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The ubiquitous presence of organophosphate esters (OPEs) in the environment has prompted growing concerns about their potential health risks, particularly their endocrine-disrupting effects. This study comprehensively evaluated the endocrine-disrupting properties of six emerging OPEs: five aryl-OPEs (2-ethylhexyl diphenyl phosphate (EHDPP), tris (2-biphenylyl) phosphate (TBPP), resorcinol bis (diphenyl phosphate) (RDP), 4-hydroxyphenyl diphenyl phosphate (para-OH-TPHP), and 3-hydroxyphenyl diphenyl phosphate (meta-OH-TPHP) and one alkyl-OPE, triallyl phosphate (TAP). Our findings revealed that all tested aryl-OPEs exhibited antagonistic effects on one or more hormone receptors. Importantly, para-OH-TPHP demonstrated the most potent antagonistic activity, inhibiting estrogen receptor α (ERα), thyroid hormone receptor β (TRβ), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) with the concentration of test compounds showing 20 % relative inhibitory concentration (RIC 20 ) value below 10 -6 mol/L (M). RDP antagonized ERα and cortical receptors (GR and MR), TBPP affected TRβ and GR, while EHDPP and meta-OH-TPHP targeted MR. Regarding steroidogenesis, para-OH-TPHP significantly inhibited genes for estrogen (cyp19) and cortisol synthesis (cyp11b2), and along with meta-OH-TPHP, EHDPP, TAP, and RDP downregulated cyp11a1, a rate-limiting enzyme in hormone synthesis. All compounds caused malformations and swimming abnormalities in zebrafish embryos/larvae at concentrations of 10 -7 M or higher, with para-OH-TPHP showing nearly 50 % peak induction. Furthermore, the six compounds tested influenced genes associated with the hypothalamic-pituitary-gonadal (HPG) axis in both zebrafish larvae and adult female zebrafish, in addition to affecting the reproductive behavior of zebrafish. A weighted scoring system was employed to rank the endocrine-disrupting potency of the OPEs, with para-OH-TPHP exhibiting the highest risk, followed by EHDPP, RDP, TBPP, meta-OH-TPHP, and TAP. Collectively, our results highlight the significant endocrine-disrupting effects of emerging OPEs, underscoring the urgent need for further research to assess their potential health implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (Pax3) gene is involved in neural tube closure. However, the exact mechanism between Pax3 and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of Pax3 on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and Pax3 were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of Pax3. These results suggest that decreased expression of Pax3 impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Overexpression of Poly (ADP-ribose) polymerase (PARP) is associated with many diseases such as oncological diseases. Several PARP-targeting radiotracers have been developed to detect tumor in recent years. Two 18 F labelled probes based on Olaparib and Rucaparib molecular scaffolds have been evaluated in clinical trials, but their slow hepatic clearance hinders their tumor imaging performance. Although a number of positron emission tomography (PET) probes with lower liver uptake have been designed, the tumor to background ratios remains to be low. Therefore, we designed a probe with low lipid-water partition coefficient to solve this problem., Methods: A pyridine-containing quinazoline-2,4(1 H,3 H)-dione PARP-targeting group was rationally designed and used to conjugate with the chelator 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to prepare the lead compound named as SMIC-2001 for radiolabeling. In vitro experiments, the lipid-water partition coefficient, stability, binding affinity, and cellular uptake of [ 68 Ga]Ga-SMIC-2001 were determined. In vivo experiments, the U87MG xenograft models were used to evaluate its tumor imaging properties., Results: [ 68 Ga]Ga-SMIC-2001 showed a low Log D 7.4 (-3.82 ± 0.06) and high affinity for PARP-1 (48.13 nM). In vivo study revealed that it exhibited a high tumor-to-background contrast in the U87MG xenograft models and mainly renal clearance. And the ratios of tumor to main organs were high except for the kidney (e.g. tumor to liver ratio reached 2.20 ± 0.51) at 60 min p.i., Conclusion: In summary, pyridine-containing quinazoline-2,4(1 H,3 H)-dione is a novel PARP-targeting molecular scaffold for imaging probe development, and [ 68 Ga]Ga-SMIC-2001 is a highly promising PET probe capable of imaging tumors with PARP overexpression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, CO 2 electrolysis, particularly the electrochemical reduction of CO 2 to CO in zero-gap systems, has gained significant attention. While Ag-coated gas diffusion electrodes are commonly used in state-of-the-art systems, heterogenized molecular catalysts like bis-coordinated homoleptic silver(I) N,N-bis(arylimino)-acenaphthene (Ag-BIAN) complexes are emerging as a promising alternative due to their tunability and high mass activity. In this study, the influence of ink composition on the performance of Ag-BIAN-based GDEs in zero-gap electrolyzers (ZGEs) are systematically explored at 60 °C and 600 mA cm⁻ 2 . Sedimentation analyses across various solvents informed the selection of optimal solvent-catalyst and solvent-carbon additive combinations, streamlining the GDE optimization process and reducing associated costs and time. These results demonstrate that solvent choice and dilution state of the ink are critical factors impacting CO 2 reduction, achieving faradaic efficiencies for CO production (FE CO ) up to 67% at 600 mA cm⁻ 2 with catalyst loadings as low as 0.2 mg cm⁻ 2 . These findings lay the groundwork for advancing from homogeneous H-type cells to industrial ZGE systems through tailored ink engineering., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Astrocyte-derived IL-3 activates the corresponding receptor IL-3Rα in microglia. This cross-talk between astrocytes and microglia ameliorates the pathology of Alzheimer's disease in mice. In this study we investigated the role of IL-3/IL-3Rα cross-talk and its regulatory mechanisms in ischemic stroke. Ischemic stroke was induced in mice by intraluminal occlusion of the right middle cerebral artery (MCA) for 60 min followed by reperfusion (I/R). Human astrocytes or microglia subjected to oxygen-glucose deprivation and reoxygenation (OGD/Re) were used as in vitro models of brain ischemia. We showed that both I/R and OGD/Re significantly induced decreases in astrocytic IL-3 and microglial IL-3Rα protein levels, accompanied by pro-inflammatory activation of A1-type astrocytes and M1-type microglia. Importantly, astrocyte-derived VEGFD acting on VEGFR3 of astrocytes and microglia contributed to the cross-talk dysfunction and pro-inflammatory activation of the two glial cells, thereby mediating neuronal cell damage. By using metabolomics and multiple biochemical approaches, we demonstrated that IL-3 supplementation to microglia reversed OGD/Re-induced lipid metabolic reprogramming evidenced by upregulated expression of CPT1A, a rate-limiting enzyme for the mitochondrial β-oxidation, and increased levels of glycerophospholipids, the major components of cellular membranes, causing reduced accumulation of lipid droplets, thus reduced pro-inflammatory activation and necrosis, as well as increased phagocytosis of microglia. Notably, exogenous IL-3 and the VEGFR antagonist axitinib reestablished the cross-talk of IL-3/IL-3Rα, improving microglial lipid metabolic levels via upregulation of CPT1A, restoring microglial phagocytotic function and attenuating microglial pro-inflammatory activation, ultimately contributing to brain recovery from I/R insult. Our results demonstrate that VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives pro-inflammatory activation, causing lipid metabolic reprogramming of microglia. These insights suggest VEGFR3 antagonism or restoring IL-3 levels as a potential therapeutic strategy for ischemic stroke., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Thirty-four Chinese families (each consisting of a mother and two children) were recruited to participate in this study. The firstborn children had an average age of 12.00 ± 2.07 years, while the second-born children averaged 7.57 ± 2.51 years old. The families were randomly divided into mediation and control groups. The mothers in the mediation group underwent mediation training, whereas those in the control group received no treatment. Analysis of variance (ANOVA) and Chi-square tests were utilized to analyze data on sibling conflict. Results indicated that the mothers in the mediation group reported significantly less negative behavior in helping their children resolve sibling disputes compared to those in the control group. Mediation group mothers reported significantly fewer sibling conflicts compared to control group mothers. No significant differences were observed between children in the mediation group and the control group regarding positive and negative behaviors recorded by mothers. These results indicate that mediation training may better equip Chinese mothers with the ability to resolve sibling conflicts in their families.

