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Abstract Oncostatin M (OSM) is a unique Interleukin 6 (IL-6) family cytokine that plays pivotal roles in numerous biological events by signaling via two types of receptor complexes. While type I OSM receptor complex is formed by glycoprotein 130 (gp130) heterodimerization with Leukemia Inhibitory Factor receptor (LIFR), type II OSM receptor complex is composed of gp130 and OSM receptor (OSMR). OSM is an important contributor to multiple inflammatory diseases and cancers while OSM inhibition has been shown to be effective at reducing symptoms, making OSM an attractive therapeutic target. Using cryogenic electron microscopy (cryo-EM), we characterize full extracellular assemblies of human type I OSM receptor complex and mouse type II OSM receptor complex. The juxtamembrane domains of both complexes are situated in close proximity due to acute bends of the receptors. The rigid N-terminal extension of OSM contributes to gp130 binding and OSM signaling. Neither glycosylation nor pro-domain cleavage of OSM affects its activity. Mutagenesis identifies multiple OSM and OSMR residues crucial for complex formation and signaling. Our data reveal the structural basis for the assemblies of both type I and type II OSM receptor complexes and provide insights for modulation of OSM signaling in therapeutics.

Abstract Background Lipid-lowering therapy (LLT) plays a central role in managing atherosclerotic cardiovascular disease (ASCVD) risk, but its underuse is reported in over 40% of the qualified population in the United States. Studies on factors, particularly actionable factors associated with guideline-directed LLT are limited. Methods This study evaluated participants from the Multi-Ethnic Study of Atherosclerosis (MESA) on their qualification for LLT at exam 5 (2010–2012) according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on cholesterol management. Participants were categorized as on-LLT or off-LLT at the following exam (2016–2018). Multi-variable relative risk (RR) models were used to analyze between LLT usage and factors prior to 2013, including age, gender, race/ethnicity, education level and medical insurance, income, smoking, body mass index (BMI), diabetes, hypertension, and presence of coronary artery calcium (CAC). Results Among the 2114 participants qualified for LLT at exam 5 with an average age of 70.7, 1,129 (53.4%) were on LLT while 985 (46.6%) were off LLT at exam 6. Black participants were less likely to be on LLT compared to the reference white participants (RR 0.80, 95% confidence interval CI 0.71–0.90). Higher BMI showed borderline significant association with LLT. Comorbidities of diabetes and hypertension were positively associated with LLT use (RR 1.39 and 1.23, 95% CI 1.27–1.52 and 1.10–1.36, respectively). CAC score > 0 as an indicator of subclinical ASCVD was strongly associated with LLT too, independent of other demographic or comorbidity factors (RR 1.38, 95% CI 1.21–1.56). Conclusions This study identifies key factors influencing LLT use among MESA participants. Black participants were less likely to be on LLT, highlighting healthcare disparities. CAC presence was strongly associated with LLT use, suggesting that CAC measurement could be an actionable factor to improve adherence to LLT guidelines.

Colletotrichum species are significant pathogens of various economic plant hosts worldwide. In this study, 45 Colletotrichum isolates were obtained from symptomatic walnut leaves of walnut anthracnose in Shaanxi and Sichuan Provinces. In conjunction with morphological evidence and multi-gene phylogenetic analyses of internal transcribed spacer (ITS), actin (act), chitin synthase 1 (chs1), glyceraldehyde-3-phosphate dehydrogenase (gapdh) and beta-tubulin (tub2) sequences support the introduction of three new species, namely Colletotrichum cordae, C. guangyuanense and C. juglandium. Five species of Colletotrichum were identified to be C. fioriniae of the C. acutatum species complex, C. karsti of the C. boninense species complex, C. gloeosporioides, C. mengyinense and C. siamense of the C. gloeosporioides species complex. The three new species are described and illustrated in this paper and compared with taxa in the Colletotrichum gloeosporioides species complex. The current results improve the understanding of Colletotrichum species causing walnut anthracnose in China.

Abstract Owing to the instability of gelatine in hygrothermal environments, gelatine-based cultural heritage undergo various deterioration processes, such as cracking, peeling, warping, curling and fracture, posing significant threats to its long-term preservation. Building on previous research, this study investigates the stability of polyol glycidyl ether–gelatine composite films under high-humidity and high-temperature conditions using ethylene glycol diglycidyl ether (EGDE) as a model compound. The hygrothermal ageing properties of EGDE–gelatine composite films are evaluated in terms of macrosize, mesoscopic structure, surface properties and mechanical properties. Results indicate that EGDE enhances the dimensional stability and swelling ratios of the composite films, stabilizes the pore structure and distribution and maintains the hydrophilicity and molecular structural stability under hygrothermal ageing conditions. Furthermore, the incorporation of EGDE leads to superior stress–strain properties of the composite films in such challenging environments. This study provides valuable experimental data for the preparation and conservation applications of gelatine-based cultural heritage materials.

Abstract The tomb of Marquis Yi of Zeng was unearthed in 1978 at Leiguudun in Suizhou City, Hubei Province, China. This is the largest wooden coffin in rock pit and vertical cave in the Warring States period in China. The large wooden coffin components provide reliable material data for the study of the feudal burial system in the pre-Qin period and have high value. In this paper, the wooden coffin excavated from the tomb of Marquis Yi of Zeng was studied. By understanding the composition of wood, studying the weight gain rate, shrinkage rate, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compression resistance, the wood reinforced by rosin and epoxy resin was compared, and the reinforcement effect and principle of the two reinforcement methods were discussed. The study found that the wood properties of rosin reinforced group were better than those of epoxy reinforced group in the aspects of compressive strength, weight gain rate and volume shrinkage rate, and the mechanical properties of wood were significantly improved. In addition, methanol or ethanol can be used to dissolve the rosin shellac in this strengthening process, which can achieve reversible strengthening treatment. The results provide valuable examples and research ideas for the selection of different conservation techniques of large wooden cultural relics unearthed in the middle and lower reaches of the Yangtze River during the Warring States Period.

