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Abstract Food‐derived peptides have garnered significant attention in research due to their multifaceted functionalities, abundant availability, efficient utilization of agricultural by‐products, and environmentally sustainable preparation methods. These peptides play a crucial role in human health, yet their precise mechanisms of action remain largely unexplored, posing challenges in their screening, preparation, and effective application utilizing protein‐based raw materials. This review offers an extensive examination of 19 types of bioactive peptides derived from food. The sources of food‐derived bioactive peptides are well concluded and the classifications are made according to their potential health benefit based on five primary systems: general bodily functions, the nervous system, the cardiovascular system, the metabolic system, and the immune system. This review specifically highlights the multifaceted impacts of tasty peptides on human health, extending beyond their gustatory effects. Furthermore, it explores the interplay between various functions of bioactive peptides, noting a progression from basic to advanced functionalities. Antioxidant activity and the modulation of key enzymes are identified as fundamental actions that are interconnected with other functional properties. This implies that a single bioactive peptide could exhibit multiple beneficial effects. The key role of antioxidant capabilities is underscored based on their broad influence and straightforward assessment. This comprehensive analysis aims to deepen the systematic understanding of the diverse benefits offered by various food‐derived peptides.

The decision-making process of wind–photovoltaic–hydropower systems involves knowledge from many fields. Influenced by the knowledge level of the decision-maker and the attribute information of the scheme set, there exists a certain uncertainty in the indicator weights. In view of this, this paper proposes a stochastic multi-criteria decision-making framework for scheduling of wind–photovoltaic–hydropower systems, which overcomes the difficulty of uncertainty in indicator weights or even completely unknown information about indicator weights at the time of decision-making. The Stochastic Multi-criteria Acceptability Analysis (SMAA) theory and the VIKOR model are introduced, and the proposed SMAA–VIKOR model makes the indicator weight space explicit. The study shows that the proposed SMAA–VIKOR model can overcome the obstacle of decision-makers’ lack of information on indicator weights. The ranking acceptability indicators calculated by the model show a more obvious trend of advantages and disadvantages, which gives full confidence to the decision-making group to formulate a plan to be implemented. It breaks through the bottleneck of group decision-making, which is difficult to make effective decisions due to the condition of incomplete information, and enriches the library of stochastic multi-criteria decision-making methods for the scientific formulation of scheduling schemes of wind–photovoltaic–hydropower systems under uncertainty conditions. HIGHLIGHTS A stochastic multi-criteria decision-making framework for wind–photovoltaic–hydropower systems is proposed.; The SMAA–VIKOR model is proposed to clarify the indicator weight space.; The proposed SMAA–VIKOR model can overcome the obstacle of decision-makers’ lack of information on indicator weights.;

Abstract Background The saprophytic filamentous fungus Trichoderma reesei represents one of the most prolific cellulase producers. The bulk production of lignocellulolytic enzymes by T. reesei not only relies on the efficient transcription of cellulase genes but also their efficient secretion after being translated. However, little attention has been paid to the functional roles of the involved secretory pathway in the high-level production of cellulases in T. reesei. Rab GTPases are key regulators in coordinating various vesicle trafficking associated with the eukaryotic secretory pathway. Specifically, Rab7 is a representative GTPase regulating the transition of the early endosome to the late endosome followed by its fusion to the vacuole as well as homotypic vacuole fusion. Although crosstalk between the endosomal/vacuolar pathway and the secretion pathway has been reported, the functional role of Rab7 in cellulase production in T. reesei remains unknown. Results A TrRab7 was identified and characterized in T. reesei. TrRab7 was shown to play important roles in T. reesei vegetative growth and vacuole morphology. Whereas knock-down of Trrab7 significantly compromised the induced production of T. reesei cellulases, overexpression of the key transcriptional activator, Xyr1, restored the production of cellulases in the Trrab7 knock-down strain (Ptcu-rab7 KD) on glucose, indicating that the observed defective cellulase biosynthesis results from the compromised cellulase gene transcription. Down-regulation of Trrab7 was also found to make T. reesei more sensitive to various stresses including carbon starvation. Interestingly, overexpression of Snf1, a serine/threonine protein kinase known as an energetic sensor, partially restored the cellulase production of Ptcu-rab7 KD on Avicel, implicating that TrRab7 is involved in an energetic adaptation to carbon starvation which contributes to the successful cellulase gene expression when T. reesei is transferred from glucose to cellulose. Conclusions TrRab7 was shown to play important roles in T. reesei development and a stress response to carbon starvation resulting from nutrient shift. This adaptation may allow T. reesei to successfully initiate the inducing process leading to efficient cellulase production. The present study provides useful insights into the functional involvement of the endosomal/vacuolar pathway in T. reesei development and hydrolytic enzyme production.

Abstract Background Soft tissue recurrence of giant cell tumor of bone (GCTB) is rare. This study aims to provide its prevalence, recurrent locations, risk factors, effective detection methods and a modified classification for this recurrence. Methods Patients with soft tissue recurrence after primary surgery for GCTB were screened from January 2003 to December 2022. General data, recurrence frequency, types according to an original classification (type-I: peripheral ossification; type-II: central ossification; type-III: without ossification), a modified classification with more detailed subtypes (type I-1: ≤ 1/2 peripheral ossification; type I-2: ≥ 1/2 peripheral ossification; type II-1: ≤ 1/2 central ossification; type II-2: ≥ 1/2 central ossification; type III: without ossification), locations, detection methods such as ultrasonography, X-ray, CT or MRI, Musculoskeletal Tumor Society (MSTS) scores were recorded. Multivariate regression analysis was conducted to identify risk factors for recurrence frequency. Results A total of 558 recurrent cases were identified from 2009 patients with GCTB. Among them, 32 were soft tissue recurrence. The total recurrence rate was 27.78% (558/2009). Soft tissue recurrence rate was 5.73% among 558 recurrent cases, and 1.59% among 2009 GCTB patients, respectively. After excluding one patient lost to follow-up, 10 males and 21 females with the mean age of 28.52 ± 9.93 (16–57) years were included. The definitive diagnosis of all recurrences was confirmed by postoperative pathology. The interval from primary surgery to the first recurrence was 23.23 ± 26.12 (2–27) months. Eight recurrences occurred from primary GCTB located at distal radius, followed by distal femur (6 cases). Recurrence occurred twice in 12 patients and 3 times in 7 patients. Twenty-seven recurrences were firstly detected by ultrasonography, followed by CT or X-ray (10 cases in each). Types at the first recurrence were 5 cases in type-I, 8 in type-II and 18 in type-III. According to the modified classification, 3 patients in type I-1, 2 in type I-2, 1 in type II-1, 7 in type II-2, and 18 in type III. The mean MSTS score was 26.62 ± 4.21 (14—30). Neither Campanacci grade nor recurrence type, modified classification and other characters, were identified as risk factors. Conclusions Soft tissue recurrence of GCTB may recur for more than once and distal radius was the most common location of primary GCTB that would suffer a soft tissue recurrence. Ultrasonography was a useful method to detect the recurrence. Since no risk factors were discovered, a careful follow-up with ultrasonography was recommended.

