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Although the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota–metabolites–targets–signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.

Abstract Background To investigate the impact of optic disc torsion (ODT), horizontal disc tilt (HDT) angle, and ovality index (OI) on different retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) segments in healthy myopic eyes. Methods ODT and OI were measured from fundus photographs. HDT angle, peripapillary RNFL, and macular GCIPL were measured by swept-source optical coherence tomography (SS-OCT). The association between optic disc morphology and the RNFL/GCIPL thickness were evaluated, with age and axial length (AL) adjusted. Results Among 530 healthy myopic eyes of 284 participants (mean age: 41.7 years, mean spherical equivalent: − 7.70 D, and mean AL: 26.6 mm), 335 eyes (63.2%) had temporal disc torsion (temporal group) and 195 eyes (36.8%) had nasal disc torsion (nasal group). For the nasal group, a larger OI was associated with thinner superior-to-superonasal GCIPL (β = − 7.465 to − 6.972, both P = 0.024) and temporal RNFL sectors (β = − 49.596 to − 27.748, P ≤ 0.014). For the temporal group, a larger OI was associated with thinner superior-to-nasal (β = − 50.255 to − 22.093, P ≤ 0.006) and thicker temporal RNFL sectors (β = 29.015 to 56.890, P ≤ 0.003). Additionally, a larger HDT angle was associated with thinner superior-to-nasal RNFL sectors (β = − 0.559 to − 0.242, P ≤ 0.036) and thinner superior-to-superotemporal GCIPL sectors (β = − 0.084 to − 0.069, P ≤ 0.037). Conclusions The optic disc tortional direction was associated with the measurement of different RNFL and GCIPL sectors independent of the AL and age. These should be considered when constructing a myopic normative database.

Abstract Myc-associated Zinc-finger Protein (MAZ) has been implicated in the malignant progression of various tumors. However, its expression and functional relationship of MAZ in melanoma have not been previously investigated. This study confirms elevated expression of MAZ in melanoma, correlating with poor patient prognosis. Furthermore, our findings demonstrate that MAZ enhances melanoma progression by promoting proliferation, migration and invasion. It is worth noting that we found that MAZ can target and regulate the transcription of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3), a core subunit of mitochondrial complex I, to enhance mitochondrial metabolism and thus promote malignant progression of melanoma. Predictive modeling indicates that the co-expression of MAZ and NDUFS3 could serve as a potential prognostic marker for melanoma patients.

Abstract Bladder cancer (BCa) exhibits the escalating incidence and mortality due to the untimely and inaccurate early diagnosis. Urinary exosome metabolites, carrying critical tumor cell information and directly related to bladder, emerge as promising non-invasive diagnostic biomarkers of BCa. Herein, the magnetic 3D ordered macroporous zeolitic imidazolate framework-8 (magMZIF-8) is synthesized and used for efficient urinary exosome isolation. Notably, beyond retaining the single crystals and micropores of conventional ZIF-8, MZIF-8 is further enhanced with highly oriented and ordered macropores (150 nm) and the large specific surface area (973 m2·g–1), which could enable the high purity and yield separation of exosomes via leveraging the combination of size exclusion, affinity, and electrostatic interactions between magMZIF-8 and the surfaces of exosome. Furthermore, the magnetic and hydrophilic properties of magMZIF-8 will further simplify the process and enhance the efficiency of separation. After conditional optimization, a 50 mL of urine is sufficient for exosome metabolomics analysis, and the time for isolating exosomes from 42 urine samples was 2 hours only. Incorporating machine learning algorithms with LC-MS/MS analysis of the metabolic patterns obtained from isolated exosomes, early-stage BCa patients were differentiated from healthy controls, with area under the curve (AUC) value of 0.844–0.9970 in the training set and 0.875-1.00 in the test set, signifying its potential as a reliable diagnostic tool. This study offers a promising approach for the non-invasive and efficient diagnosis of BCa on a large scale via exosome metabolomics. Graphical Abstract