Objectives: Childbearing histories-for example, parity and age at first birth-matter for the health outcomes of mid- and later-life women. There is growing evidence that childbearing may shape cognitive outcomes. However, previous research is not definitive due to its inability to account for selection. Selection is critical to address given that multiple factors, including socioeconomic background and cognition in adolescence, place women at risk for both specific childbearing experiences and poor cognitive functioning., Methods: We analyze the 1979 National Longitudinal Survey of Youth (NLSY79) (N=3,668), a longitudinal nationally representative dataset from the US that began collecting data during respondents' late teens and early 20s. We estimate the average treatment effects (ATEs) of childbearing histories on midlife memory and cognition using propensity-score matching techniques that incorporate an expansive set of early-life factors., Results: In models adjusting for early life covariates, we find that any births, high parity, and early first birth are associated with worse self-reported memory, but not cognitive functioning scores. After addressing the influence of early life factors through matching techniques, the only robust differences relate to any births and early first births with self-reported memory., Discussion: Selection into specific childbearing experiences partially drives the link between childbearing and cognition at mid-life, with cascading implications into later life. We suggest incorporating childbearing and early life factors into models to identify social determinants of memory and cognitive functioning., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Manganese is a key metal involved in the catalysis of natural photosynthesis. Thus, the investigation of Mn-based electrocatalysts for water oxidation is of high importance. This work reports the doping of Mo into α-MnO2 nanorods to improve the water oxidation performance. The doping of Mo can transform the microstructure of α-MnO2 from nanorods into nanosphere superstructures. As a dopant, Mo expands the α-MnO2 lattice to result in a decrease in the average oxidation state of Mn and the generation of oxygen vacancies, which are beneficial to water oxidation catalysis. Under optimized doping, the OER overpotential of Mo/α-MnO2 is reduced by 80 mV (at 10 mA/cm2) compared with pure α-MnO2., (© 2024 Wiley‐VCH GmbH.)

A multi-feature fusion DCNN model for automated evaluation of lumbar vertebrae L1 on chest combined with clinical information and radiomics permits estimation of volumetric bone mineral density for evaluation of osteoporosis., Purpose: To develop a multi-feature deep learning model based on chest CT, combined with clinical information and radiomics to explore the feasibility in screening for osteoporosis based on estimation of volumetric bone mineral density., Methods: The chest CT images of 1048 health check subjects were retrospectively collected as the master dataset, and the images of 637 subjects obtained from a different CT scanner were used for the external validation cohort. The subjects were divided into three categories according to the quantitative CT (QCT) examination, namely, normal group, osteopenia group, and osteoporosis group. Firstly, a deep learning-based segmentation model was constructed. Then, classification models were established and selected, and then, an optimal model to build bone density value prediction regression model was chosen., Results: The DSC value was 0.951 ± 0.030 in the testing dataset and 0.947 ± 0.060 in the external validation cohort. The multi-feature fusion model based on the lumbar 1 vertebra had the best performance in the diagnosis. The area under the curve (AUC) of diagnosing normal, osteopenia, and osteoporosis was 0.992, 0.973, and 0.989. The mean absolute errors (MAEs) of the bone density prediction regression model in the test set and external testing dataset are 8.20 mg/cm 3 and 9.23 mg/cm 3 , respectively, and the root mean square errors (RMSEs) are 10.25 mg/cm 3 and 11.91 mg/cm 3 , respectively. The R-squared values are 0.942 and 0.923, respectively. The Pearson correlation coefficients are 0.972 and 0.965., Conclusion: The multi-feature fusion DCNN model based on only the lumbar 1 vertebrae and clinical variables can perform bone density three-classification diagnosis and estimate volumetric bone mineral density. If confirmed in independent populations, this automated opportunistic chest CT evaluation can help clinical screening of large-sample populations to identify subjects at high risk of osteoporotic fracture., (© 2024. The Author(s).)

Background: Decidualization is a critical step in establishing pregnancy in mammals. Successful decidualization depends on intricate gland-stromal crosstalk. Clusterin (Clu) is a ubiquitously secreted protein in physiological fluids that is involved in numerous physiological functions. However, the role of Clu in decidualization is not fully understood., Results: In this study, we examined the expression pattern of Clu during early pregnancy in mice and explored its potential function in decidualization. Our results revealed that Clu was expressed in the uterine glands on Days 1-2 of early pregnancy and on Days 5-8 during decidualization after embryo implantation, as well as in glands at the interimplantation site. Additionally, ovariectomized mice exhibited significant upregulation of Clu expression in the uterine glands 3 h after in vivo estrogen injection. Trem2, a receptor for Clu, was detected in the decidual region of mice on Days 5-8 of early pregnancy, where it mediates Clu to regulate the decidual region. Furthermore, we observed that recombinant CLU protein increased the expression of the decidualization marker molecules insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL) in decidual cells. However, this upregulation was not observed when Trem2 expression was inhibited with siRNA., Conclusions: Uterine gland-derived Clu, a new paracrine modulator, may participate in early pregnancy by influencing the decidualization process mediated by Trem2 in mice., (© 2024. The Author(s).)

In clinical settings, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) are commonly employed in brain imaging to assist clinicians in determining the type of stroke in patients. However, these modalities are associated with potential hazards or limitations. In contrast, microwave imaging emerges as a promising technique, offering advantages such as non-ionizing radiation, low cost, lightweight, and portability. The primary challenges faced by microwave tomography include the severe ill-posedness of the electromagnetic inverse scattering problem and the time-consuming nature and unsatisfactory resolution of iterative quantitative algorithms. This paper proposes a learning electric field enhancement imaging method (LEFEIM) to achieve quantitative brain imaging based on a microwave tomography system. LEFEIM comprises two cascaded networks. The first, based on a convolutional neural network, utilizes the electric field from the receiving antenna to predict the electric field distribution within the imaging domain. The second network employs the electric field distribution as input to learn the dielectric constant distribution, thereby realizing quantitative brain imaging. Compared to the Born Iterative Method (BIM), LEFEIM significantly improves imaging time, while enhancing imaging quality and goodness-of-fit to a certain extent. Simultaneously, LEFEIM exhibits anti-noise capabilities.

