Search

Abstract Objective The aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Methods A cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy. Results Among the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P

Abstract The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were subjected to lipopolysaccharide (LPS)-induced sepsis, and cardiac function was assessed in IRG1 knockout (IRG1-/-) and wild-type mice. Exogenous 4-octyl itaconate (4-OI) supplementation was also examined for its protective effects. In vitro, bone marrow-derived macrophages and RAW264.7 cells were treated with 4-OI following Nuclear factor, erythroid 2 like 2 (NRF2)–small interfering RNA administration to elucidate the underlying mechanisms. Our results indicate that IRG1 deficiency exacerbates myocardial injury during sepsis, while 4-OI administration preserves cardiac function and reduces inflammation. Mechanistic insights reveal that 4-OI activates the NRF2/HO-1 pathway, promoting macrophage polarization and attenuating inflammation. These findings underscore the protective role of the IRG1/itaconate axis in SIMD and suggest a therapeutic potential for 4-OI in modulating macrophage responses.

Abstract Background Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. Methods Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. Results The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. Conclusions Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Abstract Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term ‘organoids’ is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.

Ischemic heart failure rates rise despite decreased acute myocardial infarction (MI) mortality. Excessive myofibroblast activation post-MI leads to adverse remodeling. LIM kinases (LIMK1 and LIMK2) regulate cytoskeleton homeostasis and are pro-fibrotic markers in atrial fibrillation. However, their roles and mechanisms in postinfarction fibrosis and ventricular remodeling remain unclear. This study found that the expression of LIMKs elevated in the border zone (BZ) in mice MI models. LIMK1/2 double knockout (DKO) restrained pathological remodeling and reduced mortality by suppressing myofibroblast activation. By using adeno-associated virus (AAV) with a periostin promoter to overexpress LIMK1 or LIMK2, this study found that myofibroblast-specific LIMK2 overexpression diminished these effects in DKO mice, while LIMK1 did not. LIMK2 kinase activity was critical for myofibroblast proliferation by using AAV overexpressing mutant LIMK2 lack of kinase activity. According to phosphoproteome analysis, functional rescue experiments, co-immunoprecipitation, and protein-protein docking, LIMK2 led to the phosphorylation of β-catenin at Ser 552. LIMK2 nuclear translocation also played a role in myofibroblast proliferation after MI with the help of AAV overexpressing mutant LIMK2 without nuclear location signal. Chromatin immunoprecipitation sequencing identified that LIMK2 bound to Lrp6 promoter region in TGF-β treated cardiac fibroblasts, positively regulating Wnt signaling via Wnt receptor internalization. This study demonstrated that LIMK2 promoted myofibroblast proliferation and adverse cardiac remodeling after MI, by enhancing phospho-β-catenin (Ser552) and Lrp6 signaling. This suggested that LIMK2 could be a target for the treatment of postinfarction injury.

Abstract Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer—which are believed to be connected to the malfunction of multigene and multilevel cell signaling network—remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

Abstract Background N‐acetyltransferase 10 (NAT10) serves as a critical enzyme in mediating the N4‐acetylcytidine (ac4C) that ensures RNA stability and effective translation processes. The role of NAT10 in driving the advancement of breast cancer remains uninvestigated. Methods We observed an increase in NAT10 expression, both at mRNA level through the analysis of the Cancer Genome Atlas (TCGA) database and at the protein level of tumor tissues from breast cancer patients. We determined that a heightened expression of NAT10 served as a predictor of an unfavorable clinical outcome. By screening the Cancer Cell Line Encyclopedia (CCLE) cell bank, this expression pattern of NAT10 was consistency found across almost all the classic breast cancer cell lines. Results Functionally, interference of NAT10 expression exerts an inhibitory effect on proliferation and invasion of breast cancer cells. By using ac4C RNA immunoprecipitation (ac4c‐RIP) and acRIP‐qPCR assays, we identified a reduction of ac4C enrichment within the ATP binding cassette (ABC) transporters, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), consequent to NAT10 suppression. Expressions of MDR1 and BCRP exhibited a positive correlation with NAT10 expression in tumor tissues, and the inhibition of NAT10 in breast cancer cells resulted in a decrease of MDR1 and BCRP expression. Therefore, the overexpressing of MDR1 and BCRP could partially rescue the adverse consequences of NAT10 depletion. In addition, we found that, remodelin, a NAT10 inhibitor, reinstated the susceptibility of capecitabine‐resistant breast cancer cells to the chemotherapy, both in vitro and in vivo. Conclusion The results of our study demonstrated the essential role of NAT10‐mediated ac4c‐modification in breast cancer progression and provide a novel strategy for overcoming chemoresistance challenges.

Multi-channel neural electrodes as a crucial means are of great significance for information exchange between the brain and computers. Herein, we present a 16-channel Si-based active neural probe system that achieves a monolithic integration between the electrodes and circuits in a single probe, making it a standalone integrated electrophysiology recording system. The ASIC prepared on a base (2×2mm2) is a 16-channel analog frontend (AFE) for neural recording, and each channel has a low-noise amplifier (LNA), a bandpass filter (BPF), a buffer and a current bias circuit. The 258 neural signal recording electrodes (22×24μm2) are densely packed on a 50 μm thick, 100 μm wide, and 3 mm long shank. The ASIC of neural probe, internal interconnecting wires are all implemented in commercial SMIC 0.18 μm CMOS technology. The neural probe system achieves a 3.6 μVrms input-referred noise (IRN) in a bandwidth of 1.1Hz-10 kHz, 70.8 μW power consumption, 0.0785 mm2 area per channel, as well as an AFE gain of 58.1 dB Furthermore, the impedances of the Au electrodes can be obtained as 0.5–2.1 MΩ at a frequency of 1 kHz. The functionality of a 16-channel silicon-based neural probe is validated in an in-vivo experiment on lab rats.

Objective: The purpose of this systematic review was to examine the association between folic acid supplementation during pregnancy and the risk of preeclampsia. Methods: Relevant studies were included by searching Embase, PubMed, Scope, Web of science, Cochrane Library databases. Studies were reviewed according to prespecified inclusion and exclusion criteria. Study characteristics were summarized, and study quality was assessed. Risk ratios (RR) and 95% confidence intervals (CI) were used as indicators of effect to assess the relationship between folic acid supplementation and risk of preeclampsia. Results: The protocol of this study was prospectively registered with the PROSPERO (registration No. CRD42022380636). A total of nine studies were included, divided into three groups according to the type of study, containing a total of 107 051 and 105 222 women who were supplemented and not supplemented with folic acid during pregnancy. The results showed that folic acid supplementation during pregnancy could not be proven to reduce the risk of preeclampsia. Conclusion: The results of the study suggest that folic acid supplementation alone is not associated with a decreased risk of pre-eclampsia,but the inferences are somewhat limited by the low methodological quality of the included literature, and therefore higher quality studies are needed to prove this point.