Osteosarcoma (OS) is a rare but aggressive malignancy. Despite previous reports, molecular characterization of this disease is not well understood, and little is known regarding OS in Chinese patients. Herein, we analyzed the genomic signatures of 73 Chinese OS cases. TP53, NCOR1, LRP1B, ATRX, RB1, and TFE3 were the most frequently mutated gene in our OS cohort. In addition, the genomic analysis of Western OS patients was performed. Notably, there were remarkable disparities in mutational landscape, base substitution pattern, and tumor mutational burden between the Chinese and Western OS cohorts. Specific molecular mechanisms, including DNA damage repair (DDR) gene mutations, copy number variation (CNV) presence, aneuploidy, and intratumoral heterogeneity, were associated with disease progression. Additionally, 30.1% of OS patients carried clinically actionable alterations, which were mainly enriched in PI3K, MAPK, DDR, and RTK signaling pathways. A specific molecular subtype incorporating DDR alterations and CNVs was significantly correlated with distant metastasis‐free survival and event‐free survival, and this correlation was observed in all subgroups with different characteristics. These findings comprehensively elucidated the genomic profile and revealed novel prognostic factors in OS, which would contribute to understanding this disease and promoting precision medicine of this population.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Abstract Background Traditional process for clinically significant prostate cancer (csPCA) diagnosis relies on invasive biopsy and may bring pain and complications. Radiomic features of magnetic resonance imaging MRI and methylation of the PRKY promoter were found to be associated with prostate cancer. Methods Fifty-four Patients who underwent prostate biopsy or photoselective vaporization of the prostate (PVP) from 2022 to 2023 were selected for this study, and their clinical data, blood samples and MRI images were obtained before the operation. Methylation level of two PRKY promoter sites, cg05618150 and cg05163709, were tested through bisulfite sequencing PCR (BSP). The PI-RADS score of each patient was estimated and the region of interest (ROI) was delineated by 2 experienced radiologists. After being extracted by a plug-in of 3D-slicer, radiomic features were selected through LASSCO regression and t-test. Selected radiomic features, methylation levels and clinical data were used for model construction through the random forest (RF) algorithm, and the predictive efficiency was analyzed by the area under the receiver operation characteristic (ROC) curve (AUC). Results Methylation level of the site, cg05618150, was observed to be associated with prostate cancer, for which the AUC was 0.74. The AUC of T2WI in csPCA prediction was 0.84, which was higher than that of the apparent diffusion coefficient ADC (AUC = 0.81). The model combined with T2WI and clinical data reached an AUC of 0.94. The AUC of the T2WI-clinic-methylation-combined model was 0.97, which was greater than that of the model combined with the PI-RADS score, clinical data and PRKY promoter methylation levels (AUC = 0.86). Conclusions The model combining with radiomic features, clinical data and PRKY promoter methylation levels based on machine learning had high predictive efficiency in csPCA diagnosis.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Full conversion of glucose and xylose from lignocellulosic hydrolysates is required for obtaining a high ethanol yield. However, glucose and xylose share flux in the pentose phosphate pathway (PPP) and glycolysis pathway (EMP), with glucose having a competitive advantage in the shared metabolic pathways. In this work, we knocked down ZWF1 to preclude glucose from entering the PPP. This reduced the [NADPH] level and disturbed growth on both glucose or xylose, confirming that the oxidative PPP, which begins with Zwf1p and ultimately leads to CO2 production, is the primary source of NADPH in both glucose and xylose. Upon glucose depletion, gluconeogenesis is necessary to generate glucose-6-phosphate, the substrate of Zwf1p. We re-established the NADPH regeneration pathway by replacing the endogenous NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene TDH3 with heterogenous NADP + -GAPDH genes GDH, gapB, and GDP1. Among the resulting strains, the strain BZP1 (zwf1Δ, tdh3::GDP1) exhibited a similar xylose consumption rate before glucose depletion, but a 1.6-fold increased xylose consumption rate following glucose depletion compared to the original strain BSGX001, and the ethanol yield for total consumed sugars of BZP1 was 13.5% higher than BSGX001. This suggested that using the EMP instead of PPP to generate NADPH reduces the wasteful metabolic cycle and excess CO2 release from oxidative PPP. Furthermore, we used a copper-repressing promoter to modulate the expression of ZWF1 and optimize the timing of turning off the ZWF1, therefore, to determine the competitive equilibrium between glucose-xylose co-metabolism. This strategy allowed fast growth in the early stage of fermentation and low waste in the following stages of fermentation.