An example of palladium/norbornene-catalyzed C-H/N-H cycloaddition of carbazoles with 2-bromobenzoic acids is presented, in which a collection of important carbazoles is expeditiously obtained. Derivatives, including acyl halides, α-oxocarboxylic acids, anhydrides, and even amides, are all allowed. Preliminary mechanistic studies reveal that a rare six-membered spiropalladacycle is involved.

As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zou, Xu, Cao, Zhang, Zhang and Zhao.)

S-adenosylmethionine (SAM) as a major methyl donor plays a key role in methylation modification in vivo, and its disorder was closely related to neural tube defects (NTDs). However, the exact mechanism between SAM deficiency and NTDs remained unclearly. Hence, we investigated the association between histone methylation modification and cell differentiation in NTDs mice induced by SAM deficiency. The levels of SAM and SAH (S-adenosylhomocysteine) were determined by enzyme linked immunosorbent assay (ELISA). The level of histone methylation, β-catenin were analyzed by Western blot, reversing transcription and quantitative PCR (RT-qPCR) and immunofluorescence. The results showed that the incidence rate of NTDs induced by ethionine were 46.2%. Post treatment of ethionine combined with SAM, the incidence rate of NTDs was reduced to 26.2%. The level of SAM was significantly decreased (p < 0.05) and a reduction in the SAM/SAH ratio was observed after entionine treatment. The SAM deficiency caused the reduction of H3K27me3 modifications and the elevated UTX activity (p < 0.05), and inhibited the expressions of β-catenin. The differentiations of NSCs into neurons and oligodendrocytes were inhibited under SAM deficiency (p < 0.05). These results indicated that the SAM deficiency led to reduce H3K27me3 modifications, prevented the β-catenin signaling pathway and NSCs differentiation, which provided an understanding of the novel function of epigenetic regulation in NTDs., (© 2024 Wiley Periodicals LLC.)

Objective. In the field of steady-state visual evoked potential brain computer interfaces (SSVEP-BCIs) research, convolutional neural networks (CNNs) have gradually been proved to be an effective method. Whereas, majority works apply the frequency domain characteristics in long time window to train the network, thus lead to insufficient performance of those networks in short time window. Furthermore, only the frequency domain information for classification lacks of other task-related information. Approach. To address these issues, we propose a time-frequency domain generalized filter-bank convolutional neural network (FBCNN-G) to improve the SSVEP-BCIs classification performance. The network integrates multiple frequency information of electroencephalogram (EEG) with template and predefined prior of sine-cosine signals to perform feature extraction, which contains correlation analyses in both template and signal aspects. Then the classification is performed at the end of the network. In addition, the method proposes the use of filter banks divided into specific frequency bands as pre-filters in the network to fully consider the fundamental and harmonic frequency characteristics of the signal. Main results. The proposed FBCNN-G model is compared with other methods on the public dataset Benchmark. The results manifest that this model has higher accuracy of character recognition accuracy and information transfer rates in several time windows. Particularly, in the 0.2 s time window, the mean accuracy of the proposed method reaches62.02%±5.12%, indicating its superior performance. Significance. The proposed FBCNN-G model is critical for the exploitation of SSVEP-BCIs character recognition models., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Chemical synthesis of unconventional topologically close-packed intermetallic nanocrystals (NCs) remains a considerable challenge due to the limitation of large volume asymmetry between the components. Here, a series of unconventional intermetallic Frank-Kasper C15 phase Ir 2 M (M = rare earth metals La, Ce, Gd, Tb, Tm) NCs is successfully prepared via a molten-salt assisted reduction method as efficient electrocatalysts for hydrogen evolution reaction (HER). Compared to the disordered counterpart (A1-Ir 2 Ce), C15-Ir 2 Ce features higher Ir-Ce coordination number that leads to an electron-rich environment for Ir sites. The C15-Ir 2 Ce catalyst exhibits excellent and pH-universal HER activity and requires only 9, 16, and 27 mV overpotentials to attain 10 mA cm -2 in acidic, alkaline, and neutral electrolytes, respectively, representing one of the best HER electrocatalysts ever reported. In a proton exchange membrane water electrolyzer, the C15-Ir 2 Ce cathode achieves an industrial-scale current density of 1 A cm -2 with a remarkably low cell voltage of 1.7 V at 80 °C and can operate stably for 1000 h with a sluggish voltage decay rate of 50 µV h -1 . Theoretical investigations reveal that the electron-rich Ir sites intensify the polarization of *H 2 O intermediate on C15-Ir 2 Ce, thus lowering the energy barrier of the water dissociation and facilitating the HER kinetics., (© 2024 Wiley‐VCH GmbH.)