Abstract Metal oxide nanostructures with single-atomic heteroatom incorporation are of interest for many applications. However, a universal and scalable synthesis approach with high heteroatom concentrations represents a formidable challenge, primarily due to the pronounced structural disparities between Mhetero–O and Msub–O units. Here, focusing on TiO2 as the exemplified substrate, we present a diethylene glycol-assisted synthetic platform tailored for the controlled preparation of a library of M1-TiO2 nanostructures, encompassing 15 distinct unary M1-TiO2 nanostructures, along with two types of binary and ternary composites. Our approach capitalizes on the unique properties of diethylene glycol, affording precise kinetic control by passivating the hydrolytic activity of heteroatom and simultaneously achieving thermodynamic control by introducing short-range order structures to dissipate the free energy associated with heteroatom incorporation. The M1-TiO2 nanostructures, characterized by distinctive and abundant M–O–Ti units on the surface, exhibit high efficiency in photochromic photothermal catalysis toward recycling waste polyesters. This universal synthetic platform contributes to the preparation of materials with broad applicability and significance across catalysis, energy conversion, and biomedicine.

Abstract Background Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. Methods Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. Results After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p

Abstract Nucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.

Abstract The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-β and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.

Abstract Background and aim Appendiceal adenocarcinoma, an exceedingly rare malignancy, sparks debate on the optimal surgical approach—appendectomy or right hemicolectomy—for early-stage cases. This study aims to investigate the impact of these two surgical methods on the survival prognosis of patients with early appendiceal adenocarcinoma. Method Utilizing a multicenter medical database, we gathered data from 168 patients diagnosed with T1 stage appendiceal adenocarcinoma admitted between January 2008 and January 2015. This study aims to compare the impact of different treatment modalities on the prognosis of appendiceal adenocarcinoma in these two groups. Result In patients diagnosed with T1 appendiceal adenocarcinoma, the survival prognosis was not significantly improved with right hemicolectomy compared to appendectomy. Out of one hundred twenty-seven patients undergoing right colon resection, only three exhibited lymphatic metastasis, resulting in a rate of 2.3%. Conclusion Simple appendectomy can fulfill the objective of achieving radical tumor resection, rendering right hemicolectomy unnecessary.

Background: Stroke is the main cause of death and disability worldwide. There are divergent views regarding the effects of acupuncture in managing acute ischemic stroke (AIS). The purpose of this study was to assess the safety and effectiveness of acupuncture for acute ischemic stroke. Methods: We conducted a comprehensive search across the PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and SinoMed databases from their inception until October 3, 2023. Two reviewers screened eligible randomized controlled trials (RCTs) according to criteria and extracted data using a pre-established form. Cochrane tool was used for risk of bias assessment, and Revman 5.3 was used for subsequent meta-analysis. The GRADE tool will be used to assess the quality of evidence. Results: Thirty-one RCTs were included, involving 3604 patients. Meta-analysis showed that compared with conventional treatments (CTs), acupuncture combined with CTs could improve in National Institutes of Health Stroke Scale (NIHSS) and Efficiency (MD:1.70, 95 %CI [-2.27, -1.14], P < 0.00001;RR: 1.21, 95 %CI [1.12, 1.31], P < 0.00001,);On the Chinese Stroke Scale (CSS) and effectiveness based on CSS, acupuncture showed positive effects (MD:4.33, 95 %CI [-5.67, -2.98], P < 0.00001; RR: 1.26, 95 %CI [1.13, 1.41], P < 0.0001). Furthermore, ADL, Fugl-Meyer Assessment Scale (FMA), prognosis analyses also showed the effectiveness of acupuncture. (SMD: 0.98, 95 % CI [0.64, 1.31], P < 0.00001; MD: 16.46, 95 %CI [12.56, 20.35], P < 0.00001; RR: 0.38, 95 %CI [0.16, 0.89], P = 0.03). However, the certainty of evidence was low. Conclusion: According to current evidence, Acupuncture may be effective and safe for AIS. The future still needs high-quality evidence to support this conclusion. Protocol registration: PROSPERO (CRD42023464998).