Abstract Background The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. Methods This hospital-based, cross-sectional study was conducted at the Third People’s Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. Results The study included participants primarily between the ages of 20–40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. Conclusion Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

Based on previous research, it's unclear about the signaling pathway involved in the negative regulation of T-lymphocyte proliferation in thymus by monochromatic red light. Newly hatched chicks were randomly assigned divided into white (WL), red (RL), green (GL), and blue (BL) light treatments. Three days later, each light treatment group was further divided into intact, sham operation, and pinealectomy groups. The findings revealed that RL led to an increase in the expression of RORα and RORγ, while p-AKT/p-GSK3β/β-catenin/CyclinD1 expression in the thymus of chicks were decreased. Conversely, GL showed opposite results compared to RL. After pinealectomy, accompanied with the expression of RORα and RORγ increased under four light, p-AKT/ p-GSK3β/ β-catenin/ CyclinD1 expression were decreased. In vitro, exogenous melatonin increased the p-AKT/β-catenin/CyclinD1 expression in the thymic lymphocytes of chick reared under RL. The stimulative effect of melatonin was enhanced by SR3335 (RORα antagonist) or GSK298 (RORγ antagonist), while it was attenuated by SR1078 (RORα/RORγ agonist), LY-294 (PI3K antagonist) and HY-102 (AKT antagonist). These results demonstrate that RORα/RORγ negatively regulate monochromatic red light induced-T-lymphocyte proliferation in the thymus, possibly through the PI3K/AKT/p-GSK3β (Ser9) signaling pathway.

ABSTRACT Microsatellites or simple sequence repeats (SSRs) are prevalent across various organisms' genomes. However, their distribution patterns and evolutionary dynamics in reptile genomes are rarely studied systematically. We herein conducted a comprehensive analysis of SSRs in the genomes of 36 reptile species. Our findings revealed that the total number of SSRs ranged from 1,840,965 to 7,664,452, accounting for 2.16%–8.19% of the genomes analyzed. The relative density ranged from 21,567.82 to 81,889.41 bp per megabase (Mbp). The abundance of different SSR categories followed the pattern of imperfect SSR (I‐SSR) > perfect SSR (P‐SSR) > compound SSR (C‐SSR). A significant positive correlation was observed between the number of SSRs and genome size (p = 0.0034), whereas SSR frequency (p = 0.013) or density (p = 0.0099) showed a negative correlation with genome size. Furthermore, no correlation was found between SSR length and genome size. Mononucleotide repeats were the most common P‐SSRs in crocodilians and turtles, whereas mononucleotides, trinucleotides, or tetranucleotides were the most common P‐SSRs in snakes, lizards, and tuatara. P‐SSRs of varying motif sizes showed nonrandom distribution across different genic regions, with AT‐rich repeats being predominant. The genomic SSR content of the squamate lineage ranked the highest in abundance and variability, whereas crocodilians and turtles showed a slowly evolving and reduced microsatellite landscape. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that genes harboring P‐SSRs in the coding DNA sequence regions were primarily involved in the regulation of transcription and translation processes. The SSR dataset generated in this study provides potential candidates for functional analysis and calls for broader‐scale analyses across the evolutionary spectrum.

IntroductionRare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood–brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd2O3) during pregnancy, and its involved mechanism of BGA injury.MethodsWe used rat model to investigated the mechanisms of the offspring’s neural damage that Nd2O3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators.ResultsMaternal Nd2O3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring’s neural development and weakening their spatial learning ability. Nd2O3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd2O3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability.ConclusionMaternal exposure to Nd2O3 affects the offspring’s BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children’s gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd2O3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd2O3, such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention.

ObjectiveTo evaluate the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetic peripheral neuropathy (DPN) in Hunan Province, and establish and verify the prediction model.MethodsThis was a retrospective study involving 4908 patients, all patients were randomly divided into the training dataset(3436 cases)and the validation dataset (1472 cases) in a ratio of 7:3. Electroneurogram, clinical signs,and symptoms were used to evaluate neuropathy. Least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal factors, and multifactorial logistic regression analysis was used to build a clinical prediction model. Calibration plots, decision curve analysis (DCA), and subject work characteristic curves (ROC) were used to assess the predictive effects.ResultThe prevalence of PDPN was 33.2%, and the multivariate logistic regression model showed that peripheral artery disease, duration of diabetes, smoking, and HBA1c were independent risk factors for PDPN in patients with type 2 diabetes. ROC analysis results showed that the AUC of the established prediction model was 0.872 in the training dataset and 0.843 in the validation dataset. The calibration curve and decision curve show that the model has good consistency and significant net benefit.Conclusion33.2% of DPN patients had PDPN in Hunan Province, China. Peripheral artery disease, duration of diabetes, smoking, and HBA1c are risk factors for PDPN in patients with type 2 diabetes. The prediction model is based on the above factors, which can well predict the probability of PDPN.

Resorcinol bis(diphenylphosphate) (RDP) is an emerging pollutant that has been frequently detected in aquatic environments, although its toxicity is poorly characterized. To understand how RDP affects the neural system, two-month-old zebrafish were exposed to RDP at concentrations of 0.1 and 10 μg/L for 60 days. Following exposure, behavioral assessments were conducted, revealing the emergence of anxiety-like symptoms and memory deficits among the adult fish exposed to RDP, especially at the higher concentration. The increased blood–brain barrier (BBB) permeability (4.67–5.58-fold higher than the control group), reduced expression of tight junction proteins and the rapid brain RDP bioaccumulation (15.63 ± 2.34 ng/g wet weight) indicated the neurotoxicity of RDP. Excess reactive oxygen species synthesis (2.20–2.50-fold) was induced by RDP, leading to mitochondrial dysfunction and decreased production of neurotransmitters in the brain, specifically serotonin (5-HT; 16.3 %) and dopamine (DA; 18.1 %). Metabolomic analysis revealed that the low-toxicity RDP dose up-regulated lipid-related metabolites, while the high-toxicity dose up-regulated arachidonic acid metabolism and disrupted amino acid metabolism, including tryptophan and tyrosine metabolism related to dopaminergic and serotonergic pathways. The dysregulation of genes in various cellular processes was identified by transcriptomics, mainly involved in cell adhesion molecules and gap junctions, and oxidative phosphorylation, which were directly associated with BBB permeability and oxidative stress, respectively. Correlation analysis of microbiome-metabolite-host links built a mechanistic hypothesis for alterations in gut microbiota (Actinobacteriota and Proteobacteria) induced by high-dose RDP leading to the alteration of tryptophan, tyrosine, and arachidonic acid metabolism, decreasing the production of 5-HT and DA through the gut-brain axis. This study provides valuable insights into the mechanism underlying RDP-induced neurotoxicity in zebrafish, which can inform ecological risk assessments.

