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The Schlafen (SLFN) gene family has emerged as a critical subject of study in recent years, given its involvement in an array of cellular functions such as proliferation, differentiation, immune responses, viral infection inhibition, and DNA replication. Additionally, SLFN genes are linked to chemosensitivity, playing a pivotal role in treating malignant tumors. Human SLFNs comprise three domains: the N-terminal, middle (M), and C-terminal. The N- and C-terminal domains demonstrate nuclease and helicase/ATPase activities, respectively. Meanwhile, the M-domain likely functions as a linker that connects the enzymatic domains of the N- and C-terminals and may engage in interactions with other proteins. This paper aims to present a comprehensive overview of the SLFN family’s structure and sequence, examine its significance in various tumors, and explore its connection with immune infiltrating cells and immune checkpoints. The objective is to assess the potential of SLFNs as vital targets in cancer therapy and propose novel strategies for combined treatment approaches.

Electromagnetic transient (EMT) simulation plays a critical role in understanding the dynamic behavior and fast transients involved in wind farms (WFs). However, as WFs continue to develop on a large scale, the increasing number of wind turbines and network nodes poses significant challenges for efficient EMT simulation of WFs. To address this issue, we propose a fine-grained network decoupling method for doubly-fed induction generator (DFIG) based WFs. This paper first establishes the decoupling algorithm for core electrical equipment of DFIG-based WFs. By employing device-level fine-grained decoupling, the dimensionality of the admittance matrix for WF is effectively reduced, significantly decreasing the computational load. Additionally, this paper establishes a scalable computational framework by integrating multi-threaded parallel computation into the simulation process, which enhances efficiency further. The proposed method is compared with detailed models in Matlab/Simulink to verify efficiency and accuracy. Simulation results demonstrate that this method significantly improves simulation efficiency, achieving a two-order-of-magnitude speedup with 50 wind turbines, and it maintains high simulation accuracy, with a maximum relative error of 1.68%.

Abstract Background Multiple genetic and epigenetic regulatory mechanisms are crucial in the development and tumorigenesis process. Transcriptional regulation often involves intricate relationships and networks with post-transcriptional regulatory molecules, impacting the spatial and temporal expression of genes. However, the synergistic relationship between transcription factors and N6-methyladenosine (m6A) modification in regulating gene expression, as well as their influence on the mechanisms underlying the occurrence and progression of non-small cell lung cancer (NSCLC), requires further investigation. The present study aimed to investigate the synergistic relationship between transcription factors and m6A modification on NSCLC. Methods The transcription factor NFIC and its potential genes was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). The association of NFIC and its potential target genes were validated through ChIP-qPCR and dual-luciferase reporter assays. Additionally, the roles of NFIC and its potential genes in NSCLC were detected in vitro and in vivo through silencing and overexpression assays. Results Based on multi-omics data, the transcription factor NFIC was identified as a potential tumor suppressor of NSCLC. NFIC was significantly downregulated in both NSCLC tissues and cells, and when NFIC was overexpressed, the malignant phenotype and total m6A content of NSCLC cells was suppressed, while the PI3K/AKT pathway was inactivated. Additionally, we discovered that NFIC inhibits the expression of METTL3 by directly binding to its promoter region, and METTL3 regulates the expression of KAT2A, a histone acetyltransferase, by methylating the m6A site in the 3’UTR of KAT2A mRNA in NSCLC cells. Intriguingly, NFIC was also found to negatively regulate the expression of KAT2A by directly binding to its promoter region. Conclusions Our findings demonstrated that NFIC suppresses the malignant phenotype of NSCLC cells by regulating gene expression at both the transcriptional and post-transcriptional levels. A deeper comprehension of the genetic and epigenetic regulatory mechanisms in tumorigenesis would be beneficial for the development of personalized treatment strategies.

