Search

Abstract Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14R117, a critical residue located within a druggable pocket at the FGF14/Nav1.6 PPI interface. We found that 1028 modulates FGF14/Nav1.6 complex assembly and depolarizes the voltage-dependence of Nav1.6 channel inactivation with nanomolar potency by modulating the intramolecular interaction between the III-IV linker and C-terminal domain of the Nav1.6 channel. Consistent with the compound’s effects on Nav1.6 channel inactivation, 1028 enhances MSN excitability ex vivo and accumbal neuron firing rate in vivo in murine models. Systemic administration of 1028 maintains behavioral motivation preferentially during motivationally deficient conditions in murine models. These behavioral effects were abrogated by in vivo gene silencing of Fgf14 in the NAc and were accompanied by a selective reduction in accumbal dopamine levels during reward consumption in murine models. These findings underscore the potential to selectively regulate complex behaviors associated with neuropsychiatric disorders through targeting of PPIs in neurons.

Abstract Purpose Swelling in the lower limbs after total knee arthroplasty (TKA) affects surgical outcomes. Prolonged swelling requires monitoring and remote management during home-based rehabilitation. Causes of swelling vary but, so far, no indicators are available to monitor and identify causes of lower limb swelling, making it difficult to implement targeted interventions. This study aimed to find the indicators to monitor and identify the causes of lower limb swelling during home-based rehabilitation after TKA by literature research and consulting experts from various disciplines. Methods The Delphi method was used. Based on literature research and analysis, a set of candidate indicators was developed. Fifteen experts from different disciplines evaluated the validity of the indicators and provided modification suggestions. Results After two rounds of Delphi consultations, consensus was reached. Agreement scores ranged from 4.40 to 5.00, with low variability (standard deviation 0.00–0.91) and high consistency (coefficient of variation 0.00–0.20). P was less than 0.05 in Kendall’s W with an agreement rate of 80.00–100%. In the final set of indicators, there were five primary indicators (representing four swelling causes and a general category), along with 23 secondary indicators and 40 tertiary indicators. Conclusions This study preliminarily established indicators for at-home identification of post-TKA swelling caused by four distinct reasons. Further research is needed to validate the value of these indicators in distinguishing the causes of swelling.

Abstract Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing. We found that the dominant fibroblast subgroup in keloids is mechanoresponsive group, which showed enhanced mechanotransduction and migration. This mechanoresponsive fibroblast subgroup is likely to be the key cell population and confer aggressive growth of keloids. The results also indicate that the endothelial cells and keratinocytes in keloid involve in endothelial-mesenchymal and epithelial-mesenchymal transitions. This study demonstrated the mechanoresponsive fibroblasts and multiple cellular mesenchymal processes could pave the way for further investigations into the keloid aggressiveness.

68Ge is the parent nuclide of radioactive nuclide 68Ga used in positron emission tomography (PET) diagnostic imaging，which is converted into 68Ga by a 68Ge/68Ga generator for clinical diagnostic imaging applications. Currently，there are 13 kinds of 68Ga labeled radiopharmaceuticals in China that have entered clinical practice and have good application prospects in tumor imaging such as high-grade endocrine tumors and prostate cancer. Therefore，with the approval and widespread use of 68Ga radiopharmaceuticals，68Ge has broad application prospects in both domestic and international markets.In addition,68Ge can also be widely used as a calibration source for PET scanners.China Institute of Atomic Energy (CIAE) plans to build a 75 MeV cyclotron with the maximum beam current of 800 μA and the proton energy range of 75 MeV. It will be used to focus on the production of 68Ge nuclide.This article used the Monte Carlo program FLUKA to simulate in detail the production of 68Ge nuclides yield，reaction products，the variation of impurity nuclide production with cooling time，and long-life nuclides affecting separation processes by irradiating gallium nickel alloy targets and niobium gallium capsule targets in medium to high energy proton cyclotron.The simulation results can provide the useful reference for the production，separation，and purification of 68Ge in medium to high energy cyclotron.

