AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

Programming of in Situ Tumor Vaccines via Supramolecular Nanodrug/Hydrogel Composite and Deformable Nanoadjuvant for Cancer Immunotherapy.

The development of in situ tumor vaccines offers promising prospects for cancer treatment. Nonetheless, the generation of plenary autologous antigens in vivo and their codelivery to DC cells along with adjuvants remains a significant challenge. Herein, we developed an in situ tumor vaccine using a supramolecular nanoparticle/hydrogel composite (ANPMTO/ALCD) and a deformable nanoadjuvant (PPER848). The ANPMTO/ALCD composite consisted of ß-cyclodextrin-decorated alginate (Alg-g-CD) and MTO-encapsulated adamantane-decorated nanoparticles (ANPMTO) through supramolecular interaction, facilitating the long-term and sustained production of plenary autologous antigens, particularly under a 660 nm laser. Simultaneously, the produced autologous antigens were effectively captured by nanoadjuvant PPER848 and subsequently transported to lymph nodes and DC cells, benefiting from its optimized size and deformability. This in situ tumor vaccine can trigger a robust antitumor immune response and demonstrate significant therapeutic efficacy in inhibiting tumor growth, suppressing tumor metastasis, and preventing postoperative recurrence, offering a straightforward approach to programming in situ tumor vaccines.

Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Identification of sudden cardiac death from human blood using ATR-FTIR spectroscopy and machine learning.

OBJECTIVE: The aim of this study is to identify a rapid, sensitive, and non-destructive auxiliary approach for postmortem diagnosis of SCD, addressing the challenges faced in forensic practice. METHODS: ATR-FTIR spectroscopy was employed to collect spectral features of blood samples from different cases, combined with pathological changes. Mixed datasets were analyzed using ANN, KNN, RF, and SVM algorithms. Evaluation metrics such as accuracy, precision, recall, F1-score and confusion matrix were used to select the optimal algorithm and construct the postmortem diagnosis model for SCD. RESULTS: A total of 77 cases were collected, including 43 cases in the SCD group and 34 cases in the non-SCD group. A total of 693 spectrogram were obtained. Compared to other algorithms, the SVM algorithm demonstrated the highest accuracy, reaching 95.83% based on spectral biomarkers. Furthermore, by combing spectral biomarkers with age, gender, and cardiac histopathological changes, the accuracy of the SVM model could get 100%. CONCLUSION: Integrating artificial intelligence technology, pathology, and physical chemistry analysis of blood components can serve as an effective auxiliary method for postmortem diagnosis of SCD.

Uric acid to albumin ratio as a novel predictor for coronary slow flow phenomenon in patients with chronic coronary syndrome and non-obstructive coronary arteries.

BACKGROUND: The plasma uric acid to albumin ratio (UAR) is considered as a novel indicator for Inflammation. However, the association between UAR and coronary slow flow phenomenon (CSFP) remains unclear. METHODS: A total of 1328 individuals with chronic coronary syndrome (CCS) receiving coronary angiography (CAG) and found no obvious obstructive stenosis (< 40%) were included in this study. 79 individuals developed CSFP and were divided into CSFP group. The 1:2 age-matched patients with normal coronary blood flow were allocated to the control group (n = 158). The clinical characteristics, laboratory parameters including uric acid, albumin ratio, UAR and the angiographic characteristics were compared between the two groups. RESULTS: Patients with CSFP had a higher level of uric acid (392.3 ± 85.3 vs. 273.8 ± 71.5, P < 0.001), UAR (10.7 ± 2.2 vs. 7.2 ± 1.9, P < 0.001), but a lower level of plasma albumin (36.9 ± 4.2 vs. 38.5 ± 3.6, P = 0.003). Moreover, UAR increased as the numbers of vessels involved in CSFP increased. The logistic regression analysis demonstrated that UAR was independent predictors for CSFP. The Receiver operating characteristic (ROC) curve analysis showed that when UAR was more than 7.9, the AUC was 0.883 (95% CI: 0.840-0.927, p < 0.001), with the sensitivity and specificity were 78.2% and 88.2% respectively. CONCLUSION: Combined uric acid with plasma albumin, UAR could serve as an independent predictor for CSFP.

