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Abstract Loop closure detection (LCD) plays an important role in visual simultaneous location and mapping (SLAM), as it can effectively reduce the cumulative errors of the SLAM system after a long period of movement. Convolutional neural networks (CNNs) have a significant advantage in image similarity comparison, and researchers have achieved good results by incorporating CNNs into LCD. The LCD based on CNN is more robust than traditional methods. As the deep neural network frameworks from AlexNet and VGG to ResNet have become smaller while maintaining good accuracy, indoor LCD does not need robots to finish a large number of complex processing operations. To reduce the complexity of deep neural networks, this paper presents a new lightweight neural network based on MobileNet V2. We propose a strategy to use Efficient Channel Attention (ECA) to insert into Compressed MobileNet V2 (ECMobileNet) for reducing operands while maintaining precision. A corresponding loop detection method is designed based on the average distribution of ECMobileNet feature vectors combined with Euclidean distance matching. We used TUM datasets to evaluate the results, and the experimental results show that this method outperforms the state-of-the-art methods. Although the model was trained only on the indoorCVPR dataset, it also demonstrated superior performance on the TUM datasets. In particular, the proposed approach is more lightweight and highly efficient than the current existing neural network approaches. Finally, we used TUM datasets to test LCD based on ECMobileNet in PTAM, and the experimental results show that this lightweight neural network is feasible.

Abstract Objective This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion. Methods Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness. Result(s) 20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients. Conclusions Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure . Trial registration Retrospectively registered (The PROSPERO registration number: CRD42022360161).

Monolayer-protected nanoclusters are ideal models for understanding the correlations between structures and properties of inorganic nanoparticles, especially for those molecules with identical sizes but comparable structures. Here, we controllably prepared and structurally determined a valence-neutral Au24+xAg20‑x(SPhtBu)26 (0 < x < 4) nanocluster with comparable structure features to a well-known Au12Ag32(SPhF2)30 cluster. The Au24+xAg20‑x(SPhtBu)26 cluster contained a hollow Au12@M20 metallic kernel (M = Au/Ag), 12 Au1(SR)2 staples, and two bridging SR molecules, and its average molecular formula was determined to be Au26.3Ag17.7(SPhtBu)26, as evidenced by X-ray crystallography and electrospray ionization mass spectrometry. Because of the ligand effect and the asymmetrical arrangement of the Au dopants in the dodecahedral cage, the Au24+xAg20‑x(SPhtBu)26 nanocluster exhibited lower molecular symmetry relative to Au12Ag32(SPhF2)30 in terms of the dodecahedral kernel and motif shell structures. Besides, the strong π–π interaction in Au24+xAg20‑x(SPhtBu)26 contributed to its enhanced photoluminescence intensity compared with Au12Ag32(SPhF2)30. The study, herein, extends the 44-metal-atom cluster family, thereby enabling us to better understand the correlations between their structures and properties at the atomic level.

Abstract Background To investigate the nutritional status of patients with aortic dissection (AD) treated with using 3D printing-assisted stent graft fenestration and explore the important factors affecting the nutrition status of patients with different numbers of fenestrations (holes). Methods Ninety-nine hospitalized patients with AD in a grade A tertiary hospital in Nanjing from January 2020 to December 2020 were selected as the study subjects. According to the different number of fenestrations, the patients were divided into four groups: one fenestration (group A), two fenestrations (group B), three fenestrations (group C) and four fenestrations (group D); and the nutrition status of patients in the four groups was analyzed. Then, according to whether the calories provided via infusion reached the 80% goal calories (25 kcal/kg/day) on postoperative day 5, the patients were assigned to the Reached group and Not reached group, and their inflammatory parameters, including white blood cell (WBC) and C-reactive protein (CRP), on postoperative days 1 and 5 were analyzed. Results Compared with patients in group B (18.8%), C (19.4%) and D (6.7%), patients in group A (48.6%) had the highest rate of reaching the nutrition requirement (80% goal calories). Further, in the Reached group, WBC count and CRP concentration were significantly reduced on postoperative day 5 compared with postoperative day 1, and the proportion of patients with abnormal WBC count was significantly decreased. In contrast, although the CRP concentration on postoperative day 5 in the Not reached group was significantly lower than that on postoperative day 1, no significant changes in WBC count were observed. Conclusion In 3D printing-assisted stent graft fenestration for AD, multiple fenestrations (holes) were associated with a low rate of reaching nutrition requirements, which might be related to imflammation. Therefore, effective nutritional support should be given to patients with multiple fenestrations after operation to improve their nutritional status and prognosis.

Incorporating carbon footprints into the production efficiency framework to construct a standardized technology model for cleaner production in black soil regions is of great significance for improving the soil environment and the sustainable development of agriculture. This study used an orthogonal experimental design and the DEA–Malmquist method to calculate the carbon footprint and total factor productivity of orthogonal experimental groups of cleaner production technologies for maize cultivation in China’s black soil region and then identified integrated models of cleaner production technology in the black soil region. The results showed that the carbon footprint of maize cultivation and total factor productivity were generally higher in the experimental group using cleaner production techniques than in the control group. Still, none of them reached the optimum. In the future, the synergistic effect of technological progress and technological efficiency enhancement should be brought into play, and the integrated models of “Soil testing and formulation + Full mobile sprinkler irrigation + Straw tilling and field return” and “No tillage in spring + Soil testing and formulation + Straw tilling and field return” should be promoted in semi-arid and semi-humid black soil regions, which can improve the low carbon productivity of maize by 20.3% and 15.4%, respectively.

cAMP-dependent protein kinase (PKA) activity regulates protein phosphorylation, with Na+ playing a crucial role in PKA activity. The aim of this study was to investigate the effects of different Na+ concentrations on PKA activity and protein phosphorylation level in postmortem muscle. The study consisted of two experiments: (1) NaCl of 0, 20, 100, 200 and 400 mM was added to a muscle homogenate incubation model to analyze the effect of Na+ concentration on PKA activity, and (2) the same concentrations were added to pure PKA in vitro incubation models at 4 °C to verify the effect of Na+ on PKA activity. The PKA activity of the muscle homogenate model increased with storage time in groups with different Na+ concentrations. High concentrations of Na+ inhibited sarcoplasmic protein phosphorylation. The PKA activity at 24 h of storage and the sarcoplasmic protein phosphorylation level at 12 h of storage in the group with 200 mM Na+ was lower than that of the other groups. After 1 h incubation, the PKA activity of samples in the 200 mM Na+ group was inhibited and lower than that in the other Na+ groups in the in vitro incubation model. These results suggest that the Na+ concentration at 200 mM could better inhibit PKA activity. This study provided valuable insights for enhancing curing efficiency and improving meat quality.