BackgroundThere is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.MethodsSelection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.ResultsA total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.DiscussionThe improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.

This study aims to investigate the protective effects of the extract of Sophora japonica L. (Sophora extract) and vitamin C (VC) on UV-induced damage in HaCaT cells. HaCaT cells were cultured in vitro and divided into different groups: Control group (without UV irradiation or treatment with Sophora extract, VC, or their combination), UV radiation group, 125 μg/mL Sophora extract group (with UV irradiation and treatment with Sophora extract), 125 μg/mL vitamin C group (with UV irradiation and treatment with VC), and 125 μg/mL combination group (with UV irradiation, Sophora extract and VC at a mass ratio of 1:1). The inhibitory effects of Sophora extract, VC, and their combination on reactive oxygen species (ROS) production and mitochondrial ROS in UV-irradiated HaCaT cells were measured using fluorescence staining and enzyme-linked immunosorbent assay. Immunofluorescence staining and enzyme-linked immunosorbent assay were also employed to evaluate the expression levels of cyclobutane pyrimidine dimers (CPDs) and the inflammatory cytokine IL-6 in UV-irradiated HaCaT cells treated with Sophora extract, VC, or their combination. The results showed that the total ROS inhibition rates of Sophora extract, VC, and the combination in UVA-treated HaCaT cells were 38.23%±9.23%, 27.20%±6.87%, and 64.13%±4.08%, respectively. The combination significantly enhanced the total ROS inhibition rate compared to the individual treatments (P

Forest fires constitute a widespread and impactful natural disaster, annually ravaging millions of hectares of forests and posing a severe threat to human life and property. Accurate quantitative prediction of forest fire spread is essential for devising swift risk management strategies and implementing effective firefighting approaches. In response to this imperative, this study introduces a Forest Fire Spread Behavior Prediction (FFSBP) model, encompassing two integral components: the Forest Fire Spread Process Prediction (FFSPP) model and the Forest Fire Spread Results Prediction (FFSRP) model. The FFSPP model involves the prediction of the direction and speed of forest fire spread, achieved through a fusion of the Cellular Automata model and the Wang Zhengfei model. On the other hand, the FFSRP model focuses on forecasting the extent of the burned area, leveraging machine learning methods. To validate the efficacy of the proposed models, a real case study is undertaken using the “3.29 Forest Fire” incident in China. The FFSPP model is validated against this case, while the FFSRP model is assessed using a real fire dataset obtained from Montesinho National Forest Park in Portugal. Results from the validation process reveal that during the natural development period of the “3.29 Forest Fire,” the FFSPP model predicts a burned area of 286.81 hm2, with an associated relative error of 28.94%. This relative error is notably smaller than those observed in the Farsite and Prometheus fire behavior simulation models. Additionally, the FFSRP model demonstrates commendable predictive performance, particularly in the context of small and medium-sized fire scenarios. These findings underscore the potential of the FFSBP model as a valuable tool in enhancing forest fire prediction accuracy and facilitating more robust risk mitigation and firefighting strategies.

Abstract Prostate cancer is a common malignant tumor at present, and there are still adverse reactions after radical prostatectomy. As many as 30% of patients complain of urinary incontinence (UI). This review begins with the pathophysiological basis of post‐prostatectomy urinary incontinence (PPUI) and describes the maintenance of normal urine control function, anatomical changes, and urodynamic maintenance of PPUI. Then, we talk about the various influencing factors of UI, for example, the differences caused by the basic condition of the patient, the length of the membranous urinary tract, the level of prostate‐specific antigen before operation, the method and technique of operation, and so on. Last, we introduce all kinds of treatments of PPUI in detail. It includes noninvasive conservative treatment, traditional surgical treatment, emerging stem cell therapy treatment, and postoperative psychotherapy of PPUI. The present situation of the treatment of UI after prostatectomy is summarized, and the prospect of the technology is put forward.

At the current stage, the automation level of GNSS RTK equipment is low, and manual operation leads to decreased accuracy and efficiency in setting out. To address these issues, this paper has designed an algorithm for automatic setting out that resolves the common problem of reduced accuracy in conventional RTK. First, the calculation of the laser rotation center is conducted using relevant parameters to calibrate the instrument’s posture and angle. Then, by analyzing the posture information, the relative position and direction of the instrument to the point to be set out are determined, and the rotation angles in the horizontal and vertical directions are calculated. Following this, the data results are analyzed, and the obtained rotation angles are output to achieve automatic control of the instrument. Finally, a rotating laser composed of servo motors and laser modules is used to control the GNSS RTK equipment to locate the set-out point, thereby determining its position on the ground and displaying it in real-time. Compared to traditional GNSS RTK equipment, the proposed automatic setting out algorithm and the developed GNSS laser RTK equipment reduce the setting out error from 15 mm to 10.3 mm. This reduces the barrier to using GNSS RTK equipment, minimizes human influence, enhances the work efficiency of setting out measurements, and ensures high efficiency and stability under complex conditions.

Objective: This study aimed to investigate the diagnostic value of a combination of anti-extractable nuclear antigens (anti-ENA) antibodies, anti-cardiolipin antibodies (ACA), and anti-β2-glycoprotein 1 (anti-β2 GPI) antibodies in patients with systemic lupus erythematosus (SLE). Methods: A total of 646 SLE patients diagnosed in our hospital between January 2020 and April 2023 were randomly selected as study subjects, while 2075 non-SLE subjects during the same period were selected as the control group. The levels of anti-extractable nuclear antigen (ENA) antibody, ACA, and anti-β2 GPI antibodies were measured, and their diagnostic value for SLE was analyzed using binary logistic regression and receiver operating characteristic (ROC) analysis. Results: The rates of positive anti-RNP, anti-Sm, anti-Sjögren's syndrome (SS-A), and anti–SS–B antibodies in the SLE patient group were significantly higher than those in the control group, with all differences being statistically significant (P

Background and purposeAdjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD).MethodsPatients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0–1, 0–2, and 0–3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population.ResultsA total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0–5) vs. 1(0–4) vs. 1(0–4) vs. 3(0–5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45–1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78–2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64–1.64, P = 0.912). The adjusted OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27–0.98, P = 0.042) and 0.50 (95% CI, 0.26–0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18–0.94, P = 0.036), and the OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11–0.74, P = 0.011) and 0.25 (95% CI, 0.09–0.67, P = 0.006).ConclusionsIntra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO.Clinical trial registrationhttp://www.clinicaltrials.gov, Unique identifier: NCT03370939.

