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Abstract UFMylation is a highly conserved ubiquitin-like post-translational modification that catalyzes the covalent linkage of UFM1 to its target proteins. This modification plays a critical role in the maintenance of endoplasmic reticulum proteostasis, DNA damage response, autophagy, and transcriptional regulation. Mutations in UFM1, as well as in its specific E1 enzyme UBA5 and E2 enzyme UFC1, have been genetically linked to microcephaly. Our previous research unveiled the important role of UFMylation in regulating mitosis. However, the underlying mechanisms have remained unclear due to the limited identification of substrates. In this study, we identified Eg5, a motor protein crucial for mitotic spindle assembly and maintenance, as a novel substrate for UFMylation and identified Lys564 as the crucial UFMylation site. UFMylation did not alter its transcriptional level, phosphorylation level, or protein stability, but affected the mono-ubiquitination of Eg5. During mitosis, Eg5 and UFM1 co-localize at the centrosome and spindle apparatus, and defective UFMylation leads to diminished spindle localization of Eg5. Notably, the UFMylation-defective Eg5 mutant (K564R) exhibited shorter spindles, metaphase arrest, spindle checkpoint activation, and a failure of cell division in HeLa cells. Overall, Eg5 UFMylation is essential for proper spindle organization, mitotic progression, and cell proliferation.

This paper reports on the successful synthesis of a novel alumina powder with a unique rose-like structure composed of alumina platelets, using the molten salt method. The synthesized powder was then utilized to prepare alumina ceramic with impressive mechanical properties. The influences of the synthesizing temperature of alumina powder on the microstructure and mechanical properties of alumina ceramic are investigated in details. The results indicate that the alumina ceramic prepared using the rose-like powder synthesized at 800 °C exhibits a high relative density of 99.5 %, flexural strength of 408.2 ± 18.7 MPa, and fracture toughness of 6.14 ± 0.63 MPa m1/2. The work presented in this paper will provide a useful guideline for the preparation of high-performance alumina ceramic materials in the future.

AbstractContext Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI).Objective To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology.Materials and methods Forty male Sprague–Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC–MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated.Results Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p

In the context of China’s swift urbanization and heightened sustainability challenges, SMCEs in the construction industry play a critical role in driving both economic growth and sustainable development. This pioneering study introduces an integrative approach blending sustainability-oriented strategies (SSs) with financing guarantees, addressing key obstacles faced by these firms. Leveraging a multi-agent computational model, we dissect the dynamic interplay among construction SMCEs, governmental bodies, financial institutions, and guarantors, underscoring the transformative impact of financing guarantees on sustainable advancement. Our investigation reveals that optimally structured financing guarantees not only resolve funding challenges but also actively foster adherence to sustainability practices. This dual functionality positions such financial instruments as key enablers of SMCEs’ quest for sustainability, aligning economic objectives with ecological imperatives. Furthermore, we spotlight the transformative effect of strategic management on elevating SMCEs’ commitment to sustainable operations. Collectively, these insights offer actionable pathways for SMCEs embarking on sustainability endeavors, showcasing innovative financial solutions that do not detract from their economic prosperity.

In this paper, a high-yield Hf-modified SiHfBOC ceramic precursor was developed, and a high-pressure assisted impregnation pyrolysis method was proposed to achieve the preparation of 3D PyC–Cf/SiHfBOC composites. This high-pressure assisted impregnation method significantly improves impregnation filling effect of the precursor in and between fiber bundles compared to dozens of traditional impregnation cycles. After undergoing just 9 precursor infiltration pyrolysis (PIP) cycles, the composites achieved relative density of approximately 90% and density of 1.64 g/cm3. The critical temperature difference of the 3D PyC–Cf/SiHfBOC composites after the shock of room temperature (RT)–1000 ℃ is as high as 650 ℃, which is twice that of traditional ceramic materials, showing good thermal shock resistance. Under the effect of Hf modification, a dense HfO2–SiO2 oxide layer (thickness of 93 μm) was formed in situ on the surface of the 3D PyC–Cf/SiHfBOC composites, effectively preventing further erosion of the composite matrix by high-temperature oxidation gas. Even in the ultra-high-temperature oxygen-containing environment at 1800 ℃, it still exhibits an excellent non-ablative result (with a linear ablation rate of 0.83×10−4 mm/s). This work not only enriches the basic research on lightweight ultra-high-temperature ceramic composites converted from Hf ceramic precursors, but also provides strong technical support for their applications in ultra-high-temperature non-ablative thermal protection materials for high-speed aircraft.

