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Abstract Background Approximately 25–30% of patients with acute myeloid leukemia (AML) have FMS-like receptor tyrosine kinase-3 (FLT3) mutations that contribute to disease progression and poor prognosis. Prolonged exposure to FLT3 tyrosine kinase inhibitors (TKIs) often results in limited clinical responses due to diverse compensatory survival signals. Therefore, there is an urgent need to elucidate the mechanisms underlying FLT3 TKI resistance. Dysregulated sphingolipid metabolism frequently contributes to cancer progression and a poor therapeutic response. However, its relationship with TKI sensitivity in FLT3-mutated AML remains unknown. Thus, we aimed to assess mechanisms of FLT3 TKI resistance in AML. Methods We performed lipidomics profiling, RNA-seq, qRT-PCR, and enzyme-linked immunosorbent assays to determine potential drivers of sorafenib resistance. FLT3 signaling was inhibited by sorafenib or quizartinib, and SPHK1 was inhibited by using an antagonist or via knockdown. Cell growth and apoptosis were assessed in FLT3-mutated and wild-type AML cell lines via Cell counting kit-8, PI staining, and Annexin-V/7AAD assays. Western blotting and immunofluorescence assays were employed to explore the underlying molecular mechanisms through rescue experiments using SPHK1 overexpression and exogenous S1P, as well as inhibitors of S1P2, β-catenin, PP2A, and GSK3β. Xenograft murine model, patient samples, and publicly available data were analyzed to corroborate our in vitro results. Results We demonstrate that long-term sorafenib treatment upregulates SPHK1/sphingosine-1-phosphate (S1P) signaling, which in turn positively modulates β-catenin signaling to counteract TKI-mediated suppression of FLT3-mutated AML cells via the S1P2 receptor. Genetic or pharmacological inhibition of SPHK1 potently enhanced the TKI-mediated inhibition of proliferation and apoptosis induction in FLT3-mutated AML cells in vitro. SPHK1 knockdown enhanced sorafenib efficacy and improved survival of AML-xenografted mice. Mechanistically, targeting the SPHK1/S1P/S1P2 signaling synergizes with FLT3 TKIs to inhibit β-catenin activity by activating the protein phosphatase 2 A (PP2A)-glycogen synthase kinase 3β (GSK3β) pathway. Conclusions These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

ABSTRACT Aims/Introduction Type 2 diabetes mellitus is a major metabolic disease that seriously endangers life and health, but women with gestational diabetes mellitus are at increased risk for developing type 2 diabetes mellitus. This study aimed to evaluate the effectiveness of postpartum lifestyle intervention on the prevention of type 2 diabetes mellitus, and the effect of lifestyle intervention on glycemic outcomes and anthropometric measures. Materials and Methods We searched PubMed and other databases to retrieve articles published before May 21, 2023, on randomized controlled trials of postnatal lifestyle interventions (diet and/or physical activity) in women with gestational diabetes mellitus. We estimated the pooled odds ratios using fixed or random effects models and conducted a subgroup analysis of the different intervention methods to explore differences in the different lifestyle interventions. Results The review included 17 randomized controlled trials. Overall, lifestyle changes started after a pregnancy complicated by gestational diabetes mellitus an 11% (RR = 0.89; 95% CI: 0.74–1.07) reduction in diabetes risk; significant differences were found for weight (MD = −1.33; 95% CI: [−1.76; −0.89], P

Abstract Background Postoperative hypoparathyroidism caused by parathyroid injury is a problem faced by thyroid surgeons. The current technologies for parathyroid imaging all have some defects. Methods Patients with differentiated thyroid carcinoma (DTC) who underwent unilateral thyroidectomy plus ipsilateral central lymph node dissection were recruited. We dissected the main trunk of the superior thyroid artery entering the thyroid gland and placed the venous indwelling tube into the artery. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results A total of 132 patients enrolled in this single-arm clinical trial, 105 of them completed retrograde catheterization via the superior artery. The sensitivity was 69.23 and 83.33% respectively. The specificity was 72.91 and 64.89%. The accuracy was 72.91 and 64.89%. The PPV was 85.71 and 81.08%. The NPV was 22.58 and 45.45%. There were no patients with allergic reactions to the methylene blue, or methylene blue toxicity. Conclusions Retrograde injection of methylene blue via the superior thyroid artery is an effective and safe method to visualize parathyroid glands. This method can accurately locate the target organ by ultraselecting the blood vessel and injecting the contrast agent while avoiding background contamination and reducing the amount of contrast agent. Trial registration Clinical trial registration numbers and date of registration: ChiCTR2300077263、02/11/2023.

Background and aim: This study applied Six Sigma metrics to facilitate the quality control (QC) review for hospital glucose meters. Materials and methods: QC data from a period of six months on all hospital glucose meters were extracted from the data management system. Sigma values for each meter at two QC levels were calculated and evaluated each month by combining the imprecision, the absolute bias between the meter mean and all-meter mean, and the standards from ISO 15179:2013. The effectiveness of using Sigma values in identifying meters with possible quality problems for further Levey-Jennings QC chart review was assessed. Results: More than 80 % of the meter's Sigma values within the six months were greater than 4 at either QC level. At the high QC level, twice as many Sigma values were below 4 than the low QC level. Including Sigma values 4, 3.5 or 3 in the criteria for the QC review reduced the number of chart review to 32.8 %, 11.2 % or 3.5 %, respectively. Conclusions: The majority of the glucose meters examined in this study demonstrated optimal Sigma values. The Sigma metrics-based approach could be a valuable tool to guide an effective QC review of glucose meters for quality improvement.

Summary: Conventional type 1 dendritic cells (cDC1s) are critical for innate sensing of cancer, yet they are scarce in the tumor microenvironment (TME). Here, we present a protocol to identify and isolate cDC1 subsets from murine implantable tumors for subsequent transcriptomic profiling using a flow sorting-based strategy. We describe steps for cell culture of mouse tumors, tumoral growth, dissociation and isolation of tumoral cells, extracellular staining, and cell sorting. We then detail procedures for RNA isolation, mRNA library preparation, and sequencing.For complete details on the use and execution of this protocol, please refer to Papadas et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Nucleophosmin 1 (NPM1) gene‐mutated acute myeloid leukemia (NPM1mut AML) is classified as a subtype with a favorable prognosis. However, some patients fail to achieve a complete remission or relapse after intensified chemotherapy. Genetic abnormalities in concomitant mutations contribute to heterogeneous prognosis of NPM1mut AML patients. Methods In this study, 91 NPM1‐mutated and FLT3‐ITD wild‐type (NPM1mut/FLT3‐ITDwt) AML patients with intermediate‐risk karyotype were enrolled to analyze the impact of common genetic co‐mutations on chemotherapeutic outcome. Results Our data revealed that TET1/2 (52/91, 57.1%) was the most prevalent co‐mutation in NPM1mut AML patients, followed by IDH1/2 (36/91, 39.6%), DNMT3A (35/91, 38.5%), myelodysplastic syndrome related genes (MDS‐related genes) (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 genes) (35/91, 38.5%), FLT3‐TKD (27/91, 29.7%) and GATA2 (13/91, 14.3%) mutations. Patients with TET1/2mut exhibited significantly worse relapse‐free survival (RFS) (median, 28.7 vs. not reached (NR) months; p = 0.0382) compared to patients with TET1/2wt, while no significant difference was observed in overall survival (OS) (median, NR vs. NR; p = 0.3035). GATA2mut subtype was associated with inferior OS (median, 28 vs. NR months; p

