Prognostic Impact of Serum Homocysteine-Lowering Therapy on Patients with Hemorrhagic Stroke and Its Influence on National Institutes of Health Stroke Scale and China Stroke Scale Scores.

Objective: This study aimed to investigate the prognostic impact of serum homocysteine-lowering therapy on patients with hemorrhagic stroke (HS) and its influence on their National Institutes of Health Stroke Scale (NIHSS) and China Stroke Scale (CSS) scores. Methods: A double-blind study involving 120 patients with HS and hyperhomocysteinemia (Hhcy) who were admitted to our hospital was conducted in 2021. They were evenly divided into two groups: the control group (n=60) received low-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy, while the study group (n=60) received high-dose folic acid, methylcobalamin, and vitamin B6. The prognosis of each group was compared using the NIHSS and CSS to assess the neurological function of the patients. Results: Before treatment, the levels of oxidative stress markers and vascular endothelial function markers were comparable between the two groups (t = 0.051, 0.015, 0.010, 0.011, 0.013, 0.022, P = .960, .988, .992, 0.991, .989, 0.982). However, after treatment, the study group exhibited higher levels of MDA and ET-1 compared to the control group (t = 3.418, 1.978, P < .001). Additionally, SOD, GSH-Px, and PON1 levels were lower in the study group (t = 3.435, 3.783, 2.735, 3.893, P < .001). The NIHSS scores before treatment were comparable among patients (t = 0.058, P = 0.954), but after treatment, the study group showed significantly lower NIHSS scores (t = 20.105, P < .001). Similarly, the CSS scores before treatment were comparable (t = 0.046, P = .963), but the CSS scores in the study group after treatment were significantly lower (t = 5.027, P < .001). Conclusions: High-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy can improve oxidative stress and vascular endothelial function in HS patients. This treatment also enhances prognosis and ameliorates neurological deficits. Therefore, it holds significant clinical potential and should be considered for broader adoption.

Microbial mechanism of enhancing methane production from anaerobic digestion of food waste via phase separation and pH control.

Phase separation and pH control are commonly used to improve methane production during anaerobic digestion (AD) of food waste, but their influencing mechanisms have not been fully discovered through microbial analysis. In this study, single-phase AD (SPAD), two-phase AD without pH control (TPAD-pHUC), and TPAD with fermentation pH controlled at 6.0 and 4.5 were conducted. The results showed that phase separation decreased the ratio of total bacteria to total archaea in the methanogenic phase. At the organic loading rate (OLR) of 1.9 g/(L·d), methanogenesis was dominated by acetoclastic Methanosaeta in both SPAD and TPAD-pHUC, while elevated Methanoculleus and active hydrogen production initiated a shift from the acetoclastic to hydrogenotrophic pathway in SPAD as OLR increased, eventually resulting in excessive acidification at OLR 3.2 g/(L·d). TPAD-pHUC was dominated by Methanosaeta with scarce hydrogen production genes, and thus maintained a delicate balance between fewer acidogens and methanogens at OLR 3.2-3.7 g/(L·d). TPAD with pH control exhibited higher methane yield (460-482 ml/g) at OLR 1.9 g/(L·d) due to the enhancement of protein degradation and the conversion from methylated compounds to methane by Methanosarcina. High Na+ concentration facilitated the proliferation of hydrogen production bacteria, but inhibited acetoclastic methanogenesis at OLR 2.4 g/(L·d). In comparison with SPAD and pH control, TPAD without pH control, integrating 4 d acidogenesis and 22 d methanogenesis, exhibited the best and steady performance at OLR 3.7 g/(L·d) with methane production exceeding 370 ml/g.

An injectable bone paste of poly (lactic acid)/zinc-doped nano hydroxyapatite composite microspheres for skull repair.

In this study, poly (lactic acid)/zinc-doped nano hydroxyapatite (PLA/nano-ZnHA) composite microspheres were prepared and formed into injectable bone paste with sodium alginate (SA) and polyvinyl alcohol (PVA) for bone defect repair. The effect of component of bone paste on injectability and zinc doping content related biological properties were mainly discussed. An injectable bone paste of PLA/nano-ZnHA composite microspheres (CM) was formed in mass ratio of (2.5-25):(0.25-4): (0-2.5):(20-65) of CM, SA, PVA and water with the favorable injectability (average force:4.46±1.72 N). In vitro 5%-10% zinc doping content displayed significantly higher promotion on cell proliferation and osteogenic differentiation than 15%-20% zinc doping content. Furthermore, in vivo the significant promoting effect of 0-5% zinc doping in ZnHA on bone repair was observed. Although 5% zinc doping content did not show a significant enhancement in bone volume/tissue volume (BV/TV), it has the ability to improve the bone mineral density (BMD) in early stage of bone repair compared with the 0% zinc doping content. The PLA/nano-ZnHA composite microsphere injectable paste with convenient surgical operation and well filling ability has the potential to become a competitive tissue repair material.

