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Abstract The primary objective of this study was to identify the factors associated with the development of depressive symptoms in elderly breast cancer (BC) patients and to construct a nomogram model for predicting these symptoms. We recruited 409 patients undergoing BC treatment in the breast departments of two tertiary-level hospitals in Jiangsu Province from November 2023 to April 2024 as our study cohort. Participants were categorized into depressed and non-depressed groups based on their clinical outcomes. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors for depression among BC patients. Multivariate analysis revealed that monthly income, pain score, family support score, and physical activity score significantly influenced the onset of depression in older BC patients (P

Abstract Background Previous studies have reported the link between hypoxic conditions and NLRP3 inflammasome-mediated pulpal inflammation in the progression of pulpitis. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the role of HIF-1α in the regulation of NLRP3 inflammasome pathway via NF-κB signaling under hypoxic conditions with or without LPS in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. Methods HIF-1α plasmids or siRNAs were used to upregulate or downregulate HIF-1α in HDPFs, respectively. The effect of hypoxia with or without LPS on the NF-κB signaling and NLRP3 inflammasome pathway was analyzed by immunofluorescence staining, qRT-PCR, western blotting and ELISA. Results The hypoxic conditions alone induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling in a time-dependent manner in HDPFs. The upregulation of HIF-1α further promoted hypoxia-induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. In comparison, downregulation of HIF-1α inhibited ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Additionally, LPS plus hypoxia further promoted HIF-1α expression and NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Conclusions HIF-1α served as a positive regulator of NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling in HDPFs in the sterile pulpal inflammation and caries-related pulpitis microenvironment. The finding of a novel functional HIF-1α-NF-κB-NLRP3 axis provides insight into the link between the hypoxic microenvironment and pulpal inflammation, thus supporting a promising therapeutic strategy for the control of pulpal inflammation.

Abstract Background Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. Methods After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. Results Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. Conclusions Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

Abstract Purpose Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. Methods Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. Results We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p

Fish have excellent swimming performance, and one key factor is their ability to autonomously adjust body stiffness, which can help them efficiently swim at different speeds and complex environments. At present, the variable‐stiffness design of robotic fish still suffers from structural complexity, severe deformation, and small variation range, which limits the application of variable‐stiffness theory in robotic fish. In this article, a variable‐stiffness tail is designed based on layer‐jamming for robotic fish, which can conveniently achieve online stiffness adjustment while maintaining the optimal stiffness distribution and the shape is unaffected. A modeling method for the tail is proposed by combining the mechanical characteristics of the layer‐jamming structure with the pseudo‐rigid body model. To validate the performance of the tail, a series of experiments are conducted, which show that the stiffness variation range of the tail is around 10 times, and the accuracy of the model in predicting the kinematics of the tail is also verified. Moreover, the thrust tests demonstrate that stiffness adjustment is beneficial for fish swimming at different frequencies. The proposed variable‐stiffness tail will promote the development of efficient underwater biomimetic robots.

In this study, the surface of ZL104 was ultrasonically rolled (USRP) to provide better overall mechanical properties and corrosion resistance. USRP experiments were conducted on the surface by setting different parameters to improve the performance of ZL104 after strengthening. The results of the gradient residual stress test showed that the specimen with parameter 350N, 4-pass had 95.5% increase in residual stress and better fatigue resistance. The corrosion resistance of the specimen with a parameter of 500N, 3-pass was superior to that of the original specimen, with an increase of about 50%. The surface roughness test results showed that the surface roughness was reduced by about 38%-50% after USRP treatment. Meanwhile, the microstructure (OM, SEM) results showed that the surface grains were refined and the hardness increased from 105.45HV to 197.61 HV after USRP processing, and the properties were optimized.

BackgroundT cell receptor (TCR)-T cell therapy is an innovative form of cancer immunotherapy that genetically modifies patients’ T cells to target and destroy cancer cells. However, the current status of clinical trials of TCR-T cell therapy for the treatment of cancer remains unclear. This study aimed to comprehensively analyze the registration trials related to TCR-T cell therapy for the treatment of cancer.MethodsA comprehensive search was conducted in the Trialtrove database for all clinical trials related to TCR-T cell therapy registered by August 1, 2024. Inclusion criteria focused on trials targeting TCR-T cell therapy for oncology, and excluded observational studies and incomplete data. Statistical analysis was performed on key trial characteristics, with between-group comparisons utilizing chi-square or Fisher’s exact tests.ResultsAnalysis of 174 eligible clinical trials revealed that TCR-T cell therapy exhibits significant efficacy across various tumor types, particularly in refractory hematologic malignancies and certain solid tumors. Additionally, combining TCR-T cell therapy with other immunotherapies enhanced these anti-tumor effects.ConclusionTCR-T cell therapy holds substantial promise for cancer treatment. Future research should focus on optimizing treatment protocols, enhancing efficacy, and minimizing prices to fully realize the potential of this therapy.