This paper focuses on the mechanical behaviour, seismic application in steel frame connections and steel structure of shape memory alloy (SMA) plates. This study commenced by examining the hysteretic response of SMA plates subjected to cyclic tension tests, considering two different loading paths. Subsequently, a self-centring steel frame connection equipped with SMA plates and washers (SC-PW) was examined via quasi-static cyclic loading tests, and comparatively satisfactory self-centring behaviour was observed. However, the degradation of the initial stiffness of the SC-PW due to an initial imperfection was observed. An improvement strategy was proposed to overcome the degradation of the hysteretic behaviour (e.g., initial stiffness) of the SC-PW. Disc springs with a larger stiffness and preloads were introduced to overcome the degradation of the initial stiffness of the SC-PW, and the validation was confirmed via detailed finite element (FE) analyses. To improve the computation efficiency, a simplified FE model was developed to reproduce the hysteretic responses of the connection. Based on the simplified FE model, a six-storey prototype structure, i.e., a self-centring hybrid steel frame (SCHSF), equipped with the improved connection was developed, and the structural dynamic responses were investigated via nonlinear response history analyses, where mainshock–aftershock sequences were considered. The influence of the SMA material properties on the seismic behaviour of the prototype structure was investigated.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1–28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P

China’s coal-fired power plants emit over 5.7 billion tons of CO2 annually. To realize the dual carbon goals in time, it is necessary to reduce the carbon emissions of coal-fired power plants. Microalgae carbon fixation can efficiently absorb CO2 through photosynthesis and convert it into biomass, which is a highly promising technology for carbon reduction in coal-fired power plants. Light guide tubes can flexibly change the light distribution in a photobioreactor, while optical fibers can transmit light centrally with low light loss. Therefore, a microalgae photobioreactor with an optical fiber/light guide tube is proposed to expand the light-receiving area of the microalgae suspension, increase the light-harvesting of microalgal cells, and promote carbon fixation via microalgae photosynthesis. The optical simulation software was used to trace the propagation of light in the optical fiber/light guide tube, and the light intensity distribution of the tube wall was obtained. Microalgae cultivation experiments were conducted in various photobioreactors and under different input light energy conditions. The change trends of biomass yield, carbon sequestration rate, and chlorophyll content were obtained, and the impact of built-in optical fiber /light guide tubes on carbon fixation via microalgae was investigated. Results indicated that the light intensity emitted from the optical fiber terminal decreased precipitously from 30 mm to 140 mm along the side of the light guide tube. Additionally, the tube exhibited a concentrated light-emitting range. Adding a conical reflector to reflect the transmitted light at the tube bottom and designing a stepped optical fiber to emit input light from different steps can optimize the light-emitting effect of the light guide tube and make the light distribution in the microalgae photobioreactor more uniform, so that the microalgal cells far away from the light source area can receive the light energy to photosynthesize and fix carbon. At a light input of 3.3 W/L, the minimum light intensity on the side surface of the light guide comprising a two-stage stepped optical fiber and conical reflector was 47 μmol/(m2·s). The average light intensity was 64 μmol/(m2·s), representing a 2.6-fold increase compared to the light guide tube lacking both the optical fiber and any enhancements beyond its top section. After seven days of cultivation, the microalgae concentration in the stepped fiber photobioreactor (SF-PBR) could reach 1.9 g/L, which was 46.2% higher than that of the photobioreactor inserted with flat-end fiber optic light guide (FF-PBR) and 111.1% higher than that of the photobioreactor with only top-fed light (LG-PBR). When the light input was escalated to 5.0 W/L, a high microalgae concentration of 2.8 g/L was achieved at 7 d. Meanwhile, the average carbon sequestration rate of 608.3 mg/(L·d) was obtained, exhibiting 1.9-fold augmentation compared to the control LG-PBR.

The dynamic matrix square root (DMSR) problem is a recurring nonlinear challenge in many engineering disciplines. Although the original zeroing neural network (OZNN) shows potential for handling such problems, it faces challenges in robustness and convergence. To address these limitations, we developed a simplified activation function, the simplified signal power activation function (SSPAF), which accelerates convergence. Building on this, we introduced a dual integral enhancement term, leading to the design of the rapid dual integral neural dynamic (R-DIND) model to further enhance convergence accuracy, speed, and robustness. Mathematically, the R-DIND model aligns more closely with calculus principles, showcasing unique advantages over existing ZNN models. Theoretical analysis and extensive experiments demonstrated that the R-DIND model has inherent structural advantages over the RNDAC model. Results showed that the R-DIND model improves residual precision from $10^{-2}$ to $10^{-6}$ under the same noise conditions. Furthermore, its robustness and applicability were confirmed when applied to higher-order and more complex matrix problems with harmonic noise.

Matrix inversion is a fundamental operation utilized across numerous disciplines such as mathematics, engineering, and control theory. The original zeroing neural network (OZNN) method has proven effective in tackling the challenge of time-varying matrix inversion (TVMI) under ideal conditions. The integration-enhanced zeroing neural network (IEZNN) is commonly used to handle TVMI issues in the presence of various types of noise. In this paper, we have enhanced the IEZNN model’s tolerance to noise by introducing a dual integral component, resulting in the dual noise tolerant zeroing neural network (DNTZNN) model. We have further improved this model by incorporating a positive odd activation function to create the triple noise tolerant zeroing neural network (TNTZNN). This advancement enables the TNTZNN to effectively solve TVMI problems despite various noise disturbances. Consequently, the TNTZNN model demonstrates excellent convergence and robustness even under noisy conditions. Furthermore, theoretical analysis grounded on the Lyapunov theorem validates the convergence and resilience of the TNTZNN model against diverse forms of noise. Computational simulations further substantiate the superior efficacy of the proposed TNTZNN model in resolving TVMI problems.