In order to enhance the synchronization of welding robot arms and improve welding quality, this study proposes a fuzzy PID-based improved deviation coupling multi-axis synchronous control method. Firstly, in response to the intricacies inherent in the compensation mechanism of the deviation coupling control structure and the substantial volume of system computation, the integration of average speed and sub-average speed is proposed to optimize the speed compensator. This integration aims to mitigate speed synchronization errors, minimize synchronization adjustment time, and elevate overall system synchronization performance. Moreover, the fuzzy PID algorithm is employed to design the controller to realize the single-motor adaptive control, leading to improvement in both system stability and dynamic response performance. Finally, a simulation model for six-axis synchronization control and an experimental platform were developed. Both simulation and experimental results demonstrate that the improved deviation coupling control method exhibits superior synchronization performance. The proposed multi-axis synchronous control method effectively heightens the synchronous performance of the six-degrees-of-freedom robotic arm.

High strength and toughness are contradictory in ceramic materials. Improving the toughness of ceramics through the introduction of a ductile phase to dissipate energy is usually at the sacrifice of strength, stiffness, and the ability to operate at high temperature. Here we developed a simple approach to fabricate isotropic alumina monolithic ceramic characterized by a unique combination of high strength (405.4 MPa), high toughness (5.62 MPa m1/2) and thermal shock resistance toughness (746.2 °C), displaying a non-brittle fracture behavior. A clear picture of the toughening mechanism was depicted. This work highlights a practical guideline for development of bioinspired structural alumina ceramic.

A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1–7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 μM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 μM.

In the field of marine engineering, the friction and wear experienced by rotating mechanisms are recognized as significant contributors to the failure of marine machinery. In order to enhance the safety and dependability of marine ship operations, the implementation of on-line oil wear debris particle detection sensors enables the on-line monitoring of oil and facilitates the rapid identification of abnormal wear locations. This paper provides a critical review of the recent research progress and development trends in the field of sensors for on-line detection of oil wear debris particles. According to the method of sensor detection, wear debris particle detection sensors can be classified into two distinct categories: electrical and non-electrical sensors. Electrical sensors encompass a range of types, including inductive, capacitive, and resistive sensors. Non-electrical sensors encompass a range of technologies, such as image processing sensors, optical sensors, and ultrasonic sensors. Finally, this review addresses the future research directions for wear debris particle detection sensors in light of the challenging problems currently faced by these sensors.

Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc), especially tropical race 4 (TR4), presents the foremost menace to the global banana production. Extensive efforts have been made to search for efficient biological control agents for disease management. Our previous study showed that Streptomyces sp. XY006 exhibited a strong inhibitory activity against several phytopathogenic fungi, including F. oxysporum. Here, the corresponding antifungal metabolites were purified and determined to be two cyclic lipopeptide homologs, lipopeptin A and lipopeptin B. Combined treatment with lipopeptin complex antagonized Foc TR4 by inhibiting mycelial growth and conidial sporulation, suppressing the synthesis of ergosterol and fatty acids and lowering the production of fusaric acid. Electron microscopy observation showed that lipopeptide treatment induced a severe disruption of the plasma membrane, leading to cell leakage. Lipopeptin A displayed a more pronounced antifungal activity against Foc TR4 than lipopeptin B. In pot experiments, strain XY006 successfully colonized banana plantlets and suppressed the incidence of FWB, with a biocontrol efficacy of up to 87.7%. Additionally, XY006 fermentation culture application improved plant growth parameters and induced peroxidase activity in treated plantlets, suggesting a possible role in induced resistance. Our findings highlight the potential of strain XY006 as a biological agent for FWB, and further research is needed to enhance its efficacy and mode of action in planta.

Abstract The binding of plasma proteins to nanomedicines is widely considered detrimental to their delivery to tumors. Here, the design of OxPt/SN38 nanoparticle containing a hydrophilic oxaliplatin (OxPt) prodrug in a coordination polymer core and a hydrophobic cholesterol‐conjugated SN38 prodrug on the lipid shell for active tumor targeting is reported. OxPt/SN38 hitchhikes on low‐density lipoprotein (LDL) particles, concentrates in tumors via LDL receptor‐mediated endocytosis, and selectively releases SN38 and OxPt in acidic, esterase‐rich, and reducing tumor microenvironments, leading to 6.0‐ and 4.9‐times higher accumulations in tumors over free drugs. By simultaneously crosslinking DNA and inhibiting topoisomerase I, OxPt/SN38 achieved 92–98% tumor growth inhibition in five colorectal cancer tumor models and prolonged mouse survival by 58–80 days compared to free drug controls in three human colorectal cancer tumor models without causing serious side effects. The study has uncovered a novel nanomedicine strategy to co‐deliver combination chemotherapies to tumors via active targeting of the LDL receptor.