Abstract Background Intermuscular bones (IBs) are segmental intramembranous ossifications located within myosepta. They share similarities with tendon ossification, a form of heterotopic ossification (HO). The mechanisms underlying IB formation remain incompletely understood. Results In this study, we systematically analyzed transcriptome data across multiple tissues, species, time points, and resolutions in teleosts. First, we identified IB-specific expression genes using the tau index method. Through cross-species comparisons of the tendon development process, we discovered that candidate genes were primarily enriched in extracellular matrix organization, ossification, regulation of angiogenesis, and other related processes. We also revealed that some of these candidate genes are abnormally expressed in runx2b −/− zebrafish, which lack IBs. To clarify the trajectory of cell differentiation during IB formation, we demonstrated that myoseptal stem cells differentiate into osteoblasts, fibroblasts, and tenocytes in runx2b +/+ zebrafish. However, in runx2b −/− zebrafish, the differentiation of myoseptal stem cell into osteoblast was inhibited, while differentiation into clec3bb + tenocyte and fibroblast was enhanced. Additionally, runx2b deficiency led to the upregulation of clec3bb expression in the clec3bb + tenocyte cluster. Notably, a compensatory effect was observed in cell differentiation and gene expression in runx2b −/− zebrafish, suggesting that runx2b and the candidate genes, such as clec3bb, were involved in the gene network of IB development. Conclusions The results elucidate cell differentiation process during tendon ossification in teleosts and identify the key factor clec3bb involved in this process. These findings provide a foundation for understanding tendon ossification in teleosts and for further research on tendon ossification in mammals.

Abstract Background Rice blast is a devastating disease caused by Magnaporthe grisea, and it is not well controlled globally. As a Traditional Chinese Medicine, Artemisia argyi has been proven to have inhibitory effects on a variety of phytopathogenic fungi. Here, we used bioactivity-guided isolation method and transcriptomics to clarify the antifungal active compounds in A. argyi and their antifungal mechanisms. Results In vitro studies showed that the absolute ethanol extract (AEE) of A. argyi had a strong inhibitory effect on the growth of M. grisea, with a low EC50 value of 1.156 mg/mL, and could cause the destruction of hyphae cell membrane and the leakage of cell contents. To identify the active constituents, we fractionated the AEE using macroporous adsorption resin and silica gel column chromatography. The active fraction (Fr.F-1) was fractionated and had even higher antifungal activity than AEE. The results showed that both AEE and Fr.F-1 could impact primary metabolic pathways and reactive oxygen species homeostasis of M. grisea, decrease the content of reducing sugars and downregulate the expression of genes related to starch and sucrose metabolism. Further fractionation of Fr.F-1 led to the identification of two polymethoxylated flavonoids (eupatilin and 3,5,3ʹ-trihydroxy-7,8,4ʹ-trimethoxyflavone), both of which had antifungal activity and they worked synergistically in Fr.F-1. Finally, we also investigated the effect of AEE, Fr.F-1 and eupatilin on rice blast control. The results showed that AEE, Fr.F-1 and eupatilin application strongly enhanced rice resistance to M. grisea. Conclusion In brief, these findings indicate that Fr.F-1 subfraction from A. argyi and its main components polymethoxylated flavonoids confer inhibiting activities to M. grisea. This discovery can effectively alleviate the degradation pressure of A. argyi by-products, promote the healthy development of its industry, and provide new a strategy for the development of new botanical fungicides to control rice blast. Graphical Abstract

Abstract The cladding of fast reactor fuel rods, made of stainless steel, presents significant challenges in cutting due to its ductility, which leads to increased tool wear and poor cut quality with traditional mechanical methods. Laser cutting has emerged as a superior alternative, offering non-contact precision, high efficiency, and suitability for radioactive environments. This study systematically investigates the effects of laser cutting parameters—cutting speed, focal position, power, and gas pressure—on the cutting quality of simulated fast reactor fuel rods. The results show that optimal cutting is achieved with a cutting speed of 1 m/min, a focal position between − 20 and − 25 mm, a laser power between 7200 and 9600 W, and a gas pressure of 10 MPa. These parameters provide the best balance between cutting efficiency, surface roughness, and minimal slag formation. This study contributes valuable insights into optimizing laser cutting technology for nuclear fuel rod processing, with potential applications in fuel reprocessing and decommissioning.

