Allicin affects immunoreactivity of osteosarcoma cells through lncRNA CBR3-AS1.

Objective: To analyze the effect of allicin on the immunoreactivity of osteosarcoma (OS) cells and further explore whether its mechanism is related to the long non-coding Ribonucleic Acid (lncRNA) CBR3-AS1/miR-145-5p/GRP78 axis, so as to provide clinical evidence. Methods: The human OS cell line Saos-2 was treated with allicin at 25, 50, and 100 µmol/L, respectively, to observe changes in cell biological behaviors. Subsequently, CBR3-AS1 abnormal expression vectors were constructed and transfected into Saos-2 to discuss their influence on OS. Furthermore, the regulatory relationship between allicin and the CBR3-AS1/miR-145-5p/GRP78 axis was validated by rescue experiments. Finally, a nude mice tumorigenesis experiment was carried out to analyze the effects of allicin and CBR3-AS1/miR-145-5p/GRP78 axis on the growth of living tumors. Alterations in T-lymphocyte subsets were also detected to assess the effect of allicin on OS immunoreactivity. Results: With the increase of allicin concentration, Saos-2 activity decreased and apoptosis increased (P < 0.05). In addition, the expression of CBR3-AS1 and GRP78 decreased after allicin intervention, while miR-145-5p increased (P < 0.05). Silencing CBR3-AS1 led to reduced Saos-2 activity, enhanced apoptosis, and activated mitophagy and endoplasmic reticulum stress (P < 0.05). In the rescue experiment, the effect of CBR3-AS1 on OS cells was reversed by silencing miR-145-5p, while the impact of miR-145-5p was reversed by GRP78. Finally, the tumorigenesis experiment in nude mice confirmed the regulatory effects of allicin and CBR3-AS1/miR-145-5p/GRP78 on tumor growth in vivo. Meanwhile, it was seen that allicin activated CD4+CD8+ in OS mice, confirming that allicin has the effect of activating OS immunoreactivity. Conclusions: Allicin activates OS immunoreactivity and induces apoptosis through the CBR3-AS1/miR-145-5p/GRP78 molecular axis.

Glycnsisitin A: A promising bicyclic peptide against heart failure that facilitates TFRC-mediated uptake of iron in cardiomyocytes.

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A-C (1-3), with distinctive C-C and C-O-C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori.

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

Polyvinyl chloride and polybutylene adipate microplastics affect peanut and rhizobium symbiosis by interfering with multiple metabolic pathways.

Microplastics (MPs), widely presented in cultivated soil, have caused serious stresses on crop growth. However, the mechanism by which MPs affect legumes and rhizobia symbiosis is still unclear. Here, peanut seedlings were inoculated with Bradyrhizobium zhanjiangense CCBAU 51778 and were grown in vermiculite with 3 %/5 % (w/w) addition of PVC (polyvinyl chloride)-MPs/PBAT (polybutylene adipate)-MPs. PVC-MPs and PBAT-MPs separately decreased nodule number by 33-100 % and 2.62-80.91 %. Transcriptome analysis showed that PVC-MPs affected more DEGs (differentially expressed genes) than PBAT-MPs, indicating PVC-MPs were more devastating for the symbiosis than PBAT-MPs. Functional annotation revealed that PVC-MPs and PBAT-MPs enriched DEGs related to biosynthesis pathways such as flavonoid, isoflavonoid, and phenylpropanoid, in peanut. And when the dose increased from 3 % to 5 %, PVC-MPs mainly enriched the pathways of starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, diterpenoid biosynthesis, etc.; PBAT-MPs enriched cysteine and methionine metabolism, photosynthesis, MAPK signaling, and other pathways. These significantly enriched pathways functioned in reducing nodule number and promoting peanut tolerance to MPs stresses. This study reveals the effect of PVC-MPs and PBAT-MPs on peanut and rhizobium symbiosis, and provides new perspectives for legume production and environmental safety.

A photothermal assisted zinc-air battery cathode based on pyroelectric and photocatalytic effect.