Ascorbate peroxidase (APX) is a crucial H2O2 scavenger that utilizes ascorbic acid as an electron donor and plays a significant role in plant stress resistance. This study aims to identify and characterize the Brassica napus L. APX gene family through genome and transcriptome sequencing, while also revealing their expression profile under low-temperature stress via transcriptome and proteome analysis. The results indicate the presence of 18 genes with three different conserved domains distributed in Brassica napus L., which can be classified into three major branches based on phylogenetic analysis. Eleven members were predicted to have the low-temperature response component (LTR). Most APX genes exhibit up-regulated transcriptional expression under low temperature stress, particularly APX2, APX4, APX12, and APX18. In terms of proteomics data, only six members (APX2, APX4, APX8, APX12, APX17, and APX18) showed temporal specificity in their expression patterns. Therefore, this study provides valuable insights into the complexity of the APX family in the functional characterization of its genes for future research.

Recent studies revealed that programmed cell death ligand 1 (PD-L1) expression was associated with unfavorable prognosis in various solid tumors, but its clinical relevance for pancreatic cancer has not yet been well established. This meta-analysis summarizes the potential prognostic value of PD-L1 in pancreatic cancer. A quantitative meta-analysis was performed by a systematic search of databases including PubMed, EMBASE, Web of Science, Cochrane library, Scopus and Ovid for eligible studies on the prognostic significance of PD-L1 in pancreatic cancer patients. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated to evaluate the strength of the link between PD-L1 expression and clinical prognosis of patients. Seventeen eligible studies with 2669 patients were included in our study. A significant association was observed between PD-L1 abundance and poor overall survival (OS) of patients with pancreatic cancers, with a pooled hazard ratio (HR) of 1.902, 95% CI: 1.657-2.184. Sensitivity analysis confirmed the reliability of our results. Subgroup analysis shows that differences in regions and detection methods of PD-L1 did not change the overall predictive value of PD-L1 for poor prognosis in pancreatic cancer patients. This meta-analysis indicated that the expression of PD-L1 is associated with a worse OS in pancreatic cancer patients. Additionally, PD-L1 may act as a potential parameter for predicting poor prognosis and thus providing a promising target for anticancer therapy in pancreatic cancer.

Abstract Zebrafish is a widely used model organism for investigating human diseases, including hematopoietic disorders. However, a comprehensive methylation baseline for zebrafish primary hematopoietic organ, the kidney marrow (KM), is still lacking. We employed Oxford Nanopore Technologies (ONT) sequencing to profile DNA methylation in zebrafish KM by generating four KM datasets, with two groups based on the presence or absence of red blood cells. Our findings revealed that blood contamination in the KM samples reduced read quality and altered methylation patterns. Compared with whole-genome bisulfite sequencing (WGBS), the ONT-based methylation profiling can cover more CpG sites (92.4% vs 70%–80%), and exhibit less GC bias with more even genomic coverage. And the ONT methylation calling results showed a high correlation with WGBS results when using shared sites. This study establishes a comprehensive methylation profile for zebrafish KM, paving the way for further investigations into epigenetic regulation and the development of targeted therapies for hematopoietic disorders.

There is an urgent need for clean recycling strategies to address the increase in food waste (FW) and the harvesting of microalgae (MA). In this study, biogas production potential and operational stability were evaluated by testing combinations of FW and MA mixed at five different ratios. Co-digestion of FW and MA improved substrate biodegradability, achieving a decomposition rate of 0.45/d (FW/MA = 1:1), which is 1.25 to 1.55 times higher than that of MA or FW alone. Co-digestion of FW and MA resulted in a synergistic effect, improving biogas yield by 2.04–26.86%. Four mathematical models were applied to estimate biological degradation and biogas production kinetics, and the Cone model performed better than the other models in terms of reliability and accuracy. The abundance of Bacteroidetes, Firmicutes, and Synergistetes peaked at FW/MA = 1:1. At the same ratio, the genera Methanospirillum, Methanocorpusculum, and Methanomethylovorans were also found to have increased in abundance. The optimal ratio was found to be 1:1 for co-digestion of FW and MA, which is a feasible approach for simultaneous bioenergy production and biomass waste co-disposal.

Abstract Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3 Δ/Δ) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe thrombocytopenia is observed in animals with diminished LCM, although there is no change in MK ploidy distribution, uncoupling endoreduplication and platelet production. When HSC isolated from a microenvironment essentially devoid of LCM reconstitute hematopoiesis in lethally irradiated mice, the absence of LCM increases HSC in BM, blood and spleen, and the recapitulation of thrombocytopenia. In contrast, following a competitive transplant using minimal numbers of WT HSC together with HSC from a microenvironment with diminished LCM, sufficient WT HSC-generated LCM regulates a normal HSC pool and prevents thrombocytopenia. Importantly, LCM are conserved in humans.

This paper reviews the composition, development, and operation mechanism of domestic and foreign fire protection technical regulations and standards. Considering the development and problems of China's fire protection standard system and fire protection technical standards, this paper recommends fire safety professional engineering design specialization, suggests key research fields pertaining to fire protection technical standards, and elucidates how a performance-based fire protection technical standard system can be established.

The EAST ICRF system operating space has been extended in power and phase control with a low-level RF system for the new double-strap antenna. Then the multi-step power and periodic phase scanning experiment were conducted in L-mode plasma, respectively. In the power scanning experiment, the stored energy, radiation power, plasma impedance and the antenna's temperature all have positive responses during the short ramp-ups of PL,ICRF. The core ion temperature increased from 1 keV to 1.5 keV and the core heating area expanded from |Z|≤5cm to |Z|≤10cm during the injection of ICRF waves. In the phasing scanning experiment, in addition to the same conclusions as the previous relatively phasing scanning experiment, the superposition effect of the fluctuation of stored energy, radiation power and neutron yield caused by phasing change with dual antenna, resulting in the amplitude and phase shift, was also observed. The active control of RF output facilitates the precise control of plasma profiles and greatly benefits future experimental exploration.