The ratoon rice cropping pattern is an alternative to the double-season rice cropping pattern in central China due to its comparable annual yield and relatively lower cost and labor requirements. However, the impact of the ratoon rice cropping pattern on greenhouse gas (GHG) emissions and yields in the double-season rice region requires further investigation. Here, we compared two cropping patterns, fallow-double season rice (DR) and fallow-ratoon rice (RR), by using two early-season rice varieties (ZJZ17, LY287) and two late-season rice varieties (WY103, TY390) for DR, and two ratoon rice varieties (YLY911, LY6326) for RR. The six varieties constituted four treatments, including DR1 (ZJZ17 + WY103), DR2 (LY287 + TY390), RR1 (YLY911), and RR2 (LY6326). The experimental results showed that conversion from DR to RR cropping pattern significantly altered the GHG emissions, global warming potential (GWP), and GWP per unit yield (yield-scaled GWP). Compared with DR, the RR cropping pattern significantly increased cumulative methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) emissions by 65.73%, 30.56%, and 47.13%, respectively, in the first cropping season. Conversely, in the second cropping season, the RR cropping pattern effectively reduced cumulative CH4, N2O, and CO2 emissions by 79.86%, 27.18%, and 30.31%, respectively. RR led to significantly lower annual cumulative CH4 emissions, but no significant difference in cumulative annual N2O and CO2 emissions compared with DR. In total, the RR cropping pattern reduced the annual GWP by 7.38% and the annual yield-scaled GWP by 2.48% when compared to the DR cropping pattern. Rice variety also showed certain effects on the yields and GHG emissions in different RR cropping patterns. Compared with RR1, RR2 significantly increased annual yield while decreasing annual GWP and annual yield-scaled GWP. In conclusion, the LY6326 RR cropping pattern may be a highly promising strategy to simultaneously reduce GWP and maintain high grain yield in double-season rice regions in central China.

The term “viscoelastic pipe” refers to high polymer pipes that exhibit both elastic and viscoelastic properties. Owing to their widespread use in water transport systems, it is important to understand the transient flow characteristics of these materials for pipeline safety. Despite extensive research, these characteristics have not been sufficiently explored. This study evaluates the impact of friction models on the transient flow of viscoelastic pipes across various Reynolds numbers by employing an energy analysis approach. Given the complexity and computational demands of two-dimensional models, this paper compares the accuracy of one-dimensional and quasi-two-dimensional models. Notably, the superiority of the quasi-two-dimensional model in simulating viscoelastic pipelines is demonstrated. Owing to the interaction between pressure waves and fluid within viscoelastic pipes, fluid–structure coupling significantly attenuates pressure waves during transmission. These findings shed light on the constitutive properties of viscoelastic pipes and the influence of pipe wall friction models on transient hydraulic characteristics, building upon prior studies focused on elastic pipes. Nevertheless, numerous factors affecting transient flow in viscoelastic pipes remain unexplored. This paper suggests further analysis of strain effects, starting with temperature and pipe dynamics, to enhance the understanding of the coupling laws and flow mechanisms in viscoelastic pipelines.

In recent years, the development of hydrogen energy has been widely discussed, particularly in combination with renewable energy sources, enabling the production of “green” hydrogen. With the significant increase in wind power generation, a promising solution for obtaining green hydrogen is the development of wind-to-hydrogen (W2H) systems. However, the high proportion of wind power and electrolyzers in a large-scale W2H system will bring about the problem of renewable energy consumption and frequency stability reduction. This paper analyzes the operational characteristics and economic feasibility of mainstream electrolyzers, leading to the proposal of a coordinated hydrogen production scheme involving both a proton exchange membrane (PEM) electrolyzer and an alkaline (ALK) electrolyzer. Subsequently, a coordinated control based on Model Predictive Control (MPC) is proposed for system frequency regulation in a large-scale W2H islanded microgrid. Finally, simulation results demonstrate that the system under PEM/ALK electrolyzers coordinated control not only flexibly accommodates fluctuating wind power but also maintains frequency stability in the face of large disturbances. Compared with the traditional system with all ALK electrolyzers, the frequency deviation of this system is reduced by 25%, the regulation time is shortened by 80%, and the demand for an energy storage system (ESS) is reduced. The result validates the effectiveness of MPC and the benefits of the PEM/ALK electrolyzers coordinated hydrogen production scheme.

