient immune evasion in tumour microenvironment.

Mycophagous Mite, Tyrophagus putrescentiae, Prefers to Feed on Entomopathogenic Fungi, except Metarhizium Generalists.

(1) Background: The mycophagous mite, Tyrophagus putrescentiae, was found to feed on entomopathogenic fungi (EPF) in our previous experiments, which seriously impacted the culture and preservation of fungal strains. Therefore, it is necessary to investigate the biological characteristics of the occurrence and damage to EPF. (2) Methods: The mite's growth and development and feeding preference were surveyed by comparative culture and observation; also, optical and electronic microscopies were employed. (3) Results: T. putrescentiae could survive normally after being fed on seven EPF species, including Purpureocillium lilacinum, Marquandii marquandii, Cordyceps fumosorosea, Beauveria bassiana, Metarhizium flavoviride, Lecanicillium dimorphum, and Metacordyceps chlamydosporia. The first four fungi were the mite's favorites with their greater feeding amount and shorter developmental duration. Interestingly, the mite could also feed on Metarhizium anisopliae and Metarhizium robertsii, but this led to the mite's death. After feeding on M. anisopliae and M. robertsii, the mites began to die after 24 h, and the mortality rate reached 100% by 72 h. Observation under optical microscopy and scanning electron microscopy revealed that the conidia of M. anisopliae and M. robertsii adhered to the mite's surface, but there was no evidence of penetration or invasion. However, dissection observation indicated that the two Metarhizium species germinate and grow within the mite's digestive tract, which implies that Metarhizium generalists with broad-spectrum hosts and the production of destruxins have acaricidal activity toward the mycophagous mites.

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma.

Beta-1,3-glucuronosyltransferase (B3GAT3), overexpressed in hepatocellular carcinoma (HCC) and negatively correlated to prognosis, is a promising target for cancer therapy. Currently, no studies have reported small molecule inhibitors of B3GAT3. In this study, we designed and synthesized a series of small-molecule inhibitors of B3GAT3 through virtual screening and structure optimization. The lead compound TMLB-C16 exhibited potent B3GAT3 inhibitory activity (KD = 3.962 µM) by effectively suppressing proliferation and migration, and inducing cell cycle arrest and apoptosis in MHCC-97H (IC50= 6.53 ± 0.18 µM) and HCCLM3 (IC50= 6.22 ± 0.23 µM) cells. Furthermore, compound TMLB-C16 demonstrated favorable pharmacokinetic properties with a relatively high bioavailability of 68.37%. It significantly inhibited tumor growth in both MHCC-97H and HCCLM3 xenograft tumor models without causing obvious toxicity. These results indicate that compound TMLB-C16 is an effective small molecule inhibitor of B3GAT3, providing a basis for the future development of B3GAT3-targeted drugs.

Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections.

BACKGROUND: The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. RESULTS: This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. CONCLUSIONS: This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease.

Isoliquiritigenin (ISL) is a chalcone-type flavonoid derived from the root of licorice with antioxidant, anti-inflammatory, anti-tumour and neuroprotective properties. ISL has been proven to downregulate the productions of IL-1ß, TNF-α and IL-6 by macrophages. However, detailed molecular mechanisms of this modulation remain elusive. Here, ISL suppressed Syk phosphorylation and CD80, CD86, IL-1ß, TNF-α and IL-6 expressions in lipopolysaccharide-stimulated macrophages ex vivo. ApoC3-transgenic (ApoC3TG) mice had more activated macrophages. ISL was also able to downregulate the inflammatory activities of macrophages from ApoC3TG mice. Administration of ISL inhibited Syk activation and inflammatory activities of macrophages in ApoC3TG mice in vivo. The treatment of ISL further alleviated MCD-induced non-alcoholic fatty liver disease (NAFLD) in wild-type and ApoC3TG mice, accompanied by less recruitment and activation of liver macrophages. Due to the inhibition of Syk phosphorylation, ISL-treated macrophages displayed less production of cytoplasmic ROS, NLRP3, cleaved-GSDMD and cleaved-IL-1ß, suggesting less inflammasome activation. Finally, the molecular docking study demonstrated that ISL bound to Syk directly with the Kd of 1.273 × 10-8 M. When the Syk expression was knocked down by its shRNA, the inhibitory effects of ISL on activated macrophages disappeared, indicating that Syk was at least one of key docking-molecules of ISL. Collectively, ISL could alleviate MCD-induced NAFLD in mice involved with the inhibition of macrophage inflammatory activity by the blockade of Syk-induced inflammasome activation.

