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Carotid artery stenosis is the main cause of cerebral watershed infarction (CWI). In recent years, increasing attention has been given to treating this condition. The present study aimed to investigate how Verteporfin-eluting stent (VPES) modulates the YAP signaling pathway to inhibit restenosis of the carotid artery and alleviate CWI. Through transcriptome sequencing and functional experiments, it was found that VP could regulate the Yes-associated protein (YAP) signaling pathway and effectively suppress the proliferation and migration of smooth muscle cells (SMCs). Further investigation revealed that VPES could inhibit carotid artery restenosis through the YAP signaling pathway in a rabbit model, reducing the occurrence of CWI., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical statement: All animal experiments were approved by the Animal Ethical and Welfare Committee of Huaihe Hospital of Henan University., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Two previously undescribed chroman type polyketides, trichrontides A (1) and B (2), along with four known homologous compounds, were isolated from the endophytic fungus Trichoderma sp. YUD24002, which was associated with Aconitum forrestii Stapf.. Their structures were confirmed using NMR and HR-ESI-MS techniques. Furthermore, the absolute configurations of the two new compounds were elucidated through TDDFT ECD calculations and Mosher's methods. Notably, compound 1 exhibited significant antifungal activity against Alternaria panax, with a minimum inhibitory concentration (MIC) of 16 μg/mL, while compound 2 demonstrated evident antifungal activity against Epicoccum nigrum, with a MIC of 32 μg/mL., (© 2024 Wiley‐VCH GmbH.)

A fascinating feature of land plants is their ability to continually initiate new tissues and organs throughout their lifespan, driven by a pool of pluripotent stem cells located in meristems. In seed plants, various types of meristems are initiated and maintained during the sporophyte generation, while their gametophytes lack meristems and rely on sporophyte tissues for growth. In contrast, seed-free vascular plants, such as ferns, develop meristems during both the sporophyte and gametophyte generations, allowing for the independent growth of both generations. Recent findings have highlighted both conserved and lineage-specific roles of the HAIRY MERISTEM (HAM) family of GRAS-domain transcriptional regulators in various meristems throughout the land plant lifecycle. Here, we review and discuss how HAM genes maintain meristem indeterminacy in both sporophytes and gametophytes, with a focus on studies performed in two model species: the flowering plant Arabidopsis thaliana and the fern Ceratopteris richardii. Additionally, we summarize the crucial and tightly regulated functions of the microRNA171 (miR171)-HAM regulatory modules, which define HAM spatial patterns and activities during meristem development across various meristem identities in land plants., (© 2024 The Author(s). Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Natural products (NPs) have a long history as sources for drug discovery, more than half of approved drugs are related to NPs, which also exhibit multifaceted advantages in the clinical treatment of complex diseases. However, bioactivity screening of NPs, target identification, and design optimization require continuously improved strategies, the complexity of drug mechanism of action and the limitations of technological strategies pose numerous challenges to the development of new drugs. This review begins with an overview of bioactivity- and target-based drug development patterns for NPs, advances in NP screening and derivatization, and the advantages and problems of major targets such as genes and proteins. Then, target-based drugs as well as identification and validation methods are further discussed to elucidate their mechanism of action. Subsequently, the current status and development trend of the application of traditional and emerging technologies in drug discovery and development of NPs are systematically described. Finally, the collaborative strategy of multi-technology integration and multi-disciplinary intersection is emphasized for the challenges faced in the identification, optimization, activity evaluation, and clinical application of NPs. It is hoped to provide a systematic overview and inspiration for exploring new drugs from natural resources in the future., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. This study was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2022-I2M-1-018, 2021-I2M-1-031), National Key Research and Development Program of China (no. 2022YFC3501803) and Beijing Nova Program (20230484482)., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study evaluated the accuracy of non-invasive prenatal testing (NIPT-SGDs) for dominant monogenic genetic diseases associated with fetal structural abnormalities and to assess the feasibility of clinical application., Methods: Pregnant women requiring prenatal diagnosis due to fetal structural abnormalities were enrolled. Maternal peripheral blood was analyzed for cell-free DNA (cfDNA) using coordinative allele-aware target enrichment sequencing (COATE-seq). This assessed fetal allele depth distribution, fraction and variation ratio. The variation's origin was then determined to obtain fetal variation information. Finally, NIPT-SGDs results were confirmed via invasive prenatal diagnosis (IPD)., Results: Upon examination of 113 samples using NIPT-SGDs, COATE-seq successfully analyzed 112 for fetal variation, excluding one due to hemolysis. The study detected six positive cases, yielding a 5.36% detection rate. These disorders included tuberous sclerosis complex (TSC1 and TSC2 being its causative genes), Noonan syndrome (PTPN11), polycystic kidney disease (PKD1), and Kabuki syndrome (KMT2D), occurring twice each, except for Noonan and polycystic kidney disease. Two false positives were due to the mother being a genetic mosaicism. Compared to invasive whole-exome sequencing (WES), NIPT-SGDs did not detect nine positive cases of IPD dominant monogenic diseases, accurately identifying 90.18% (101/112) of the actual positive and negative cases., Conclusion: Our findings demonstrate the clinical utility of NIPT-SGDs using COATE-seq in effectively identifying fetuses with dominant single-gene disorders. Furthermore, this method can be applied to all fetuses., Competing Interests: Declarations Conflict of interest The authors declare no conficts of interest. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Guizhou Provincial People’s Hospital (2023–45)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The river course is a transitional area connecting the source and receiving water bodies. The dissolved organic matter (DOM) in the river course is an important factor affecting the aquatic environment and ecological health. However, there are shortcomings in studying the differences and quantitative contributions of river DOM in different seasons and sources. In this study, ultraviolet-visible (UV-vis) and three-dimensional fluorescence spectra were used to characterize the optical properties, analyze the spatiotemporal changes, and establish the quantitative relationship between environmental factors and DOM in the inflow rivers of Baiyangdian Lake. The results showed that the relative DOM concentrations in summer and autumn were significantly higher than those in the other seasons (P < 0.001) and that the DOM source (S R  < 1) was mainly exogenous. The fluorescence abundance of protein-like substances (C1 + C2 + C3) was the highest in spring, whereas that of humus C4 was the highest in autumn. Moreover, the inflow rivers exhibited strong autogenetic characteristics (BIX > 1) throughout the year. Self-organizing maps (SOM) indicated that the main driving factors of water quality were NO 3 - -N in spring, autumn, and winter and DO, pH, and chemical oxygen demand (COD) in summer. Random forest analysis showed that the fluorescent components (C1-C4) were closely related to the migration and transformation of nitrogen, and pH and nitrogen were the main predictors of each component. The Mantel test and structural equation model (SEM) showed that temperature and NO 3 - -N significantly influenced the DOM concentration, components, and molecular properties in different seasons. Moreover, the river source also affected the distribution mechanism of DOM in the water body. Our study comprehensively analyzed the response of DOM in inflow rivers in different seasons and water sources, providing a basis for further understanding the driving mechanisms of water quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work described herein., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Psoriasis is a complex and chronic inflammatory disease. Current drugs help control the symptoms of psoriasis but make no cure, urging discovery of novel drugs. We report in this paper the discovery of new phosphodiesterase 4 (PDE4) inhibitors for treatment of psoriasis. We designed and synthesized 45 new compounds, among which 14h exhibited IC 50 of 0.57 nM for PDE4D and >4100-fold selectivity over other PDE families. Compound 14h inhibited release of inflammatory cytokines of TNF-α (IC 50 = 34.2 μM) and IL-6 (IC 50 = 40.9 μM) in Raw264.7 cells and reduced the expression of IL-1β and IL-17A in the skin of psoriasis mice. In addition, 14h alleviated IMQ-induced psoriasis in the mouse model and reduced the erythema level, scales, and thickness of the back skin of the mice. In short, our results suggested that PDE4 inhibitor 14h is a strong candidate for the topical treatment of psoriasis.