The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60℃, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2–) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2– were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09–0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %–22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.

The design for large-scale offshore systems like renewable energy systems as well as ship structures represents the key factor for the investigation and application of such devices. The existing guide for design schemes of offshore systems cannot cover novel large-scale design demand for recent offshore systems, as a result of the fast-growing scale of offshore systems but the late update of guides. To this end, this paper proposes a novel risk estimation approach of alternative design schemes for large-scale offshore systems as a basis to support the design scheme determinations. Initially, the risks of design schemes are analyzed by fault tree analysis. Subsequently, Bayesian networks and fuzzy sets are employed to calculate the reliability of alternative designs that comply with, or deviate from, the existing guides. The risk level of alternative designs is assessed to ensure the better performance of alternative design schemes in terms of safety. The Bayesian network approach proposed also accretions the weak links in the alternative designs. The results of this paper contribute to enhancing the survivability of offshore systems, such as renewable energy systems as well as ship structures.

The reinforced corrosion resistance composite coating was fabricated by laser cladding (LC) on the laser weld seam (WS) of S30408. The uniform microstructure, good tensile strength of WS and the LC coating were investigated, the mechanism of this LC coating reinforced the corrosion resistance of WS was extensively researched. The results revealed that WS consisted of face-centered cubic (fcc) austenite, and body-centered cubic (bcc) ferrite. The LC coating consisted of fcc. Amounts of the granular precipitates were distributed near the ferrites in WS. The tensile strength of WS was increased due to the synergistic effect of the solution/fine grain strengthening. Corrosion resistance of the LC coating was higher than that of the weld seam. Passivation films were produced due to the chemical reaction between Co/Cr/Fe and water/oxygen.

Abstract Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers – or ‘curlamers’ – determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

Abstract Background Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis. Methods Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay. Results H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis. Conclusion METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis.

ABSTRACTCandida auris has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, C. auris possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB’s activity against C. auris. LNP also potentiates the antifungal activity of AmB against other medically important species of Candida and Cryptococcus. Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome bc1). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of C. auris in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome bc1 inhibitor for combating drug-resistant C. auris infections.

Energy-intensive load benefits from low electricity tariff and carbon emission, since they occupy certain amounts in the total cost of the product. This paper considers energy-intensive load participation in the electricity as well as carbon trading to reduce the cost. Firstly, an electricity-carbon model is established based on the correlation value method to calculate the carbon emissions of energy-intensive load based on their electricity consumption to realize the carbon amount. Afterwards, the baseline method is used to allocate free carbon emission quotas to energy-intensive load and a reward-penalty carbon trading price mechanism considering offset is proposed. Next, the objective function to achieve maximum benefits, and to reduce output fluctuation, and to improve new energy accommodation is proposed. The case studies show that, by comparing multi-objective function optimization, the optimization target proposed in this paper can effectively reduce wind power output fluctuations and improve wind power accommodation. Through the total participation in carbon trading and electricity market income, multi-objective optimization can increase the system income while ensuring that energy-intensive load meets production requirements under the premise of reducing carbon emissions, verifying the effectiveness of the low-carbon optimal operation model proposed in this paper.

Abstract Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system’s regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future.

Abstract Now, no recommendations of gestational weight gain (GWG) after gestational diabetes mellitus (GDM) diagnosis for Chinese women was made. This study aimed to explore the optimal GWG after oral glucose tolerance test (OGTT) for Chinese women with GDM. The GWG status of 11,570 women was retrospectively analyzed. Binary regression model and restricted cubic spline were used to estimate the association between GWG after OGTT and the predicted probability of adverse outcomes. Based on above, the optimal GWG was defined as the range that not exceed 1% increase in the predicted probability from the lowest point. Results shown that every increased one unit GWG after OGTT was associated with higher risks of macrosomia, cesarean section and LGA, and lower risk of preterm birth. According to the WHO and Working Group on Obesity in China (WGOC) recommended pre-pregnancy BMI category, the optimal GWG were proposed: 3.66 to 6.66 kg/3.66 to 6.66 kg in underweight group, 3.07 to 6.50 kg/3.02 to 6.40 kg in normal weight group, 1.06 to 2.73 kg/0 to 1.99 kg in overweight group, and not applicable/− 0.22 to 2.53 kg in obese group, respectively. Therefore, it is necessary to classified Chinese population based on the WGOC recommended pre-pregnancy BMI category, that influenced the contribution of pre-pregnancy BMI groups and the optimal GWG recommendation for GDM women with overweight or obesity.