The dual function of cGAS-STING signaling axis in liver diseases.

Numerous liver diseases, such as nonalcoholic fatty liver disease, hepatitis, hepatocellular carcinoma, and hepatic ischemia-reperfusion injury, have been increasingly prevalent, posing significant threats to global health. In recent decades, there has been increasing evidence linking the dysregulation of cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING)-related immune signaling to liver disorders. Both hyperactivation and deletion of STING can disrupt the immune microenvironment dysfunction, exacerbating liver disorders. Consequently, there has been a surge in research investigating medical agents or mediators targeting cGAS-STING signaling. Interestingly, therapeutic manipulation of the cGAS-STING pathway has yielded inconsistent and even contradictory effects on different liver diseases due to the distinct physiological characteristics of intrahepatic cells that express and respond to STING. In this review, we comprehensively summarize recent advancements in understanding the dual roles of the STING pathway, highlighting that the benefits of targeting STING signaling depend on the specific types of target cells and stages of liver injury. Additionally, we offer a novel perspective on the suitability of STING agonists and antagonists for clinical assessment. In conclusion, STING signaling remains a highly promising therapeutic target, and the development of STING pathway modulators holds great potential for the treatment of liver diseases.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Genome-centric metagenomics and methanogenic pathway analysis for acclimated anaerobic digestion of chicken manure with high ammonia stressed under thermophilic condition.

Thermophilic anaerobic digestion (AD) of animal manure offers various environmental benefits but the process requires a microbial community acclimatized to high ammonia. In current study, a lab-scale continuous stirred tank reactor (CSTR) fed with chicken manure was operated under thermophilic condition for 450 days in total. Results showed that the volumetric methane production decreased from 445 to 328 and sharply declined to 153 mL L-1·d-1 with feeding total solid (TS) step increased from 5% to 7.5% and 10%, respectively. While, after a long-term stop feeding for 80 days, highly disturbed reactor was able to recover methane generation to 739 mL L-1·d-1 at feeding TS of 10%. Isotope analysis indicted acetate converted to methane through the syntrophic acetate oxidation and hydrogenotrophic methanogenesis (SAO-HM) pathway increased from 33% to 63% as the concentration of ammonium increased from 2493 to 6258 mg L-1. Significant different in the genome expression of the SAO bacterial from 0.09% to 1.23%, combining with main hydrogenotrophic partners (Methanoculleus spp. and Methanothermobacter spp.) contented of 2.1% and 99.9% during inhibitory and recovery stages, respectively. The highly expressed KEGG pathway in level 3 (enzyme genes) for the Recovery sludge combining with the extraordinary high abundance of genera Halocella sp. suggested that Halocella sp. might be a highly efficient hydrolytic and acidogenic microorganism and enhance the process of SAO during carbon metabolic flow to methane. This report will be a basis for further study of AD studies on high nitrogen content of poultry manure.

Accuracy of traditional open-tray impression, stereophotogrammetry, and intraoral scanning with prefabricated aids for implant-supported complete arch prostheses with different implant distributions: An in vitro study.