Aldehyde dehydrogenase 2 (ALDH2), a pivotal enzyme in the metabolism of toxic aldehydes produced by oxidative stress, has been demonstrated to play a cardioprotective role in cardiovascular diseases. Antrodia cinnamomea triterpenoids (ACT) is a medicinal mushroom with anti-inflammatory and antioxidant properties, and our previous study found that ACT can exert anti-fatty liver effects by regulating ALDH2. This study aimed to elucidate the impact of ACT and its monomer on cardiac hypertrophy and investigate the relationship between its pharmacological mechanism and ALDH2. Through examining cardiac morphology and expression levels of hypertrophic biomarkers, ACT significantly reduced myocardial hypertrophy induced by angiotensin II (Ang II) and transverse aortic constriction (TAC)surgery in wild-type mice, but not in ALDH2 knockout mice. In vitro, ACT and its monomeric dehydrosulphurenic acid (DSA) inhibited the hypertrophic phenotype of Ang II-stimulated neonatal cardiac myocytes (NRCMs) in an ALDH2-dependent manner. Regarding the pharmacological mechanism, it was observed that ACT and DSA restored ALDH2 expression and activity in myocardial tissues of WT-Ang II/TAC mice and Ang II-induced NRCMs. Furthermore, it inhibited oxidative stress and improved mitochondrial quality control (MQC) homeostasis in an ALDH2-dependent manner. We screened SNW1, a transcriptional coactivator, as a DSA-binding protein by “target fishing” and cellular enthusiasm transfer assay techniques and validated that SNW1 promoted ALDH2 transcription and translation levels through synergistic interaction with the transcription factor RXR. In conclusion, the findings demonstrate that ACT/DSA upregulates ALDH2 expression via regulating SNW1/RXR, thereby inhibiting oxidative stress and maintaining MQC homeostasis, and then protects against cardiac hypertrophy.

BackgroundCoptis deltoidea C.Y. Cheng et Hsiao (CD), commonly used in the treatment of heat-toxin congestion and excessiveness. However, CD needs to be processed with wine for alleviating the bitter and cold of CD, meanwhile, reducing the gastrointestinal damage. The research assessed the discrepant effects of CD on gastrointestinal system before and after processing with wine, and explore the potential mechanisms.MethodsThe ingredients in CD and CD processed with wine (PCD) were performed on Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS). The mice were treated with CD and PCD once a day for 6 weeks (0.65 and 2.6 g/kg, i.g.). The pathological changes of gastrointestinal tract were evaluated, and the serum inflammatory factors and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) RelA (p65) protein of tissues were determined. The short chain fatty acids (SCFAs) of feces were analyzed by UPLC-MS, the gut microbiota (GM) changes were performed on 16 S rRNA sequencing.ResultsIngredients analysis declared that the alkaloids, flavonoids, phenylpropanoid compounds were the main metabolites in CD and PCD. CD reduced body weight and food intake, and the effect of CD on fecal water content increased first and then decreased with the prolongation of administration time, while its effect on intestinal transport time was exactly the opposite, reduced the SCFAs contents of feces. CD caused different degree of damage to the gastrointestinal tract, and the effect on the small intestine and colon was more obvious, which increased the expression of NF-κB p65 and elevated the inflammatory factors levels. PCD were weaker than that of CD. In addition, CD and PCD can change the composition of GM, and reduced the levels of Lactobacillus, Allobaculum, Ruminococcus, and norank_f_S24-7, increased the levels of Akkermansia, Dorea, Bacteroides, and Blautia at the genus level. However, PCD induced a milder effect of GM dysregulation than that of CD.ConclusionCD can cause damage to the gastrointestinal tract, which may be related to the GM disorders, SCFAs changes-mediated by GM, abnormal NF-κB p65 expression and increased inflammatory factors levels, interestingly, PCD had a lower effect than CD, which may be related to the differences in the types and contents of ingredients in CD after processing. And this study provided data support for the mechanism of processing with wine to alleviate “bitter-cold injury the stomach” of CD.

Abstract The pathogenesis of Alzheimer's disease (AD) remains unclear, but revealing individual differences in functional connectivity (FC) may provide insights and improve diagnostic precision. A hierarchical clustering-based autoencoder with functional connectivity was proposed to categorize 82 AD patients from the Alzheimer's Disease Neuroimaging Initiative. Compared to directly performing clustering, using an autoencoder to reduce the dimensionality of the matrix can effectively eliminate noise and redundant information in the data, extract key features, and optimize clustering performance. Subsequently, subtype differences in clinical and graph theoretical metrics were assessed. Results indicate a significant inter-subject heterogeneity in the degree of FC disruption among AD patients. We have identified two neurophysiological subtypes: subtype I exhibits widespread functional impairment across the entire brain, while subtype II shows mild impairment in the Limbic System region. What is worth noting is that we also observed significant differences between subtypes in terms of neurocognitive assessment scores associations with network functionality, and graph theory metrics. Our method can accurately identify different functional disruptions in subtypes of AD, facilitating personalized treatment and early diagnosis, ultimately improving patient outcomes.

