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Despite more effective chemotherapy combined with limb-salvage surgery for the osteosarcoma treatment, survival rates for osteosarcoma patients have stagnated over the past three decades due to the poor prognosis. Osteosarcoma cancer stem cells (OSCs) are responsible for the growth and metastasis of osteosarcoma. The existence of OSCs offers a theoretical explanation for therapeutic failures including tumor recurrence, metastasis, and drug resistance. Understanding the pathways that regulate properties of OSCs may shed light on mechanisms that lead to osteosarcoma and suggest better modes of treatment. In this study, we showed that the expression level of Kruppel-like factor 4 (KLF4) is highly associated with human osteosarcoma cancer stemness. KLF4-overexpressed osteosarcoma cells displayed characteristics of OSCs: increased sphere-forming potential, enhanced levels of stemness-associated genes, great chemoresistance to adriamycin and CDDP, as well as more metastasis potential. Inversely, KLF4 knockdown could reduce colony formation in vitro and inhibit tumorigenesis in vivo, supporting an oncogenic role for KLF4 in osteosarcoma pathogenesis. Furthermore, KLF4 was shown to activate the p38 MAPK signaling pathway to promote cancer stemness. Altogether, our studies uncover an essential role for KLF4 in regulation of OSCs and identify KLF4–p38 MAPK axis as a potential therapeutic target for osteosarcoma treatment.

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2.

Abiotic stresses are various environmental factors that inhibit a normal plant growth and limit the crop productivity. Plant scientists have been attempting for a long time to understand how plants respond to these stresses and find an effective and feasible solution in mitigating their adverse impacts. Exogenous calcium ion as an essential element for the plant growth, development and reproduction has proven to be effective in alleviating plant stresses through enhancing its resistance or tolerance against them. With a comprehensive review of most recent advances and the analysis by VOSviewer in the researches on this focus of “exogenous calcium” and “stress” for last decade, this paper summarizes the mechanisms of exogenous calcium that are involved in plant defensive responses to abiotic stresses and classifies them accordingly into six categories: I) stabilization of cell walls and membranes; II) regulation of Na + and K + ratios; III) regulation of hormone levels in plants; IV) maintenance of photosynthesis; V) regulation of plant respiratory metabolism and improvement of root activities; and VI) induction of gene expressions and protein transcriptions for the stress resistance. Also, the progress and advances from the updated researches on exogenous calcium to alleviate seven abiotic stresses such as drought, flooding, salinity, high temperature, low temperature, heavy metals, and acid rain are outlined. Finally, the future research perspectives in agricultural production are discussed.

Sinocrassula cuonaensis , a new species of Crassulaceae from southern Xizang, is described and illustrated based on molecular and morphological evidence. Phylogenetically, it is sister to S. densirosulata with robust support. Morphologically, this new species is similar to S. indica var. viridiflava, S. densirosulata , and S. jiaozishanensis in having glabrous indumentum and long inflorescences, but it can be easily distinguished by its rosulate, thick, and near-cylindrical basal leaves, greenish white flowers, and sub-rectangular nectar scales. A key for identification of the genus, including the new species, is provided.

Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.

Biochar is a promising soil amendment, but its long-term consecutive effects on greenhouse tomato systems are insufficiently explored. To investigate the dynamic and accumulative effects of consecutive biochar application on soil chemical properties and tomato ( Solanum lycopersicum L.) yield and quality, a three-year arched shed field experiment was conducted with five biochar rates: 0 (CK), 0.5 (T1), 1.0 (T2), 2.0 (T3), and 4.0 (T4) kg·m - ². Soil chemical properties, tomato growth, yield components, and fruit quality were analyzed. Results showed biochar slightly increased soil electrical conductivity (all below salinization threshold); only T4 significantly raised soil pH (by 0.4 units) and organic matter (by 132.8%) vs . CK. Annual differences in soil available potassium diminished to non-significance, while available phosphorus was 50.8% (T2) and 63.0% (T3) higher than CK. Tomato plant height and dry matter increased with biochar rate; T1-T4 improved fruits per plant (2.0%-17.0%) and single fruit weight (7.0%-16.0%) over CK, with T2 (13.7%-24.1%) and T3 (19.8%-33.2%) achieving the highest significant yield increases. For quality, T2 had the highest comprehensive index, followed by T1 and T3, with their three-year average scores up by 33.1%, 15.4%, and 15.4% respectively. In conclusion, 1.0-2.0 kg·m - ² biochar optimally enhanced tomato yield and nutritional/organoleptic quality, with no significant interannual cumulative effects of biochar rate on yield or quality—providing theoretical and technical support for high-quality greenhouse tomato production.