Abstract Background Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. Methods In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. Results Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. Conclusion The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Abstract Vaccination is a fundamental tool in preventing infectious diseases. However, due to the wide array of vaccines available, comprehending the entire vaccine landscape can be a daunting task. To tackle this complexity, this study employs advanced network analysis methods capable of capturing the intricate relationships within multivariate datasets. The objective is to investigate how the vaccination landscape has evolved both before and after the COVID-19 pandemic. This study examined vaccination data in the Nanan District of Chongqing, China, spanning from 2016 to 2022. Additionally, the network topological characteristics were computed and scrutinized across 2326 sliding windows. The investigation focused on assessing alterations in the topological structure of the vaccination network before and after the COVID-19 pandemic, encompassing analyses at both macro and mesoscale levels. Furthermore, at the micro level, this study delved into the correlation degrees of selected vaccine nodes within the vaccination network. The analysis unveiled that the correlation and activity within the vaccination network showed a noticeable enhancement in strength in the wake of the COVID-19 pandemic, especially during the spring and winter months. However, the community structure and the average interactions between vaccines displayed a diminishing trend post-pandemic. Among the analyzed vaccines, the HepA vaccine emerged as the one with the highest average node-degree centrality rank. A closer examination of the node-degree centrality ranking chart within the vaccination network disclosed fluctuations in the rankings of various vaccine types across different time periods and seasons. In contrast, vaccines incorporated into NIP exhibited a remarkable degree of consistency, which is attributed to children adhering to a fixed vaccination schedule, rendering NIP vaccines less susceptible to disruptions and enhancing their stability within the vaccination network. This study offers valuable insights into the dynamics of the vaccination network, shedding light on the impact of the COVID-19 pandemic, seasonal variations, and the ever-shifting correlation patterns among different vaccine types. These discoveries enrich our comprehension of vaccination trends and have the potential to guide forthcoming endeavors aimed at refining vaccination strategies and enhancing public health outcomes, not only in the Nanan District but also in analogous settings.

Abstract The widespread use of biogas and biomass fuels in facility agro‐industrial parks has led to a significant increase in their carbon emissions. A day‐ahead optimal scheduling model for an integrated energy system (IES) is proposed, that considers the coupling of biomass and power to gas (P2G) to reduce carbon emissions during the operation of an industrial park. The proposed model incorporates the two evaluation indices of the economy of and carbon emissions by the IES of the park, and formulates and solves a multi‐objective optimization problem by using the ε‐constraint method. From among the solutions to the Pareto front, we choose the scheduling strategy that delivers the optimal performance in case of multiple objectives by using the fuzzy decision method. Finally, the validity of the proposed model was verified by considering the IES of an agriculture–industrial park in the northwest region of China.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut–pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids’ (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut–pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

The intelligent detection of chili peppers is crucial for achieving automated operations. In complex field environments, challenges such as overlapping plants, branch occlusions, and uneven lighting make detection difficult. This study conducted comparative experiments to select the optimal detection model based on YOLOv8 and further enhanced it. The model was optimized by incorporating BiFPN, LSKNet, and FasterNet modules, followed by the addition of attention and lightweight modules such as EMBC, EMSCP, DAttention, MSBlock, and Faster. Adjustments to CIoU, Inner CIoU, Inner GIoU, and inner_mpdiou loss functions and scaling factors further improved overall performance. After optimization, the YOLOv8 model achieved precision, recall, and mAP scores of 79.0%, 75.3%, and 83.2%, respectively, representing increases of 1.1, 4.3, and 1.6 percentage points over the base model. Additionally, GFLOPs were reduced by 13.6%, the model size decreased to 66.7% of the base model, and the FPS reached 301.4. This resulted in accurate and rapid detection of chili peppers in complex field environments, providing data support and experimental references for the development of intelligent picking equipment.

Abstract Over 16 million children have been detected positive for the coronavirus disease 2019 (COVID-19) in the United States since the outbreak of the pandemic. In general, children infected with severe acute respiratory syndrome coronavirus type 2 tend to have lighter symptoms than adults. However, in some cases, the infection can develop into severe forms, such as multisystem inflammatory syndrome in children. Moreover, long-term public health preventive interventions have had some negative effects on the physical and mental health of children. Given the important role that vaccination plays in reducing severe illness and mortality, it is essential for the efficient implementation of vaccination in the pediatric population. Nevertheless, parental distrust of vaccination, especially with regard to its safety and efficacy, hinders this process. Herein, we comprehensively summarize the available data on the safety and effectiveness of COVID-19 vaccine in children. The results show that the currently approved COVID-19 vaccine is safe and effective for children. Although two doses of vaccine in children seem insufficient to prevent Omicron infection, the booster dose provides enhanced protection against infection and severe illness. Most importantly, the bivalent vaccine has been approved for use in the pediatric population to extend the immune response to currently circulating Omicron variant. And the immune protection afforded to newborns after maternal vaccination appears to last only 6 months. Therefore, in the current situation where the rate of virus mutation is accelerating and the COVID-19 pandemic is still severe, it is crucial to extend vaccine protection to children over 6 months of age to weave a tighter safety net.