Time-varying problems are prevalent in engineering, presenting a significant challenge due to the fluctuations in parameters and goals at different time points. The zeroing neural network (ZNN), a specialized form of recurrent neural network (RNN) developed by Zhang et al., has gained attention for its rapid convergence speed and robustness making it a valuable tool for real-time solving of diverse time-varying problems. This review article explores the practical applications of ZNN across various domains in the past two decades, specifically focusing on robot manipulator path tracking, motion planning, and chaotic systems. The comprehensive scope of this review is essential for researchers and beginners looking to grasp the efficacy of ZNN in addressing practical challenges in diverse fields.

Abstract The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

Abstract Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well‐established repressive activity, ETO2 directly activates transcription of MYB, among other genes. The ETO2‐activated signature is associated with a poorer prognosis in erythroleukemia but also in other acute myeloid and lymphoid leukemia subtypes. Mechanistically, ETO2 colocalizes with EP300 and MYB at enhancers supporting the existence of an ETO2/MYB feedforward transcription activation loop (e.g., on MYB itself). Both small‐molecule and PROTAC‐mediated inhibition of EP300 acetyltransferases strongly reduced ETO2 protein, chromatin binding, and ETO2‐activated transcripts. Taken together, our data show that ETO2 positively enforces a leukemia maintenance program that is mediated in part by the MYB transcription factor and that relies on acetyltransferase cofactors to stabilize ETO2 scaffolding activity.

Abstract Background Myeloid cells play critical roles in the regulation of myocardial injury and repair. Clonal hematopoiesis (CH)‐related mutations in genes, such as Ten‐eleven Translocation 2 (TET2), can impair myeloid cells and are associated with increased risk of cardiovascular disease (CVD). How Tet2 loss‐of‐function (LOF) impacts myeloid cells and disrupts normal myocardial repair remains unclear. Methods We established ischemia‐induced myocardial infarction (MI) in a myeloid‐specific Tet2‐deficient mouse model. The echocardiographic assessment was conducted to evaluate the cardiac function. Histological analysis was performed to evaluate morphological changes in infarcted areas and fibrosis. To monitor the dynamic changes of myeloid cells in cardiac tissues during cardiac remodeling after MI, we performed longitudinal analysis on subsets of myeloid cells using flow cytometry. We performed immunofluorescence (IF) staining to examine the DNA damage and genome instability caused by Tet2 LOF. Gene expression was assessed by real‐time qRT‐PCR. Stimulator of Interferon Genes (STING) pathway activation was assessed using various methods, including Western blotting, flow cytometry, ELISA and IF staining of key signaling proteins involved in this pathway. Additionally, H‐151 was used as a pharmacological tool to antagonize augmented STING activation in the murine MI model. Results We observed a substantial increase of neutrophils in the post‐MI mice, which contributes to adverse outcomes during heart repair. Mechanistically, Tet2‐deficient myeloid cells exhibited increased genome instability, accompanied with augmented activation of the STING pathway. Furthermore, the use of H‐151 a covalent STING binder that targets the cysteine residue at position 91 and functions as a potent STING antagonist, led to a substantial decrease in neutrophil populations in Tet2‐deficient mice following myocardial infarction, thereby reversing adverse cardiac outcomes. Conclusion Our novel findings establish the rationale for targeting the cGAS‐STING pathway as a promising therapeutic strategy to mitigate cardiovascular disease risk in individuals with clonal hematopoiesis harboring TET2 loss‐of‐function mutations. Highlights Myeloid‐specific Tet2 depletion promotes neutrophil expansion upon myocardium infarction (MI); Tet2‐deficient myeloid cells exhibit increased genome instability and cGAS‐STING overactivation; STING antagonist H‐151 treatment reduces neutrophil expansion in Tet2‐deficient mice after MI and mitigates deleterious cardiac outcomes.

BackgroundThe rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth.ObjectiveThis study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors.MethodsFor this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use.ResultsAmong the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14–3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43–7.64; 95%CI: 2.36–20.42; p

Carotenoids are essential components in tea quality, contributing to leaf color and aroma. However, little information about carotenoids in different tea cultivars and their biosynthesis regulation mechanism during leaf development is known. Here we analyzed carotenoids by HPLC in the buds and leaves of 113 tea cultivars harvested on the same day. By profile clustering, carotenoids were divided into five groups. Same group cultivars displayed divergence in the total content of carotenoids but a similar molar ratio. To figure out the molecular mechanisms of this phenomenon, we further characterized all functional lycopene cyclases, which are the branch point of the carotenoid biosynthesis pathway. Two β-lycopene cyclases (CsLCYB1 and CsLCYB2) and one ε-lycopene cyclase (CsLCYE1) were cloned. Subcellular localization analysis showed that all cloned CsLCYs were localized in plastids. Enzyme activity assays in E. coli indicated both CsLCYBs catalyzed lycopene into β-carotene, and CsLCYE1 produced δ-carotene and ε-carotene. We found CsLCYB1 and CsLCYE1 predominantly expressed in leaf, while CsLCYB2 was mainly expressed during flowering stages. Suppression by antisense oligonucleotides reduced CsLCYB1 and CsLCYE1 transcripts and led to reduction of both β,β-branch and β,ε-branch carotenoids in leaf. The expression levels of CsLCYB1 showed a significant positive correlation with β,β-branch carotenoids in leaf. Our study provides carotenoid profiles of different tea cultivars, which can assist tea producers in selecting cultivars of interest. Meanwhile, we proposed the molecular mechanism of carotenoids reflecting the tenderness of tea plant leaf from a metabolic flux perspective, and suggested lycopene cyclase that could be applied to the breeding of tea varieties with different branch carotenoids.

Abstract To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.

Abstract Background Notopterygii Rhizoma et Radix (NRR) is commonly used for the treatment of inflammation-linked diseases. Phenethylferulate (PF) is high content in NRR crude, but its anti-inflammatory effect remains unclear. Therefore, we aimed to investigate the anti-inflammatory properties of PF and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods The effect of PF on cell viability was measured by MTT assay. The anti-inflammatory properties of PF were studied by detecting the levels of inflammatory mediators and cytokines using enzyme-linked immunosorbent assay (ELISA). Furthermore, the anti-inflammatory mechanisms of PF were determined by Western blot analysis. Results PF was not cytotoxic to RAW 264.7 macrophages at the concentrations of below 48 μM. ELISA showed that PF conspicuously inhibited overproduction of prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Western blot analysis showed that PF remarkably suppressed overproduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), the phosphorylation of inhibitor of NF-κB kinase α (IκB-α), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, as well as the degradation and subsequent nuclear translocation of p65. Conclusions PF is a potent inhibitor of inflammation acting on nuclear factor kappa-B (NF-κB), Akt and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-stimulated RAW 264.7 macrophages. This work provides evidence for the suitability of PF as a therapeutic candidate for the management of inflammatory-mediated immune disorders.