Abstract Background The CRISPR/Cas9 technology is being employed as a convenient tool for genetic engineering of the industrially important filamentous fungus Trichoderma reesei. However, multiplex gene editing is still constrained by the sgRNA processing capability, hindering strain improvement of T. reesei for the production of lignocellulose-degrading enzymes and recombinant proteins. Results Here, a CRISPR/Cas9 system based on a multiple sgRNA processing platform was established for genome editing in T. reesei. The platform contains the arrayed tRNA−sgRNA architecture directed by a 5S rRNA promoter to generate multiple sgRNAs from a single transcript by the endogenous tRNA processing system. With this system, two sgRNAs targeting cre1 (encoding the carbon catabolite repressor 1) were designed and the precise deletion of cre1 was obtained, demonstrating the efficiency of sgRNAs processing in the tRNA−sgRNA architecture. Moreover, overexpression of xyr1-A824V (encoding a key activator for cellulase/xylanase expression) at the ace1 (encoding a repressor for cellulase/xylanase expression) locus was achieved by designing two sgRNAs targeting ace1 in the system, resulting in the significantly enhanced production of cellulase (up to 1- and 18-fold on the Avicel and glucose, respectively) and xylanase (up to 11- and 41-fold on the Avicel and glucose, respectively). Furthermore, heterologous expression of the glucose oxidase gene from Aspergillus niger ATCC 9029 at the cbh1 locus with the simultaneous deletion of cbh1 and cbh2 (two cellobiohydrolase coding genes) by designing four sgRNAs targeting cbh1 and cbh2 in the system was acquired, and the glucose oxidase produced by T. reesei reached 43.77 U/mL. Besides, it was found the ER-associated protein degradation (ERAD) level was decreased in the glucose oxidase-producing strain, which was likely due to the reduction of secretion pressure by deletion of the major endogenous cellulase-encoding genes. Conclusions The tRNA−gRNA array-based CRISPR-Cas9 editing system was successfully developed in T. reesei. This system would accelerate engineering of T. reesei for high-level production of enzymes including lignocellulose-degrading enzymes and other recombinant enzymes. Furthermore, it would expand the CRISPR toolbox for fungal genome editing and synthetic biology.

Abstract To evaluate whether single acetabular column can be reserved and the effect of reconstruction with femoral head plus total hip replacement (THR) for primary malignant peri-acetabulum tumors. From 2007 to 2015, nineteen patients with primary malignant peri-acetabulum tumors were enrolled. All cases underwent single column resection with clear surgical margins. Ten of the 19 tumor’s resections were assisted by computer navigation. Femoral heads were applied to reconstruct anterior or posterior column defects; THR was used for joint reconstruction. The surgical safety, oncologic outcome and prosthesis survivorship and function were evaluated by regular follow-up. The average follow-up period was 65.9 months. Surgical margins contained wide resection in 12 cases and marginal resection in 7 cases. One patient with Ewing's sarcoma died 14 months postoperative due to lung metastasis. One case with chondrosarcoma had recurrence. One prosthesis was removed due to infection. The average MusculoSkeletal Tumor Society (MSTS) function score was 83.7%. Due to the relative small number of cases, there was no significant difference in the recurrence rate and prosthesis failure rate between the navigation group and non-navigation group. Single column resection and reconstruction with femoral head autograft plus THR is an effective, safe method with less complication rate and better functional outcome for patients with peri-acetabular tumors.

Abstract Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6–15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1–14.2) before the lengthening to 0.3 cm (− 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%–53.3%) before the lengthening to 96.3% (86.7%–100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti‐FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non‐human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long‐term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

The yellow-margin box turtle, Mauremys mutica, is valued in traditional Chinese medicine for its perceived health benefits, including anti-cancer properties. Beyond the traditional application, this study found that anti-liver cancer peptides could be derived from the turtle shell glue hydrolysates (TSGH) through enzymatic hydrolysis using various proteases. The anti-liver cancer mechanisms of these peptides were explored and selected using network pharmacology, molecular docking technology, and validated with an in vitro HepG2 cell model. Results showed that pepsin hydrolysate showed the most promising inhibition of liver cancer cell growth. Among the identified and slected peptides (FDF, FSG, LLLPKP, and NGY), FDF was found to be the most effective inhibitor of liver cancer cell proliferation. FDF showed a positive correlation with increased intracellular lactate dehydrogenase (LDH) release and malondialdehyde (MDA) concentration, as well as a decrease in superoxide dismutase (SOD) activity. Furthermore, a significant rise in the mRNA expression of Caspase-3, tumor necrosis factor α (TNF-α), and Interleukin-1β (IL-1β) was observed. This suggests that FDF promotes apoptosis in HepG2 cells through apoptotic pathways, oxidative stress, and inflammation. These results highlight the potential of turtle shell glue (TSG) peptides in the development of novel anti-tumor drugs, providing a foundation for further exploration of TSG utilization.

Abstract Background The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering. Results To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter. Conclusions XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

Abstract The development of semiconductor photocatalysts is of great significance for the realization of efficient photocatalytic hydrogen evolution (PHE). AgIn5S8, as an emerging ternary metal sulfide photocatalyst, possesses the advantages of suitable bandgap (1.7–2.0 eV), environment‐friendly elements, and strong photostability, which holds great potential to realize high‐efficiency PHE. Although AgIn5S8‐based photocatalysts have achieved promising research progresses, their PHE performances are still far below the level of commercial applications. In this review, the basic semiconductor properties of AgIn5S8 and PHE mechanism are first introduced in detail. Subsequently, the development process and PHE activities of AgIn5S8‐based photocatalysts are systematically summarized, mainly including morphology control, Schottky junction formation through cocatalyst loading, and construction of different types of heterojunctions. Finally, the current issues and the possible solutions of AgIn5S8‐based photocatalysts in future studies are presented.

Abstract Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition without optimal diagnostic markers nor clear molecular etiological insights. Plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, but their role in intestinal I/R injury remains unknown. Here we screen the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identify circEZH2_005 as a significantly downregulated exosomal circRNA. In parallel, circEZH2_005 is also reduced in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. Exosomal circEZH2_005 displays a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 is highly expressed in intestinal crypt cells. CircEZH2_005 upregulation promotes the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1, and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may serve as a biomarker for intestinal I/R injury and targeting the circEZH2_005/hnRNPA1/Gprc5a axis may be a potential therapeutic strategy for intestinal I/R injury.