One of the ways Aflatoxin B1 damages the liver is through ferroptosis. Ferroptosis is characterized by the build-up of lipid peroxides and reactive oxygen species (ROS) due to an excess of iron. Dietary supplements have emerged as a promising strategy for treating ferroptosis in the liver. The flavonoid component hesperetin, which is mostly present in citrus fruits, has a number of pharmacological actions, such as those against liver fibrosis, cancer, and hyperglycemia. However, hesperetin's effects and mechanisms against hepatic ferroptosis are still unknown. In this study, 24 male C57BL/6 J mice were randomly assigned to CON, AFB1 (0.45 mg/kg/day), and AFB1+ hesperetin treatment groups (40 mg/kg/day). The results showed that hesperetin improved the structural damage of the mouse liver, down-regulated inflammatory factors (Cxcl1, Cxcl2, CD80, and F4/80), and alleviated liver fibrosis induced by aflatoxin B1. Hesperetin reduced hepatic lipid peroxidation induced by iron accumulation by up-regulating the levels of antioxidant enzymes (GPX4, GSH-Px, CAT, and T-AOC). It is worth noting that hesperetin not only improved lipid peroxidation but also maintained the dynamic balance of iron ions by reducing ferritin autophagy. Mechanistically, hesperetin's ability to regulate ferritin autophagy mostly depends on the PI3K/AKT/mTOR/ULK1 pathway. In AFB1-induced HepG2 cells, the addition of PI3K inhibitor (LY294002) and AKT inhibitor (Miransertib) confirmed that hesperetin regulated the PI3K/AKT/mTOR/ULK1 pathway to inhibit ferritin autophagy and reduced the degradation of ferritin in lysosomes. In summary, our results suggest that hesperetin not only regulates the antioxidant system but also inhibits AFB1-induced ferritin hyperautophagy, thereby reducing the accumulation of iron ions to mitigate lipid peroxidation. This work provides a fresh perspective on the mechanism behind hesperetin and AFB1-induced liver damage in mice.

Objective: Intracerebral hemorrhage (ICH) is a severe stroke that can adversely affect patient outcomes due to the accompanying inflammatory response. As a result, there is a growing interest in studying inflammation in ICH. We systematically reviewed relevant articles using the Web of Science to understand the literature on this subject. This study aims to provide a comprehensive overview of the field through bibliometric analysis, highlight its current status, identify frontiers, and speculate on future directions. Methods: We conducted a bibliometric analysis of the global English literature on inflammation related to ICH research based on the Web of Science from 1993 to the present to address publication trends and research hotspots. Results: A total of 885 publications were included from 1993 to 2023. These articles were authored by 7375 researchers from 1639 organizations in 68 countries and published in 571 journals. Collectively, they cited 48,980 references from 5621 journals. The author who published the most articles was Dr. Zhang, John H. Interestingly, 6 of the top ten most published authors were from China. Regarding the countries that published the most articles, China was at the top of the list, followed by the United States. The most frequently used keywords were “Inflammation”, “Neuroinflammation”, and “Microglia”. Regarding journal publication and reference citations, Stroke was the most published and cited journal. Conclusions: Over the past 30 years, there has been considerable progress in scientific research concerning inflammation in the context of ICH. The pivotal themes of these studies have been immune cells and inflammatory mediators. It is worth noting, however, that most of the published literature on inflammation in ICH pertains to preclinical studies, with comparatively fewer clinical investigations. Several challenges must be addressed to translate these promising research achievements into clinical practice.

Abstract Background Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. Results Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H2O2 or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. Conclusion Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF. Graphical Abstract

Abstract A recent study investigated the impact of culture of Asian groups on leadership attainment in the U.S. It revealed that East Asians (EAs) are less likely than South Asians (SAs) and white people (WP) to attain leadership positions, and SAs may even surpass WP in leadership attainment. The study explained that the underrepresentation of EAs in leadership positions in the U.S. (the so called bamboo ceiling) is partly because EAs communicate less assertively. Specifically, EA cultures value collectivism (e.g., humility and harmony), which are at odds with western cultures that value individualism (e.g., extraversion and assertiveness), whereas SA cultures are congruent with western cultures. However, the study did not distinguish the different impact of home culture (i.e., EA cultures) and host culture (i.e., western cultures) on US-born EAs versus foreign-born EAs. We argue that for US-born EAs (i.e., second generation EAs), host culture plays a more important role than home culture in their growth and they may not be underrepresented in leadership attainment compared to WP. The bamboo ceiling effect is mostly demonstrated among foreign-born EAs (i.e., first generation EAs) who are shaped mainly under the home culture. We support the argument by conducting analysis on one of the datasets in the original study and a new dataset from Fortune’s 40-under-40 list. Our study suggests that when studying the underrepresentation of leadership attainment for EAs, US-born EAs and foreign-born EAs should not be aggregated in one category. Considering the ethnic EA group, the bamboo ceiling phenomenon may exist mainly among foreign-born EAs because US-born EAs, with a median age of 21.3, are much younger than the general American population, who may not be experienced enough to be considered for leadership positions in established large companies.

Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

ABSTRACT: It has been shown that monochromatic green light and blue light promote skeletal muscle development in early (P0-P26) and later growth stages (P27-P42), respectively. This study further investigated the effects of monochromatic light combinations on myogenesis and myofiber types transformation in broilers. Here, a total of 252 chicks were exposed to monochromatic light [red (R), green (G), blue (B), or white light (W)], and monochromatic light combination [green and blue light combination (GB), blue and green light combination (BG), red and blue combination (RB)] until P42. Compared with other groups, GB significantly increased body weight, and muscle organ index, both proportions of larger-size myofibers and oxidative myofibers in the pectoralis major (PM) and gastrocnemius muscle (GAS). Meanwhile, GB up-regulated the abundance of oxidative genes MYH7B and MYH1B, transcription factors PAX7 and Myf5, antioxidant proteins Nrf2, HO-1, and GPX4, and the activities of antioxidant enzymes CAT, GPx, and T-AOC, but down-regulated the abundance of glycolytic related genes MYH 1A, MyoD, MyoG, Mstn, Keap1, TNFa, and MDA levels. Consistent with the change of myofiber pattern, GB significantly reduced serum thyroid hormone (TH) levels, up-regulated skeletal muscle deiodinase DIO3 expression and down-regulated deiodinase DIO2 expression, which may directly lead to the reduction of intramuscular TH levels to affect myofiber types transformation. In contrast, the proportion of fast glycolytic muscle fibers increased in the RR with increasing TH levels. After thyroidectomy, the above parameters were inversed and resulted in no significant difference of each color light treatment group. These data suggested that GB significantly increased the proportion of oxidative muscle fibers and antioxidant capacity in skeletal muscle of broilers, which was regulated by TH-DIO2/DIO3 signaling pathway.