Circular RNA circTIE1 drives proliferation, migration, and invasion of glioma cells through regulating miR-1286/TEAD1 axis.

Recent studies have verified that circRNAs (circular RNAs) play a critical role in glioma occurrence and malignant progression. However, numerous circRNAs with unknown functions remain to be explored with further research. qPCR (quantitative real-time polymerase chain reaction) was employed to detect circTIE1 expression in glioma tissues, NHAs (normal human astrocytes), and glioma cellular lines (U87, U118, U251, T98G, LN229). Cell viability was evaluated by CCK-8 assay. Cellular proliferation was evaluated by a 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay. Cell migration and aggression were both evaluated by transwell and migration assays. The direct binding and regulation among circTIE1, miR-1286 and TEAD1 was identified by western blotting, qPCR, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Xenografts were generated by injecting glioma cells orthotopically into the brains of nude mice. Immunohistochemistry staining was implemented to evaluate the expression of the proliferation markers ki67 and TEAD1. We found that circTIE1 (circBase ID: hsa_circ_0012012) was upregulated in glioma tissues and glioma cellular lines in contrast to NBT (normal brain tissues) and NHA. CircTIE1 knockdown inhibited glioma cell viability, proliferation, migration and aggression both in vitro and in vivo. Mechanistically, circTIE1 could upregulate TEAD1 expression via miR-1286 sponging, and TEAD1 is a well-known functional gene that could promote malignant advancement in glioma. This research found a novel circRNA, circTIE1, which is an essential marker of glioma progression and diagnosis and may be anticipated to become a crucial target for molecular targeted therapy of glioma.

Surface microtopography construction and osteogenic properties evaluation of bulk polylactic acid implants.

In this study, polylactic acid (PLA) microspheres were used as the raw material to construct bulk implants with surface microtopography through hot pressing and heat treatment, and the microtopographical structures were regulated through the sizes of the PLA microspheres. The surface microtopographies of PLA implants were successfully constructed using micron-sized bulges, which showed a wave-like structure. The ridge width of bulges ranged from 1.64 ± 0.16 µm to 82.52 ± 14.38 µm and the valley depth ranged from 0.49 ± 0.07 µm to 37.35 ± 6.78 µm according to the sizes of microspheres. The nanoindentation tests showed that the modulus and hardness of PLA implants were gradually increased with the decrease in microsphere sizes. The surface microtopography resulted in a slight increase in the hydrophobicity of the PLA implants, but no significant differences were observed. Cells cultured on the implant surface with microtopography exhibited varying morphological responses, and significantly increased osteogenic activity was observed relative to a PLA flat film. This study demonstrated that the surface microtopography derived from PLA microspheres could regulate cellular response and activate osteogenic properties of PLA implants.

EIF4A3 induced circGRIK2 promotes the malignancy of glioma by regulating the miR-1303/HOXA10 axis.

In recent years, the role of circular RNAs (circRNAs) in glioma has become increasingly important. However, there are still many newly discovered circRNAs with unknown functions that require further study. In this study, circRNA sequencing, qPCR, MTS, EdU, Transwell, and other assays were conducted to detect the expression and malignant effects of a novel circRNA molecule, circGRIK2, in glioma. qPCR, western blotting, RIP, and luciferase reporter gene experiments were used to investigate the downstream molecular mechanisms of circGRIK2. Our study found that circGRIK2 was highly expressed in glioma and promoted glioma cell viability, proliferation, invasion, and migration. Mechanistically, circGRIK2 acted as a competitive sponge for miR-1303, upregulating the expression of HOXA10 to exert its oncogenic effects. Additionally, the RNA-binding protein EIF4A3 could bind to and stabilize circGRIK2, leading to its high expression in glioblastoma. The discovery of circGRIK2 in this study not only contributes to a better understanding of the biological mechanisms of circGRIK2 in glioma but also provides a new target for molecular targeted therapy.

WinRoots: A High-Throughput Cultivation and Phenotyping System for Plant Phenomics Studies Under Soil Stress.

