A Novel Score to Predict Individual Risk for Future Alzheimer's Disease: A Longitudinal Study of the ADNI Cohort.

Background: Identifying high-risk individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer's disease (AD) is crucial for early intervention. Objective: This study aimed to develop and validate a novel clinical score for personalized estimation of MCI-to-AD conversion. Methods: The data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Two-thirds of the MCI patients were randomly assigned to a training cohort (n = 478), and the remaining one-third formed the validation cohort (n = 239). Multivariable logistic regression was performed to identify factors associated with MCI-to-AD progression within 4 years. A prediction score was developed based on the regression coefficients derived from the logistic model and tested in the validation cohort. Results: A lipidomics-signature was obtained that showed a significant association with disease progression. The MCI conversion scoring system (ranged from 0 to 14 points), consisting of the lipidomics-signature and five other significant variables (Apolipoprotein ɛ4, Rey Auditory Verbal Learning Test immediate and delayed recall, Alzheimer's Disease Assessment Scale delayed recall test, Functional Activities Questionnaire, and cortical thickness of the AD signature), was constructed. Higher conversion scores were associated with a higher proportion of patients converting to AD. The scoring system demonstrated good discrimination and calibration in both the training cohort (AUC = 0.879, p of Hosmer-Lemeshow test = 0.597) and the validation cohort (AUC = 0.915, p of Hosmer-Lemeshow test = 0.991). The risk classification achieved excellent sensitivity (0.84) and specificity (0.75). Conclusions: The MCI-to-AD conversion score is a reliable tool for predicting the risk of disease progression in individuals with MCI.

Distribution and Determinants of Anterior Chamber Angle and Anterior Chamber Volume in Young Chinese Adults.

PURPOSE: Current study aimed to understand the distribution and determinants of anterior chamber angle (ACA) and anterior chamber volume (ACV) in Chinese young adults, which can help fill current data gaps and aid in early detection and intervention for high-risk population of primary angle closure glaucoma. METHODS: This cross-sectional study utilized data from 2014 participants who completed questionnaire and eye examination in September 2021. ACV and ACA were measured using a Pentacam tomographer. Spherical equivalent (SE) was evaluated by autorefractor without cycloplegia. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated using Corvis-ST. Axial length (AL), corneal radius (CR), anterior chamber depth (ACD), and white to white were assessed using the IOL Master. RESULTS: A total of 1635 students were included in the analysis. The mean ACV and AVA were 194.74 ± 32.30 µL and 38.81 ± 4.84°, respectively. Males have a larger ACV and wider ACA than females. ACV was positively correlated with ACA (r = 0.24, p < 0.001), and the correlation was stronger for non-myopic students than for myopic students. Multivariable linear regression model showed that AL (ß = 2.41), CR (ß = -4.12), CCT (ß = -0.11), ACD (ß = 97.93), and bIOP (ß = 0.40) were associated with ACV, and CCT (ß = -0.01), CR (ß = 0.38), and ACD (ß = 7.41) were associated with ACA (all p < 0.05). Random forest model indicated that ACD was the most critical predictor of both ACV and ACA. CONCLUSIONS: This study reported the distribution and determinants of ACA and ACV. Deeper ACD was associated with larger ACV and wider ACA.

Mmu-let-7a-5p inhibits macrophage apoptosis by targeting CASP3 to increase bacterial load and facilities mycobacterium survival.

We have been trying to find a miRNA that can specifically regulate the function of mycobacterial host cells to achieve the purpose of eliminating Mycobacterium tuberculosis. The purpose of this study is to investigate the regulation of mmu-let-7a-5p on macrophages apoptosis and its effect on intracellular BCG clearance. After a series of in vitro experiments, we found that mmu-let-7a-5p could negatively regulate the apoptosis of macrophages by targeting Caspase-3. The extrinsic apoptosis signal axis TNFR1/FADD/Caspase-8/Caspase-3 was inhibited after BCG infection. Up-regulated the expression level of mmu-let-7a-5p increase the cell proliferation viability and inhibit apoptosis rate of macrophages, but down-regulated its level could apparently reduce the bacterial load of intracellular Mycobacteria and accelerate the clearance of residual Mycobacteria effectively. Mmu-let-7a-5p has great potential to be utilized as an optimal candidate exosomal loaded miRNA for anti-tuberculosis immunotherapy in our subsequent research.

Evaluation of the safety, immunogenicity and protective effect of an attenuated Pseudomonas plecoglossicida strain ΔgacS as the live vaccine for the large yellow croaker (Larimichthys crocea).