Spatiotemporal information on individual trajectories in urban rail transit is important for operational strategy adjustment, personalized recommendation, and emergency command decision-making. However, due to the lack of journey observations, it is difficult to accurately infer unknown information from trajectories based only on AFC and AVL data. To address the problem, this paper proposes a spatiotemporal probabilistic graphical model based on adaptive expectation maximization attention (STPGM-AEMA) to achieve the reconstruction of individual trajectories. The approach consists of three steps: first, the potential train alternative set and the egress time alternative set of individuals are obtained through data mining and combinatorial enumeration. Then, global and local potential variables are introduced to construct a spatiotemporal probabilistic graphical model, provide the inference process for unknown events, and state information about individual trajectories. Further, considering the effect of missing data, an attention mechanism-enhanced expectation-maximization algorithm is proposed to achieve maximum likelihood estimation of individual trajectories. Finally, typical datasets of origin-destination pairs and actual individual trajectory tracking data are used to validate the effectiveness of the proposed method. The results show that the STPGM-AEMA method is more than 95% accurate in recovering missing information in the observed data, which is at least 15% more accurate than the traditional methods (i.e., PTAM-MLE and MPTAM-EM).

Objective: Tai Chi (TC) is a complementary therapy for knee osteoarthritis (KOA). Although systematic reviews (SRs) and meta-analyses (Mas) of efficacy studies have been published, the results remain uncertain, and their quality has not yet been fully evaluated. Here, we summarize the existing SRs/Mas, evaluate their quality and level of evidence, and provide a reference for the effectiveness of TC. Methods: SRs/Mas of TC therapy for KOA published before February 2023 were retrieved from eight databases in Chinese and English. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, and the Risk of Bias in Systematic (ROBIS) scale were used to assess methodological quality, reporting quality, and risk of bias. Results: Seven SRs/Mas were finally included. One was deemed high quality by AMASTAR-2, while the rest were of critically low quality. In the PRISMA2020 assessment, the response rate of “Yes” for Q7, Q15, Q22, Q24, and Q27 was less than 50%. In the ROBIS assessment, three reports in Phase 3 were high risk and four were low risk. In the efficacy assessment, TC has shown varying degrees of improvement in physical function, pain, stiffness, 6-minute walk test, mental quality of life, TUG, and balance in patients with KOA. Conclusion: TC effectively treats KOA-associated pain, stiffness, body function, and mental quality of life. However, the low methodological quality of the studies and the high risk of migration reduced their reliability. Therefore, these conclusions should be taken with caution. High-quality, large-sample research is needed to provide stronger and more scientific evidence.

Antibiotic resistance has become a serious threat to global public health and economic development. Rapid and accurate identification of a patient status for antimicrobial resistance (AMR) are urgently needed in clinical diagnosis. Here we describe the development of an assay method for activity fingerprinting of AMR β-lactamases using panels of 7 β-lactam antibiotics in 35 min. New Deli Metallo β-lactamase-1 (NDM-1) and penicillinase were demonstrated as two different classes of β-lactamases. The panel consisted of three classes of antibiotics, including: penicillins (penicillin G, piperacillin), cephalosporins (cefepime, ceftriaxone, cefazolin) and carbapenems (meropenem and imipenem). The assay employed a scheme combines the catalytic reaction of AMR β-lactamases on antibiotic substrates with a flow-injected thermometric biosensor that allows the direct detection of the heat generated from the enzymatic catalysis, and eliminates the need for custom substrates and multiple detection schemes. In order to differentiate classes of β-lactamases, characterization of the enzyme activity under different catalytic condition, such as, buffer composition, ion strength and pH were investigated. This assay could provide a tool for fast diagnosis of patient AMR status which makes possible for the future accurate treatment with selected antibiotics.

Genome-wide analyses of maize populations have clarified the genetic basis of crop domestication and improvement. However, limited information is available on how breeding improvement reshaped the genome in the process of the formation of heterotic groups. In this study, we identified a new heterotic group (X group) based on an examination of 512 Chinese maize inbred lines. The X group was clearly distinct from the other non-H&L groups, implying that X × HIL is a new heterotic pattern. We selected the core inbred lines for an analysis of yield-related traits. Almost all yield-related traits were better in the X lines than those in the parental lines, indicating that the primary genetic improvement in the X group during breeding was yield-related traits. We generated whole-genome sequences of these lines with an average coverage of 17.35× to explore genome changes further. We analyzed the identity-by-descent (IBD) segments transferred from the two parents to the X lines and identified 29 and 28 IBD conserved regions (ICRs) from the parents PH4CV and PH6WC, respectively, accounting for 28.8% and 12.8% of the genome. We also identified 103, 89, and 131 selective sweeps (SSWs) using methods that involved the π, Tajima’s D, and CLR values, respectively. Notably, 96.13% of the ICRs co-localized with SSWs, indicating that SSW signals concentrated in ICRs. We identified 171 annotated genes associated with yield-related traits in maize both in ICRs and SSWs. To identify the genetic factors associated with yield improvement, we conducted QTL mapping for 240 lines from a DH population (PH4CV × PH6WC, which are the parents of X1132X) for ten key yield-related traits and identified a total of 55 QTLs. Furthermore, we detected three QTL clusters both in ICRs and SSWs. Based on the genetic evidence, we finally identified three key genes contributing to yield improvement in breeding the X group. These findings reveal key loci and genes targeted during pedigree breeding and provide new insights for future genomic breeding.

White and thermal (brown and beige) adipose tissue energy storage and oxidative regulation pathways play a central role in maintaining the energy balance throughout the body, and the dysregulation of these pathways is closely related to glucose and lipid metabolism disorders and adipose tissue dysfunction, including obesity, chronic inflammation, insulin resistance, mitochondrial dysfunction, and fibrosis. Recent epigenetic studies have identified the novel regulatory element LSD1, which controls the above parameters, and have provided new mechanistic possibilities for re-encoding the fate and function of adipocytes. In this review, we outline the current advances in adipocyte metabolism in physiology and disease and discuss possible strategies for LSD1 to alter the phenotype of adipose tissue and thus influence energy utilization to improve metabolic health.