Abstract Gestational diabetes mellitus (GDM) is a major complication of pregnancy. GDM is associated with a higher risk of adverse pregnancy outcomes (APO). The purpose of this study was to assess the association between third-trimester platelet to lymphocyte ratio (PLR) and high-sensitivity C-reactive protein (hsCRP) concentration and the risk of APO in GDM pregnant women. This study selected 406 non-elderly gestational diabetes patients diagnosed in the Renmin Hospital of Wuhan University from May 2021 to February 2023 as the research objects. According to the presence or absence of APO, they were divided into an APO group (n = 171) and a non-APO group (n = 235). Logistic regression model to evaluate the correlation between PLR and hsCRP and APO in women with GDM; Restricted cubic spline analyses was used to explore nonlinear correlations between PLR or hsCRP and the risk of APO; ROC curve analysis of the diagnostic performance of PLR and hsCRP for APO in women with GDM. APO occurred in 171 of the 406 included participants. Compared with the non-APO group, patients in the APO group had higher PLR and hsCRP levels. The incidence of APO was positively associated with PLR and the hsCRP level in each logistic regression model (P

Abstract Background Gastropoda, the largest class within the phylum Mollusca, houses diverse gut microbiota, and some gastropods serve as intermediate hosts for parasites. Studies have revealed that gut bacteria in gastropods are associated with various biological aspects, such as growth, immunity and host–parasite interactions. Here, we summarize our current knowledge of gastropod gut microbiomes and highlight future research priorities and perspectives. Methods A literature search was undertaken using PubMed, Web of Science and CNKI for the articles on the gut microbiota of gastropods until December 31, 2022. We retrieved a total of 166 articles and identified 73 eligible articles for inclusion in this review based on the inclusion and exclusion criteria. Results Our analysis encompassed freshwater, seawater and land snails, with a specific focus on parasite-transmitting gastropods. We found that most studies on gastropod gut microbiota have primarily utilized 16S rRNA gene sequencing to analyze microbial composition, rather than employing metagenomic, metatranscriptomic, or metabolomic approaches. This comprehensive review provided an overview of the parasites carried by snail species in the context of gut microbiota studies. We presented the gut microbial trends, a comprehensive summary of the diversity and composition, influencing factors, and potential functions of gastropod gut microbiota. Additionally, we discussed the potential applications, research gaps and future perspectives of gut microbiomes in parasite-transmitting gastropods. Furthermore, several strategies for enhancing our comprehension of gut microbiomes in snails were also discussed. Conclusions This review comprehensively summarizes the current knowledge on the composition, potential function, influencing factors, potential applications, limitations, and challenges of gut microbiomes in gastropods, with a specific emphasis on parasite-transmitting gastropods. These findings provide important insights for future studies aiming to understand the potential role of gastropod gut microbiota in controlling snail populations and snail-borne diseases. Graphical abstract

Benzo[a]pyrene (B[a]P) is a food contaminant toxic for cardiovascular diseases. The nuclear translocation of Arylhydrocarbon receptor (AhR) plays an important role in B[a]P-induced oxidative stress and vascular diseases. We confirmed that B[a]P promoted ROS production in vascular smooth muscle cells (VSMCs) in vitro and in vivo, associated with the nuclear translocation of AhR. It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR. However, from the posttranslational modification level, the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear. Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation, and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs, suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR. Next, siRNAs of O-linked N-acetylglucosamine transferase (OGT), O-GlcNAcase (OGA) and OGA inhibitor PUGNAc were used. SiOGT blocks but siOGA and PUGNAc promote B[a]P -dependent AhR nuclear translocation and oxidative stress. Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR. Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress. Our findings highlight a new perspective for AhR nuclear translocation regulated by the competitive modification between phosphorylation and O-GlcNAcylation.

Abstract Ca2+ signal-generation through inter-membrane junctional coupling between endoplasmic reticulum (ER) STIM proteins and plasma membrane (PM) Orai channels, remains a vital but undefined mechanism. We identify two unusual overlapping Phe-His aromatic pairs within the STIM1 apical helix, one of which (F394-H398) mediates important control over Orai1-STIM1 coupling. In resting STIM1, this locus is deeply clamped within the folded STIM1-CC1 helices, likely near to the ER surface. The clamped environment in holo-STIM1 is critical—positive charge replacing Phe-394 constitutively unclamps STIM1, mimicking store-depletion, negative charge irreversibly locks the clamped-state. In store-activated, unclamped STIM1, Phe-394 mediates binding to the Orai1 channel, but His-398 is indispensable for transducing STIM1-binding into Orai1 channel-gating, and is spatially aligned with Phe-394 in the exposed Sα2 helical apex. Thus, the Phe-His locus traverses between ER and PM surfaces and is decisive in the two critical STIM1 functions—unclamping to activate STIM1, and conformational-coupling to gate the Orai1 channel.

Mesenchymal stromal cells (MSCs) contribute to the microenvironment regulating normal and malignant hematopoiesis, and thus may support subpopulations of cancer cells to escape therapeutic pressure. Here, we engineered bone marrow MSCs to express a synthetic CD19-sensor receptor to detect and display interacting primary CD19+ leukemia cells in coculture. This implementation provides a versatile platform facilitating ex vivo drug response profiling of primary CD19+ leukemia cells in coculture with high-sensitivity and scalability.

Abstract Background Platelet (PLT) count at diagnosis plays an important role in cancer development and progression in solid tumors. However, it remains controversial whether PLT count at diagnosis influences therapeutic outcome in patients with non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML). Methods This study analyzed the relationship between PLT count at diagnosis and genetic mutations in a cohort of 330 newly diagnosed non-APL AML patients. The impact of PLT count on complete remission, minimal residual disease status and relapse-free survival (RFS) were evaluated after chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results Our studies showed that patients with DNMT3A mutations have a higher PLT count at diagnosis, while patients with CEBPA biallelic mutations or t(8;21)(q22; q22) translocation had lower PLT count at diagnosis. Furthermore, non-APL AML patients with high platelet count (> 65 × 109/L) at diagnosis had worse response to induction chemotherapy and RFS than those with low PLT count. In addition, allo-HSCT could not absolutely attenuated the negative impact of high PLT count on the survival of non-APL AML patients. Conclusion PLT count at diagnosis has a predictive value for therapeutic outcome for non-APL AML patients.

