Search

Abstract Objective The aim of this study was to explore the clinical application value of two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign, borderline ovarian tumors (BOTs), and malignant ovarian epithelial tumors (OETs). Methods The clinical data of 108 patients who underwent surgery for pathologically confirmed of OETs at Peking University People’s Hospital between December 2018 and November 2023 were retrospectively studied. The diagnostic value of 2D-US combined with CEUS for diagnosing OETs was analyzed using chi-square tests, receiver operating characteristic (ROC) curves, and random forest models. Results Among the 108 cases of OETs, 23 were benign, 34 were BOTs, and 51 were malignant. Chi-square tests confirmed that the perfusion pattern of the contrast agent plays an important role in the differential diagnosis of OETs. Compared with those in the benign group, the BOTs were not significantly different in terms of perfusion phase and enhancement intensity, but the regression time of the BOTs was earlier (P

The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), poses a significant threat to food security, necessitating effective management strategies. While chemical control remains a primary approach, understanding the toxicity and detoxification mechanisms of different insecticides is crucial. In this study, we conducted leaf-dipping bioassays to assess the toxicity of quinalphos and beta-cypermethrin·emamectin benzoate (β-cyp·EMB) on S. frugiperda larvae. Additionally, we assessed the response of alterations in CarE, GST, MFO, and AChE activities to sublethal concentrations of these insecticides over various treatment durations. Results indicated that β-cyp·EMB exhibited higher toxicity than quinalphos in S. frugiperda. Interestingly, the highest activities of GST, CarE, MFO, and AChE were observed at 6 h exposure to LC10 and LC25 of β-cyp·EMB, surpassing equivalent sublethal concentrations of quinalphos. Subsequently, GST and CarE activities exposure to β-cyp·EMB steadily decreased, while MFO and AChE activities exposure to both insecticides was initially decreased then increased. Conversely, two sublethal concentrations of quinalphos notably enhanced GST activity across all exposure durations, with significantly higher than β-cyp·EMB at 12–48 h. Similarly, CarE activity was also increased at various durations. Our research has exhibited significant alterations in enzyme activities exposure to both concentration and duration. Furthermore, Pearson correlation analysis showed significant correlations among these enzyme activities at different treatment durations. These findings contribute to a better understanding of detoxification mechanisms across different insecticides, providing valuable insights for the rational management of S. frugiperda populations.

Summary: Integrins play critical roles in connecting the extracellular matrix and actin. While the upregulation of integrins is thought to promote cancer stemness and metastasis, the mechanisms underlying their upregulation in cancer stem cells (CSCs) remain poorly understood. Herein, we show that USP22 is essential in maintaining breast cancer cell stemness by promoting the transcription of integrin β1 (ITGB1). Both genetic and pharmacological inhibition of USP22 largely impaired breast CSCs self-renewal and prevented their metastasis. Reconstitution of integrin β1 partially rescued USP22-null breast cancer metastasis. USP22 functions as a bona fide deubiquitinase to protect the proteasomal degradation of the forkhead box M1 (FoxM1), a transcription factor for tumoral ITGB1 gene transcription. Immunohistochemistry staining detected a positive correlation among USP22, FoxM1, and integrin β1 in human breast cancers. Collectively, our study identifies the USP22-FoxM1-integrin β1 signaling axis as critical for cancer stemness and offers a potential target for antitumor therapy.

To study the graded alcohol precipitation components of fucoidan from Undaria pinnatifida and its hypoglycemic activity in vitro, this study used Undaria pinnatifida as raw material, extracted Undaria pinnatifida fucoidan gum through CaCl2 solution, and precipitated it step by step to obtain four sets of polysaccharide samples (UPP-45, UPP-55, UPP-65, and UPP-75). Determined their molecular weight, total sugar content, uronic acid content, protein content, sulfate content and monosaccharide composition and analyzed by ultraviolet spectrum (UV), Fourier transform infrared spectra(FT-IR) and scanning electron microscopy(SEM). The inhibition of polysaccharides on α-amylase and α-glucosidase was determined to explore their hypoglycemic activity in vitro. The results showed that the higher the concentration of alcohol precipitation, the higher the proportion of small molecular weight polysaccharide. The highest total sugar content of UPP-65 was 84.38%, and the protein of the crude polysaccharide and sulfate contents of UPP-45 were significantly different from those of other components (P

In this paper, Cinnamomum cassia polysaccharide (CCP) was extracted and purified, and its physicochemical properties, antioxidant and hypoglycemic activities were investigated. The polysaccharide yield was optimized by the response surface test with three conditions: Temperature, time and liquid-solid ratio. Then the physicochemical properties of purified CCP were investigated by high performance liquid chromatography, thermogravimetric analysis and other methods, meanwhile, its antioxidant and hypoglycemic activities were tested in vitro. Results indicated that the optimum extraction conditions as follow: Extraction temperature 90 ℃, extraction time 2.5 h, liquid-solid ratio 20:1 (mL/g), extraction twice, under these conditions, the average yield was 3.22%. The relative molecular weight of CCP was 1.95×106 Da, the total sugar content was 90.11%±1.24%, and it was stable within 230 ℃. Both Fourier-transform infrared and nuclear magnetic hydrogen spectra showed that CCP had α, β-glycosidic bonds and other structures, in addition, Congo red staining showed that it might not have triple helix structure. Activity assays showed that CCP had good scavenging effect on DPPH·, ABTS+∙, ·OH, with IC50 values of 0.191, 2.835 and 3.221 mg/mL, respectively, and the total reducing power value of the polysaccharide at 6 mg/mL was 1.18. In addition, CCP also had inhibitory activity against α-amylase and α-glucosidase, with IC50 values of 0.189 and 0.340 mg/mL. In this study, a high molecular weight Cinnamomum cassia polysaccharide was extracted and purified, which had good antioxidant and hypoglycemic activities, which may provide a basis for the functional development and utilization of Cinnamomum cassia.

