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In the pursuit of sustainable construction practices, the utilization of recycled concrete has emerged as a pivotal strategy, distinguished by its commitment to resource conservation and environmental stewardship. Nevertheless, the inherent micro-porosity and micro-cracking within the old mortar of recycled concrete may lead to weak bonding performance at the interfacial transition zone, culminating in diminished strength, reduced density, and elevated water absorption rates compared to conventional concrete, which critically impairs its performance in cold climates subjected to freeze-thaw cycles. Consequently, this paper provides a structured examination of the frost resistance properties of recycled concrete subjected to freeze-thaw cycling. Initially, the study delineates the mechanisms of frost-induced damage in recycled concrete by synthesizing the degradation pathways observed in both conventional and recycled concrete during freeze-thaw exposure. Subsequently, a detailed analysis is conducted to identify the pivotal factors affecting frost resistance, encompassing the proportion and moisture affinity of recycled aggregates, the addition of silica fume and fly ash, the water-to-cement ratio, and the degree of water saturation. In the final segment, the study compiles and reviews the strategies for bolstering the frost resistance of recycled concrete, including the incorporation of air-entraining admixtures, fiber reinforcement, and aggregate modification approaches. The objective of this research is to offer a thorough comprehension of recycled concrete, with a concentration on the mechanisms of frost damage, the critical determinants of frost resistance, and interventions to augment its resilience against freezing conditions. On this basis, the present paper, in conjunction with the characteristics and current research status of recycled concrete, proposes recommendations for the application of recycled concrete in cold regions. This review is anticipated to facilitate researchers in gaining a comprehensive understanding of the freeze-thaw characteristics of recycled concrete and the measures to enhance its frost resistance. Furthermore, it aims to assist engineering and technical personnel in selecting appropriate treatment methods to improve the frost resistance of recycled concrete in cold regions, thereby promoting the practical engineering application of recycled concrete in such areas.

Triple-negative breast cancer (TNBC) is characterized by high invasion, prone metastasis, frequent recurrence and poor prognosis. Unfortunately, the curative effects of current clinical therapies, including surgery, radiotherapy, chemotherapy and immunotherapy, are still limited in patients with TNBC. In this study, we showed that the heterogeneous expression at the protein level and subcellular location of mesothelin (MSLN), a potential target for chimeric antigen receptor-T (CAR-T) cell therapy in TNBC, which is caused by acidification of the tumor microenvironment, may be the main obstacle to therapeutic efficacy. Alkalization culture or sodium bicarbonate administration significantly promoted the membrane expression of MSLN and enhanced the killing efficiency of MSLN-CAR-T cells both in vitro and in vivo, and the same results were also obtained in other cancers with high MSLN expression, such as pancreatic and ovarian cancers. Moreover, mechanistic exploration revealed that the attenuation of autophagy-lysosome function caused by microenvironmental alkalization inhibited the degradation of MSLN. Hence, alkalization of the microenvironment improves the consistency and high expression of the target antigen MSLN and constitutes a routine method for treating diverse solid cancers via MSLN-CAR-T cells.

Ensuring representativeness of collected samples is the most critical requirement of water sampling. Unmanned surface vehicles (USVs) have been widely adopted in water sampling, but current USV sampling path planning tend to overemphasize path optimization, neglecting the representative samples collection. This study proposed a modified A* algorithm that combined remote sensing technique while considering both path length and the representativeness of collected samples. Water quality parameters were initially retrieved using satellite remote sensing imagery and a deep belief network model, with the parameter value incorporated as coefficient Q in the heuristic function of A* algorithm. The adjustment coefficient k was then introduced into the coefficient Q to optimize the trade-off between sampling representativeness and path length. To evaluate the effectiveness of this algorithm, Chlorophyll-a concentration (Chl-a) was employed as the test parameter, with Chaohu Lake as the study area. Results showed that the algorithm was effective in collecting more representative samples in real-world conditions. As the coefficient k increased, the representativeness of collected samples enhanced, indicated by the Chl-a closely approximating the overall mean Chl-a and exhibiting a gradient distribution. This enhancement was also associated with increased path length. This study is significant in USV water sampling and water environment protection.

Brucella abortus (B.abortus) is a zoonotic bacterial pathogen that causes chronic host infections. The eradication of brucellosis using antibiotic therapy is often incomplete or slow. In a mouse model, the predominance of alternatively activated macrophages (also known as M2) plays an essential role in sustaining chronic infection. The underlying functional mechanism by which M2 sustains chronic infection remains unclear. Here, we show that B. abortus can enter M2 via triggering receptor expressed on myeloid cells 2 (TREM2) and promotes the upregulation of TREM2 expression of M2 in a type IV secretion system (T4SS)-dependent manner. Increased TREM2 enhances B. abortus growth within M2 by suppressing intracellular ROS production, preventing M2 pyroptosis via suppression of mitochondrial ROS (mROS), and promoting M2 proliferation by increasing β-catenin expression. In line with these results, downregulation of TREM2 expression suppressed B. abortus intracellular growth and M2 proliferation and induced M2 pyroptosis. In our mouse model, upregulation of TREM2 expression sustained the accumulation of M2 and B. abortus chronic infection, whereas downregulation of TREM2 expression restricted M2 proliferation and chronic infection. Collectively, our results suggest that targeting TREM2 may be a potential adjunct to antibiotic therapy for the prevention of chronic Brucella infection.