Abstract Improved energy utilisation, precision, and quality are critical in the current trend of low-carbon green manufacturing. In this study, three abrasive belts were prepared at various wear stages and characterised quantitatively. The effects of abrasive belt wear on the specific grinding energy partition were investigated by evaluating robotic belt grinding of titanium plates. A specific grinding energy model based on subdivided tangential forces of cutting and sliding was developed for investigating specific energy and energy utilisation coefficient E UC. The surface morphology and Abbott–Firestone curves of the belts were introduced to analyse the experimental findings from the perspective of the micro cutting behaviour. The specific grinding energy increased with abrasive belt wear, especially when the belt was near the end of its life. Moreover, the belt wear could lead to a predominance change of sliding and chip formation energy. The highest E UC was observed in the middle of the belt life because of its retained sharp cutting edge and uniform distribution of the grit protrusion height. This study provides guidance for balancing the energy consumption and energy utilization efficiency of belt grinding.

The Time-Varying Matrix Inversion (TVMI) problem is integral to various fields in science and engineering. Countless studies have highlighted the effectiveness of Zeroing Neural Networks (ZNNs) as a dependable approach for addressing this challenge. To effectively solve the TVMI problem, this paper introduces a novel Efficient Anti-Noise Zeroing Neural Network (EANZNN). This model employs segmented time-varying parameters and double integral terms, where the segmented time-varying parameters can adaptively adjust over time, offering faster convergence speeds compared to fixed parameters. The double integral term enables the model to effectively handle the interference of constant noise, linear noise, and other noises. Using the Lyapunov approach, we theoretically analyze and show the convergence and robustness of the proposed EANZNN model. Experimental findings showcase that in scenarios involving linear, constant noise and noise-free environments, the EANZNN model exhibits superior performance compared to traditional models like the Double Integral-Enhanced ZNN (DIEZNN) and the Parameter-Changing ZNN (PCZNN). It demonstrates faster convergence and better resistance to interference, affirming its efficacy in addressing TVMI problems.

Alpinia officinarum Hance is rich in carbohydrates and is flavored by natives. The polysaccharide fraction 30 is purified from the rhizome of A. officinarum Hance (AOP30) and shows excellent immunoregulatory ability when administered to regulate immunity. However, the effect of AOP30 on the intestinal epithelial barrier is not well understood. Therefore, the aim of this study is to investigate the protective effect of AOP30 on the intestinal epithelial barrier using a lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction model and further explore its underlying mechanisms. Cytotoxicity, transepithelial electrical resistance (TEER) values, and Fluorescein isothiocyanate (FITC)–dextran flux are measured. Simultaneously, the protein and mRNA levels of tight junction (TJ) proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, are determined using Western blotting and reverse-transcription quantitative polymerase chain reaction methods, respectively. The results indicate that AOP30 restores the LPS-induced decrease in the TEER value and cell viability. Furthermore, it increases the mRNA and protein expression of ZO-1, Occludin, and Claudin-1. Notably, ZO-1 is the primary tight junction protein altered in response to LPS-induced intestinal epithelial dysfunction. Additionally, AOP30 downregulates the production of TNFα via the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, the findings of this study indicate that AOP30 can be developed as a functional food ingredient or natural therapeutic agent for addressing intestinal epithelial barrier dysfunction. It sheds light on the role of AOP30 in improving intestinal epithelial function.

Summary: Current diagnostic methods for diabetic nephropathy (DN) lack precision, especially in early stages and monitoring progression. This study aims to find potential biomarkers for DN progression and evaluate their accuracy. Using serum samples from healthy controls (NC), diabetic patients (DM), early-medium stage DN (DN-EM), and late-stage DN (DN-L), researchers employed quantitative proteomics and Mfuzz clustering analysis revealed 15 proteins showing increased expression during DN progression, hinting at their biomarker potential. Combining Mfuzz clustering with weighted gene co-expression network analysis (WGCNA) highlighted five candidates (HMGB1, CD44, FBLN1, PTPRG, and ADAMTSL4). HMGB1 emerged as a promising biomarker, closely correlated with renal function changes. Experimental validation supported HMGB1’s upregulation under high glucose conditions, reinforcing its potential as an early detection biomarker for DN. This research advances DN understanding and identifies five potential biomarkers, notably HMGB1, as a promising early monitoring target. These findings set the stage for future clinical diagnostic applications in DN.

Background. Moyamoya disease (MMD) leads to nerve injury. Exosomes are touted as bio-shuttles for the delivery of distinct biomolecules inside the cells. Recently, UCH-L1 was shown to play a vital role in nerve injury. However, it is still unknown whether UCH-L1 can improve the nerve injury of MMD. Materials and Methods. Exosomes were isolated from the serum of patients with MMD and healthy controls. The total RNA was extracted from the exosomes, and the level of GFAP and UCH-L1 between the serum exosomes of the two groups was analyzed by a quantitative reverse transcription-polymerase chain reaction and western blot. Exosome labeling and uptake by SH-SY5Y cells were observed by confocal laser microscopy. Cell counting kit-8 assay and flow cytometry were used to determine the viability and apoptosis of SH-SY5Y cells, respectively. Results. Exosomes were successfully isolated and identified from serum. The expression of GFAP and UCH-L1 was significantly higher in the serum-derived exosomes from MMD patients compared with the healthy controls (P

Abstract INTRODUCTION Although the multimorbidity–dementia association has been widely addressed, little is known on the long‐term trajectory of multimorbidity (TOM) in preclinical dementia. METHODS Based on the Health and Retirement Study, burden of multimorbidity was quantified with the total number of eight long‐term conditions (LTC). Patterns of TOM before dementia diagnosis were investigated with mixed‐effects models. RESULTS In 1752 dementia cases and 5256 matched controls, cases showed higher and faster increasing predicted number of LTC than controls, with a significant case–control difference from 20 years prior to dementia diagnosis. Larger increases in number of LTC during preclinical phase of dementia were found in White participants, females, those whose age at dementia onset was younger, and those who were less educated. DISCUSSION Our findings emphasize the faster accumulation of multimorbidity in prodromal dementia than in natural aging, as well as effect modifications by age and sex. Highlights TOM increased faster in prodromal dementia than in natural ageing. Patterns of TOM by dementia status diverged at 20 years before dementia diagnosis. Patterns of TOM were modified by age and sex.

During grinding complex components with difficult-to-machine materials, compliance grinding tools often experience shortened life and weakened performance due to intense temperature rise. This paper presents a novel solution strategy of preparing crystal-structured compliance tools using multi jet fusion (MJF), and five structures were selected to evaluates its feasibility and grinding performance. The macro and micro elastic deformation of the tools were analyzed by combining finite element and experiment. The results show that the crystal structure provides similar macroscopic stiffness of the tools and introduces microscopic compliance anisotropy. The crystal structure resulted in a reduction of the grit pull-out ratio by more than 82.60 %, while also alleviating the adhesion of flexible substrates adhesion and the prevention of abrasive layer fall-off, leading to prolonged tool life. Furthermore, compliant grinding tools with a crystal structure achieved comparable material removal capacity, lower surface roughness, and higher energy efficiency. In addition, they used only 29.06 % to 36.22 % of the material consumed in manufacturing. Notably, the material removal rate (MMR) of the star-structure tool can reached 94.72 % of the solid-structure tool. The diamond-structure tool exhibited the lowest ground Ra, accompanied by a reduction in grinding temperature of 19.4 °C.