IntroductionFibroblast activation protein (FAP) overexpression on cancer-associated fibroblasts (CAFs) is associated with poor prognosis and worse clinical outcomes. Selective ablation of pro-tumorgenic FAP+ stromal cells with CAR-T cells may be a new therapeutic strategy. However, the clinical use of FAP-CAR T cells is suggested to proceed with caution for occasional poor efficacy and induction of on-target off-tumor toxicity (OTOT), including lethal osteotoxicity and cachexia. Hence, more investigations and preclinical trials are required to optimize the FAP-CAR T cells and to approve their safety and efficacy.MethodsIn this study, we designed second-generation CAR T cells targeting FAP with 4-1BB as a co-stimulatory molecule, and tested their cytotoxicity against FAP-positive cells (hFAP-HT1080 cells and a variety of primary CAFs) in vitro and in Cell line-derived xenograft (CDX) and a patient-derived xenograft (PDX) model.ResultsResults showed that our FAP-CAR T cells were powerfully potent in killing human and murine FAP-positive tumor cells and CAFs in multiple types of tumors in BALB/c and C57BL/6 mice and in patient-derived xenografts (PDX) model. And they were proved to be biologically safe and exhibit low-level OTOT.DiscussionTaken together, the human/murine cross-reactive FAP-CAR T cells were powerfully potent in killing human and murine FAP positive tumor cells and CAFs. They were biologically safe and exhibit low-level OTOT, warranting further clinical investigation into our FAP-CAR T cells.

Abstract Complex oxide heterointerfaces provide a spacious arena for creating emergent phenomena that are unattainable in the constituent bulk counterparts. Herein, The BaTiO3/La1‐xSrxMnO3 [BTO/LSMO (x)] superlattice (SL) as a model system to investigate the intimately coupled interfacial effects and their resultant phenomena is focused on. The experimental and Density Functional Theory (DFT) calculations reveal that the induced magnetism on Ti originates from both the charge transfer process between Mn and Ti at the titanate/manganite heterointerfaces and the cation intermixing, both contributing comparably to the overall magnetic effect. Upon changing x, the orbital reconstruction of the Mn 3d electrons, tailored by the strain state of the LSMO (x) layers, efficiently modifies the magnetic exchange coupling between Mn–Ti and Mn–Mn at the interfaces, which are proved to account for the modulations of the macroscopic magnetism of the SLs. This work demonstrates the significance of interfacial reconstructions for magnetism, paving a new pathway to manipulate the magnetic properties of artificial oxide heterostructures.

Abstract Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957–0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610–0.684, p

Abstract Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

Abstract Background Immunogenic cell death (ICD) has been identified as regulated cell death, which is sufficient to activate the adaptive immune response. This study aimed to research ICD-related genes and create a gene model to predict pancreatic ductal adenocarcinoma (PAAD) patients’ prognosis. Methods The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. The PAAD samples were classified into two subtypes based on the expression levels of ICD-related genes using consensus clustering. Based on the differentially expressed genes (DEGs), a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the prognosis of PAAD patients. Moreover, colony formation assay was performed to confirm the prognostic value of those genes. Results We identified two ICD cluster by consensus clustering, and found that the the ICD-high group was closely associated with immune-hot phenotype, favorable clinical outcomes. We established an ICD-related prognostic model which can predict the prognosis of pancreatic ductal adenocarcinoma. Moreover, depletion of NT5E, ATG5, FOXP3, and IFNG inhibited the colony formation ability of pancreatic cancer cell. Conclusion We identified a novel classification for PAAD based on the expression of ICD-related genes, which may provide a potential strategy for therapeutics against PAAD.

Abstract Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.

Abstract Background Proper adjustments of metabolic thermogenesis play an important role in thermoregulation in endotherm to cope with cold and/or warm ambient temperatures, however its roles in energy balance and fat accumulation remain uncertain. Our study aimed to investigate the effect of previous cold exposure (10 and 0 °C) on the energy budgets and fat accumulation in the striped hamsters (Cricetulus barabensis) in response to warm acclimation. The body mass, energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST), serum thyroid hormone levels (THs: T3 and T4), and the activity of brown adipose tissue (BAT), indicated by cytochrome c oxidase (COX) activity and uncoupling protein 1 (ucp 1) expression, were measured following exposure to the cold (10 °C and 0 °C) and transition to the warm temperature (30 °C). Results The hamsters at 10 °C and 0 °C showed significant increases in energy intake, RMR and NST, and a considerable reduction in body fat than their counterparts kept at 21 °C. After being transferred from cold to warm temperature, the hamsters consumed less food, and decreased RMR and NST, but they significantly increased body fat content. Interestingly, the hamsters that were previously exposed to the colder temperature showed significantly more fat accumulation after transition to the warm. Serum T3 levels, BAT COX activity and ucp 1 mRNA expression were significantly increased following cold exposure, and were considerably decreased after transition to the warm. Furthermore, body fat content was negatively correlated with serum T3 levels, BAT COX activity and UCP1 expression. Conclusion The data suggest that the positive energy balance resulting from the decreased RMR and NST in BAT under the transition from the cold to the warm plays important roles in inducing fat accumulation. The extent of fat accumulation in the warm appears to reflect the temperature of the previous cold acclimation.

A DC model is proposed for amorphous oxide semiconductor (AOS) thin-film transistors (TFTs) applicable to various active layer thicknesses. With the back surface potential and its coupling with the front surface potential being considered, an explicit potential solution is developed. Then, the analytical drain current and physical definition of threshold voltage are derived based on a non-chargesheet expression of free charge density. It is verified that in the previous models for AOS TFTs, typically ignoring the back surface potential and the active layer thickness effects could result in obvious deviations in the values of parameters during the characterization of DC performance, especially for scaled devices with low channel thicknesses. By comparing with numerical calculations and experimental data, this model is validated to be more suitable for AOS TFTs with decreased dimensions, which could give more realistic distributions of the density of states in the channel during parameter extraction.

Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.