Pneumocystis jiroveci pneumonia (PCP) is frequently reported in lymphoma patients treated with rituximab-contained regimens. There is a trend toward a difference in PCP risk between bi- and tri-weekly regimens. The aims of this systemic review and meta-analysis were to estimate the risk for PCP in these patients, compare the impact of different regimens on the risk, and evaluate the efficacy of prophylaxis. The cohort studies with incept up to January 2014 were retrieved from the Cochrane Library, Medline, Embase, and Web of Science databases. Studies that compared the incidence of PCP in patients with and without rituximab treatment were conducted. Studies that reported the results of prophylaxis were concentrated to evaluate the efficacy of prophylaxis. Fixed effect Mantel-Haenszel model was chosen as the main analysis method. Funnel plots were examined to estimate the potential selection bias. Egger's test and Begg's test were used for the determination of possible small study bias. Eleven cohort studies that met the inclusion criteria were finally included. Results indicated that rituximab was associated with a significantly increased risk for PCP (28/942 vs 5/977; risk ratio: 3.65; 95% confidence interval 1.65 to 8.07; P=0.001), and no heterogeneity existed between different studies (I2=0%). Little significant difference in PCP risk was found between bi-weekly and tri-weekly regimens (risk ratio: 3.11; 95% confidence interval 0.92 to 10.52, P=0.068). PCP risk was inversely associated with prophylaxis in patients treated with rituximab (0/222 vs 26/986; risk ratio: 0.28; 95% confidence interval 0.09 to 0.94; P=0.039). In conclusion, PCP risk was increased significantly in lymphoma patients subjected to rituximab-contained chemotherapies. Difference in PCP risk between bi-weekly and tri-weekly regimens was not significant. Additionally, prophylaxis was dramatically effective in preventing PCP in rituximab-received lymphoma patients, suggesting that rituximab should be recommended for these patients.

Isoxazoline structures are widely found in natural products and are rich in biological activities. This study discloses the development of a series of novel isoxazoline derivatives by introducing acylthiourea fragments to access insecticidal activity. All synthetic compounds were examined for their insecticidal activity against Plutella xylostella, with results showing moderate to strong activity. Based on this, the structure–activity relationship analysis was carried out via the constructed three-dimensional quantitative structure–activity relationship model to further guide the structure optimization, resulting in the optimal compound 32. The LC50 of compound 32 against Plutella xylostella was 0.26 mg/L, demonstrating better activity than the positive control, ethiprole (LC50 = 3.81 mg/L), avermectin (LC50 = 12.32 mg/L), and compounds 1–31. The insect GABA enzyme-linked immunosorbent assay demonstrated that compound 32 might act on the insect GABA receptor, and the molecular docking assay further illustrated the mode of action of compound 32 with the GABA receptor. In addition, the proteomics analysis indicated that the action of compound 32 on Plutella xylostella was multi-pathway.

Anredera cordifolia, a climber and member of the Basellaceae family, has long been a traditional medicine used for the treatment of hyperglycemia in China. Two water-soluble polysaccharides, ACP1-1 and ACP2-1, were isolated from A. cordifolia seeds by hot water extraction. The two fractions, ACP1-1 and ACP2-1 with molecular weights of 46.78 kDa ± 0.03 and 586.8 kDa ± 0.05, respectively, were purified by chromatography. ACP1-1 contained mannose, glucose, galactose in a molar ratio of 1.08:4.65:1.75, whereas ACP2-1 contained arabinose, ribose, galactose, glucose, mannose in a molar ratio of 0.9:0.4:0.5:1.2:0.9. Based on methylation analysis, ultraviolet and Fourier transform-infrared spectroscopy, and periodate oxidation the main backbone chain of ACP1-1 contained (1→3,6)-galacturonopyranosyl residues interspersed with (1→4)-residues and (1→3)-mannopyranosyl residues. The main backbone chain of ACP2-1 contained (1→3)-galacturonopyranosyl residues interspersed with (1→4)-glucopyranosyl residues.

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords “NLRP3” and “extracellular vesicles” appeared most frequently. Besides, researches on COVID-19–induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19–induced ALI and may be a target for the treatment of COVID-19.