Abstract Background Depression is a significant health concern among children and adolescents. Previous epidemiological studies on depressive symptoms in this population have yielded inconsistent findings. This study aims to systematically estimate the prevalence of depressive symptoms among Chinese children and adolescents. Method A comprehensive literature search was conducted in both English (PubMed, EMBASE) and Chinese (China National Knowledge Infrastructure, WANFANG) databases from their inception until October 15, 2024. This meta-analysis employed a random-effects model to estimate the pooled prevalence of depressive symptoms. Results A total of 439 eligible studies, comprising 1,497,524 participants, were included in the analysis. The pooled point prevalence of depressive symptoms among children and adolescents was found to be 26.17% (95% CI 25.00–27.41%), with significant heterogeneity among studies (I2 = 100%, p

Top-down environmental policies aim to mitigate environmental risks but inevitably lead to economic losses due to the market entry or exit of enterprises. This study developed a universal dynamic agent-based supply chain model to achieve tradeoffs between environmental risk reduction and economic sustainability. The model was used to conduct high-resolution daily simulations of the dynamic shifts in enterprise operations and their cascading effects on supply chain networks. It includes production, consumption, and transportation agents, attributing economic features to supply chain components and capturing their interactions. It also accounts for adaptive responses to daily external shocks and replicates realistic firm behaviors. By coupling high spatial–temporal resolution firm-level data from 18 916 chemical enterprises, this study investigates the economic and environmental impacts of an environmental policy resulting in the closure of 1800 chemical enterprises over three years. The results revealed a significant economic loss of 25.8 billion USD, ranging from 23.8 billion to 31.8 billion USD. Notably, over 80% of this loss was attributed to supply chain propagation. Counterfactual analyses indicated that implementing a staggered shutdown strategy prevented 18.8% of supply chain losses, highlighting the importance of a gradual policy implementation to prevent abrupt supply chain disruptions. Furthermore, the study highlights the effectiveness of a multi-objective policy design in reducing economic losses (about 29%) and environmental risks (about 40%), substantially enhancing the efficiency of the environmental policy. The high-resolution simulations provide valuable insights for policy designers to formulate strategies with staggered implementation and multiple objectives to mitigate supply chain losses and environmental risks and ensure a sustainable future.

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

Abstract Hypertrophic scar (HTS) formation is a pathological fibrotic skin disease, with no satisfactory treatments available currently. Inducing apoptosis of HTS-derived fibroblasts (HSFs) are becoming promising approaches. In this research, we aim to improve the technology with co-delivery COX-2 and TGF-β1 siRNAs and further investigate the underlying mechanism. Firstly, the HSFs were transfected with 1 µg/ml COX-2 and/or TGF-β1 siRNAs, and proved that the apoptosis of HSFs was greater induced by COX-2/TGF-β1 siRNAs than either COX-2 or TGF-β1 siRNA alone by flow cytometry. To investigate the impact of co-silencing TGF-β1 and COX-2 mRNA expression in vivo, we established HTSs model in rat tails. Our results confirmed that co-silencing of TGF-β1 and COX-2 mRNA expression could significantly alleviate the HTS formation in vivo. Furthermore, we explored the potential molecular mechanism and revealed that the protein levels of TP53, Bcl-2 and Caspase-3 were downregulated while Bax and Cleaved Caspase-3 were upregulated in the COX-2/TGF-β1 siRNA groups compared with HKP group. Taken together, our results demonstrated that simultaneous silencing of COX-2 and TGF-β1 expression by siRNAs induced HSF apoptosis through a TP53 mediated caspase pathway. Therefore, COX-2/TGF-β1 siRNAs might serve as a novel and effective therapeutic alternative for HTSs treatments.

Abstract In this work, the rapid and efficient preparation of isolated galloyl glucoside tautomer free radical inhibitors was investigated using Saxifraga tangutica as a raw material. Four highly polar galloyl glucoside tautomers, 3-O-galloyl-α-d-glucose ⇌ 3-O-galloyl-β-d-glucose (Fr2-1-1), 2-O-galloyl-α-d-glucose ⇌ 2-O-galloyl-β-d-glucose (Fr2-1-2/2-1-3), 1-O-galloyl-β-d-glucose (Fr2-2-1), and 6-O-galloyl-α-d-glucose ⇌ 6-O-galloyl-β-d-glucose (Fr2-3-1/Fr2-3-2), were obtained via two-step medium-pressure liquid chromatography (with solid loading instead of conventional liquid injection) and one-step high-performance chromatography coupled with on-line RPLC-DPPH techniques for targeted isolation. This separation integration technique not only increases sample intake and reduces time cost but also visualizes each step of targeted separation. All four compounds were isolated from the plant for the first time. In vitro antioxidant activity assays by DPPH (1,1‑diphenyl-2-picrylhydrazyl) revealed that Fr2-1-2/Fr2-1-3 (IC50: 5.52 ± 0.32 μM), Fr2-2-1 (IC50: 7.22 ± 0.57 μM), and Fr2-3–1/Fr2-3-2 (IC50: 7.36 ± 0.25 μM) had superior free radical scavenging abilities and that both were superior to that of quercetin (IC50: 18.61 ± 3.55 μM). Oxidative stress assays revealed that Fr2-1-2/Fr2-1-3 significantly inhibited oxidative stress damage in H2O2-induced HepG2 cells, decreased the level of ROS (P