The primary driver of increasing atmospheric concentrations of nitrous oxide (N 2 O) is the use of organic and synthetic fertilizer to increase agricultural crop production. Current global estimates are based on IPCC N 2 O emission factor (EF) calculations, although there are shortcomings as many of the N 2 O EFs are derived from measurements during the cropping season. These neglect the fallow season, and do not adequately account for double or even triple cropping systems or legacy effects on soil N 2 O emissions in the following year. In this study, we assessed the legacy effect of fertilization on soil N 2 O fluxes using data from a long-term double-cropping field experiment with summer maize and winter wheat in rotation, in which no nitrogen (N; NN) and balanced manure with synthetic N (MN) fertilized treatments were switched to allow an assessment of legacy effects. Based on high-frequency measurements of N 2 O and previous data, we calculated that the historical N fertilization, or legacy effect, explained 23 % of the annual flux of 0.81 kg N ha -1  yr -1 in the first season of observation. In the following three seasons, the legacy effect of the previous N fertilization regime decreased to a negligible level, with N 2 O emissions mainly driven by in-season fertilization. Our data show that, on average, the seasonal EF for N 2 O was about 0.11 % higher in response to the previous N fertilization. Our study indicates that the current N 2 O EF may severely underestimate emissions because studies ignore legacy effects on N 2 O emissions from zero N plots and only compare zero N with N fertilization treatments for a given season or year to derive seasonal or annual N 2 O EF., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black)., Medthods and Findings: A total of 4,712 plasma proteins were measured using SomaScan in blood samples collected in 1990 to 1992 from 11,761 midlife participants (aged 46 to 70 years) and in 2011 to 2013 from 5,183 late-life participants (aged 66 to 90 years). The de novo ARIC PACs were constructed by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and validated in the remaining one-third of healthy participants at the corresponding time point. We also computed 3 published PACs. We estimated age acceleration for each PAC as residuals after regressing each PAC on chronological age. We also calculated the change in age acceleration from midlife to late life. We examined the associations of age acceleration and change in age acceleration with mortality through 2019 from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in participants (irrespective of health) after excluding the training set. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. We externally validated the midlife PAC using the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 data. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC PACs and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per 1 standard deviation were 1.65 and 1.38 (both p < 0.001) for all-cause mortality, 1.37 and 1.20 (both p < 0.001) for CVD mortality, 1.21 (p = 0.028) and 1.04 (p = 0.280) for cancer mortality, and 1.68 and 1.36 (both p < 0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to the HRs for late-life age acceleration. The association between the change in age acceleration and cancer mortality was not significant. The external validation of the midlife PAC in MESA showed significant associations with mortality, as observed for midlife participants in ARIC. The main limitation is that our PACs were constructed in midlife and late-life participants. It is unknown whether these PACs could be applied to young individuals., Conclusions: In this longitudinal study, we found that the ARIC PACs and published PACs were similarly associated with an increased risk of mortality. These findings suggested that PACs show promise as biomarkers of biological age. PACs may be serve as tools to predict mortality and evaluate the effect of anti-aging lifestyle and therapeutic interventions., Competing Interests: B.L. is a full-time employee of the biopharmaceutical company Alkahest, Inc. P.L.L’s institute receives grants from NIH., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of radiopharmaceuticals based on fibroblast activation protein inhibitors (FAPIs) have been developed and translated into the clinic. Though some of them such as radiolabeled FAPI-04 probes have achieved favorable in vivo imaging performance, further improvement is still highly desired for obtaining radiopharmaceuticals with a high theranostics potential. In this study, we innovatively designed an FAPI ligand SMIC-3002 by changing the core quinoline motif of FAPI-04 to the quinolinium scaffold. The engineered molecule was further radiolabeled with 68 Ga to generate a positron emission tomography (PET) probe, [ 68 Ga]Ga-SMIC-3002, which was then evaluated in vitro and in vivo. [ 68 Ga]Ga-SMIC-3002 demonstrated high in vitro stability, nanomolar affinity for FAP (8 nM for protein, 23 nM for U87MG cells), and specific uptake in FAP-expressing tumors, with a tumor/muscle ratio of 19.1 and a tumor uptake of 1.48 ± 0.03 ID/g% at 0.5 h in U87MG tumor-bearing mice. In summary, the quinolinium scaffold can be successfully used for the development of the FAP-targeted tracer. [ 68 Ga]Ga-SMIC-3002 not only shows high potential for clinical translation but also offers insights into designing a new generation of FAPI tracers.

In interval reproduction tasks, animals must remember the event starting the interval and anticipate the time of the planned response to terminate the interval. The interval reproduction task thus allows for studying both memory for the past and anticipation of the future. We analyzed previously published recordings from the rodent medial prefrontal cortex [J. Henke et al. , eLife 10 , e71612 (2021)] during an interval reproduction task and identified two cell groups by modeling their temporal receptive fields using hierarchical Bayesian models. The firing in the "past cells" group peaked at the start of the interval and relaxed exponentially back to baseline. The firing in the "future cells" group increased exponentially and peaked right before the planned action at the end of the interval. Contrary to the previous assumption that timing information in the brain has one or two time scales for a given interval, we found strong evidence for a continuous distribution of the exponential rate constants for both past and future cell populations. The real Laplace transformation of time predicts exponential firing with a continuous distribution of rate constants across the population. Therefore, the firing pattern of the past cells can be identified with the Laplace transform of time since the past event while the firing pattern of the future cells can be identified with the Laplace transform of time until the planned future event., Competing Interests: Competing interests statement:M.W.H. is a cofounder of Cognitive Scientific AI, Inc., which could conceivably benefit indirectly from this publication.

Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses., (© 2024. The Author(s).)

Background: Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate the protein expression and enzyme activity of cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key enzyme that converts 2-5% of sevoflurane into equimolar amounts of hexafluoroisopropanol (HFIP) and F - . This study aims to explore whether ethanol exposure could alter sevoflurane metabolism through CYP2E1 modulation, potentially explaining the increased MAC observed in alcohol users., Methods: Eighty adult male Sprague-Dawley (SD) rats were randomly divided into two groups and received either 50% ethanol (dose: 3 g/kg) or 0.9% saline twice daily by gavage. After 1, 2, 3, and 4 weeks of gavage, ten rats were randomly selected from each group to undergo 1-hour anesthesia with 2.3% sevoflurane. Blood samples were collected after anesthesia to measure the concentration of free HFIP using gas chromatography. Additionally, the left lobe tissue of the liver was collected for the analysis of CYP2E1 protein expression by Western blot and CYP2E1 enzyme activity by colorimetric assay. Correlations between these parameters were analyzed using Pearson's correlation., Results: In the ethanol group, CYP2E1 expression, activity, and the concentration of free HFIP were significantly higher at all time points compared to the control group (P < 0.05), except for protein expression in the first week (P > 0.05). Within-group comparisons indicated no significant changes in any of the parameters for the control group (P > 0.05). In the ethanol group, there was no difference in free HFIP concentration between the first and second weeks (P > 0.05), but a significant increase was observed in the third and fourth weeks (P < 0.01); protein expression and enzyme activity significantly varied over time, especially showing a notable increase from the first to the third and fourth weeks (P < 0.05). Correlation analysis revealed strong positive correlations between free HFIP concentration and CYP2E1 activity (r = 0.7898), free HFIP concentration and CYP2E1 expression (r = 0.8418), and CYP2E1 activity and expression (r = 0.8740), all with P < 0.001., Conclusions: Ethanol exposure increased both the expression and enzymatic activity of CYP2E1, consequently enhancing the metabolism of sevoflurane., (© 2024. The Author(s).)

Flexible zinc-air batteries are leading power sources for next-generation smart wearable electronics. However, flexible zinc-air batteries suffer from the highly-corrosive safety risk and limited lifespan due to the absence of reliable solid-state electrolytes (SSEs). Herein, a single-anion conductive SSE with high-safety is constructed by incorporating a highly amorphous dual-cation ionomer into a robust hybrid matrix of functional carbon nanotubes and polyacrylamide polymer. The as-fabricated SSE obtains dual-penetrating ionomer-polymer networks and hierarchical ionic highways, which contribute to mechanical robustness with 1200 % stretchability, decent water uptake and retention, and superhigh ion conductivity of 245 mS ⋅ cm -1 and good Zn anode reversibility. Remarkably, the flexible solid-state zinc-air batteries delivers a high specific capacity of 764 mAh ⋅ g -1 and peak power density of 152 mW ⋅ cm -2 as well as sustains excellent cycling stability for 1050 cycles (350 hours). This work offers a new paradigm of OH - conductors and broadens the definition and scope of OH - conductors., (© 2024 Wiley-VCH GmbH.)