Hydrogen peroxide (H2O2) steaming, a green and highly efficient delignification method, has been demonstrated to provide a wood skeleton with a very low content of residual lignin in the manufacturing of transparent wood. It usually requires a long reaction time and a large amount of H2O2 because the piece of wood is treated using steaming equipment. Herein, a H2O2 solution steaming method was developed for the highly efficient removal of lignin from wood. Specifically, several wood samples were simultaneously immersed in a hot H2O2 solution to obtain delignified wood with a relatively high content of residual lignin, which provided a high strength and preserved the cellulose skeleton. Subsequently, the delignified wood with a relatively high content of residual lignin was further treated with H2O2 steam to obtain a very low lignin delignified wood. Compared with the previous H2O2 steaming method, the reaction time and used H2O2 volume of the H2O2 solution steaming method was reduced by 37.3% and 52.7%, respectively. All-biomass transparent wood could be obtained by infiltrating the delignified wood with cellulose acetate, which showed both a high transmittance of 83.0% and a low thermal conductivity of 0.30 Wm−1K−1.

Background: Lipid-lowering therapy is very important in secondary prevention of coronary heart disease (CHD). In many clinical trials, it has been found that Sodium Tanshinone IIA Sulfonate Injection (STS) have a lipid-lowering effect while reducing major cardiovascular events in patients with CHD. However, up to now, there is no system review on the effectiveness and safety of STS affecting blood lipids.Purpose: The aim of this review is to systematically assess the effects of STS on blood lipid levels in patients with CHD.Methods: Until Mar 2021, five databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database) were searched for randomized controlled trials (RCTs) about STS treating patients with CHD. Risk bias was assessed for included studies according to Cochrane handbook. The primary outcome was total cholesterol (TC). The secondary outcomes were triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and adverse events (AEs).Results: A total of 27 trials including 2,445 CHD patients met the eligibility criteria. Most trials had high risks in random sequence generation, allocation concealment, blinding of patients and personal, blinding of outcome assessment. Meta-analysis showed that STS significantly reduced plasma TC levels [MD = −1.34 mmol/l 95% CI (−1.59, −1.09), p < 0.00001, I2 = 98%], TG levels [MD = −0.49 mmol/l 95% CI (−0.62, −0.35), p < 0.00001, I2 = 97%], LDL-c levels [MD = −0.68 mmol/l (−0.80, −0.57), p < 0.00001, I2 = 96%], increased HDL-c levels [MD = 0.26 mmol/l (0.15, 0.37), p < 0.00001, I2 = 97%], without increasing the incidence of AEs [RR = 1.27 95% CI (0.72, 2.27), p = 0.94, I2 = 0%] in patients with CHD.Conclusion: STS can safely and effectively reduce plasma TC, TG and LDL-c levels in patients with CHD, and improve plasma HDL-c levels. However, these findings require careful recommendation due to the low overall quality of RCTs at present. More multi-center, randomized, double-blind, placebo-controlled trials which are designed follow the CONSORT 2010 guideline are needed.

Abstract Background Several targeted immunotherapies have recently showed significant advances in treatment of non-small cell lung cancer (NSCLC), including antibodies and inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1). Methods Tumor tissue samples were prospectively collected from 183 patients with NSCLC including lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). PD-L1 expression level was measured by immunohistochemistry assay and tumor mutational burden (TMB) status was assessed by next generation sequencing. Correlations between PD-L1 expressions, TMB status with clinicopathological characteristics were analyzed. Results PD-L1 expression was detected in 37% of ADC group and 55% in SQCC group while all clinicopathological characteristics were found comparable between these two groups. PD-L1 expression was negatively associated with overall survival in ADC group (P

Nanoparticles can stimulate tumour microenvironment to promote anti-tumour immunity. Here, the authors show that the combination of delivering drugs by a nanoscale coordination polymer and anti-PD-L1 is synergistic in treating murine colorectal cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of gastrointestinal cancer. However, biomarkers correlated with the efficacy of ICIs in gastrointestinal cancer are still lacking. In this study, we performed 395-plex immune oncology (IO)-related gene target sequencing in tumor samples from 96 patients with metastatic gastrointestinal cancer patients treated with ICIs, and a linear support vector machine learning strategy was applied to construct a predictive model. ResultsAll 96 patients were randomly assigned into the discovery (n=72) and validation (n=24) cohorts. A 24-gene RNA signature (termed the IO-score) was constructed from 395 immune-related gene expression profiling using a machine learning strategy to identify patients who might benefit from ICIs. The durable clinical benefit rate was higher in patients with a high IO-score than in patients with a low IO-score (discovery cohort: 92.0% vs 4.3%, p