Background: The aqueous extraction of sesame oil is a traditional process that generates a large amount of melanoidins. However, little is known about the characteristics and bioactive functions of these melanoidins., Results: Electronic tongue, fluorescence emission spectroscopy, and Fourier transform infrared spectroscopy analyses indicated that melanoidins from sesame residues (MELs) are brown macromolecular compounds with protein skeletons and heteroaromatic ring structures, a bitter taste, and instability in strong oxidative and reductive environments. The MELs demonstrated inhibitory effects on α-glucosidase, α-amylase and pancreatic lipase in vitro. These MELs mitigated weight loss in mice with type 2 diabetes (T2DM), reduced their fasting blood glucose to 54.73% (500 mg kg -1 day -1 ) of the initial value, increased the glycogen levels in the liver and skeletal muscles, lowered blood lipid levels, and protected the liver. Western blot analysis revealed that MELs inhibited the activities of enzymes such as PEPCK, FBPase, and G6Pase through the IRS-1/PI3K/Akt and AMPK pathways, increased the activity of the enzymes hexokinase (HK) and pyruvate kinase (PK), enhanced liver glycolytic ability, and promoted liver glycogen synthesis, thereby reducing blood glucose levels in T2DM mice. Moreover, MELs reduced the ratio of Firmicutes to Bacteroides (F/B) in the intestines of T2DM mice, increased the relative abundance of beneficial bacteria such as Lactobacillus, Coprococcus, and Ruminococcus, and reduced the propionic acid content., Conclusions: Melanoidins can regulate T2DM by activating the IRS-1/PI3K/Akt and AMPK-signaling pathways and ameliorating gut microbiota imbalances in T2DM mice. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Hexafluoropropylene Oxide Dimer Acid (GenX or HFPO-DA), a fluorochemical used in industrial applications such as non-stick coatings and water-repellent textiles, has emerged as a replacement for perfluorooctanoic acid (PFOA). Its widespread use has led to detection in air, soil, and drinking water, raising concerns about potential health impacts. This study investigates the effects of exposure to environmentally relevant levels of GenX on placental and offspring development in mice. Female mice were exposed to GenX for short-term (11 days) or subchronic (100 days) durations. Both short-term and subchronic exposure resulted in alterations in body weight gain, placental weight, and placental efficiency. Dams exposed subchronically also exhibit altered fetal weight and impaired placental structure. In the labyrinth layer of placenta, subchronic exposure to GenX caused disordered vasculature, characterized by enlarged vessel lumens, discontinuous signals of maternal (MCT1) and fetal (MCT4) vascular networks, and impaired mitochondria in fetal sinus endothelial cells. The placental mRNA profile revealed imbalanced expression of factors essential for proper angiogenesis, with increased levels of Vegfa and Angpt1, and decreased levels of Tie2. Additionally, male pups of the subchronically exposed dams exhibited higher birth weight, increased weight gain and reduced anogenital distance (AGD), while premature puberty onset was observed in female pups. This study provides the first evidence that subchronic exposure to environmentally relevant levels of GenX affects placental angiogenesis, potentially contributing to altered development in offspring. These findings offer new insights into the health impacts of GenX on reproductive development and raise concerns about its safety as a PFOA alternative., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xinyi Mu reports financial support was provided by the National Natural Science Foundation of China. Xinyi Mu reports financial support was provided by Natural Science Foundation of Chongqing. If there are other authors, they 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.)

Predation reduces the population density of prey, affecting its fitness and population dynamics. Few studies have connected trait changes with fitness consequences in prey and the molecular basis and metabolic mechanisms of such changes in bat-insect systems. This study focuses on the responses of Helicoverpa armigera to different predation risks, focusing on echolocating bats and their calls. Substantial modifications were observed in the nocturnal and diurnal activities of H. armigera under predation risk, with enhanced evasion behaviors. Accelerated development and decreased fitness were observed under predation risks. Transcriptomic and metabolomic analyses indicated that exposure to bats induced the upregulation of amino acid metabolism- and antioxidant pathway-related genes, reflecting shifts in resource utilization in response to oxidative stress. Exposure to bat predation risks enhanced the activity of DNA damage repair pathways and suppressed energy metabolism, contributing to the observed trait changes and fitness decreases. The current results underscore the complex adaptive strategies that prey species evolve in response to predation risk, enhancing our understanding of the predator-prey dynamic and offering valuable insights for innovative and ecologically informed pest management strategies., (© 2024. The Author(s).)