Using shallow-water buoy observations, reanalysis data, and numerical models, this study analyzes the variations in sea temperature and significant wave height (SWH) caused by two sequential tropical cyclones (TCs) ‘Lionrock’ and ‘Kompasu’ in October 2021 in the northeast Beibu Gulf, South China Sea. The results show that the sea surface temperature (SST) cooling of the nearshore waters was larger than the offshore water in the basin of the gulf, with the cooling amplitude and rate decreasing and the cooling time lagging behind wind increasing from coast to offshore. The near-surface temperature at the buoy station had a maximum decrease of 2.8 °C after ‘Lionrock’, and the decrease increased slightly to 3 °C after the stronger wind of ‘Kompasu’. The total decrease of 4.6 °C indicates that the sequential TCs had a superimposed effect on the cooling of the Beibu Gulf. The heat budget analysis revealed that the sea surface heat loss and the Ekman pumping rate in the nearshore waters during ‘Kompasu’ (−535 W/m2 and 5.8 × 10−4 m/s, respectively) were significantly higher than that (−418 W/m2 and 4 × 10−4 m/s) during ‘Lionrock’. On the other hand, the SST cooling (−1.2 °C) during the second TC is smaller than (−1.6 °C) the first weaker TC in the gulf basin, probably due to the deepening of the mixed layer. During the observation period, the waves in the Beibu Gulf were predominantly wind-driven. The maximum SWHs reached 1.58 m and 2.3 m at the bouy station near shore during the two TCs, and the SWH variation was highly correlated to the wind variation with a correlation of 0.95. The SWH increases from the nearshore to offshore waters during the TCs. The SAWN and ARCIRC coupled model results suggest that wave variations in the Beibu Gulf are primarily influenced by water depth, bottom friction, and whitecapping. Two days after the TCs, sea surface cooling and high waves appeared again due to a cold air event.

Previous meta-analyses of multiple studies have suggested that dietary intake and blood concentrations of carotenoids, as well as dietary supplement of certain carotenoids, play a role in reducing the risk of cancer. However, the conclusions of these studies have been subject to controversy. We conducted an umbrella review of meta-analyses to comprehensively analyze and evaluate the evidence pertaining the association between carotenoids and cancer outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases of meta-analyses and systematic reviews up to June 2023. Our selection criteria encompassed meta-analyses of cohort and case-control studies, as well as randomized controlled clinical trials, which investigated the associations between carotenoids and cancer risk. We also determined the levels of evidence for these associations with AMSTAR 2 criteria. We included 51 eligible articles, including 198 meta-analyses for qualitative synthesis in the umbrella review. Despite the presence of moderate to high heterogeneity among the studies, dietary intake, supplementation, and blood concentrations of carotenoids were inversely associated with the risk of total cancer, and certain specific cancers of lung, digestive system, prostate, breast, head and neck, and others. Subgroup analysis also showed that individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, zeaxanthin, and lycopene) offer certain protection against specific types of cancers. However, high doses of carotenoid supplements, especially β-carotene, significantly increased the risk of total cancer, lung cancer, and bladder cancer. Our umbrella meta-analysis supported that high intake of dietary carotenoids as a whole food approach could be more beneficial in reducing cancer risk. Concurrently, the findings suggest that the efficacy of single-carotenoid supplementation in cancer prevention remains a subject of controversy.

Optimized fertilizer use improves crop yield and mitigates environmental pollution associated with crop production. Fertilizer and plant density are core strategies to ensure food security and cope with climate change. However, little is known about the long-term interactive effect of reduced nitrogen (N) and increased density on yield and C (Carbon) balance. In this study, field experiments were conducted in a double-cropping rice region to evaluate long-term effects on yield and carbon footprint (CF) by crop-based and soil-based methods. Treatments were set for 10% reduction in N coupling with conventional density (N1D1), 20% higher density (N1D2), 40% higher density (N1D3), and 20% reduction in N coupling with conventional density (N2D1), 20% higher density (N2D2), and 40% higher density (N2D3), with the prevailing practices as control, conventional plant density, and fertilizer dose. Results showed that the yield continued to increase with increasing density; under the same density, reducing N by 10% is more beneficial for yield improvement and for CH4 emission reduction. Compared with CK, reducing N application by 10% generally increased the annual yields by 7.34–23.25% on average, and reduced CH4 emissions by 16.19–22.11%, resulting in a reduced crop-based carbon footprint of 22.24–26.82%, and a reduced soil-based carbon footprint of 22.08–32.85%. While reducing N application by 20% increased the annual yields by 5.00–20.19% and reduced the CH4 emission by 1.66–4.93%, it reduced crop-based carbon footprints by 1.81–10.05% and reduced soil-based carbon footprints by 7.22–19.86%. As density increased, the crop-based CF decreased, whereas the soil-based CF increased. Overall, the highest yield and the lowest soil-based CF and unit yield CF (CFy) were observed in N1D3. Regarding sustainability, a 10% reduction in N, along with an increase in density to 40%, can be recommended for double-cropping rice production.

There is a growing interest in the similarities and differences in reading processes in L1 and L2. Some researchers propose that reading shares commonalities across languages, while others state that each language has particularities that would affect reading processes. One way to better understand the reading processes is by using eye-tracking methodologies to explore reading processes online. This review focuses on the research done about reading processes in bilinguals to understand the effect of L1 in L2 processing. We found that most of the studies followed two methods of comparison: Bilinguals vs. monolinguals and L1 vs. L2. In general, bilinguals presented longer times in all reading measures; however, the results are discussed based on different characteristics of the studies and the type of comparison.

The environmental/economic dispatch (EED) of power systems addresses the environmental pollution problems caused by power generation at the operational level, offering macroscopic control without requiring additional construction and remediation costs, garnering widespread attention in recent years. This paper undertakes a comprehensive review of existing EED models, categorizing them according to the control of atmospheric pollutants into total air pollutant control (TAPC) and control considering the spatial and temporal diffusion (STD) of atmospheric pollutants. In addition, various methods employed to address the EED problems, as well as the current state of research on multi-area EED models, are presented. Finally, this paper analyzes and summarizes the literature on existing EED models, highlighting the deficiencies of the current work and future research directions. Through these explorations, the authors find that controlling the EED model by considering TAPC is more suitable for general macro planning, whereas the EED model considering the STD of air pollutant emissions enables more precise and effective control. Summarizing such models and techniques is conducive to developing dispatch plans adapted to local conditions, which is significantly beneficial for public welfare and government management, promoting sustainable and environmentally friendly power system dispatch methods.