Objective: To examine the impact of ginger volatile oil (GVO) on the growth of MDA-MB-231 breast cancer cells in the presence of bisphenol A (BPA) by modulating the diversity of gut microbiota. Methods: MDA-MB-231 breast cancer cells were injected subcutaneously into the right armpit of female BALB/c Nude (nu/nu) mice to create a triple negative breast cancer model. Thirty nude mice were randomly divided into 5 groups: control group (distilled water every day), BPA control group (distilled PEG-400+ DMSO + cyclodextrin every day), BPA + GVO (0.25 mL/kg) group, BPA + GVO (0.5 mL/kg) group, BPA + GVO (1 mL/kg) group, 6 mice in each group; The drug was given by gavage once a day for 4 weeks. At the end of the experiment, the changes of tumor mass and tumor volume were observed and compared in 5 groups of tumor-bearing mice. High-throughput sequencing (16S rRNA) was used to detect the changes of gut microflora in each group. Results: The volume and weight of breast cancer decreased in the low, medium and high dose groups of GVO. Among them, the difference between the high-dose group and the BPA group reached a significant level (P

Objectives: To investigate the effect of different designs of movable parts and prosthetic materials on the stress distribution of supporting tissues in mandibular free end dentition defects using three-dimensional finite element analysis of digital Roach attachments. Material and methods: A 3D model of a patient with Kennedy class I mandibular edentulous conditions was generated, and twelve prosthesis models were applied, combining two designs of removable parts and six types of CAD/CAM restorative materials with different elastic modulus (conventional zirconia, ultra-translucent zirconia, Polyetheretherketone (PEEK), Lithium disilicate, Nanoceramic resin, and resin composite (Paradigm MZ100, 3 M ESPE)). The stress distribution of abutment periodontal ligament, edentulousmucosa, and junction of attachment were analyzed using finite element analysis. Results: The stress value of the buccal neck of the periodontal ligament and the maximum compressive stress of the distal periodontal ligament of the design with clasp arms were higher than those without clasp arms, while the stress on the junction of attachment and the displacement of the mucosa in the edentulous area were smaller. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended to be used as the fixed part of Roach attachment. Conclusion: CAD/CAM Roach attachments with clasp arms are recommended for the protection of mucosal soft tissue. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended as the fixed part of Roach attachment for patients with free end defect of mandibular dentition. Clinical significance: This study provides references for the design with clasp arms and the selection of clinical fixed-movable prosthetic materials. Clinicians should consider the design of attachments and selection of appropriate manufacturing materials carefully to avoid negative impacts on patients' periodontal support tissues.

Abstract The cGAS-STING signaling pathway has emerged as a promising target for immunotherapy development. Here, we introduce a light-sensitive optogenetic device for control of the cGAS/STING signaling to conditionally modulate innate immunity, called ‘light-inducible SMOC-like repeats’ (LiSmore). We demonstrate that photo-activated LiSmore boosts dendritic cell (DC) maturation and antigen presentation with high spatiotemporal precision. This non-invasive approach photo-sensitizes cytotoxic T lymphocytes to engage tumor antigens, leading to a sustained antitumor immune response. When combined with an immune checkpoint blocker (ICB), LiSmore improves antitumor efficacy in an immunosuppressive lung cancer model that is otherwise unresponsive to conventional ICB treatment. Additionally, LiSmore exhibits an abscopal effect by effectively suppressing tumor growth in a distal site in a bilateral mouse model of melanoma. Collectively, our findings establish the potential of targeted optogenetic activation of the STING signaling pathway for remote immunomodulation in mice.

This study employs a 3D discrete element method (DEM) to simulate cone penetration tests (CPTs) in granular soils, taking into account the effect of temperature. A coupled thermal mechanical model is developed to allow for heat transfer and storage in the granular materials. The CPT simulations are conducted on granular samples prepared at various temperatures, with the specific heat and velocity of thermal conductivity being identified as two critical factors that influence sample heating time. Additionally, the thermal expansion coefficient is a crucial parameter that is closely related to the porosity of the sample. As the sample temperature increases, the particles expand, resulting in an increase in cone resistance.

Abstract Background MSM are at high risk of HIV infection. Previous studies have shown that the cell cycle regulation plays an important role in HIV-1 infection, especially at the G2/M checkpoint. ATR, Chk1, Cdc25C and CDK1 are key genes of G2/M checkpoint. However, the association between SNPs of these genes and susceptibility to HIV-1 infection and AIDS progression remains unknown. Methods In this study, 42 tSNPs from the above four G2/M checkpoint genes were genotyped in 529 MSM and 529 control subjects from northern China to analyze this association. Results The results showed that rs34660854 A and rs75368165 A in ATR gene and rs3756766 A in Cdc25C gene could increase the risk of HIV-1 infection (P = 0.049, OR = 1.234, 95% CI 1.001–1.521; P = 0.020, OR = 1.296, 95% CI 1.042–1.611; P = 0.011, OR = 1.392, 95% CI 1.080–1.794, respectively), while Chk1 rs10893405 (P = 0.029, OR = 1.629, 95% CI 1.051–2.523) were significantly associated with AIDS progression. Besides, rs34660854 (P = 0.019, OR = 1.364, 95% CI 1.052–1.769; P = 0.022, OR = 1.337, 95% CI 1.042–1.716, under Codominant model and Dominant model, respectively) and rs75368165 (P = 0.006, OR = 1.445, 95% CI = 1.114–1.899; P = 0.007, OR = 1.418, 95% CI 1.099–1.831, under Codominant model and Dominant model, respectively) in ATR gene, rs12576279 (P = 0.013, OR = 0.343, 95% CI 0.147-0.800; P = 0.048, OR = 0.437, 95% CI 0.192–0.991, under Codominant model and Dominant model, respectively) and rs540436 (P = 0.012, OR = 1.407, 95% CI 1.077–1.836; P = 0.021, OR = 1.359, 95% CI 1.048–1.762, under Codominant model and Dominant model, respectively) in Chk1 gene, rs3756766 (P = 0.013, OR = 1.455, 95% CI 1.083–1.954; P = 0.009, OR = 1.460, 95% CI 1.098–1.940, under Codominant model and Dominant model, respectively) in Cdc25C gene and rs139245206 (P = 0.022, OR = 5.011, 95% CI 1.267–19.816; P = 0.020, OR = 5.067, 95% CI 1.286–19.970, under Codominant model and Recessive model, respectively) in CDK1 gene were significantly associated with HIV-1 infection under different models. Conclusions We found that genetic variants of G2/M checkpoint genes had a molecular influence on the occurrence of HIV-1 infection and AIDS progression in a northern Chinese MSM population.