Background: For glioma patients, the long-term advantages of dendritic cells (DCs) immunization remain unknown. It is extremely important to develop new treatment strategies that enhance the immunotherapy effect of DC-based vaccines. DCs exposed to glioma stem cells (GSCs) are considered promising vaccines against glioma. Methods: Glioma stem cells were isolated from mouse glioma GL261 cells (GCs). Both were subjected to severe (47°C) and mild (42°C) heat shock to induce immunogenic cell death (ICD). Membrane mobilization of calreticulin (CRT) and release of heat shock proteins (HSPs) were detected by flow cytometry. Dendritic cells were then exposed to heat-inactivated cells and co-culturing of T cells tested for immunotherapeutic efficacy in vitro. In vivo, we investigated the GSC targeting effect of the GSC-DC vaccine combined with CD47 blockade. Results: Heat shock induced ICD in GCs and GSCs, as indicated by significant release of calreticulin, HSP70, and HSP90. Heat shock condition ICD lysates induce maturation and activation-associated marker expression on monocyte-derived DCs. Accordingly, DCs pulsed with GCs and GSCs inactivated reduced colony formation, sphere formation, migration, and invasion of glioma and GSCs in vitro. Glioma stem cell-DC vaccine in combination with anti-CD47 antibody significantly enhanced survival in mice with glioma, induced production of interferon (IFN)-γ, and enhanced T-cell expansion in vivo. Of note, DCs pulsed with inactivated GSCs were more effective to control tumor growth than DCs pulsed with inactive GCs. Conclusions: Severe heat shock induces ICD in vitro. These data showed that administration of anti-CD47 antibody combined with GSC-DC vaccine may represent an effective immunotherapeutic strategy for cancer patients in clinical.

Shellfish cultivation is a sustainable method of providing human food and can help remove large amounts of CO2 from the atmosphere. Over the last two decades, longline-based structures have dominated farming systems. So far, the innovative technologies for open-ocean shellfish farming remain stagnant and need to be developed. As such, this paper preliminarily studies the operation and survivability abilities of an innovative shellfish farm under extreme wave conditions. To that end, an efficient numerical scheme with a robust implicit finite element method is established. First, the numerical modeling of a single module of the shellfish farm is conducted and the numerical results are verified against physical model tests. Then, the numerical modeling is implemented in a full-scale shellfish farm containing nine floating rafts with suspended lantern nets in a 3×3 configuration exposed to extreme wave conditions. Different angles of wave attack and shellfish rafts with and without lantern nets are fully considered, allowing an assessment of the operation and survivability abilities of the shellfish farm under extreme wave conditions in various situations. The results highlight that the angle of wave attack significantly affected the energy absorption of the mooring system. Moreover, non-linear instability such as subharmonics, which existed in the motion dynamics, can be manipulated to avoid resonant motions. This study provides insights into the evaluation of the safety design of a shellfish farm at both operational and survivability levels. The numerical method can also model other advanced offshore marine structures with multi-modules, such as floating bridges, airports, and even floating energy islands.

BackgroundMonoclonal antibodies against programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) have emerged as critical tools in cancer treatment. However, concerns regarding their potential cutaneous and mucosal toxicity, along with severe complications, have drawn clinical attention. Further research is warranted to investigate the adverse reactions and treatment strategies associated with PD-1 monoclonal antibodies.MethodsWe present a detailed case report of a laryngeal cancer patient who developed toxic epidermal necrolysis (TEN) after treatment with PD-1 monoclonal antibody. We analyzed the etiology, diagnosis, and treatment approaches by integrating clinical manifestations, pathological examinations, and literature research.ResultsAfter PD-1 monoclonal antibody therapy, the patient exhibited systemic rash, bullae, and epidermal detachment, which subsequently involved the tracheal and bronchial mucosa, resulting in dyspnea. The patient recovered after treatments with steroids, macrolides, immunoglobulins, and etanercept, along with repeated removal of scabs via bronchoscopy. Literature reviewing suggests a potential association between PD-1 monoclonal antibodies and the pathogenesis of Steven Johnson’s Syndrome (SJS) and Toxic epidermal necrolysis (TEN), possibly due to immune dysregulation. Treatment consists of immediate discontinuation of suspicious drugs, essential supportive therapy, and systemic corticosteroid administration, with the addition of immunosuppressants and/or immunoglobulins needed.ConclusionThe mucocutaneous toxicity induced by PD-1 monoclonal antibodies is not limited to the surface of the skin but also in deep mucosal layers, potentially leading to life-threatening complications. Therefore, when using PD-1 monoclonal antibodies, clinicians should closely monitor adverse events and apply appropriate treatments as soon as possible to prevent severe complications.

BackgroundAsiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression.MethodsBehavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA.ResultsThis study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic–pituitary–adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis.ConclusionsThese results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.

ObjectiveRadical hysterectomy has been established as the standard treatment for early stage cervical cancers. Despite numerous efforts to standardize the technique for radical hysterectomy across varying extents of tumor invasion, success has been inconsistent. Total Müllerian Compartment Resection (TMCR), an ontogenetic compartment-based oncologic surgery initially developed for open procedures by Professor Höckel, offers a standardized approach applicable to all patients with locally confined tumors. This method holds promise for achieving thorough oncologic clearance while maintaining acceptable complication rates. Moreover, robotic-assisted surgery may further reduce morbidity compared to open surgery. In this context, we provide a detailed step-by-step description of robotically assisted Total Müllerian Compartment resection (R-TMCR) for cervical cancer and present feasibility data from a cohort of 20 patients.Subjects and methods20 patients with stage IA1-IB2 cervical cancer, robot-assisted resection of the Müllerian embryonic compartment was undertaken. Key metrics such as operative duration, intraoperative blood loss, and postoperative complication rates were meticulously recorded and analyzed.ResultsThe duration of the surgery varied from 185 to 500 minutes, with intraoperative blood loss ranging between 5 mL and 300 mL. Postoperative hemoglobin levels dropped by -15 to 40 g/L from their preoperative values. Notably, there were no instances necessitating conversion to open surgery, and no intraoperative complications occurred. The rate of postoperative complications was 0%. Over the follow-up period, which averaged 18 months, there were no observed locoregional recurrences of cervical cancer, nor were there any deaths attributed to cervical cancer during this time.ConclusionThe application of robotic Müllerian compartment resection in the surgical treatment of cervical cancer is both safe and feasible. Utilizing robotic technology enables more precise and refined surgical outcomes. Combining embryonic compartment-based radical hysterectomy with the principles of membrane anatomy can standardize and optimize the surgical process, helping surgeons master radical hysterectomy more quickly and effectively.

IntroductionThe advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies.MethodsThis retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute’s CTCAE v5.0.ResultsNotably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute’s CTCAE v5.0 for grading).ConclusionsThe study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents.

Air blast fireball of the composite explosive is an important way to destroy the target and effectively determines the damage effect. Herein, based on the effect of aluminum powder content on the explosion reaction kinetics of HMX-based aluminized explosives, the cylindrical charges with positive gradient structure (PGS) and negative gradient structure (NGS) were designed and prepared to control the structure and size of air blast fireball. The PGS cylinders exhibited lateral shuttle-shaped flame/fireball and the width of the fireball was 3.901 m, which was increased by about 14% compared with homogeneous cylinders. The NGS cylinders led to the vertical shuttle-shaped flame/fireball that the height of the air blast fireball reached 4.049 m, and had longer durations of the fireball. The numerical fitting results show that the lateral shuttle-shaped flame/fireball and vertical shuttle-shaped flame/fireball gradually changed into spherical-like flame/fireball with an increase from 0 to 30 wt% of outer and inner layer HMX content, respectively. The vertical shuttle flame/fireball gradually changed into a spherical-like flame/fireball with the increase of HMX content. This is a feasible way to regulate the shape and size of the air blast fireball through gradient adjusting the distribution of HMX and Al, which could provide an effective strategy to improve the damage effect.

Primary hepatoid adenocarcinoma of the lung (HAL) is an exceptionally rare subtype of lung cancer that mimics the morphology and biological behavior of hepatocellular carcinoma. Although reports in the literature are limited, HAL is known for its high malignancy and poor prognosis, thus drawing increasing attention. We present the case of a patient with a mass-like consolidation with central necrosis initially misdiagnosed as inflammation at another medical institution despite a percutaneous lung biopsy. After ineffective anti-inflammatory treatment, she was referred to our hospital. We performed another lung biopsy, obtaining five samples from different angles, and eventually diagnosed her with HAL. Surprisingly, her serum alpha-fetoprotein (AFP) levels were extraordinarily high, leading to the successful diagnosis of HAL. Here, we present a case report and a related literature review.

BackgroundSystemic inflammatory response represented by C-reactive protein to albumin ratio (CAR) was shown to be associated with long-term outcome in patients with hepatocellular carcinoma (HCC). We conducted a meta-analysis to investigate the prognostic value of preoperative CAR in patients undergoing hepatectomy for HCC.MethodsWe searched four databases (PubMed, Embase, Scopus and Cochrane Library) from inception to May 10th, 2024. Studies investigating the prognostic value of preoperative CAR in HCC patients after hepatectomy. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Data from individual studies were aggregated to calculate the pooled hazard ratio (HR) using a random-effects model.ResultsA total of 11 studies included 4,066 patients were finally analyzed in the meta-analysis. Overall, the higher preoperative CAR was associated with poorer OS (HR 1.92, 95% CI 1.67 to 2.22, I2 = 0%) and DFS (HR 1.79, 95% CI 1.59 to 2.02, I2 = 0%) rate. Furthermore, subgroup analyses indicated that CAR could be a prognostic biomarker for patients with HCC regardless of regions and cut-off value.ConclusionOur meta-analysis indicates that higher preoperative CAR level is associated with poorer OS and DFS, it may be a good prognostic marker of survival outcomes after hepatectomy in patients with HCC. However, future prospective trials are necessary to validate the conclusion.Systematic review registrationThe study protocol was registered in the Open Science Framework (https://osf.io/uavt8).