Abstract Protein-S-glutathionylation is a post-translational modification involving the conjugation of glutathione to protein thiols, which can modulate the activity and structure of key cellular proteins. Glutaredoxins (GLRX) are oxidoreductases that regulate this process by performing deglutathionylation. However, GLRX has five cysteines that are potentially vulnerable to oxidative modification, which is associated with GLRX aggregation and loss of activity. To date, GLRX cysteines that are oxidatively modified and their relative susceptibilities remain unknown. We utilized molecular modeling approaches, activity assays using recombinant GLRX, coupled with site-directed mutagenesis of each cysteine both individually and in combination to address the oxidizibility of GLRX cysteines. These approaches reveal that C8 and C83 are targets for S-glutathionylation and oxidation by hydrogen peroxide in vitro. In silico modeling and experimental validation confirm a prominent role of C8 for dimer formation and aggregation. Lastly, combinatorial mutation of C8, C26, and C83 results in increased activity of GLRX and resistance to oxidative inactivation and aggregation. Results from these integrated computational and experimental studies provide insights into the relative oxidizability of GLRX’s cysteines and have implications for the use of GLRX as a therapeutic in settings of dysregulated protein glutathionylation.

Abstract Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 experimentally-validated or manually-curated interactions collected from more than 3,000 literatures as well as 4,537,709 predicted interactions inferred via six computational algorithms by reanalyzing 32 scRNA-seq datasets and bulk RNA-seq data across 25 cancer types. The communications between tumor cells and 14 types of immune cells were characterized, and the involved ligand-receptor interactions were further integrated. 14190 human and 3650 mouse integrated ligand-receptor interactions with supplemented corresponding function information were also stored in the TICCom database. Our database would serve as a valuable resource for investigating TIC communications.

The carbon emissions are essential for climate change and 26% of the world's carbon emissions are related to transport. But focusing only on fewer carbon emissions might be biased at times. In order to keep a balance be-tween economic growth and carbon emissions reduction, this paper evaluated the performance of carbon control by considering the input factors and output factors together, which is more comprehensive and reliable. Firstly, this paper has calculated the transport carbon emissions reduction efficiency (TCERE) based on the model of super SBM with undesirable outputs. The input factors include capital stock, labor force and fossil energy con-sumption. And the output factors include gross domestic product and carbon dioxide emissions. Then the influenc-ing factors of TCERE were analyzed using econometric models. The economic growth, transport structure, tech-nology level and population density were posited as influencing factors. This paper creatively proposed the per capita nighttime lights brightness as a new indicator for economic growth. An empirical study was conducted in East China from 2013 to 2017, and this study has found that the relationship between TCERE and economic growth shows an U-shape. Besides, transport structure and technology level both show a positive impact on TCERE. The implications of our findings are that: (a) The TCERE declines slower in East China, giving us reason to believe that the improvement of TCERE is predictable; (b) When economic growth exceeds the turning point, economic growth is conducive to the improvement of TCERE. We could develop the economy boldly and confident-ly; (c) Increased investment in railway and waterway transportation infrastructure projects is needed to strengthen the structure of the railway and waterway transportation systems. Furthermore, the general public and businesses should be encouraged to prefer rail or river transportation; (d) Investment in scientific and technological innova-tion should be enhanced in order to produce more efficient energy-use methods.

In digital cameras, we find a major limitation: the image and video form inherited from a film camera obstructs it from capturing the rapidly changing photonic world. Here, we present vform, a bit sequence array where each bit represents whether the accumulation of photons has reached a threshold, to record and reconstruct the scene radiance at any moment. By employing only consumer-level complementary metal–oxide semiconductor (CMOS) sensors and integrated circuits, we have developed a spike camera that is 1000× faster than conventional cameras. By treating vform as spike trains in biological vision, we have further developed a spiking neural network (SNN)-based machine vision system that combines the speed of the machine and the mechanism of biological vision, achieving high-speed object detection and tracking 1000× faster than human vision. We demonstrate the utility of the spike camera and the super vision system in an assistant referee and target pointing system. Our study is expected to fundamentally revolutionize the image and video concepts and related industries, including photography, movies, and visual media, and to unseal a new SNN-enabled speed-free machine vision era.

