Novel insights into dimethylsulfoniopropionate cleavage by deep subseafloor fungi.

Dimethylsulfoniopropionate (DMSP), a key organic sulfur compound in marine and subseafloor sediments, is degraded by phytoplankton and bacteria, resulting in the release of the climate-active volatile gas dimethylsulfide (DMS). However, it remains unclear if dominant eukaryotic fungi in subseafloor sediments possess specific abilities and metabolic mechanisms for DMSP degradation and DMS formation. Our study provides the first evidence that fungi from coal-bearing sediments ∼2 km below the seafloor, such as Aspergillus spp., Chaetomium globosum, Cladosporium sphaerospermum, and Penicillium funiculosum, can degrade DMSP and produce DMS. In Aspergillus sydowii 29R-4-F02, which exhibited the highest DMSP-dependent DMS production rate (16.95 pmol/µg protein/min), two DMSP lyase genes, dddP and dddW, were identified. Remarkably, the dddW gene, previously observed only in bacteria, was found to be crucial for fungal DMSP cleavage. These findings not only extend the list of fungi capable of degrading DMSP, but also enhance our understanding of DMSP lyase diversity and the role of fungi in DMSP decomposition in subseafloor sedimentary ecosystems.

Optical Creation of Skyrmions by Spin Reorientation Transition in Ferrimagnetic CoHo Alloys.

Manipulating magnetic skyrmions by means of a femtosecond (fs) laser pulse has attracted great interest due to their promising applications in efficient information-storage devices with ultralow energy consumption. However, the mechanism underlying the creation of skyrmions induced by an fs laser is still lacking. As a result, a key challenge is to reveal the pathway for the massive reorientation of magnetization from trivial to nontrivial topological states. Here, we studied a series of ferrimagnetic CoHo alloys and investigated the effect of a single laser pulse on the magnetic states. Thanks to the time-resolved magneto-optical Kerr effect and imaging techniques, we demonstrate that the laser-induced phase transitions from single domains into a topological skyrmion phase are mediated by the transient in-plane magnetization state, in real time and space domains, respectively. Combining experiments and micromagnetic simulations, we propose a two-step process for creating skyrmions through laser pulse irradiation: (i) the electron temperature enhancement induces a spin reorientation transition on a picosecond (ps) timescale due to the suppression of perpendicular magnetic anisotropy (PMA) and (ii) the PMA slowly restores, accompanied by out-of-plane magnetization recovery, leading to the generation of skyrmions with the help of spin fluctuations. This work provides a route to control skyrmion patterns using an fs laser, thereby establishing the foundation for further exploration of topological magnetism at ultrafast timescales.

Effect of ultrasound-guided lumbar square muscle block on stress response in patients undergoing radical gastric cancer surgery.

BACKGROUND: Radical surgery is a common treatment for patients with gastric cancer; however, it can lead to postoperative complications and intestinal barrier dysfunction. Ultrasound-guided quadratus lumborum block is often used for postoperative analgesia, but its effects on stress response and intestinal barrier function are not well understood. AIM: To investigate the effects of an ultrasound-guided quadratus lumborum block on stress response and intestinal barrier function in patients undergoing radical surgery for gastric cancer. METHODS: A total of 100 patients undergoing radical surgery for gastric cancer were randomly categorized into observation and control groups. Plasma adrenaline and cortisol levels, intestinal mucosal barrier indexes, and complication rates were compared between the two groups before, during, and 1 day after surgery. RESULTS: The observation group had significantly lower plasma adrenaline and cortisol levels during surgery and at 1 day postoperatively than that of the control group (P < 0.05). Additionally, intestinal barrier indexes (endotoxin and D-dimer) at 1 day postoperatively were significantly lower in the observation group than in the control group (P < 0.05). CONCLUSION: Ultrasound-guided quadratus lumborum block could reduce stress response, protect intestinal barrier function, and decrease the incidence of complications in patients undergoing radical surgery for gastric cancer. This technique has the potential for clinical applications.

SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells.

Leukemia arises from blockage of the differentiation/maturation of hematopoietic progenitor cells at different stages with uncontrolled proliferation of leukemic cells. However, the signal pathways that block cell differentiation remain unclear. Herein we found that SUMOylation of the M2 isoform of pyruvate kinase (PKM2), a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis. SUMOylation of PKM2 lysine 270 (K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of PKM2 recruits and promotes degradation of RUNX1 via a SUMO-interacting motif, resulting in blockage of myeloid differentiation of NB4 and U937 leukemia cells. Replacement of wild type PKM2 with a SUMOylation-deficient mutant (K270R) abrogated the interaction with RUNX1, and the blockage of myeloid differentiation in vitro and in xenograft model. Our results establish PKM2 as an essential modulator of leukemia cell differentiation and a potential therapeutic target, which may offer synergistic effect with differentiation therapy in the treatment of leukemia.

Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis.

AIMS AND OBJECTIVE: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. MATERIALS AND METHODS: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. RESULTS: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. CONCLUSION: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Pyruvate kinase M2 phosphorylates H2AX and promotes genomic instability in human tumor cells.

Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP, a rate-limiting reaction in glycolysis. M2 isoform of PK (PKM2) is the predominant form of PK expressed in tumors. In addition to its well established cytosolic functions as a glycolytic enzyme, PKM2 displays nuclear localization and important nonmetabolic functions in tumorigenesis. Herein, we report that nuclear PKM2 interacts with histone H2AX under DNA damage conditions. Depletion of PKM2 decreased the level of serine 139-phosphorylated H2AX (γ-H2AX) in response to DNA damage. The in vitro kinase assay reveals that PKM2 directly phosphorylates H2AX at serine 139, which is abolished by the deletion of FBP-binding pocket of PKM2 (PKM2-Del515-520). Replacement of wild type PKM2 with the kinase dead mutant PKM2-Del515-520 leads to decreased cell proliferation and chromosomal aberrations under DNA damage conditions. Together, we propose that PKM2 promotes genomic instability in tumor cells which involves direct phosphorylation of H2AX. These findings reveal PKM2 as a novel modulator for genomic instability in tumor cells.

A Novel Role for Pyruvate Kinase M2 as a Corepressor for P53 during the DNA Damage Response in Human Tumor Cells.

The pyruvate kinase (PK) is a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, yielding one molecule of ATP. The M2 isoform of PK (PKM2) is predominantly expressed in normal proliferating cells and tumors, and both metabolic and non-metabolic activities for the enzyme in promoting tumor cell proliferation have been identified. However, the exact roles of PKM2 in tumor initiation, growth and maintenance are not yet fully understood. Using immunoprecipitation-coupled LC-MS/MS in MCF7 cells exposed to DNA-damaging agent, we report that the nuclear PKM2 interacts directly with P53 protein, a critical safeguard for genome stability. Specifically, PKM2 inhibits P53-dependent transactivation of the P21 gene by preventing P53 binding to the P21 promoter, leading to a nonstop G1 phase. As a result, PKM2 expression provides a growth advantage for tumor cells in the presence of a DNA damage stimulus. In addition, PKM2 interferes with phosphorylation of P53 at serine 15, known to stimulate P53 activity by the ATM serine/threonine kinase. These findings reveal a new role for PKM2 in modulating the DNA damage response and illustrate a novel mechanism of PKM2 participating in tumorigenesis.

Formulation and characterization of Brucea javanica oil microemulsion for improving safety.

OBJECTIVE: This study engaged in investigation of optimal formulation, characteristics analysis of Brucea javanica oil microemulsion (BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo. METHODS: Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant, cosurfactant and oil phases. Subsequent stability testing of BJOM was performed by dilution, centrifugation and accelerated stability testing. The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material. These results were utilized to evaluate the safety of BJOM by haemolytic, irritative and allergic testing in vitro. In addition, the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), with particular emphasis given to potential uses in cancer treatment. RESULTS: The most suitable method of preparation for BJOM was found to be a one to one ratio (Km 1:1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio. The microemulsion droplets of BJOM possessed a spherical shape, uniform size and average diameter of 23.8 nm. The expiration date of BJOM was found to be 568 d. The safety study demonstrated no hemolysis activity at the experimental BJOM concentrations; however, mild hemolysis was observed at higher concentrations of Brucea javanica oil emulsion (BJOE), a common commercially available product. Irritation observed upon BJOM treatment can be primarily attributed to Brucea javanica oil (BJO) with little influence of BJOM excipients. In addition, BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs. The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells, with BJOM demonstrating significantly more dramatic anticancer activity. CONCLUSION: An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.

Top-down fabrication of sub-nanometre semiconducting nanoribbons derived from molybdenum disulfide sheets.

Developments in semiconductor technology are propelling the dimensions of devices down to 10 nm, but facing great challenges in manufacture at the sub-10 nm scale. Nanotechnology can fabricate nanoribbons from two-dimensional atomic crystals, such as graphene, with widths below the 10 nm threshold, but their geometries and properties have been hard to control at this scale. Here we find that robust ultrafine molybdenum-sulfide ribbons with a uniform width of 0.35 nm can be widely formed between holes created in a MoS2 sheet under electron irradiation. In situ high-resolution transmission electron microscope characterization, combined with first-principles calculations, identifies the sub-1 nm ribbon as a Mo5S4 crystal derived from MoS2, through a spontaneous phase transition. Further first-principles investigations show that the Mo5S4 ribbon has a band gap of 0.77 eV, a Young's modulus of 300GPa and can demonstrate 9% tensile strain before fracture. The results show a novel top-down route for controllable fabrication of functional building blocks for sub-nanometre electronics.

Sucrose monolaurate synthesis with Protex 6L immobilized on electrospun TiO2 nanofiber.

TiO(2) nanofibers with uniform diameter about 125 nm were prepared based on sol-gel process and electrospinning technology. Protex 6L, an industrial alkaline protease, was covalently immobilized on TiO(2) nanofiber through γ-aminopropyltriethoxysilane modification and glutaraldehyde crosslinking. With 2 (v/v)% glutaraldehyde as crosslinker, the enzyme loading is about 201 mg (g nanofiber membrane)(-1), and the specific activity of the immobilized Protex 6L is 2.45 µmol h(-1) ml(-1) mg(-1) protein for synthesis of sucrose monolaurate from sucrose and vinyl laurate. The optimal condition for sucrose monolaurate production is 5% (v/v) water content in DMSO/2-methyl-2-butanol solvent mixture and 50 °C. Under this condition, 97% conversion was achieved within 36 h by nanofibrous Protex 6L, which is corresponding to a productivity 34 times higher than that of most widely used Novozym 435. After 10 cycles reuse, nanofibrous Protex 6L retained 52.4% of its original activity.