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Abstract Background We aimed to study the prognostic risk factors affecting patients with anaplastic thyroid carcinoma (ATC), develop a clinical prognostic model, and assess patient survival outcomes. Methods Patients with anaplastic thyroid carcinoma from 2000 to 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. The dataset was divided into training (70%) and validation (30%) sets based on a 7:3 ratio. Univariate and LASSO regression analyses were performed on clinical variables from the training set to identify independent prognostic factors. Independent prognostic factors were determined by Univariate and lasso regression according to the clinical variables of the training set, and a nomogram model was established to construct a prognostic model based on the contribution degree of the predictors. The prognostic model was evaluated and internally verified by C-index, ROC curve and calibration curve. Results A total of 713 ATC patients were included in the SEER database. LASSO regression results indicated that age, marital status, race, tumor size, whether the primary lesion was limited to the thyroid gland, surgery, radiotherapy and chemotherapy, were associated with overall survival(OS) prognosis of ATC, and were used to construct nomograms. In the training cohort, the OS nomogram’s C-index was 0.708 (95% CI 0.672–0.745); in the internal validation cohort, the C-index was 0.677 (95% CI 0.620–0.735). ROC curves demonstrated that the OS nomogram exhibits excellent predictive accuracy and discriminative ability. Calibration curves indicated strong consistency between the OS nomogram’s predicted survival rates and actual survival rates. Conclusions We established a survival prediction model for ATC, which can assist clinicians in assessing patient prognosis and making personalized treatment decisions.

Abstract Using acrylic acid advanced ester and styrene as raw materials, the long-chain polyester polymer, polyacrylic acid advanced ester-styrene pour point depressant (P-PPD), was synthesized by molecular design, and its structure was characterized by infrared spectroscopy and nuclear magnetic resonance. In addition, this study experimentally investigated the effect of P-PPD on the phase equilibrium and induction time of natural gas hydrate inhibitors in deionized water (DW) and crude oil/water (O/W) systems, respectively. Polyvinylpyrrolidone (PVP) and mono ethylene glycol (EG) were selected as representatives of kinetic hydrate inhibitor (KHIs) and thermodynamic hydrate inhibitor (THIs), respectively. The results exhibit that P-PPD played a sight role in the phase equilibrium of hydrate, while the addition of P-PPD significantly prolonged the induction time of methane hydrate both in O/W + PVP, OW + EG and O/W + PVP + EG system, indicating that the addition of as-synthesized PPD has a synergistic inhibition effect on the nucleation ability of methane hydrate and can prevent hydrate from formatting during oil and gas transport process, and thus guarantee the flow assurance. The findings of this work will provide a data reference for the hybrid use of hydrate inhibitors and pour point depressants in oil and gas transport.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Abstract Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues (‘glycofluoroforms’) using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow.

Abstract High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ).

Objective There is still a lack of systematic understanding of the evolution process of the Lianzhou Basin since the Mesozoic and its response to karstic development. Methods Based on the comprehensive analysis of the latest field geological investigations, hydrogeological drilling, dissolution experiments, and three-dimensional geological modelling, the tectonic evolution stages of the basin can be divided, and the karstification of each stage can be discussed by considering the existing geological data. Results Before the Cretaceous, carbonate rocks with strong dissolution were successively deposited under the rise or fall movement of the crust, which laid a material foundation for karstic development. The Indosinian movement caused vertically multilayered strata to form an E-W-trending structure, and the Yanshanian movement made the straddle-oblique superimposed a NE-SW-trending structure. They controlled the geological structures, spatial distribution, and dissolution behaviors of carbonate strata. And the distribution of mountains and river system were established. However, karst generally does not develop. An intracontinental and intermountain faulted confluence lake basin formed from the Cretaceous to the Palaeogene, the slow crustal uplift strengthened the karstification around the basin, and it currently retains the early karst platform. Later, they were buried-filled-consolidated by alluvial deposits; therefore, karst basically stopped developing, generating a thick-covered red strata basin. Since the Neogene, the rapid uplift of the crust has led to the continuous elevation of mountains around the basin, deepening of rivers, and strong development of karst, shaping multilevel karst platforms. When part of the Cretaceous red strata in the basin are denuded or cut through, karstification is reactivated. After many changes and penetrations of water systems, the graben basin formed, with karst strata covered by Quaternary sediments, Tectonic evolution controls karstic development, karstification influences the internal structure of the basin, and soil structure causes karst ground collapse. Conclusion This study can provide a scientific basis and guidance for understanding karst collapse conditions in covered karst areas.