Abstract Klebsiella pneumoniae is a widespread pathogen of several human diseases. The emergence of multidrug-resistant K. pneumoniae makes the treatment of these diseases a significant challenge. The application of bacteriophages is a potential approach for dealing with the emergence of multidrug-resistant pathogenic bacteria. This study isolates a novel bacteriophage vB_KleM_KB2 that infects the multidrug-resistant clinical isolates of K. pneumoniae. The bacteriophage exhibits a short latent period of 10 min, and can effectively lyse the bacterium within 60 min. Notably, the bacteriophage can completely inhibit the growth of the host bacterium at the initial concentration of 107 CFU/mL with a low multiplicity of infection of 0.001, which proves its high lytic activity. Furthermore, the bacteriophage shows high environmental tolerances, which can facilitate the practical application of the bacteriophage. Analysis of the bacteriophage genome shows that the bacteriophage possesses a novel genome sequence and can represent a new bacteriophage genus. Considering the high lytic activity, short latent period, high stability, and novel genetic background, bacteriophage vB_KleM_KB2 enriches the bacteriophage library and provides a new alternative for controlling the diseases caused by multidrug-resistant pathogenic K. pneumoniae.

Abstract Objective White spot lesions (WSLs), the earliest evidence of enamel demineralization, are considered amenable to intervention to achieve a remineralized or arrested state of caries. The management of WSLs is quite challenging, and there is no definitive cure as yet. We performed a network meta-analysis to assess the efficacy of seven therapies for WSLs and gave a hierarchy of them. Materials and methods We systematically searched the PubMed, EMBASE, Cochrane, and Web of Science databases (last search: July 2022) to identify all relevant studies. We limited our search to studies published in English. Randomized controlled designed in vitro/clinical trials related to the efficacy of the seven therapies for WSLs were included. Data extraction was performed independently by two reviewers. The risk of bias (ROB) 2.0 tool from Cochrane and a previous in vitro methodological tool will be used for the quality assessment. Variations in quantitative light-induced fluorescence (QLF), laser fluorescence (LF), and lesions area were the primary outcome measures. Standard mean difference (SMD) was used as the effect size for the Network meta-analysis (NMA). Consistency and inconsistency tests were conducted. The hierarchy of 7 treatment effects was evaluated using surface probabilities under cumulative ranking (SUCRA). Publication bias was evaluated using a bias plot. Results Forty-two articles were included in the systematic review. Thirty-one of them, with a total of 1906 participants, were included in the network meta-analysis. The studies owned a low and moderate risk of bias. This analysis does not suffer from significant inconsistency. The difference between 4 groups ‘self-assembled peptide (SAP) P11-4’, ‘P11-4 + Fluoride Varnish (FV)’, ‘Resin Infiltration (RI)’, ‘casein phosphor peptides-amorphous calcium fluoride phosphate (CPP-ACFP)’ and the 'Control' group was found to be statistically significant. Compared to the ‘FV’ and ‘casein phosphor peptides-amorphous calcium phosphate (CPP-ACP)’ groups, the ‘P11-4 + FV” group and ‘RI” group made a significant difference. The hierarchy was evident in the SUCRA values of 7 therapies. P11-4 + FV and RI were considered effective therapies compared to the control group or the FV group (gold standard group). Conclusions The available evidence suggests that resin infiltration and P11-4 in combination with fluoride varnish had advantages over gold standard (FV). The effect of tricalcium phosphate-based drugs and fluoride is not very noticeable. Overall, drugs based on P11-4 and resin infiltration will be better therapies. Using more than two drugs in combination also would increase efficacy.

Objective The association between prepregnancy body mass index (BMI) or gestational weight gain (GWG) and adverse pregnancy outcomes among Chinese women with gestational diabetes mellitus (GDM) is unknown. This study aims to evaluate such association by synthesising the evidence.Design Systematic review and meta-analysis.Data sources PubMed, Web of Science, Scopus, EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wangfang, and China Science and Technology Journal Database searched from inception to 11 August 2023.Eligibility criteria Prospective cohort studies, retrospective cohort studies and case–control studies estimating the relationship of abnormal prepregnancy BMI (including underweight, overweight or obesity) or inappropriate GWG (including excess GWG or insufficient GWG) with adverse pregnancy outcomes of interest were included. Outcomes included macrosomia, caesarean section, preterm birth, gestational hypertension, large for gestational age (LGA) and small for gestational age (SGA).Data extraction and synthesis Two reviewers independently selected studies, extracted the data and assessed the risk of bias. OR estimate and its 95% CI were pooled using Stata software fixed-effect model. Subgroup analysis, meta-regression and sensitivity analysis were performed to ensure credibility of the results.Results Twenty-three studies (eighteen retrospective cohort studies, three prospective cohort studies and two case control studies) involving 57 013 Chinese women with GDM were identified. Meta-analysis results showed that compared with GDM women with normal weight, GDM women with underweight were at a higher risk of SGA (OR=1.79 (1.54 to 2.07), five studies involving 31 967 women); women with overweight had higher risks of macrosomia (OR=1.65 (1.49 to 1.82), eleven studies involving 41 683 women), caesarean section (OR=1.48 (1.38 to 1.59), ten studies involving 34 935 women), preterm birth (OR=1.27 (1.13 to 1.43), eight studies involving 38 295 women) and LGA (OR=1.73 (1.54 to 1.95), seven studies involving 31 342 women) and women with obesity had higher risks of macrosomia (OR=2.37 (2.04 to 2.76), eleven studies involving 41 683 women), caesarean section (OR=2.07 (1.84 to 2.32), nine studies involving 34 829 women), preterm birth (OR=1.31 (1.09 to 1.57), eight studies involving 38 295 women) and LGA (OR=2.63 (2.15 to 3.21), six studies involving 31 236 women). Regard to GWG, compared with Chinese GDM women with sufficient GWG, GDM women with excessive GWG had higher risks of macrosomia (OR=1.74 (1.58 to 1.92), twelve studies involving 40 966 women), caesarean section (OR=1.44 (1.36 to 1.53), nine studies involving 36 205 women) and LGA (OR=2.12 (1.96 to 2.29), twelve studies involving 42 342 women); women with insufficient GWG conversely had higher risks of preterm birth (OR=1.59 (1.45 to 1.74), nine studies involving 37 461 women) and SGA (OR=1.38 (1.27 to 1.51), ten studies involving 41 080 women).Conclusions For Chinese women with GDM, abnormal prepregnancy BMI or inappropriate GWG were related to higher risks of many adverse pregnancy outcomes. Therefore, medical staff should pay more attention to the weight management of GDM women during pregnancy.