Process evaluation and its application in clinical research of acupuncture: preliminary considerations. / è¿‡ç¨‹è¯„ä»·åŠå ¶åœ¨é’ˆåˆºä¸´åºŠç ”ç©¶ä¸­åº”ç”¨çš„æ€è€ƒä¸Žå»ºè®®.

As an important supplementary approach to randomized controlled trial, process evaluation(PE) aims to evaluate implementation of complex intervention and contextual factors associated with variation in outcomes, in order to explain the observed results in a comprehensive manner. However, PE has not been well applied in the clinical research of acupuncture. Based on existing literature, this paper summarized the main methodological frameworks of PE, as well as the status-quo of its application in acupuncture research. Meanwhile, it explored the research perspectives and implementation factors that were potentially relevant to PE in parallel with acupuncture trials. In addition, the paper put forward preliminary considerations on key contents corresponding to each step during the development of PE for acupuncture trials, in order to provide useful reference and innovative pathway for future studies that strive for comprehensive evaluation of acupuncture's effect.

Differential evaluation of sulfur oxides in the natural lake water samples by carbazole-furan fluorescent probe.

Water bodies are frequently polluted, with sulfur oxides being the most common form of water pollution. Therefore, developing a detection mechanism for sulfur oxides in water bodies is particularly urgent. A new fluorescent probe YX-KZBD was designed and developed. This probe releases fluorescent signals with its own sulfurous acid recognition site, detects sulfurous acid based on the Michael addition reaction, and evaluates the pollution degree of sulfur oxides in the water environment through the transformation mode of the sulfur cycle. This probe has high energy transfer efficiency in aqueous solutions. In addition, the fluorescence data obtained by analyzing the water samples were linearly fitted with the gene abundance values of the functional genes of sulfur-producing bacteria, and a significant correlation was obtained. The Kriging interpolation model was used to evaluate the sulfate content distribution at each sampling point to understand the distribution of sulfur oxides in natural water intuitively. The fluorescence signal excited by the probe was also combined with a real-time quantitative polymerase chain reaction (qPCR), and sulfate-reducing and sulfur-oxidizing bacteria were introduced in the sulfur cycle, providing a new method to assess the extent of water pollution effectively.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

BACKGROUND: Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. METHODS: A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. RESULTS: The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. CONCLUSION: The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.

Determining nitrogen topdressing rates in accordance with actual seedling density and crop nitrogen status in direct-seeded rice.

BACKGROUND: Adjusting nitrogen (N) input based on actual seedling density (ASD) and plant N status is a practical approach for improving the yield stability of direct-seeded rice. However, the adjustment of topdressing N rates has been empirical in the past. This study aimed to establish a quantitative approach for determining N topdressing rates during tillering (Ntil ) and panicle development (NPI ) based on ASD and crop N status in direct-seeded rice. Field experiments were conducted involving 12 treatments, consisting of four Ntil and three seeding rates in 2017, and eight treatments combining seeding rate, Ntil , and NPI in 2020. RESULTS: Linear regression analysis revealed that the tiller number at panicle initiation (TILPI ) was predominantly influenced by ASD and Ntil . The determination coefficients (R2 ) of the regression models ranged from 0.887 to 0.936 across the four-season experiments. The results indicated that Ntil could be determined accurately using ASD and the target maximum tiller number. Similarly, grain yield was influenced significantly by the N uptake at panicle initiation (NUPPI ) and NPI , with R2 of 0.814 and 0.783 in the early and late seasons of 2020, respectively. This suggested that NPI could be calculated based on NUPPI and the target grain yield. CONCLUSION: The findings offer a quantitative method for establishing N topdressing rates for tillering and panicle development, relying on the monitoring of actual seedling density and plant N status in direct-seeded rice production. © 2023 Society of Chemical Industry.

Analyzing MC-LR distribution characteristics in natural lakes by a novel fluorescence technology.

The death of aquatic and terrestrial organisms caused by cyanobacterial blooms has been a topic of considerable concern since the 19th century. Microcystin-LR (MC-LR) produced by cyanobacterial blooms threaten natural ecosystems and human health. Therefore, establishing an effective monitoring and early warning system to detect MC-LR in water bodies is crucial. However, rapidly and intuitively assessing the distribution traits of MC-LR in lakes is a challenging task due to the complexities and expenses associated with conventional detection methods. To overcome these technical limitations, we introduce a novel and effective method for evaluating the distribution of MC-LR in lakes. This method is achieved by using a fluorescence probe (BAD) technology, marking the first application of this technology in evaluating the distribution of MC-LR in natural lake environments. The probe BAD is endowed with unique functions through clever functionalization modification. Experimental results exhibit that BAD has different fluorescence signals at various lake sampling points. The correlation analysis of fluorescence data and physicochemical indicators determines that the fluorescence data of the probe exhibit good correlation with MC-LR, implying that BAD is capable of detecting MC-LR in lakes. Moreover, the introduction of fluorescence technology to achieve the intuitive distribution of MC-LR in the entire plateau lake. This study provides a new method for evaluating the distribution of MC-LR in plateau lakes. It opens a new avenue for exploring the relationship between cyanobacterial blooms and MC-LR in natural waters.