Zinc-air battery as one of the new generations of battery system, its theoretical specific energy is as high as 1086 Wh kg-1, specific capacity up to 820 mAh/g, and zinc has the advantages of environmental friendliness, resource abundance, low cost and good safety, so it has attracted much attention. However, due to its slow reaction kinetic process, zinc-air battery will produce a large charging overpotential usually up to 2 V, it is far beyond the theoretical voltage of 1.65 V, so reducing the overpotential of zinc-air batteries is extremely necessary, and the most common way to solve this problem is to use excellent catalyst cathode to improve the oxygen reduction and oxygen evolution kinetics of zinc-air batteries. So we developed a new photothermal assisted zinc-air battery system with Hollow carbon nanosphere@poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene)@CdS(HCN@PVTC@CdS) photocathode, the pyroelectric and photocatalysis effect can effectively promote the reaction kinetics and reduce the reaction overpotential. With the pyroelectric and photocatalysis synergistic effect, the zinc-air has displayed a high discharge potential of 1.33 V and a low charging potential of 1.5 V with good cycle stability. This multi-assist technology with built-in electric and light fields paves the way for the development of high-performance zinc-air batteries and other energy storage systems.

Whole-cycle management of women with epilepsy of child-bearing age: ontology construction and application.

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.

Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.

Mitigation of electromagnetic pulses interfering with Thomson parabola ion spectrometers at XG-III laser facility.

The Thomson parabola ion spectrometer is vulnerable to intense electromagnetic pulses (EMPs) generated by a high-power laser interacting with solid targets. A metal shielding cage with a circular aperture of 1 mm diameter is designed to mitigate EMPs induced by a picosecond laser irradiating a copper target in an experiment where additionally an 8-ns delayed nanosecond laser is incident into an aluminum target at the XG-III laser facility. The implementation of the shielding cage reduces the maximum EMP amplitude inside the cage to 5.2 kV/m, and the simulation results indicate that the cage effectively shields electromagnetic waves. However, the laser-accelerated relativistic electrons which escaped the target potential accumulate charge on the surface of the cage, which is responsible for the detected EMPs within the cage. To further alleviate EMPs, a lead wall and an absorbing material (ECCOSORB AN-94) were added before the cage, significantly blocking the propagation of electrons. These findings provide valuable insights into EMP generation in large-scale laser infrastructures and serve as a foundation for electromagnetic shielding design.

Upconversion 3D Bioprinting for Noninvasive In Vivo Molding.

Tissue engineered bracket materials provide essential support for the physiological protection and therapeutics of patients. Unfortunately, the implantation process of such devices poses the risk of surgical complications and infection. In this study, an upconversion nanoparticles (UCNPs)-assisted 3D bioprinting approach is developed to realize in vivo molding that is free from invasive surgery. Reasonably designed UCNPs, which convert near-infrared (NIR) photons that penetrate skin tissues into blue-violet emission (300-500 nm), induce a monomer polymerization curing procedure in vivo. Using a fused deposition modeling coordination framework, a precisely predetermined trajectory of the NIR laser enables the manufacture of implantable medical devices with tailored shapes. A proof of the 3D bioprinting of a noninvasive fracture fixation scaffold is achieved successfully, thus demonstrating an entirely new method of in vivo molding for biomedical treatment.

IKBKE promotes the ZEB2-mediated EMT process by phosphorylating HMGA1a in glioblastoma.