Importance: Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited., Objective: To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset., Design, Setting, and Participants: The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement., Interventions: Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg)., Main Outcomes and Measures: The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality., Results: Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23])., Conclusions and Relevance: In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting., Trial Registration: ClinicalTrials.gov Identifier: NCT04915729.

Background: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window., Methods: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis., Results: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design., Discussion: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety., Trial Registration Number: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147)., Competing Interests: Competing interests: XC reported grant support from the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality. YS reported honoraria from Boehringer Ingelheim (China) Investment Co. The other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A silver-mediated cascade trifluoromethylthiolation/cyclization of unactivated alkenes has been investigated. This strategy employs AgSCF 3 as the trifluoromethylthiolating reagent to obtain a variety of useful trifluoromethylthiolated tricyclic imidazol derivatives in reasonable yields. Preliminary mechanistic studies indicate that the present reaction takes place via a radical process. This method is distinguished by its atom economy, wide functional group compatibility, operational simplicity and product diversity.

The recent discovery of the pivotal role of the central nervous system in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, whereas tumors can establish local autonomic and sensory neural networks to transmit signals into the central nervous system, thereby affecting brain activity. This review aims to summarize the latest research in brain-tumor cross-talk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathologic mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment., (©2024 The Authors; Published by the American Association for Cancer Research.)

Given the vulnerability of large and medium-sized mammal communities to climate change and human disturbances, understanding the spatial-temporal dynamics of these communities is essential for effective conservation planning. However, in many biodiversity hotspots, precise biological community assessments are insufficient. From 2012 to 2022, we deployed 784 camera traps in eight nature reserves (including sub-reserves) and one State Forest Farm (SFF, less strictly protected than a reserve) to study the composition and distribution of large and medium-sized mammals in tropical Xishuangbanna. The findings revealed the following: (1) Forty-three species, encompassing six orders, 17 families, and 37 genera, were documented. Among the species in historical data, nine species were not detected in this survey. (2) Smaller and more fragmented reserves lacked larger body-sized predators and herbivores, and most common species showed lower relative population abundance. Conversely, the SFF exhibited high mammal diversity. (3) The community composition of large and medium-sized mammals varied significantly across the nine sites, particularly among threatened species. Our findings highlight the uneven distribution of these mammal communities in Xishuangbanna, with rare and large-sized species facing increased vulnerability to rapid environmental changes. Moreover, the findings demonstrate the importance of considering species specificity and uniqueness in conservation planning for maintaining regional-scale biodiversity., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

1,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ] could promote phosphorus (P) absorption in the duodenum of broilers. The vitamin D receptor (VDR) mediates the action of 1,25-(OH) 2 D 3 . However, it remains unknown whether and how VDR is involved in promoting P absorption in the duodenum of broilers by 1,25-(OH) 2 D 3 . The objective of the current study was to investigate the effect of added 1,25-(OH) 2 D 3 levels on P absorption, mRNA or protein expression levels of VDR, retinoid X receptor (RXR), type IIb sodium-phosphate cotransporter (NaPi-IIb), inorganic phosphate transporter (PiT) 1 and PiT-2, and the enrichments of VDR bound to DNA promoters of the above P transporters in the ligated duodenal loops of Arbor Acres male broilers. The duodenal loops were perfused with solutions (pH = 6.0) containing 0 (control), 12.5, or 25.0 ng/L of 1,25-(OH) 2 D 3 for up to 40 min. The results indicated that the addition of either 12.5 or 25.0 ng/L 1,25-(OH) 2 D 3 to the perfusates increased (P < 0.04) P absorption percentage and rate, as well as the mRNA expression levels of VDR, RXR, NaPi-IIb, and PiT-2, alongside protein expression levels of VDR, NaPi-IIb, and PiT-2, whereas it did not affect (P > 0.10) PiT-1 mRNA and protein expression levels. Moreover, 1,25-(OH) 2 D 3 administration increased (P < 0.01) the enrichments of VDR bound to NaPi-IIb and PiT-2 DNA promoter regions in the ligated duodenal loops of broilers, which were in line with their mRNA expression levels. These findings suggest that 1,25-(OH) 2 D 3 increased P absorption possibly through VDR-mediated transactivation of NaPi-IIb and PiT-2 genes in the duodenum of Arbor Acres male broilers., Competing Interests: Conflict of interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (Copyright © 2024. Published by Elsevier Inc.)

Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision-cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking. In this study, PCLS prepared from male mouse liver tissue (mPCLS), healthy human liver tissue (hhPCLS), and cirrhotic human liver tissue (chPCLS) were cultured for 48 h with varying concentrations of the three compounds. Our findings indicate that NRG reduced collagen type 1 (COL1A1) expression in a concentration-dependent manner in both mPCLS and chPCLS, decreased fibrosis-related gene expression, and significantly lowered pro-collagen type 1 (PCOL1A1) levels in the culture medium by 54 ± 21% (mPCLS) and 78 ± 35% (chPCLS). Furthermore, NRG effectively inhibited IL-1β and TNF-α in mPCLS and IL-1β in chPCLS on both gene and protein levels. AA specifically reduced COL1A1 and PCOL1A1 in chPCLS, while ICA selectively downregulated Col1a1 and Acta2 gene expression in mPCLS. This study suggests NRG's potential as an effective antifibrotic agent, warranting further investigation into its mechanisms and therapeutic applications in liver fibrosis., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) enhances tumor immune escape and leads to tumor growth., Purpose: To investigate the expression of Siglec-15 in diffuse gliomas and its correlation with tumor magnetic resonance imaging (MRI) features., Material and Methods: This study included 57 patients with gliomas. Morphological MRI features, including the largest tumor diameter, enhancement category, location, calcification, cysts, and hemorrhage, were visually rated. Apparent diffusion coefficient (ADC) values were calculated in tumor region. MRI morphologic features and ADC were compared between patients with positive and negative Siglec-15 expression. Receiver operating characteristic (ROC) curves were further constructed to assess the diagnostic performance., Results: Siglec-15 was expressed in immunocytes, such as macrophages in the peritumoral area. Siglec-15 expression was positive in 20/57 (35.09%) patients, with higher expression in patients with IDH-mutant gliomas and lower grade gliomas. The tumor diameter was significantly smaller in patients with positive Siglec-15 expression than in those with negative expression for all patients ( P  = 0.017) and for patients with IDH-mutant gliomas ( P  = 0.020). Moreover, ADC values of the tumor were significantly higher in patients with positive Siglec-15 expression than in those with negative expression for all patients ( P  = 0.027). The areas under the ROC curve (AUCs) of the diameter and ADC were 0.702 and 0.686, respectively. A combination of these two parameters generated an improved AUC of 0.762., Conclusion: Siglec-15 was expressed in immunocytes such as macrophages in the peritumoral area, with a positive rate of 35.09%. Positive Siglec-15 expression in diffuse gliomas was correlated with smaller tumor size and higher ADC values., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