IntroductionMyocardial ischemia/reperfusion (I/R) injury remains a major obstacle in cardiovascular therapies. Hydrogen sulfide (H2S) shows promise for mitigating I/R injury, but conventional delivery methods, such as NaHS injections or adenovirus-mediated CSE gene therapy, face low efficiency and systemic side effects. This study explores the use of angiotensin 1 (AT1) peptide-conjugated CdSe/ZnS quantum dots (QDs) for targeted delivery of cystathionine-γ-lyase (CSE) plasmids to the myocardium, aiming to boost local H2S production and minimize I/R injury.MethodsCdSe/ZnS QDs were conjugated with AT1 peptides to create a nanocarrier system capable of delivering the CSE plasmid specifically to the myocardium. In vivo fluorescence imaging confirmed heart-specific accumulation. Myocardial infarct size, cardiac function, cell death, and oxidative stress were evaluated. Endoplasmic reticulum stress and mitophagy markers, including CHOP/GRP78/eIF2α, were analyzed, and the CHOP gene's role was further assessed using an adenovirus vector.ResultsThe AT1-conjugated nanocarriers significantly increased CSE expression in the myocardium, as confirmed by fluorescence imaging, without affecting other organs. This localized delivery reduced myocardial infarct size, improved cardiac function, and decreased oxidative stress and cell death. Importantly, a reduction in endoplasmic reticulum stress and mitophagy markers was observed, suggesting that cardioprotection was mediated via the CHOP/GRP78/eIF2α signaling pathway. Reintroduction of CHOP using an adenovirus vector reversed these protective effects, confirming the pathway's involvement.DiscussionThis study demonstrates that AT1 peptide-conjugated QDs can effectively deliver CSE plasmids to the heart, providing significant protection against I/R injury through enhanced localized H2S production. This approach offers a promising, targeted, and side-effect-free therapy for myocardial I/R injury, with potential for clinical translation.

ObjectiveHigh-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed.MethodsWe used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer.ResultsRNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer.ConclusionThe successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated response to infection in the body. Effective treatment of sepsis poses a significant challenge in today’s clinical field. In recent years, enteral nutrition has garnered significant attention as an essential supportive therapeutic strategy. Serving as a means to provide ample nutritional support directly through the gastrointestinal tract, enteral nutrition not only addresses the nutritional depletion caused by the disease but also holds potential advantages in regulating immune function, maintaining intestinal mucosal barrier integrity, and promoting tissue repair. This article delves into the latest advancements of enteral nutrition in the treatment of sepsis, with a particular focus on its application effectiveness in clinical practice, potential mechanisms, and challenges faced. By examining relevant basic and clinical research, the aim is to provide a deeper understanding of nutritional therapy for sepsis patients and offer valuable insights for future research and clinical practice.

Financial product recommendation algorithms are mainly product-centered. This article proposes a two-stage recommendation optimization algorithm based on item popularity and user features, named CPCF-TSP, that can make full use of the demographic characteristics of users and mitigate the problem of users being more inclined to choose “hot” financial products. A popularity weight factor is introduced to normalize popularity and modify Pearson's similarity function. The modified Pearson's similarity function is combined with popularity normalization and user features to improve modeling performance. The two-stage recommendation optimization procedure was combined with a collaborative filtering algorithm to improve recommendation precision. CPCF-TSP fully considers user features in building a hybrid recommendation model and solves the problem of user cold-start. It can also mitigate popularity deviations and improve recommendation precision. MovieLens data and Santander Bank client trading data were used in a case study. The results show that the algorithm reduces inaccuracy in the calculation of the weights for recommendation popularity and similarity and is especially suitable for recommending financial products in which user information can be easily collected and the number of users is far greater than the number of products considered.

The widespread presence of micro(nano)plastics (MNPs) has generated public concern. Studies have indicated that MNPs can accumulate in mammalian bones; however, research on the skeletal toxicity and underlying molecular mechanisms of MNPs in aquatic organisms remains limited. We subjected zebrafish embryos to three varying levels (1, 10, 100 μg/mL) of polystyrene nanoplastics (PSNPs) exposure over a period of 7 days in our research. The results revealed that PSNPs significantly reduced the body length and hatching rate of zebrafish, leading to skeletal deformities. mRNA level analysis showed significant upregulation of sp7, sparc, and smad1 genes transcription by PSNPs. Moreover, PSNPs markedly downregulated the mRNA levels associated with runx2a, bmp2a, and bmp4. Further investigations demonstrated that PSNPs dramatically increased ROS levels in zebrafish larvae, with significant downregulation of transcription levels of sod1 and cat genes, resulting in a sharp increase in transcription levels of apoptosis-related regulatory genes bcl-2 and bax. Furthermore, PSNPs led to a marked rise in Caspase 3 activity in zebrafish larvae, suggesting the initiation of apoptosis. PSNPs also notably inhibited alkaline phosphatase (AKP) activity. Compared to a 4-day exposure, a 7-day exposure to PSNPs intensified abnormalities across multiple indicators. In summary, our research indicates that PSNPs cause significant oxidative stress in zebrafish larvae, resulting in apoptosis. Moreover, PSNPs disrupt the transcription of genes related to skeletal development through the bone morphogenetic protein (BMP) pathway, further disrupting skeletal development processes and ultimately resulting in skeletal deformities in zebrafish larvae. This study provides new insights into the skeletal toxicity of MNPs.