Lignocellulosic biomass is an abundant and renewable bioresource for the production of biofuels and biochemical products. The classical biorefinery process for lignocellulosic degradation and conversion comprises three stages, i.e., pretreatment, enzymatic saccharification, and fermentation. However, the complicated pretreatment process, high cost of cellulase production, and insufficient production performance of fermentation strains have restricted the industrialization of biorefinery. Consolidated bioprocessing (CBP) technology combines the process of enzyme production, enzymatic saccharification, and fermentation in a single bioreactor using a specific microorganism or a consortium of microbes and represents another approach worth exploring for the production of chemicals from lignocellulosic biomass. The present review summarizes the progress made in research of CBP technology for lignocellulosic biomass conversion. In this review, different CBP strategies in lignocellulose biorefinery are reviewed, including CBP with natural lignocellulose-degrading microorganisms as the chassis, CBP with biosynthetic microorganisms as the chassis, and CBP with microbial co-culturing systems. This review provides new perspectives and insights on the utilization of low-cost feedstock lignocellulosic biomass for production of biochemicals.

Background: In the context of sepsis patients, hypertension has a significant impact on the likelihood of developing sepsis-associated acute kidney injury (S-AKI), leading to a considerable burden. Moreover, sepsis is responsible for over 50 % of cases of acute kidney injuries (AKI) and is linked to an increased likelihood of death during hospitalization. The objective of this research is to develop a dependable and strong nomogram framework, utilizing the variables accessible within the first 24 h of admission, for the anticipation of S-AKI in sepsis patients who have hypertension. Methods: In this study that looked back, a total of 462 patients with sepsis and high blood pressure were identified from Nanfang Hospital. These patients were then split into a training set (consisting of 347 patients) and a validation set (consisting of 115 patients). A multivariate logistic regression analysis and a univariate logistic regression analysis were performed to identify the factors that independently predict S-AKI. Based on these independent predictors, the model was constructed. To evaluate the efficacy of the designed nomogram, several analyses were conducted, including calibration curves, receiver operating characteristics curves, and decision curve analysis. Results: The findings of this research indicated that diabetes, prothrombin time activity (PTA), thrombin time (TT), cystatin C, creatinine (Cr), and procalcitonin (PCT) were autonomous prognosticators for S-AKI in sepsis individuals with hypertension. The nomogram model, built using these predictors, demonstrated satisfactory discrimination in both the training (AUC = 0.823) and validation (AUC = 0.929) groups. The S-AKI nomogram demonstrated superior predictive ability in assessing S-AKI within the hypertension grade I (AUC = 0.901) set, surpassing the hypertension grade II (AUC = 0.816) and III (AUC = 0.810) sets. The nomogram exhibited satisfactory calibration and clinical utility based on the calibration curve and decision curve analysis. Conclusion: In patients with sepsis and high blood pressure, the nomogram that was created offers a dependable and strong evaluation for predicting S-AKI. This evaluation provides valuable insights to enhance individualized treatment, ultimately resulting in improved clinical outcomes.

The optimized operation of an inter-basin water transfer system is a widely used approach to achieving optimized regional water resource allocation. The costs of water transfers vary considerably, depending on the composition of the water source, the target audience and the route and distance of the transfer. This study proposes a multi-scenario optimization model for the operation of inter-basin water transfer-supply systems that balances the cost–benefit relationships. A two-objective optimization model is first established including minimizing the sum of squared water supply deficits and the cost of water transfers. Three water transfer scenarios are developed for different cost–benefit relationships. Based on these scenarios, the established optimization model is further converted into a single-objective optimization model to avoid the direct calculation of complex water transfer costs. The model is finally solved to obtain water transfer schemes. The proposed model is applied to the eastern route of the South-to-North Water Diversion Project in China. The results show that with a contracted diversion of 60% of the Yangtze River, the reliability of the water supply is 78.2% and the water shortage index is 2.8%, which is a compromise between balancing the water shortage index and the volume and cost of water transfer. HIGHLIGHTS A multi-scenario optimization model for the operation of inter-basin water transfer-supply systems considering cost–benefit relationships is proposed.; The established optimization model is converted based on developed scenarios to avoid the direct calculation of complex water transfer costs.; The proposed model is applied to the eastern route of the South-to-North Water Diversion Project in China.;

Abstract Osteosarcoma is the most common malignant bone tumor, tending to be aggressive and recurrent. The therapeutic development for treating osteosarcoma has been largely hampered by the lack of effective and specific targets. Using kinome-wide CRISPR-Cas9 knockout screens, we systematically revealed a cohort of kinases essential for the survival and growth of human osteosarcoma cells, in which Polo-like kinase 1 (PLK1) appeared as a specific prominent hit. PLK1 knockout substantially inhibited proliferation of osteosarcoma cells in vitro and the tumor growth of osteosarcoma xenograft in vivo. Volasertib, a potent experimental PLK1 inhibitor, can effectively inhibit the growth of the osteosarcoma cell lines in vitro. It can also disrupt the development of tumors in the patient-derived xenograft (PDX) models in vivo. Furthermore, we confirmed that the mode of action (MoA) of volasertib is primarily mediated by the cell-cycle arrest and apoptosis triggered by DNA damage. As PLK1 inhibitors are entering phase III clinical trials, our findings provide important insights into the efficacy and MoA of the relevant therapeutic approach for combating osteosarcoma.

Abstract Background Computer-assisted navigation has made bone sarcoma resections more precise. However, further clinical studies involving accuracy analyses under navigation are still warranted. Methods A retrospective study for analysis of computer-assisted navigation accuracy was carried out. Between September 2008 and November 2017, 39 cases of bone sarcomas around the knee joint were resected under computer-assisted navigation. The control group comprised 117 cases of bone sarcomas around the knee treated by limb salvage surgery wherein bony cutting was achieved freehand. The length difference (LD) was defined as the specimen length minus the planned resection length. The LDs were detected in both groups and compared. The margin accuracy (MA) was defined as the achieved margin minus the desired margin at the bone cutting site and was detected in the navigation group. Results The LDs between the postoperative specimen length and the preoperative planned length were compared. In the navigation group, the LD was 0.5 ± 2.5 mm (range, − 5 to 5 mm), while in the freehand group, the LD was 3.4 ± 9.6 mm (range, − 20 to 29 mm), with a significant difference (P

