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We present a potentially eco-friendly, cost-efficient strategy for synthesizing high-purity Li 2 S, a key precursor for sulfide-based solid electrolytes. While these electrolytes surpass conventional organic counterparts in both safety and performance, their widespread application is hindered by the high cost of Li 2 S. Here, a solvent-free metathesis route is developed, in which thiourea serves as an S 2 ⁻ donor to sulfurize LiOH, enabling scalable Li 2 S production (∼100 g per batch) with significantly reduced projected costs. During the process, intermediates (H 2 NCN, H 2 O) are transformed into benign gases (CO 2 , NH 3 ) that spontaneously leave the system, thereby driving Li 2 S formation without Δ G mix limitations. The as-synthesized Li 2 S is successfully applied to prepare sulfide-based solid electrolytes such as Li 10 GeP 2 S 12 and argyrodite-Li 5.5 PS 4.5 Cl 1.5 , achieving laboratory-scale (1 kg) production costs reduction of up to 27.5% and 92.9%, respectively. Furthermore, all-solid-state batteries employing Li 5.5 PS 4.5 Cl 1.5 demonstrate electrochemical performance comparable to those fabricate with commercial Li 2 S. This scalable methodology thus may provide a proming pathway to bridge low-cost Li 2 S synthesis with the practical deployment of sulfide-based solid electrolytes, which may accelerate the commercialization of high-performance all-solid-state batteries. Sulfide solid electrolytes show potential for safer, higher-performance batteries, but costly Li 2 S precursors hinder commercial adoption. Here, authors develop a scalable, potentially eco-friendly Li 2 S synthesis method that reduces its production costs, which could facilitate wider deployment of sulfide solid electrolytes.

Recent studies have uncovered that TIPE2 is involved in the development of cancer. However, less research has been conducted on the role of TIPE2 in melanoma. Our study aims to elucidate the mechanism of action of TIPE2 in the development of melanoma. We examined TIPE2 expression in paracarcinoma tissue and melanoma tissues and found that TIPE2 expression was downregulated in melanoma tissue compared with paracarcinoma tissue. Overexpression of TIPE2 significantly inhibited the proliferation of melanoma cells in vitro and even inhibited tumor formation in vivo. The CCK8 assay results indicated that TIPE2 overexpression suppressed the proliferation of melanoma cells. The colony-forming ability and wound healing ability of TIPE2-overexpressing melanoma cells were significantly reduced compared with those of control cells. Moreover, immunohistochemistry experiments using a nude mouse tumor model showed consistent results. TIPE2 inhibited the phosphorylation of MEK and ERK. In summary, TIPE2 suppresses the proliferation and migration of melanoma cells by affecting proliferation-related factors and possibly by regulating the MEK/ERK pathway. TIPE2 could be used to inhibit melanoma growth and is a potential drug target for future drug development.

Perovskite-type lithium ionic conductors were explored in the (LixLa1−x/3)ScO3 system following their syntheses via a high-pressure solid-state reaction. Phase identification indicated that a solid solution with a perovskite-type structure was formed in the range 0 ≤ x < 0.6. When x = 0.45, (Li0.45La0.85)ScO3 exhibited the highest ionic conductivity and a low activation energy. Increasing the loading of lithium as an ionic diffusion carrier expanded the unit cell volume and contributed to the higher ionic conductivity and lower activation energy. Cations with higher oxidation numbers were introduced into the A/B sites to improve the ionic conductivity. Ce4+ and Zr4+ or Nb5+ dopants partially substituted the A-site (La/Li) and B-site Sc, respectively. Although B-site doping produced a lower ionic conductivity, A-site Ce4+ doping improved the conductive properties. A perovskite-type single phase was obtained for (Li0.45La0.78Ce0.05)ScO3 upon Ce4+ doping, providing a higher ionic conductivity than (Li0.45La0.85)ScO3. Compositional analysis and crystal-structure refinement of (Li0.45La0.85)ScO3 and (Li0.45La0.78Ce0.05)ScO3 revealed increased lithium contents and expansion of the unit cell upon Ce4+ co-doping. The highest ionic conductivity of 1.1 × 10−3 S cm−1 at 623 K was confirmed for (Li0.4Ce0.15La0.67)ScO3, which is more than one order of magnitude higher than that of the (LixLa1−x/3)ScO3 system.