The lattice Boltzmann method is employed in the current study to simulate the heat transfer characteristics of sinusoidal-temperature-distributed heat sources at the bottom of a square cavity under various conditions, including different amplitudes, phase angles, initial positions, and angular velocities. Additionally, a machine learning-based model is developed to accurately predict the Nusselt number in such a sinusoidal temperature distribution of heat source at the bottom of a square cavity. The results indicate that (1) in the phase angle range from 0 to π, Nu basically shows a decreasing trend with an increase in phase angle. The decline in Nu at an accelerated rate is consistently observed when the phase angle reaches 4π/16. The corresponding Nu decreases as the amplitude increases at the same phase angle. (2) The initial position of the sinusoidal-temperature-distributed heat source Lc significantly impacts the convective heat transfer in the cavity. Moreover, the decline in Nu was further exacerbated when Lc reached 7/16. (3) The optimal overall heat transfer effect was achieved when the angular velocity of the non-uniform heat source reached π. As the angular velocity increases, the local Nu in the square cavity exhibits a gradual and oscillatory decline. Notably, it is observed that Nu at odd multiples of π surpasses that at even multiples of π. Furthermore, the current work integrates LBM with machine learning, enabling the development of a precise and efficient prediction model for simulating Nu under specific operational conditions. This research provides valuable insights into the application of machine learning in the field of heat transfer.

Solutes segregating at the grain boundary (GB) have a significant influence on the mechanical and chemical properties of steel. In this study, the segregation effects of Si, P, and S on γ-Fe ∑5 (210)[001] GB were systematically analyzed with solution energy, segregation energy, and tensile tests by using a first principles calculation. Si, P, and S are preferred to segregate at substitutional sites in the first layer near the GB. The variation in atomic configuration and electron distribution were investigated by the analysis of bond lengths, charge density, charge density difference, and density of states (DOS), which is caused by the atomic size and electronegativity of solute atoms. Through tensile tests, it was found that Si has a strengthening effect on GB, while P and S exhibit embrittlement effects at low concentration. As the concentration of solutes increase, the segregation sites of P are different from the others owing to the tendency to form Fe3P. The exhibited embrittlement effect is mitigated at first and then aggravated. However, in both cases Si and S show aggravating embrittlement effects on GB cohesion, while the effect of Si changes from strengthening to embrittlement. This work provides comprehensive insights into the effects of Si, P, and S, which will be a useful guidance in steel design.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol–maleimide “click” chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine–BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

Distribution network scheduling (DNS) is the basis for distribution network management, which is computed in a periodical way via solving the formulated mixed-integer programming (MIP). To achieve the online scheduling, a provably robust learn-to-optimize approach for online DNS is proposed in this paper, whose key lies in the transformation of the MIP-based DNS into the simple linear program problem with a much faster solving time. It formulates the parametric DNS model to construct the offline training dataset and then proposes the provably robust learning approach to learn the integer variables of MIP. The proposed learning approach is adversarial to minor perturbation of input scenario. After training, the learning model can predict the integer variables to achieve online scheduling. Case study verifies the acceleration effectiveness for online DNS.

BackgroundBreast cancer is a relatively heterogeneous disease in the older population. Survival in older breast cancer patients is not only affected by tumor-related factors, but also by geriatric assessment domains. How tumor clinical factors and geriatric factors specifically affect the survival rate of older patients and how to combine these two factors to predict the risk of death in older patients with breast cancer remain clinical questions to be addressed.MethodWe used the Peking Union Medical College Hospital database to identify older patients (≥65 years) who were newly diagnosed with breast cancer between January 2013 and December 2019. Of the 641 eligible patients, we retrospectively analyzed the clinical and geriatric data of 556 patients who formed our study population. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors and construct a nomogram to predict the 1-, 3-, and 5-year survival rates. The performance of the constructed nomogram was evaluated using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsMultivariate Cox regression analysis revealed seven independent prognostic factors associated with OS in older patients with breast cancer: age, tumor stage, lymph node stage, intrinsic molecular subtype, functional status, comorbidities, and psychological state. Nomogram based on these seven factors yielded excellent performance, with area under the ROC curve (AUROC) of 0.748. Similarly, the nomogram for BCSS had an AUROC of 0.760. Moreover, the calibration curve and DCA revealed good predictive accuracy between the actual and predicted probabilities.ConclusionIndependent prognostic factors for OS and BCSS in older patients with breast cancer in China were determined in our study. A novel nomogram for predicting the 1-, 3-, and 5-year OS and BCSS in this patient population was developed and validated. The nomogram exhibited good accuracy, indicating its potential for clinical decision making and improving outcomes.

A large amount of nuclear waste produced in the process of nuclear energy utilization has always been a key problem to be solved urgently for nuclear safety. At present, “deep geological disposal” is a feasible method and generally accepted by many countries. The oxygen content in the near field environment of the waste container will decrease to anaerobic conditions, and hydrogen will permeation into the internal materials of container for a long time. Hydrogen evolution corrosion may cause a risk of hydrogen embrittlement. The harm of hydrogen embrittlement in metal container is far more severe than predictable uniform corrosion. It is a research hotspot that the microorganisms impact on the corrosion behavior of container materials in the deep geological environment. Microbial corrosion in deep geological environments can be divided into two types: aerobic microbial corrosion and anaerobic microbial corrosion. There is a type of hydrogen consuming microorganism in the natural environment that uses the oxidation of hydrogen as the energy for its life activities. This provides a new approach for us to study reducing the hydrogen embrittlement sensitivity of nuclear waste container materials.

BackgroundVentricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI). Cardiogenic shock (CS) is a common complication of VSR and an important factor affecting its prognosis. CS can occur in either an immediate or delayed manner after VSR; however, studies on the risk factors associated with immediate or delayed CS are scarce.MethodsWe retrospectively studied patients diagnosed with VSR after MI and admitted to the West China Hospital between September 2009 and August 2023. Demographic data, medical history, physical examination results, electrocardiograms, and echocardiographic and hematological data were extracted from electronic medical records or archived records. CS was defined as hypotension (

Introduction Interventions at the mild cognitive impairment (MCI) stage prevent or delay the progression of cognitive decline. In recent years, several studies have shown that physical exercise combined with transcranial direct current stimulation (tDCS) effectively delays the disease and promotes cognitive recovery in patients with MCI. This study aims to determine whether Tai Chi (TC) combined with tDCS can significantly improve memory in patients with MCI compared with TC or tDCS alone.Methods and analysis This clinical trial will use a 2×2 factorial design, enrolling 128 community-dwelling MCI patients, randomly categorised into four groups: TC, tDCS, TC combined with tDCS and the health education group. Outcome measures will include the Chinese Wechsler Memory Scale-Revised, Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure Test. All assessments will be conducted at baseline and 3 months after the intervention. All analyses will use intention-to-treat or per-protocol methods.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of the Fujian University of Traditional Chinese Medicine (2022KY-002–01). The results of the study will be disseminated through peer-reviewed publications and at scientific conferences.Trial registration number ChiCTR2200059316.

Background: GSTM1 deletion was reported to be associated with CKD progression in cohort studies. However, the results of case‒control studies were conflicting. The association between GST genes and CKD progression needs to be studied in China. Therefore, we conducted this case‒control study and systematic review for Southwest China to outline the association between GST genes and CKD. Methods: CKD patients and healthy controls were enrolled from June 1, 2022 to 1 August 2022. Reported case‒control studies were identified by searching databases until 1 September 2022 for meta-analysis. Results: Significant associations were found between deletions of GSTM1 and GSTT1 and CKD risk (all P 0.05) in Southwest China. Then, we conducted a meta-analysis on 30 studies and found positive associations between deletions of GSTM1 and GSTT1 and CKD risk (all P 0.05). Stratification analysis for ethnicity only showed a significant association in Southern Asia (P

Inadequate invasion and excessive apoptosis of trophoblast cells are associated with the development of preeclampsia. Vitamin D deficiency in pregnant women may lead to an increased risk of preeclampsia. However, the underlying mechanisms by which vitamin D is effective in preventing preeclampsia are not fully understood. The objectives of this study were to investigate the role of lysosome-associated membrane glycoprotein 3 (LAMP3) in the pathogenesis of preeclampsia and to evaluate whether vitamin D supplementation would protect against the development of preeclampsia by regulating LAMP3 expression. Firstly, the mRNA and protein levels of LAMP3 were significantly upregulated in the placentas of preeclampsia patients compared to normal placentas, especially in trophoblast cells (a key component of the human placenta). In the hypoxia/reoxygenation (H/R)-exposed HTR-8/Svneo trophoblast cells, LAMP3 expression was also upregulated. H/R exposure repressed cell viability and invasion and increased apoptosis of trophoblast cells. siRNA-mediated knockdown of LAMP3 increased cell viability and invasion and suppressed apoptosis of H/R-exposed trophoblast cells. We further found that 1,25(OH)2D3 (the hormonally active form of vitamin D) treatment reduced LAMP3 expression in H/R exposed trophoblast cells. In addition, 1,25(OH)2D3 treatment promoted cell viability and invasion and inhibited apoptosis of H/R-exposed trophoblast cells. Notably, overexpression of LAMP3 abrogated the protective effect of 1,25(OH)2D3 on H/R-exposed trophoblast cells. Collectively, we demonstrated trophoblast cytoprotection by vitamin D, a process mediated via LAMP3.

IntroductionIn the face of increasingly severe global climate change and environmental challenges, reducing carbon emissions has become a key global priority. Deep learning, as a powerful artificial intelligence technology, has demonstrated significant capabilities in time series analysis and pattern recognition, opening up new avenues for carbon emission prediction and policy development.MethodsIn this study, we carefully collected and pre-processed four datasets to ensure the reliability and consistency of the data. Our proposed TCN-LSTM combination architecture effectively leverages the parallel computing capabilities of TCN and the memory capacity of LSTM, more efficiently capturing long-term dependencies in time series data. Furthermore, the introduction of an attention mechanism allows us to weigh important factors in historical data, thereby improving the accuracy and robustness of predictions. ResultsOur research findings provide novel insights and methods for advancing carbon emission prediction. Additionally, our discoveries offer valuable references for decision-makers and government agencies in formulating scientifically effective carbon reduction policies. As the urgency of addressing climate change continues to grow, the progress made in this paper can contribute to a more sustainable and environmentally conscious future. DiscussionIn this paper, we emphasize the potential of deep learning techniques in carbon emission prediction and demonstrate the effectiveness of the TCN-LSTM combination architecture. The significant contribution of this research lies in providing a new approach to address the carbon emission prediction problem in time series data. Moreover, our study underscores the importance of data reliability and consistency for the successful application of models. We encourage further research and application of this method to facilitate the achievement of global carbon reduction goals.