The problem of inverting dynamic complex matrices remains a central and intricate challenge that has garnered significant attention in scientific and mathematical research. The zeroing neural network (ZNN) has been a notable approach, utilizing time derivatives for real-time solutions in noiseless settings. However, real-world disturbances pose a significant challenge to a ZNN’s convergence. We design an accelerated dual-integral structure zeroing neural network (ADISZNN), which can enhance convergence and restrict linear noise, particularly in complex domains. Based on the Lyapunov principle, theoretical analysis proves the convergence and robustness of ADISZNN. We have selectively integrated the SBPAF activation function, and through theoretical dissection and comparative experimental validation we have affirmed the efficacy and accuracy of our activation function selection strategy. After conducting numerous experiments, we discovered oscillations and improved the model accordingly, resulting in the ADISZNN-Stable model. This advanced model surpasses current models in both linear noisy and noise-free environments, delivering a more rapid and stable convergence, marking a significant leap forward in the field.

In digital product and ion scheduling centers, order–factory allocation, factory–mold allocation, and mold routing can be performed centrally and efficiently to maximize the utilization of manufacturing resources (molds). Therefore, in this paper, a manufacturing resource (molds)-sharing mechanism based on the Internet of Things (IoT) and a cyber-physical production system (CPPS) is designed to realize the coordinated allocation of molds and production scheduling. A mixed-integer mathematical model is developed to optimize the cost structure and obtain a reasonable profit solution. A heuristic algorithm based on evolutionary reversal is used to solve the problem. The numerical results show that based on the digital coordinated production scheduling method, distributed two-stage assembly manufacturing with shared molds can effectively reduce the order delay time and increase potential benefits for distributed production enterprises.

The early identification of rotten potatoes is one of the most important challenges in a storage facility because of the inconspicuous symptoms of rot, the high density of storage, and environmental factors (such as temperature, humidity, and ambient gases). An electronic nose system based on an ensemble convolutional neural network (ECNN, a powerful feature extraction method) was developed to detect potatoes with different degrees of rot. Three types of potatoes were detected: normal samples, slightly rotten samples, and totally rotten samples. A feature discretization method was proposed to optimize the impact of ambient gases on electronic nose signals by eliminating redundant information from the features. The ECNN based on original features presented good results for the prediction of rotten potatoes in both laboratory and storage environments, and the accuracy of the prediction results was 94.70% and 90.76%, respectively. Moreover, the application of the feature discretization method significantly improved the prediction results, and the accuracy of prediction results improved by 1.59% and 3.73%, respectively. Above all, the electronic nose system performed well in the identification of three types of potatoes by using the ECNN, and the proposed feature discretization method was helpful in reducing the interference of ambient gases.

Abstract Aero-engine fan blades often use a cavity structure to improve the thrust-to-weight ratio of the aircraft. However, the use of the cavity structure brings a series of difficulties to the manufacturing and processing of the blades. Due to the limitation of blade manufacturing technology, it is difficult for the internal cavity structure to achieve the designed contour shape, so the blade has uneven wall thickness and poor consistency, which affects the fatigue performance and airflow dynamic performance of the blade. In order to reduce the influence of uneven wall thickness, this paper proposes a grinding allowance extraction method considering the double dimension constraints (DDC) of the inner and outer contours of the hollow blade. Constrain the two dimensions of the inner and outer contours of the hollow blade. On the premise of satisfying the outer contour constraints, the machining model of the blade is modified according to the distribution of the inwall contour to obtain a more reasonable distribution of the grinding allowance. On the premise of satisfying the contour constraints, according to the distribution of the inwall contour, the machining model of the blade is modified to obtain a more reasonable distribution of the grinding allowance. Through the grinding experiment of the hollow blade, the surface roughness is below Ra0.4 μm, and the contour accuracy is between − 0.05~0.14 mm, which meets the processing requirements. Compared with the allowance extraction method that only considers the contour, the problem of poor wall thickness consistency can be effectively improved. It can be used to extract the allowance of aero-engine blades with hollow features, which lays a foundation for the study of hollow blade grinding methods with high service performance.

Abstract Cell fusion plays a critical role in cancer progression and metastasis. However, effective modulation of the cell fusion behavior and timely evaluation on the cell fusion to provide accurate information for personalized therapy are facing challenges. Here, it demonstrates that the cancer cell fusion behavior can be efficiently modulated and precisely detected through employing a multifunctional delivery vector to realize cancer targeting delivery of a genome editing plasmid and a molecular beacon‐based AND logic gate. The multifunctional delivery vector decorated by AS1411 conjugated hyaluronic acid and NLS‐GE11 peptide conjugated hyaluronic acid can specifically target circulating malignant cells (CMCs) of cancer patients to deliver the genome editing plasmid for epidermal growth factor receptor (EGFR) knockout. The cell fusion between CMCs and endothelial cells can be detected by the AND logic gate delivered by the multifunctional vector. After EGFR knockout, the edited CMCs exhibit dramatically inhibited cell fusion capability, while unedited CMCs can easily fuse with human umbilical vein endothelial cells (HUVEC) to form hybrid cells. This study provides a new therapeutic strategy for preventing cancer progression and a reliable tool for evaluating cancer cell fusion for precise personalized therapy.

Abstract The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18–29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.

Strawberry is an extensively planted horticulture crop with multiple economic values. Vacuolar phosphate transporter (FaVPT1) can promote phosphate and sugar accumulation and improve strawberry fruit quality, however, its transcription regulatory mechanism remains unknown. Here, we report a GRAS superfamily transcription factor (TF) SCARECROW-LIKE8 (FaSCL8) which regulates FaVPT1 expression to control strawberry fruit ripening and quality. The promoter of FaVPT1 was used as a bait to screen the octoploid strawberry cDNA library by yeast one hybrid to obtain the candidate TFs including FaSCL8. FaSCL8 was located in the nucleus and was mainly expressed in fruit, its expression level was increased rapidly during ripening, and induced by exogenous phytohormones including ABA, GA, IAA, and ethylene, as well as sucrose. FaSCL8 can directly combine with the FaVPT1 promoter and regulate its expression in vitro and in vivo. The results of Agrobacterium-mediated transient infection of strawberry fruits showed that overexpression of FaSCL8 could increase soluble sugar, anthocyanin, and phosphorus content, promoting fruit ripening, while decreasing expression of FaSCL8 showed the opposite phenotype. The expression levels of fruit ripening and quality-related genes including FaVPT1, were improved in the over-expressed fruits of FaSCL8, while receded in the FaSCL8-silenced fruits. In conclusion, this study found that FaSCL8 can regulate FaVPT1 expression to improve phosphorus and sugar accumulation in strawberry fruits and promote fruit ripening, providing a new regulation mechanism of strawberry fruit ripening by phosphorus, a macroelement key to fruit quality improvement.