Summary: The typical genomic feature of acute myeloid leukemia (AML) M3 subtype is the fusion event of PML/RARα, and ATRA/ATO-based combination therapy is current standard treatment regimen for M3 subtype. Here, a machine-learning model based on expressions of PML/RARα targets was developed to identify M3 patients by analyzing 1228 AML patients. Our model exhibited high accuracy. To enable more non-M3 AML patients to potentially benefit from ATRA/ATO therapy, M3-like patients were further identified. We found that M3-like patients had strong GMP features, including the expression patterns of M3 subtype marker genes, the proportion of myeloid progenitor cells, and deconvolution of AML constituent cell populations. M3-like patients exhibited distinct genomic features, low immune activity and better clinical survival. The initiative identification of patients similar to M3 subtype may help to identify more patients that would benefit from ATO/ATRA treatment and deepen our understanding of the molecular mechanism of AML pathogenesis.

Three evident and meaningful characteristics of disruptive technology are the zeroing effect that causes sustaining technology useless for its remarkable and unprecedented progress, reshaping the landscape of technology and economy, and leading the future mainstream of technology system, all of which have profound impacts and positive influences. The identification of disruptive technology is a universally difficult task. Therefore, this paper aims to enhance the technical relevance of potential disruptive technology identification results and improve the granularity and effectiveness of potential disruptive technology identification topics. According to the life cycle theory, dividing the time stage, then constructing and analyzing the dynamic of technology networks to identify potential disruptive technology. Thereby, using the Latent Dirichlet Allocation (LDA) topic model further to clarify the topic content of potential disruptive technologies. This paper takes the large civil unmanned aerial vehicles (UAVs) as an example to prove the feasibility and effectiveness of the model. The results show that the potential disruptive technology in this field is the data acquisition, main equipment, and ground platform intelligence.

Background Small for gestational age (SGA) poses a significant concern for newborns, being linked to neonatal complications and potential metabolic disorders in adulthood, especially when born to mothers with gestational diabetes mellitus (GDM), elevating their risk of complications and mortality. However, the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM remain unclear.Aim To identify the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM.Method This case–control study was conducted among 1910 women with GDM in China. Data were collected by the integrated electronic medical record system. Using 1:4 propensity score matching analysis, we adjusted for gestational age as confounder. Univariate and multivariate analyses were performed to identify risk factors.Results Risk factors for SGA born to mothers with GDM included a history of low birth weight, gestational hypertension, oligohydramnios, short maternal height, underweight pre-pregnancy body mass index and inadequate weight growth. While SGA was protected by weakly positive ketonuria levels in the first trimester, multiparous, anaemia and previous uterine scar were protective factors for SGA. Moreover, 2-hour postprandial glucose and haemoglobin A1c in the second trimester, as well as the 0-hour and 2-hour 75 g oral glucose tolerance test (OGTT) were linked to risk of SGA.Conclusions SGA infants are the result of multifactorial interactions among GDM pregnant women. Notably, glycaemic control levels were associated with SGA. There is a need for enhanced perinatal monitoring and antenatal care to reduce SGA.

Background Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods.Methods In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encoding Cxcl10, Nrf2 (an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments’ efficacy and mechanism.Results CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+ T cells, interferon-γ+ cytotoxic T lymphocytes (CTLs), GzmB+ CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+ and exhausted CD4+ T cells.Conclusions MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.