In order to improve the antioxidant activity of Zizania latifolia polysaccharides, sulfate it and explore the optimum modification conditions. Polysaccharides was extracted by water extraction and alcohol precipitation method from Zizania latifolia, then it was separated and purified to obtain a new type of water-soluble polysaccharide. Using formamide as solvent, polysaccharides were sulfated by sulfur trioxide-pyridine method. The degree of substitution (DS) was set as the examination index, the optimal sulfonation conditions were selected by response surface method. Through the free radical scavenging rate trial in vitro, compared with natural polysaccharides, to explore the changes of antioxidant activity of sulfated polysaccharides in vitro. The results showed that the optimum reaction conditions obtained as polysaccharide 100 mg, time 4 h, temperature 70 ℃, sulfur trioxide-pyridine complex 2.6 g. The optimum DS was 1.79. Thermogravimetric analysis showed that the fastest weight loss rate of Zizania latifolia polysaccharides was 16.48% at 46.38 ℃, and the sulfated polysaccharides was 2.92% at 65.04 ℃. In the antioxidant test in vitro, the IC50 of free radical scavenging ability of Zizania latifolia polysaccharides to DPPH·, ·OH and ABTS+· were 3.49, 3.28 and 12.70 mg/mL respectively. The sulfated polysaccharides of Zizania latifolia polysaccharides were 0.39, 1.00 and 1.82 mg/mL respectively, and the positive control (VC) was 0.069, 0.17 and 0.077 mg/mL respectively. In summary, sulfation modification can enhance the thermal stability of Zizania latifolia polysaccharides and enhance its free radical scavenging ability to some extent.

Abstract Introduction The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare. Methods We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare. We built bulk‐natural language processing pipelines to extract structured information from clinical notes and stored them in common data models. We developed multimodal AI/machine learning (ML) tools and tutorials to enrich the toolbox of the multidisciplinary workforce to analyze multimodal healthcare data. We have created a fertile ground to cross‐pollinate clinicians and AI scientists and train the next generation of AI health workforce to collaborate effectively. Results Our work has democratized access to unstructured health information, AI/ML tools and resources for healthcare, and collaborative education resources. From 2017 to 2022, this has enabled studies in multiple clinical specialties resulting in 68 peer‐reviewed publications. In 2022, our cross‐discipline efforts converged and institutionalized into the Center for Collaborative AI in Healthcare. Conclusions Our Collaborative AI in Healthcare initiatives has created valuable educational and practical resources. They have enabled more clinicians, scientists, and hospital administrators to successfully apply AI methods in their daily research and practice, develop closer collaborations, and advanced the institution‐level learning health system.

Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P

Abstract Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia‐reperfusion injury (CIRI), in addition to the blood‐brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)‐responsive neutrophil‐targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Abstract. Background:. High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. Methods:. Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. Results:. Fourteen DEGs, ADIPOQ, ALPK2, BARX1, CD37, CNR2, COL5A3, FABP4, FAP, GPR68, ITGBL1, MOXD1, PODNL1, SFRP2, and TRAF3IP3, were upregulated in metastatic tumors in every database while CADPS, GATA4, STAR, and TSPAN8 were downregulated. ALPK2, FAP, SFRP2, GATA4, STAR, and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC (P = 0.0002 and P = 0.0001, respectively). Conclusions:. This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2, which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

The extraction process of polysaccharide from Sophora japonica was optimized, and the single polysaccharide component (named SJP) was purified, then the structure characterization and antioxidant activity of SJP were investigated. Using crude polysaccharide yield as evaluation index, single factor combined with response surface method were used to explore the optimal conditions of water extraction of Sophora japonica polysaccharide. The crude polysaccharide extracted under the optimal conditions was further purified by deproteinization, dialysis and Sephadex G-200 gel column chromatography. The molecular weight of SJP was determined by high performance liquid chromatography (HPLC), and its chemical composition was analyzed. Congo red experiment and X-ray diffraction (XRD) analysis was applied to characterize the SJP structure. With the free radical scavenging rate and total reducing power as indicators, the antioxidant activity of SJP was investigated. The results showed that the optimal extraction conditions were solid-liquid ratio of 1:20 g/mL, extraction time of 120 min and alcohol precipitation concentration of 60%. Under these conditions, the polysaccharide yield was verified with 3.94%. HPLC results showed that SJP was a homogeneous polysaccharide with the molecular weight of 2.32×106 Da. The contents of total sugar, protein and uronic acid in SJP were 93.47%±0.83%, 1.62%±0.13% and 7.13%±0.51%, respectively. Congo red experiment showed that SJP did not contain triple helix structure, and XRD results indicated that SJP had low crystallinity and amorphous structure. The IC50 values of SJP for scavenging DPPH, OH and ABTS+ radicals were 1.09, 4.31 and 1.39 mg/mL, respectively, and the total reducing power was 0.57 at concentration of 5 mg/mL, indicating that SJP had certain antioxidant activity. In conclusion, the process of extracting and purifying polysaccharide from Sophora japonica in this study was feasible, and the obtained polysaccharide had high purity and exhibited good antioxidant activity.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Abstract Background Worldwide, frozen embryo transfer (FET) has become a new strategy for the treatment of infertility. The success of FET is closely related to endometrial receptivity. Does uterine artery Doppler during the implantation window predict pregnancy outcome from the first FET? Methods A total of 115 retrospectively collected cycles were included in the study, with 64 cycles of clinical pregnancy and 51 cycles of nonclinical pregnancy; There were 99 nonabsent end-diastolic flow (NAEDF) cycles and 16 absent end-diastolic flow (AEDF) cycles. The differences in uterine artery Doppler findings between different pregnancy outcomes were investigated. The clinical pregnancy rate and spontaneous abortion rate in the NAEDF and AEDF groups were compared. The predictive value of uterine artery Doppler during the implantation window in the success rate of pregnancy from the first FET was also investigated. Results Between the clinical pregnancy group and the nonclinical pregnancy group, there were no significant differences in the mean resistance index (mRI) (Z = -1.065, p = 0.287), mean pulsatility index (mPI) (Z = -0.340, p = 0.734), and mean peak systolic/end-diastolic velocity(mS/D) (Z = -0.953, p = 0.341); there were significant differences in the mean peak systolic velocity (mPSV) (Z = -1.982, p = 0.048) and mean end-diastolic velocity (mEDV) (Z = -2.767, p = 0.006). Between the NAEDF and AEDF groups, there was no significant difference in the clinical pregnancy rate (χ2 = 0.003, p = 0.959), and there was a significant difference in the spontaneous abortion rate (χ2 = 3.465, p = 0.019). Compared with uterine artery Doppler alone, its combination with artificial abortion history, waist-to-hip ratio, LH (Luteinizing hormone) of P (Progesterone) administration day, mPSV and mEDV had a higher predictive value regarding clinical pregnancy from the first FET [ROC-AUC 0.782, 95% CI (0.680–0.883) vs. 0.692, 95% CI (0.587–0.797)]. Conclusions Uterine artery Doppler, particularly mPSV and mEDV during the implantation window, was useful for predicting clinical pregnancy, and AEDF was related to spontaneous abortion in the first trimester. Uterine artery Doppler combined with artificial abortion history, waist-to-hip ratio, LH of P administration day, mPSV and mEDV have a higher predictive value than uterine artery Doppler alone regarding the pregnancy from the first FET.