Distiller’s grains are the main solid biomass waste from the ethanol industry and the brewing process, featuring a wide range of sources, high carbon content, and a rich variety of elements. Owing to rich cellulose, lignin, crude protein and starch after fermentation and distillation, the distiller’s grains are the ideal precursors for biomass carbon materials. Distiller’s grains-based carbon materials are prepared by high-temperature pyrolysis or hydrothermal treatment as well as physical or chemical activation, using distiller’s grains as the carbon source. Because of their high carbon content, large specific surface area, pore structure and rich variety of elements, the distiller’s grains-based carbon materials have been widely concerned and studied. Herein, the current research status of the distiller’s grains-based carbon materials is reviewed in terms of raw material composition, preparation methods and applications fields. For the distiller’s grains produced by different regions and brewing methods, the main differences lay in the ratio of components such as cellulose, lignin and crude protein, and in the content of elements such as N, S and P. Typical preparation methods of the distiller’s grains-based carbon materials are summarized and compared, including pyrolysis, hydrothermal method and activation method. Also, the development tendency of preparation method is pointed out. In addition, the progress of current applications of the distiller’s grains-based carbon materials in energy (supercapacitors, batteries), environment (heavy metal ion adsorption, sewage purification), agriculture (soil improvement, slow-release fertilizer carrier) and catalytic fields (oxygen reduction, organic pollutant degradation) are introduced. Finally, the problems in the preparation and application of the distiller’s grains-based carbon materials are proposed, and their future development and application are prospected.

In this paper, we present a novel coordinated method tailored to address the dynamic multi-target hunting control problem in multi-agent systems, offering significant practical value. Our approach encompasses several key components: initially, we introduce a task allocation model that integrates a fuzzy inference system with a particle swarm optimization algorithm. This hybrid model efficiently allocates hunting tasks for scattered evading targets, effectively transforming the dynamic multi-target hunting problem into multiple dynamic single-target-hunting problems. This transformation enhances the speed and efficacy of task allocation. Subsequently, we propose an attraction/repulsive model grounded in potential field theory. This model facilitates the coordinated hunting of each target by organizing agents into subgroups. Relying solely on relative position and velocity information between agents and targets, our model simplifies computation, while maintaining effectiveness. Furthermore, the coordination of hunting activities for each target is achieved through a series of agent subgroups, guided by our proposed motion model. This systematic approach ensures a cohesive and efficient hunting strategy. Finally, we validate the effectiveness and feasibility of our proposed method through simulation results. These results provide empirical evidence of the method’s efficacy and potential applicability in real-world scenarios.

IntroductionSignal transducer and activator of transcription 3 (STAT3) is ubiquitously hyper-activated in numerous cancers, rendering it an appealing target for therapeutic intervention.Methods and resultsIn this study, using structure-based virtual screening complemented by molecular dynamics simulations, we identified ten potential STAT3 inhibitors. The simulations pinpointed compounds 8, 9, and 10 as forming distinct hydrogen bonds with the SH2 domain of STAT3. In vitro cytotoxicity assays highlighted compound 4 as a potent inhibitor of gastric cancer cell proliferation across MGC803, KATO III, and NCI-N87 cell lines. Further cellular assays substantiated the ability of compound 4 to attenuate IL-6-mediated STAT3 phosphorylation at Tyr475. Additionally, oxygen consumption rate assays corroborated compound 4's deleterious effects on mitochondrial function.DiscussionCollectively, our findings position compound 4 as a promising lead candidate warranting further exploration in the development of anti-gastric cancer therapeutics.

The use of non-food lignocellulosic biomass to produce ethanol fits into the strategy of a global circular economy with low dependence on fossil energy resources. Xylose is the second most abundant sugar in lignocellulosic hydrolysate, and its utilization in fermentation is a key issue in making the full use of raw plant materials for ethanol production and reduce production costs. Saccharomyces cerevisiae is the best ethanol producer but the organism is not a native xylose user. In recent years, great efforts have been made in the construction of xylose utilizing S. cerevisiae strains by metabolic and evolutionary engineering approaches. In addition, managing global transcriptional regulation works provides an effective means to increase the xylose utilization capacity of recombinant strains. Here we review the common strategies and research advances in the research field in order to facilitate the researches in xylose metabolism and xylose-based fermentation.

With the explosive development of research on phosphorescent carbon dots (CDs), it is of great significance to explore their mechanisms and establish the relationship among mechanism–structure–property. However, owing to the diversity of carbon dot structure, there is still no definite and unified model to describe them. In this review, the phosphorescent emission mechanism (including the promotion of ISC process and the stabilization of triplet exciton) and the factors affecting the property of CDs (including the carbon core state, surface state, the synergistic effect of the above-mentioned, and environmental factors) are summarized and elaborated. Then, the basic principles of the synthesis of modulated phosphorescent CDs are also summarized and their application fields are introduced. The full text is committed to finding out the shortcomings of current research through reference, finally summarizing problems, and putting forward prospects.

There exists a mutually beneficial relationship between flourishing 3D printing technology and traditional chemical industry. The rational and effective adoption of materials and subject knowledge in the field of chemistry and chemical engineering is conducive to the improvement of 3D printing technology. While the development of 3D printing, as an advanced technology of additive manufacturing, also helps promote the research and practice process in the field of chemistry and chemical engineering through its material transformation ability. In this review, the concept, process, techniques, and advantages of 3D printing is introduced at the beginning. Then, the current application status of common chemical materials in 3D printing field and the future development trend of chemical industry under the influence of 3D printing are summarized. Besides, the risks and countermeasures are assessed and analyzed on issues that become visible in the field of 3D printing, especially those about hazardous chemicals, chemical ethics, social security, and market order. It is expected that in the future, 3D printing, chemical engineering, and other disciplines involved, will help each other and develop sustainably together.