Abstract Background The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in colitis is unexplored. Results Here, we found RhoB was dramatically increased in colon tissues of ulcerative colitis (UC) patients and mice with DSS-induced colitis. Compared with wild type mice, RhoB +/− and RhoB −/− mice developed milder DSS-induced colitis and increased goblet cell numbers and IEC proliferation. Decreased RhoB promoted goblet cell differentiation and epithelial regeneration through inhibiting Wnt signaling pathway and activating p38 MAPK signaling pathway. Moreover, increased SCFA-producing bacteria and SCFA concentrations were detected in intestinal microbiome of both RhoB +/− and RhoB −/− mice and upregulated SCFA receptor expression was also observed. Conclusions Taken together, a higher level of RhoB is associated with UC, which also contributes to UC development through modulating cell signaling and altering intestinal bacterial composition and metabolites. These observations suggest that RhoB has potential as a biomarker and a treatment target for UC. Video Abstract

Abstract Background and aims The therapeutic efficacy of single-dose mesenchymal stromal cell (MSC) therapy for heart failure (HF) remains inconsistent. This study aimed to investigate whether infusion with two-dose human umbilical cord MSC (hUCMSCs) could be therapeutically superior to single-dose therapy in a rat model of dilated cardiomyopathy (DCM) and explored the underlying mechanisms. Methods Male Sprague–Dawley rats were intraperitoneally injected with doxorubicin (DOX) to establish a DCM model and randomized to intravenously receive single-dose or two-dose hUCMSCs at an interval of 14 days. Their left ventricular (LV) systolic and diastolic functions were analyzed by echocardiography. The percentages of Th1, Th2, Th17, and Treg cells in the heart, spleen, lymph nodes, and peripheral blood and the levels of serum cytokines in individual rats were analyzed by flow cytometry and cytometric bead assay, respectively. The degrees of cardiac fibrosis and cardiomyocyte apoptosis were examined by histology. The importance of indoleamine 2,3-dioxygenase (IDO), an activator of Treg differentiation, in the therapeutic effect of hUCMSCs on inflammation and heart function of rats was determined after induction of IDO over-expression (IDO-OE) using IFN-γ (1 ng/ml) and TNF-α (10 ng/ml) stimulation or silencing (IDO-KD) using small interfering RNA (siRNA) technology. Results Compared with the single dose, two-dose hUCMSCs were more effective in improving LV performance, attenuating cardiac dilation, reducing cardiomyocyte apoptosis and cardiac fibrosis. Two-dose hUCMSC therapy significantly increased Treg number in the heart and peripheral blood, accompanied by increased cardiac IDO expression. Compared with the control hUCMSCs, IDO-OE hUCMSCs significantly enhanced Treg and Th2 cell responses and decreased systemic Th17 cell responses and Th1 cell numbers in the mediastinal lymph nodes. Treatment with IDO-OE hUCMSCs significantly improved LV remodeling and dysfunction. However, treatment with IDO-KD hUCMSCs had opposite effects in rats. Conclusions Administration of two-dose hUCMSCs has better therapeutic effects than single-dose therapy for inhibiting myocardial inflammation to improve LV function in DCM rats. These effects are associated with upregulating IDO expression and its systemic anti-inflammatory activities.

Cubic rock salt can lower down or break the rare earth transition barrier through interstitial or vacancy defects owing to its great deformation and rotation flexibility. Here, we demonstrate that oxygen vacancies in SrO are induced by proper oxidization and atmosphere adjustment, resulting in defects with various depths and crystal field distortion. The thermally assisted tunneling from defects to 5D4 state and electronic population decrease on 5D3 state of Tb3+ are observed by the deformation of adjacent oxygen octahedral structure. Finally, the as-prepared SrO: 0.01 ​Tb3+ phosphors, commercial BaMgAl10O17: Eu2+ blue phosphor, and CaAlSiN3: Eu2+ red phosphor are mixed and coated onto 280 ​nm deep-ultraviolet LED chip to assemble white light-emitting LED device. The LEDs show CCT of 3850 ​K, 4136 ​K, and 4741 ​K, with color rendering index of 90.3, 90.8, and 92.1, respectively. These insights will advance the fundamental knowledge of crystal engineering in cubic rock salt, and enable new ways to manipulate energy transfer and electronic transition via defects.

IntroductionAlzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder that primarily affects older individuals. N7-methylguanosine (m7G) is a common RNA chemical modification that impacts the development of numerous diseases. Thus, our work investigated m7G-related AD subtypes and established a predictive model.MethodsThe datasets for AD patients, including GSE33000 and GSE44770, were obtained from the Gene Expression Omnibus (GEO) database, which were derived from the prefrontal cortex of the brain. We performed differential analysis of m7G regulators and examined the immune signatures differences between AD and matched-normal samples. Consensus clustering was employed to identify AD subtypes based on m7G-related differentially expressed genes (DEGs), and immune signatures were explored among different clusters. Furthermore, we developed four machine learning models based on the expression profiles of m7G-related DEGs and identified five important genes from the optimal model. We evaluated the predictive power of the 5-gene-based model using an external AD dataset (GSE44770).ResultsA total of 15 genes related to m7G were found to be dysregulated in patients with AD compared to non-AD patients. This finding suggests that there are differences in immune characteristics between these two groups. Based on the differentially expressed m7G regulators, we categorized AD patients into two clusters and calculated the ESTIMATE score for each cluster. Cluster 2 exhibited a higher ImmuneScore than Cluster 1. We performed the receiver operating characteristic (ROC) analysis to compare the performance of four models, and we found that the Random Forest (RF) model had the highest AUC value of 1.000. Furthermore, we tested the predictive efficacy of a 5-gene-based RF model on an external AD dataset and obtained an AUC value of 0.968. The nomogram, calibration curve, and decision curve analysis (DCA) confirmed the accuracy of our model in predicting AD subtypes.ConclusionThe present study systematically examines the biological significance of m7G methylation modification in AD and investigates its association with immune infiltration characteristics. Furthermore, the study develops potential predictive models to assess the risk of m7G subtypes and the pathological outcomes of patients with AD, which can facilitate risk classification and clinical management of AD patients.

Aims: The objectives of this study were to identify clinical predictors of the Traditional Chinese medicine (TCM) clinical index for diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, develop a clinical prediction model, and construct a nomogram. Methods: We collected the TCM clinical index from 3590 T2DM recruited at the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2019 to October 2020. The participants were randomly assigned to either the training group (n = 3297) or the validation group (n = 1426). TCM symptoms and tongue characteristics were used to assess the risk of developing DPN in T2DM patients. Through 5-fold cross-validation in the training group, the least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection. In addition, using multifactor logistic regression analysis, a predictive model and nomogram were developed. Results: A total of eight independent predictors were found to be associated with the DPN in multivariate logistic regression analyses: advanced age of grading (odds ratio/OR 1.575), smoke (OR 2.815), insomnia (OR 0.557), sweating (OR 0.535), loose teeth (OR 1.713), dry skin (OR 1.831), purple tongue (OR 2.278). And dark red tongue (OR 0.139). The model was constructed using these eight predictor's medium discriminative capabilities. The area under the curve (AUC) of the training set is 0.727, and the AUC of the validation set is 0.744 on the ROC curve. The calibration plot revealed that the model's goodness-of-fit is satisfactory. Conclusions: We established a TCM prediction model for DPN in patients with T2DM based on the TCM clinical index.