In this work, a new method for failure analysis of electronic components, high speed camera, is used to investigate burnout failure location of GaN HEMTs under RF overdrive stress. Based on the high speed camera system and the RF test system, we can filter out most of the burn flashes, and clearly locate the weak parts of devices. To further explain the burnout mechanism, a long-term (100 h) RF overdrive stress experiment was carried out and the significant degradation was observed. The drain-source current decreases and the threshold voltage drifts forward. These phenomena show that the degradation of RF overdrive stress is based on hot electron effect (HEE), which is related to the electric field. Besides, Electroluminescence (EL) tests are used and the non-uniform but strong luminescence characteristics of the gate were found, which indicates the strong electric field is the main cause of burnout. We also explore the correlation between burnout and ambient temperature. It was found that the influence of ambient temperature on the burnout was limited. At last, a TCAD simulation is carried out to confirm the temperature and electric field distribution in the device when burnout. It can be found that the electric field inside the device exceeded the breakdown electric field of GaN, which further proves that the burnout caused by RF overdrive is mainly due to electric field rather than temperature.

Wine grape quality is influenced by the variety and growing environment, and the quality of the grapes has a significant impact on the quality of the wine. Tannins are a crucial indicator of wine grape quality, and, therefore, rapid and non-destructive methods for detecting tannin content are necessary. This study collected spectral data of Pinot Noir and Chardonnay using a geophysical spectrometer, with a focus on the 500–1800 nm spectrum. The spectra were preprocessed using Savitzky–Golay (SG), first-order differential (1D), standard normal transform (SNV), and their respective combinations. Characteristic bands were extracted through correlation analysis (PCC). Models such as partial least squares (PLS), support vector machine (SVM), random forest (RF), and one-dimensional neural network (1DCNN) were used to model tannin content. The study found that preprocessing the raw spectra improved the models’ predictive capacity. The SVM–RF model was the most effective in predicting grape tannin content, with a test set R2 of 0.78, an RMSE of 0.31, and an RE of 10.71%. These results provide a theoretical basis for non-destructive testing of wine grape tannin content.

We describe the survey design and science goals for One-hundred-deg ^2 DECam Imaging in Narrowbands (ODIN), a NOIRLab survey using the Dark Energy Camera (DECam) to obtain deep (AB ∼ 25.7) narrowband images over an unprecedented area of sky. The three custom-built narrowband filters, N 419, N 501, and N 673, have central wavelengths of 419, 501, and 673 nm and respective FWHM of 7.5, 7.6, and 10.0 nm, corresponding to Ly α at z = 2.4, 3.1, and 4.5 and cosmic times of 2.8, 2.1, and 1.4 Gyr, respectively. When combined with even deeper, public broadband data from the Hyper Suprime-Cam, DECam, and in the future, the Legacy Survey of Space and Time, the ODIN narrowband images will enable the selection of over 100,000 Ly α -emitting (LAE) galaxies at these epochs. ODIN-selected LAEs will identify protoclusters as galaxy overdensities, and the deep narrowband images enable detection of highly extended Ly α blobs (LABs). Primary science goals include measuring the clustering strength and dark matter halo connection of LAEs, LABs, and protoclusters, and their respective relationship to filaments in the cosmic web. The three epochs allow for the redshift evolution of these properties to be determined during the period known as Cosmic Noon, where star formation was at its peak. The narrowband filter wavelengths are designed to enable interloper rejection and further scientific studies by revealing [O ii ] and [O iii ] at z = 0.34, Ly α and He ii 1640 at z = 3.1, and Lyman continuum plus Ly α at z = 4.5. Ancillary science includes similar studies of the lower-redshift emission-line galaxy samples and investigations of nearby star-forming galaxies resolved into numerous [O iii ] and [S ii ] emitting regions.

Alpinia officinarum Hance, a well known agricultural product in the Lei Zhou peninsula, is generally rich in polysaccharides. In order to enhance the use of A. officinarum Hance polysaccharides (AOP) in functional food, AOP was extracted using an ultrasonic-assisted extraction method, and the ultrasonic extraction parameters of AOP was optimized. Furthermore, this study investigated the physicochemical and antioxidant activities of AOPs. In addition, the structural properties were preliminarily determined using Fourier-transform infrared spectroscopy (FTIR), high performance size exclusion chromatography, and a Zetasizer. Ultimately, this study explored the mechanism underlying the antioxidant activities of AOP. The results showed that the optimal ultrasonic-assisted extraction parameters were as follows: ultrasonic time, 6 min; ratio of water to material, 12 mL/g; and ultrasonic power, 380 W. Under these conditions, the maximum yield of AOPs was 5.72%, indicating that ultrasonic-assisted extraction technology is suitable for extracting AOPs due to the reduced time and water usage. Additionally, AOPs were purified using graded alcohol precipitation, resulting in three fractions (AOP30, AOP50, and AOP70). AOP30 had the lowest molecular weight of 11.07 kDa and mainly consisted of glucose (89.88%). The half inhibitory concentration (IC50) value of AOP30 and AOP70 was lower than that of AOP50 in the ability to scavenge the ABTS radical, while a reverse trend was observed in reducing ferric ions. Notably, the antioxidant activities of AOPs were highly correlated with their polydispersity index (Mw/Mn) and Zeta potential. AOP30, a negatively charged acidic polysaccharide fraction, exhibited electron donating capacities. Additionally, it displayed strong antioxidant abilities through scavenging 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radicals and reducing ferric ions. In conclusion, the present study suggests that AOP30 could be developed as an antioxidant ingredient for the food industry.

Summary: Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called “trained immunity.” However, the specificity and cell types responsible for this response remain poorly defined. We established a model of trained immunity in mice in response to Mycobacterium avium infection. scRNA-seq analysis revealed that HSPCs activate interferon gamma-response genes heterogeneously upon primary challenge, while rare cell populations expand. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, and a single dose of recombinant interferon gamma exposure was sufficient to induce similar training. Mice transplanted with influenza-trained HSPCs displayed enhanced immunity against M. avium challenge and vice versa, demonstrating cross protection against antigenically distinct pathogens. Together, these results indicate that heterogeneous responses to infection by HSPCs can lead to long-term production of bone marrow derived macrophages with enhanced function and confer cross-protection against alternative pathogens.