Abstract Microorganisms possess the capability to impact virtually any form of cultural heritage, leading to contamination, degradation, and even combined degradation, where diverse microorganism communities facilitate the decay of wooden materials. This study aims to analyze the microbial diversity of the wooden structure bridge at the Shahe Ancient bridge site in Xi'an. The objective is to investigate the correlation between microbial species and the state of wood degradation, as well as explore the relationship between wood microbial species and the potential influence of the wood preservation environment on its long-term preservation. Simultaneously, the conventional laboratory separation technique was employed to isolate the microorganisms that were contaminated by experimental ancient wood. This was done to assess the inhibitory effect of two fungicides on the dominant microorganisms found in ancient wood, identify the most effective inhibitor, and subsequently establish an experimental foundation for safeguarding ancient bridge wood structures. The primary objective of this research was to establish microbial control criteria for the enduring conservation of historical sites, while also equipping conservators with scientifically-guided data to inform future research and restoration endeavors. Graphical Abstract

Abstract Somatic cell nuclear transfer (SCNT) successfully clones cynomolgus monkeys, but the efficiency remains low due to a limited understanding of the reprogramming mechanism. Notably, no rhesus monkey has been cloned through SCNT so far. Our study conducts a comparative analysis of multi-omics datasets, comparing embryos resulting from intracytoplasmic sperm injection (ICSI) with those from SCNT. Our findings reveal a widespread decrease in DNA methylation and the loss of imprinting in maternally imprinted genes within SCNT monkey blastocysts. This loss of imprinting persists in SCNT embryos cultured in-vitro until E17 and in full-term SCNT placentas. Additionally, histological examination of SCNT placentas shows noticeable hyperplasia and calcification. To address these defects, we develop a trophoblast replacement method, ultimately leading to the successful cloning of a healthy male rhesus monkey. These discoveries provide valuable insights into the reprogramming mechanism of monkey SCNT and introduce a promising strategy for primate cloning.

Abstract Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC.

Abstract Purpose This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. Experimental design Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. Results The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively). Conclusions A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Cysteine reactivity serves as a significant indicator of protein function and can be affected by phosphorylation events. Experimental approaches have been developed to investigate this effect, but the scale is still relatively limited. Machine‐learning approaches promise to accelerate the investigation of these phenomena. In this study, protein sequence information, distances to the closest phosphorylation sites, and the membership score of the intrinsically disordered region were used to represent the cysteine. Following the feature selection using an elastic net model, two groups of binary classifiers based on XGBoost were built to predict the occurrence and the direction of the reactivity change as a response to phosphorylation events, respectively. In addition, function enrichment analysis was performed on proteins/genes predicted to have reactivity changes. XGBoost performed the best in the independent test with AUC of 0.8192 and 0.9203 for the prediction of the change's occurrence and direction, respectively. The use of two binary classifiers successively resulted in an accuracy of 0.7568 in predicting whether reactivity would be unchanged, increased, or decreased. The enrichment analysis revealed the association of proteins carrying reactivity‐changed cysteine residues with various disease‐related pathways, particularly cancer, autosomal dominant diseases, and viral infections. Changes in cysteine reactivity influenced by phosphorylation are site‐specific and can be predicted by XGBoost algorithms. Our model provides an efficient alternative way to explore the cysteine reactivity upon phosphorylation at the proteome‐wide level, facilitating the investigation of protein functions and their clinical insights. Our code is available on GitHub (https://github.com/DarinaOsamu/predictors‐of‐cysteine‐reactivity‐changes).

The enrichment and migration patterns of different chemical elements record paleoclimatic information in loess formations. The chemical elemental measurements of 245 samples from the Shiyang profile in the Weinan Region were compared with the geochemical characteristics of typical wind-formed profiles, and the paleoclimatic evolution was discussed. The results showed the following: (1) the standardized curves of the cumulative concentrations of SiO2, Al2O3, and CaO along with the Upper Continental Crust (UCC) in the Shiyang profile exhibited significant similarities with typical wind-formed profiles. This strongly suggests that the Shiyang profile has a wind-formed origin. (2) The mean value of the chemical index of alteration (CIA) of the Shiyang profile is 62.06, indicating that the Shiyang profile has been in the stage of primary chemical weathering. (3) The ratios of K2O/Al2O3, TiO2/Al2O3, and Fe2O3/Al2O3 in the Shiyang profile are comparable to those found in typical wind-formed profiles, suggesting a common source area and supporting the premise that the Shiyang profile is of wind-induced origin.(4) The regional climate has undergone a series of transitions: from a dry and cool phase in the early Holocene to warm and humid yet unstable conditions in the middle Holocene, and returning to dry and cool during the late Holocene.

As a star two-dimensional material, molybdenum disulfide (MoS2) shows a good potential in the field of electrochemical hydrogen evolution reaction (HER) due to its low price, special physicochemical properties and a small theoretical Gibbs free energy of hydrogen adsorption. However, some disadvantages such as poor electroconductivity and inert basal planes hinder its further improvement of HER activity. Therefore, adopting carbon materials with good electrical conductivity and large specific surface area to composite with MoS2 is one of the popular strategies to improve the electrical conductivity and increase the exposure of catalytically active sites for constructing highly efficient MoS2-based electrocatalysts. Herein, in this review, we firstly gave a brief introduction of the MoS2 structure and the basic HER principle. Then, the synthesis method, catalytic performance and reaction mechanism of utilizing different carbon materials to improve the HER activity of MoS2 were summarized in detail. Finally, the existing problems and future opportunities for preparing highly active and low cost electrocatalysts assisted by carbon materials are prospected.

ObjectivesDim light at night contributes to neurodegenerative diseases by causing neuroinflammation. In the central nervous system, the activation of microglia is a significant contributor to neuroinflammation. Therefore, there is an urgent need to find an intervention to treat the neuroinflammatory response caused by dim light at night. Melatonin is a rhythmic hormone whose synthesis is suppressed during the day. In this study, we attempt to explore whether and how melatonin improves hippocampal neuroinflammation in mice exposed to dim blue light at night.Materials and MethodsIn vivo, a total of 36 male C57BL6/J mice that exposed to no light at night, dim blue light at night, and dim blue light at night with melatonin treatment. In vitro, the corticosterone-induced BV2 cells with or without melatonin treatment were used.ResultsBoth in vivo and in vitro experiments showed melatonin treatment significantly reduced dim blue light -induced hippocampal microglial activation and the expression of inflammatory factors IL-1β and TNF-α. This improved effect of melatonin is related to its receptor MT2 rather than MT1. The MT2 blockers significantly increased mRNA levels of M1-type activation marker CD86 and inflammatory cytokines IL-1β and TNF-α in melatonin-treated BV2 cells. Binding of melatonin to its receptor MT2 downregulated the expression of inflammatory proteins P-P65 and NLRP3, consequently inhibited the CD80 expression and M1-type activation in microglia. Furthermore, consistent with the decrease in microglial activation and inflammatory response after melatonin treatment, we also observed a reduction in hippocampal neuron loss and damage to the HT22 cells.ConclusionOur findings suggested that melatonin may regulate microglial polarization through MT2/NF-kB-NLRP3 pathway and improves dim blue light -induced hippocampal neuroinflammation in mice.