Sanjiang Plain is intensively used for rice production, and ditch drainage diffuse pollution prevention is crucial. Groundwater, rich in Fe ions, is the main source of irrigation water in this region. In this study, pyrite and zero-valent iron (ZVI) (sponge iron and iron scraps) were used as substrates to identify the synergistic influence of exogenous Fe2+ addition and solid iron substrates on pollutant removal in constructed wetlands. Based on the results, iron substrates hardly improved the ammonia removal, mainly because of the physical structure and oxidation activity. At a hydraulic retention time longer than 8 h, the pollution removal efficiency in the zero-valent iron (ZVI) substrate treatment increased significantly, and the removal of nitrate (NO3−-N) and total phosphorus (TP) in the iron scrap substrate treatment reached about 60% and 70%, respectively. The high-throughput sequencing results showed a significant increase in the abundance of microorganisms involved in denitrification and phosphate accumulation in biofilms on ZVI substrates. The highest diversities of such microorganisms in biofilms on iron scraps were found for denitrifying bacteria (Pseudomonas), nitrate-reducing Fe (II)-oxidizing bacteria (Acidovorax), and Dechloromonas with autotrophic denitrification and phosphate accumulation, with a 43% cumulative abundance. Dechloromonas dominated in the iron sponge substrate treatment. The highest relative abundance of Acidovorax was found in the mixed iron substrate (pyrite, sponge iron, and iron scraps) treatment. The addition of ZVI substrate significantly improved the removal of NO3−-N and TP and reduced the hydraulic retention time through the continuous release of Fe2+ and the promotion of microbial growth. When designing constructed wetlands for treating paddy field drainage, the appropriate addition of iron scrap substrates is recommended to enhance the pollutant removal efficiency and shock load resistance of CWs.

Abstract Bisphenol A (BPA) is a monomer to produce polycarbonate plastics and can be released into the environment through human activities, leading to its accumulation in animals, plants and humans through direct contact or environmental exposure. Epidemiological studies have reported that BPA exposure is associated with metabolic disorders. The pancreas is an important endocrine organ and plays an important role in metabolic disorders. To explore the possible long-term effects of BPA exposure on neonatal health, bioinformatic methods were used to identify differentially expressed genes (DEGs) by comparing the neonatal pancreas after maternal exposure to BPA with the adult pancreas after direct exposure to BPA. Two datasets about BPA exposure and pancreatic abnormality, GSE82175 and GSE126297 in Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were collected. Control (or BPA-exposed) offspring (maternal exposure) and Control (or BPA-exposed) adults (direct exposure) were defined as Control (or BPA) groups. The results showed that BPA disturbed the normal function of the pancreas in both offspring and adults, with offspring showing higher susceptibility to BPA than adults. Seventeen insulin secretion-related DEGs (Stxbp5l, Fam3d, Mia3, Igf1, Hif1a, Aqp1, Kif5b, Tiam1, Map4k4, Cyp51, Pde1c, Rab3c, Arntl, Clock, Edn3, Kcnb1, and Krt20) in the BPA group were identified, and 15 regulator DEGs (Zfp830, 4931431B13Rik, Egr1, Ddit4l, Cep55, G530011O06Rik, Hspa1b, Hspa1a, Cox6a2, Ibtk, Banf1, Slc35b2, Golt1b, Lrp8, and Pttg1) with opposite expression trends and a regulator gene Cerkl with the similar expression trend in the Control and BPA groups were identified. Hif1α might be an important molecular target for pancreatic cancer caused by BPA exposure, and pregnancy is a critical window of susceptibility to BPA exposure.

Ribosome biogenesis is a fundamental process in eukaryotic cells. NOTCHLESS (NLE) is involved in 60S ribosome biogenesis in yeast, but its role in Arabidopsis (A. thaliana) remains exclusive. Here, we found that Arabidopsis NLE (AtNLE) is highly conservative in phylogeny, which encoding a WD40-repeat protein. AtNLE is expressed in actively dividing tissues. AtNLE-GFP is localized in the nucleus. AtNLE physically interacts with the MIDAS domain of AtMDN1, a protein involved in the biogenesis of the 60S ribosomal subunit in Arabidopsis. The underexpressing mutant nle-2 shows short roots and reduced cell number in the root meristem. In addition, the null mutant nle-1 is embryo lethal, and defective embryos are arrested at the early globular stage. This work suggests that AtNLE interacts with AtMDN1, and AtNLE functions in root and embryo development.

Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer. In order to explore the influence to hepatocellular carcinoma, a novel cold water-soluble polysaccharide was separated from Rhodiola rosea L. root (RLP) and then its structure and anti-cancer activities were tested. The chemical compositions and high performance gel permeation chromatography (HPGPC) results indicated that RLP was an acid heteropolysaccharide with the molecular weight of about 1.15×106 Da. Furthermore, ion chromatography (IC), Fourier transform infrared (FT-IR) and nuclear magnetic resoance (NMR) further indicated that RLP was main composed of →2,4)-α-Rha(1→, →5)-α-L-Araf-(1→, α-D-Glu, →6)-β-D-Galp-(1→, β-D-Man and →4)-α-GalpA-(1→. In vivo antitumor activities of RLP were carried out by using H22 tumor-bearing mice model. The results shown that RLP (100 and 300 mg/kg) could inhibit tumor growth of H22 cells from 23.59 % to 45.52 % and protect thymuses and spleen without damage. In addition, according to cell cycle, AV-FITC/PI and JC-1, RLP could induce dose-dependent apoptosis of H22 cells via S phase arrested which was through a mitochondrial related pathway. Our data indicated that RLP has a broader application prospect in anti-tumor preparations.

Food-derived peptides have been extensively studied for their benefits in humans. Hen eggs, characterized by high protein and digestibility, are an excellent source of food-derived bioactive peptides. This review summarizes the preparation methods, purification, and identification of hen egg-derived peptides (HEPs). The preparation methods mainly include enzymatic hydrolysis, microbial fermentation, and chemical synthesis. Genetic engineering is an emerging trend of HEP preparation. Then, we summarize the biological activities of HEPs, such as antioxidant activities, enzyme inhibitory activity, and antibacterial activity, of which the enzyme inhibitory activity is comprehensively summarized for the first time. The structure–activity relationship and underlying mechanism of the HEPs are further elucidated. Finally, the applications, future challenges, and opportunities of HEPs were mainly discussed in the food and non-food sectors. We focus on the potential applications of HEPs in intestinal health and assembly delivery and provide a reference for the further utilization and commercial development of HEPs.