Soil moisture is an important factor that affects terrestrial ecosystems and biological growth and development, and water deficit is one of the major environmental factors threatening vegetation restoration on the Loess Plateau. The purpose was to identify the change in the soil water deficit characteristics from grassland to forestland on the Loess Plateau. In this study, we measured the soil water storage and deficit in abandoned grassland, shrubland, pioneer forestland and climax forestland along with vegetation succession in situ monitor. The results showed that the soil water content and the soil water storage with natural vegetation recovery from the abandoned grassland to shrubland and forestland showed a gradual declining trend. While on the contrary, the soil water deficit was increasing during succession, it was more severe in the deep soil than in the shallow soil layers. And the soil water deficit in July and September of the rainy season as well as that the vigorous growing period of plants was more serious than that in May and November, which are in the non-rainy season on the Chinese Loess Plateau. The vegetation types and soil depth were the key factors affecting the soil water deficiency status in the process of vegetation succession. Water-saving measures should be taken during the vigorous growing period of plants especially for those forest with natural restoration ages >50a on the Loess Plateau. The results could have great potential in the sustainable development of forestry and provide a theoretical basis for effective water management and reasonable vegetation restoration in semiarid loess regions.

Rapid identification of peanut seed quality is crucial for public health. In this study, we present a terahertz wave imaging system using a convolutional neural network (CNN) machine learning approach. Terahertz waves are capable of penetrating the seed shell to identify the quality of peanuts without causing any damage to the seeds. The specificity of seed quality on terahertz wave images is investigated, and the image characteristics of five different qualities are summarized. Terahertz wave images are digitized and used for training and testing of convolutional neural networks, resulting in a high model accuracy of 98.7% in quality identification. The trained THz-CNNs system can accurately identify standard, mildewed, defective, dried and germinated seeds, with an average detection time of 2.2 s. This process does not require any sample preparation steps such as concentration or culture. Our method swiftly and accurately assesses shelled seed quality non-destructively.

Landfilled metallurgical residues are valuable raw materials for the recovery of strategic vanadium resources. However, efficient separation of vanadium from these residues is challenging due to its strong oxidation resistance and coating within silicate inclusions. To address this issue, this study proposes an enhanced leaching process utilizing the synergistic effect of O3-catalyzed ultrasonic field in a low concentration sulfuric acid system. Results show that following a 10-minute O3 and ultrasonic treatment, the direct leaching rate of vanadium experienced a remarkable 46.7 % increase. Quenching experiments revealed a hierarchical order of active species within the reaction process:⋅OH >⋅O2−> H+, with⋅OH oxidation exhibiting the most pronounced capacity for disrupting the inclusion structure. Electron Paramagnetic Resonance analysis indicated that the highest⋅OH yield arose from the combined application of ultrasound and ozone. Kinetic investigations demonstrated that the vanadium leaching process is governed by interfacial chemical reactions. The activation energy of vanadium oxidation leaching under ultrasonic-O3 conditions was determined to be 40.41 kJ/mol, representing a 20.19 % reduction compared to ultrasonic conditions alone. Through the integration of analysis, characterization, and comparative evaluations, it was discerned that the synergistic impact of ultrasonic and ozone treatments significantly enhances the breakdown of silicate inclusions by low-concentration HF, particularly in the conversion of SiOSi bonds into SiOH bonds and SiF bonds. In summary, the refined leaching methodology incorporating ozone catalysis in conjunction with ultrasonic treatment provides a new idea for the separation and extraction of refractory residual vanadium.

Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166-co-n-butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166-co-n-butyl acrylate9) copolymer (P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury. Materials and methods: Thirty rats were randomly divided into two groups. The treatment group received hydrogel and transparent film dressing 30 min to 1 h post-burn, while the control group received only cotton dressing. The wound area was measured, and the wound closure rate was calculated on days 3, 7, and 14 post-surgery. Tissue samples were collected from each rat on these days and stored at −80 °C for histological analysis using H&E, Masson and immunohistochemical staining. This analysis assessed factors such as granulation tissue length, re-epithelialization, re-angiogenesis, collagen deposition, inflammatory cell infiltration, and collagen production. Clinical and histological assessments at 14 days showed more rapid healing in the hydrogel dressing group compared to the control group. Conclusion: Our results indicate that the design of our hydrogel for cooling injury wounds effectively improves healing and mitigates the damage from low temperatures.