SiO 2 multishell hollow spheres (MHSs) as supports have multiple porous layers and internal voids, which present notable advantages in regulating mass transport and chemical reactions. However, practical applications of SiO 2 MHSs are severely hindered because of their high costs and low production efficiency issues. Herein, it is overcome these obstacles by developing a precursor hydrolysis method and demonstrate a cost-effective production of void-ratio tunable SiO 2 MHSs on a large scale, which has a much lower cavitation temperature (25 °C) and one order of magnitude decrease in cost. In addition, the new method can also be applied to fabricate TiO 2 and SnO 2 hollow spheres (HSs). In particular, an NH 4 Cl precipitation-pyrolysis strategy is developed to tune the pore diameters and pore distributions of SiO 2 MHSs with different void ratios. SiO 2 MHSs with varying void ratios and pore distributions have the broadest controlling release time ranges (30-430 h). The precursor hydrolysis method and NH 4 Cl precipitation-pyrolysis strategy offer adequate stimulus to push forward SiO 2 MHSs from laboratory-scale to industry-scale applications., (© 2024 Wiley‐VCH GmbH.)

Introduction: To investigate current practices, changes, and perceptions of rheumatologists regarding GC use in RA patients., Methods: A cross-sectional survey was conducted using a structured questionnaire between April and August 2023. Rheumatologists from 31 province-level regions of Mainland China were invited to participate. Chi-squared tests were adopted to investigate the differences by sociodemographic characteristics., Results: 1,717 rheumatologists from 598 hospitals completed the survey with a response rate of 92%. Up to 60% of participants expressed currently infrequent initiation of GC co-therapy with csDMARDs (hardly ever 7.0%; occasionally 24.6%; sometimes 29.1%), accompanied by a decline of frequency over time reported in 64.2%. Regarding attitudes towards bridging therapy with GC, 604 (35.2%) participants supported this approach, 468 (27.3%) opposed it, and 645 (37.6%) remained inconclusive. Time to GC discontinuation in context of csDMARDs was commonly reported within 6 months in current practice which has been narrowed over time. Reasons for chronic GC use were mostly reported due to suboptimal disease control, followed by the need of RA complications, and pre-existing comorbidities. After failure of GC cessation, majority of respondents (84.4%) would escalate RA therapy (commonly by addition of JAK inhibitors, TNF inhibitors), which usually or often facilitated the GC cessation. The most frequently reported advantages and weaknesses of GC were rapid and strong efficacy, adverse events, respectively. Regarding long-term low-dose GC use for RA, the percentage of respondents who supported, opposed, or depended on the situation were 15.9%, 17.2%, and 66.9%, respectively., Conclusions: The current data demonstrate that GC initiation for RA treatment is not as frequent as before and the awareness of GC discontinuation is growing in current practice. Attitudes towards GC co-therapy with csDMARDs vary considerably and long-term low-dose GC use remain situation dependent., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Hepatitis E caused by the hepatitis E virus (HEV) is prevalent worldwide. In China, considerable shifts in the epidemiology of hepatitis E have been observed over the last two decades, with ongoing changes in the prevalence of HEV., Methods: This study, in conjunction with the health examinations for students and workers, aims to estimate the seroprevalence and assess the risk factors of HEV infection in general population in Hebei province, China. Epidemiological information was collected using a specific questionnaire and blood samples were collected from each participant during the process of health examination. Anti-HEV IgG and IgM in sera were tested using the Wantai ELISA assay kits. Logistic regression modelling was used to identify associated risk factors., Results: The average positive rate of anti-HEV IgG in students (6-25 years) was 3.4%. One (0.2%) student was anti-HEV IgM positive, while also testing positive for IgG. The HEV seroprevalence was not related to students' gender, school, or family residence. In occupational populations, the overall seropositivity rate was 13.3% for anti-HEV IgG and 0.67% for IgM. HEV seropositivity increased significantly with age, ranging from 3.8% to 18.6% in age groups, and differed significantly among four occupation groups: farmers (17.6%), food supply workers (18.0%), other non-farm workers (14.7%) and healthcare workers (5.9%) (p = 0.002). Multivariable logistic analysis confirmed the significant correlations of seroprevalence with age and occupation., Conclusions: The study found a low seroprevalence of HEV in children and young adults in Hebei Province, China. Advanced age correlates with higher seroprevalence in occupational populations, indicating an accumulation of HEV infection over time. Seroprevalence varied significantly among different occupation groups, suggesting the important role of occupational exposure for HEV infection., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C 2 C 12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the influence of early psychological intervention on AIDS patients receiving hospital-led case management., Methods: Between December 2022 and May 2023, 100 cases of AIDS patients were gathered at the Fifth Hospital of Shijiazhuang. They were randomly assigned to either a psychological intervention group or a conventional intervention group. Each group consists of 50 individuals affected by AIDS. The conventional intervention group received care through traditional care models. In contrast, the psychological intervention group received immediate psychological support upon being screened positive for HIV antibodies, in addition to the conventional intervention group. The intervention period for both groups lasted 3 months, during which medication adherence, adverse emotional conditions, self-management skills, and quality of life were compared., Results: During the intervention period, the psychological intervention group exhibited higher medication adherence than the conventional intervention group. Post-intervention, the levels of anxiety as assessed by the SAS and the degree of depression as evaluated by the SDS of the conventional intervention group were higher than those of the psychological intervention group. Additionally, the psychological intervention group demonstrated higher scores in 7 dimensions the total score on the self-management ability scale, and a higher score in the WHOQOL-HIV-BREF compared to the conventional intervention group., Conclusion: In the context of hospital-led case management for AIDS, early psychological intervention in patients has been shown to enhance medication adherence, reduce negative emotions, improve self-management skills, and enhance overall quality of life.