In this study, a polysaccharide was extracted and separated from seabuckthorn fruits by water extraction. The physicochemical characteristics were characterized, including monosaccharide composition, molecular weight, microscopic characterization, thermal stability, and rheological properties. Four models were used to evaluate its antioxidant activity in vitro. The results showed that the main component of the polysaccharide was an acidic pectin polysaccharide with a molecular weight of 37.82×104 Da. It was mainly composed of fucose, rhamnose, arabinose, galactose, glucose, xylose, and glucuronic acid with a molar ratio of 0.244: 0.098: 0.265: 0.075: 0.091: 0.081: 0.103. It also contained α- and β-glycoside bonds and carbonyl, carboxyl, aldehyde and hydroxyl groups, with three spiral and lamellar structures. The polysaccharide had strong thermal stability whose solution exhibited pseudoplastic properties. Seabuckthorn berry polysaccharide had a strong antioxidant capacity in vitro and showed significant scavenging ability on DPPH free radicals. In addition, it presented chelating ability on Fe2+. In conclusion, seabuckthorn fruit polysaccharide has the potential to serve as functional food additives.

Human activities have caused different degrees of land-use change on different topographic gradients, with impacts on the landscape and ecosystem. Effectively preventing and addressing ecological risk (ER) and achieving harmonious coexistence between humans and nature are important aspects of sustainable development. In this study, we used Gansu Province as an example, adopted five periods of land-use data in 1980, 1990, 2000, 2010 and 2020, and used the geoinformatic Tupu method and the terrain distribution index to study land-use changes under different topographic gradients, and then constructed the landscape ecological risk assessment (LERA) model based on the landscape pattern index to analyze landscape ecological risk (LER) spatiotemporal changes under different topographic gradients, and finally explored the LER driving factors using the geodetector model. The results showed that (1) the dominant land-use types were unused land and grassland, accounting for approximately 74% of the land. The situation of transferring and changing each type was more drastic. The distribution and changes in cropland and built-up land were easily found in low topographic gradient areas with low elevations and small slopes; the distribution and changes in woodland, grassland and water areas were easily found in high topographic gradient areas with high elevations and large slopes. (2) The landscape ecological risk index (LERI) was 0.018, 0.019, 0.019, 0.019 and 0.020, respectively, with spatial expressions of high in the northwest and low in the southeast. Low LER was concentrated in high topographic gradient ecological reserves; high LER was concentrated in low topographic gradient human interference areas and high topographic gradient natural environmental complex areas. (3) Natural factors mainly acted on the LER on moderate and high topographic position gradients; socioeconomic factors mainly acted on the LER on low topographic position gradients. Human interference interacted with natural factors more than human interference alone on LER. This study can provide a scientific basis for ensuring ecological security and sustainable development in areas with complex topography and geomorphology.

Ecological management zoning plays a significant role in optimizing resource utilization, improving ecosystem service function, and promoting coordinated regional development. Taking Hexi Corridor as a representative region of the Mountain–Oasis–Desert composite system in arid regions of Asia, this study analyzed the spatial and temporal evolution of ecosystem service values and explored the influencing mechanism based on the optimal parameters-based geographical detector model. We have comprehensively divided ecological management zones and proposed corresponding control strategies. The results show that (1) the Hexi Corridor is characterized by regional differentiation, which is composed of three systems: The southern mountain system, central oasis system, and northern desert system. The mountain system is mainly composed of forestland and grassland, the oasis system is mainly composed of cropland, and the desert system is mainly composed of unused land. The conversion of land use mainly involves the conversion of unused land to cropland and grassland, while grassland is mainly converted to cropland. (2) The ecosystem service value of the Hexi Corridor increased significantly and demonstrated agglomeration characteristics in space. The highest value areas are mainly distributed in the southern mountain, with higher value and medium areas mainly distributed in the central oasis, and the lowest value areas are mainly located in the northern desert. (3) Socio-economic factors greatly influence the spatial differentiation of ecosystem service values in the Hexi Corridor, with natural environmental factors having less impact. Additionally, the internal interaction of natural environmental factors is the most significant. (4) The Hexi Corridor is divided into three ecological management zones: Ecological function protection zone, ecological and agricultural coordinated development zone, and ecological and urbanization coordinated development zone. This research has important reference value for global ecological management in arid regions.

Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (LT7-SS-DOX and DT7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand LT7 (HAIYPRH) and its retro-inverso analog DT7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX. In conclusion, the coupling of antitumor drugs with the DT7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.