IKBKE (Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Epsilon) is an important oncogenic protein in a variety of tumors, which can promote tumor growth, proliferation, invasion and drug resistance, and plays a critical regulatory role in the occurrence and progression of malignant tumors. HMGA1a (High Mobility Group AT-hook 1a) functions as a cofactor for proper transcriptional regulation and is highly expressed in multiple types of tumors. ZEB2 (Zinc finger E-box Binding homeobox 2) exerts active functions in epithelial mesenchymal transformation (EMT). In our current study, we confirmed that IKBKE can increase the proliferation, invasion and migration of glioblastoma cells. We then found that IKBKE can phosphorylate HMGA1a at Ser 36 and/or Ser 44 sites and inhibit the degradation process of HMGA1a, and regulate the nuclear translocation of HMGA1a. Crucially, we observed that HMGA1a can regulate ZEB2 gene expression by interacting with ZEB2 promoter region. Hence, HMGA1a was found to promote the ZEB2-related metastasis. Consequently, we demonstrated that IKBKE can exert its oncogenic functions via the IKBKE/HMGA1a/ZEB2 signalling axis, and IKBKE may be a prominent biomarker for the treatment of glioblastoma in the future.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Application of intraarterial superselective indocyanine green angiography in bypass surgery for adult moyamoya disease.

Background: Extracranial-intracranial (EC-IC) bypass surgery is the main treatment approach to moyamoya disease, and an accurate assessment of the patency of anastomosis is critical for successful surgery. So far, the most common way to do this is the intraoperative intravenous indocyanine green (ICG) video-angiography. Intra-arterial ICG-VA has been applied to treat peripheral cerebral aneurysms, spinal arteriovenous fistulas, and dural arteriovenous fistulas, but few reports have concerned the use of arterial injection of ICG to evaluate anastomotic patency. This research aims to explore the feasibility and effects of catheter-guided superficial temporal artery injection of ICG in the evaluation of anastomotic patency after bypass surgery. Methods: In this study, 20 patients with moyamoya disease or syndrome who underwent bypass surgery were divided into two groups, one who received intravenous ICG angiography and the other who received intra-arterial ICG angiography, to compare the two injection methods for vascular anastomosis patency. We conducted conventional intraoperative digital subtraction angiography (DSA) in a hybrid operating room during extracranial-intracranial (EC-IC) bypass surgery, including the additional step of injecting ICG into the main trunk of the superficial temporal artery (STA) through a catheter. Results: Intra-arterial injection of indocyanine green video-angiography (ICG-VA) indicated good patency of the vascular anastomosis when compared with conventional digital subtraction angiography (DSA) and intravenous ICG-VA, confirming the feasibility of using the arterial injection of ICG for assessing anastomotic patency. And intra-arterial ICG-VA results in faster visualization than intravenous ICG-VA (p < 0.05). Besides, ICG-VA through arterial injection provided valuable information on the vascular blood flow direction after the bypass surgery, and allowed for visual inspection of the range of cortical brain supply from the superficial temporal artery and venous return from the cortex. Moreover, arterial injection of ICG offered a rapid dye washout effect, reducing the repeat imaging time. Conclusion: This study indicates that intra-arterial ICG-VA has good effects in observing the direction of blood flow in blood vessels and the range of cortical brain supply from the STA, which reflects blood flow near the anastomosis and provides additional information that may allow the postoperative prediction of cerebral hyperperfusion syndrome. However, the procedure of intra-arterial ICG-VA is relatively complicated compared to intravenous ICG-VA.

Comprehensive Transcriptome and Metabolome Analyses Reveal Primary Molecular Regulation Pathways Involved in Peanut under Water and Nitrogen Co-Limitation.

The yield and quality of peanut (Arachis hypogaea L.), an oil crop planted worldwide, are often limited by drought stress (DS) and nitrogen (N) deficiency. To investigate the molecular mechanism by which peanut counteracts DS and N deficiency, we conducted comprehensive transcriptomic and metabolomic analyses of peanut leaves. Herein, 829 known differentially accumulated metabolites, 324 differentially expressed transcription factors, and 5294 differentially expressed genes (DEGs) were identified under different water and N conditions. The transcriptome analysis demonstrated that drought-related DEGs were predominantly expressed in "glycolysis/gluconeogenesis" and "glycerolipid metabolism", while N-deficiency-related DEGs were mainly expressed in starch and sucrose metabolism, as well as in the biosynthesis of amino acid pathways. The biosynthesis, transport, and catabolism of secondary metabolites accounted for a large proportion of the 1317 DEGs present in water and N co-limitation. Metabolomic analysis showed that the metabolic accumulation of these pathways was significantly dependent on the stress conditions. Additionally, the roles of metabolites and genes in these pathways, such as the biosynthesis of amino acids and phenylpropanoid biosynthesis under different stress conditions, were discussed. The results demonstrated that different genes, metabolic pathways, and metabolites were related to DS and N deficiency. Thus, this study elucidates the metabolic pathways and functional genes that can be used for the improvement of peanut resistance to abiotic stress.