Objective The dysregulation of the human high-temperature requirement A (HtrA) family of serine proteases is associated with many malignancies. However, there are few reports on HtrAs in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the expression, prognostic value, and biological functions of HtrAs in HNSCC. Methods The RNA-sequencing data and clinical data of HNSCC were downloaded from The Cancer Genome Atlas (TCGA) database. The GSE30784 and GSE31056 datasets from the Gene Expression Omnibus (GEO) database were used for further verification. This study explored the differential expression of HtrAs and assessed their potential impact on the prognosis of HNSCC patients using a survival module. Correlations between clinical characteristics and HtrA expression levels were then explored using a Wilcoxon rank sum test. A Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed using “clusterProfile” in the R software. A Pearson/Spearman correlation test was applied to analyze the relationship between HtrAs and immune infiltration level/checkpoint genes. Validation of HtrA expression levels were carried out by RT-PCR and western blot in human squamous carcinoma cell lines (Fadu and Cal-27) and human non-tumorigenic bronchial epithelium cells (BEAS-2B). Finally, through cell transfection, CCK-8, Ki-67 immunofluorescence, and flow cytometry assays, the effect of HtrA3 knockdown on the malignant biological behavior of HNSCC cells was explored. Results The gene expression levels of HtrAs were significantly upregulated and associated with patient age, TNM stage, clinical stage, and TP53 mutation status in the TCGA-HNSCC cohort. High expressions of HtrA1/3 were associated with shorter overall survival, shorter progress-free interval, and lower disease-specific survival in HNSCC. A nomogram for HtrAs was constructed and validated. HtrA-related genes were significantly enriched in the immune response and cell apoptosis pathway. In addition, the expression of HtrAs showed significant correlations with B cells, M cells, DC cell infiltration, and immune infiltration checkpoint (CD276, TNFRSF14). Validation of HtrA expression was carried out by RT-PCR and western blot. Results of in vitro experiments indicated that HtrA3 gene knockdown inhibits the proliferation of FaDu and Cal-27 cells while concurrently promoting apoptosis. Conclusions HtrA3 shows significant potential as both a prognostic marker and a promising therapeutic target for HNSCC, highlighting its relevance and importance in future research and potential clinical applications.

BackgroundAscending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive.MethodsA total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMS-susceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS.ResultsThe occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p

Background: Esophageal squamous cell carcinoma (ESCC) is a malignancy usually associated with smoking or alcohol consumption. The involvement of long noncoding RNAs (lncRNAs) in the regulation of tumor development and metastasis through molecular mechanisms has been unveiled by accumulating evidence. However, the function of lncRNA SUMO1 Pseudogene 3 (lncSUMO1P3) essential to ESCC development remains obscure. Methods: Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis were done to measure RNA and protein levels. Functional assays were carried out to examine the changes in ESCC cell phenotype. Supported by bioinformatics analysis, mechanism assays were done for assessment of putative interactions among different genes. Results: LlncSUMO1P3 was aberrantly up-regulated in ESCC cell lines, and lncSUMO1P3 deficiency could hamper cell proliferation, migration and invasion as well as epithelial-mesenchymaltransition (EMT) in ESCC while lncSUMO1P3 overexpression led to the opposite consequences. LncSUMO1P3 could competitively bind to microRNA-486-5p (miR-486-5p) or PHD finger protein 8 (PHF8) to modulate CD151 expression. CD151 was also verified to regulate ESCC cell biological behaviors. Conclusion: Our study revealed that lncSUMO1P3, up-regulated in ESCC cells, could sponge miR-486-5p and recruit PHF8 to up-regulate CD151, thus influencing the malignant behaviors of ESCC cells.

Ovarian cancer is insensitive to immunotherapy and has a high mortality rate. CDK4/6 inhibitors (CDK4/6i) regulate the tumor microenvironment and play an antitumor role. Our previous research demonstrated that lymphocyte aggregation (tertiary lymphoid structures, TLSs) was observed after CDK4/6i treatment. This may explain the synergistic action of CDK4/6i with the anti-PD1 antibody. However, the key mechanism by which CDK4/6i promotes TLS formation has not been elucidated. We examine the link between TLS and prognosis. Animal models and high-throughput sequencing were used to explore the potential mechanism by which CDK4/6i promotes TLS formation. Our results showed the presence of TLSs was associated with a favorable prognosis for ovarian cancer. CDK4/6i promoted TLS formation and enhanced the immunotherapeutic effect of the anti-PD1 antibody. The potential mechanism of CDK4/6i affecting the formation of TLS may be through modulating SCD1 and its regulatory molecules ATF3 and CCL4. Our findings provide a theoretical basis for the application of CDK4/6i in ovarian cancer.

Alzheimer’s disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE’s risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aβ deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved from ClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.

Abstract Hypoxia inducible factor‐1α (HIF‐1α) plays a critical role in cellular adaptation to hypoxia and it is a potential therapeutic target for anti‐cancer drugs. Applying high‐throughput screening, here it is found that HI‐101, a small molecule containing an adamantaniline moiety, effectively reduces HIF‐1α protein expression. With the compound as a hit, a probe (HI‐102) is developed for target identification by affinity‐based protein profiling. The catalytic β subunit of mitochondrial FOF1‐ATP synthase, ATP5B, is identified as the binding protein of HI‐derivatives. Mechanistically, HI‐101 promotes the binding of HIF‐1α mRNA to ATP5B, thus inhibiting HIF‐1α translation and the following transcriptional activity. Further modifications of HI‐101 lead to HI‐104, a compound with good pharmacokinetic properties, exhibiting antitumor activity in MHCC97‐L mice xenograft model, and HI‐105, the most potent compound with an IC50 of 26 nm. The findings provide a new strategy for further developing HIF‐1α inhibitors by translational inhibition through ATP5B.

Abstract Background Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD. Methods Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis. Results There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p

Abstract Background Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. Results Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. Conclusions Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

Abstract As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.

A novel, unified control design is proposed for software-defined inverters (SDIs) to operate in either grid-forming (GFM) or grid-following (GFL) mode in AC grids/microgrids and to switch between the two modes seamlessly. The proposed GFM and GFL controls are systematically developed and analytically synthesized based on the dynamic state space models of the inverter, its output filters, and its terminal voltage and current at the AC grid/microgrid. The proposed GFM and GFL controls have, a) a nonlinear nominal output tracking control as the seed design, and b) a constraint-enforcing control. The GFM nominal control tracks frequency, voltage-magnitude, and angle, while the GFL nominal control tracks frequency as well as real and reactive power references. Tracking of either GFM or GFL output vector is ensured under the recursive Lyapunov design paradigm, naturally resulting in consistent current and voltage control laws. This paradigm allows the implementation of constraint-enforcing control that ensures that the frequency, voltage, power, and current injections dynamically satisfy their operational constraints in the presence of load variations and intermittent renewable power sources. Stability and convergence of the proposed GFM and GFL controls, and constraint enforcement are concluded analytically, and their effectiveness is demonstrated through simulations.