Abstract The conversion of CO2 into fuels and valuable chemicals is one of the central topics to combat climate change and meet the growing demand for renewable energy. Herein, we show that the formate dehydrogenase from Clostridium ljungdahlii (ClFDH) adsorbed on electrodes displays clear characteristic voltammetric signals that can be assigned to the reduction and oxidation potential of the [4Fe‐4S]2+/+ cluster under nonturnover conditions. Upon adding substrates, the signals transform into a specific redox center that engages in catalytic electron transport. ClFDH catalyzes rapid and efficient reversible interconversion between CO2 and formate in the presence of substrates. The turnover frequency of electrochemical CO2 reduction is determined as 1210 s−1 at 25 °C and pH 7.0, which can be further enhanced up to 1786 s−1 at 50°C. The Faradaic efficiency at −0.6 V (vs. standard hydrogen electrode) is recorded as 99.3% in a 2‐h reaction. Inhibition experiments and theoretical modeling disclose interesting pathways for CO2 entry, formate exit, and OCN− competition, suggesting an oxidation‐state‐dependent binding mechanism of catalysis. Our results provide a different perspective for understanding the catalytic mechanism of FDH and original insights into the design of synthetic catalysts.

A new type of resonant magnetic perturbation (RMP), generated by helical coils, is proposed for controlling the edge localized mode (ELM) in H-mode tokamak plasmas. The helical coil optimization utilizes the MARS-F code (Liu et al 2000 Phys. Plasmas 7 3681) computed linear resistive fluid response of the plasma to the applied RMP field. The optimal helical coils are found to be located near the outboard mid-plane of the torus, with relatively simple shape but tilted towards the equilibrium magnetic field line pitch. Compared to the window-frame ELM control coils, the optimal helical coils require 2–4 times less current, in order to achieve the same ELM control performance specified by various figures of merit adopted in this work. The results from the present study show a promising path forward in achieving ELM control with RMP fields in tokamak plasmas.

Kinetic equilibrium reconstructions make use of profile information such as particle density and temperature measurements in addition to magnetics data to compute a self-consistent equilibrium. They are used in a multitude of physics-based modeling. This work develops a multi-layer perceptron (MLP) neural network (NN) model as a surrogate for kinetic Equilibrium Fitting (EFITs) and trains on the 2019 DIII-D discharge campaign database of kinetic equilibrium reconstructions. We investigate the impact of including various diagnostic data and machine actuator controls as input into the NN. When giving various categories of data as input into NN models that have been trained using those same categories of data, the predictions on multiple equilibrium reconstruction solutions (poloidal magnetic flux, global scalars, pressure profile, current profile) are highly accurate. When comparing different models with different diagnostics as input, the magnetics-only model outputs accurate kinetic profiles and the inclusion of additional data does not significantly impact the accuracy. When the NN is tasked with inferring only a single target such as the EFIT pressure profile or EFIT current profile, we see a large increase in the accuracy of the prediction of the kinetic profiles as more data is included. These results indicate that certain MLP NN configurations can be reasonably robust to different burning-plasma-relevant diagnostics depending on the accuracy requirements for equilibrium reconstruction tasks.

ObjectiveTo establish a nomogram model incorporating markers of echocardiography and N-terminal pro brain natriuretic peptide (NT-proBNP) for predicting adverse outcomes of patent ductus arteriosus (PDAao) in very low birth weight infants and to evaluate the predictive values of the model.MethodsA prospective study was conducted for very low birth weight infants who were admitted from May 2019 to September 2020. An echocardiogram and blood NT-proBNP test were carried out in the first 48 h after birth, and the arterial duct remained open in all patients. Other data collected included clinical symptoms and infant characteristics. A nomogram model was established to predict the risk of PDAao (including severe BPD, IVH, NEC or death). Internal verifications were performed for the nomogram, and the discrimination and calibration of the model were evaluated by the C-index and calibration curve.ResultsEighty-two infants were enrolled and divided into an adverse outcome (AO) group and normal outcome (NO) group with 41 patients in each group. PDA diameter, PDA maximum flow velocity, left atrium diameter/aortic diameter (LA/AO) ratio and NT-proBNP level were independent risk factors for PDAao and were included in the nomogram model. The model presented good discrimination with a C-index of 0.917 (95% CI 0.859–0.975). The calibration curves in showed high consistency and indicated good Correspondence: between the event incidence predicted by the nomogram model and the true incidence of PDAao.ConclusionThe nomogram model incorporating the PDA diameter, PDA maximum flow velocity, LA/AO ratio and NT-proBNP level in the first 48 h could early predict the later occurrence of PDAao in very low birth weight infants.