Background: Lactate, as an essential clinical evaluation index of septic shock, is crucial in the incidence and progression of septic shock. This study aims to investigate the differential expression, regulatory relationship, clinical diagnostic efficacy, and immune infiltration of lactate metabolism-related genes (LMGs) in septic shock.Methods: Two sepsis shock datasets (GSE26440 and GSE131761) were screened from the GEO database, and the common differentially expressed genes (DEGs) of the two datasets were screened out. LMGs were selected from the GeneCards database, and lactate metabolism-related DEGs (LMDEGs) were determined by integrating DEGs and LMGs. Protein-protein interaction networks, mRNA-miRNA, mRNA-RBP, and mRNA-TF interaction networks were constructed using STRING, miRDB, ENCORI, and CHIPBase databases, respectively. Receiver operating characteristic (ROC) curves were constructed for each of the LMDEGs to evaluate the diagnostic efficacy of the expression changes in relation to septic shock. Finally, immune infiltration analysis was performed using ssGSEA and CIBERSORT.Results: This study identified 10 LMDEGs, including LDHB, STAT3, LDHA, GSR, FOXM1, PDP1, GCDH, GCKR, ABCC1, and CDKN3. Enrichment analysis revealed that DEGs were significantly enriched in pathways such as pyruvate metabolism, hypoxia pathway, and immune-inflammatory pathways. PPI networks based on LMDEGs, as well as 148 pairs of mRNA-miRNA interactions, 243 pairs of mRNA-RBP interactions, and 119 pairs of mRNA-TF interactions were established. ROC curves of eight LMDEGs (LDHA, GSR, STAT3, CDKN3, FOXM1, GCKR, PDP1, and LDHB) with consistent expression patterns in two datasets had an area under the curve (AUC) ranging from 0.662 to 0.889. The results of ssGSEA and CIBERSORT both showed significant differences in the infiltration of various immune cells, including CD8 T cells, T regulatory cells, and natural killer cells, and LMDEGs such as STAT3, LDHB, LDHA, PDP1, GSR, FOXM1, and CDKN3 were significantly associated with various immune cells.Conclusion: The LMDEGs are significantly associated with the immune-inflammatory response in septic shock and have a certain diagnostic accuracy for septic shock.

IntroductionGranulomatous mastitis (GM) is a chronic inflammatory breast disease. In recent years, the role of Corynebacterium in GM onset has received more and more attention. This study aims to detect the dominant bacterium in GM patients and analyze the association between clinical characteristics and infectious factors.MethodsIn this study, 88 samples from 44 GM patients, six acute lactation mastitis (ALM) patients, and 25 non-inflammatory breast disease (NIB) patients were divided into a GM pus group, a GM tissue group, an ALM pus group, and a NIB tissue group; then, 16S ribosomal DNA sequencing was used to explore their microbiota. The clinical data of all 44 GM patients were also retrospectively collected and analyzed to determine their relationship with infection.ResultsThe median age of the 44 GM patients was 33 years, and 88.6% of patients had primary-onset cases, while 11.4% were recurrences; additionally, 89.5% of patients were postpartum and 10.5% were nulliparous. The serum prolactin level was abnormal in nine patients (24.3%). Samples from 15 GM patients (34.1%) had a Corynebacterium abundance of >1% (1.08–80.08%), with eight (53.3%) displaying an abundance of >10%. Corynebacterium was the only genus with significant differences between the GM pus group and the other three groups (p < 0.05). Corynebacterium kroppenstedtii was the predominant Corynebacterium species. Among clinical characteristics, a statistical difference in breast abscess formation was observed according to Corynebacterium abundance in Corynebacterium-positive and- negative patients (p < 0.05).DiscussionThis study explored the relationship between Corynebacterium infection and GM, compared the clinical characteristics between Corynebacterium-positive and- negative patients, and provided support for the role of Corynebacterium species-in particular, C. kroppenstedtii-in the pathogenesis of GM. The detection of Corynebacterium can predict GM onset, especially in patients with high prolactin levels or a history of recent lactation.

MoP is a promising anode material choice for alkali ion storage ascribed to its superior electrochemical performance. However, severe volume expansion and poor stability limited its output performance. Here, well-dispersed MoP nanoparticles are confined in carbon nanofiber skeleton by facile electrospinning method, further introduction of titania enhances the interfacial reaction and structure stability. As a result, the carbon nanofiber encapsulated MoP/TiO2 composite exhibited 150 mAh g−1 at 1 A g−1 for 4000 cycles, without obvious capacity decay. The homogenous dispersion and heterostructure construction contribute to its superior performance. This design provides a simple way for the phosphide preparation.