The alkaline protease from Bacillus licheniformis strain 2709 (AprE 2709) is widely used in Chinese industries but faces stability challenges under high-temperature conditions. This study employed molecular modeling and mutagenesis to identify Asn residues at positions 61, 160, and 211 as key sites affecting the stability of AprE 2709. By leveraging the additive and cooperative effects of mutations, the mutant enzyme AprE 2709 (N61G/N160G/N211G) was engineered, exhibiting enhanced thermostability and catalytic activity. The mutant demonstrated a 2.89-fold increase in half-life at 60 °C and a 1.56-fold improvement in catalytic efficiency compared to the wild-type enzyme. Structural analysis revealed that the improved thermostability was due to altered electrostatic interactions and strengthened hydrophobic contacts. Targeting Asn residues prone to deamidation presents a promising strategy for improving protein heat tolerance. These findings not only enhance our understanding of enzyme stability but also lay a foundation for future research aimed at optimizing alkaline proteases for diverse industrial applications, particularly in high-temperature processes.

The potential of fermentation broth of Ganoderma lucidum (FBG) in improving the quality of Chinese steamed bread (CSB) was firstly evaluated. The sensory quality scores of CSB treated by FBG are significantly higher than that of CSB in the control, and texture profile analysis also indicates the increase of CSB hardness and chewiness caused by FBG. Observation on micro-structure of CSB shows that formation of larger pores and expansion of starch granules are the important reasons for the improvement of CSB specific volume (volS), and granule expansion is due to that gluten network distributed in CSB is destroyed as a result of cross-linkage of flour proteins catalyzed by laccase, which makes starch granules releasing from the network easily contact with steam or other enzymes during the proofing and steaming of dough. Moreover, FBG contains amylases which not only convert amylopectin to amylose, but also degrade starch to glucose, maltose and polysaccharides, correspondingly resulting in changes of amylose/amylopectin (Ae/An) ratio of flour and CSB volS, and the latter is because more CO2 produced by the yeast during CSB making leads to the larger pore area in crumb. Both hardness and chewiness are determined by the comprehensive effect of protein cross-linkage, Ae/An ratio and volS change, and this viewpoint gives a logical explanation for the effects of 0.025–0.10 ml/g of FBG on hardness and chewiness of CSB.

Background Squamous cell carcinoma (SCC) is a highly heterogeneous and aggressive cancer type with significant global mortality. While environmental and genetic risk factors contribute to its development, the underlying mutational processes remain poorly characterized. Mutational signatures, which reflect specific patterns of somatic mutations, provide critical insights into the molecular mechanisms driving tumorigenesis. However, a comprehensive analysis of mutational signatures across SCC subtypes and their associations with clinical outcomes is lacking. Methods We conducted a comprehensive analysis from 16 publicly available cohorts representing four SCC subtypes: lung SCC (LSCC), head and neck SCC (HNSC), esophageal SCC (ESCC), and cervical SCC (CESC). Based on COSMIC v3.3, we identified representative mutational signatures of each cancer type. Associations between signatures, clinical parameters, and survival outcomes were evaluated using Kaplan–Meier analysis, Cox regression, and Fisher’s exact tests. Results Eight representative single-base substitution (SBS) signatures were identified across the four SCC subtypes. Common signatures included APOBEC-associated SBS2/SBS13 and aging-related SBS5, while subtype-specific signatures such as tobacco-related SBS4 and replication-associated SBS16 were also observed. Notably, SBS16 was significantly associated with shorter overall survival in ESCC, HNSC, and LSCC. In contrast, SBS10b was associated with improved survival in CESC. Furthermore, we found significant associations between specific gene mutations and mutational signatures. For example, PIK3CA mutations were positively correlated with APOBEC signatures in LSCC and ESCC, while KRAS exhibited a negative association with APOBEC signatures in CESC. Distinct mutation patterns in genes like PIK3CA and TP53 were observed in tumors with and without specific signatures, highlighting the interplay between mutational processes and driver mutations. Subtype-specific clustering based on signature fractions revealed potential associations with clinical factors, such as smoking history and anatomic site. Conclusion Our study provides a detailed characterization of shared and subtype-specific mutational signatures across SCCs, offering insights into their molecular heterogeneity and underlying carcinogenic processes. The associations between mutational signatures, clinical outcomes, and gene mutations underscore the potential of mutational signatures as biomarkers for prognosis and personalized therapy. These findings enhance our understanding of SCC biology and pave the way for precision oncology approaches tailored to individual genomic profiles.

Curcumin’s ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with anti-inflammatory effects. Curcumin was loaded in PEG-60 hydrogenated castor oil and puronic F127 mixed nanomicelles (Cur-RH60/F127-MMs). Cur-RH60/F127-MMs was prepared using the thin film dispersion method. The morphology and releasing characteristics of nanomicelles were evaluated. The uptake and permeability of Cur-RH60/F127-MMs were investigated using RAW264.7 and Caco-2 cells, and their bioavailability and in vivo/vitro anti-inflammatory activity were also evaluated. The results showed that Cur-RH60/F127-MMs have regular sphericity, possess an average diameter smaller than 20 nm, and high encapsulation efficiency for curcumin (89.43%). Cur-RH60/F127-MMs significantly increased the cumulative release of curcumin in vitro and uptake by cells (p < 0.01). The oral bioavailability of Cur-RH60/F127-MMs was much higher than that of curcumin-active pharmaceutical ingredients (Cur-API) (about 9.24-fold). The treatment of cell lines with Cur-RH60/F127-MMs exerted a significantly stronger anti-inflammatory effect compared to Cur-API. In addition, Cur-RH60/F127-MMs significantly reduced OVA-induced airway hyperresponsiveness and inflammation in an in vivo experimental asthma model. In conclusion, this study reveals the possibility of formulating a new drug delivery system for curcumin, in particular nanosized micellar aqueous dispersion, which could be considered a perspective platform for the application of curcumin in inflammatory diseases of the airways.