BackgroundThe effects of angioplasty on intracranial atherosclerotic disease (ICAD)-related acute large-vessel occlusion stroke (LVOS) are unknown. We analyzed the efficacy and safety of angioplasty or stenting for ICAD-related LVOS and the optimal treatment duration.MethodsPatients with ICAD-related LVOS from a prospective cohort of the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemia Stroke registry were classified as follows: the early intraprocedural angioplasty and/or stenting (EAS) group was defined as the strategy using angioplasty or stenting without mechanical thrombectomy (MT) or one attempt of MT; the non-angioplasty and/or stenting (NAS) group, MT procedure without any angioplasty; and the late intraprocedural angioplasty and/or stenting (LAS) group, using same angioplasty techniques following two or more passes of MT. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days. Other efficacy outcomes included mRS scores 0–1, mRS 0–2, and successful recanalization. Death within 90 days, and symptomatic ICH were safety endpoints. We use propensity score method to diminish the effect of treatment-selection bias. The odds ratio of recanalization rate and mRS score among EAS, NAS, and LAS groups were examined by unadjusted and adjusted logistic regression analysis among unweighted samples and inverse probability of treatment weighting (IPTW) samples.ResultsWe divided 475 cases into three groups. Functional outcomes at 90 days were better in the EAS group than in the NAS and LAS groups. The proportion of mRS 0–1, mRS 0–2, and successful recanalization cases were the highest in the EAS group. However, after IPTW, mortality rate among the three groups were similar (EAS vs. NAS vs. LAS: 19.0 vs. 18.1 vs. 18.7%, p = 0.98) as well as symptomatic intracranial hemorrhage within 24 h however, mortality rate and symptomatic intracranial hemorrhage among the three groups were similar. Logistic regression analysis in unweighted samples and IPTW samples both showed that EAS group had better outcomes. IPTW-adjusted logistic regression analysis demonstrated that the EAS group had better outcomes (mRS 0–1) than the NAS group (adjusted odds ratio [aOR], 0.55; 95% confidence interval [CI]: 0.34–0.88, p = 0.01) and LAS (aOR, 0.39; 95% CI: 0.22–0.68, p = 0.001).ConclusionsAngioplasty and/or stenting should be performed at an early stage for ICAD-related acute LVOS.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Background: Delayed reocclusion (DR) after successful recanalization in acute basilar artery occlusion (BAO) patients, which is associated with clinical deterioration and poor outcome, has not been well studied. The current study is aimed to predict DR after successful endovascular therapy in acute BAO patients. Method: 187 consecutive patients presenting with acute BAO and undergoing endovascular treatment (EVT) were selected in Beijing Tiantan Hospital from January 2012 to July 2018. Computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) within 7 days of the thrombectomy was used to identify reocclusion of the target vessel. Multivariable logistic regression analysis was used to evaluate associated factors and clinical impact. Results: DR was observed in 17 of 169 successfully reperfused patients (10.1%). Patients with DR had higher frequency of intracranial atherosclerotic stenosis (ICAS) (94.1% vs. 61.8%; P = 0.01), higher frequency of intracranial angioplasty during EVT (88.2% vs. 57.2%; P = 0.02), lower frequency of stent-retriever use during EVT (52.9% vs. 78.9%; P = 0.03) and a lower proportion of modified Thrombolysis In Cerebral Infarction (mTICI) 3 reperfusion (41.2% vs. 78.3%; P

The development of high-throughput sequencing technology has made it possible to develop molecular markers such as EST-SSR from transcriptome sequences in non-model plants such as bulbous flowers. However, the EST-SSR markers that have been developed are weakly validated and low polymorphic due to the short read size and poor quality of the assembled sequences. This study therefore used the CandiSSR pipeline to identify 550 potential polymorphic SSR loci among 487 homologous unigenes based on the transcriptomic sequences of three varieties of colored calla lily, and 460 of these loci with appropriate flanking sequences were suitable for primer pairs design. A further validation with 200 randomly selected EST-SSRs demonstrated an increase of more than 30% and 100% in amplification validity and polymorphism, respectively, in comparison with our previous study. In addition, since most of the current varieties of colored calla lily are hybridized from a few species, which have low genetic diversity, we subsequently identified primary core germplasm for 160 colored calla lily accessions using the aforementioned 40 polymorphic EST-SSRs. It was concluded that the core germplasm containing 42 accessions derived from the M strategy incorporated into the software Power Core was the most representative of all 160 original germplasm, as evidenced by the preservation of 100% of the EST-SSR variation, with a higher level of genetic diversity and heterogeneity (Nei = 0.40, I = 0.66, PIC = 0.43). This study provides a practical example of polymorphism EST-SSR markers developed from multiple transcriptomes for non-model plants. A future breeding program for colored calla lily will also benefit from the core germplasm defined by those molecular markers.

Triphenyl phosphate (TPHP) is a widely used flame retardant and plasticizer and has been detected extensively in environmental media, wildlife and human bodies. Several epidemiological and animal studies have revealed that TPHP exposure is positively associated with glucose homeostasis disruption and diabetes. However, the effects of TPHP on hepatic glucose homeostasis and the underlying mechanisms remain unclear. The present work aimed to investigate the cytotoxicity and glucose metabolism disruption of TPHP and its metabolite diphenyl phosphate (DPHP) within hepatocytes. The cell viability assay undertaken on human normal liver (L02) cells showed that TPHP exhibited more potent hepatotoxicity than DPHP. RNA sequencing (RNA-seq) data showed that TPHP and DPHP presented different modes of toxic action. Insulin resistance is one of the predominant toxicities for TPHP, but not for DPHP. The insulin-stimulated glucose uptake and glycogen synthesis were impaired by TPHP, while DPHP exhibited no significant impairment on these factors. TPHP exposure induced endoplasmic reticulum (ER) stress, and the ER stress antagonist 4-PBA restored the impairment of insulin-stimulated glucose uptake and glycogen synthesis induced by TPHP. TPHP could also induce liver ER stress and insulin resistance in mice. Taken together, the results suggested that TPHP induces more potent insulin resistance through ER stress than its metabolite DPHP.

The mechanical state of the process zone at the crack-tip is one of the main factors that affect crack initiation and growth in the long-term safe operation of oil and gas pipelines. Many tests showed that the stress and strain fields in the fracture-tip process zone can be used to define the crack propagation behavior. The goal of this paper is to improve the Hutchinson, Rice, and Rosengren (HRR) model by using cubic asymptotic polynomials to describe the stress-strain field at the crack-tip, as well as to validate the model by a thorough comparison with full-scale burst test results that account for the fracture zone's mechanical properties. The asymptotic polynomial elastic viscoplastic distribution model of stress-strain displacement field at the crack-tip is developed, and the HRR method is modified reasonably. The crack propagation test of the X80 steel pipeline in the burst test site is carried out. Experimentally, the distribution of stress and strain field in the crack-tip process zone of the X80 testing pipeline is obtained, then compared with the theoretical solution. The final results showed consistency, and the elastic viscoplastic model matched well with the running fracture test data for the X80 gas pipeline. Besides, the stress and strain fields distribution in the crack-tip process zone is verified through the full-scale test of the X80 steel pipeline, which provides a theoretical basis for the integrity evaluation of the steel pipeline.