Tofu has captivated researchers' attention due to its distinctive texture and enrichment in nutritional elements, predominantly soybean protein. Coagulants play a critical role in promoting coagulation during tofu production, directly influencing its texture, quality, and physicochemical characteristics. Currently, the impact of coagulant characteristics on coagulation, as well as the underlying mechanisms, remain unclear. This review provides a summary of research progress on salt coagulants, acid coagulants, enzyme coagulants, novel coagulants, polysaccharide additives, and various coagulant formulations. The coagulation mechanisms of various coagulants are also discussed. Accordingly, this paper seeks to offer reliable theoretical guidance for the development of novel coagulants and the realization of fully automated tofu production.

In power grid surveying, it is often necessary to fuse panchromatic and multispectral imagery for the design of power lines. Despite the abundance of deep learning networks for fusing these images, the results often suffer from spectral information loss or structural blurring. This study introduces a fusion model specifically tailored for power grid surveying that significantly enhances the representation of spatial-spectral features in remote sensing images. The model comprises three main modules: a TransforRS-Mamba module that integrates the sequence processing capabilities of the Mamba model with the attention mechanism of the Transformer to effectively merge spatial and spectral features; an improved spatial proximity-aware attention mechanism (SPPAM) that utilizes a spatial constraint matrix to greatly enhance the recognition of complex object relationships; and an optimized spatial proximity-constrained gated fusion module (SPCGF) that integrates spatial proximity constraints with residual connections to boost the recognition accuracy of key object features. To validate the effectiveness of the proposed method, extensive comparative and ablation experiments were conducted on GF-2 satellite images and the QuickBird (QB) dataset. Both qualitative and quantitative analyses indicate that our method outperforms 11 existing methods in terms of fusion effectiveness, particularly in reducing spectral distortion and spatial detail loss. However, the model's generalization performance across different data sources and environmental conditions has yet to be evaluated. Future research will explore the integration of various satellite datasets and assess the model's performance in diverse environmental contexts.

Background: Obesity accelerates the development of lumbar disease and increase the risk during surgery. Unilateral biportal endoscopic discectomy (UBE) is a newly developed minimally invasive technique, which refers to the spinal surgery under unilateral double-channel endoscopic surgery. Therefore, the purpose of this study is whether UBE decompression alone can bring good clinical results to young obese patients with lumbar degenerative diseases., Methods: The patients with lumbar diseases who underwent UBE and open surgery (open discectomy) in our hospital from February 2020 to February 2022 were selected as young (age ≤ 44 years old) and obesity (BMI ≥ 30 kg/m 2 ). The patients were evaluated with VAS, ODI, JOA and modified Macnab score before operation, 1 month, 6 months and 12 months after operation. Nerve root function sensation, muscle strength and tendon reflex were evaluated. The operation time, estimated blood loss, postoperative hospital stay, incidence of postoperative complications and reoperation rate were recorded. MRI quantitative lumbar multifidus muscle (LMM) comparison was performed 12 months after operation., Results: 77 patients were included, and the scores of VAS, ODI and JOA were similar in the two groups during the last follow-up. There were no difference in nerve root function sensation, muscle strength or tendon reflex. However, one month after operation, the VAS back score and ODI improvement in the UBE group were significantly better than those in the open group, which were 2.44 ± 0.97, 33.10 ± 6.78 and 2.93 ± 0.79 and 36.13 ± 5.84, respectively, with a statistically significant difference ( p  = 0.020 and 0.038). According to the modified Macnab criteria, UBE group, the excellent and good rate was 97.2%. The excellent and good rate of open group was 97.6%. The estimated blood loss and postoperative hospital stay in UBE group (36.81 ± 17.81, 3.92 ± 1.32) were significantly better than those in open group (104.88 ± 31.41, 6.41 ± 1.94), with a statistically significant difference ( p  = 0.010). There was no significant difference in operation time between the two groups ( p  = 0.070). The number of complications in UBE group was 2 (5.6%) and open group was 4 (9.8%). The fat infiltration rate of 19.3%+11.0% in UBE group was significantly lower than that of 27.0%±13.9% in open group ( p  = 0.010)., Conclusion: UBE has the advantage of early recovery in the treatment of lumbar degenerative diseases in young obese patients, and reduces the damage to LMM, so it has a good clinical effect., 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., (© 2024 Ma, Li, Geng, Yan, Jiang, Tu, Chen, Wu and Nong.)

This study presents the development of highly efficient Surface-Enhanced Raman Scattering (SERS) substrates through femtosecond (fs) laser processing of crystalline silicon (Si), resulting in mountain-like microstructures. These microstructures, when decorated with gold nanoparticles (Au NPs), exhibit remarkable SERS performance due to the creation of concentrated hotspots. The enhanced Raman signals originate from the excitation of localized surface plasmon resonance (LSPR) of the Au NPs and the multi-scale rough morphology of the Si substrates. Finite-element method simulations confirm the electromagnetic field enhancement in narrow gaps, supporting the experimental observations. The fabricated substrates show high uniformity, oxidation resistance, long-term stability, and exceptional reproducibility, making them ideal for molecular detection, especially in food safety applications. A remarkable enhancement factor (EF) of 10 10 is attained in the detection of Malachite Green (MG), boasting a limit of detection (LoD) as low as 10 -14 M. This underscores the immense potential of this technique for achieving highly sensitive and dependable SERS-based sensing capabilities.