Fracture propagation in shale under in situ conditions is a critical but poorly understood mechanical process in hydraulic fracturing for deep shale gas reservoirs. To address this, hydraulic fracturing experiments were conducted on hollow double-wing crack specimens of the Longmaxi shale under conditions simulating the ground surface (confining pressure σcp=0, room temperature (Tr)) and at depths of 1600 m (σcp=40 MPa, Ti=70 °C) and 3300 m (σcp=80 MPa, high temperature Ti=110 °C) in the study area. High in situ stress was found to significantly increase fracture toughness through constrained microcracking and particle frictional bridging mechanisms. Increasing the temperature enhances rather than weakens the fracture resistance because it increases the grain debonding length, which dissipates more plastic energy and enlarges grains to close microdefects and generate compressive stress to inhibit microcracking. Interestingly, the fracture toughness anisotropy in the shale was found to be nearly constant across burial depths, despite reported variations with increasing confining pressure. Heated water was not found to be as important as the in situ environment in influencing shale fracture. These findings emphasize the need to test the fracture toughness of deep shales under coupled in situ stress and temperature conditions rather than focusing on either in situ stress or temperature alone.

The occurrence mechanism of coal and gas outburst disasters is still unclear. According to the rheological hypothesis, gas-bearing coal and rock may enter the “strength limit neighborhood” under long-term load, and it is more likely to be destroyed by external impact disturbance. The “strength limit neighborhood” of gas-bearing coal rock under different loading conditions is studied to find the influence law of entering this state, and the corresponding micro-discrimination criteria are established,” using the self-developed triaxial test system of rock rheological disturbance effect and the seepage experimental device of coal rock rheological disturbance effect, the rheological disturbance experiment of gas-bearing coal rock under different confining pressures, different gas pressures and axial pressures was carried out. The coal rock before and after rheological disturbance was analyzed and compared by means of nuclear magnetic resonance, and the T2 spectrum curve, porosity and pore size distribution under different loading conditions were obtained. The test results show that: ① In the rheological process of coal rock under different loading conditions, there is a critical value for the sensitivity of external disturbance. When the applied force is less than this critical value, after the impact disturbance, the porosity of coal rock decreases and the specimen is compressed closely. When the force is greater than this critical value, after the impact disturbance, the large pore size of coal rock increases obviously, the T2 spectrum curve shifts to the right, and the peak height increases, It shows that the stress threshold is the key to determine whether the coal rock enters the “strength limit neighborhood”. ② Confining pressure and gas pressure have opposite mechanical properties to coal rock. It is shown in the compressive capacity, damage degree, long-term strength and “strength limit neighborhood”. Among them, the greater the confining pressure, the earlier the coal rock enters the “strength limit neighborhood;” The greater the gas pressure, The greater the gas pressure, the earlier the coal rock enters the neighborhood. ③ the pore size distribution and T2 spectrum curve of coal rock can directly reflect the internal and external micro-variation characteristics of rock’s “strength limit neighborhood.” ④The constitutive equation of axial pressure, confining pressure and gas pressure determined by the porosity of coal rock can be used to judge the timing of coal rock entering the “strength limit neighborhood” under different loading conditions. As a criterion for entering the “strength limit neighborhood,” the greater the confining pressure, the greater the stress threshold when entering the “strength limit neighborhood,” the greater the gas pressure, and the smaller the stress threshold when entering the “strength limit neighborhood.”

Liver cancer is a common type of cancer worldwide, with over 90% of cases being hepatocellular carcinoma (HCC). The discovery of new targets holds promise for improving the prognosis of HCC patients. Zinc finger protein 677 (ZNF677), a member of the Kruppel C2H type 2 zinc finger family, has been implicated in the progression of several tumors. However, its specific role in HCC remains unclear. In this study, we investigated the role of ZNF677 in HCC progression. Our analysis revealed low expression of ZNF677 in HCC, which correlated with patient prognosis. Functionally, ZNF677 suppressed the growth, migration, invasion, and stemness of HCC cells. Additional data confirmed its ability to block the stemness of HCC cells. Mechanistically, ZNF677 achieved these effects by targeting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) axis. In summary, ZNF677 inhibits both growth and stemness in hepatoma cells via modulation of the PI3K/Akt axis.