Neptunium is one of long-life radioelements, whose speciation in different condition of underground water and soil type, including the adsorption characteristics and adsorption mechanism on some soils, is a critical field. The adsorption behavior of Np(Ⅴ) on muscovite minerals was studied by combining theoretical calculations and static adsorption experiments, providing a reference for evaluating the safety of nuclear waste disposal sites in this work. The adsorption behavior of 239Np(Ⅴ) by different particle sizes of muscovite was studied using characterization methods such as X-ray diffraction(XRD), scanning electron microscopy(SEM), material specific surface area(BET), and NaI(Tl) gamma spectroscopy. Explored the effects of factors such as time, pH value, and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} on the adsorption of Np(Ⅴ) by muscovite with different particle sizes. Combining density functional based on first principles, B3LYP was selected as the functional and 6-31G* as the basis group, and quantum chemical calculations were carried out to obtain the dissociation constant(pKa) values of the sites, in order to describe the electronic behavior of the skeleton structure. The experimental results show that different particle sizes of muscovite have an impact on the adsorption of Np(Ⅴ), and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} in the environment also affect the adsorption distribution coefficient. However, as the particle size of muscovite decreases, more active sites are exposed, and the trend of adsorption distribution coefficient varies. Based on the SEM image and adsorption distribution coefficient curve, it can be seen that as the grinding mesh size of the sample increases, the end face increases, and even layered muscovite is peeled off. In the alkaline region, the adsorption distribution coefficient slightly increases, but the adsorption distribution coefficient is all less than 100. A small amount of Np(Ⅴ) is enriched in fine-grained to extremely fine-grained minerals, related to finer sediment. The adsorption of Np(Ⅴ) by muscovite is weak and not dominant. Np(Ⅴ) mainly migrates with groundwater in muscovite minerals.

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF-α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF-α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF-α inhibitor, providing a promising lead compound for developing an antipsoriatic agent.

Summary: Background: Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Methods: Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Findings: Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVRmeta-temporal (r = 0.78). Area under curve (AUC) was 0.93 for Aβ− vs Aβ+ and 0.94 for tau− vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ− vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ− or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Interpretation: Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. Funding: NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

BackgroundRegulated cell death (RCD) is a genetically controlled form of cell death that plays an important role in organogenesis, tissue remodeling, and pathogenesis of cancers. Transforming growth factor-beta-activation kinase 1 (TAK1) is a member of the serine/threonine protein kinase family, which can respond to internal and external stimuli and participate in inflammatory responses through multiple signaling pathways and cellular processes. In the last two decades, the regulatory roles of TAK1 at the crossroads of multiple RCD pathways, including apoptosis, necroptosis, pyroptosis, and PANoptosis were revealed by 801 articles retrieved from the Web of Science Core Collection database. To analyze global research trends and hotspots concerning the role of TAK1 in RCD, the bibliometric and visualized analysis were applied in the current study.MethodsThe data for this bibliometrics study were retrieved from the Web of Science Core Collection database. The search formula was (TS=(Apoptosis) OR TS=(pyroptosis) OR TS=(Necroptosis) OR TS=(PANoptosis) OR TS=(Autophagy) OR TS=(Ferroptosis) OR TS=(cuproptosis)) AND ((TS=(TAK1)) OR TS=(MAP3K7)). The co-occurrence and co-cited analysis on basic bibliometric parameters were conducted by VOSviewer. The dual-map overlay of journals, citation bursts, keyword timelines, and keyword bursts were analyzed by CiteSpace.ResultsA total of 801 articles from 46 countries have been included in the analysis. The number of publications demonstrates a consistent increase from 1999 to 2024. The primary research institutions driving this field are Osaka University Notably, the Journal of Biological Chemistry stands out as the most popular journal in this domain. These publications collectively involve contributions from 4663 authors, with Jun Tsuji emerging as a prolific author. Jun Tsuji also gains the highest co-citation frequency. Emerging research hotspots are encapsulated by keywords, including apoptosis, NF-κB, inflammation, autophagy, and TNFα.ConclusionThis is the first bibliometric and visualized study to analyze the global trends and hotspots of TAK1 in RCD. Based on the analysis of 801 articles, the results provide a retrospective and comprehensive visualized view of the research hotspots and frontiers of TAK1 at the crossroads of multiple RCD signaling pathways and propose ideas for guiding their future investigations in molecular mechanisms and therapeutic strategies in this field.