Abstract Background Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. Methods Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. Results Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P

Abstract A bias-independent inter-modulation method is proposed and demonstrated for measuring low-frequency modulation and bias half-wave voltages of Mach-Zehnder modulators (MZMs). The method consists of simultaneous sinusoidal modulation on the modulation and bias ports of the MZM under test. Sinusoidal-modulated sidebands heterodyne with each other and generate the desired inter-modulation products after photodetection, which allows extracting both the modulation depth and half-wave voltage for the modulation and bias ports of the MZM. Our method is independent of bias voltages of the MZM, which can be canceled out by carefully choosing the sinusoidal-modulation frequencies. Moreover, the proposed method enables the low swing voltage for measuring both the modulation depth and half-wave voltage of MZMs. Experiments indicate that the proposed method features the simple setup and high accuracy for low-frequency response measurement ranging from 1 Hz to 1 MHz.

Abstract Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Chemoresistance leads to poor responses to conventional therapy in patients with osteosarcoma. The discovery of novel effective therapeutic targets and drugs is still the main focus of osteosarcoma research. Nuclear receptors (NRs) have shown substantial promise as novel therapeutic targets for various cancers. In the present study, we performed a drug screen using 29 chemicals that specifically target 17 NRs in several different human osteosarcoma and osteoblast cell lines. The retinoic acid receptor beta (RARb) antagonist LE135, peroxisome proliferator activated receptor gamma (PPARg) antagonist T0070907, liver X receptor (LXR) agonist T0901317 and Rev-Erba agonist SR9011 significantly inhibited the proliferation of malignant osteosarcoma cells (U2OS, HOS-MNNG and Saos-2 cells) but did not inhibit the growth of normal osteoblasts. The effects of these NR modulators on osteosarcoma cells occurred in a dose-dependent manner and were not observed in NR-knockout osteosarcoma cells. These NR modulators also significantly inhibited osteosarcoma growth in vivo and enhanced the antitumour effect of doxorubicin (DOX). Transcriptomic and immunoblotting results showed that these NR modulators may inhibit the growth of osteosarcoma cells by regulating the PI3K/AKT/mTOR and ERK/mTOR pathways. DDIT4, which blocks mTOR activation, was identified as one of the common downstream target genes of these NRs. DDIT4 knockout significantly attenuated the inhibitory effects of these NR modulators on osteosarcoma cell growth. Together, our results revealed that modulators of RARb, PPARg, LXRs and Rev-Erba inhibit osteosarcoma growth both in vitro and in vivo through the mTOR signaling pathway, suggesting that treatment with these NR modulators is a novel potential therapeutic strategy.

To obtain high-quality walnut meal protein, the process conditions for extraction of walnut meal protein by alkaline solubilization and acid precipitation method and purification of walnut meal protein by glycolytic enzyme were optimized by single-factor experiments and response surface method, respectively, and the functional properties such as solubility, water absorption, and emulsification were analyzed. The optimal extraction process conditions were: pH12, temperature 55 ℃, time 90 min, and material-liquid ratio 1:40 g/mL. Under these conditions, the extraction rate of walnut meal protein could reach 81.89%±1.64%, and its settling point was pH4.5. The optimal purification process conditions were: pH4.5, material-to-liquid ratio 1:40 g/mL, enzymatic digestion time 129 min, enzymatic digestion temperature 53°C, and enzyme addition 0.4%. The purity of walnut meal protein purified under these conditions could reach 94.48%±1.83%. The results of functional properties of walnut protein showed that its solubility was 24.82%, water absorption 3.06 g/g, oil absorption 3.15 g/g, emulsification 16.10 m2/g, emulsification stability 38.87 min, foaming 30.53% and foaming stability 75.44% under the same pH conditions, and the purified walnut protein had better functional properties.

Background & Aims: Gastrointestinal cancer stem cell marker doublecortin-like kinase (DCLK1) is strongly associated with poor outcomes in colorectal cancer (CRC). Although DCLK1’s regulatory effect on the tumor immune microenvironment has been hypothesized, its mode of action has not been shown previously in vivo, which hampers the potential intervention based on this molecule for clinical practice. Methods: To define the immunomodulatory mechanisms of DCLK1 in vivo, we generated DCLK1-/- tumor cells by Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) and developed subcutaneous and intestinal orthotopic transplantation tumor models. Tumor tissues were harvested and subjected to immunofluorescence staining, flow cytometry analysis of tumor-infiltrating immune cell populations, tumor myeloid-derived suppressor cell (MDSC) sorting by isolation kit and then co-culture with spleen T cells, and RNA sequencing for transcriptomic analysis. Results: We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Collectively, we validated that DCLK1 promotes tumor growth in CRC through recruitment of T-cell–suppressive MDSCs. Conclusions: DCLK1-mediated immune suppression in tumor models allows escaping from the host’s antitumor response. Because DCLK1 is one of the most common markers in gastrointestinal tumors, these results identify a precise therapeutic target for related clinical interventions.

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose- and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.

Cerebral ischemia is a serious disease that triggers sequential pathological mechanisms, leading to significant morbidity and mortality. Although most studies to date have typically focused on the lysosome, a single organelle, current evidence supports that the function of lysosomes cannot be separated from that of the endolysosomal system as a whole. The associated membrane fusion functions of this system play a crucial role in the biodegradation of cerebral ischemia-related products. Here, we review the regulation of and the changes that occur in the endolysosomal system after cerebral ischemia, focusing on the latest research progress on membrane fusion function. Numerous proteins, including N-ethylmaleimide-sensitive factor and lysosomal potassium channel transmembrane protein 175, regulate the function of this system. However, these proteins are abnormally expressed after cerebral ischemic injury, which disrupts the normal fusion function of membranes within the endolysosomal system and that between autophagosomes and lysosomes. This results in impaired “maturation” of the endolysosomal system and the collapse of energy metabolism balance and protein homeostasis maintained by the autophagy-lysosomal pathway. Autophagy is the final step in the endolysosomal pathway and contributes to maintaining the dynamic balance of the system. The process of autophagosome-lysosome fusion is a necessary part of autophagy and plays a crucial role in maintaining energy homeostasis and clearing aging proteins. We believe that, in cerebral ischemic injury, the endolysosomal system should be considered as a whole rather than focusing on the lysosome. Understanding how this dynamic system is regulated will provide new ideas for the treatment of cerebral ischemia.

