Metabolic responses of HeLa cells to silica nanoparticles by NMR-based metabolomic analyses

Silica nanoparticles are increasingly used in the biomedical fields due to their excellent solubility, high stability and favorable biocompatibility. However, despite being considered of low genotoxicity, their bio-related adverse effects have attracted particular concern from both the scientific field and the public. In this study, human cervical adenocarcinoma cells (HeLa line) were exposed to 0.01 or 1.0 mg/mL of hydrophilic silica nanoparticles. The H-1 NMR spectroscopy coupled with multivariate statistical analysis were used to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media. At the early stage of silica nanoparticles-exposure, no obvious dose-effect of HeLa cell metabolome was observed, which implied that cellular stress-response regulated the metabolic variations of HeLa cell. Silica nanoparticles induced the increases of lipids including triglyceride, LDL, VLDL and lactate/alanine ratio and the decreases of alanine, ATP, choline, creatine, glycine, glycerol, isoleucine, leucine, phenylalanine, tyrosine, and valine, which involved in membrane modification, catabolism of carbohydrate and protein, and stress-response. Subsequently, a complicated synergistic effect of stress-response and toxicological-effect dominated the biochemical process and metabolic response, which was demonstrated in the reverse changes of some metabolites including acetate, ADP, ATP, choline, creatine, glutamine, glycine, lysine, methionine, phenylalanine and valine between 6 and 48 h post-treatment of silica nanoparticles. The toxicological-effects induced by high-dosage silica nanoparticles could be derived from the elevated levels of ATP and ADP, the utilization of glucose and amino acids and the production of metabolic end-products such as glutamate, glycine, lysine, methionine, phenylalanine, and valine. The results indicated that it is important and necessary to pursue further the physiological responses of silica nanoparticles in animal models and human before their practical use. NMR-based metabolomic analysis helps to understand the biological mechanisms of silica nanoparticles and their metabolic fate, and further, it offers an ideal platform for establishing the bio-safety of existing and new nanomaterials.Silica nanoparticles are increasingly used in the biomedical fields due to their excellent solubility, high stability and favorable biocompatibility. However, despite being considered of low genotoxicity, their bio-related adverse effects have attracted particular concern from both the scientific field and the public. In this study, human cervical adenocarcinoma cells (HeLa line) were exposed to 0.01 or 1.0 mg/mL of hydrophilic silica nanoparticles. The H-1 NMR spectroscopy coupled with multivariate statistical analysis were used to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media. At the early stage of silica nanoparticles-exposure, no obvious dose-effect of HeLa cell metabolome was observed, which implied that cellular stress-response regulated the metabolic variations of HeLa cell. Silica nanoparticles induced the increases of lipids including triglyceride, LDL, VLDL and lactate/alanine ratio and the decreases of alanine, ATP, choline, creatine, glycine, glycerol, isoleucine, leucine, phenylalanine, tyrosine, and valine, which involved in membrane modification, catabolism of carbohydrate and protein, and stress-response. Subsequently, a complicated synergistic effect of stress-response and toxicological-effect dominated the biochemical process and metabolic response, which was demonstrated in the reverse changes of some metabolites including acetate, ADP, ATP, choline, creatine, glutamine, glycine, lysine, methionine, phenylalanine and valine between 6 and 48 h post-treatment of silica nanoparticles. The toxicological-effects induced by high-dosage silica nanoparticles could be derived from the elevated levels of ATP and ADP, the utilization of glucose and amino acids and the production of metabolic end-products such as glutamate, glycine, lysine, methionine, phenylalanine, and valine. The results indicated that it is important and necessary to pursue further the physiological responses of silica nanoparticles in animal models and human before their practical use. NMR-based metabolomic analysis helps to understand the biological mechanisms of silica nanoparticles and their metabolic fate, and further, it offers an ideal platform for establishing the bio-safety of existing and new nanomaterials

Quasi-unit regularity and QB-rings

Some relations for quasiunit regular rings and QB-rings, as well as for pseudounit regular rings and QB ∞-rings, are obtained. In the first part of the paper, we prove that (an exchange ring R is a QB-ring) ⟺ (whenever x ∈ R is regular, there exists a quasiunit regular element w ∈ R such that x = xyx = xyw for some y ∈ R) ⟺ (whenever aR + bR = dR in R; there exists a quasiunit regular element w ∈ R such that a + bz = dw for some z ∈ R). Similarly, we also give necessary and sufficient conditions for QB ∞-rings in the second part of the paper.Отримано деякi спiввiдношення для квазiодиничних регулярних кiлець та QB-кiлець, а також для псевдоодиничних регулярних кiлець та QB∞-кiлець. У першiй частинi статтi доведено, що (кiльце R з властивiстю замiни є QB-кiльцем) ⇔ (якщо x∈R є регулярним, то iснує квазiодиничний регулярний елемент w∈R такий, що x=xyx=xyw для деякого y∈R) ⇔ (якщо aR+bR=dR in R в R, то iснує квазiодиничний регулярний елемент w∈R такий, що a+bz=dw для деякого z∈R). Аналогiчним чином отриманi необхiднi та достатнi умови для QB∞-кiлець наведено у другiй частинi статтi