The fall armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), a common agricultural pest known for its extensive migration and wide host ranges, causes considerable harm to maize (Zea mays L.). In this study, we utilized two molecular marker genes, COI and Tpi, to compare the genetic characteristics of the collected original samples. Additionally, through an interactive study between S. frugiperda larvae and six maize varieties aiming to understand the insect’s adaptability and resistance mechanisms, our analysis revealed that both the COI and Tpi genes identified S. frugiperda as the corn strain. Further examination of the larvae showed significant differences in nutritional indices, digestive, and detoxification enzyme activities. Special maize varieties were found to offer higher efficiency in nutrient conversion and assimilation compared with common varieties. This study revealed adaptations in S. frugiperda’s digestive and detoxification processes in response to the different maize varieties. For instance, larvae reared on common maize exhibited elevated amylase and lipase activities. Interestingly, detoxification enzyme activities exhibited different patterns of variation in different maize varieties. The Pearson correlation analysis between nutritional indices, enzyme activities, and the nutritional content and secondary metabolites of maize leaves provided deeper insights into the pest’s adaptability. The results highlighted significant relationships between specific nutritional components in maize and the physiological responses of S. frugiperda. Overall, our findings contribute substantially to the understanding of S. frugiperda’s host plant adaptability, offering critical insights for the development of sustainable pest management strategies.

Abstract Background Bacteria usually secrete a variety of extracellular enzymes to degrade extracellular macromolecules to meet their nutritional needs and enhance their environmental adaptability. Bacillus cereus 0–9, a biocontrol bacterial strain isolated from wheat roots, has three genes annotated as encoding amylases in the genome, but their functions are unknown, and whether they are involved in the colonization process of the bacterium remains to be further studied. Methods Mutant gene strains and fluorescently tagged strains were constructed by homologous recombination, and amylase protein was expressed in the prokaryotic Escherichia coli BL21(DE3) expression system. The iodine staining method was used to measure the activity of amylase proteins. We further observed the colonization abilities of the test strains in wheat roots through frozen section technology. Results The results showed that there were three amylase-encoding genes, amyC, amyP and amyS, in the B. cereus 0–9 genome. Among the three amylase encoding genes, only amyS produced extracellular amylase whose secretion was related to signal peptide at position 1–27. The AmyS protein encoded by the amyS gene is an α-amylase. The growth of Rhizoctonia cerealis was inhibited 84.7% by B. cereus 0–9, but the biocontrol ability of the ΔamyS strain decreased to 43.8% and that of ΔamyS/amyS was restored when the amyS gene was complemented. Furthermore, the biocontrol ability of the ΔamySec strain was decreased to 46.8%, almost the same as that of the ΔamyS mutant. Due to the deletion of the amyS gene, the colonization capacities of ΔamyS (RFP) and ΔamySec (RFP) in wheat roots decreased, while that of ΔamyS/amyS (RFP) was restored after the amyS gene was complemented, indicating that the amyS gene influences the colonization of B. cereus 0–9 in wheat roots. In addition, the colonization and biocontrol abilities of the mutant were restored after the addition of sugars, such as glucose and maltose. Conclusions B. cereus 0–9 encodes three genes annotated as amylases, amyC, amyP and amyS. Only the deletion of the amyS gene with a signal peptide did not produce extracellular amylase. The AmyS protein encoded by the amyS gene is an α-amylase. Our results indicated that the amyS gene is closely related to the colonization abilities of B. cereus 0–9 in wheat roots and the biocontrol abilities of B. cereus 0–9 to fight against R. cerealis. The extracellular amylase produced by B. cereus 0–9 can hydrolyze starch and use glucose, maltose and other nutrients to meet the needs of bacterial growth. Therefore, it is very possible that the secretion and hydrolytic activities of extracellular amylase can promote the colonization of B. cereus 0–9 in wheat roots and play important roles in the prevention and control of plant diseases. Our results contribute to exploring the mechanisms of microbial colonization in plant roots.

Abstract Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)‐induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD‐M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD‐M protected against CTX‐induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia‐Shigella. Importantly, PPD‐M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad‐spectrum antibiotics. Moreover, PPD‐M promoted the production of microbiota‐derived immune‐enhancing metabolites including cucurbitacin C, l‐gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S‐epoxy‐stearic acid, and 9′‐carboxy‐gamma‐chromanol. KEGG topology analysis showed that the PPD‐M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.

ABSTRACT: Lung cancer has the highest incidence and mortality rate worldwide. Immunotherapy is a universal treatment for lung cancer, but its overall treatment remains a challenge. Tumor immunoediting is a process in which the immune system restricts or promotes tumor development through elimination, equilibrium, and escape to change tumor immunogenicity and obtain an immunosuppressive mechanism to promote disease progression. An increasing number of immunotherapy drugs, including monoclonal antibody-targeting drugs and chimeric antigen (Ag) receptor-modified T cells (CAR-T cells), have been used in clinical therapy. Additionally, cancer vaccine development and new clustered regularly spaced short palindromes (CRISPR)- based combination therapies against cancer open up new avenues for immunotherapy. However, these immunotherapies cause autoimmune induction and non-specific inflammation, with many limitations. The development and study of nanoparticle systems have shown the possibility of localization, pharmacokinetic programming, and immunomodulator co-delivery. Rapid advances in nanotechnology over the past decade have provided a strategic impetus for cancer immunotherapy improvements. Nanotechnology advancements in various aspects, such as virus-like size, high surface-volume ratio, and surface modifications to precisely target specific cell types, can be investigated through cancer vaccine and immunomodulator delivery system development. This review presents the current immunotherapy approaches for lung cancer and emphasizes the current process and prospects of the fusion of cancer immunotherapy, nanotechnology, bioengineering, and drug delivery.