In order to provide a good solution for the treatment and utilization of construction waste, especially waste concrete and to promote the development of green construction to some extent, in this paper, a new composite shear wall filled with demolished concrete lumps (DCLs) and self-compacting concrete (SCC) was proposed, and its seismic performance after fire was investigated. Based on quasi-static tests of four composite shear walls filled with DCLs and SCC, three after a standard fire and one contrastive specimen without fire, the effects of fire exposure time, fire-retardant coating on the edge constraint steel pipe column, and the width-thickness ratio on seismic performance of composite shear walls after fire were studied. The failure patterns, bearing capacity, hysteretic loops, ductility, skeleton curves, rigidity degradation curves, and energy dissipation of shear walls were analyzed and compared. Test results indicate that the bearing capacity of the shear wall after 60 min of standard fire is slightly lower than the contrastive specimen without fire, but specimens still have good seismic performance. The interlayer displacement angle of the shear wall after a fire still meets the requirement of regulations. The fire-retardant coating on the edge of concealed steel pipe column has a limited effect on the seismic performance of specimens after a fire. The horizontal bearing capacity and energy dissipation capacity of shear walls after a fire can obviously be improved by properly increasing the width-thickness ratio.

Background Extralevator abdominoperineal excision (ELAPE) has been recommended for treating low rectal cancer due to its potential advantages in improving surgical safety and oncologic outcomes as compared to conventional abdominoperineal excision (APE). In ELAPE, however, whether the benefits of intraoperative position change to a prone jackknife position outweighs the associated risks remains controversial. This study is to introduce a modified position change in laparoscopic ELAPE and evaluate its feasibility, safety and the long-term therapeutic outcomes. Methods Medical records of 56 consecutive patients with low rectal cancer underwent laparoscopic ELAPE from November 2013 to September 2016 were retrospectively studied. In the operation, a perineal dissection in prone jackknife position was firstly performed and the laparoscopic procedure was then conducted in supine position. Patient characteristics, intraoperative and postoperative outcomes, pathologic and 5-year oncologic outcomes were analyzed. Results The mean operation time was 213.5 ± 29.4 min and the mean intraoperative blood loss was 152.7 ± 125.2 ml. All the tumors were totally resected, without intraoperative perforation, conversion to open surgery, postoperative 30-day death, and perioperative complications. All the patients achieved pelvic peritoneum reconstruction without the usage of biological mesh. During the follow-up period, perineal hernia was observed in 1 patient, impaired sexual function in 1 patient, and parastomal hernias in 3 patients. The local recurrence rate was 1.9% and distant metastasis was noted in 12 patients. The 5-year overall survival rate was 76.4% and the 5-year disease-free survival rate was 70.9%. Conclusions Laparoscopic ELAPE with modified position change is a simplified, safe and feasible procedure with favorable outcomes. The pelvic peritoneum can be directly closed by the laparoscopic approach without the application of biological mesh.

Solid dispersion (SD) is a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble drugs. This work investigated the effects of carrier material lipophilicity and preparation method on the properties of andrographolide (AG)–SD. The SDs of AG and the carrier materials, polyethylene glycol (PEG) and PEG grafted with carbon chains of different length (grafted PEG), have been prepared by spray-drying and vacuum-drying methods. In AG–SDs prepared by the different preparation methods with the same polymer as carrier material, the intermolecular interaction, 5% weight-loss temperature, the melting temperature (Tm), surface morphology, crystallinity, and dissolution behavior have significant differences. In the AG–SDs prepared by the same spray-drying method with different grafted PEG as carrier material, Tm, surface morphology, crystallinity, and dissolution behavior had little difference. In the AG–SDs prepared by the same vacuum-drying method with different grafted PEG as carrier material, the crystallinity and Tm decreased, and the dissolution rate of AG increased with the increase of grafted PEG lipophilicity. The preparation method has an important effect on the properties of SD. The increase of carrier material lipophilicity is beneficial to the thermal stability of SD, the decrease of crystallinity and the increase of dissolution rate of a poorly water-soluble drug in the SD.