STATEMENT OF PROBLEM: Conventional impression techniques for complete arch implant-supported fixed dental prostheses (CIFDPs) are technique sensitive. Stereophotogrammetry (SPG) and intraoral scanning (IOS) may offer alternatives to conventional impression making. PURPOSE: The purpose of this in vitro study was to assess the accuracy and passive fit of IOS with prefabricated aids, SPG, and open tray impression (OI) for CIFDPs with different implant distributions. MATERIAL AND METHODS: Three definitive casts with 4 parallel implants (4-PARA), 4 inclined implants (4-INCL), and 6 parallel implants (6-PARA) were fabricated. Three recording techniques were tested: IOS with prefabricated aids, SPG, and OI. The best and the worst scans were selected to fabricate 18 milled aluminum alloy frameworks. The trueness and precision of distance deviation (∆td and ∆pd), angular deviation (∆tθand ∆pθ), root mean square errors (∆tRMS for ∆pRMS), and passive fit score of frameworks were recorded. Two-way ANOVA was applied. RESULTS: SPG showed the best trueness and precision (95%CI of ∆td/∆tθ/∆tRMS, 31 to 39 µm, 0.22 to 0.28 degrees, 20 to 23 µm; 95%CI of ∆pd/∆pθ/∆pRMS, 9 to 11 µm, 0.06 to 0.08 degrees, 8 to 10 µm), followed by OI (61 to 83 µm, 0.33 to 0.48 degrees, 28 to 48 µm; 66 to 81 µm, 0.29 to 0.38 degrees, 32 to 41 µm) and IOS (143 to 193 µm, 0.37 to 0.50 degrees, 81 to 96 µm; 89 to 111 µm, 0.27 to 0.31 degrees, 51 to 62 µm). Tilted implants were associated with increased distance deviation. Increased implant number was associated with improved recording precision. The passive fit of frameworks was negatively correlated with the RMS error, and the correlation coefficient was -0.65 (P=.003). CONCLUSIONS: SPG had the best accuracy. Implant distributions affected implant precision. The RMS error can be used to evaluate the passive fit of frameworks.

Optimized Cationic Lipid-assisted Nanoparticle for Delivering CpG Oligodeoxynucleotides to Treat Hepatitis B Virus Infection.

PURPOSE: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. METHODS: We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. RESULTS: We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. CONCLUSION: We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection.

PABPN1 functions as a predictive biomarker in colorectal carcinoma.

PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

1H NMR-guided isolation of hasubanan alkaloids from the alkaloidal extract of Stephania longa.

1H NMR-guided fractionation led to the isolation of 16 alkaloids from the alkaloidal extract of Stephania longa, including 11 new hasubanan alkaloids (1-11) and five known alkaloids (12-16). Interestingly, compounds 2 and 11 are typically considered protonated tertiary amine compounds, whereas compounds 1 and 10 are regarded as oxidized versions of the corresponding compounds. Their gross structures were determined through an extensive analysis of spectroscopic data (NMR (nuclear magnetic resonance) and HRESIMS (high resolution electrospray ionization mass spectroscopy)), and their absolute configurations were established by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. The new (3) and a known (12) compounds in all isolates displayed stronger antineuroinflammatory effects (IC50 values of 1.8 and 11.1 µM, respectively) than minocycline (IC50 value of 15.5 µM) against NO production on LPS-activated BV2 cells.

Structurally various p-terphenyls with neuraminidase inhibitory from a sponge derived fungus Aspergillus sp. SCSIO41315.

Guided by Global Natural Products Social molecular networking, 14 new p-terphenyl derivatives, asperterphenyls A-N (1-14), together with 20 known p-terphenyl derivatives (15-34), were obtained from a sponge derived fungus Aspergillus sp. SCSIO41315. Among them, new compounds 2-8 and 15-17 were ten pairs of enantiomers. Comprehensive methods such as chiral-phase HPLC analysis, ECD calculations and X-ray diffraction analysis were applied to determine the absolute configurations. Asperterphenyls B (2) and C (3) represented the first reported natural p-terphenyl derivatives possessing a dicarboxylic acid system. Asperterphenyl A (1) displayed neuraminidase inhibitory activity with an IC50 value of 1.77 ± 0.53 µM and could efficiently inhibit infection of multiple strains of H1N1 with IC50 values from 0.67 ± 0.28 to 1.48 ± 0.60 µM through decreasing viral plaque formation in a dose-dependent manner, which suggested that asperterphenyl A (1) might be exploited as a potential antiviral compound in the pharmaceutical fields.

LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles.