Case report: Olverembatinib monotherapy: the chemotherapy-free regimen for an elderly patient with relapsed Ph-positive acute lymphoblastic leukemia

Background: The advent of first- and second-generation BCR/ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, has markedly improved the clinical outcomes of patients with philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+-ALL). However, due to acquired drug resistance, most Ph+-ALL patients experience relapse. Thus, third-generation BCR/ABL1 TKIs, including ponatinib and olverembatinib, have been developed with the aim of overcoming drug resistance.Case report: A 79-year-old woman presented with intermittent fever and fatigue for 4 days. After comprehensive cytogenetic examination, the patient was diagnosed with Ph+-B-ALL. Starting on 22 September 2021, a combined regimen of flumatinib and vincristine/prednisone (VP) was administered for seven cycles, followed by flumatinib maintenance therapy. The patient remained in first complete molecular remission (1st CMR) for 19 months. On 12 March 2023, she again complained of fatigue and loss of appetite for nearly a month. A comprehensive examination showed Ph+-B-ALL relapse with additional E255V mutation, although T315I mutation was negative. In view of her frail physical condition, she received olverembatinib monotherapy and achieved second CMR (second CMR). No severe toxicities were recorded except for mild fatigue. At present, she has been in second CMR for over 6 months.Conclusion: For elderly patients with relapsed Ph+-ALL, olverembatinib monotherapy may offer a novel option with a good safety profile, suggesting the feasibility of a chemo-free regimen

Establishment of a Standardized Liver Fibrosis Model with Different Pathological Stages in Rats

Objective. To establish a standardized animal model for liver fibrosis with the same assessment criteria for liver fibrosis studies that have been established on a unified platform. Methods. The standardized liver fibrosis model was established using Sprague-Dawley (SD) rats that either received an intraperitoneal injection of carbon tetrachloride (CCl4) in small dosages or ingested an ethanol solution. Results. The definite corresponding rules among modeling of different weeks and corresponding serology indices as well as different pathological staging can be observed by modeling with small dosages and slow, individualized, and combined administrations. Conclusion. This method can be used for the standardized establishment of a liver fibrosis model in rats across 5 pathological stages, ranging from S0 to S4, with a high success rate (89.33%) and low death rate (17.3%) because of the application of multiple hypotoxic chemicals for modeling. We refer to the criteria of Histological Grading and Staging of Chronic Hepatitis for Fibrosis established by the 10th World Digestive Disease Academic Conference in Los Angeles in September 1994 (revised in November 2000)

Identificación de las poblaciones de pota saltadora (Ommastrephes bartramii) en el Pacífico Norte a partir de la morfología de estatolitos y mandíbulas