Abstract Background The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. Methods/design A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. Discussion To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. Trial registration number ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

Abstract Background Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. Methods A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. Results Caregivers tended to underestimate children’s weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children’s physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children’s nutrition intake and physical activity, and preferred online approaches. Conclusions Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

PurposeTo develop artificial intelligence (AI)-based deep learning (DL) models for automatically detecting the ischemia type and the non-perfusion area (NPA) from color fundus photographs (CFPs) of patients with branch retinal vein occlusion (BRVO).MethodsThis was a retrospective analysis of 274 CFPs from patients diagnosed with BRVO. All DL models were trained using a deep convolutional neural network (CNN) based on 45 degree CFPs covering the fovea and the optic disk. We first trained a DL algorithm to identify BRVO patients with or without the necessity of retinal photocoagulation from 219 CFPs and validated the algorithm on 55 CFPs. Next, we trained another DL algorithm to segment NPA from 104 CFPs and validated it on 29 CFPs, in which the NPA was manually delineated by 3 experienced ophthalmologists according to fundus fluorescein angiography. Both DL models have been cross-validated 5-fold. The recall, precision, accuracy, and area under the curve (AUC) were used to evaluate the DL models in comparison with three types of independent ophthalmologists of different seniority.ResultsIn the first DL model, the recall, precision, accuracy, and area under the curve (AUC) were 0.75 ± 0.08, 0.80 ± 0.07, 0.79 ± 0.02, and 0.82 ± 0.03, respectively, for predicting the necessity of laser photocoagulation for BRVO CFPs. The second DL model was able to segment NPA in CFPs of BRVO with an AUC of 0.96 ± 0.02. The recall, precision, and accuracy for segmenting NPA was 0.74 ± 0.05, 0.87 ± 0.02, and 0.89 ± 0.02, respectively. The performance of the second DL model was nearly comparable with the senior doctors and significantly better than the residents.ConclusionThese results indicate that the DL models can directly identify and segment retinal NPA from the CFPs of patients with BRVO, which can further guide laser photocoagulation. Further research is needed to identify NPA of the peripheral retina in BRVO, or other diseases, such as diabetic retinopathy.

Alpine grassland is the main ecosystem on the Qinghai-Tibet Plateau (QTP). Degradation and restoration of alpine grassland are related to ecosystem function and production, livelihood, and wellbeing of local people. Although a large number of studies research degraded alpine grassland, there are debates about degradation patterns of alpine grassland in different areas and widely applicable ecological restoration schemes due to the huge area of the QTP. In this study, we used the meta-analysis method to synthesize 80 individual published studies which were conducted to examine aboveground and underground characteristics in non-degradation (ND), light degradation (LD), moderate degradation (MD), heavy degradation (HD), and extreme degradation (ED) of alpine grassland on the QTP. Results showed that aboveground biomass (AGB), belowground biomass (BGB), Shannon-Wiener index (H′), soil moisture (SM), soil organic carbon (SOC), soil total nitrogen (TN), and available nitrogen (AN) gradually decreased along the degradation gradient, whereas soil bulk density (BD) and soil pH gradually increased. In spite of a tendency to soil desertification, losses of other soil nutrients and reduction of enzymes, there was no linear relationship between the variations with degradation gradient. Moreover, the decreasing extent of TN was smaller in areas with higher precipitation and temperature, and the decreasing extent of AGB, SOC, and TN was larger in areas with a higher extent of corresponding variables in the stage of ND during alpine grassland degradation. These findings suggest that in areas with higher precipitation and temperature, reseeding and sward cleavage can be used for restoration on degraded alpine grassland. Fencing and fertilization can be used for alpine grassland restoration in areas with lower precipitation and temperature. Microbial enzymes should not be used to restore degraded alpine grassland on a large scale on the QTP without detailed investigation and analysis. Future studies should pay more attention to the effects of climate factors on degradation processes and specific ecological restoration strategies in different regions of the QTP.