This study proposes a hybrid model based on the combination of Sand Cat Swarm Optimization (SCSO), Echo State Network (ESN), Gated Recurrent Unit (GRU), Least Squares Method (LSM), and Markov Chain (MC) to improve the accuracy of annual runoff prediction. Firstly, conduct correlation analysis on multi-factor data related to runoff to determine the input of the model. Secondly, the SCSO algorithm is used to optimize the parameters of the ESN and GRU models, and the SCSO-ESN and SCSO-GRU models are established. Next, the prediction results of these two models are coupled using LSM to obtain the preliminary prediction results of the SCSO-ESN-GRU model. Finally, the initial prediction results are corrected for errors using MC to get the final prediction results. Choose Changshui Station and Lanxi Station for experiments, and evaluate the predictive performance of the model through five evaluation indicators. The results show that the combined prediction model corrected by the MC achieved the optimal prediction performance at both experimental stations. This study emphasizes that using a combination prediction model based on Markov chain correction can significantly improve the accuracy of annual runoff prediction, providing a reliable basis for predicting annual runoff in complex watersheds. HIGHLIGHTS A new hybrid sand cat swarm optimization-echo state network-gated recurrent unit-Markov chain (SCSO-ESN-GRU-MC) model is proposed for annual runoff prediction.; A new SCSO algorithm is used to optimize the parameters of the prediction model.; Least squares method is used to couple the ESN and GRU models for annual runoff prediction.; MC is used to correct errors in annual runoff prediction results.; The proposed model achieves the best prediction results at both experimental stations.;

Although new-type energetic materials have been investigated extensively, there is a challenge on how to integrate energy density and mechanical properties of energetic materials simultaneously. Herein, a versatile approach was proposed to design energetic materials with high energy density, reactivity, and flexibility based on a bio-inspired strategy. By mimicking the “brick-and-mortar” structure within a natural nacre, the energetic film with alternative layers of polytetrafluoroethylene (PTFE) and boron (B) was successfully fabricated. The nacre-mimetic PTFE/B energetic film exhibited excellent reaction heat (4413.9 J⋅g−1) and bright combustion flame, which may originate from the exothermic reaction mechanism between fluorine (F) and B. Even more remarkably, such PTFE/B energetic film revealed prominent mechanical flexibility reported for the first time. These findings indicate that the nacre-mimetic strategy provides an effective route to engineer energetic materials with high energy density, reactivity, and flexibility.

ObjectiveThe study in this paper aims to investigate the impacts of cabin atmosphere quality on the comfort and the work efficiency of crew member aboard the ship, thereby the degree of thermal comfort of ship air conditioning system can be improved.MethodAirpak software is used to simulate and analyze the temperature, relative humidity, PMV-PPD and air age in the four air supply and return modes of a typical single-occupant cabin of a ship, namely ‘different side up and down cycles’, ‘same side up and down cycles’, ‘different side down and up cycles’, and ‘same side down and up cycles’. ResultsThe simulation results show that the temperature in the cabin can be kept constant at 24℃, humidity can be maintained at about 50% and the humidity field distribution can be more uniform, while PMV (predicted mean vote) distribution is more uniform with its value tending to zero, and the air age PPD (predicted percentage of dissatisfied) distribution is more uniform with a very low value in the cabin.ConclusionUsing the optimization principle of lattice order theory, the air supply and return mode of ‘different side up and down cycles’ is the optimal scheme for a single-occupant cabin of a ship.

Abstract Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer.

Abstract This research added rare Earth elements Ce to the P110-grade oil casing steel to reveal their influence on the inclusions and tensile properties. The content of cerium in the steel varied from 0 to 452 ppm. Based on the classical thermodynamic calculation, the predominance diagram of Re-containing inclusions in P110-grade steel was obtained. The evolution route of the inclusions composition with the increasing cerium content in the steel was xCaO⋅yAl2O3 → Al2O3–CeAlO3 → Ce2O3–CeAlO3 → Ce2O3–Ce2O2S → Ce2O2S, which agreed well with the thermodynamic analysis. As the cerium content at 235 ppm, the size of Ce containing inclusions has a minimal size at 2.82 μm. Suitable Ce content can modify the big-size xCaO⋅yAl2O3 inclusions into small-size Re-containing inclusions. The results demonstrate that the tensile performance of this steel can be improved as the cerium content increases from 0 to 235 ppm. However, once the cerium content exceeds 235 ppm, further increases in cerium content led to a decline in performance. The experimental results shows that the presence of large-sized Ce2O2S inclusions and the change of microstructure, will lead to the decrease in tensile performance.

Abstract Background Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear. Methods Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results. Results Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P

Abstract Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Abstract Background Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. Results In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. Conclusions These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age

Abstract Background Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. Methods The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. Conclusion Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Abstract Ancient murals have suffered from continuous damage over time, and especially paint loss disease. Therefore, disease labeling, as the basis for ancient mural restoration, plays an important role in the protection of cultural relics. The predominant method of disease labeling is currently manual labeling, which is highly dependent on expert experience, time consuming, inefficient and results in inconsistent accuracy of the marking effect. In this paper, we propose a labeling framework for paint loss disease of ancient murals based on hyperspectral image classification and segmentation. The proposed framework involves first the extraction of features from the hyperspectral image, and then image segmentation is performed based on the spatial features to obtain more accurate region boundaries. Then, the hyperspectral image’s regions are classified based on their spatial-spectral characteristics, and the candidate areas of paint loss disease are obtained. Finally, by leveraging the true color image segmentation results, the proposed disease labeling strategy combines the results of classification and segmentation to propose the final paint loss disease labeling areas. The experimental results show that the proposed method can not only combine the hyperspectral space and spectral information effectively to obtain accurate labeling of paint loss disease, but can also mark the paint loss disease not easily observed using ordinary digital cameras. Compared with the state-of-the-art methods, the proposed framework could be promising for accurate and effective paint loss disease labeling for ancient murals.