Background: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited. Methods: A total of 2475 pregnant women from the Ma’anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children. Results: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). Conclusion: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age.

Background The maternal intrauterine immune environment may affect offspring long‐term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children. Methods and Results This study enrolled 1803 mother–child pairs from the Ma'anshan birth cohort (2013–2014). Placental mRNA expression of inflammatory cytokines (interleukin‐1β [IL‐1β], IL‐10, monocyte chemoattractant protein‐1, tumor necrosis factor‐α, IL‐4, IL‐6, IL‐8, C‐reactive protein, and interferon‐γ) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78) was quantified using real‐time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL‐1β, monocyte chemoattractant protein‐1, C‐reactive protein, IL‐6, IL‐8, IL‐10) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, glucose‐related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase‐1 and glucose‐related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL‐6, heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children's risk of high fasting blood glucose. Conclusions This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.

Triaxial compression tests were conducted on frozen sandy soils under a constant minimum principal stress (σ3 = 1.6 MPa) and various intermediate principal stresses (σ2 = 1.6, 3.4, 5.2, 7.0, 8.8, 9.8 MPa). The purpose of the research was to investigate the influence of intermediate principal stress on mechanical properties of frozen soil, and to establish a constitutive model to predict the stress-strain relationship of frozen soil under complex stress state. The test results obtained demonstrated that the crack damage stress and failure stress initially increase and then decrease with an increase in the intermediate principal stress. However, the crack initiation stress exhibits an initial increase up to a specific value, after which it stabilizes. From the perspective of crack propagation, the influence mechanism of intermediate principal stress on the strength was discussed. With the variation of stress state, the difference between intermediate principal strain and minimum principal strain gradually increases. The deformation difference was revealed using the stress superposition principle and Poisson's effect. Finally, the constitutive model based on the Weibull distribution and Drucker-Prager strength criterion can accurately represent the stress-strain relationships of frozen sandy soils under true triaxial stress states.

In situ phase separation precipitates play an important role in enhancing the thermoelectric properties of copper sulfides by suppressing phonon transmission. In this study, Cu1.8S composites were fabricated by melting reactions and spark plasma sintering. The complex structures, namely, micron-PbS, Sb2S3, nano-FeS, and multiscale pores, originate from the introduction of FePb4Sb6S14 into the Cu1.8S matrix. Using effective element (Fe) doping and multiscale precipitates, the Cu1.8S+0.5 wt% FePb4Sb6S14 bulk composite reached a high dimensionless figure of merit (ZT) value of 1.1 at 773 K. Furthermore, the modulus obtained for this sample was approximately 40.27 GPa, which was higher than that of the pristine sample. This study provides a novel strategy for realizing heterovalent doping while forming various precipitates via in situ phase separation by natural minerals, which has been proven to be effective in improving the thermoelectric and mechanical performance of copper sulfides and is worth promoting in other thermoelectric systems.

Abstract Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells.

Abstract The axle box of high-speed train adopts double row tapered roller bearings as transmission parts, and the reliability of bearings directly affects the safety of train operation. Tapered roller bearings can withstand axial and radial loads, their service life being closely related to the distribution of contact stress. The test object is the axle box bearing of high-speed train. According to bearing’s structural characteristics, based on the digital speckle correlation method (DSCM) and machine vision, the contact stress distribution detection devices for rollers and complete sets of bearings are developed respectively and an effective detection method is proposed. The contact stress data of the bearing which has reached the service life and the new bearing under the condition of no lubrication and grease lubrication are collected and normalized. Through the geometric relationship, based on the measured data of the selected detection points, the normal and tangential contact stress distribution of the roller and raceway under different contact conditions is obtained by data fitting. The test can be used as an evaluation basis for the effectiveness of bearing modification and provide reference for bearing design.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Abstract One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Abstract Background The caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality. Methods This study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs). Results Among included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally. Conclusions This large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further transcriptome profiling identified the pivotal signaling pathways and hub genes in response to acidosis. Collectively, these findings provide strong evidences for a critical role of acidosis in ADSCs impairment with ischemic condition and suggest treatments focus on tissue pH balance and acidosis-mediated hub genes may have therapeutic potential in stem cell-based application.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