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

Abstract A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst’s superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond.

We propose a structure utilizing a double-layer aluminum ring resonator embedded in a dielectric layer of metamaterial to demonstrate the appearances of unidirectional reflectionlessness, asymmetric reflection, and asymmetric transmission for the incident linear and circular polarizations. A significant feature of this structure is that it allows multiple functions to be implemented in the same structure without changing any structure parameters. For the vertical incident x- and y-polarizations, not only significant unidirectional reflectionlessness and asymmetric reflection effects are verified but also the strong linear to circular polarization conversions are illustrated in both transmission and reflection modes. For the vertical incidences of right-handed and left-handed circular polarizations, unidirectional reflectionlessness and asymmetric reflection are also demonstrated in detail. In addition, when linearly or circularly polarized waves are incident obliquely, the structure exhibits a stable asymmetric transmission phenomenon within a wide incident angle range. Furthermore, it also supports the occurrences of unidirectional reflectionlessness and asymmetric reflection stably within wide ranges of incident angle, resonator spacing, and rotation angle of the upper aluminum ring.

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that a reevaluation of current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective and safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis therapy, metabolic targets therapy, and nanomedicine therapy. The tumorigenesis and development of osteosarcoma is closely related to angiogenesis. Thus, anti-angiogenesis therapy is crucial to treat osteosarcoma; however, recent clinical trials found that it has insufficient efficacy. To solve this problem, the causes of treatment failure and improve treatment strategies should be investigated. This review focuses on summarizing the pathophysiological mechanisms of angiogenesis in osteosarcoma and recent advances in anti-angiogenesis treatment of osteosarcoma. We also discuss some clinical studies, with the aim of providing new ideas to improve treatment strategies for osteosarcoma and the prognosis of patients.

BackgroundThe development of internet technology has greatly increased the ability of patients with chronic obstructive pulmonary disease (COPD) to obtain health information, giving patients more initiative in the patient-physician decision-making process. However, concerns about the quality of website health information will affect the enthusiasm of patients’ website search behavior. Therefore, it is necessary to evaluate the current situation of Chinese internet information on COPD. ObjectiveThis study aims to evaluate the quality of COPD treatment information on the Chinese internet. MethodsUsing the standard disease name “慢性阻塞性肺疾病” (“chronic obstructive pulmonary disease” in Chinese) and the commonly used public search terms “慢阻肺” (“COPD”) and “肺气肿” (“emphysema”) combined with the keyword “治疗” (“treatment”), we searched the PC client web page of Baidu, Sogou, and 360 search engines and screened the first 50 links of the website from July to August 2021. The language was restricted to Chinese for all the websites. The DISCERN tool was used to evaluate the websites. ResultsA total of 96 websites were included and analyzed. The mean overall DISCERN score for all websites was 30.4 (SD 10.3; range 17.3-58.7; low quality), no website reached the maximum DISCERN score of 75, and the mean score for each item was 2.0 (SD 0.7; range 1.2-3.9). There were significant differences in mean DISCERN scores between terms, with “chronic obstructive pulmonary disease” having the highest mean score. ConclusionsThe quality of COPD information on the Chinese internet is poor, which is mainly reflected in the low reliability and relevance of COPD treatment information, which can easily lead consumers to make inappropriate treatment choices. The term “chronic obstructive pulmonary disease” has the highest DISCERN score among commonly used disease search terms. It is recommended that consumers use standard disease names when searching for website information, as the information obtained is relatively reliable.