Pseudomonas plecoglossicida is one of most important pathogenic bacterial species in large yellow croaker and several other commercially valuable fish species. In our previous study, a GacS deficient mutant (ΔgacS) was constructed and its virulence showed substantially attenuated. In present study, the safety, immunogenicity and protective effect of the ΔgacS were evaluated in large yellow croaker as a live-attenuated vaccine candidate. It was shown that the ΔgacS strain exhibited good safety to large yellow croaker and there was no mortality or clinical symptoms observed in all fish that infected by ΔgacS strain with the doses range from 2 × 105～107 CFU per fish via intraperitoneal injection (IP) or immersion (IM), and almost all bacteria were cleaned up in the spleen of the fish at 14-day post infection. Specific antibodies could be detected at 7-day and 14-day post infection by direct agglutination method, and the valences of antibodies and bactericidal activities of the serum were significant increased with vaccination doses and vaccination time. Moreover, the expressions of some molecules and cytokines involved in specific immune responses were detected in the ΔgacS strain immunization group and control group. After challenged by the wild-type (WT) strain XSDHY-P, the relative percentage survival (RPS) showed highly correlated with the immunized dosage regardless of vaccination methods. It showed that the RPS of the IP groups were 39.47 %, 57.89 %, 71.05 % with the immune dosage in a descending order, respectively, and the RPS of the IM groups were 26.31 %, 36.84 %, 76.31 % with the immune dosage in a descending order, respectively. In summary, the ΔgacS strain exhibited safety and good protective effect to large yellow croaker and was a potential live vaccine candidate.

Experiments Validated the Development of Zebrafish Embryos and Toxicological Mechanism of Borneols in Perinatal Period.

BACKGROUND: Studies have confirmed that high dose borneol has perinatal toxicity and has a certain effect on embryonic development. However, there is little about the effect of borneol on the development of zebrafish embryos. Therefore, we compared the effects of D-borneol, L-borneol and synthetic borneol on the growth and development of zebrafish embryos, and predicted the possible mechanism of perinatal toxicity. METHODS: The embryonic mortality rate, hatching rate, and heart rate of each group were recorded at 48 hpf to compare the effects of borneols on the development of zebrafish embryos. Network pharmacology and molecular docking technology were used to predict the possible mechanism of perinatal toxicity. RESULTS: We found that borneols increased the mortality at 24 and 48 hpf, inhibited the autonomous movement behavior at 24 hpf, and affected the hatching rate and heart rate at 48 hpf. Network pharmacology analysis showed that borneols had the same toxic targets in the perinatal period and were involved in regulating perinatal toxicity by regulating pathways in cancer, chemical carcinogenesis-receptor activation, PI3K-Akt and others. Molecular docking showed that the binding activity of the active ingredients and the core target was at a medium level, and the binding activity of the borneols active ingredients and the core target was not much different. CONCLUSION: Three kinds of borneol on the development of zebrafish embryos were different. The toxicity of L-borneol was the lowest. The mechanisms of perinatal toxicity were related to inflammation, apoptosis, cell cycle and growth, differentiation and reproduction.

Quantum Interference and Coherent Population Trapping in a Double Quantum Dot.

Quantum interference is a natural consequence of wave-particle duality in quantum mechanics, and is widely observed at the atomic scale. One interesting manifestation of quantum interference is coherent population trapping (CPT), first proposed in three-level driven atomic systems and observed in quantum optical experiments. Here, we demonstrate CPT in a gate-defined semiconductor double quantum dot (DQD), with some unique twists as compared to the atomic systems. Specifically, we observe CPT in both driven and nondriven situations. We further show that CPT in a driven DQD could be used to generate adiabatic state transfer. Moreover, our experiment reveals a nontrivial modulation to the CPT caused by the longitudinal driving field, yielding an odd-even effect and a tunable CPT. Our results broaden the field of CPT, and open up the possibility of quantum simulation and quantum computation based on adiabatic passage in quantum dot systems.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Reconstituted HDL ameliorated renal injury of diabetic kidney disease in mice.

Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high-density lipoprotein (rHDL) ameliorated renal injury in eNOS-/- dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non-diabetes), eNOS-/- dbdb (diabetes), and eNOS-/- dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS-/- dbdb mice at Week 16 at 5 µg/g body weight in ~100 µL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS-/- dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.

Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1.

The obstacle to effectively treating Diffuse Large B-cell Lymphoma (DLBCL) lies in the resistance observed toward standard therapies. Identifying therapeutic targets that prove effective for relapsed or refractory patients poses a significant challenge. OTUD3, a deubiquitinase enzyme, is overexpressed in DLBCL tissues. However, its role in DLBCL has not been investigated. Our study has brought to light the multifaceted impact of OTUD3 in DLBCL. Not only does it enhance cell survival through the deubiquitination of MYL12A, but it also induces CD8+ T cell exhaustion within the local environment by deubiquitinating PD-L1. Our findings indicate that the OTUD3 inhibitor, Rupatadine, exerts its influence through competitive binding with OTUD3. This operation diminishes the deubiquitination of both MYL12A and PD-L1 by OTUD3. This research unveils the central and oncogenic role of OTUD3 in DLBCL and highlights the potential clinical application value of the OTUD3 inhibitor, Rupatadine. These findings contribute valuable insights into addressing the challenges of resistant DLBCL cases and offer a promising avenue for further clinical exploration.