ABSTRACTObjective To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia.Methods Children (

Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

G protein-coupled receptor-associated sorting protein 2 (GPRASP2) deficiency has been implicated in immunological inflammation, cancers, and neurological disorders. Our previous work revealed that the pathogenic mutation in GPRASP2 was responsible for X-linked recessive syndromic hearing loss (SHL). Given the specific high expression of GPRASP2 in the spiral ganglion, GPRASP2 likely contributes to the maintenance and functionality of neurons, potentially playing a role in synaptic transmission. The impact of GPRASP2 deficiency on spiral ganglion cells (SGCs) and their underlying pathogenic mechanisms will be investigated in this study. The primary culture of SGCs obtained from mouse cochleae was treated with Gprasp2-targeting short hairpin RNA (Gprasp2-shRNA) via lentivirus infection. The results showed that GPRASP2 deficiency enhanced SGCs apoptosis and decreased cell viability. Meanwhile, a significant abnormality of mitochondrial morphology and decreased membrane potential were observed in GPRASP2-deficient SGCs. These effects could be mitigated by treatment with the mitochondrial division inhibitor 1 (Mdivi-1). In addition to enhancing SGCs apoptosis and decreasing cell viability, GPRASP2 deficiency also inhibited the development of SGCs in mouse cochlear explant culture. Our study further revealed that this deficiency resulted in increased phosphorylation of AMPK and activation of the AMPK/DRP1 pathway, promoting SGCs apoptosis. These findings provide insight into the pathogenic mechanisms by which GPRASP2 deficiency is implicated in auditory dysfunction.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Partially aromatic polyamides owing to their excellent thermal stability are widely used in high temperature applications, however, like their aliphatic counterparts, they are readily flammable and more challenging to process. In this work, several organophosphorus flame retardants were synthesized and compounded with partially aromatic polyamide and evaluated for their processability, thermal, and fire behaviour. The compounds containing a commercial flame retardant, Exolit® OP 1230 (EX), and two new flame retardants, namely 1,4-phenylenebis(diphenylphosphine oxide) (MP) and (1,1′-biphenyl]-4,4′-diylbis(diphenylphosphine oxide) (BP), showed self-extinguishing capability (i.e., UL94 V0 class) with 4 wt% phosphorus (P) loading, together with a substantial reduction in the pHRR (up to 47 %), with respect to the pristine PAP. Rheological measurements on extended timescales were used to assess the melt stability of partially aromatic polyamide compounds. The presence of MP and BP in the polymer matrix did not trigger any excessive degradation phenomena such as chain scission, branching, or crosslinking reactions, thus, allowing a stable processability similar to a pristine partially aromatic polyamide sample. Finally, analysis of evolved gases during thermal decomposition revealed that MP and BP mainly exert a flame inhibition effect quite early in the decomposition process.

ObjectiveTo investigate the impact of diaphragmatic breathing combined with limb training on lower limb lymphedema following surgery for gynecological cancer.MethodsFrom January 2022 to May 2022, 60 patients with lower limb lymphedema post-gynecologic cancer surgery were chosen. They were split into a control group (n = 30) and a treatment group (n = 30). The control group underwent complex decongestive therapy (CDT) for managing lower limb lymphedema after gynecologic cancer surgery, while the treatment group received diaphragmatic breathing combined with limb coordination training alongside CDT. Both groups completed a 4-week treatment regimen. The lower limb lymphedema symptoms were evaluated using the genital, lower limb, buttock, and abdomen (GCLQ) scores; bilateral lower limb circumference measurements; and anxiety and depression scores.ResultsCompared to sole CDT administration, individuals undergoing diaphragmatic breathing coupled with limb coordination training experienced notable reductions in scores for the self-perceived symptom assessment questionnaire (GCLQ), bilateral lower limb circumference, as well as anxiety and depression scores.ConclusionThe incorporation of diaphragmatic breathing combined withalongside limb coordination training can accelerate and augment the efficacy of treating lower limb lymphedema post-gynecologic cancer surgery.