The hot compression bonding (HCB) in a Fe–9Cr-1.5W-0.3Ti alloy, under three conditions: (i) coarse-grained; (ii) fine-grained hot isostatic pressed (HIP); and (iii) fine-grained nano-oxide dispersion strengthened (ODS), was performed at 800 °C with strains of 10% and 30% and followed by soaking treatment at 1000 °C for 4 h. The effects of grain size and nano-oxide particles on the interfacial microstructure evolution and healing mechanism were systematically investigated. The results showed that grain boundary bulging and small recrystallized grains formed along the straight bonding interface of the coarse-grained alloy were related to discontinuous dynamic recrystallization behavior. In contrast, a layer of fine recrystallized grains was located at the bonding interface of the fine-grained HIP alloy, which was a typical rotation dynamic recrystallization behavior. Although the interfacial recrystallization behavior of the fine-grained ODS alloy was also rotation dynamic recrystallization, nano-oxide particles inhibited interfacial recrystallization and oxide transformation. Based on the interfacial bonding ratio considering different features of HCB, the ranking of interface bonding ability was coarse-grained alloy

Wall bushing is the core insulator of 40.5 kV air insulation switchgear, and its insulation performance determines the insulation level and service life of the switchgear. Wall bushing often appears partial discharge, insulation aging, grounded breakdown, and other problems after a period of operation. The main reason is the partial discharge of the equipotential line for the wall bushing. In this paper, the influence of the wall bushing equipotential line on the electric field distribution is systematically analyzed to improve the operating reliability and service life of the 40.5 kV wall bushing. Based on the electric field simulation of the equipotential line, the feasibility of the traditional live detection method is given. The characteristic gas detection method is proposed through air electrolysis, thermal decomposition, early warning of the development trend of the internal suspension defect state. Finally, it proposes corresponding preventive measures to avoid the development of internal suspension defect of wall bushing into a sudden grounding, and ensure the reliability of the system operation.

Larix olgensis is an economically important tree species native to northeastern China. The use of somatic embryogenesis (SE) is efficient and enables the rapid production of varieties with desirable qualities. Here, isobaric labeling via tandem mass tags was used to conduct a large-scale quantitative proteomic analysis of proteins in three critically important stages of SE in L. olgensis: the primary embryogenic callus, the single embryo, and the cotyledon embryo. We identified 6269 proteins, including 176 shared differentially expressed proteins across the three groups. Many of these proteins are involved in glycolipid metabolism, hormone response/signal transduction, cell synthesis and differentiation, and water transport; proteins involved in stress resistance and secondary metabolism, as well as transcription factors, play key regulatory roles in SE. The results of this study provide new insights into the key pathways and proteins involved in SE in Larix. Our findings have implications for the expression of totipotency, the preparation of synthetic seeds, and genetic transformation.

The two-dimensional sample entropy marks a significant advance in evaluating the regularity and predictability of images in the information domain. Unlike the direct computation of sample entropy, which incurs a time complexity of O(N2) for the series with N length, the Monte Carlo-based algorithm for computing one-dimensional sample entropy (MCSampEn) markedly reduces computational costs by minimizing the dependence on N. This paper extends MCSampEn to two dimensions, referred to as MCSampEn2D. This new approach substantially accelerates the estimation of two-dimensional sample entropy, outperforming the direct method by more than a thousand fold. Despite these advancements, MCSampEn2D encounters challenges with significant errors and slow convergence rates. To counter these issues, we have incorporated an upper confidence bound (UCB) strategy in MCSampEn2D. This strategy involves assigning varied upper confidence bounds in each Monte Carlo experiment iteration to enhance the algorithm’s speed and accuracy. Our evaluation of this enhanced approach, dubbed UCBMCSampEn2D, involved the use of medical and natural image data sets. The experiments demonstrate that UCBMCSampEn2D achieves a 40% reduction in computational time compared to MCSampEn2D. Furthermore, the errors with UCBMCSampEn2D are only 30% of those observed in MCSampEn2D, highlighting its improved accuracy and efficiency.

This paper thoroughly analyses the role of drift in the sensitive region in the single-event effect (SEE), with the aim of enhancing the single-particle radiation resistance of N-type metal-oxide semiconductor field-effect transistors (MOSFETs). It proposes a design for a Si-based device structure that extends the lightly doped source–drain region of the N-channel metal-oxide semiconductor (NMOS), thereby moderating the electric field of the sensitive region. This design leads to a 15.69% decrease in the charge collected at the leaky end of the device under the standard irradiation conditions. On this basis, a device structure is further proposed to form a composite metal-oxide semiconductor (MOS) by connecting a pn junction at the lightly doped source–drain end. By adding two charge paths, the leakage collection charge is further reduced by 13.85% under standard irradiation conditions. Moreover, the deterioration of the drive current in the purely growing lightly doped source–drain region can be further improved. Simulations of single-event effects under different irradiation conditions show that the device has good resistance to single-event irradiation, and the composite MOS structure smoothly converges to a 14.65% reduction in drain collection charge between 0.2 pC/μm and 1 pC/μm Linear Energy Transfer (LET) values. The incidence position at the source-to-channel interface collects the highest charge reduction rate of 28.23%. The collecting charge reduction rate is maximum, at 17.12%, when the incidence is at a 45-degree angle towards the source.

The environmental vibrations of tunnels and soil caused by metro operations is one of the most important issues in the field of environmental geotechnical engineering. Recent studies in metro-induced vibrations have revealed significant uncertainties in the vibration responses of tunnels and the surrounding soil. A two-step method of obtaining train loads considering uncertainty was introduced. The first step was to obtain the train loads via an inverse model based on measurements, and the second step was to quantify the uncertainty of train loads based on complex principal component analysis. A portion of a tunnel of the Beijing metro was selected as the object of study, where the vertical accelerations on the rail and on the tunnel wall were measured under different train speeds of 35, 45 and 55 km/h. Inputting the train loads based on the measured rail accelerations into an axisymmetric numerical model, established using ANSYS, the vibration responses of the tunnel wall in a probabilistic framework were calculated and were compared with the measured results. By using an accuracy index that considers both calculation bias and uncertainty, the accuracy of the calculated vibration response was quantitatively evaluated. It can be concluded that the calculated vibration response can reflect the actual vibration level and uncertainty of the tunnel wall. The accuracies of the calculated results under different speeds were generally high while showing a slight difference in amplitude.

The enhancement of rectification efficiency in 2.45 GHz microwave wireless weak energy transmission systems is centred on rectifier device selection. The overall rectification efficiency of traditional rectifier devices is low in weak energy density situations, failing to fulfil the commercial requirements of this region. The subthreshold swing of the emerging device TFET exceeds 60 mV/dec, which has the advantages of a large open-state current and a small off-state current in the corresponding region of the weak energy density. In view of this, this paper designs a double-gate plasma rectifier TFET with an embedded n+ heavily doped layer on the basis of a PNPN-structured TFET, where the device is simulated with the MixedMode module of Silvaco TCAD 2018, the rectification efficiency at −10 dBm is 44.12%, which is 10.61% higher than that of the PNPN-TFET, and the efficiency in the weak energy density region is generally 10% or more than that of commercial HSMS devices, showing obvious rectification advantages.