Nano-surface layers were prepared on the surface of 6061 aluminum alloy using the ultrasonic surface rolling process (USRP). The surface morphology, surface roughness, microstructure, hardness, and corrosion resistance of 6061 aluminum alloy were systematically characterized using X-ray diffraction (XRD), laser scanning confocal microscopy (LSCM), optical microscope(OM), scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and other testing methods. The results showed that ultrasonic surface rolling strengthening did not change the surface phase composition of 6061 aluminum alloy. It changed the size of the surface phases and the distance between the phases while refining the surface grains. The static pressures has a great influence on the surface properties of 6061 aluminum alloy. The best surface properties were obtained under 500N static pressures. The surface hardness reached 129.5HV0.5, the surface morphology was flat and continuous, the surface roughness was reduced to Ra0.191μm, and the corrosion resistance was significantly improved.

In this paper, single-diode model (SDM) and double-diode model (DDM) parameters of the French RTC solar cell and the Photowatt PWP 201 photovoltaic (PV) module were extracted by combining five metaheuristic algorithms with three simulation current calculation methods (i.e., approximation method, Lambert W method and Newton–Raphson method), respectively. It was found that the parameter-extraction accuracies of the Lambert W (LW) method and the Newton–Raphson (NR) method are always approximately equal and higher than that of the approximation method. The best RMSEs (root mean square error) obtained by using the LW or the NR method on the solar cell and the PV module are 7.72986 × 10−4 and 2.05296 × 10−3 for SDM parameter extraction and 6.93709 × 10−4 and 1.99051 × 10−3 for DDM parameter extraction, respectively. The latter may be the highest parameter-extraction accuracy reported on the solar cell and the PV module so far, which is due to the adoption of more reasonable DDM parameter boundaries. Furthermore, the convergence curves of the LW and the NR method basically coincide, with a convergence speed faster than that of the approximation method. The robustness of a parameter-extraction method is mainly determined by the metaheuristic algorithm, but it is also affected by the simulation current calculation method and the parameter-extraction object. In a word, the approximation method is not suitable for application in PV-model parameter extraction because of incorrect estimation of the simulation current and the RMSE, while the LW and NR methods are suitable for the application for accurately calculating the simulation current and RMSE. In terms of saving computation resources and time, the NR method is superior to the LW method.

In environments where silent communication is essential, such as libraries and conference rooms, the need for a discreet means of interaction is paramount. Here, we present a single-electrode, contact-separated triboelectric nanogenerator (CS-TENG) characterized by robust high-frequency sensing capabilities and long-term stability. Integrating this TENG onto the inner surface of a mask allows for the capture of conversational speech signals through airflow vibrations, generating a comprehensive dataset. Employing advanced signal processing techniques, including short-time Fourier transform (STFT), Mel-frequency cepstral coefficients (MFCC), and deep learning neural networks, facilitates the accurate identification of speaker content and verification of their identity. The accuracy rates for each category of vocabulary and identity recognition exceed 92% and 90%, respectively. This system represents a pivotal advancement in facilitating secure and efficient unobtrusive communication in quiet settings, with promising implications for smart home applications, virtual assistant technology, and potential deployment in security and confidentiality-sensitive contexts.

Objective This study explored whether plant-based and animal-based dietary patterns are associated with plasma glucose levels during oral glucose tolerance test in women with gestational diabetes mellitus (GDM).Design A prospective cohort study was conducted using a Food Frequency Questionnaire to collect dietary data. Dietary patterns were derived using principal component analysis. Multivariate logistic regression analysis was performed to explore the association between dietary patterns and plasma glucose levels. Stratified analyses were conducted according to maternal age, prepregnancy body mass index (BMI) and other confounders.Setting and participants The study, conducted in January 2022 in two hospitals in Fujian, China, involved 424 women diagnosed with GDM using a 75 g 2-hour oral glucose tolerance test at 24–28 gestational weeks.Results Six maternal dietary patterns (plant based and animal based) were identified. Participants with plant-based pattern had lower 2-hour plasma glucose levels than those with animal-based pattern (β=−0.314; 95% CI (−0.596 to –0.032)). After adjusting the regression model covariates, this significant association remained (β=−0.288; 95% CI (−0.568 to –0.008)) and appeared more pronounced in women aged 30 years or above and those with prepregnancy BMI

The prerequisite for underwater vehicles to accomplish various underwater tasks is to obtain real-time position information about themselves in the underwater environment using internal or external sensors, which is known as underwater positioning and navigation technology. This paper presents a general review of underwater vehicle positioning and navigation technology and illustrates the importance of underwater terrain-aided navigation technology. It also summarizes its general structure and describes the principles and functions of each component. The paper mainly analyzes various mainstream methods applied to underwater terrain-aided navigation, focuses on terrain suitability analysis and terrain matching algorithms, which play a central role in the analysis. Additionally, the research progress of terrain-aided navigation technology is described, and the research methods of terrain suitability analysis, terrain matching navigation, and the latest technology applications are compared. Some shortcomings of the current underwater terrain-aided navigation technology are presented, and future research directions are foreseen to provide a basis for subsequent research.