Abstract The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICESaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection.

Abstract Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that associates with aberrant activation of B lymphocytes and excessive autoantibodies. Interleukin 10 (IL-10)/interleukin 35 (IL-35) and IL-10/IL-35-producing regulatory B cells have been demonstrated to possess immunosuppressive functions during systemic lupus erythematosus. Here, we detected the proportion of CD19+CD24highCD27+ B cells as well as IL-10 and IL-35 levels in peripheral blood of SLE patients and healthy individuals, and investigated their relations with clinical features of SLE. Methods 41 SLE patients and 25 healthy controls were recruited. The patients were divided into groups based on SLEDAI score, anti-dsDNA antibody, rash, nephritis and hematological disorder. Flow cytometry was used to detect the proportion of CD24hiCD27+ B cells. ELISA was used to detect serum levels of IL-10 and IL-35. Results Our results showed that the CD19+CD24highCD27+ B population was decreased in active SLE patients, and anti-correlated with the disease activity. Of note, we found significant increase of IL-10 and decrease of IL-35 in SLE patients with disease activity score > 4, lupus nephritis or hematological disorders compared to those without related clinical features. Conclusions Reduced CD19+CD24highCD27+ B cells expression may be involved in the pathogenesis of SLE. Moreover, we supposed that IL-35 instead of IL-10 played a crucial role in immune regulation during SLE disease.

Abstract We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of “candidate ciliopathy genes.” From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. Histological and morphological evidence of phenotypes found in ciliopathies in knockout mouse lines are presented as examples (genes Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1). Phenotyping data and descriptions generated on IMPC mouse line are useful for mechanistic studies, target discovery, rare disease diagnosis, and preclinical therapeutic development trials. Here we demonstrate the effective use of the IMPC phenotype data to uncover genes with no previous role in ciliary biology, which may be clinically relevant for identification of novel disease genes implicated in ciliopathies.

Abstract MicroRNAs (miRNAs or miRs) are a class of noncoding single-stranded RNAs that can regulate gene expression by binding to the untranslated sequences at the 3 ' end of messenger RNAs. The microRNA-34 family is dysregulated in various human diseases. It is considered as a tumor-suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. As a member of the miRNA-34 family, miR-34b-5p serves as a powerful regulator of a suite of cellular activities, including cell growth, multiplication, development, differentiation, and apoptosis. It promotes or represses disease occurrence and progression by participating in some important signaling pathways. This review aimed to provide an overview and update on the differential expression and function of miR-34b-5p in pathophysiologic processes, especially cancer and injury. Additionally, miR-34b-5p‐mediated clinical trials have indicated promising consequences for the therapies of carcinomatosis and injury. With the application of the first tumor-targeted microRNA drug based on miR-34a mimics, it can be inferred that miR-34b-5p may become a crucial factor in the therapy of various diseases. However, further studies on miR-34b-5p should shed light on its involvement in disease pathogenesis and treatment options.

A pre-column derivatization liquid chromatographic method was developed for the simultaneous determination of both glucosamine and galactosamine in selected food samples. The derivatization of glucosamine and galactosamine with 9-fluorenylmethoxycarbonyl chloride was accomplished under alkaline conditions and UV irradiation. When the detection wavelength was 265 nm and acetonitrile-0.1% phosphoric acid was the mobile phase at a flow rate of 1.0 mL/min, the linear range of ultraviolet intensity of glucosamine and galactosamine was 10–100 μg/mL,correlation coefficient of glucosamine was 0.9994 and correlation coefficient of galactosamine was 0.9993. The standard recovery of three kinds of food was in the range of 94.09–114.5%, the relative standard deviation (RSD) was 0.38–5.29%, the detection limit was 1.0 mg/kg, and the quantitative limit was 4.0 mg/kg. The results of this research indicate that this method is suitable for the simultaneous determination of glucosamine and galactosamine in food.

Background Despite abundant evidence linking dyslipidaemia to an increased risk of hyperuricaemia, the exact association between each component of dyslipidaemia and hyperuricaemia remains controversial. Thus, the objective of this research was to examine the correlation between dyslipidaemia and its components, as well as hyperuricaemia in Chinese people over the age of 60.Methods In this study, 4018 participants over 60 years without hyperuricaemia were investigated from 2014 to 2020. The association between each dyslipidaemia component and hyperuricaemia was evaluated employing Cox proportional hazards models. This research conducted further stratified and sensitivity analyses to assess the potential relationship.Results A total of 1155 participants suffered from hyperuricaemia (28.75%) at the time of the 6-year follow-up survey. In multivariable-adjusted analyses, compared to participants with normal lipid levels, those with dyslipidaemia had 1.28 times the risk (95% confidence interval 1.12 to 1.47) of experiencing hyperuricaemia. The hazard ratios (HR) (95% CI) comparing high TC, high TG, high LDL-C, and low HDL-C of dyslipidaemia with the regular group were 0.99 (0.72 to 1.37), 1.30 (1.07 to 1.57), 1.02 (0.70 to 1.50), and 1.20 (1.00 to 1.44), respectively. There was a nonlinear dose-response between TG, HDL-C, and serum uric acid (SUA).Conclusions Dyslipidaemia and its two distinct types, high TG and low HDL-C, increased hyperuricaemia incidence in this prospective cohort. Further research should be undertaken to investigate the possible reverse causality between different components of dyslipidaemia and hyperuricaemia.