The morphology of the liquid precipitation phase of micro alloys Ti， Nb， and V in 42CrMo steel continuous casting billets was observed， as well as the changes of the liquid precipitation phase after heating and rolling， then the formation mechanism was derived by using thermodynamic calculations. The results showed that Ti and Nb precipitated in the form of composite carbonitrides can be observed in 42CrMo steel 410 mm ×530 mm continuous casting billets with Ti 0. 012%，Nb 0. 030%， V 0. 030%， N 0. 003 5%， which was formed a micrometer scale liquid precipitation phase. Those with higher Ti content（70%-83%）were mostly polygonal blocks， while others with higher Nb content（70%-85%）were mostly thin films or irregular blocks， and no significant V segregation in the liquid phase； The carbonitrides precipitation phases of Ti and Nb can dissolve and grow together， the liquid precipitation with higher Nb content grew into blocks with the liquid precipitation with higher Ti content as the core， while some phases nucleate and grew with sulfides as the core or basal planes； There were many carbonitrides liquid precipitation phase in the center of continuous casting billets， and their sizes were relatively large （ up to 35 μm）， but its quantity and size under the surface were relatively small （below 10μm）； After heating and rolling the continuous casting billet at 1 200 ℃， liquid precipitation phase can be partially dissolved， resulting in a decrease in quantity and size， and it will break during the rolling process.

Abstract Lithium-ion batteries (LIBs) and plastics are pivotal components of modern society; nevertheless, their escalating production poses formidable challenges to resource sustainability and ecosystem integrity. Here, we showcase the transformation of spent lithium cobalt oxide (LCO) cathodes into photothermal catalysts capable of catalyzing the upcycling of diverse waste polyesters into high-value monomers. The distinctive Li deficiency in spent LCO induces a contraction in the Co−O6 unit cell, boosting the monomer yield exceeding that of pristine LCO by a factor of 10.24. A comprehensive life-cycle assessment underscores the economic viability of utilizing spent LCO as a photothermal catalyst, yielding returns of 129.6 $·kgLCO −1, surpassing traditional battery recycling returns (13–17 $·kgLCO −1). Solar-driven recycling 100,000 tons of PET can reduce 3.459 × 1011 kJ of electric energy and decrease 38,716 tons of greenhouse gas emissions. This work unveils a sustainable solution for the management of spent LIBs and plastics.

Abstract Excessive uric acid (UA) is associated with age-related cataract. A previous study showed that a high UA level in the aqueous humor stimulated the senescence of lens epithelial cells (LECs), leading to cataract progression. To better understand the underlying mechanisms, we investigated UA-driven senescence in human lens tissue samples obtained during surgery, rat lens organ cultures, and in vivo experiments, using senescence-associated β-galactosidase (SA-β-gal) staining, electronic microscopy, Western blotting, and histological analyses. Initially, we identified markedly higher expressions of NLRP3 and caspase-1 in the lens capsules of hyper-uricemic patients compared to normo-uricemic patients. This increase was accompanied by a significant rise in the SA-β-gal positive rate. We next built a cataract model in which rat lenses in an organ culture system were treated with an increasing dosage of UA. Notably, opacification was apparent in the lenses treated with 800 μM of UA starting on the fifth day. Mechanistically, UA treatment not only significantly induced the expression of NLRP3, caspase-1, and IL-1β, but also upregulated the levels of SA-β-gal and the senescence regulators p53 and p21. These effects were fully reversed, and lens opacification was ameliorated by the addition of MCC950, a selective NLRP3 antagonist. Moreover, an in vivo model showed that intravitreal UA injection rapidly induced cataract phenotypes within 21 days, an effect significantly mitigated by co-injection with MCC950. Together, our findings suggest that targeting the UA-induced NLRP3 inflammasome with MCC950 could be a promising strategy for preventing cataract formation associated with inflammageing.

In the present work, cast iron was used as the carbon source to fabricate WC particle gradient-reinforced W–Cu composites. The results revealed that the surface layer of W–Cu composites after carbonization can be divided into a complete carbonization zone and core-shell structure transition zone, the thickness of the carbonized layer increased gradually with the extension of treatment time. In addition to the W phase and Cu phase, WC and Fe3W3C phases are formed in the surface layer. The hardness and compressive strength of the surface layer show a trend of first increasing and then decreasing, and the arc erosion resistance of the surface layer gradually improves with the treatment time extending. The C atoms diffusion relationship between carbonization layer thickness (D), sintering temperature (T), and treatment time (t) of W–Cu composites with cast iron can be fitted as follows: D=1.9287×1013texp(‐929231RT).