Liver fibrosis is a wound-healing process characterized by excess formation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Previous studies show that both EZH2, an epigenetic regulator that catalyzes lysine 27 trimethylation on histone 3 (H3K27me3), and long non-coding RNA H19 are highly correlated with fibrogenesis. In the current study, we investigated the underlying mechanisms. Various models of liver fibrosis including Mdr2-/-, bile duct ligation (BDL) and CCl4 mice were adapted. We found that EZH2 was markedly upregulated and correlated with H19 and fibrotic markers expression in these models. Administration of EZH2 inhibitor 3-DZNeP caused significant protective effects in these models. Furthermore, treatment with 3-DZNeP or GSK126 significantly inhibited primary HSC activation and proliferation in TGF-ß-treated HSCs and H19-overexpreesing LX2 cells in vivo. Using RNA-pull down assay combined with RNA immunoprecipitation, we demonstrated that H19 could directly bind to EZH2. Integrated analysis of RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) further revealed that H19 regulated the reprogramming of EZH2-mediated H3K27me3 profiles, which epigenetically promoted several pathways favoring HSCs activation and proliferation, including epithelial-mesenchymal transition and Wnt/ß-catenin signaling. In conclusion, highly expressed H19 in chronic liver diseases promotes fibrogenesis by reprogramming EZH2-mediated epigenetic regulation of HSCs activation. Targeting the H19-EZH2 interaction may serve as a novel therapeutic approach for liver fibrosis.

Accuracy of intraoral scan with prefabricated aids and stereophotogrammetry compared with open tray impressions for complete-arch implant-supported prosthesis: A clinical study.

OBJECTIVES: The aim of this clinical study was to compare the accuracy of intraoral scan system (IOS) with prefabricated aids and stereophotogrammetry (SPG) compared with open tray implant impression (OI) for complete-arch implant-supported fixed dental prostheses (CIFDP). MATERIALS AND METHODS: Patients needing CIFDP were enrolled in this study. OI, reference standard, IOS with prefabricated aids, and SPG were performed for each patient. Distance and angle deviations between all pairs of abutment analogs, root mean square (RMS) errors between the aligned test and reference model, and chairside time were measured. The effect of inter-abutment distance, jaw (maxilla or mandible), number of implants, and arch length on deviations was analyzed. The mixed effect model was applied to analyze deviations and RMS errors. RESULTS: Fifteen consecutive individuals (6 females and 9 males, 47-77 years old) with 22 arches (9 upper and 13 lower jaws) and 115 implants were included. There was no significant difference in distance deviation comparing SPG and IOS with OI (p > .05). IOS showed a significantly greater angle deviation and RMS errors than SPG (median 0.40° vs. 0.31°, 69 µm vs. 45 µm, p < .01). The inter-abutment distance was negatively correlated with the accuracy of SPG and IOS (p < .05). The chairside time for IOS, SPG, and OI was 10.49 ± 3.50, 14.71 ± 2.86, and 20.20 ± 3.01 min, respectively (p < .01). CONCLUSIONS: The accuracy of SPG and IOS with prefabricated aids was comparable. IOS was the most efficient workflow.

Cathepsin C promotes colorectal cancer metastasis by regulating immune escape through upregulating CSF1.

Since metastasis remains the primary reason for colorectal cancer (CRC) associated death, a better understanding of the molecular mechanism underlying CRC metastasis is urgently needed. Here, we elucidated the role of Cathepsin C (CTSC) in promoting CRC metastasis. The expression of CTSC was detected by real-time PCR and immunohistochemistry in the human CRC cohort. The metastatic capacities of CTSC-mediated metastasis were analyzed by in vivo metastasis model. Elevated CSTC expression was positively associated with tumor differentiation, tumor invasion, lymph node metastasis, and AJCC stage and indicated poor prognosis in human CRC. CTSC overexpression in CRC cells promoted myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) recruitment by the CSF1/CSF1R axis. In contrast, the knockdown of CSF1 reduced CTSC-mediated MDSCs and TAMs infiltration and CRC metastasis. Depletion of either MDSCs or TAMs decreased CTSC-mediated CRC metastasis. In human CRC tissues, CTSC expression was positively associated with intratumoral MDSCs and TAMs infiltration. Furthermore, the combination of CTSC inhibitor AZD7986 and anti-PD-L1 antibody blocked CTSC-induced CRC metastasis. CTSC overexpression promoted MDSCs and TAMs infiltration by CSF1/CSF1R axis. Interruption of this oncogenic loop may provide a promising treatment strategy for inhibiting CTSC-driven CRC metastasis.