The rapid development of electric vehicles (EVs) has benefited from the fact that more and more countries or regions have begun to attach importance to clean energy and environmental protection. This paper focuses on the optimization of EV charging, which cannot be ignored in the rapid development of EVs. The increase in the penetration of EVs will generate new electrical loads during the charging process, which will bring new challenges to local power systems. Moreover, the uncoordinated charging of EVs may increase the peak-to-valley difference in the load, aggravate harmonic distortions, and affect auxiliary services. To stabilize the operations of power grids, many studies have been carried out to optimize EV charging. This paper reviews these studies from two aspects: EV charging forecasting and coordinated EV charging strategies. Comparative analyses are carried out to identify the advantages and disadvantages of different methods or models. At the end of this paper, recommendations are given to address the challenges of EV charging and associated charging strategies.

Cracked tooth is a common dental hard tissue disease.The involvement of cracks directly affects the selection of treatment and restoration of the affected teeth.It is helpful to choose more appropriate treatment options and evaluate the prognosis of the affected tooth accurately to determine the actual involvement of the crack.However, it is often difficult to accurately and quantitatively assess the scope of cracks at present.So it is necessary to find a real method of early quantitative and non-destructive crack detection.This article reviews the current clinical detection methods and research progress of cracked tooth in order to provide a reference for finding a clinical detection method for cracked tooth.

Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCμ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCμ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine’s expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy.

Introduction: Carboplatin (CBP) is a DNA damaging drug used to treat various cancers, including advanced melanoma. Yet we still face low response rates and short survival due to resistance. Triptolide (TPL) is considered to have multifunctional antitumor effects and has been confirmed to enhance the cytotoxic effects of chemotherapeutic drugs. Herein, we aimed to investigate the knowledge about the effects and mechanisms for the combined application of TPL and CBP against melanoma.Methods: Melanoma cell lines and xenograft mouse model were used to uncover the antitumor effects and the underlying molecular mechanisms of the alone or combined treatment of TPL and CBP in melanoma. Cell viability, migration, invasion, apoptosis, and DNA damage were detected by conventional methods. The rate-limiting proteins of the NER pathway were quantitated using PCR and Western blot. Fluorescent reporter plasmids were used to test the NER repair capacity.Results: Our results showed that the presence of TPL in CBP treatment could selectively inhibit NER pathway activity, and TPL exerts a synergistic effect with CBP to inhibit viability, migration, invasion, and induce apoptosis of A375 and B16 cells. Moreover, combined treatment with TPL and CBP significantly inhibited tumor progression in nude mice by suppressing cell proliferation and inducing apoptosis.Discussion: This study reveals the NER inhibitor TPL which has great potential in treating melanoma, either alone or in combination with CBP.

Biosensors based on allosteric transcription factors have been widely used in synthetic biology. In this study, we utilized the Acinetobacter ADP1 transcription factor PobR to develop a biosensor activating the PpobA promoter when bound to its natural ligand, 4-hydroxybenzoic acid (4HB). To screen for PobR mutants responsive to 4-hydroxyphenylpyruvate(HPP), we developed a dual selection system in E. coli. The positive selection of this system was used to enrich PobR mutants that identified the required ligands. The following negative selection eliminated or weakened PobR mutants that still responded to 4HB. Directed evolution of the PobR library resulted in a variant where PobRW177R was 5.1 times more reactive to 4-hydroxyphenylpyruvate than PobRWT. Overall, we developed an efficient dual selection system for directed evolution of biosensors.

ObjectiveThis study aimed to establish a predictive model for occult lymph node metastasis (LNM) in patients with clinical stage I-A non-small cell lung cancer (NSCLC) based on contrast-enhanced CT.MethodsA total of 598 patients with stage I–IIA NSCLC from different hospitals were randomized into the training and validation group. The “Radiomics” tool kit of AccuContour software was employed to extract the radiomics features of GTV and CTV from chest-enhanced CT arterial phase pictures. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was applied to reduce the number of variables and develop GTV, CTV, and GTV+CTV models for predicting occult lymph node metastasis (LNM).ResultsEight optimal radiomics features related to occult LNM were finally identified. The receiver operating characteristic (ROC) curves of the three models showed good predictive effects. The area under the curve (AUC) value of GTV, CTV, and GTV+CTV model in the training group was 0.845, 0.843, and 0.869, respectively. Similarly, the corresponding AUC values in the validation group were 0.821, 0.812, and 0.906. The combined GTV+CTV model exhibited a better predictive performance in the training and validation group by the Delong test (p