Due to the challenge of cleaving O-O bonds at single Co sites, mononuclear Co complexes typically show poor selectivity for the four-electron (4e - ) oxygen reduction reaction (ORR). Herein, we report on selective 4e - ORR catalyzed by a Co porphyrin with a hanged Zn II ion. Inspired by Cu/Zn-superoxide dismutase, we designed and synthesized 1-CoZn with a hanging Zn II at the second sphere of a Co porphyrin. Complex 1-CoZn is much more effective than its Zn-lacking analogues to catalyze the 4e - ORR in neutral aqueous solutions, giving an electron number of 3.91 per O 2 reduction. With spectroscopic studies, the hanging Zn II was demonstrated to be able to facilitate the electron transfer from Co II to O 2 , through an electronic "pull effect", to give Co III -superoxo. Theoretical studies further suggested that this "pull effect" plays crucial roles in assisting O-O bond cleavage. This work is significant to present a new strategy of hanging a Zn II to improve O 2 activation and O-O bond cleavage., (© 2024 Wiley-VCH GmbH.)

Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the structure-activity correlation is an important prerequisite for the rational design of high-efficiency electrocatalysts at the atomic level. However, the effect of coordination environment on electrocatalytic oxygen evolution reaction (OER) remains enigmatic. In this work, the regulation of proton transfer involved in water oxidation by coordination engineering based on Co 3 (PO 4 ) 2 and CoHPO 4 is reported. The HPO 4 2- anion has intermediate pK a value between Co(II)-H 2 O and Co(III)-H 2 O to be served as an appealing proton-coupled electron transfer (PCET) induction group. From theoretical calculations, the pH-dependent OER properties, deuterium kinetic isotope effects, operando electrochemical impedance spectroscopy (EIS) and Raman studies, the CoHPO 4 catalyst beneficially reduces the energy barrier of proton hopping and modulates the formation energy of high-valent Co species, thereby enhancing OER activity. This work demonstrates a promising strategy that involves tuning the local coordination environment to optimize PCET steps and electrocatalytic activities for electrochemical applications. In addition, the designed system offers a motif to understand the structure-efficiency relationship from those amino-acid residue with proton buffer ability in natural photosynthesis., (© 2024 Wiley‐VCH GmbH.)

Multinuclear metal clusters are ideal candidates to catalyze small molecule activation reactions involving the transfer of multiple electrons. However, synthesizing active metal clusters is a big challenge. Herein, on constructing an unparalleled Co 4 (SO 4 ) 4 cluster within porphyrin-based metal-organic frameworks (MOFs) and the electrocatalytic features of such Co 4 (SO 4 ) 4 clusters for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is reported. The reaction of Co II sulfate and metal complexes of tetrakis(4-pyridyl)porphyrin under solvothermal conditions afforded Co 4 -M-MOFs (M═Co, Cu, and Zn). Crystallographic studies revealed that these Co 4 -M-MOFs have the same framework structure, having the Co 4 (SO 4 ) 4 clusters connected by metalloporphyrin units through Co─N pyridyl bonds. In the Co 4 (SO 4 ) 4 cluster, the four Co II ions are chemically and symmetrically equivalent and are each coordinated with four sulfate O atoms to give a distorted cube-like structure. Electrocatalytic studies showed that these Co 4 -M-MOFs are all active for electrocatalytic OER and ORR. Importantly, by regulating the activity of the metalloporphyrin units, it is confirmed that the Co 4 (SO 4 ) 4 cluster is active for oxygen electrocatalysis. With the use of Co porphyrins as connecting units, Co 4 -Co-MOF displays the highest electrocatalytic activity in this series of MOFs by showing a 10 mA cm -2 OER current density at 357 mV overpotential and an ORR half-wave potential at 0.83 V versus reversible hydrogen electrode (RHE). Theoretical studies revealed the synergistic effect of two proximal Co atoms in the Co 4 (SO 4 ) 4 cluster in OER by facilitating the formation of O─O bonds. This work is of fundamental significance to present the construction of Co 4 (SO 4 ) 4 clusters in framework structures for oxygen electrocatalysis and to demonstrate the cooperation between two proximal Co atoms in such clusters during the O─O bond formation process., (© 2024 Wiley‐VCH GmbH.)

The photocatalytic reduction of CO 2 to high-value fuels has been proposed as a solution to the energy crisis caused by the depletion of energy resources. Despite significant advancements in photocatalytic CO 2 reduction catalyst development, there are still limitations such as poor CO 2 adsorption/activation and low charge transfer efficiency. In this study, we employed a defect-induced heterojunction strategy to construct atomic-level interface Cd-O bonds and form Bi 2 MoO 6 /Zn 0.5 Cd 0.5 S heterojunctions. The sulfur vacancies (V S ) formed in Bi 2 MoO 6 /Zn 0.5 Cd 0.5 S acted as activation sites for CO 2 adsorption. While the interfacial stability provided by the Cd-O bonds served as an electron transfer channel that facilitated the movement of electrons from the interface to the catalytic site. The V S and Cd-O bonds simultaneously influence the distribution of charge, inducing the creation of an interface electric field that facilitates the upward displacement of the center of the d-band. This enhances the adsorption of reaction intermediates. The optimized Bi 2 MoO 6 /Zn 0.5 Cd 0.5 S heterostructure exhibited high selectivity and stability of photoelectrochemical properties for CO, generating 42.97 μmol⋅g -1 ⋅h -1 of CO, which was 16.65-fold higher than Zn 0.5 Cd 0.5 S under visible light drive. This research provides valuable insights for designing photocatalyst interfaces with improved CO 2 adsorption conversion efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

A new CeCO 3 OH@(hexagonal/cubic phases-CdS) (CeCO 3 OH@(H/C-CdS)) composite catalyst was facilely synthesized by a simple microinjection titration-stirring method, in which CdS nanoparticles were dispersed on the surface of CeCO 3 OH nanolines. The optimal conditions for the preparation of composite catalysts with high photocatalytic performance were determined by single-factor experiments and response surface experiments. Under these conditions, the degradation rate of 30 mL 2.000 g/L rhodamine B (Rh B) by CeCO 3 OH@(H/C-CdS) in a photocatalytic reaction for 1 h at 25 °C was up to 86.81 % and its degradation rate in a photocatalytic reaction for 150 min was up to 99.62 %. The degradation rate could be maintained above 80 % even after six times recycling. Especially, the photocatalytic degradation efficiency of 2.000 g/L Rh B on the composite catalyst under sunlight and at room temperature for 30 min reached 97.66 %. Meanwhile, the large size of CeCO 3 OH considerably alleviated the agglomeration of CdS, providing more adsorption and active sites for visible light-mediated degradation of Rh B. Importantly, the Z-scheme charge transfer realized by CdS and CeCO 3 OH enhanced the efficient separation of photogenerated electrons and holes, and successfully inhibited the recombination of photogenerated electrons with holes. At the same time, owing to the low energy band difference between the two phases of CdS, charge was transferred between the hexagonal and cubic phases, leaving more effective photogenerated charge to participate in the degradation of Rh B. The synergism of the heterophase junction and heterojunction and the presence of oxygen and sulfur vacancies considerably enhanced the degradation performance of the catalyst. Thus, this study provides a new strategy for the modification and enhanced visible-light catalysis performance of CdS-based catalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Understanding electronic effects on catalysis from a mechanism point of view is of fundamental significance but is also challenging. We herein report on electronic effects on the oxygen reduction reaction (ORR) with Fe porphyrins. By using Fe III tetraphenylporphyrin (TPP-Fe) and Fe III tetra(pentafluorophenyl)porphyrin (TPFP-Fe), we showed their different electrochemical and chemical behaviors for ORR. Mechanism studies revealed that the Fe III -superoxo species of TPP-Fe can undergo smooth protonation with trifluoroacetic acid (TFA) but the electron-deficient Fe III -superoxo species of TPFP-Fe cannot be protonated with TFA. The Fe III -superoxo reactivity difference between TPP-Fe and TPFP-Fe is the origin of their different catalytic ORR behaviors., (© 2024 Wiley-VCH GmbH.)