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

BackgroundThere is a link between cardiovascular diseases and intestinal permeability, but it is not clear. This review aimed to elucidate intestinal permeability in cardiovascular diseases by meta-analysis.MethodsMultidisciplinary electronic databases were searched from the database creation to April 2023. All included studies were assessed for risk of bias according to the Joanna Briggs Institute Critical Appraisal Checklist. The heterogeneity of each study was estimated using the I2 statistic, and the data were analyzed using Review Manager 5.3 and Stata 16.0.ResultsIn total, studies in 13 pieces of literature were included in the quantitative meta-analysis. These studies were conducted among 1,321 subjects mostly older than 48. Patients had higher levels of intestinal permeability markers (lipopolysaccharide, d-lactate, zonulin, serum diamine oxidase, lipopolysaccharide-binding protein, intestinal fatty acid binding protein, and melibiose/rhamnose) than controls (standard mean difference SMD = 1.50; 95% CI = 1.31–1.88; p

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

Background Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation. Methods We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways. Results We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1. Conclusions USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.

In this study, lemon peel residue powders were modified by microwave, high-speed shear and ultra-fine grinding, respectively, to improve its quality and the comprehensive utilization rate of lemon processing by-products. The morphological structure and thermal stability before and after modification were characterized by scanning electron microscopy, Fourier infrared spectroscopy and thermogravimetric analysis. The physicochemical and functional properties were measured to evaluate the overall quality of the lemon peel residue powders after different modifications. The results showed that the structure of lemon peel residue powders was loosened after these three modifications and the main functional groups were not significantly changed after the modification. The thermal stability of lemon peel residue powders was significantly improved after microwave and high-speed shear modification (P

Abstract Background Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015–2017 that covered all 31 mainland Chinese provinces. Methods A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000—500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500–100 m) and B (

Abstract Developing in situ/operando spectroscopic techniques with high sensitivity and reproducibility is of great importance for mechanistic investigations of surface-mediated electrochemical reactions. Herein, we report the fabrication of highly ordered rhombic gold nanocube superlattices (GNSs) as substrates for surface-enhanced infrared absorption spectroscopy (SEIRAS) with significantly enhanced SEIRA effect, which can be controlled by manipulating the randomness of GNSs. Finite difference time domain simulations reveal that the electromagnetic effect accounts for the significantly improved spectroscopic vibrations on the GNSs. In situ SEIRAS results show that the vibrations of CO on the Cu2O surfaces have been enhanced by 2.4 ± 0.5 and 18.0 ± 1.3 times using GNSs as substrates compared to those on traditional chemically deposited gold films in acidic and neutral electrolytes, respectively. Combined with isotopic labeling experiments, the reaction mechanisms for C-C coupling of CO electroreduction on Cu-based catalysts are revealed using the GNSs substrates.

Abstract The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence‐based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti‐angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)‐positive and deficient DNA mismatch repair (dMMR)/microsatellite instability‐high (MSI‐H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

Abstract Understanding the structure-stability relationship of catalysts is imperative for the development of high-performance electrocatalytic devices. Herein, we utilize operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) to quantitatively monitor the evolution of Cu single-atom catalysts (SACs) during the electrochemical reduction of CO2 (CO2RR). Cu SACs are converted into 2-nm Cu nanoparticles through a reconstruction process during CO2RR. The evolution rate of Cu SACs is highly dependent on the substrates of the catalysts due to the coordination difference. Density functional theory calculations demonstrate that the stability of Cu SACs is highly dependent on their formation energy, which can be manipulated by controlling the affinity between Cu sites and substrates. This work highlights the use of operando ATR-SEIRAS to achieve mechanistic understanding of structure-stability relationship for long-term applications.