Starch was the main source of carbohydrates in people's daily diet, and its digestibility was an important factor affecting the body's postprandial blood glucose level. In this paper, the effect of xylose on the in vitro digestive properties of corn starch and its mechanism of action were investigated. The in vitro digestibility of starch was evaluated by an in vitro simulated digestion system after different additions of xylose (5%, 10%, and 15%), and the mechanisms of xylose on α-amylase and α-glucosidase, as well as its effect on blood glucose fluctuation through enzyme inhibition kinetics, molecular docking, and human glycemic index (GI) tests. The results showed that the digestive hydrolysis of corn starch was inhibited by different amounts of xylose, and the IC50 values of xylose on α-glucosidase and α-amylase were 205.35 and 4.75 mg/mL, respectively, which belonged to the mixed type inhibitors. Xylose interacted with amino acid residues of α-glucosidase and α-amylase through hydrogen bonding with binding energies of −3.05 and −5.30 kcal/mol, respectively. Additionally, the GI value of plant-based peptidoglycan milk decreased from 58 to 45 after the addition of xylose, which demonstrated that xylose was effective in decreasing the fluctuation of postprandial blood glucose. The results could provide scientific data to support the research and application of xylose in nutritional and health foods.

Abstract Background Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. Methods RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. Conclusions Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites. Graphical Abstract

Abstract Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P

Since there is insufficient evidence to determine the best treatment of transurethral laser lithotripsy (TLL) in ureteral stones, this study compared the effectiveness and safety of TLL using high-power (HP) (100 W) and low-power (LP) (20 W) laser settings. All patients with maximally sized ureteral stones who were planned for transurethral holmium laser lithotripsy were enrolled in this open study. One of the two laser setting groups–LP or HP–was allocated to each alternate patient. Using IBM SPSS Statistics 24, the treatment groups were compared for operating time, intraoperative and postoperative problems (up to 1 year), and rates of stone-free recovery. Welch tests were employed to compare continuous data, whereas Fisher’s exact or Chi-square tests were used to assess categorical variables. At P < 0.05, statistical significance was established. A total of 207 individuals were included and preoperative data were comparable between the two groups. The HP group had a considerably greater ablation rate and a significantly shorter procedure duration (42.61 ± 11.74 min) than the LP group (78.56 ± 25.91 min) (P = 0.025). The Overactive Bladder Symptom Score and International Prostate Symptom Score were considerably higher in the HP group than in the LP group. Treatment effectiveness was considerably impacted by the location of the ureteral stone, according to univariate and multivariate logistic regression models. A HP laser setting of up to 100 W greatly shortens the duration of the process for treating ureteral stones without raising the risk of problems.

To overcome challenges in the traditional melt casting process of zine alloys, such as oxidative burnout, compositional segregation, and grain coarsening, this study carried out hot compression deformation tests on Zn-0.5Mg-0.05Fe alloys prepared by powder metallurgy. The results show that increasing deformation temperature and decreasing strain rate reduce rheological stress. The hot compression deformation process exhibits three phases, as rheological stress increases, work hardening, dynamic softening, and steady-state fluidization are observed, respectively. An intrinsic equation for the hot compression process is derived as = 1.334 × 1010 × [sinh(0.0053σ)]7.62947exp(-109.931691/RT). Processing conditions for Zn-0.5Mg-0.05Fe alloy are determined from a processing map, suggesting that a safe zone of 25°C–130 °C deformation temperatures with 0.13s−1-0.36s−1 strain rates, and 120°C–200 °C deformation temperatures with 0.01s−1-0.6s−1 strain rates. Electron Back-scattering Patterns (EBSD) and Transmission Electron Microscope (TEM) results show both discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) during the hot deformation compression process. DRX reduces deformation resistance, refines the grains, and improves the mechanical properties of the alloys. This study provides theoretical insights and process guidance for preparing degradable zinc alloys with excellent mechanical properties.

Abstract Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl3) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H+ toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.

Abstract Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Abstract Timely understanding of the preservation status of archaeological human bones is the foundation for conducting scientific archaeological work. This paper applies Micro-CT technology to analyze the microscopic preservation status of ancient human femora unearthed from the Rui State site in Liangdai Village, Hancheng, Shaanxi, the Chejiasi Cemetery in Baoji, and the Ouerping Cemetery in Xizhou Village, Yushe, Shanxi, and obtained imaging results and cortical bone porosity (Ct.Po), bone volume fraction (BV/TV), and bone density (BMD) parameters for 9 samples. The results show that the poorly preserved fragile group has lower Ct.Po, BV/TV, and BMD, and macroscopically presents fragile and porous features; while the well-preserved dense group has relatively higher Ct.Po, BV/TV, and BMD, and macroscopically appears solid and dense. This study employs Micro-CT technology to analyze the micro-preservation status of human bones from historical periods, confirming the effectiveness of this technology in revealing the microstructure of ancient human bones, and providing a reference for establishing a human bone preservation status evaluation system.