Improving proton transfer is vital for electrocatalysis with porous materials. Although several strategies are reported to assist proton transfer in channels, few studies are dedicated to improving proton transfer at the local environments of active sites in porous materials. Herein, we report on new Co-corrole-based porous organic polymers (POPs) with improved proton transfer for electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). By tuning the pore sizes and installing proton relays at Co corrole sites, we designed and synthesized POP-2-OH with improved proton transfer both in channels and at local Co active sites. This POP shows remarkable activity for both electrocatalytic ORR with E 1/2 =0.91 V vs RHE and OER with η 10 =255 mV. Therefore, this work is significant to present a strategy to improve active site local proton transfer in porous materials and highlight the key role of such structural functionalization in boosting oxygen electrocatalysis., (© 2024 Wiley-VCH GmbH.)

Herein, the precise fabrication of Sb 2 S 3 and low Se content Sb 2 Se y S 3- y indoor photovoltaics is reported, and a measurement protocol for photovoltaic performance is suggested and applied. Insertion of the SnO 2 buried layer decreases the thickness and parasitic absorption of the CdS layer. The introduction of minor Se into Sb 2 S 3 and the use of spiro -OMeTAD:TMT-TTF improve the charge transport of indoor photovoltaics. Using a white light-emitting diode (LED) under illuminance of 1000, 500, and 200 lx with color temperatures of 3347 and 6103 K, indoor photovoltaics with fluorine doped tin oxide (FTO)/SnO 2 (17 nm)/CdS (20 nm)/Sb 2 S 3 / spiro -OMeTAD:TMT-TTF/Au exhibit power conversion efficiency (PCE) values of 17.59, 16.66, 16.44, 16.56, 15.50, and 14.07%, respectively. Indoor photovoltaics with FTO/SnO 2 (17 nm)/CdS (20 nm)/Sb 2 Se y S 3- y (Sb/S/Se = 1:1.42:0.06)/ spiro -OMeTAD:TMT-TTF/Au achieve PCE values of 18.53, 17.62, 17.07, 17.30, 16.24, and 15.38%, respectively. The PCE values of 17.59, 16.66, and 16.44% are the highest values reported for Sb 2 S 3 indoor photovoltaics, and the other PCEs are all reported for the first time. Considering the trillion-dollar-sized market from the Internet of Things (IoT), this work can further bring an unprecedented thrust to the development of self-powered IoT devices by harvesting energy from indoor photovoltaics, thereby realizing the recycling of photon energy and reducing the use of batteries and the emission of CO 2 .

Objective: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs., Methods: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI., Results: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events., Conclusions: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials., (© 2024. The Author(s).)

Based on the carbon emission accounting method for domestic sewage, combined with the current situation of rural domestic sewage treatment, the carbon emissions of traditional schemes and source separation schemes under the three scenarios of single household, multi-household, and pipeline treatments were calculated. The results showed that the net carbon emissions （calculated as CO 2 ） of the single household, multi-household, and pipeline treatment traditional schemes were 1.21, 3.37, and 2.69 kg·m -3 , respectively. The net carbon emissions （calculated as CO 2 ） of the single household, multi-household, and pipeline treatments in source separation schemes were -0.50, -0.04, and -0.54 kg·m -3 , respectively, achieving zero or even negative carbon emissions. The direct and indirect carbon emissions of the source separation scheme were lower than those of the traditional scheme under all three scenarios. The carbon compensation measures in the source separation scheme mainly came from the land use of urine after storage and treatment. By separating blackwater from graywater at the source, the Source Separation Program achieved resource utilization of highly concentrated pollutants in blackwater, reducing emissions while generating significant carbon offsets. Therefore, efforts should be made to promote the separation and treatment of rural domestic sewage sources, improve the utilization rate of rural domestic sewage resources, and achieve green and low-carbon development of rural domestic sewage treatment.

Influenza viruses present a significant threat to global health. The production of a universal vaccine is considered essential due to the ineffectiveness of current seasonal influenza vaccines against mutant strains. mRNA technology offers new prospects in vaccinology, with various candidates for different infectious diseases currently in development and testing phases. In this study, we encapsulated a universal influenza mRNA vaccine. The vaccine encoded influenza hemagglutinin (HA), nucleoprotein (NP), and three tandem repeats of matrix protein 2 (3M2e). Twice-vaccinated mice exhibited strong humoral and cell-mediated immune responses in vivo. Notably, these immune responses led to a significant reduction in viral load of the lungs in challenged mice, and also conferred protection against future wild-type H1N1, H3N2, or H5N1 influenza virus challenges. Our findings suggest that this mRNA-universal vaccine strategy for influenza virus may be instrumental in mitigating the impact of future influenza pandemics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The next generation phased array radio telescopes, such as the Square Kilometre Array (SKA) low frequency aperture array, suffer from RF interference (RFI) because of the large field of view of antenna element. The classical station beamformer used in SKA-low is resource efficient but cannot deal with the unknown sidelobe RFI. A real-time adaptive beamforming strategy is proposed for SKA-low station, which trades the capability of adaptive RFI nulling at an acceptably cost, it doesn't require hardware redesign but only modifies the firmware accordingly. The proposed strategy uses a Parallel Least Mean Square (PLMS) algorithm, which has a computational complexity of 4N+2 and can be performed in parallel. Beam pattern and output SINR simulation results show deeply nulling performance to sidelobe RFI, as well as good mainlobe response similar to the classical beamformer. The convergence performance depends on the signal-and-interference environments and step size, wherein too large a step size leads to a non-optimal output SINR and too small a step size leads to slow convergence speed. FPGA implementation demonstrations are implemented and tested on a NI FPGA module, and test results demonstrate good real-time performance and low slice resource consumption.