Abstract The significance means of the seismic reinforcement effect of a pile-anchor system for slope reinforcement has been widely recognized. However, cases of deformation failure and instability sliding of the pile-anchor system itself and the reinforced slope under seismic action continue to be recorded. Therefore, it is crucial to evaluate the seismic performance of slopes reinforced by a pile-anchor system to prevent the system’s failure. Current evaluation models of a slope reinforced by a pile-anchor system mainly focus on slope stability; however, the safety of the pile-anchor system itself is not sufficiently considered in these models. Consequently, in this study, we propose a multi-objective optimization evaluation (MOE) model for evaluating the seismic performance of slopes reinforced by a pile-anchor system that considers slope stability, safety of the pile-anchor system, and dynamic response of the slope. This model considers slope displacement, acceleration amplification factor of a slope, pile displacement, and anchor displacement as negative indexes, and anti-slide pile bending moment, shear force, and anchor axial force as intermediate indexes. The comprehensive weight of relevant indexes is obtained by combining subjective and objective weights, and the seismic reinforcement effect of the pile-anchor system is evaluated subsequently. In conclusion, the MOE model proposed in this study provides a novel solution for the optimization evaluation of a slope reinforced by a pile-anchor system in forthcoming projects.

Abstract Mid-infrared hyperspectral imaging has become an indispensable tool to spatially resolve chemical information in a wide variety of samples. However, acquiring three-dimensional data cubes is typically time-consuming due to the limited speed of raster scanning or wavelength tuning, which impedes real-time visualization with high spatial definition across broad spectral bands. Here, we devise and implement a high-speed, wide-field mid-infrared hyperspectral imaging system relying on broadband parametric upconversion of high-brightness supercontinuum illumination at the Fourier plane. The upconverted replica is spectrally decomposed by a rapid acousto-optic tunable filter, which records high-definition monochromatic images at a frame rate of 10 kHz based on a megapixel silicon camera. Consequently, the hyperspectral imager allows us to acquire 100 spectral bands over 2600-4085 cm−1 in 10 ms, corresponding to a refreshing rate of 100 Hz. Moreover, the angular dependence of phase matching in the image upconversion is leveraged to realize snapshot operation with spatial multiplexing for multiple spectral channels, which may further boost the spectral imaging rate. The high acquisition rate, wide-field operation, and broadband spectral coverage could open new possibilities for high-throughput characterization of transient processes in material and life sciences.

In order to achieve the goal of autonomous networks and improve the automation of network operation, an autonomous network model was explored.The model introduced algorithms such as multidimensional data automatic clustering, adaptive sliding time window mechanism, user traffic loss assessment model based on spatiotemporal sequence correlation, fault propagation graph based on graph theory and spatiotemporal clustering, and builded automation capabilities through network event management, fault self-identification, self-positioning, self-scheduling, and intelligent quality inspection.The goal is achieving L4 advanced intelligent network by 2025.

The segmentation of airborne lidar scanning (ALS) point clouds is one of the basic tasks in remote sensing field. The existed learning-based methods have acquired satisfactory performance, however, the training process requires a large amount of labeled data, which limits their wide application to some extent. Weakly-supervised learning of point clouds could achieve competitive results but far from perfect compared to fully supervised methods. In this article, we propose a weakly-supervised method for semantic segmentation of ALS point clouds based on learning of line and plane points. In addition, as basic feature units widely existing in large-scale scenes, both line and plane features could provide certain supervisory signals for training. Specifically, we extract line and plane points through two hand-crafted methods, which achieve offline line and plane point extraction. The extracted line and plane points are considered as additional supervisory signals, and consequently two auxiliary tasks could be constructed based on prediction of line and plane points, respectively. Furthermore, a multistage learning framework is proposed to embed the two auxiliary tasks into existing network, which makes the feature learning of network in the line-plane-object way. Moreover, we introduce an improved pseudolabel generation strategy based on prediction-consistency of contiguous models, which could generate high-quality pseudolabels so that to improve the performance of network. Extensive experiments conducted on three ALS point cloud datasets, i.e., ISPRS, LASDU, and DFC2019, demonstrate that the proposed method achieves considerable gains upon the baseline with respect to F1 score and overall accuracy under 0.1$\%$, 0.5$\%$, and 0.05$\%$ weak labels.