Cephalopods are becoming increasingly important in global fisheries as a result of increased landings and are playing an important ecological role in the trophic dynamics of marine ecosystems. Ommastrephes bartramii is a pelagic cephalopod species with two widely distributed spawning stocks in the North Pacific Ocean. It is also a major fishing target for the Chinese squid jigging fleets. Successful separation of these two spawning stocks is critical to fisheries management, but tends to be challenging because of their similar morphology. In this study we attempted to identify the stocks based on discriminant analyses of 9 morphological variables of statolith and 12 variables of beaks measured for O. bartramii samples in the North Pacific. A significant difference was revealed in the standardized beak and statolith variables between sexes in the northeast (NE) stock (P 0.05), whereas the NW stock showed no significant difference in either sex for the statolith variables (P > 0.05). The same sex also revealed different patterns with different hard structures between the two stocks. In t-tests females showed significant differences between stocks in statolith morphology (P 0.05), but showed no difference between cohorts (P > 0.05) in beak morphometric variables. With the combination of two standardized hard parts, correct classification of stepwise discriminant analysis (SDA) was raised by nearly 20% compared with using only one structure, although overlaps of the NW stock were still found in the scatter-plots. It is concluded that adding more appropriate hard structure variables will effectively increase the success of separating geographic stocks by the SDA method.Los cefalópodos son cada vez más importantes en las pesquerías mundiales como consecuencia de su volumen de capturas, jugando un importante rol en la red trófica de los ecosistemas marinos. Ommastrephes bartramii es una especie de cefalópodo pelágico con dos poblaciones de desove de amplia distribución en el Pacífico Norte. Asímismo, es un importante objetivo de las flotas pesqueras chinas de potera automática. La adecuada identificación de sus dos poblaciones de desove es fundamental para la gestión de esta pesquería, siendo una difícil tarea debido a su morfología similar. En este estudio se pretende identificar los stocks en función de los análisis discriminantes de nueve variables morfológicas del estatolito y doce variables de las mandíbulas, obtenidas en muestras de O. bartramii del Pacífico Norte. Se hallaron diferencias significativas entre sexos en las variables mandíbula y estatolito para el stock del noreste (stock NE) (P 0.05), las medidas del estatolito no mostraron diferencias significativas en ambos sexos para el stock NO (P > 0.05). Para cada sexo, también se hallaron diferencias entre las estructuras duras de ambos stocks. Los tests T-Student mostraron diferencias entre las hembras de ambos stocks en relación a la morfología del estatolito (P 0.05), no observándose diferencias entre las cohortes de machos (P > 0.05) en las variables morfométricas de la mandíbula entre los dos stocks. En comparación con el uso de una sola estructura dura, el estudio conjunto de ambas estructuras mediante análisis discriminante incrementó en cerca de un 20% la correcta asignación a los diferentes stocks, a pesar de algunos solapamientos observados en los diagramas de dispersión del stock NO. Se puede considerar que el empleo adicional de estructuras duras adecuadas aumentará la probabilidad de identificar los stocks mediante análisis discriminante

Microbial production of hyaluronic acid: current state, challenges, and perspectives

Hyaluronic acid (HA) is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid with a molecular weight up to 6 million Daltons. With excellent viscoelasticity, high moisture retention capacity, and high biocompatibility, HA finds a wide-range of applications in medicine, cosmetics, and nutraceuticals

Heterologous expression, biochemical characterization, and overproduction of alkaline α-amylase from Bacillus alcalophilus in Bacillus subtilis

<p>Abstract</p> <p>Background</p> <p>Alkaline α-amylases have potential applications for hydrolyzing starch under high pH conditions in the starch and textile industries and as ingredients in detergents for automatic dishwashers and laundries. While the alkaline α-amylase gains increased industrial interest, the yield of alkaline α-amylases from wild-type microbes is low, and the combination of genetic engineering and process optimization is necessary to achieve the overproduction of alkaline α-amylase.</p> <p>Results</p> <p>The alkaline α-amylase gene from <it>Bacillus alcalophilus </it>JN21 (CCTCC NO. M 2011229) was cloned and expressed in <it>Bacillus subtilis </it>strain WB600 with vector pMA5. The recombinant alkaline α-amylase was stable at pH from 7.0 to 11.0 and temperature below 40°C. The optimum pH and temperature of alkaline α-amylase was 9.0 and 50°C, respectively. Using soluble starch as the substrate, the <it>K</it>_mand <it>V</it>_maxof alkaline α-amylase were 9.64 g/L and 0.80 g/(L·min), respectively. The effects of medium compositions (starch, peptone, and soybean meal) and temperature on the recombinant production of alkaline α-amylase in <it>B. subtilis </it>were investigated. Under the optimal conditions (starch concentration 0.6% (w/v), peptone concentration 1.45% (w/v), soybean meal concentration 1.3% (w/v), and temperature 37°C), the highest yield of alkaline α-amylase reached 415 U/mL. The yield of alkaline α-amylase in a 3-L fermentor reached 441 U/mL, which was 79 times that of native alkaline α-amylase from <it>B. alcalophilus </it>JN21.</p> <p>Conclusions</p> <p>This is the first report concerning the heterologous expression of alkaline α-amylase in <it>B. subtilis</it>, and the obtained results make it feasible to achieve the industrial production of alkaline α-amylase with the recombinant <it>B. subtilis</it>.</p

Dimethyl 2,2′-[ethane-1,2-diylbis(sulfanedi­yl)]dibenzoate

The title compound, C18H18O4S2, was synthesized by the reaction of 1,2-dibromo­ethane with methyl thio­salicylate. The complete molecule is generated by crystallographic twofold symmetry: two methyl benzoate units are linked by an –S–(CH2)2–S– bridging chain with a gauche S—CH2—CH2—S torsion angle [72.88 (16)°]. The two aromatic rings form a dihedral angle of 79.99 (6)°. In the crystal, adjacent mol­ecules are linked into a three-dimensional network by non-classical C—H⋯O hydrogen bonds