The main aim of this paper is to explore new approaches to structural design and to solve the problem of lightweight design of structures involving multivariable and multi-objectives. An integrated optimization design methodology is proposed by combining intelligent optimization algorithms with generative design. Firstly, the meta-model is established to explore the relationship between design variables, quality, strain energy, and inherent energy. Then, employing the Non-dominated Sorting Genetic Algorithm III (NSGA-III), the optimal frameworks of the structure are sought within the entire design space. Immediately following, a structure is rebuilt based on the principle of cooperative equilibrium. Furthermore, the rebuilt structure is integrated into a generative design, enabling automatic iteration by controlling the initial parameter set. The quality and rigidity of the structure under different reconstructions are evaluated, resulting in solution generation for structural optimization. Finally, the optimal structure obtained is validated. Research outcomes indicate that the quality of structures generated through the comprehensive optimization method is reduced by 27%, and the inherent energy increases by 0.95 times. Moreover, the overall structural deformation is less than 0.003 mm, with a maximum stress of 3.2 MPa—significantly lower than the yield strength and meeting industrial usage standards. A qualitative study and analysis of the experimental results substantiate the superiority of the proposed methodology for optimized structural design.

In the structural design of serial robots, topology and dimensional parameters design are independent, making it challenging to achieve synchronous optimization design between the two. To address this issue, a topology-and-dimension-parameter integrated optimization method (TPOM) is proposed by setting critical variables to connect topology layout and dimensional features. Firstly, the topology layout is extracted by the edge detection technique. Structural manufacturability reconstruction is conducted by measuring the dimensions of the layout through a program. Additionally, for the reconstructed structural layout, critical variables are set using three-dimensional software (SOLIDWORKS2021). The experiments primarily involve critical variables, quality, and deformation as variables. Then, the response surface methodology is selected to construct the stiffness–mass metamodel, and based on this, the structural deformation is analyzed. Lastly, the multi-objective genetic algorithm (MOGA) is employed to optimize the critical variables, and an optimized structure is established for validation. The results indicate that the proposed method (TPOM) reduces the mass of the structure by 15% while maintaining its stiffness. In addition, the deformation of the whole structure is less than 0.352 mm, which meets the requirements of industrial applications. Through quantitative analysis of the experimental results, the feasibility and superiority of the proposed method have been demonstrated.

Abstract Background This study aimed to investigate the transmission of cytomegalovirus (CMV) via breast milk in low birth weight (LBW) and premature infants and its effects. Methods PubMed, Medline, Cochrane Library, and Embase were searched for studies (without language and time restriction) published before March 27, 2020, that examined the effect of CMV transmitted by breast milk on LBW and premature infants. The rates of breast milk-acquired CMV infection, CMV-related symptoms, and CMV-related sepsis-like syndrome (CMV-SLS) in LBW and premature infants were pooled from each study. Results Eighteen studies with 1920 LBW and premature infants were included. The pooled CMV infection rate from breast milk for infants fed untreated breast milk was significantly higher than those fed frozen breast milk [19.3, 95% confidence interval (CI) = 11.8–29.9% vs. 13.5, 95% CI = 8.0–22.0%, P

IntroductionHigh intake of dietary fiber is associated with lower incidence of cardiovascular diseases. Dietary fiber, functions as a prebiotic, has a significant impact on intestinal bacteria composition and diversity. The intestinal flora and metabolites generated by fermentation of dietary fiber not only affect the health of intestine but also play a role in many extra-intestinal diseases, such as obesity, diabetes and atherosclerosis. However, the role and the mechanism by which a high fiber diet contributes to the development of myocardial infarction is still unclear.Methods and resultsHere we used an in vivo mouse model to investigate whether dietary fiber intake could protect against myocardial infarction. Our study demonstrated high fiber diet significantly improved cardiac function, reduced infarct size and prevented adverse remodeling following myocardial infarction. The protective effects of high fiber diet had a strong relation with its attenuation of inflammation. Moreover, we observed that high fiber diet could modulate the composition of intestinal flora and differentially impacted metabolites production, including the biosynthesis of bile acids and linoleic acid metabolism.ConclusionOverall, the findings of this study provided mechanistic insights into the curative effect of dietary fiber on myocardial infarction with a specific emphasis on the potential role of microbiota-metabolism-immunity interactions.

Calla lily (Zantedeschia spp.) have great aesthetic value due to their spathe-like appearance and richness of coloration. However, embryonic callus regeneration is absent from its current regeneration mechanism. As a result, constructing an adequate and stable genetic transformation system is hampered, severely hindering breeding efforts. In this research, the callus induction effectiveness of calla lily seed embryos of various maturities was evaluated. The findings indicated that mature seed embryos were more suitable for in vitro regeneration. Using orthogonal design experiments, the primary elements influencing in vitro regeneration, such as plant growth regulators, genotypes, and nanoscale materials, which was emergent uses for in vitro regeneration, were investigated. The findings indicated that MS supplemented with 6-BA 2 mg/L and NAA 0.1 mg/L was the optimal medium for callus induction (CIM); the germination medium (GM) was MS supplemented with 6-BA 2 mg/L NAA 0.2 mg/L and 1 mg/L CNTs, and the rooting medium (RM) was MS supplemented with 6-BA 2 mg/L NAA 0.7 mg/L and 2 mg/L CNTs. This allowed us to verify, in principle, that the Agrobacterium tumefaciens-mediated genetic transformation system operates under optimal circumstances using the GUS reporter gene. Here, we developed a seed embryo-based genetic transformation regeneration system, which set the stage for future attempts to create new calla lily varieties.

Uncovering the dynamics of active sites in the working conditions is important yet challenging. Here the authors identify dynamic-coupling oxygen on atomically dispersed iridium sites during oxygen evolution reaction using in situ techniques.

Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca2+ through L-type Ca2+ channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca2+/calmodulin/MLCK/myosin II pathway.

The ornamental crabapple is a multipurpose landscaping tree that bears brilliant fruit throughout the winter. However, whether or not its fruit persists after maturation is specifically correlated to cultivar characteristics. In this work, we screened two different types that display fruit-retention (“Donald Wyman,” “Red Jewel,” and “Sugar Tyme”) and fruit-abscission (“Radiant” and “Flame”) in Northern China across the whole winter using multi-year successional records. Fruit-abscission was determined predominantly by the abscission zone established at the base of the pedicel, regardless of fruit size and pedicel length, according to the results of the comparative research. The primary physiological rationale was the accumulation of hydrolases activity (pectinesterase, cellulase, polygalacturonase, and β-glucosidase). Comparative transcriptomics further identified a number of upregulated DEGs involved in the synthesis pathways of canonical phytohormones, such as ethylene, jasmonic acid, abscisic acid, and cytokinin, as well as 12 transcription factors linked in downstream signaling in fruit-abscission cultivars. Finally, a model incorporating multi-layered modulation was proposed for the fruit abscission of ornamental crabapple. This study will serve as the foundation for the development of fruit-viewing crabapples that have an extended ornamental lifetime.