Abstract Background Toxocara canis, the most prevalent helminth in dogs and other canines, is one of the socioeconomically important zoonotic parasites, particularly affecting pediatric and adolescent populations in impoverished communities. However, limited information is available regarding the proteomes of female and male adult T. canis. To address this knowledge gap, we performed a comprehensive proteomic analysis to identify the proteins with differential abundance (PDAs) and gender-specifically expressed proteins between the two sexes adult T. canis. Methods The comparative proteomic analysis was carried out by the Orbitrap mass spectrometry (MS) with asymmetric track lossless (Astral) analyzer. The difference analysis was conducted using t-test and the proteins verification was achieved through parallel reaction monitoring (PRM). The potential biological functions of identified adult T. canis proteins and PDAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The domain, transcription factor and subcellular localization of the identified proteins and PDAs were analyzed by InterPro, AnimalTFDB 4.0 and Cell-mPLOC 2.0 databases, respectively. Results A total of 8565 somatic proteins of adult T. canis were identified. Compared to male adult, 682 up-regulated PDAs and 844 down-regulated PDAs were identified in female adult with P-values 1, including 139 proteins exclusively expressed in female and 272 proteins exclusively expressed in male. The GO annotation analysis using all PDAs revealed that the main biological processes, cellular components and molecular functions corresponded to aminoglycan metabolic process, extracellular region and protein tyrosine phosphatase activity, respectively. The KEGG analysis using all PDAs showed that the pathways were mainly associated with adipocytokine signaling pathway, proximal tubule bicarbonate reclamation and PPAR signaling pathway. Conclusions This study reveals the differential protein expression between female and male adult T. canis, providing valuable resource for developing the novel intervention strategies against T. canis infection in humans and animals, especially from the perspective of sexual development and reproduction. Graphical abstract

Nitrile rubber latex was prepared by conventional emulsion polymerization combined with low-temperature batch polymerization process, the latex was hydrogenated with self-made ruthenium catalyst, and the influence of catalyst amount and hydrogen pressure on the hydrogenation effect of nitrile rubber latex was systematically studied. The results showed that the average particle size of the prepared nitrile rubber latex was 69.13 nm, and the particle size of the latex remained basically unchanged and the latex remained stable before and after hydrogenation. The higher the hydrogen pressure was, the better the catalytic hydrogenation effect was. When the mass fraction of catalyst was 0.017 5%, degree of hydrogenation of the product was more than 99% and no gel was obtained.

Abstract Background It was reported that more than 96% of autism spectrum disorder (ASD) children are accompanied with different degrees of sensory processing abnormalities, and up to 50% of ASD children exhibit abnormal auditory response. Studies have confirmed that some ASD children’s abnormal auditory response may be related to their abnormal auditory processing. Prior research demonstrated that ASD children’s auditory processing has high heterogeneity, thus, ASD children’s auditory processing may have different developmental trajectories. However, no study has concentrated on the developmental trajectories of ASD children’s auditory processing. In addition, auditory processing plays a crucial role in ASD children’s language development, thus, ASD children’s different language development outcomes may be related to different auditory processing development tracks. Therefore, this study aims to explore the developmental trajectory of auditory processing in ASD children and analyze the relationship between different developmental trajectories of auditory processing and language impairment. Methods/Design In this study, 220 ASD children aging 3 years and 0 months to 4 years and 11 months are recruited as the research objects, and their demographic characteristics are collected. The subjects are tested for peripheral hearing, intelligence, and autism symptoms. Furthermore, ASD children’s auditory processing and language development are evaluated at baseline, 1 year, and 2 years later. In addition, ASD children’s auditory processing is evaluated by electrophysiological test and the Preschool Auditory Processing Assessment Scale. Moreover, ASD children’s language skills are assessed using the Language Development Assessment Scale for Children Aged 1–6. The various categories of the developmental trajectory of ASD children’s auditory processing are examined through the latent category growth model. Additionally, a hierarchical regression model is developed to analyze the predictive impact of different auditory processing development trajectories on language impairment in ASD children. Discussion This longitudinal study will explore the categories of auditory processing developmental trajectories in ASD children, and analyze the relationship between different categories of auditory processing developmental trajectories and language development, providing new ideas and targeted targets for the rehabilitation training of language impairment in ASD children, as well as promoting early and accurate interventions for ASD children.