ABSTRACT: Nanodiamonds (NDs) are emerging as a promising platform for theranostic particles since they offer a single platform that possesses multiple important properties. These include a simple mechanism of synthesis, small size, chemical inertness, a variety of available surface functional groups, good biocompatibility, stable fluorescence, and a long fluorescence lifetime. The use of NDs to deliver anticancer drugs has been an important ND application since NDs can increase chemosensitivity, sustain drug release, and minimize drug side effects. These unique properties have stimulated the application of NDs to cancer imaging and therapy. In this review, we offer a brief introduction of ND structure and their functional properties. This is followed by a summary of recent uses of NDs for imaging purposes, including fluorescent imaging, magnetic resonance imaging (MRI), and other imaging technologies. Special concern is given to studies focusing on NDs use for anticancer drug delivery, anticancer gene delivery, photothermal and photodynamic therapies, and multifunctional combination therapy. We then discuss ND biocompatibility and toxicity in various cells and animal models. Finally, we also discuss the main problems to be solved by future research before NDs can be put to clinical use. The purpose of this review is to provide a side-by-side comparison of studies reporting ND-mediated cancer imaging therapy so that readers can assess the potential clinical applications of ND and have the background necessary to understand the clinical test results associated with ND-related therapy in animals and humans.

El-Shennawy et al. report that ACE2+ circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2.

Tumor-initiating cells with reprogramming plasticity or stem-progenitor cell properties (stemness) are thought to be essential for cancer development and metastatic regeneration in many cancers; however, elucidation of the underlying molecular network and pathways remains demanding. Combining machine learning and experimental investigation, here we report CD81, a tetraspanin transmembrane protein known to be enriched in extracellular vesicles (EVs), as a newly identified driver of breast cancer stemness and metastasis. Using protein structure modeling and interface prediction-guided mutagenesis, we demonstrate that membrane CD81 interacts with CD44 through their extracellular regions in promoting tumor cell cluster formation and lung metastasis of triple negative breast cancer (TNBC) in human and mouse models. In-depth global and phosphoproteomic analyses of tumor cells deficient with CD81 or CD44 unveils endocytosis-related pathway alterations, leading to further identification of a quality-keeping role of CD44 and CD81 in EV secretion as well as in EV-associated stemness-promoting function. CD81 is coexpressed along with CD44 in human circulating tumor cells (CTCs) and enriched in clustered CTCs that promote cancer stemness and metastasis, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights machine learning as a powerful tool in facilitating the molecular understanding of new molecular targets in regulating stemness and metastasis of TNBC.

ObjectiveTo evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis.MethodsThe literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis.ResultsA total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events.ConclusionProbiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.

This study aimed to isolate polysaccharides from Penthorum chinense Pursh and evaluate their rheological characteristics, physicochemical properties, and antioxidant activity. The optimal conditions for the maximal extraction yield of Penthorum chinense Pursh polysaccharides (4.05 ± 0.12%) were determined by employing a single-factor test and response surface methodology which included an extraction time of 3 h, a liquid–solid ratio of 20 mL/g, and three separate extraction times. The rheological experiments showcased that the P. chinense polysaccharides exhibited typical shear-thinning behavior, with their apparent viscosity being influenced by various parameters such as concentration, pH, temperature, salt content, and freeze–thaw. The purified polysaccharides (PCP-100), having an average molecular weight of 1.46 × 106 Da, mainly consisted of glucose (18.99%), arabinose (22.87%), galactose (26.72%), and galacturonic acid (21.89%). Furthermore, the PCP-100 exhibited high thermal stability and displayed an irregular sheet-like morphology. Its superior reducing power and free radical scavenging ability implied its significant antioxidant activity in vitro. Collectively, these findings provide important insights for the future application of P. chinense polysaccharides in the food industry.

Circulating tumor cell (CTC) clusters are more efficient at mediating metastasis as compared to single cells and are associated with poor prognosis in breast cancer. Here, the authors show that ICAM1 is enriched in CTC clusters and its loss suppresses cell-cell interaction and CTC cluster formation, and propose ICAM1 as a therapeutic target for treating breast cancer metastasis.

Cancer metastasis is largely incurable and accounts for 90% of breast cancer deaths, especially for the aggressive basal-like or triple negative breast cancer (TNBC). Combining patient database analyses and functional studies, we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis, such as miR-206 that inhibits stemness and metastasis of TNBC. Here we report that the integrin receptor CD49b-encoding ITGA2, a direct target of miR-206, promotes breast cancer stemness and metastasis. ITGA2 knockdown suppressed self-renewal related mammosphere formation and pluripotency marker expression, inhibited cell cycling, compromised migration and invasion, and therefore decreased lung metastasis of breast cancer. ITGA2 overexpression reversed miR-206-caused cell cycle arrest in G1. RNA sequencing analyses revealed that ITGA2 knockdown inhibits genes related to cell cycle regulation and lipid metabolism, including CCND1 and ACLY as representative targets, respectively. Knockdown of CCND1 or ACLY inhibits mammosphere formation of breast cancer cells. Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest. ACLY-encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA levels. CCND1 knockdown further mimics ITGA2 knockdown in abolishing lung colonization of breast cancer cells. We identified that the low levels of miR-206 as well as high expression levels of ITGA2, ACLY and CCND1 are associated with an unfavorable relapse-free survival of the patients with estrogen receptor-negative or high grade breast cancer, especially basal-like or TNBC, possibly serving as potential biomarkers of cancer stemness and therapeutic targets of breast cancer metastasis.

Management of chronic pain is one of the most difficult problems in modern practice. Grafted human telomerase reverse transcriptase–immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) with inducible galanin (GAL) expression have been considered to be a potentially safe and controllable approach for the alleviation of chronic pain. Therefore, in this study, we aimed to assess the feasibility of hTERT-BMSCs/Tet-on/GAL cells secreting GAL under the transcriptional control of doxycycline (Dox) for controllable pain relief. After transplanted into the subarachnoid space of neuropathic rats induced by spared nerve injury of sciatic nerve, their analgesic actions were investigated by behavioral tests. The results showed that the pain-related behaviors, mechanical allodynia, and thermal hyperalgesia were significantly alleviated during 1 to 7 weeks after grafts of hTERT-BMSCs/Tet-on/GAL cells without motor incoordination. Importantly, these effects could be reversed by GAL receptor antagonist M35 and regulated by Dox induction as compared with control. Moreover, the GAL level in cerebrospinal fluid and spinal GAL receptor 1 (GalR1) expression were correlated with Dox administration, but not GAL receptor 2 (GalR2). Meanwhile, spinal protein kinase Mζ (PKMζ) expression was also inhibited significantly. Taken together, these data suggest that inducible release of GAL from transplanted cells was able to produce controllable pain relief in neuropathic rats via inhibiting the PKMζ activation and activating its GalR1 rather than GalR2. This provides a promising step toward a novel stem cell–based strategy for pain therapy.