Association of carbohydrate intake from different sources with all-cause and cardiovascular mortality among chronic kidney disease populations: assessment of 1999-2018 National Health and Nutrition Examination Survey participation.

This study analysed the data from the NHANES (1999-2018) to examine how different sources of carbohydrate intake affected the all-cause and cardiovascular mortality of 11,302 chronic kidney disease (CKD) patients. The data were adjusted for other factors using various methods. The results showed that CKD patients (stages 1-2 and 3-5) who consumed more carbohydrates from whole grains, fruits, vegetables and less carbohydrates from fruit juice or sauces had lower mortality rates. Replacing fat intake with carbohydrates from whole grains (HR = 0.86[0.78-0.95]), fruits (raw) (HR = 0.79[0.70-0.88]) and non-starchy vegetables (HR = 0.82[0.70-0.96]), but not protein intake, was linked to lower all-cause mortality. The fibre content in carbohydrates might partly account for the benefits of selected carbohydrate intake. This study provided practical recommendations for optimising the carbohydrate sources in CKD patients.

Virome Analysis of Aconitum carmichaelii Reveals Infection by Eleven Viruses, including Two Potentially New Species.

Aconitum carmichaelii is a herbaceous herb indigenous to China that has been cultivated for traditional medicine for centuries. Virus-like symptoms of A. carmichaelii plants were observed on leaves in some A. carmichaelii plantations in Zhanyi and Wuding Counties, Yunnan Province, southwest China. High-throughput sequencing (HTS) was performed on 28 symptomatic plants, and the results revealed infection with 11 viruses, including 2 novel viruses and 9 previously described viruses: Aconitum amalgavirus 1 (AcoAV-1), aconite virus A (AcVA), cucumber mosaic virus (CMV), currant latent virus (CuLV), apple stem grooving virus (ASGV), chilli veinal mottle virus (ChiVMV), tomato spotted wilt orthotospovirus (TSWV), tobacco vein distorting virus (TVDV), and potato leafroll virus (PLRV). Two novel viruses tentatively named Aconitum potyvirus 1 and Aconitum betapartitivirus 1, were supported by sequence and phylogenetic analysis results of their genomes. We proposed the names Potyvirus aconiti and Betapartitivirus aconiti. RT-PCR assays of 142 plants revealed the predominance and widespread distribution of CMV, AcVA, and AcoPV-1 in plantations. The detection of isolates of CuLV, ASGV, ChiVMV, TSWV, TVDV, and PLRV infections for the first time in A. carmichaelii expands their known host ranges.

Effect of FoxO1 on Cardiomyocyte Apoptosis and Inflammation in Viral Myocarditis via Modultion of the TLR4/NF-κB Signaling Pathway.

To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1ß, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1ß and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.

Comparison of wound complications between one-stage and two-stage brachiobasilic arteriovenous fistula: A meta-analysis.

Research assessing the outcome of brachiobasilic arteriovenous fistulas (BB-AVF) after a one- and two-stage technique was conducted. A strict review of the comprehensive literature up to May 2023 was carried out using four databases-PubMed，Embase, Cochrane Library and web of science. Inclusion and exclusion criteria developed for the study were then applied to assess the quality of the literature, it was decided to review 12 interrelated studies.95% confidence intervals (Cl) and odds ratios (OR) were calculated using fixed effects models. The data were meta-analysed using RevMan 5.3 software. The results showed that two-stage technique with BB-AVF reduced surgical site haematoma (SSH) formation, (OR, 2.28; 95% CI, 1.24-4.17, p = 0.008), and also reduced surgical site wound infection (SSWI) (OR, 1.86; 95% CI, 1.17-2.94, p = 0.008). There are, however, several small sample sizes in the selected studies for this meta-analysis, so caution should be used when processing their values. There are more high-quality studies with large sample sizes that should be considered for future meta-analyses.