Background Despite the great achievements made in immune-checkpoint-blockade (ICB) in cancer therapy, there are no effective predictive biomarkers in gastrointestinal (GI) cancer.Methods This study included 93 metastatic GI patients treated with ICBs. The first cohort comprising 73 GI cancer patients were randomly assigned into discovery (n=44) and validation (n=29) cohorts. Comprehensive genomic profiling was performed on all samples to determine tumor mutational burden (TMB) and copy-number alterations (CNAs). A subset of samples was collected for RNA immune oncology (IO) panel sequencing, microsatellite instability (MSI)/mismatch repair and program death ligand 1 (PD-L1) expression evaluation. In addition, 20 gastric cancer (GC) patients were recruited as the second validation cohort.Results In the first cohort of 73 GI cancer patients, a lower burden of CNA was observed in patients with durable clinical benefit (DCB). In both the discovery (n=44) and validation (n=29) subsets, lower burden of CNA was associated with an improved clinical benefit and better overall survival (OS). Efficacy also correlated with a higher TMB. Of note, a combinatorial biomarker of TMB and CNA may better stratify DCB patients from ICB treatment, which was further confirmed in the second validation cohort of 20 GC patients. Finally, patients with lower burden of CNA revealed increased immune signatures in our cohort and The Cancer Genome Atlas data sets as well.Conclusions Our results suggest that the burden of CNA may have superior predictive value compared with other signatures, including PD-L1, MSI and TMB. The joint biomarker of CNA burden and TMB may better stratify DCB patients, thereby providing a rational choice for GI patients treated with ICBs.

Abstract The goal of this work was to investigate the tumor mutational burden (TMB) in Chinese patients with gynecologic cancer. In total, 117 patients with gynecologic cancers were included in this study. Both tumor DNA and paired blood cell genomic DNA were isolated from formalin-fixed paraffin-embedded (FFPE) specimens and blood samples, and next-generation sequencing was performed to identify somatic mutations. TP53, PTEN, ARID1A, and PIK3CA alterations were significantly different in various types of gynecologic cancers (p = 0.001, 1.15E-07, 0.004, and 0.009, respectively). The median TMB of all 117 gynecologic tumor specimens was 0.37 mutations/Mb, with a range of 0–41.45 mutations/Mb. Despite the lack of significant difference, endometrial cancer cases had a higher median TMB than cervical and ovarian cancer cases. Younger gynecologic cancer patients (age

Abstract Graphene aerogels with high surface areas, ultra-low densities and thermal conductivities have been prepared to exploit their wide applications from pollution adsorption to energy storage, supercapacitor, and thermal insulation. However, the low mechanical properties, poor thermal stability and electric conductivity restrict these aerogels’ applications. In this paper, we prepared mechanically strong graphene aerogels with large BET surface areas, low thermal conductivities, high thermal stability and electric conductivities via hydrothermal reduction and supercritical ethanol drying. Annealing at 1500 °C resulted in slightly increased thermal conductivity and further improvement in mechanical properties, oxidation temperature and electric conductivity of the graphene aerogel. The large BET surface areas, together with strong mechanical properties, low thermal conductivities, high thermal stability and electrical conductivities made these graphene aerogels feasible candidates for use in a number of fields covering from batteries to sensors, electrodes, lightweight conductor and insulation materials.

Tetraethyl orthosilicate was selected as a matrix of heat insulating materials among three silanes, and an anti-infrared radiation fiber was chosen as a reinforcement for silica aerogel insulation composite. The silica aerogel was combined well and evenly distributed in the anti-infrared radiation fiber. The heat insulation effect was improved with the increase in thickness of the aerogel insulation material, as determined by the self-made aerospace insulation material insulation performance test equipment. The 15 mm and 30 mm thick thermal insulation material heated at 250 °C for 3 h, the temperatures at the cold surface were about 80 °C and 60 °C, respectively, and the temperatures at 150 mm above the cold surface were less than 60 °C and 50 °C, respectively. The silica aerogel composites with various thicknesses showed good thermal insulation stability. The silica insulation composite with a thickness of 15 mm exhibited good heat insulation performance, meets the thermal insulation requirements of general equipment compartments under low-temperature and long-term environmental conditions. The thermal conductivity of prepared silica aerogel composite was 0.0191 W·m−1·k−1 at room temperature and 0.0489 W·m−1·k−1 at 500 °C.