The thyroid gland is an important and essential endocrine organ for the human body that regulates metabolism, growth and development by secreting thyroid hormones. Thyroid nodules are irregular masses caused by lesions that can reflect the main clinical manifestation of thyroid abnormalities. Delineating the boundaries of thyroid nodules from ultrasound images is an indispensable part of computer-aided diagnosis systems and medical imaging diagnosis for thyroid diseases. However, automatic segmentation of thyroid nodules is still a challenging task because of the similarity between the heterogeneous appearance and its background. In this study, we propose a novel framework for thyroid nodule segmentation that exploits multiscale anatomical features to build a late-stage fusion method based on adversarial training. The introduced architecture can handle blurred and uneven tissue regions during the thyroid nodule segmentation process. By adversarial training approaches, our segmentation block S adopts a framework with three different fusion scales, and discrimination block D employs a fully convolutional encoder-decoder architecture. Extensive experimental results demonstrate that AMSeg outperforms popular methods in terms of thyroid nodule segmentation. The proposed framework achieves Dice, Hd95 (95% Hausdorff distance), Jaccard, and precision values of 83.06%, 23.13, 74.18%, and 87.82%, respectively. As an end-to-end network, the AMSeg can effectively replace manual segmentation methods and has great prospects in clinical applications.

Abstract In this paper, we consider multi-sensor with partly overlapping field of view (FoV) in the labeled random finite set (L-RFS) framework. This is different from most existing multi-sensor tracking algorithms, where the sensors are assumed to have the same FoV. We describe the partly overlapping FoV by modeling probability field of detection for individual sensors in whole observation area and can be seen as the same range of FoV. We consider all these using generalized labeled multi-Bernoulli filter in labeled RFS framework. Besides, we also propose a measurement-driven target birth model. Finally, the effectiveness of the proposed algorithm is verified by experiments.

Lignin is a kind of natural green polymer with abundant active functional groups and designable molecular structure. In this work, the quaternized lignosulfonate (QLS) with amphoteric characteristic was prepared through chemical modification using lignosulfonate sodium (LS). Then, a lignin-confined multilayered two-dimensional composite (QLS/ZnO) was prepared by one-step dynamic hydrothermal method using QLS, zinc nitrate, and hexamethylenetetramine. The QLS/ZnO has a regular pie-shaped structure, which is composed of 3–5 layers of two-dimensional nanosheets with a thickness of ∼10 ​nm. It shows excellent ultraviolet light absorption performance and active photoelectron scavenging performance, and thus showing great application potential in polymer materials. The water polyurethane (WPU) and polyvinyl alcohol (PVA) films showed excellent UV shielding performance and good mechanical properties when doped with the QLS/ZnO. The tensile strength of WPU + 0.6 wt% QLS/ZnO and PVA + 0.8 wt% QLS/ZnO composite films is increased by 49% and 24%, respectively, and the elongation at break is increased by 138% and 33%. Furthermore, the composite films showed excellent anti-UV aging resistance after being aged under strong UV irradiation for 14 days. This work is of great significance to the high-value application of industrial lignin in the field of nano-functional materials.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Background: Analysis of the tumour necrosis rate is an important method to evaluate the effect of neoadjuvant chemotherapy for osteosarcoma. However, at present, there is no specific imaging method to evaluate this effect. The purpose of this study was to evaluate the changes in blood supply after chemotherapy by measuring the CT enhancement rate and to analyse the correlation between the CT enhancement rate and the tumour necrosis rate. Methods: Patients with primary osteosarcoma of the extremities treated in our institute from 2016 to 2017 were analysed retrospectively. In total, 103 eligible patients were enrolled in the study, including 67 males and 36 females, with an average age of 17.7 (6–54) years. Sixty cases had tumour sites in the femur, 25 in the tibia, 10 in the humerus, and eight in other sites. All patients received neoadjuvant chemotherapy including methotrexate, cisplatin + doxorubicin and ifosfamide before surgical treatment. All patients underwent enhanced CT examination of the same tumour site before and after the neoadjuvant chemotherapy protocol. The CT value before and after chemotherapy was measured and the enhancement rate was calculated. The change in the CT enhancement rate after chemotherapy was analysed. Changes in the CT enhancement rate were compared between patients with a tumour necrosis rate greater than 90% and those with one 90% and 1.62 (median 1.52, range 1.00–2.41) in the group with a necrosis rate 90% and 1.53 (median 1.43, range 1.00–2.83) in the group with a necrosis rate 90% decreased by 29.0% (median 28%, range −2.3–53%) (P

IntroductionSarcomas are classified into two types, bone sarcoma and soft tissue sarcoma (STS), which account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. There exist more than 50 subtypes within the two types of sarcoma. Each subtype is highly diverse and characterized by significant variations in morphology and phenotypes. Understanding tumor molecular genetics is helpful in improving the diagnostic accuracy of tumors that have been difficult to classify based on morphology alone or that have overlapping morphological features. The different molecular characteristics of bone sarcoma and STS in China remain poorly understood. Therefore, this study aimed to analyze genomic landscapes and actionable genomic alterations (GAs) as well as tumor mutational burden (TMB), microsatellite instability (MSI), and programmed death ligand-1 (PD-L1) expression among Chinese individuals diagnosed with primary bone sarcomas and STS.MethodsThis retrospective study included 145 patients with primary bone sarcomas (n = 75) and STS (n = 70), who were categorized based on the 2020 World Health Organization classification system.ResultsPatients diagnosed with bone sarcomas were significantly younger than those diagnosed with STS (p < 0.01). The top 10 frequently altered genes in bone sarcoma and STS were TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4.The EWSR1 fusions exhibited statistically significant differences (p < 0.01) between primary bone sarcoma and STS in terms of their altered genes. Based on the actionable genes defined by OncoKB, actionable GAs was found in 30.7% (23/75) of the patients with bone sarcomas and 35.7% (25/70) of those with STS. There were 4.0% (3/75) patients with bone sarcoma and 4.3% (3/70) patients with STS exhibited high tumor mutational burden (TMB-H) (TMB ≥ 10). There was only one patient with STS exhibited MSI-L, while the remaining cases were microsatellite stable. The positive rate of PD-L1 expression was slightly higher in STS (35.2%) than in bone sarcoma (33.3%), however, this difference did not reach statistical significance. The expression of PD-L1 in STS patients was associated with a poorer prognosis (p = 0.007). Patients with STS had a better prognosis than those with bone sarcoma, but the observed difference did not attain statistical significance (p = 0.21). Amplification of MET and MYC genes were negatively correlated with clinical prognosis in bone tumors (p