Abstract Objective This study aimed to identify the clinical characteristics of Chinese patients with ovarian endometrioid carcinoma (EC) and clear cell carcinoma (CCC) and to assess the impact of concurrent endometriosis on this group. Methods The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of EC or CCC at our center in China between 1998 and 2018. Results Of 211 patients, 73 had pure EC, and 91 had pure CCC, and the remaining 47 had mixed cancer. The proportion of EC and CCC remained stable over past 21 years. The proportion of EC declined with aging and the age of EC onset to incline to the young. And the age of CCC onset had two peaks, namely, 36 and 77 years. After review by the pathologist, the number of endometriosis cases found in the pathological section of the analysis increased to 114, accounting for 54% of patients. As the stage progressed, the appearance of endometriosis became increasingly scarce in pathological sections(p = 0.001). Compared with CCC, EC had a higher frequency of concurrent endometrial cancer (independent endometrial lesions) and estrogen and progesterone receptor expression(p = 0.000). And more patients were in premenopausal state in EC group(p = 0.040). In the pure group, multivariate analysis showed that correlation existed between relevance to endometriosis and worse outcomes(p = 0.041). In patients with mixed cancer, mixed endometrioid histology was associated with better survival than other subtypes, even with stage III or poorly differentiated tumors(p = 0.001). Conclusions CCC and EC which are common in ovarian cancer patients who have associated with endometriosis have distinct clinicopathological characteristics. Attention should be paid to ovarian cancer patients with a history of endometriosis and those with concurrent endometriosis in pathological sections.

Tsai, Zhang, Scholten et al. develop a surfactant- assisted one-pot sample preparation coupled with mass spectrometry method (SOP-MS) for label-free global single-cell proteomics. This method allows researchers to measure hundreds of proteins from single human cells, suggesting its utility for quantitative single-cell proteomics.

Cymbopogon citratus is an important functional food, widely used for flavoring in Africa and South America. In this study, a novel high-molecular-weight polysaccharide (CCP) from C. citratus was extracted, and its structural characteristics and anti-breast cancer activity in vitro were investigated. CCP contained both α and β configurations and mainly composed of galactose (36.89%), arabinose (23.97%), glucose (18.35%) and rhamnose (9.36%) with an average molecular weight of 1.98 × 106 Da. The main glycosyl residues of CCP detected by methylation analysis were 1,3,6-linked Galp, 1,3-linked Glcp, 1,5-linked Araf , T-Araf , and T-Rhap. In vitro experiments suggested that CCP significantly inhibited the proliferation of MDA-MB-231 cells, decreased the expressions of cyclin D1 and CDK4 and stocked cells at G0/G1 phase. Meanwhile, the typical morphological features of apoptotic cells were also observed. Combining with the consequences of Annexin V-FITC/PI staining, Hoechst 33258 staining and western blot analysis, CCP induced apoptosis of MDA-MB-231 cells by triggering the Fas/FasL-mediated death receptor pathway. Overall, these results provide a theoretical basis for the application of C. citratus polysaccharide as a potential anti-breast cancer agent in functional food and medicine.

Four novel triterpenoid alkaloids, siragrosvenins A–D (1–4), and two new cucurbitane-type triterpenoids, siragrosvenins E–F (5, 6), together with eight known analogs (7−14), were isolated from the roots of Siraitia grosvenorii. Compounds 1−4 possessed a rare cucurbitane-type triterpenoid scaffold, featuring an extra pyrazine unit via the Strecker reaction in the cucurbitane framework. Compound 5 displayed a 6/6/6/5/6/5-fused polycyclic ring system, with an uncommon fused furan and pyran ring in the side chain. All the structures were characterized by extensive spectroscopic analysis, including HRESIMS, NMR, and X-ray crystallographic data. It is worth noting that the DP4+ analysis method was applied for the first time to determine the absolute configurations of the trihydroxybutyl moiety in the side chain of compounds 1–4. In vitro cytotoxicity screening found that compounds 4, 8, 9, 13, and 14 exhibited remarkable cytotoxic activities against three cell lines with IC50 values ranging from 1.44 to 9.99 μM. Siragrosvenin D shows remarkable cytotoxic activity on MCF-7 cells. As a result, it inhibited the proliferation of MCF-7 cells and reduced their viability via the induction of G2/M phase arrest and significantly induced apoptosis in MCF-7 cells.

Most of the terminal lakes in inland basins, which account for half of the world's lake reserves, have been shrinking at an alarming rate in recent years. In a Terminal Lake Basin, changes in the water level of the lake can lead to variations in the local erosion base level. From the perspective of local erosion base level, we revealed the response of river evolution to change in the water level of lake in Ebinur Lake Basin for the past 5000 years. Our results verified the three geomorphic development stages of natural decline, balance maintenance, and imbalanced decline. In modern times, the decline in the number of rivers entering the lake due to human activities has made the water level of the lake drop 15–30 times that observed from 5 kaBP–0.1 kaBP. The results showed that the average undercut erosion rate of the river entering the lake tends to increase with a rapid decrease in the water level of the lake in the past 5000 years. The instantaneous undercutting rate of the Bortala river section in the basin was 1.6–4.2 times that observed from 5 kaBP–0.1 kaBP. This result showed that a rapid decline in the water level of the lake due to human activities will accelerate the erosion of rivers. Therefore, from the perspective of geomorphology, the river erosion triggered by the rapid decline in the local erosion base level is an important reason for the continuous shrinkage of Ebinur Lake.

The optimal therapy for severe infections caused by vancomycin-resistant Enterococcus faecium (VREfm) remains unclear, but the combination of linezolid and fosfomycin may be a good choice. The 24-h static-concentration time-kill study (SCTK) was used to preliminarily explore the pharmacodynamics of linezolid combined with fosfomycin against three clinical isolates. Subsequently, a hollow-fibre infection model (HFIM) was used for the first time to further investigate the pharmacodynamic activity of the co-administration regimen against selected isolates over 72 h. To further quantify the relationship between fosfomycin resistance and bacterial virulence in VREfm, the Galleria mellonella infection model and virulence genes expression experiments were also performed. The results of SCTK showed that the combination of linezolid and fosfomycin had additive effect on all strains. In the HFIM, the dosage regimen of linezolid (12 mg/L, steady-state concentration) combined with fosfomycin (8 g administered intravenously every 8 h as a 1 h infusion) not only produced a sustained bactericidal effect of 3∼4 log10 CFU/mL over 72 h, but also completely eradicated the resistant subpopulations. The expression of virulence genes was down-regulated to at least 0.222-fold in fosfomycin-resistant strains compared with baseline isolate, while survival rates of G. mellonella was increased (G. mellonella survival ≥45% at 72 h). For severe infections caused by VREfm, neither linezolid nor fosfomycin monotherapy regimens inhibited amplification of the resistant subpopulations, and the development of fosfomycin resistance was at the expense of the virulence of VREfm. The combination of linezolid with fosfomycin produced a sustained bactericidal effect and completely eradicated the resistant subpopulations. Linezolid plus Fosfomycin is a promising combination for therapy of severe infections caused by VREfm.