Effect of Reducing Nitrogen Fertilization and Adding Organic Fertilizer on Net Photosynthetic Rate, Root Nodules and Yield in Peanut.

Long-term excessive application of chemical fertilizers can cause many problems, such as soil degradation and environmental pollution. Therefore, we reduced conventional nitrogen fertilization and added organic fertilizers in some cases to investigate the response of photosynthetic characteristics, root nodules and yield on reduced nitrogen fertilization. Compared to conventional nitrogen fertilization, the 25% and 35% nitrogen reduction treatments reduced the leaf area index, net photosynthetic rate, 100-fruit weight, 100-kernel weight and the yield of peanut, but had no significant effect on the kernel rate. With constant N fertilizer, adding organic fertilization alone increased leaf area index, chlorophyll, net photosynthetic rate and yield of peanut. In compounded treatments of nitrogen and organic fertilizer, the highest yields were achieved in the 25% N reduction with the 3000 kg/hm-2 organic fertilizer treatment (T3) and the 4500 kg/hm-2 organic fertilizer treatment (T4); furthermore, the net photosynthetic rate, leaf area index, yield and fertilizer contribution were significantly higher in these two treatments than in the conventional fertilizer treatments. Nitrogen fertilizer had significant effects on the quantity and fresh weight of root nodules. Concretely, nitrogen reduction increased the quantity and fresh weight of root nodules of peanut in the early stage of fertility but decreased them in the harvest stage. Nitrogen reduction with an additional organic fertilizer in the late stage of fertility increased the quantity and fresh weight of root nodules of peanut. Considering the property of root nodules was significantly positively correlated with net photosynthetic rate and yield, the arguments above may be the mechanism of the highest yields found in T3 and T4. This work can provide empirical and instructional support for a balanced fertilization strategy in peanut agriculture and high-yielding and efficient cultivation of peanut.

Long-lasting, deep effect of Saturn's giant storms.

Planetary-scale giant storms erupt on Saturn quasiperiodically. There have been at least six recorded occurrences of past eruptions, and the most recent one was in 2010, with its whole life span captured by the Cassini mission. In 2015, we used the Very Large Array to probe the deep response of Saturn's troposphere to the giant storms. In addition to the remnant effect of the storm in 2010, we have found long-lasting signatures of all mid-latitude giant storms, a mixture of equatorial storms up to hundreds of years old, and potentially an unreported older storm at 70°N. We derive an ammonia anomaly map that shows an extended meridional migration of the storm's aftermath and vertical transport of ammonia vapor by storm dynamics. Intriguingly, the last storm in 2010 splits into two distinct components that propagate in opposite meridional directions, leaving a gap at 43°N planetographic latitude.

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy.

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.

Comparative analysis of the effects of conventional and biodegradable plastic mulching films on soil-peanut ecology and soil pollution.