Additive friction stir deposition (AFSD) is a novel solid-state additive manufacturing method developed on the principle of stirring friction. Benefits from its solid-phase properties, compared with traditional additive manufacturing based on melting-solidification cycles, AFSD solves the problems of porosity, cracks, and residual stress caused by the melting-solidification process, and has a significant improvement in efficiency. In AFSD, the interaction between feedstocks and high-speed rotating print heads suffers severe plastic deformation at high temperatures below the melting point, ending up in fine, equiaxed recrystallized grains. The above characteristics make components by AFSD show similar mechanical behaviors to the forged ones. This article reviews the development of AFSD technology, elaborates on the basic principles, compares the macroscopic formability and material flow behavior of AFSD processes using different types of feedstocks, summarizes the microstructure and mechanical properties obtained from the AFSD of alloys with different compositions, and finally provides an outlook on the development trends, opportunities, and challenges to the researchers and industrial fields concerning AFSD.

Background/objectives: This study investigated the effects of palmitoleic acid (POA) consumption on liver function, intestinal microbiota, and trimethylamine- N -oxide (TMAO) levels in the serum of mice treated with 3% L-carnitine drinking water. The purpose was to highlight the impact of POA on liver injury associated with high L-carnitine intake., Methods: A correlation analysis was carried out. The physiological and biochemical results showed that the administration of POA could alleviate liver injury induced by high L-carnitine ingestion, as reflected by a reduction in liver function indices (ALT, AST, AKP, and TBA activities) and modulation of antioxidant enzyme activities (SOD, GSH-Px, MDA, and RAHFR). The study also monitored the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, to assess the impact of POA on intestinal microbiota, we conducted a 16S rRNA high-throughput sequencing analysis., Results: The findings indicated that POA administration resulted in lower levels of TMAO in treated mice. Furthermore, POA could regulate the composition of intestinal microbiota in L-carnitine mice, particularly affecting Bacteroides vulgatus , Parabacteroides distasonis , Alistipes shahii , Lachnospiraceae NK4A136 group, and Parasutterella secunda , which were closely related to liver injury., Conclusions: In summary, POA could repair liver damage caused by high intake of L-carnitine by regulating the distribution of intestinal flora and subsequently decreasing serum TMAO levels.

Competing Interests: Authors have no financial or personal relationships with other people or organisations.

Postpartum elevation of alanine aminotransferase (ALT) in mothers with chronic hepatitis B (CHB) presents a significant clinical challenge. However, the existing literature demonstrates inconsistencies regarding its incidence and predictors in mothers infected with the hepatitis B virus (HBV). Recent advancements in antiviral prophylaxis against mother-to-child transmission of HBV and postpartum cessation of antiviral therapy further complicate this issue. Our literature review, spanning PubMed, and two Chinese-language databases (CNKI and Wanfang) from 1 January 2000 to 31 December 2023 aimed to consolidate and analyse available data on the frequency and severity of postpartum ALT flares, identify risk factors, and propose a management algorithm. Data from 23 eligible studies involving 8,077 pregnant women revealed an overall incidence of postpartum ALT elevation: 25.7% for mild cases, 4.4% for moderate cases, and 1.7% for severe cases. In the subgroup of mothers who were HBeAg-positive and on antiviral prophylaxis for preventing mother-to-child transmission, postpartum intermediate and severe ALT elevations were reported with pooled rates of 5.9% and 0.8%, respectively. Importantly, none resulted in mortality or necessitated liver transplantation. Identified risk factors for postpartum ALT flares in mothers with CHB included HBV DNA levels, ALT levels during pregnancy, postpartum cessation of antiviral treatment, and HBeAg status. By leveraging this evidence and recent data on predictors of intermediate or severe postpartum ALT flares, we propose a risk-stratified algorithm for managing postpartum ALT elevation and selecting therapy in mothers with CHB, tailoring different approaches for treatment-naive vs treatment-experienced populations. These recommendations aim to provide guidance for clinical decision-making and enhance patient outcomes., Competing Interests: C.Q.P. received institutional research grants from Gilead Sciences and Wuxi Hisky Medical Technologies Co., Ltd. Other authors have no financial interests to be disclosed., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

This study established an on-line SFE-SFC-MS/MS method for the determination of mefentrifluconazole (MFZ) enantiomers and pyraclostrobin (PY) in mango and mango juice. Key parameters of SFC separation and SFE extraction have been optimized for high efficiency, sensitivity, and environmental friendliness. Enthalpy controlled enantioseparations of MFZ were recognized by thermodynamic analysis. Molecular docking estimated the enantiomeric recognition of MFZ enantiomers binding to the chiral stationary phase. The mean recoveries (RSDs) were in the range of 94.5-106.8 % (4.2-15.4 %), 91.1-103 % (3.6-10.3 %), 94.7-102.7 % (3.8-9.8 %), and 93.2-106.9 % (4.1-12.1 %) for R-MFZ, S-MFZ, racemic MFZ, and PY under 3 spiked levels of interday assays (n = 15). The LOQs of R-MFZ, S-MFZ, and PY were 0.5, 0.5, and 1 μg kg -1 . The method was further applied to real samples in Guangxi Province, China with low acute and chronic dietary risk for MFZ and PY in mango and mango juice., 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 Ltd.)