Abstract We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

Abstract Objective This study aims to evaluate the application value in neurological outcome of cerebral regional oxygen saturation (CrSO2) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal extracorporeal membrane oxygenation (ECMO) courses. Methods We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospital from July 2021 to December 2022. Continuous monitoring of CrSO2 and brain electrical activity was conducted using near-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related clinical data. Results Among the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group (AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant CrSO2 reduction (> 25% from baseline or absolute value

Objective: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). Method: A total of 84 preschool children diagnosed with ADHD, aged 4-6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence--Fourth Edition or the Wechsler Intelligence Scale for Children--Fourth Edition, and a continuous performance test. Results: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. Conclusions: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD.

The age of a forest serves as a critical indicator of both its carbon stock and its capacity for carbon volume within forest ecosystems. The high spatial and temporal resolution of forest age improves the accuracy of estimates for forest biomass, storage, and carbon stocks. Obtaining reliable forest age data across various scales remains a significant challenge. This study conducted forest age mapping at a 30 m resolution over long time series, taking into account forest disturbance events, using Xinjiang forest as a case study. In 1991, the age of forests in Xinjiang was estimated utilizing the Random Forest (RF) model, incorporating both forest inventory data and remote sensing data. Utilizing Landsat Time Series Stacked (LTSS) Data from 1991 to 2022, the LandTrendr(LT) algorithm was applied to identify forest disturbance and recovery events from 1992 to 2022 using the Google Earth Engine (GEE) platform. Finally, the forest age distribution in Xinjiang from 1991 to 2022 was mapped in conjunction with the forest disturbance events. The findings revealed that: (1) the R2 values of the RF regression models for estimating forest age exceeded 0.65, with RMSEs below 22 years and RRMSEs ranging from 0.119 to 0.183, demonstrating high credibility of the simulation results; (2) the overall accuracy of the LandTrendr algorithm in identifying forest loss and gain in the study area was 85 % or higher. From 1992 to 2022, Xinjiang experienced a net increase in forest area of 28580.69 km2; (3) the forest age distribution from 1991 to 2022 indicates a predominance of young and middle-aged forests, with the proportion of old forests remaining between 30 % and 40 %, showing a gradual annual increase. This study presents a method to improve the estimation of forest age at high resolution over extended time series. It also supplies essential data for assessing carbon storage in Xinjiang’s forests, both historically and prospectively, contributing to a deeper understanding of carbon balance in forest ecosystems within arid regions.

Abstract We examined the association between low‐calorie sweeteners (LCS) consumption during preconception, pregnancy, and breastfeeding and child health outcomes. A systematic search of electronic databases in PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov, and Google Scholar was conducted up to 21 September 2023. A random effects model with restricted maximum likelihood estimation was used for the meta‐analysis. Seventeen eligible studies were included. The standardised mean difference (SMD) and 95% confidence interval (CI) in birth weight between those who frequently consumed LCS (≥1 serve/day) during pregnancy and those who did not consume LCS was 0.04 (0.00, 0.08) (four cohort studies). Any LCS consumption during pregnancy compared with no consumption was not associated with birth weight [SMD (95% CI) = 0.03 (−0.03, 0.08)] (four cohort studies). Any LCS consumption during pregnancy was not associated with body mass index z‐scores. The weighted mean difference (95% CI) was 0.00 (−0.05, 0.06) at birth, 0.06 (−0.29, 0.40) at 6 months, −0.04 (−0.19, 0.10) at 1 year, 0.00 (−0.16, 0.17) at 3 years, and 0.10 (−0.15, 0.34) at 7 years of the child age, compared with no intake (five cohort studies). The odds of being overweight at 1 year among children exposed to LCS during pregnancy was 1.19 (OR [95% CI]: 1.19 [0.81, 1.58]) compared with unexposed children (two cohort studies). The effect sizes were not precise for all the outcomes as the 95% CI indicated the effect estimates could range from small protective to a higher risk. The effect of LCS consumption on child behaviour and cognition was inconsistent. There is not enough evidence to confirm LCS consumption during pregnancy affects birth weight and risk of overweight in children. However, frequent consumption increased birth weight and the risk of overweight at different ages, though the effects were imprecise. More robust research evidence is required as the quality of evidence is low.