Different Characteristics of Psychological and Sleep Symptoms Across Social Media Addiction and Internet Gaming Disorder in Chinese Adolescents- A Network Analysis.

OBJECTIVE: Previous research has explored a variety of mental disorders associated with Internet Gaming Disoder (IGD) and Social Media Addiction (SMA). To date, few studies focused on the network characteristics and investigated mood and sleep symptoms across SMA and IGD of adolescence at a group-specific level. This study aims to identify different characteristics of IGD and SMA and further determine the group-specific psychopathology process among adolescents. METHODS: We conducted a cross-sectional study to recruit a cohort of 7,246 adolescents who were scored passing the cutoff point of Internet Gaming Disorder Scale-Short Form and Bergen Social Media Addiction Scale, as grouped in IGD and SMA, or otherwise into the control group. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item, and Pittsburgh Sleep Quality Index were assessed for the current study, and all assessed items were investigated using network analysis. RESULTS: Based on the analytical procedure, the participants were divided into three groups, the IGD group (n=789), SMA group (n=713) and control group (n=5,744). The edge weight bootstrapping analysis shows that different groups of networks reach certain accuracy, and the network structures of the three groups are statistically different (pcontrol-IGD=0.004, pcontrol-SMA<0.001, pIGD-SMA<0.001). The core symptom of SMA is "feeling down, depressed, or hopeless", while IGD is "feeling tired or having little energy". CONCLUSION: Although IGD and SMA are both subtypes of internet addiction, the psychopathology processes of IGD and SMA are different. When dealing with IGD and SMA, different symptoms should be addressed.

Self-Anchored Van-Der-Waals Stacking Growth of Transition-Metal Dichalcogenide Nanoplates.

Transition-metal dichalcogenide (TMDs) nanoplates exhibit unique properties different from their monolayer counterparts. Controllable nucleation and growth are prerequisite and highly desirable for their practical applications. Here, a self-anchored van-der-Waals stacking growth method is developed, by which the substrate pit induced by precursor etching anchors the source material, impedes the lateral spreading of source droplets and facilitates the in situ stacking growth of high-quality TMD nanoplates with a thickness of tens to hundreds of nanometers at well-defined locations. As such, an array of TMD nanoplates with controlled lateral dimensions are produced and applied in arrayed photodetectors. This study solves the problem of controllable preparation of TMD nanoplates, holding promise for applications in electronics and optoelectronics.

A novel scoring system based on magnetic resonance imaging for the prediction of the difficulty of ultrasound-guided high-intensity focused ultrasound ablation for uterine fibroids.

OBJECTIVE: To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. MATERIALS AND METHODS: A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model. RESULTS: Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index -0.2) +1×(abdominal wall thickness -5). CONCLUSIONS: This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.

OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway.

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms.

The family of ESKAPE pathogens is comprised of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. Together they are the main contributors of nosocomial infections and are well established for their ability to "escape" antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties. In a proprietary emulsion, farnesol has been shown to be capable of disrupting S. aureus, P. aeruginosa, and A. baumannii biofilms. The current work demonstrates that this farnesol emulsion reduces the number of viable bacteria, while also leading to reductions in biomass, of the other three ESKAPE pathogens: Enterococcus faecium, Klebsiella pneumoniae, and Enterobacter, both in vitro and in an ex vivo human skin model. A concentration of 0.5 mg/mL was effective for impeding biofilm development of all three bacteria, while 1 mg/mL for E. faecium and K. pneumoniae, or 0.2 mg/mL for E. cloacae, was able to kill bacteria in established biofilms. Contrary to antibiotics, no resistance to farnesol was observed for E. faecium or K. pneumoniae. The results indicate that farnesol is effective for direct cell killing and also has the ability to induce biofilm detachment from surfaces, as confirmed using Live/Dead image analysis. Our findings confirm that farnesol emulsion is an effective broad-spectrum agent to impede ESKAPE biofilms.

Biofilm growth characteristic and footprint identification in gravity-driven ceramic membrane bioreactor with electro-coagulation under extreme conditions for roofing rainwater purification.