Soil stress, such as salinity, is a primary cause of global crop yield reduction. Existing crop phenotyping platforms cannot fully meet the specific needs of phenomics studies of plant response to soil stress in terms of throughput, environmental controllability, or root phenotypic acquisition. Here, we report the WinRoots, a low-cost and high-throughput plant soil cultivation and phenotyping system that can provide uniform, controlled soil stress conditions and accurately quantify the whole-plant phenome, including roots. Using soybean seedlings exposed to salt stress as an example, we demonstrate the uniformity and controllability of the soil environment in this system. A high-throughput multiple-phenotypic assay among 178 soybean cultivars reveals that the cotyledon character can serve as a non-destructive indicator of the whole-seedling salt tolerance. Our results demonstrate that WinRoots is an effective tool for high-throughput plant cultivation and soil stress phenomics studies.

Stimulating methane production from microalgae by alkaline pretreatment and co-digestion with sludge.

Methane production through anaerobic digestion (AD) is a solution of energy recovery from microalgae, but some features of microalgae limit the efficiency of AD. In this study, alkaline pretreatment and co-digestion with sludge were both applied to enhance the methane production from microalgae in batch experiments. The results showed that alkaline pretreatment increased the disintegration degree of microalgae from 20% to 34% at maximum after 12-h treatment, but the specific methane production (SMP) only increased from 279 to 298 ml/g volatile solids (VS). Co-digestion with sludge stimulated methane production, and the best synergy with an SMP of 343 ml/g VS occurred when the ratio of microalgae to sludge reached 2:1 based on their VS. The yield was 12.4% and 20.0% higher than those from mono digestion of microalgae and sludge, respectively, and the synergy was evaluated at 14.8%. Therefore, co-digestion is a better choice for improving methane production from microalgae.

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition.

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic activity. Further studies showed that 11e suppressed tumour growth in human breast cancer (MCF-7) xenograft models without obvious side effects. Evaluation of the mechanism revealed that 11e targeted the epithelial to mesenchymal transition (EMT) process in MCF-7 cells and inhibited HUVEC migration and then contributed to hindrance of angiogenesis. Thus, 11e may be a promising antitumour agent with excellent efficacy and low toxicity.

CD300A inhibits tumor cell growth by downregulating AKT phosphorylation in human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a primary malignant tumor of the central nervous system with the highest incidence and dismal prognosis. As a member of the CD300 glycoprotein family, CD300A plays a role in cell proliferation, apoptosis, differentiation, and immune response, but its role in solid tumors remains unknown. In this study, CD300A was observed to be overexpressed in human GBM samples using real-time PCR and western blotting. To investigate the role of CD300A in GBM, CCK8, transwell and flow cytometry analysis were performed to examine the proliferation, migration and apoptosis in GBM cell lines, respectively. From our results, knockdown of CD300A blocks cell proliferation and migration, and induces cell apoptosis in human GBM cells U251MG and U87MG. Further, we assessed AKT expression level in CD300A knockdown and negative control cells. The phosphorylation level of AKT was significantly suppressed in CD300A knockdown cells in comparison to negative control cells, suggesting that CD300A promoted tumor cell growth through the AKT pathway. In conclusion, our findings expand the knowledge of CD300A as an oncogene in solid tumor, and provide experimental and theoretical basis for further clinical application.

Neuroprotection of desferrioxamine in lipopolysaccharide-induced nigrostriatal dopamine neuron degeneration.

Inflammation and iron accumulation in the substantia nigra (SN) are implicated in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron mismanagement remain largely unknown. In the present study, an animal model induced by lipopolysaccharide (LPS) was used to evaluate iron concentration in the ventral midbrain with or without neuroinflammation. Furthermore, the iron chelator desferrioxamine (DFO) was used to explore its neuroprotective property against LPS-induced nigrostriatal degeneration. Adult C57BL/6 mice were treated with DFO (2.5 µg) commenced 3 days prior to or following microinjection of LPS into the striatum. Animal behavioral tests, as well as pathological and biochemical assays were performed to evaluate the nigrostriatal dopamine neuron degeneration and neuroprotective effects of DFO. Here, we report that the iron concentration in the ventral midbrain significantly increased following intrastriatal injection of LPS, and administration of DFO improved behavior deficits, attenuated dopamine (DA) neuron loss and striatal DA reduction, and alleviated microglial activation in the SN. These results suggest that DFO may possess neuroprotective effect against LPS-induced nigrostriatal dopamine neuron degeneration.