Dear Editor, in this study, we propose a novel linkage disequilibrium information‐based noninvasive zygosity (LDNZ) assessment method in twin pregnancies. It combines fetus‐specific allele frequency analysis with LD block to reduce the number of required single nucleotide polymorphism markers and experiment costs. LDNZ method offers a noninvasive, accurate, and cost‐effective solution for zygosity assessment, addressing the need for precise obstetric care in twin pregnancies.

Abstract Understanding the molecular mechanisms that bridge hepatic inflammation and liver injury is crucial for developing effective therapeutic strategies for drug‐induced liver injury (DILI) management. HECT domain and RCC1‐like domain 2 (HERC2) belongs to the large Herc family of ubiquitin E3 ligases, which are implicated in tissue development and inflammation. The observation reveals a pronounced HERC2 expression in specific hepatocyte subsets that proliferate in response to DILI in humans, prompting an investigation into the role of HERC2 in distinct DILI progression. Under the APAP challenge, liver‐specific HERC2‐deficient mice suffer more severe liver damage. Integrated single‐cell RNA sequencing analysis unveils a negative correlation between HERC2 and CYP2E1, a vital metabolic enzyme for xenobiotics, in hepatocytes from APAP‐challenged mice. Mechanistically, HERC2 interacts with β‐catenin to promote its ubiquitination, thereby governing CYP2E1 transcriptional regulation. Targeted hepatic delivery of lipid nanoparticle‐encapsulated HERC2‐overexpressing plasmid markedly reduces liver damage caused by APAP overdose. Collectively, these findings elucidate a previously unrecognized protective role of HERC2 in protecting against acute liver injury associated with drug metabolism disorders, highlighting its potential as a therapeutic target in treating DILI.

Polygalacturonase inhibiting proteins (PGIPs) are typical leucine-rich repeat (LRR) proteins that inhibit the activity of polygalacturonase (PG) in pathogens, but their function in promoting to plant stem development has been less studied. In this study, the PGIP gene from Zea mays was cloned and heterologously expressed in Arabidopsis thaliana, and then the plant phenotypes were observed and a set of physiological and biochemical indicators were measured. The results indicate that the ZmPGIP1 protein is expressed both in the cell membrane and cell wall. Our research observed that the heterologous expression of ZmPGIP1 significantly increased the production of lignin, cellulose and hemicellulose in transgenic lines. The stems of transgenic plants also showed a thicker cortical tissue. The increase in lignin deposition observed during histochemical staining suggests that the ZmPGIP1 gene may improve plant mechanical strength. These were tightly associated with the upregulated expression of lignin/cellulose-synthesis genes (C4H, C3H, F5H, PAL1/3, CCR1, CAD1-3/9, CCOMT, MYB58, CESA1/10) to enhance plant cell wall strength in transgenic lines. Our findings provide new perspectives on the growth regulation mechanisms of PGIP proteins in plant cell walls and provide a potential candidate gene for breeding increased disease-resistance and higher cellulose production in plants.

Background Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF.Methods This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME.Results The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively.Conclusion The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Objective: We aimed to determine whether the ABC/2 can be used as an infarct volume measurement tool for Mechanical thrombectomy (MT) in patients with Alberta Stroke Program Early CT Scores (ASPECTS)