The identification of biofilm growth footprints influencing on the biofilm detachment and breakup can advance research into how biofilms form. Thus, a gravity-driven ceramic membrane bioreactor (GDCMBR) was used to investigate the growth, detachment and breakup of biofilm using rainwater pretreated by electrocoagulation under 70-days continuous operation. The in-situ ultrasonic time-domain reflectometry (UTDR) technique was applied to non-invasively determine the biofilm thickness. Initially, the biofilm was slowly thickening, but it would collapse and became thinner after accumulating to a certain level, and then it thickened again in a later period, following a cyclic pattern of 'thickening - collapsing - thickening'. This is because the biofilm growth is related with the accumulation of flocs, however, excessive floc formation results in the biofilm being overweight till reaching the thickness limit and thus collapsing. Subsequently, the biofilm gradually thickens again due to the floc production and continuous deposition. Although the biofilm was dynamically changing, the water quality of treatment of the biofilm always remained stable. Ammonia nitrogen and total phosphorus have been almost completely removed, while CODMn removal efficiency was around 25%. And total bacteria amount in the membrane concentrate was obviously higher than that in the influent with the greater microbial activity, demonstrating the remarkable enrichment effect on bacteria. The understanding of biofilm growth characteristic and footprint identification enables us to develop rational approaches to control biofilm structure for efficient GDCMBR performance and operation lifespan.

Fabricated advanced textile for personal thermal management, intelligent health monitoring and energy harvesting.

Fabrics are soft against the skin, flexible, easily accessible and able to wick away perspiration, to some extent for local private thermal management. In this review, we classify smart fabrics as passive thermal management fabrics and active thermal management fabrics based on the availability of outside energy consumption in the manipulation of heat generation and dissipation from the human body. The mechanism and research status of various thermal management fabrics are introduced in detail, and the article also analyses the advantages and disadvantages of various smart thermal management fabrics, achieving a better and more comprehensive comprehension of the current state of research on smart thermal management fabrics, which is quite an important reference guide for our future research. In addition, with the progress of science and technology, the social demand for fabrics has shifted from keeping warm to improving health and quality of life. E-textiles have potential value in areas such as remote health monitoring and life signal detection. New e-textiles are designed to mimic the skin, sense biological data and transmit information. At the same time, the ultra-moisturizing properties of the fabric's thermal management allow for applications beyond just the human body to energy. E-textiles hold great promise for energy harvesting and storage. The article also introduces the application of smart fabrics in life forms and energy harvesting. By combining electronic technology with textiles, e-textiles can be manufactured to promote human well-being and quality of life. Although smart textiles are equipped with more intelligent features, wearing comfort must be the first thing to be ensured in the multi-directional application of textiles. Eventually, we discuss the dares and prospects of smart thermal management fabric research.

A polymeric nanoplatform enhances the cGAS-STING pathway in macrophages to potentiate phagocytosis for cancer immunotherapy.

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2', 3'-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy.

Efficacy and safety of BaitouWeng decoction for ulcerative colitis: A meta-analysis of randomized and controlled trials.

BACKGROUND: To systematically evaluate the therapeutic effect of BaitouWeng Decoction in patients with ulcerative colitis (UC), evaluate its safety and effectiveness, and provide a reference for clinical medication. METHODS: The research literature on the treatment of UC with BaitouWeng Decoction was searched in databases such as China National Knowledge Infrastructure, Wanfang Data, VIP database for Chinese Technical Periodicals, Chinese BioMedical Literature Database, and PubMed. The literature was screened by setting inclusion and exclusion criteria, strictly following the inclusion and exclusion criteria, and following the search strategy for literature screening, data extraction, and methodological quality evaluation. According to the Cochrane System Evaluation Manual, methodological quality evaluation was conducted on the included studies using the bias risk assessment tool for randomized controlled trials. For meta-analysis, Review Manager software was used. RESULTS: A total of 24 articles were included, including 2131 patients. Meta-analysis showed that compared with conventional Western medicine, BaitouWeng Decoction can significantly improve the effective rate (odds ratio = 5.10, 95% confidence interval [CI] [3.74-6.96], P < .00001), reduce the traditional Chinese medicine syndrome score (mean difference [MD] = -4.23, 95% CI [-5.17--3.30], P < .00001), Baron endoscopic score (MD = -0.68, 95% CI [-0.78--0.58], P < .00001), and intestinal lesion activity score (MD = -2.29, 95% CI [-1.15--1.03], P < .00001); improve serum factors and reduce serum tumor necrosis factor α levels (MD = -16.84, 95% CI [-19.92--13.76], P < .00001), serum interleukin-8 levels (MD = -10.41, 95% CI [-10.87--9.95], P < .00001), and increased serum interleukin-10 levels (MD = 4.96, 95% CI [2.76-7.16], P < .00001). CONCLUSION: BaitouWeng Decoction has good efficacy and safety in treating UC. BaitouWeng Decoction improved the symptoms of colitis injury and inhibited inflammatory response. However, more rigorously designed randomized controlled trials with blinding, concealment, and placebo controls should be conducted on Baitouweng decoction to generate higher quality evidence and longer-term studies on sustained benefits are needed.