Hyperspectral images are widely use due to their rich spectral information. Meanwhile, the difficult acquisition of data labels makes unsupervised classification attracts attention. Subspace clustering as an unsupervised classification method is widely used for hyperspectral image analysis because of its excellent performance and robustness. However, conventional subspace clustering does not consider the nonlinear structure of hyperspectral data, and deep subspace clustering tends to ignore the intrinsic structure of hyperspectral data. To address these problems, we developed a self-expressive learning network, ResSENet, for hyperspectral data; we then proposed the application of ResSENet under graph constraints (GC-ResSENet), considering the intrinsic graph structure of the data. Unlike conventional deep subspace clustering, our model discards the self-expressive layer; self-expressive coefficients between datasets are directly solved by the data using network parameters. Hyperparameters are used in the joint loss to balance the self-expressive properties of the data and the graph constraint terms. We evaluated GC-ResSENet by applying it to four well-known datasets, and our network achieved optimal performance. In addition, because of its abandonment of the self-expressive layer, ResSENet is theoretically capable of clustering with large datasets; thus, we evaluated it using two large datasets.

Abstract PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA+ cells. Sub-epithelial PDGFRAHi myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRALo CD55+ cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1 + cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55+ cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.

This is an essay in the field of ceramics and composites.With the increasing demand for crude oil processing technology, China′s platinum rhenium catalyst industry is also developing. Catalyst is the core material of petroleum smelting, and impregnation method is the most important preparation method of reforming catalyst. Catalytic reforming catalysts generally refer to trace rhenium catalysts. The main research direction in the future is to increase the rhenium content of the catalyst and reduce the amount of platinum in the catalyst. The characteristics of platinum-rhenium catalysts are good stability, slightly poor selectivity, long-term stable operation, and regeneration cycle that can reach 3~5 years, which have been widely used in large-scale production of semi-regenerative reforming processes. Since the late 20th century, China′s refining catalyst market has formed a′Sinopec and PetroChina′s catalyst companies, supplemented by private catalyst companies′ market structure, catalyst demand is stable at more than 10 tons per year.

Abstract Objective Early onset of adiposity rebound (AR) is considered an early indicator of obesity risk. Our objective was to investigate the association of birth outcomes and early physical growth patterns with early AR in children. Methods Study subjects (n = 2705) were enrolled from the Ma’anshan birth cohort (MABC). The body mass index (BMI), head circumference, waist circumference, and body fat were collected. Rapid weight gain (RWG) was defined by the change in weight standard-deviation score in the first two years of life. Group-based trajectory modeling (GBTM) was used to determine children’s physical growth trajectories. The age of AR was fitted using fractional polynomial function models. Results Children with very high BMI trajectories (RR = 2.83; 95% CI 2.33 to 1.40), rising BMI trajectories (RR = 3.15; 95% CI 2.66 to 3.72), high waist circumference trajectories (RR = 4.17; 95% CI 3.43 to 5.06), and high body fat trajectories (RR = 3.01; 95% CI 2.62 to 3.46) before 72 months of age were at a greater risk of experiencing early AR. Low birth weight (LBW) (RR = 1.86; 95% CI 1.28 to 2.51), preterm birth (PTB) (RR = 1.50; 95% CI 1.17 to 1.93), and small for gestational age (SGA) (RR = 1.37; 95% CI 1.14 to 1.64) associated with increased risk of early AR. Moreover, infants experiencing RWG (RR = 1.59; 95% CI 1.40 to 1.83), low BMI trajectories (RR = 1.27; 95% CI 1.06 to 1.53) and rising BMI trajectories (RR = 1.50; 95% CI 1.22 to 1.84) in the first two years were at higher risk of developing early AR subsequently. Compared to the group with non-early AR, the BMI of children with early AR tended to be lower first (from birth to 6 months of age) and then higher (from 18 to 72 months of age). Conclusions Children with overall high BMI, high waist circumference, and high body fat before 72 months of age are more likely to experience early AR, but infants with low BMI trajectories, rising BMI trajectories and infants experiencing RWG in the first two years of life similarly increase the risk of early AR. These results can help to understand the early factors and processes that lead to metabolic risks.