Acupuncture for in vitro fertilization-embryo transfer: an overview of systematic reviews. / é’ˆç¸è¾ åŠ©ä½“å¤–å—ç²¾èƒšèƒŽç§»æ¤çš„ç³»ç»Ÿè¯„ä»·å†è¯„ä»·.

OBJECTIVES: To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). METHODS: The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. RESULTS: A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. CONCLUSIONS: Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.

Use of Evidence-Based Research Approach in RCTs of Acupuncture-Related Therapies for Primary Dysmenorrhea: A Meta-Research.

OBJECTIVE: To assess the use of evidence-based research (EBR) approach in randomized controlled trials (RCTs) of acupuncture-related therapies for primary dysmenorrhea (PD). METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and China Science and Technology Journal Database were searched from January 2013 to December 2022 for RCTs of acupuncture on PD. The full text and references of each RCT were read to assess whether systematic reviews (SRs) or other types of studies with similar research questions and end-users' perspectives were cited to justify and design the trial. In addition, the discussion section were analyzed to evaluate whether trials placed the new result in the existing SRs to draw a conclusion. Multivariable logistic regression was used to find variables that associated with 3 aspects of EBR approach: (1) citing clinical studies for justification, (2) citing relevant studies that obtain the perspectives of end users, and (3) citing clinical studies for results discussion. RESULTS: Of 473 RCTs included, 45.67% (216) of the trials cited relevant similar studies, 21.56% (102) referenced to the studies that collected end-users' perspectives, and 10.99% (52) placed result in the context of the previous research. Few RCTs appropriately applied EBR approach. Among all the included studies, 3.17% (15) of the trials used SRs to inform study questions but none of them used updated SRs with acceptable quality; 1.05% (5) of the trials cited SRs of end-user's perspectives in the justification and design of the study, and only 1 trial added results in existing SR to draw a conclusion. Year of publication, language, funding, registration, ethical approval and number of sites were significantly associated with 1 of the 3 aspects of EBR approach. CONCLUSIONS: Few RCTs in acupuncture-related therapies for PD used the EBR approach to minimize research redundancy. Researchers, research institutes, funding agencies, ethics committees, journals and peer reviewers in acupuncture should make efforts to use and promote the EBR approach to ensure the value of new trials.

Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression.

Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO-/- mice had less M1 macrophages in vivo, and ENHO-/- macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.

Apolipoprotein C-III itself stimulates the Syk/cPLA2-induced inflammasome activation of macrophage to boost anti-tumor activity of CD8+ T cell.

Increased prevalence of cancer in obese individuals is involved with dyslipidemia- induced chronic inflammation and immune suppression. Although apolipoprotein C-III (ApoC3)-transgenic mice (ApoC3TG mice) or poloxamer 407 (P407)-treated mice had hyperlipidemia, CD8+ T cells with upregulated antitumor activities were observed in ApoC3TG mice, and decreased CD8+ T cell activities were observed in P407-treated mice. Increased ApoC3 expression in hepatocellular carcinoma was associated with increased infiltration of CD8+ T cells and predicted survival. Recombinant ApoC3 had no direct effects on CD8+ T cells. The upregulation of CD8+ T cells in ApoC3TG mice was due to cross-talk with context cells, as indicated by metabolic changes and RNA sequencing results. In contrast to dendritic cells, the macrophages of ApoC3TG mice (macrophagesTG) displayed an activated phenotype and increased IL-1ß, TNF-α, and IL-6 production. Coculture with macrophagesTG increased CD8+ T cell function, and the adoptive transfer of macrophagesTG suppressed tumor progression in vivo. Furthermore, spleen tyrosine kinase (Syk) activation induced by TLR2/TLR4 cross-linking after ApoC3 ligation promoted cellular phospholipase A2 (cPLA2) activation, which in turn activated NADPH oxidase 2 (NOX2) to promote an alternative mode of inflammasome activation. Meanwhile, mitochondrial ROS produced by increased oxidative phosphorylation of free fatty acids facilitated the classical inflammasome activation, which exerted an auxiliary effect on inflammasome activation of macrophagesTG. Collectively, the increased antitumor activity of CD8+ T cells was mediated by the ApoC3-stimulated inflammasome activation of macrophages, and the mimetic ApoC3 peptides that can bind TLR2/4 could be a future strategy to target liver cancer.