ABSTRACT The rapid spread of antibiotic resistance among Enterococcus has prompted considerable interest in determining the dosage regimen of linezolid combined with fosfomycin. A checkerboard assay was employed to evaluate whether linezolid combined with fosfomycin had a synergistic effect on Enterococcus isolates from the hospital, including three drug-resistant strains (MIC of linezolid [MICLZD], ≥8 mg/L; MIC of fosfomycin [MICFOF], ≥256 mg/L). The in vitro static time-kill assay, dynamic pharmacokinetic (PK)/pharmacodynamic (PD) model, and semimechanistic PK/PD model were used to explore and predict effective combined dosage regimens. The checkerboard assay and in vitro static time-kill assay demonstrated that linezolid combined with fosfomycin has a synergistic effect on drug-resistant and sensitive Enterococcus. In the in vitro PK/PD model, the dosage regimen of linezolid (8 mg/L or 12 mg/L, steady-state concentration) combined with fosfomycin (6 g or 8 g) via a 0.5-h infusion every 8 h effectively suppressed bacterial growth at 24 h with a 3 log10 CFU/mL decrease compared with the initial inocula against two resistant and one sensitive Enterococcus isolates. The semimechanistic PK/PD model predicted that linezolid (more than 16 mg/L) combined with fosfomycin (6 g or 10 g) via a 0.5-h infusion every 8 h was required to achieve a 4 log10 CFU/mL decrease at 24 h against Enterococcus isolates (MICLZD ≥ 8 mg/L and MICFOF ≥ 256 mg/L). According to the prediction of the semimechanical PK/PD model, the effect of the combination was driven by linezolid, with fosfomycin enhancing the effect. Our study is the first to explore the synergistic effects of these two drugs from a qualitative and quantitative perspective and provides a simulation tool for future studies. IMPORTANCE In this study, we found that linezolid combined with fosfomycin could kill Enterococcus in vitro and that the administered dose was significantly lower after the combination treatment, which could reduce adverse effects and the development of drug resistance. The potential mechanism of the two-drug combination against Enterococcus was revealed from a quantitative perspective, which is an important step toward dose optimization in simulated humans. We hope that our research will help build a better relationship between clinicians and patients as we work together to address the challenges of antibiotic resistance in the 21st century.

The aim of the study was to investigate the regulatory effects of policosanol on hyperlipidemia, gut microbiota and metabolic status in a C57BL/6 mouse model. A total of 35 C57BL/6 mice were assigned to 3 groups, chow (n=12), high fat diet (HFD, n=12) and HFD+policosanol (n=11), then treated for 18 weeks. Policosanol supplementation significantly reduced serum triglycerides and total cholesterol, as well as the weight of brown adipose tissue (BAT) (p0.05). Combined 16S rRNA gene sequencing and untargeted metabolomic analysis demonstrated that policosanol had regulatory effects on gut microbiota and serum metabolism in mice. In obese mice, policosanol increased the proportion of Bacteroides, decreased the proportion of Firmicutes, and increased the ratio of Bacteroides to Firmicutes (p

Integrins are cell adhesion molecules that are composed of an alpha (α) subunit and a beta (β) subunit with affinity for different extracellular membrane components. The integrin family includes 24 known members that actively regulate cellular growth, differentiation, and apoptosis. Each integrin heterodimer has a particular function in defined contexts as well as some partially overlapping features with other members in the family. As many reviews have covered the general integrin family in molecular and cellular studies in life science, this review will focus on the specific regulation, function, and signaling of integrin α2 subunit (CD49b, VLA-2; encoded by the gene ITGA2) in partnership with β1 (CD29) subunit in normal and cancer cells. Its roles in cell adhesion, cell motility, angiogenesis, stemness, and immune/blood cell regulations are discussed. The pivotal role of integrin α2 in many diseases such as cancer suggests its potential to be used as a novel therapeutic target. Keywords: Integrin α2, CD49b, Molecular mechanisms, Regulation, Signaling

Grasspea (Lathyrus sativus L.), a legume crop with excellent resistance to a broad array of environmental stressors, has, to this point, been poorly genetically characterized. High-density genetic linkage maps are critical for draft genome assembly, quantitative trait loci (QTLs) analysis, and gene mining. The lack of a high-density genetic linkage map has limited both genomic studies and selective breeding in grasspea. Here, we developed a high-density genetic linkage map of grasspea using genotyping-by-sequencing (GBS) to sequence 154 grasspea plants, comprising 2 parents and 152 F2 progeny. In all, 307.74 Gb of data was produced, including 2,108,910,938 paired-end reads, as well as 3536 SNPs mapped to seven linkage groups (LG1–LG7). With an average length of 996.52 cM per LG, the overall genetic distance was 6975.68 cM. Both the χ2 test and QTL analysis, based on the Kruskal–Wallis (KW) test and interval mapping (IM) analysis, revealed the monogenic inheritance of flower color in grasspea, with the responsible QTL located between 308.437 cM and 311.346 cM in LG4. The results can aid grasspea genome assembly and accelerate the selective breeding of new grasspea germplasm resources.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options and high mortality. The oxytocin receptor (OTR) is a class-A G protein-coupled receptor that has been linked to breast cancer, but its role in tumorigenesis and disease progression remains underexplored. OTR expression is highest in tumour-adjacent breast tissue, followed by normal and tumour tissue, indicating a potential role in the tumour microenvironment. OTR levels were higher in migrated MDA-MB-231 cells than in the control parental cells cultured in normal medium; OTR overexpression/knock-down and metastasis biomarker experiments revealed that high OTR expression enhanced metastasis capabilities. These findings align well with data from a murine breast cancer metastasis model, where metastasised tumours had higher OTR expression than the corresponding primary tumours, and high OTR expression also correlates to reduced survival in TNBC patients. OTR agonists/antagonists did not affect MDA-MB-231 cell migration, and pharmacological analysis revealed that the OT/OTR signalling was compromised. High OTR expression enhanced cell migration in an OTR ligand-independent manner, with the underlying mechanism linked to the EGF-mediated ERK1/2-RSK-rpS6 pathway. Taken together, high OTR expression seems to be involved in TNBC metastasis via increasing cell sensitivity to EGF. These results support a potential prognostic biomarker role of OTR and provide new mechanistic insights and opportunities for targeted treatment options for TNBC.