Abstract Schizophrenia (SCZ) is a chronic, highly relapsing, severe mental disorder with an unclear etiology. Cytokine-mediated neuroimmune abnormalities have been repeatedly revealed. IL-1β was reported to play a vital role in expanding the inflammatory response. However, the underlying molecular mechanism is poorly understood. In this study, we found that miR-3653-3p with the NLRP3 binding site in Targetscan was differentially expressed in miRNA high-throughput sequencing in schizophrenia (SCZ), and indeed, its downregulation in SCZ peripheral blood was also verified by RT-qPCR (P-value = 0.015). Furthermore, we found that the mRNAs of caspase 1 and IL-1β are elevated in people who suffer from SCZ (P = 0.044 and P = 0.001, respectively). Moreover, the interaction of NLRP3, Caspase1, and IL-1β was found in the peripheral blood of patients with SCZ. The expression level of miR-3653-3p was negatively correlated with NLRP3 and IL-1β mRNA contents (r = 0.487, P = 0.04 and r = 0.508, P = 0.037, respectively). NLRP3 mRNA was positively correlated with caspase1 mRNA. Meanwhile, the expression of miR-3653-3p was also negatively correlated with negative symptom subscores of PANSS (r = 0.450, P = 0.046). IL-1β mRNA is positively correlated with the total scores of PANSS (r = 0.690, P = 0.002) and the sub-scores of general psychopathology of PANSS (r = 0.583, P = 0.014). Additionally, a significant positive relationship exists between IL-1β and the total duration (r = 0.638, P = 0.006). We found that the combination of miR-3653-3p, caspase 1, and IL-1β have better diagnostic values. The results indicate that miR-3653-3p, caspase 1, and IL-1β can potentially be biomarkers of SCZ, identifying negative symptoms or a chronic course. A further understanding of the involvement of IL-1β in SCZ may be a crucial molecular effector for the chronic course to intervene.

Returning livestock manure to the cropland as organic fertilizer is a sustainable and environmentally friendly treatment method, but its application also alters the soil microenvironment. However, the impact of soil microbial community disturbance and pollutant accumulation from different types of organic fertilizers remains largely unknown in South China. To fill this gap, we investigated the effects of organic fertilizers, including chicken manure, pig manure and vermicompost on the soil bacterial and fungal communities and environmental risks. The results show that applying organic fertilizer effectively increases the soil nutrient content. High-throughput sequencing of bacteria and fungi showed that the application of different organic fertilizers had differential effects on microbial community structure, with the highest number of microbe-specific OTUs in the vermicomposting treatment. Additionally, this study found no risk of heavy metal (Cu, Zn, Pb, Cr and Cd) contamination from short-term organic fertilizer application, but there was a risk of antibiotic (ENR and CHL) contamination. Functional microorganisms regulating heavy metals and antibiotics were identified by RDA analysis. This study facilitates the screening of types of organic fertilizers that can be safely returned to the field as well as developing strategies to regulate functional microbes.

Background and aimStandardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence.MethodsThe data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors.ResultsAmong the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS.ConclusionFor HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.

Pyrethroids (PYRs) are widely used as pesticides due to low toxicity and high efficacy; however, PYRs residues have caused increasingly serious environmental and food safety problems. 3-Phenoxybenzoic acid (3-PBA), one of the major intermediate degradation products of PYRs, is more stable and toxic than the parent pesticides, and its residue can further aggravate environmental and agricultural product pollution. In recent years, filamentous fungal degradation of PYRs and 3-PBA has been reported, and research on this topic mainly focuses on strain screening, degradation characteristics, degradation pathways and localization of degradation enzymes. Unfortunately, key enzymes and their encoding genes involved in the degradation process are rarely reported. With the development of sequencing technology, molecular biology technology has provided a new strategy to mine PYR-degrading enzymes and their encoding genes in filamentous fungi. In this article, the basic properties, residues status and hazards of PYRs and 3-PBA are described. The filamentous fungi capable of degrading PYRs and 3-PBA, and their degradation pathways and degrading enzymes are reviewed. In addition, future prospects for the development of methods for screening and verification of degrading enzymes and their encoding genes are discussed. We expect that this review will provide a theoretical basis for understanding the degradation pathways and mechanisms of PYRs and 3-PBA by filamentous fungi and provide a reference for reducing residual pesticides in the environment and agricultural products.

Abstract In this work, via engineering the conformation of cobalt active center in cobalt phthalocyanine molecular catalyst, the catalytic efficiency of electrochemical carbon monoxide reduction to methanol can be dramatically tuned. Based on a collection of experimental investigations and density functional theory calculations, it reveals that the electron rearrangement of the Co 3d orbitals of cobalt phthalocyanine from the low-spin state (S = 1/2) to the high-spin state (S = 3/2), induced by molecular conformation change, is responsible for the greatly enhanced CO reduction reaction performance. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy measurements disclose accelerated hydrogenation of CORR intermediates, and kinetic isotope effect validates expedited proton-feeding rate over cobalt phthalocyanine with high-spin state. Further natural population analysis and density functional theory calculations demonstrate that the high spin Co2+ can enhance the electron backdonation via the d xz /d yz −2π* bond and weaken the C-O bonding in *CO, promoting hydrogenation of CORR intermediates.