Abstract Background Owing to the subtlety of initial symptoms associated with gastric cancer (GC), the majority of patients are diagnosed at later stages. Given the absence of reliable diagnostic markers, it is imperative to identify novel markers that exhibit high sensitivity and specificity. Circular RNA, a non‐coding RNA, plays an important role in tumorigenesis and development and is well expressed in body fluids. Aims In this study, we aimed to identify hsa_circ_0000231 as a new biomarker for the diagnosis of GC and to assess its clinical diagnostic value in serum. Methods and Results The stability and correctness of hsa_circ_0000231 was determined by agarose gel electrophoresis, Rnase R assay and Sanger sequencing. Real‐time quantitative polymerase chain reaction (qRT‐PCR) was designed to discover the expression level of hsa_circ_0000231 and whether it has dynamic serum monitoring capability. The correlation between hsa_circ_0000231 and clinicopathological parameters was analyzed by collecting clinical and pathological data from GC patients. In addition, diagnostic efficacy was assessed by constructing receiver operating characteristic curves (ROC). Hsa_circ_0000231 exhibits a stable and consistently expressed structure. In GC serum, cells, and tissues, it demonstrates reduced expression levels. Elevated expression levels observed postoperatively suggest its potential for dynamic monitoring. Additionally its expression level correlates with TNM staging and neuro/vascular differentiation. The area under ROC curve (AUC) for hsa_circ_0000231 is 0.781, indicating its superior diagnostic value compared to CEA, CA19‐9, and CA72‐4. The combination of these four indicators enhances diagnostic accuracy, with an AUC of 0.833. Conclusions The stable expression of hsa_circ_0000231 in the serum of gastric cancer patients holds promise as a novel biomarker for both the diagnosis and dynamic monitoring of GC.

The healing of damaged skin is a complex and dynamic process, and the multi-functional hydrogel dressings could promote skin tissue healing. This study, therefore, explored the development of a composite multifunctional hydrogel (HDCP) by incorporating the dopamine modified hyaluronic acid (HA-DA) and phenylboronic acid modified chitosan (CS-PBA) crosslinked using boric acid ester bonds. The integration of HA-DA and CS-PBA could be confirmed using the Fourier transform infrared spectrometer and 1H nuclear magnetic resonance analyses. The fabricated HDCP hydrogels exhibited porous structure, elastic solid behavior, shear-thinning, and adhesion properties. Furthermore, the HDCP hydrogels exhibited antibacterial efficacy against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Subsequently, the cytocompatibility of the HDCP hydrogels was verified through CCK-8 assay and fluorescent image analysis following co-cultivation with NIH-3T3 cells. This research presents an innovative multifunctional hydrogel that holds promise as a wound dressing for various applications within the realm of wound healing.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312–3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119–3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677–4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019–2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012–4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133–3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172–3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

Abstract Phenylketonuria (PKU) is the most common inherited metabolic disease in humans. Clinical screening of newborn heel blood samples for PKU is costly and time‐consuming because it requires multiple procedures, like isotope labeling and derivatization, and PKU subtype identification requires an additional urine sample. Delayed diagnosis of PKU, or subtype identification can result in mental disability. Here, plasmonic silver nanoshells are used for laser desorption/ionization mass spectrometry (MS) detection of PKU with label‐free assay by recognizing metabolic profile in dried blood spot (DBS) samples. A total of 1100 subjects are recruited and each DBS sample can be processed in seconds. This platform achieves PKU screening with a sensitivity of 0.985 and specificity of 0.995, which is comparable to existing clinical liquid chromatography MS (LC‐MS) methods. This method can process 360 samples per hour, compared with the LC‐MS method which processes only 30 samples per hour. Moreover, this assay enables precise identification of PKU subtypes without the need for a urine sample. It is demonstrated that this platform enables high‐performance and fast, low‐cost PKU screening and subtype identification. This approach might be suitable for the detection of other clinically relevant biomarkers in blood or other clinical samples.

The efficient wind power forecasting is of great significance for the safety and stability of power grid. Analysis on the high order moment of wind power time series play an important role in improving the forecasting accuracy of wind power. With the rolling subsample generalized auto-regressive conditional heteroskedasticity with skewness and kurtosis (GARCHSK) model sequence, the analysis method for conditional skewness and conditional kurtosis of wind power time series is proposed. The dynamic curves of parameter are presented by estimating the characteristic parameters in the subsample models. Moreover, the time-varying structure of high order moment of the wind power time series is analyzed. A Generalized News Impact Curve (GNIC) is proposed, and the impact of news on the conditional skewness and conditional kurtosis are measured and evaluated by the third order GNIC and the fourth order GNIC. The result of case based on the wind power data of Jiangsu power grid demonstrates that the time-varying structure of high-order moments of wind power time series is steady relatively, and the time-varying characteristics of high-order moments are further verified by GNIC.

Abstract Objective There has been increasing evidence for atypical white matter (WM) microstructure in autistic people, but findings have been divergent. The development of autistic people in early childhood is clouded by the concurrently rapid brain growth, which might lead to the inconsistent findings of atypical WM microstructure in autism. Here, we aimed to reveal the developmental nature of autistic children and delineate atypical WM microstructure throughout early childhood while taking developmental considerations into account. Method In this study, diffusion tensor imaging was acquired from two independent cohorts, containing 91 autistic children and 100 typically developing children (TDC), aged 4–7 years. Developmental prediction modeling using support vector regression based on TDC participants was conducted to estimate the WM atypical development index of autistic children. Then, subgroups of autistic children were identified by using the k-means clustering method and were compared to each other on the basis of demographic information, WM atypical development index, and autistic trait by using two-sample t-test. Relationship of the WM atypical development index with age was estimated by using partial correlation. Furthermore, we performed threshold-free cluster enhancement-based two-sample t-test for the group comparison in WM microstructures of each subgroup of autistic children with the rematched subsets of TDC. Results We clustered autistic children into two subgroups according to WM atypical development index. The two subgroups exhibited distinct developmental stages and age-dependent diversity. WM atypical development index was found negatively associated with age. Moreover, an inverse pattern of atypical WM microstructures and different clinical manifestations in the two stages, with subgroup 1 showing overgrowth with low level of autistic traits and subgroup 2 exhibiting delayed maturation with high level of autistic traits, were revealed. Conclusion This study illustrated age-dependent heterogeneity in early childhood autistic children and delineated developmental stage-specific difference that ranged from an overgrowth pattern to a delayed pattern. Trial registration This study has been registered at ClinicalTrials.gov (Identifier: NCT02807766) on June 21, 2016 ( https://clinicaltrials.gov/ct2/show/NCT02807766 ).