Replete with ammonia nitrogen and organic pollutants, landfill leachate typically undergoes treatment employing expensive and carbon-intensive integrated techniques. We propose a novel microalgae technology for efficient, low-carbon simultaneous treatment of carbon, nitrogen, and phosphorus in landfill leachate (LL). The microbial composition comprises a mixed microalgae culture with Chlorella accounting for 82.58%. After seven days, the process with an N/P ratio of approximately 14:1 removed 98.81% of NH 4 + -N, 88.62 % of TN, and 99.55% of TP. Notably, the concentrations of NH 4 + -N and TP met the discharge standards, while the removal rate of NH 4 + -N was nearly three times higher than previously reported in relevant studies. The microalgae achieved a removal efficiency of 64.27% for Total Organic Carbon (TOC) and 99.26% for Inorganic Carbon (IC) under mixotrophic cultivation, yielding a biomass of 1.18 g/L. The treatment process employed in this study results in a carbon emissions equivalent of -8.25 kgCO 2 /kgN removed , representing a reduction of 33.56 kgCO 2 compared to the 2AO + MBR process. In addition, shake flask experiments were conducted to evaluate the biodegradability of leachate after microalgae treatment. After microalgae treatment, the TOC B (Biodegradable Total Organic Carbon)/TOC ratio decreased from 56.54% to 27.71%, with no significant improvement in biodegradability. It establishes a fundamental foundation for further applied research in microalgae treatment of leachate., 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 B.V. All rights reserved.)

Objective: To explore the characteristic changes of multiple ERP components associated with attention impairments in patients with temporal lobe epilepsy (TLE)., Methods: A total of 92 patients diagnosed with TLE at Xiangya Hospital during May 2022 and January 2023 and 85 healthy controls were included in this study. Participants were asked to complete attention network test with recording of electroencephalogram., Results: Compared with healthy controls, significant lower amplitudes (cue-related N1, N2 and CNV) and longer latencies (target-related N2) were found in TLE patients. Besides classical components, other components could also reveal the impairments of attention function. Cue-related N1 (p ≤ 0.007) and N2 (p ≤ 0.01) components indicated impaired alerting and orienting network in TLE. And cue-related CNV-E component (p = 0.003) promoted the alerting network was damaged and target-related N2 component (p = 0.008) indicated the executive control network was impaired., Conclusion: These findings consummate the non-classical ERP features of attention impairments in TLE patients., Significance: The above findings have strong clinical guiding significance for early identification and intervention., Competing Interests: Conflicts of interest All authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The root of Stemona tuberosa Lour has been used to treat tuberculosis, scabies, and eczema. Polysaccharides are among its main bioactive ingredients. A low-molecular-weight (1819 Da) polysaccharide (SPS2-A) was obtained from the root of S. tuberosa Lour by optimizing three-phase partitioning, purified using an ion chromatography column, and its effects and mechanisms were investigated. Structural analysis revealed that SPS2-A contained arabinose, galactose (Gal), glucose (Glc), xylose, and mannose. The SPS2-A backbone structure comprised sugar residues →4)-α-D-Glcp-(1→, →4)-α-D-Galp-(1→, and →4,6)-β-D-Galp-(1→, while the side chain primarily comprised α-D-Glcp-(1 → connected to the O-6 position of the residue →4,6)-β-D-Galp-(1→. In vitro, SPS2-A downregulated the expression of interleukin-6 in lipopolysaccharide-induced RAW264.7 macrophages. In vivo, SPS2-A significantly downregulated the expression of myeloperoxidase, interleukin-6, interleukin-1β, and tumor necrosis factor-α in bronchoalveolar lavage fluid and lung tissue. Western blotting analysis indicated that SPS2-A reduced lung inflammation in mice with sepsis-induced acute lung injury by activating the nuclear factor κB pathway. These results suggest that SPS2-A is a potential anti-inflammatory candidate for the treatment of sepsis-induced acute lung injury., 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 B.V.)

Transition-metal-catalyzed C-H activation has proven to be a powerful tool for the late-stage modification of peptides. We herein report a method for site-selective alkylation of peptides with maleimides through Pd-catalyzed β-C(sp 3 )-H activation. In this protocol, the methionine residues within peptides serve as the directing groups, which circumvented the preinstallation and subsequent removal of the directing groups. This chemistry exhibited broad substrate scope and can be utilized for peptide ligation.

Objective: To evaluate the causal relationships between genetically predicted lifestyle factors and frailty using Mendelian randomization(MR)., Methods: We extracted summary data from genome-wide association studies conducted among individuals of European ancestry, examining lifestyle factors such as smoking, alcohol consumption, physical activity, and sedentary behaviors. The outcomes were assessed using Fried Frailty Score (FFS) and Frailty Index (FI). We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent causal effects were primarily estimated using inverse variance weighted methods. Multiple sensitivity and validation analyzes were used., Results: The IVW analyzes indicated that smoking increased frailty risk (FFS: β = 0.107, 95 % CI = 0.057 to 0.156, P < 0.001; FI: β = 0.899, 95 % CI = 0.016 to 0.191, P = 0.020.), this effect was amplified in the MVMR analysis after adjusting for alcohol consumption. Strenuous sports or other exercise(SSOE) reduced frailty risk (FFS: β = -0.473, 95 % CI = -0.646 to -0.299, P < 0.001; FI: β = -0.423, 95 % CI = -0.692 to -0.154, P = 0.002). Vigorous and moderate-to-vigorous physical activities were significantly related to lower FFS, although no effects were observed on FI. Increased television watching was linked to higher frailty incidence (FFS: β = 0.227, 95 % CI = 0.197 to 0.257, P < 0.001; FI: β = 0.297, 95 % CI = 0.249 to 0.346, P < 0.001), the impact remained persistent in MVMR adjusting for driving and computer use., Conclusion: This study suggests that modifications in smoking, alcohol consumption, and physical activity may help prevent or manage frailty., 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 B.V.)