Drought stress during sorghum emergence significantly affects seedling establishment, adversely affecting both emergence and population growth. This study investigates drought tolerance mechanisms during sorghum germination by analyzing physiological changes and transcriptomic data from two lines: W069 (drought tolerant) and W040 (drought sensitive). Under drought conditions, a phenotypic analysis revealed that W069 exhibited longer shoots and roots than W040. Additionally, physiological data indicated higher osmotic substance and lower malondialdehyde levels in W069. Using Kyoto Encyclopedia of Genes and Genome analyses, we identified three key pathways (starch and sucrose metabolism, phenylpropanoid biosynthesis, and phytohormone signaling) as pivotal in the drought response during seed germination in sorghum plants. Expression profiling revealed that most drought tolerance-related genes in the three key pathways were expressed at higher levels in the drought-tolerant cultivar W069, possibly explaining its greater stress tolerance. These findings enhance our understanding of drought-responsive gene networks in sorghum seed germination, offering potential target genes and strategies for enhancing drought tolerance in this crop.

Abstract Nuclear receptors (NRs) are important transcriptional factors that mediate autophagy, preventing podocyte injury and the progression of diabetic kidney disease (DKD). However, the role of nuclear receptor coactivators that are powerful enhancers for the transcriptional activity of NRs in DKD remains unclear. In this study, a significant decrease in Nuclear Receptor Coactivator 3 (NCOA3) is observed in injured podocytes caused by high glucose treatment. Additionally, NCOA3 overexpression counteracts podocyte damage by improving autophagy. Further, Src family member, Fyn is identified to be the target of NCOA3 that mediates the podocyte autophagy process. Mechanistically, NCOA3 regulates the transcription of Fyn in a nuclear receptor, PPAR‐γ dependent way. Podocyte‐specific NCOA3 knockout aggravates albuminuria, glomerular sclerosis, podocyte injury, and autophagy in DKD mice. However, the Fyn inhibitor, AZD0530, rescues podocyte injury of NCOA3 knockout DKD mice. Renal NCOA3 overexpression with lentivirus can ameliorate podocyte damage and improve podocyte autophagy in DKD mice. Taken together, the findings highlight a novel target, NCOA3, that protects podocytes from high glucose injury by maintaining autophagy.

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China’s pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn’s disease and thyroid diseases. Graves’ disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Microfilaments are the main component of the cell cytoskeleton and have a crucial influence on the morphology of living cells. The microfilaments provide mechanical support against applied loads and overcome competing forces that arise from various mechanisms, such as the elasticity of the cell membrane, binding reactions, and surface tension. However, modeling the mechanical properties of microfilaments is an open problem. In the present paper, we proposed a new continuum deformation energy density of microfilaments using the coarse-grained molecular force field and the local differential geometry of curves. In the new theory, the deformation energy density is a function of the microfilament’s strain and the curvature. This theory also unfolded the connections between the mechanical parameters and the coarse-grained force field. We found that the stretching stiffness and the bending stiffness are independent of the section of microfilaments. Microfilaments have a nonlinear stretching-bending term different from the classical beam theory. This means the classical beam theory cannot be directly applied to microfilaments with large deformations. Our theory provides the basis that the modified classical beam theory applies to the nonlinear mechanical behavior of cellular microfilaments.

Abstract Background The immunologic milieu at the maternal–fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers’ cognitive performance. Methods Study subjects were obtained from the Ma’anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1β, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children’s intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis. Results A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (β = − 0.53; 95% CI, − 0.92 to − 0.15), IL-6 (β = − 0.58; 95% CI, − 0.97 to − 0.19), TNF-α (β = − 0.37; 95% CI, − 0.71 to − 0.02), and IFN-γ (β = − 0.31; 95% CI, − 0.61 to − 0.03) in the placenta was negatively associated with preschoolers’ full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children’s low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children’s working memory index (WMI). After further adjusting for confounders and children’s age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children’s cognitive development was mainly concentrated in boys. Conclusions Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

Abstract Planar diffractive lenses (PDLs) with optimized but disordered structures can focus light beyond the diffraction limit. However, these disordered structures have inevitably destroyed wide-field imaging capability, limiting their applications in microscopy. Here, we introduce information entropy S to evaluate the disorder of an objective chip by using the probability of its structural deviation from standard Fresnel zone plates. Inspired by the theory of entropy change, we predict an equilibrium point $${S}_{0}=0.5$$ S 0 = 0.5 to balance wide-field imaging (theoretically evaluated by the Strehl ratio) and subdiffraction-limit focusing. To verify this, a $${NA}=0.9$$ N A = 0.9 objective chip with a record-long focal length of 1 mm is designed with $$S=0.535$$ S = 0.535 , which is the nearest to the equilibrium point among all reported PDLs. Consequently, our fabricated chip can focus light with subdiffraction-limit size of 0.44 λ and image fine details with spatial frequencies up to 4000 lp/mm experimentally. These unprecedented performances enable ultracompact reflective confocal microscopy for superresolution imaging.