Osteosarcoma is a malignant bone tumor occurring in adolescents. Surgery combined with adjuvant or neoadjuvant chemotherapy is the standard treatment. However, systemic chemotherapy is associated with serious side effects and a high risk of postoperative tumor recurrence, leading to a high amputation rate and mortality in cancer patients. Implant materials that can simultaneously repair large bone defects and prevent osteosarcoma recurrence are in urgent need. Herein, an intelligent system comprising 3D-printed titanium scaffold (TS) and pH-responsive PEGylated paclitaxel prodrugs was fabricated for bone defect reconstruction and recurrence prevention following osteosarcoma surgery. The drug-loaded implants exhibited excellent stability and biocompatibility for supporting the activity of bone stem cells under normal body fluid conditions and the rapid release of drugs in response to faintly acidic environments. An in vitro study demonstrated that five human osteosarcoma cell lines could be efficiently eradicated by paclitaxel released in an acidic microenvironment. Using mice models, we demonstrated that the drug-loaded TS can enable a pH-responsive treatment of postoperative tumors and effectively prevent osteosarcoma recurrence. Therefore, local implantation of this composite scaffold may be a promising topical therapeutic method to prevent osteosarcoma recurrence.

Abstract Current resolvable group targets tracking algorithms can only track a small number of group targets assuming the standard deviation vectors (SDVs) are known. Based on generalized labeled multi-Bernoulli filter, this paper first proposes a serial tracking algorithm, in order to save the computational cost of filter tracking large-batch and multi-structure group targets. Then, the least squares and the k-means algorithms are used to jointly estimate the SDVs and the group target states. The experimental simulation results verify the effectiveness of the proposed methods.

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Large-capacity impulse test of distribution transformer requires a large amount of instantaneous energy, while the impulse mode of conventional dedicated high-voltage line and generator requires synchronous switch, adjusted impedance, generator, etc., which has low operability and the risk of affecting system stability. To solve the problems in the large-capacity impulse test of distribution transformers, this paper proposes a high-current impulse test method based on energy storage technology, power electronics technology and intelligent control technology. The stepless continuous adjustable voltage of large capacity short circuit test, precise control of test current peak factor and stable output are realized, and the corresponding smart energy storage power supply for the large capacity test of a distribution transformer is developed. Through simulation and live test, the design of the energy storage intelligent power supply proposed in this paper greatly reduces the power supply side capacity requirements of large capacity impulse test of power distribution, and has excellent operability in field test.

Breaking–closing of the circuit breaker inevitably produces micron metal dust, significantly affecting the internal insulation state of the GIS. This paper first analyzes the force characteristics of micron metal dust and its separation characteristics inside the circuit breaker, then builds a test platform supporting 520 kV power frequency withstand voltage and 1175 kV lightning impulse withstand voltage based on true type 363 kV GIS to investigate the influence of micron foreign matter on the insulation performance of GIS. Subsequently, ANSOFT is used to simulate the electric field distortion when there is micron metal dust inside the circuit breaker, and the influence of foreign matter on the degree of electric field distortion under the action of the flow field. The characteristics of the influence of micron foreign matter on the insulation performance of foreign matter inside the GIS are summarized. Secondly, using artificial micron foreign matter, the pulse current and the UHF methods are adopted to detect the discharge amount. The sensitivity of different detection methods to the discharge detection of the micron foreign matter is analysed, plus the partial discharge characteristics of the micron foreign matter under different voltages. Afterwards, based on the test results of micron foreign matter, two improvement measures are proposed, including the treatment of foreign matter inside the GIS and the dual-light source angiography inspection, so as to reduce the influence of micron foreign matter on the insulation status of the GIS. Finally, through the AC withstand voltage test of artificial embedded foreign matter and the insulation margin check under 1.1 times lightning impact, the effectiveness of the measures proposed in this paper is verified, thus providing technical support for certifying the impact of micron foreign matter on the insulation state during equipment operation and maintenance.

Abstract Sorbicillinoids (also termed yellow pigment) are derived from either marine or terrestrial fungi, exhibit various biological activities and therefore show potential as commercial products for human or animal health. The cellulolytic filamentous fungus Trichoderma reesei is capable to biosynthesize sorbicillinoids, but the underlying regulatory mechanism is not yet completely clear. Herein, we identified a histone H3 lysine 9 (H3K9) methyltransferase, Dim5, in T. reesei. TrDIM5 deletion caused an impaired vegetative growth as well as conidiation, whereas the ∆Trdim5 strain displayed a remarkable increase in sorbicillinoid production. Post TrDIM5 deletion, the transcription of sorbicillinoid biosynthesis‐related (SOR) genes was significantly upregulated with a more open chromatin structure. Intriguingly, hardly any expression changes occurred amongst those genes located on both flanks of the SOR gene cluster. In addition, the assays provided evidence that H3K9 triple methylation (H3K9me3) modification acted as a repressive marker at the SOR gene cluster and thus directly mediated the repression of sorbicillinoid biosynthesis. Transcription factor Ypr1 activated the SOR gene cluster by antagonizing TrDim5‐mediated repression and therefore contributed to forming a relatively more open local chromatin environment, which further facilitated its binding and SOR gene expression. The results of this study will contribute to understanding the intricate regulatory network in sorbicillinoid biosynthesis and facilitate the endowment of T. reesei with preferred features for sorbicillinoid production by genetic engineering.