In agricultural production, biodegradable plastic mulching film (Bio-PMF) has the potential to replace conventional plastic mulching film (CPMF) due to its degradability, but their impacts on soil-crop ecology are controversial. In this study, from 2019 to 2021, effects of CPMF and Bio-PMF on the soil-crop ecology and soil pollution were evaluated on a peanut farm. Compared to the Bio-PMF, an overall improvement in the soil-peanut ecology under the CPMF was observed, including an increase of 10.77 ± 4.8% in peanut yield, an amelioration of four soil physicochemical properties (total P and available P in the flowering stage, total P and temperature in the mature stage), an increase of rhizobacterial relative abundances in class level (Bacteroidia, Blastocatellia, Thermoleophilia and Vicinamibacteria in the flowering stage, Nitrospira and Bacilli in the mature stage) and genus level (RB41 and Bacillus in the flowering stage, Bacillus and Dongia in the mature stage), and an enhancement of soil nitrogen metabolism abilities (ureolysis, nitrification and aerobic ammonia in the flowering stage, nitrate reduction and nitrite ammonification in the mature stage). These preserved soil nutrients and temperature, reshaped rhizobacterial communities, and enhanced soil nitrogen metabolism abilities in the mature stage were obviously correlated with peanut yield under CPMF. However, such remarkable relations were not existed under Bio-PMF. In addition, compared with Bio-PMF, CPMF significantly increased the contents of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and microplastics (MPs) in soil by 79.93, 44.55, 138.72 and 14.1%, respectively. Thus, CPMF improved soil-peanut ecology and caused serious soil pollution, while Bio-PMF introduced little pollutants into the soil and had little impact on soil-peanut ecology. Based on these, the degradation ability of CPMF or the ecological improvement capacity of Bio-PMF should be improved to obtain the environmentally and soil-crop ecology friendly plastic film in the future.

The roles and mechanism of STIM1 in tumorigenesis and metastasis.

STIM1 (stromal interaction molecule 1) is one of the key components of the store operated Ca2+ entry channel (SOCE), which is located on the endoplasmic reticulum membrane and highly expressed in most kinds of tumors. STIM1 promotes tumorigenesis and metastasis by modulating the formation of invadopodia, promoting angiogenesis, mediating inflammatory response, altering the cytoskeleton and cell dynamics. However, the roles and mechanism of STIM1 in different tumors have not been fully elucidated. In this review, we summarize the latest progress and mechanisms of STIM1 in tumorigenesis and metastasis, thereby providing insights and references for the study on STIM1 in the field of cancer biology in the future.

Green manure increases peanut production by shaping the rhizosphere bacterial community and regulating soil metabolites under continuous peanut production systems.

BACKGROUND: Green manure (GM) is a crop commonly grown during fallow periods, which has been applied in agriculture as a strategy to regulate nutrient cycling, improve organic matter, and enhance soil microbial biodiversity, but to date, few studies have examined the effects of GM treatments on rhizosphere soil bacterial community and soil metabolites from continuous cropping peanut field. RESULTS: In this study, we found that the abundances of several functionally significant bacterial groups containing Actinobacteria, Acidobacteria, and genus Sphingomonas, which are associated with nitrogen cycling, were dramatically increased in GM-applied soils. Consistent with the bacterial community results, metabolomics analysis revealed a strong perturbation of nitrogen- or carbon-related metabolisms in GM-applied soils. The substantially up-regulated beneficial metabolites including sucrose, adenine, lysophosphatidylcholine (LPC), malic acid, and betaines in GM-applied soils may contribute to overcome continuous cropping obstacle. In contrast to peanut continuous cropping, planting winter wheat and oilseed rape in winter fallow period under continuous spring peanut production systems evidently improved the soil quality, concomitantly with raised peanut pod yield by 32.93% and 25.20%, in the 2020 season, respectively. CONCLUSIONS: GMs application is an effective strategy to overcome continuous cropping obstacle under continuous peanut production systems by improving nutrient cycling, soil metabolites, and rhizobacterial properties.

Antibacterial Activity of an FtsZ Inhibitor Celastrol and Its Synergistic Effect with Vancomycin against Enterococci In Vitro and In Vivo.

Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from Tripterygium wilfordii Hook F, against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin in vitro and in vivo. CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 µg/mL. More than 50% of biofilm was eliminated by CEL at 16 µg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with Kd and IC50 values of 2.454 µM and 1.04 ± 0.17 µg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE in vitro and in vivo and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. IMPORTANCE The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE in vitro and in vivo. Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.