ObjectivesThis paper aims to analyze the influence of polar low temperature environment and ballast water capacity on the dynamic change process of the temperature field in polar ship's ballast tank. MethodsThe volume of fluid (VOF) model was used to simulate the two phases of gas and liquid, and the standard k-ε turbulence model was used to simulate the fluid movement. The numerical analysis model of heat transfer in the ballast tank of polar ships was established to analyze the dynamic change process of the temperature field of the ballast tank at low temperature, and reveal the influence mechanism of multiple ambient temperatures and multiple loading heights on the temperature field of the ballast tank. ResultsWith the continuous occurrence of heat transfer, the temperature in the area above the waterline of the side ballast tank decreases rapidly, and the cooling area extends laterally to the cabin and downward along the bulkhead respectively. When there is more ballast water, the temperature field in the cabin is relatively stable due to the large heat capacity of water, but the air heat capacity is low and the temperature field changes greatly, which is prone to cyclones and further affects the temperature field distribution in the calculation domain. Under the condition of the same ballast water capacity, the lower the external ambient temperature, the greater the difference between internal and external temperatures, the more intense the heat exchange, and the faster the temperature of the ballast tank changes. ConclusionsThe VOF two-phase flow model and the standard k-ε turbulence model can better reveal the temporal and spatial evolution characteristics of the temperature field in the ballast tank in polar low temperature environment, and analyze the influence of internal and external thermal boundary conditions on the change of the temperature field in the ballast tank, which can provide necessary technical reference for the cold/freeze protection of polar ships' ballast tanks.

Automated organ segmentation in anatomical sectional images of canines is crucial for clinical applications and the study of sectional anatomy. The manual delineation of organ boundaries by experts is a time-consuming and laborious task. However, semi-automatic segmentation methods have shown low segmentation accuracy. Deep learning-based CNN models lack the ability to establish long-range dependencies, leading to limited segmentation performance. Although Transformer-based models excel at establishing long-range dependencies, they face a limitation in capturing local detail information. To address these challenges, we propose a novel ECA-TFUnet model for organ segmentation in anatomical sectional images of canines. ECA-TFUnet model is a U-shaped CNN-Transformer network with Efficient Channel Attention, which fully combines the strengths of the Unet network and Transformer block. Specifically, The U-Net network is excellent at capturing detailed local information. The Transformer block is equipped in the first skip connection layer of the Unet network to effectively learn the global dependencies of different regions, which improves the representation ability of the model. Additionally, the Efficient Channel Attention Block is introduced to the Unet network to focus on more important channel information, further improving the robustness of the model. Furthermore, the mixed loss strategy is incorporated to alleviate the problem of class imbalance. Experimental results showed that the ECA-TFUnet model yielded 92.63% IoU, outperforming 11 state-of-the-art methods. To comprehensively evaluate the model performance, we also conducted experiments on a public dataset, which achieved 87.93% IoU, still superior to 11 state-of-the-art methods. Finally, we explored the use of a transfer learning strategy to provide good initialization parameters for the ECA-TFUnet model. We demonstrated that the ECA-TFUnet model exhibits superior segmentation performance on anatomical sectional images of canines, which has the potential for application in medical clinical diagnosis.

Abstract Background Alfalfa (Medicago sativa L.) is a perennial leguminous forage that can improve the properties of saline soil. In addition, the supplementation with fertilizer to promote soil bacterial activity is critical to improve the productivity of coastal saline soils. However, the association between fertilizer application, bacterial community characteristics, and alfalfa yield in saline soil remains unclear. Aim To understand the interaction of different fertilizer and environmental factors on soil bacterial diversity and alfalfa yield in coastal saline soil. Results A 4-year field study was conducted to examine the interaction of different fertilizer treatments and environmental factors on soil bacterial diversity and alfalfa yield in coastal saline soil in China. Three organic fertilizer treatments (fulvic acid potassium, fulvic acid potassium + wood vinegar, and fulvic acid potassium + Bacillus), one biochar treatment (bio-charcoal), one inorganic fertilizer treatment (diammonium phosphate), and a control (no fertilizer) were included. The effects of the six treatments and 15 cutting times on alfalfa yield and soil bacterial community diversity were assessed. The productivity in fulvic acid potassium + Bacillus and fulvic acid potassium treatments was 68.37 and 67.90 t·hm−2 in 4 years, which was significantly higher than that in the bio-charcoal treatment and control. Hydrothermal conditions and timing of alfalfa harvest had significant effects on the soil bacterial community. Proteobacteria, Acidobacteria, and Actinobacteria were the principal bacterial phyla detected in the soil samples, collectively accounting for approximately 60% of the total bacterial abundance. The relative abundance of Bacteroidetes, Firmicutes, and Nitrospirae was significantly correlated with alfalfa yield, and the abundance of these phyla was also affected by the maximum temperature and precipitation. Fertilizer supplementation in coastal saline soil can effectively increase the yield of alfalfa. Among the fertilizers tested, fulvic acid potassium had the strongest effect, whereas bio-charcoal fertilizer had little effect on alfalfa yield. Graphical Abstract

Abstract Background Fetal skeletal dysplasia is a diverse group of degenerative diseases of bone and cartilage disorders that can lead to movement disorder and even death. This study aims to evaluate the diagnostic yield of sonographic examination and genetic testing for fetal skeletal dysplasia. Methods From September 2015 to April 2021, the study investigated 24 cases with suspected short-limb fetuses, which were obtained from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology. To identify the causative gene, multiple approaches (including karyotype analysis, copy number variations and whole exome sequencing) were performed on these fetuses. And further segregation analysis of the candidate variant was performed in parents by using Sanger sequencing. Results ① Out of 24 cases, likely pathogenic variants in FGFR3, FBN2, COL1A2, CUL7 and DYNC2H1 were detected in 6 cases; pathogenic variants in FGFR3, IMPAD1 and GORAB were identified in other 6 cases; and variants in WNT1, FBN1, OBSL1, COL1A1, DYNC2H1 and NEK1, known as Variant of Undetermined Significance, were found in 4 cases. There were no variants detected in the rest 8 cases by the whole exome sequencing. ② Of 24 cases, 12 (50%) were found to carry variants (pathogenic or likely pathogenic) in seven genes with 12 variants. Four fetuses (16.7%) had variants of uncertain significance. Conclusion Genetic testing combining with ultrasound scanning enhances the accurate diagnosis of fatal skeletal dysplasia in utero, and then provides appropriate genetic counseling.