Drought causes a major constraint on plant growth, development, and crop productivity. Drought stress enhances the synthesis and mobilization of the phytohormone abscisic acid (ABA). Enhanced cellular levels of ABA promote the production of reactive oxygen species (ROS), which in turn induce anion channel activity in guard cells that consequently leads to stomatal closure. Although Cyclophilins (CYPs) are known to participate in the biotic stress response, their involvement in guard cell ABA signaling and the drought response remains to be established. The Arabidopsis thaliana gene ROC3 encodes a CYP. Arabidopsis roc3 T-DNA mutants showed a reduced level of ABA-activated S-type anion currents, and stomatal closure than wild type (WT). Also, roc3 mutants exhibited rapid loss of water in leaf than wild type. Two complementation lines of roc3 mutants showed similar stomatal response to ABA as observed for WT. Both complementation lines also showed similar water loss as WT by leaf detached assay. Biochemical assay suggested that ROC3 positively regulates ROS accumulation by inhibiting catalase activity. In response to ABA treatment or drought stress, roc3 mutant show down regulation of a number of stress responsive genes. All findings indicate that ROC3 positively regulates ABA-induced stomatal closure and the drought response by regulating ROS homeostasis and the expression of various stress-activated genes.

Gastric cancer is considered to be one of the most common causes of cancer death worldwide due to its high recurrence and metastasis rates. The molecule 23,24-Dihydrocucurbitacin E (DHCE) is a cucurbitacin-derived tetracyclic triterpenoid compound that has anti-tumor activity, but the exact mechanism remains to be elucidated. This research aimed to explore the effects of DHCE on human gastric cancer cells and the possible mechanisms. The results showed that DHCE suppressed proliferation, migration, and invasion of gastric cancer cells, as well as induced apoptosis and G2/M phase arrest. Mechanistically, the potential targets and pathways of DHCE were predicted using database screening and verified using a molecular docking study, fluorescence staining, and Western blot. The results indicated that DHCE obviously inhibited the kinase activity of ERK2 via targeting its ATP-binding domain, destroyed F-actin microfilament, and reduced the expression levels of Ras, p-c-Raf, ERK, p-ERK, and MMP9 proteins. Collectively, our study demonstrated that DHCE suppressed gastric cancer cells’ proliferation, migration, and invasion through targeting ERK2 and disrupting the Ras/Raf/ERK/MMP9 signaling pathway. These properties make DHCE a promising candidate drug for the further design and development of novel and effective Ras/Raf/ERK/MMP9 pathway inhibitors for treating gastric cancer.

This study explored the preliminary structural characteristics and in vivo anti-tumor activity of an acidic water-soluble polysaccharide (BCP) separated purified from Bupleurum chinense DC root. The preliminary structural characterization of BCP was established using UV, HPGPC, FT-IR, IC, NMR, SEM, and Congo red. The results showed BCP as an acidic polysaccharide with an average molecular weight of 2.01 × 103 kDa. Furthermore, we showed that BCP consists of rhamnose, arabinose, galactose, glucose, and galacturonic acid (with a molar ratio of 0.063:0.788:0.841:1:0.196) in both α- and β-type configurations. Using the H22 tumor-bearing mouse model, we assessed the anti-tumor activity of BCP in vivo. The results revealed the inhibitory effects of BCP on H22 tumor growth and the protective actions against tissue damage of thymus and spleen in mice. In addition, the JC-1 FITC-AnnexinV/PI staining and cell cycle analysis have collectively shown that BCP is sufficient to induce apoptosis and of H22 hepatocarcinoma cells in a dose-dependent manner. The inhibitory effect of BCP on tumor growth was likely attributable to the S phase arrest. Overall, our study presented significant anti-liver cancer profiles of BCP and its promising therapeutic potential as a safe and effective anti-tumor natural agent.

Radiation-induced defects are responsible for solar cell degradation. The effects of radiation and annealing on the defects of a GaAs/Ge solar cell are modeled and analyzed in this paper. The electrical performance and spectral response of solar cells irradiated with 150 keV proton are examined. Then, thermal annealing was carried out at 120°C. We found that the proportion of defect recovery after annealing decreases with increasing irradiation fluence. The minority carrier lifetime increases with decreasing defect concentration, which means that the electrical performance of the solar cell is improved. We calculated the defect concentration and minority carrier lifetime with numerical simulation and modeled an improved annealing kinetic equation with experimental results.

Connexin proteins are usually considered as tumor suppressors. Here, the authors show that connexin 26 (Cx26) regulates the self-renewal of breast cancer stem cells via a ternary complex with FAK and NANOG.

Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.

Obtaining the water volume of small- and medium-sized lakes in enclosed watersheds with scarce data is a global focus of research. River flow into a lake is an important factor affecting the water volume. However, most river flow measurement methods involve long cycles, low efficiency, and transdisciplinary expertise, making rapid assessments in ungauged basins impossible. This paper proposes a remote sensing flow estimation method based on multi-source remote sensing data, which quickly assesses river flow and provides important input data for lake water volume simulation. The cross-section flow was estimated by extracting the river width. The calculated results were consistent with the measured data, with accuracy greater than 90%. The results compared with daily data measured at hydrological stations, and the Nash coefficient was greater than 0.9. Additionally, the simulation method for lake area, water volume, and water level was constructed using river inflow input data, greatly reducing the parameters required by the conventional lake water volume simulation method. Based on the remote sensing discharge estimation method, we quickly and conveniently obtained changes in river flow into the lake, simulated lake water volume, and provided the basis for water resource management in terminal lake basins with scarce data.

This paper presents a new perspective of national power—sustainable national power (SNP)—emphasizing both the traditional comprehensive national power (CNP) and social and environmental sustainability. We propose a measurement to quantify the SNP based on the measurement of comprehensive national power and a sustainable adjusted index. In addition, density-equalizing maps are adopted to visualize the sustainable national power of countries in order to gain a better understanding for its current state and future development from a cartographic perspective. China and its neighboring countries are selected as a case study area. The results show that China outperforms other countries in most of the CNP dimensions but performs poorly in various SNP-adjusted dimensions within the study area. The composite score shows that China is with the highest regional SNP, followed by Japan, Russia, South Korea and India. Furthermore, time series of cartograms reveal evidence showing power transitions among countries. In addition, the effectiveness of cartograms for cartographic communication is discussed.