Objective: To study the effect of predictive early nutritional care intervention on gastrointestinal function, Subjective global nutritional assessment (SGA) score, serum albumin (ALB) and high-sensitivity C-reactive protein (hs CRP), quality of life and quality of sleep in patients on maintenance haemodialysis., Methods: A total of 90 cases of maintenance hemodialysis patients in our hospital were collected from March 2020 and randomly divided into two groups of 45 cases each. The control group was cared for according to routine procedures. The study group added predictive early nutritional care intervention to this control group, i.e., nutritional personalized care was adjusted according to the patient's own disease, adherence, and comorbidities. The nursing effects, improvement of gastrointestinal function, and serum indexes when the two groups were compared., Results: Before the intervention, there was no difference between the two groups regarding the improvement of gastrointestinal function, pg-sga score, or serum indexes (P > .05). After the intervention, the gastrointestinal function, pg-sga score and serum indexes in the two groups were improved, and the calorie and protein intake, the total effective rate of gastrointestinal function improvement, ALB level and quality of life score in the control group were significantly lower than those in the study group; BMI, AC, and TSF were significantly higher compared with study group; The level of hs CRP and sleep quality score in the study group were smaller than those in the study group (P < .05)., Conclusion: Through predictive early nutritional care intervention, maintenance hemodialysis patients can increase food intake and improve protein and calorie intake. In turn, it effectively improves gastrointestinal function, malnutrition and microinflammation, and improves life and sleep, which is worthy of clinical promotion.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08&#95;BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01&#95;AE (10.9%, 19/174), and CRF07&#95;BC (8.0%, 14/174) were the main genotypes. CRF08&#95;BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07&#95;BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Objective: This study aimed to explore the mechanism by which noise contributes to the development of Alzheimer's disease (AD)-like lesions., Method: Male Wistar rats (24 months) were allocated into two groups (n = 6 per groups): a noise group exposed to 98 dB sound pressure-level white noise for 4 hours daily from 8:00 to 12:00 for 30 days, and a control group without noise exposure. The cognitive functions of the rats were assessed using new-object recognition and Morris water maze tests. Then, hippocampal tissues were collected, and the levels of amyloid β 1-42 (Aβ1-42), Aβ1-40, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) were measured using enzyme-linked immunosorbent assay (ELISA). Protein expression was evaluated through Western blot., Results: Noise exposure significantly impaired cognitive and recognition abilities, increased the escape latency, and decreased the number of crossings through the platform quadrant intersection and the time spent in the target quadrant (P < 0.01). The new-object exploration and recognition index of the rats in the noise group markedly decreased (P < 0.01). ELISA results indicated increases in Aβ1-40 and Aβ1-42 levels and decreases in BDNF and TrkB levels in the rat hippocampus in the noise group (P < 0.01). Western blot analyses revealed that beta-site amyloid precursor protein (APP) cleaving enzyme 1, phosphorylated tau protein, gamma-H2A histone family, member X, checkpoint kinase 2, p53, and p21 were remarkably elevated in the noise group (P < 0.01)., Conclusion: Chronic noise exposure can cause hippocampal genetic damage in aged rats, leading to cognitive disorders and the development of lesions similar to those observed in AD. Thus, noise is a potential risk factor for neurodegenerative disorders., (Copyright © 2024 Noise & Health.)

The testis, as one of the important reproductive organs in men, has two major functions of secreting androgens and producing sperm. Androgen and spermatogenesis are the key factors for the evaluation of the testicular function. The lack of androgen or the decline of spermatogenic function is both a symbolic manifestation and a "product" of testis aging. In order to gain a deeper insight into the relationship between testis aging and overall health, this article reviews the relevant literature based on the correlation of androgen deficiency with various systemic diseases and the belief in the impacts of testis aging on the health of the cardiovascular and nervous systems through different channels, the development and progression of metabolic diseases, orthopedic diseases, PCa, kidney disease, peptic ulcer and other diseases. All these suggest that adequate attention should be paid to the studies of male reproductive health and its impact on overall health, so as to provide some new ideas and evidence for clinical diagnosis and treatment of relevant conditions.

Fossil epifoliar fungi are valuable indicators of paleoenvironment and paleoecology. The Meliolaceae, members of which typically inhabit the surface of living plants as biotrophs or pathogens, is one of the largest groups of epifoliar fungi. In this study, we report a novel fossil species of Meliolinites Selkirk (fossil Meliolaceae), Meliolinites tengchongensis , on the lower epidermis of compressed fossil Rhodoleia (Hamamelidaceae) leaves from the Upper Pliocene Mangbang Formation of Tengchong, Yunnan, southwestern China. Meliolinites tengchongensis is characterized by web-like, superficial, brown to dark brown, septate, and branching mycelia bearing 2-celled appressoria and unicellular phialides. The fungal colonies also include ellipsoidal, 5-celled, 4-septate ascospores and dark brown perithecia with suborbicular outline and verrucose surface. The well-preserved vegetative and reproductive organs help us to explore the potential disease process of the new fossil species. Besides, the presence of fungal remains indicates that the fungal taxon might have maintained its host preference since at least the Late Pliocene. Furthermore, the occurrence of both fossil fungi and their host plants in Tengchong indicate a subtropical-tropical, warm, and humid climate during the Late Pliocene, whereas the distribution pattern of the fungi on the host leaves suggests that Rhodoleia may have been a part of the middle-upper canopies in the Tengchong Late Pliocene multilayered forest.

In the present study, sensory orientation and instrumental analysis were employed to separate, purify, and identify umami peptides in Agrocybe aegerita hydrolysate. Using UPLC-ESI-Q-TOF MS, 11 potential umami peptides (EY, EG, EV, ENG, PEG, DEL, ECG, DDL, PEEL, EDCS and DGPL) were identified from the screened fractions. Moreover, sensory evaluation and E-tongue results showed that the identified umami peptides had umami attributes, within an umami threshold range of 0.0625-0.25 mg mL -1 . In addition, DDL and DEL exhibited the highest umami flavor intensity. Molecular docking analysis further showed that 4 umami peptides (namely, EY, EG, ECG, and DGPL) entered the T1R1 cavity of the umami receptor. Additionally, 4 umami peptides (namely, EV, ENG, DEL, and EDCS) could be embedded in the binding pocket of the T1R3 cavity. Furthermore, 3 umami peptides (PEG, DDL, and PEEL) strongly interacted with T1R1/T1R3. Thus, the findings collectively indicated that the predominant interacting forces between umami peptide and umami receptor are hydrogen bonding and hydrophobic interactions. Finally, it was shown that the primary binding sites of T1R1 were residues Ser109, Gln52 and Ser148, while the primary binding sites of T1R3 were residues Ser172, Arg277 and Ala170. The study identified the umami peptides in A. aegerita for the first time, which provided more information for the umami research of A. aegerita and provided the theoretical basis for the further development and utilization of A. aegerita .