With the enhancement of environmental protection and the incentive policies issued by governments, the choice of electric vehicles as a means of transportation has gradually become a new mode, so the establishment of a perfect charging station service network is a key link and an critical guarantee for accelerating the adoption of electric vehicles (EVs). In the early stage of EV charging station construction, reasonable and scientific planning is not only related to the convenient travel of users, but also related to the effective utilization of resources. To promote the development of low-carbon economy, this paper first propose a Voronoi diagram based charging station service division approach, followed by a M/G/K queuing model based approach for evaluating the charging capacity of the EV charging station. Finally, a location and volume model is constructed and solved to determine the optimal construction plan of the EV charging station with minimum total cost for the whole society. The experimental results show that the charging station planning method proposed in this paper is economical and effectively improves the charging convenience of electric vehicle users. The reasonable location setting and capacity configuration of charging stations promote the sustainable development of the power grid in the planning area, which has certain practical significance.

The utilization of optical antennas for active control of far-field radiation at the subwavelength scale is crucial in various scientific and technological applications. We propose a thermally tunable disk design of indium tin oxide (ITO) and aluminum gallium nitride (Al0.18Ga0.82As), enabling a switch between absorption and scattering. Furthermore, the control of far-field radiation pattern can be easily realized by combining ITO and Al0.18Ga0.82As to enhance or suppress emission. Our results demonstrate that hybrid structures can be dynamically tuned with temperature variations. In the proposed design, a frequency is achieved at the wavelength of 1240 nm. The thermal tunability of hybrid structures introduces new multifunctional possibilities for light manipulation, thereby enhancing the potential applications of new devices in the near-infrared range.

Abstract Gray mold is a destructive plant disease caused by a fungal pathogen Botrytis cinerea. The use of plant growth promoting rhizobacteria (PGPR) has proven to be a promising method to control this disease. Bacillus velezensis K01 was isolated from the rhizosphere of planting tomatoes. Strain K01 has a range of roles, including the ability to solubilize phytate phosphorus, stimulate resistant response, and produce indoleacetic acid (IAA), protease, cellulase, and antimicrobial substances. Strain K01 was found to inhibit 12 phytopathogenic fungi and 5 phytopathogenic bacteria. Specially, strain K01 demonstrated a biocontrol efficiency of over 78% against gray mold caused by B. cinerea on the leaves and fruits of tomato and pepper. Additionally, K01 was found to promote the growth of maize seedlings. Further genomic analysis revealed that K01 belongs to B. velezensis, which is consistent with phylogenetic analysis, average nucleotide polymorphism (ANI), and digital DNA–DNA hybridization (dDDH). The genome of strain K01 had a size of 3,927,799 bp and deduced 3866 predicted genes, with an average guanine-cytosine (GC) content of 46.5%. Based on the analyses of genomic secondary metabolites, over 18.4% of the genome was annotated to 12 gene clusters related to antimicrobial metabolite synthesis. Additionally, genome annotation and comparative genomics identified several genes associated with plant growth promotion and environmental adaption. These findings suggest that B. velezensis K01 has the potential to serve as a new biocontrol agent for management of gray mold on tomato and pepper.

Abstract Background Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The “placenta-brain axis” (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. Methods The authors performed multivariate logistic regression models between MLPT and children’s neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma’anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. Results The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. Conclusions These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.

A novel protocol was developed for the construction of highly functionalized pyridin-2(1H)-ones from 3-formylchromones, ethyl 2-(pyridin-2-yl)acetate derivatives and amines via a complex multicomponent cascade reaction involving targeted duplicated ring-opening and duplicated cyclization reactions which form skeleton-reorganized target compounds. A series of pyridin-2(1H)-ones were produced by this reaction accompanied by the formation of three bonds (one C–N and two C–C bonds) and the cleavage of one bond in one step. This protocol can be used in combinatorial and parallel syntheses of various pyridin-2(1H)-ones with potent biological activity. The advantages of this approach include simple and practical operation (multicomponent one-pot), high yields (up to 91%), and products with potential biological activity.