With the emergence and popularization of multi-homing intelligent terminals, multi-receiver D2D communication has become a hot research issue. Based on the characteristic that D2D communication can work in licensed and unlicensed spectrum, a new grouping D2D (GD2D) model contains two transmitters (one works in the licensed spectrum and the other works in the unlicensed spectrum) and one receiver is constructed in this paper. To improve the user’s quality-of-service (QoS) at the edge of the cell, we develop a novel relay selection scheme based on a social tie that considers both physical and social constraints. Furthermore, we formulate a resource allocation problem that aims to maximize the system’s energy efficiency (EE). We derive the optimal closed solutions of the expressions by the fractional programming method and the Lagrangian dual approach. Numerical results show that the proposed grouping D2D scheme can yield significant EE performance gain over the traditional cell-edge user scheme.

Abstract Melanopsin (OPN4) is a light-sensitive protein that plays a vital role in the regulation of circadian rhythms and other nonvisual functions. Current research on OPN4 has focused on mammals; more evidence is needed from non-mammalian vertebrates to fully assess the significance of the non-visual photosensitization of OPN4 for circadian rhythm regulation. There are species differences in the regulatory mechanisms of OPN4 for vertebrate circadian rhythms, which may be due to the differences in the cutting variants, tissue localization, and photosensitive activation pathway of OPN4. We here summarize the distribution of OPN4 in mammals, birds, and teleost fish, and the classical excitation mode for the non-visual photosensitive function of OPN4 in mammals is discussed. In addition, the role of OPN4-expressing cells in regulating circadian rhythm in different vertebrates is highlighted, and the potential rhythmic regulatory effects of various neuropeptides or neurotransmitters expressed in mammalian OPN4-expressing ganglion cells are summarized among them.

The adsorption characteristics of CH4 have an important influence on gas content prediction, gas extraction, and hazard prevention. Therefore, we explored the mechanism of CH4 adsorption under the action of water and temperature to grasp the influence of water and temperature on the adsorption characteristics of CH4. In this paper, a giant, regular-system Monte Carlo method is used to simulate the CH4 adsorption behavior at the molecular level under different temperatures, water contents, and the coupling of both. The results indicate that an empirical formula for the coupling effect of temperature and water content on CH4 adsorption was obtained. The impact of different effects on CH4 adsorption is as follows: coupling effect > single temperature effect > single water content effect. The optimal combination is at a temperature of 363 K and a water content of 8.31%. Compared with the CH4 adsorption capacity without water at room temperature, the CH4 adsorption capacity is reduced by 68.04% under the coupling effect of the optimal combination. Temperature has a negative effect on the adsorption of CH4, and temperature changes the adsorption capacity by changing the average molecular kinetic energy of CH4. The reason why the increase in H2O reduces the adsorption capacity of CH4 is that the interaction between H2O and the oxygen-containing functional groups of coal is stronger than that of CH4. As the water content increases, the adsorption heat decreases, thereby inhibiting the adsorption of CH4. In addition, H2O has a smaller molecular dynamics radius as compared to CH4; the larger the free volume and surface area in the pore structure, the more adsorption pores it occupies, resulting in a more significant reduction in the adsorption of CH4.

Research on odor preference is needed to improve indoor environment quality. There-fore, to create a better odor environment in the living space, it is necessary to determine the common characteristics of odor preferences in the living environment for individuals with a similar cultural background. In this study, representative odors that are found in Chinese living spaces were selected and the odor preferences and individual traits were examined using online surveys. A total of 1236 valid responses were collected and the factors affecting odor preferences were assessed, including social, geographic, and behavioral attributes, using correlation and descriptive analysis. The results revealed that gender, age, occupation, income, mode, and frequency were correlated with odor preference characteristics in the living environment and were the primary factors for the odor preference characteristics. Further analysis revealed that the odor preferences across the gender, age, income, and frequency groups were consistent with the trend for the overall characteristics. The results of the study showed that there were significant differences in odor preferences in the living environment across occupations and living patterns. Different occupational groups showed different characteristics in odor preferences, while the complexity of living patterns and the frequency of odor exposure also had a significant impact on odor preferences. These research findings will enable us to develop customized fragrance solutions based on specific olfactory preferences related to gender, age, occupation, income level, and lifestyle. Integrating the study conclusions into the spatial layout, selection of decorative materials, and ventilation design of residential spaces has practical significance for creating living environments that better meet the needs of residents.

Unique metabolites contribute to the performance of meat flavor and potential function. In this study, UHPLC-Q Exactive HF-X-based metabolomics and multivariate analysis were applied to explore the characteristic metabolites in the breast meat of Beijing-You chicken (BYC) aged 150, 300, and 450 days (D150, D300, and D450). Based on the criteria of variable importance in the projection (VIP) > 1 and p < 0.05, a total of 154 and 97 differential metabolites (DMs) were screened out compared with D450 (D450 vs. D150, D450 vs. D300), respectively. In general, the relative content of carnosine, L-L-homoglutathione, demethyloleuropein, neohesperidin dihydrochalcone, 7-chloro-2-(3,4-dimethoxyphenyl)-3,5-dihydroxy-6,8-dimethoxy-4H-chromen-4-one, glycerophospholipids, exhibited the highest abundance at D450, while balenine, anserine, L-beta-aspartyl-L-leucine, glutathione, oxidized glutathione, stearoylcarnitine, ganoderic acid alpha, oleuroside, Lysoglycerophospholipid species (LGP) presented a downward trend with age. These 210 DMs were involved in 10 significantly enriched pathways related to the synthesis and metabolism of amino acids, peptides, and glycerophospholipid, such as glutathione metabolism, histidine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tyrosine metabolism, and lysine degradation. In conclusion, this work could not only facilitate a better understanding of the differences of chicken flavor and benefit properties with age, but also provide potential valuable bioactive compounds for further research.