A dual-additive-based aqueous electrolyte was designed with a pH-buffering additive (Zn(OAc) 2 ) and an electrostatic shielding additive (TMAOAc) for high Zn plating/stripping efficiency. The buffering pair, OAc - /HOAc, can stabilize the pH value to suppress side hydrogen evolution reactions. Meanwhile, TMA + acts as a competitive cation being preferentially adsorbed on the uneven surface of the Zn anode and exerts an electrostatic shielding effect to facilitate flat Zn deposition. Such a dual-additive-based electrolyte promotes an ultra-high Zn plating/stripping efficiency of 99.9% at 1 mA cm -2 and long-term cycling stability for 3600 h at 0.5 mA cm -2 , offering valuable insights for advanced aqueous batteries.

The large water demand, insufficient deposition on the back of the leaf and the uneven distribution of droplets are the problems of traditional agricultural ground plant protection machinery, which leads to low agricultural control efficiency. Combined with the advantages of electrostatic spray technology and the characteristics of high working efficiency and low probability of droplets drift of ground sprayer, an inductive electrostatic boom spray system based on embedded electrode structure is designed and mounted on a large self-propelled boom sprayer for field testing. Based on the working characteristics of the fan nozzle and the analysis of the theory of charge, the inductive electrostatic spray device is designed. The performance of the device is tested and the rationality of the system design is verified by COMSOL numerical simulations, charge-to-mass ratio, and particle size distribution measurements. The spray deposition scanning software and the Box-Behnken experimental design method are used to analyze the spray droplet deposition rate and coverage density of the sprayer on the front and back of the target leaves. The results show that the embedded closed electrode structure designed in this paper can avoid the problem of electrode wetting, and the electric field generated by it is mainly concentrated in the spray liquid film area, and the intensity reaches 6~7 V/m. At the conventional application height (500 mm), the maximum charge-to-mass ratio is 2.91 mC/kg, and the average particle size is 168.22 μm, which is 12.87% lower than that of ordinary spray, when the spray pressure is 0.3 MPa and the electrostatic voltage is 12 kV. The results of field experiments show that the optimum combination of the working parameters with the spray speed is 8.40 m/s, the spray pressure is 0.35 MPa, the charging voltage is 11.50 kV, the amount of droplet deposition in the lower dorsal area of the blade is 1.44 µL·cm -2 . This study can provide a certain basis for the application of electrostatic spray technology in ground sprayers., Competing Interests: Author RC was employed by Beidahuang Group Heilongjiang Nenjiang Farm Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Hu, Cao, Li, Zhao, Li and Zhang.)

Spin-LEDs have been a central topic in semiconductor spintronics research and represent a promising avenue for advanced optoelectronic devices and applications. The future advancements of spin-LEDs will undoubtedly hinge on the generation and manipulation of spin-polarized population at room temperature. In this research, we elucidate the development of room-temperature spin-LEDs using quasi-2D perovskites, based on the chiral-induced spin selectivity (CISS) effect. During the carrier transfer from the chiral n 2 phase to the randomly oriented high- n phase caused by the bandgap gradient distribution, CISS works to generate non-equilibrium spin population, leading to room-temperature spin-polarized fluorescence. A spin-polarization of ∼93% is observed for the films. Finally, we realize spin-LEDs at room temperature, exhibiting a | g CP-EL | value of 0.05 and an EQE of 3.8%. This work highlights the potential of integrating dual ligands to optimize the phase distribution and crystalline orientation in quasi-2D films to achieve efficient CISS for spin-LED applications.

Background: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive., Methods and Result: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model., Conclusions: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We report Fe porphyrins bearing different meso -substituents for the electrocatalytic CO 2 reduction reaction (CO 2 RR). By replacing two and four meso -phenyl groups of Fe tetraphenylporphyrin (FeTPP) with strong electron-withdrawing pentafluorophenyl groups, we synthesized FeF 10 TPP and FeF 20 TPP, respectively. We showed that FeTPP and FeF 10 TPP are active and selective for CO 2 -to-CO conversion in dimethylformamide with the former being more active, but FeF 20 TPP catalyzes hydrogen evolution rather than the CO 2 RR under the same conditions. Experimental and theoretical studies revealed that with more electron-withdrawing meso -substituents, the Fe center becomes electron-deficient and it becomes difficult for it to bind a CO 2 molecule in its formal Fe 0 state. This work is significant to illustrate the electronic effects of catalysts on binding and activating CO 2 molecules and provide fundamental knowledge for the design of new CO 2 RR catalysts.

The water oxidation reaction, a crucial process for solar energy conversion, has garnered significant research attention. Achieving efficient energy conversion requires the development of cost-effective and durable water oxidation catalysts. To design effective catalysts, it is essential to have a fundamental understanding of the reaction mechanisms. This review presents a comprehensive overview of recent advancements in the understanding of the mechanisms of water oxidation using transition metal-based heterogeneous electrocatalysts, including Mn, Fe, Co, Ni, and Cu-based catalysts. It highlights the catalytic mechanisms of different transition metals and emphasizes the importance of monitoring of key intermediates to explore the reaction pathway. In addition, advanced techniques for physical characterization of water oxidation intermediates are also introduced, for the purpose of providing information for establishing reliable methodologies in water oxidation research. The study of transition metal-based water oxidation electrocatalysts is instrumental in providing novel insights into understanding both natural and artificial energy conversion processes.

The electrochemical CO 2 reduction reaction (eCO 2 RR) to multicarbon products has been widely recognized for Cu-based catalysts. However, the structural changes in Cu-based catalysts during the eCO 2 RR pose challenges to achieving an in-depth understanding of the structure-activity relationship, thereby limiting catalyst development. Herein, we employ constant-potential density functional theory calculations to investigate the sintering process of Cu single atoms of Cu-N-C single-atom catalysts into clusters under eCO 2 RR conditions. Systematic constant-potential ab initio molecular dynamics simulations revealed that the leaching of Cu-(CO) x moieties and subsequent agglomeration into clusters can be facilitated by synergistic adsorption of H and eCO 2 RR intermediates (e.g., CO). Increasing the Cu 2+ concentration or the applied potential can efficiently suppress Cu sintering. Both microkinetic simulations and experimental results further confirm that sintered Cu clusters play a crucial role in generating C 2 products. These findings provide significant insights into the dynamic evolution of Cu-based catalysts and the origin of their activity toward C 2 products during the eCO 2 RR., (© 2024 Wiley-VCH GmbH.)

Techniques for imaging haemodynamics use ionizing radiation or contrast agents or are limited by imaging depth (within approximately 1 mm), complex and expensive data-acquisition systems, or low imaging speeds, system complexity or cost. Here we show that ultrafast volumetric photoacoustic imaging of haemodynamics in the human body at up to 1 kHz can be achieved using a single laser pulse and a single element functioning as 6,400 virtual detectors. The technique, which does not require recalibration for different objects or during long-term operation, enables the longitudinal volumetric imaging of haemodynamics in vasculature a few millimetres below the skin's surface. We demonstrate this technique in vessels in the feet of healthy human volunteers by capturing haemodynamic changes in response to vascular occlusion. Single-shot volumetric photoacoustic imaging using a single-element detector may facilitate the early detection and monitoring of peripheral vascular diseases and may be advantageous for use in biometrics and point-of-care testing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)