Abstract Introduction To observe the clinical efficacy of ultrasound-guided stellate ganglion block (SGB) + extracorporeal shock wave therapy (ESWT) for limb spasticity in patients with ischemic stroke. Methods A total of 60 patients with post-stroke limb spasticity in our hospital were selected and randomly divided into four groups (n = 15). In the control group, patients received routine rehabilitation training. Based on routine rehabilitation training, SGB group patients underwent ultrasound-guided SGB, ESWT group patients received ESWT, and SGB + ESWT group patients received ultrasound-guided SGB combined with ESWT. The total treatment course was one month. The Modified Barthel Index (MBI) score, Fugl-Meyer Assessment and upper limb rehabilitation training system were applied to evaluate the activities of daily living, upper limb motor function and upper limb performance before and after treatment. Finally, the improvement after treatment was compared among different groups. Results After treatment, compared with the control group, the MBI score and the upper limb score based on Fugl-Meyer Assessment in the SGB, ESWT, and SGB + ESWT groups were significantly increased (P 0.05). In terms of upper limb performance ability, patients in the SGB, ESWT and SGB + ESWT groups had better fitting degree, participation and exertion of exercise than those in the control group, and the SGB + ESWT group patients had the same movement trajectory as robots. Conclusion Ultrasound-guided SGB and ESWT can reduce the muscle tension of patients, alleviate spasticity, promote the motor function of the upper limb, and improve the working performance of patients. However, the effect of SGB combined with ESWT is better.

Aiming at the problem of long slopes and weak power grids along the railway in high altitude mountainous areas, an optimization method of power supply mode and access to external power grid of CZ railway traction station is proposed. First, combined with the terrain and altitude along the railway and the characteristics of the regional power grid, a sample library of the power supply mode and access to external power grid of CZ railway traction station is designed. Secondly, combined with the train operation diagram and line ramp parameters, the full-day periodic load of each power supply arm is simulated. Then, according to the sample library, a “source-net-load” integrated simulation model is constructed in Simulink. Then, the three-phase voltage unbalance evaluation model of the power system is constructed in combination with relevant standards. Finally, the optimal wiring scheme is selected by using the evaluation model and the simulated voltage unbalance index.

Abstract The progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). DNA damage is a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Glucolipid metabolism increase and lower immune cell infiltration are associated with PUC compared to CIS. Proteomic analysis distinguishes the origins of invasive tumors (PUC-derived and CIS-derived), related to distinct clinical prognosis and molecular features. Additionally, loss of RBPMS, associated with CIS-derived tumors, is validated to increase the activity of AP-1 and promote metastasis. This study reveals the characteristics of two distinct branches (PUC and CIS) of UC progression and may eventually benefit clinical practice.

Abstract Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics.

An impact point prediction (IPP) guidance based on supervised learning is proposed to address the problem of precise guidance for the ballistic missile in high maneuver penetration condition. An accurate ballistic trajectory model is applied to generate training samples, and ablation experiments are conducted to determine the mapping relationship between the flight state and the impact point. At the same time, the impact point coordinates are decoupled to improve the prediction accuracy, and the sigmoid activation function is improved to ameliorate the prediction efficiency. Therefore, an IPP neural network model, which solves the contradiction between the accuracy and the speed of the IPP, is established. In view of the performance deviation of the divert control system, the mapping relationship between the guidance parameters and the impact deviation is analysed based on the variational principle. In addition, a fast iterative model of guidance parameters is designed for reference to the Newton iteration method, which solves the nonlinear strong coupling problem of the guidance parameter solution. Monte Carlo simulation results show that the prediction accuracy of the impact point is high, with a 3 σ prediction error of 4.5 m, and the guidance method is robust, with a 3 σ error of 7.5 m. On the STM32F407 single-chip microcomputer, a single IPP takes about 2.374 ms, and a single guidance solution takes about 9.936 ms, which has a good real-time performance and a certain engineering application value.