Introduction: In clinical diagnosis of porcine diseases, co-infection with multiple viruses often leads to similar clinical symptoms. Postweaning multisystemic wasting syndrome (PMWS) can be caused by infections with TTSuV or PCV2, while PCV2, PRV, and PPV can cause respiratory and reproductive disorders in pigs. The overlapping clinical and pathological features of these infections necessitate the development of a rapid and specific method for differentiating and detecting these four DNA viruses., Methods: In this study, four pairs of primers and TaqMan probes were designed targeting the conserved sequence of TTSuV, the Rep gene of PCV2, the gE gene of PRV, and the VP2 gene of PPV. After optimizing reaction conditions, including annealing temperature, primer concentration, and probe concentration, a quadruplex real-time PCR method was developed., Results: This method can specifically detect TTSuV1, PCV2, PRV, and PPV simultaneously, with no cross-reactivity with ASFV, CSFV, PRRSV, PEDV, PSV, and TGEV. The minimum detection limit for each virus was 10 copies/μl, and the inter-assay and intra-assay coefficients of variation ranged from 0.33% to 1.43%. Subsequently, 150 clinical samples were tested to evaluate the practical applicability of this method. The positive rates for TTSuV1, PCV2, PRV, and PPV were 8.6% (13/150), 10.67% (16/150), 14% (21/150), and 11.33% (17/150), respectively., Discussion: The results indicate that the established quadruplex real-time PCR method can assist in the accurate and rapid diagnosis of TTSuV1, PCV2, PRV, and PPV in clinical settings, providing robust support for the prevention and control of these infections., 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 Quan, Geng, Wu, Jiang, Li and Yu.)

Background: The large-scale language model, GPT-4-1106-preview, supports text of up to 128 k characters, which has enhanced the capability of processing vast quantities of text. This model can perform efficient and accurate text data mining without the need for retraining, aided by prompt engineering., Method: The research approach includes prompt engineering and text vectorization processing. In this study, prompt engineering is applied to assist ChatGPT in text mining. Subsequently, the mined results are vectorized and incorporated into a local knowledge base. After cleansing 306 medical papers, data extraction was performed using ChatGPT. Following a validation and filtering process, 241 medical case data entries were obtained, leading to the construction of a local medical knowledge base. Additionally, drawing upon the Langchain framework and utilizing the local knowledge base in conjunction with ChatGPT, we successfully developed a fast and reliable chatbot. This chatbot is capable of providing recommended diagnostic and treatment information for various diseases., Results: The performance of the designed ChatGPT model, which was enhanced by data from the local knowledge base, exceeded that of the original model by 7.90% on a set of medical questions., Conclusion: ChatGPT, assisted by prompt engineering, demonstrates effective data mining capabilities for large-scale medical texts. In the future, we plan to incorporate a richer array of medical case data, expand the scale of the knowledge base, and enhance ChatGPT's performance in the medical field., 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 Liu, Kan, Jiang, Geng, Nie and Yang.)

Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism., (© 2024. The Author(s).)

Lysine β-hydroxybutyrylation (Kbhb) is a post-translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label-free β-hydroxybutylation quantitative proteomics using brain samples of 8-month-old and 2-month-old APP/PS1 AD model mice and wild-type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle-associated enzymes including citrate synthase (CS) and succinate-CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium β-hydroxybutyrate (Na-β-OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that β-OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased β-OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated β-amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention., (© 2024 The Author(s). Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective: Thymidylate synthase (TYMS) constitutes a pivotal and potent target in the context of chemoresistance. However, the oncogenic role of TYMS has received insufficient attention., Methods: Leveraging data from the Cancer Genome Atlas (TCGA) and various public databases, we conducted an extensive investigation into the oncogenic role of TYMS across 33 cancer types. Subsequently, TYMS was inhibited using small interfering RNA (siRNA) in four different cell lines, and cell proliferation and migration were assessed using CellTiter-Glo and Transwell assays., Results: TYMS exhibited pronounced expression across a spectrum of cancers and demonstrated associations with clinical outcome in diverse cancer patient cohorts. Furthermore, genetic alterations were identified as potential influencers of overall survival in specific tumor types. Notably, the expression of thymidylate synthase correlated with tumor-infiltrating CD4+ cells in select cancers. Additionally, the functional mechanism of TYMS encompassed nucleotidase activity, chromosome segregation, and DNA replication progress. In vitro experiments further substantiated these findings, demonstrating that the suppression of TYMS impeded the cell growth and invasive capabilities of HeLa, A549, 786-O, and U87&#95;MG cells., Conclusions: This study furnishes a comprehensive understanding of the oncogenic role played by TYMS in human tumors., Competing Interests: None., (AJTR Copyright © 2024.)

The poor oxidation resistance of traditional electrolytes has hampered the development of high-voltage potassium-ion battery technology. Here, we present a cosolvent electrolyte design strategy to overcome the high-voltage limitations of potassium-ion electrolyte chemistries. The cosolvent electrolyte breaks the dissolution limitation of the salt through ion-dipole interactions, significantly enlarging the anion-rich solvation clusters, as verified by the insitu synchrotron-based wide-angle X-ray scattering experiments. Furthermore, the large anion-rich solvation clusters also facilitate the formation of an effective electrode-electrolyte interphase, thereby enhancing compatibility with high-voltage electrodes. The cosolvent electrolyte enables K||Prussian blue cells (2-4.5 V) to operate for >700 cycles with a capacity retention of 91.9%. Our cosolvent electrolyte design strategy paves new avenues for the development of high-voltage potassium-ion batteries and beyond., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood., Objective: This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α., Methods: The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA)., Results: NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group ( p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group ( p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group ( p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group ( p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group ( p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma., Conclusion: The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP., Competing Interests: The authors declare that they have no competing interests., (© 2024 Cheng et al.)

Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied Pattern-Recognition Receptors (PRRs), and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type (WT) and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contribute to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation., (© The Author(s) 2024. Published by Oxford University Press. 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.)

We propose and experimentally demonstrate a parallel ultra-fast random bit generation (RBG) scheme based on wideband chaotic microcomb, which utilizes a phase modulation and dispersive component broadening spectrum. The effective bandwidth of each comb tooth is increased by over 10-fold. Wavelet high-pass filtering (WHPF) is employed to make the probability density functions (PDFs) of the chaotic signal's amplitude unbiased, achieving high symmetry with a skewness coefficient |S| of 0.0026, and the RBG rate of a single channel reaches 200 Gbps. Furthermore, the autocorrelation properties of the random sequences from each comb tooth and the cross-correlation properties between different comb teeth are analyzed, confirming both true randomness and orthogonality. This scheme can simultaneously generate dozens of wideband chaotic combs in the wavelength range of 1500-1600 nm.