Rumen-protected glucose (RPG) and taurine (TAU) are crucial for the nutrition and physiology of ruminants, enhancing production performance and mitigating negative energy balance. This study aimed to assess the impact of RPG levels and TAU supplementation on the body weight, antioxidant capacity, immune function and stress responses in yaks before and after transport. Thirty-two healthy male yaks, aged 3 years and weighing 172.5 ± 10.2 kg, were randomly assigned to one of four dietary treatments: (1) low RPG and low TAU (LRLT), with 1% RPG and 5 g/d TAU; (2) low RPG and high TAU (LRHT), with 1% RPG and 15 g/d TAU; (3) high RPG and low TAU (HRLT), with 3% RPG and 5 g/d TAU; and (4) high RPG and high TAU (HRHT), with 3% RPG and 15 g/d TAU. The yaks were treated with the corresponding diet for 7 days, then received 9 h of transportation, and finally fed the same diet at their destination for 30 days. The weight was measured before and on days 0 and 30 after transport, and the plasma was collected before and on day 0, 10, and 30 after transport for analysis of biochemical, antioxidant, immune, and stress response indicators. We observed that transport increased plasma concentrations of total cholesterol, total protein, lactate dehydrogenase, creatine kinase, malondialdehyde, cortisol and lipopolysaccharides of yaks among treatments, while decreased their BW and plasma IL-10 concentration. Increasing TAU supplementation reduced weight loss (8.42 vs. 11.9 kg) and weight loss percent (4.83% vs. 6.87%) in yaks after transport. The concentration of MDA in plasma was lower in HRHT than in LRLT at day 0 after transport (p = 0.03). The activity of GSH-PX was higher in HRHT than in LRLT at day 10 after transport (p = 0.04). Concentrations of IL-10 at day 0 and 10 after transport was higher in HRHT than in LRLT and HRLT (p = 0.02, p = 0.01, respectively). With the increase of TAU supplementation, concentrations of IL-1β at day 30 after transport (p = 0.02), TNF-α at day 0 after transport (p = 0.02), COR at day 10 (p = 0.03) and 30 (p = 0.05) after transport as well as LPS at day 0 after transport (p = 0.04) decreased. In addition, concentrations of COR at day 0 after transport was lower in LRHT and HRHT than in LRLT (p = 0.03). Based on all the results, we demonstrated that increasing TAU supplementation levels reduced post-transport weight loss in yaks, improved their antioxidant capacity and immune function, and alleviated stress responses. Considering the effect of resistance to transport stress and costs, the optimal treatment identified in this study involved a diet containing 1% RPG and supplemented with 15 g/d TAU.

Objective: To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. Methods: We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. Results: Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P

Abstract Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Abstract Purpose Diet plays a fundamental role in promoting resilience against stress-related disorders. We aimed to examine the overall and sex-specific association between food groups and perceived stress in adults. Methods We analyzed the prospective data of 7,434 adults who completed both the 2011 and 2015 surveys of the China Health and Nutrition Survey (CHNS). The Diet Quality Questionnaire (DQQ) was used to code all the food items of 2011 dietary intake into 29 food groups, and perceived stress in 2015 was measured using a 14-item perceived stress scale (PSS-14). Univariate analysis and logistic regression models were used to examine the relationship between food groups and perceived stress. Results People who perceived a higher level of stress (PSS-14 total score > 25) made up 41.5% and 45.1% of the male and female groups, respectively (χ2 = 9.605, p = 0.002). Individuals with increased intake of food groups such as legumes, other vegetables, other fruits, yogurt, poultry, fish & seafood, fluid milk, and fruit juice were less likely to experience a higher level of psychological stress (OR range: 0.544–0.892, p

Abstract Background Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. Case presentation A patient with primary aldosteronism (PA) associated with severe Cushing’s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. Conclusion Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

Abstract Electrocatalytic nitrate reduction to ammonia holds great promise for developing green technologies for electrochemical ammonia energy conversion and storage. Considering that real nitrate resources often exhibit low concentrations, it is challenging to achieve high activity in low-concentration nitrate solutions due to the competing reaction of the hydrogen evolution reaction, let alone considering the catalyst lifetime. Herein, we present a high nitrate reduction performance electrocatalyst based on a Co nanosheet structure with a gradient dispersion of Ru, which yields a high NH3 Faraday efficiency of over 93% at an industrially relevant NH3 current density of 1.0 A/cm2 in 2000 ppm NO3 - electrolyte, while maintaining good stability for 720 h under −300 mA/cm2. The electrocatalyst maintains high activity even in 62 ppm NO3 - electrolyte. Electrochemical studies, density functional theory, electrochemical in situ Raman, and Fourier-transformed infrared spectroscopy confirm that the gradient concentration design of the catalyst reduces the reaction energy barrier to improve its activity and suppresses the catalyst evolution caused by the expansion of the Co lattice to enhance its stability. The gradient-driven design in this work provides a direction for improving the performance of electrocatalytic nitrate reduction to ammonia.

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

Abstract Objective Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. Backgrounds Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. Methods Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. Results This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. Conclusion This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.