Integrating serum metabolomics analysis and network pharmacology to reveal the potential mechanism of Shengmai Jianghuang San in the treatment of nasopharyngeal carcinoma.

Shengmai Jianghuang San (SMJHS) is a traditional Chinese herbal compound reported to inhibit Nasopharyngeal Carcinoma (NPC) progression and enhance radiosensitivity. However, the specific active ingredients and regulatory mechanisms of SMJHS against NPC, particularly under hypoxic conditions, remain unclear. In this study, Sprague-Dawley (SD) rats were gavaged with Shengmai Jianghuang San (SMJHS), and their blood was collected from the abdominal aorta. UHPLC-Q-Exactive orbitrap MS/MS was used to identify the metabolite profiles of SMJHS drug-containing serum. A molecular network of the active compositions in SMJHS targeting NPC was constructed through network pharmacology and molecular docking. The HIF-1α/VEGF pathway was in key positions. The effects of SMJHS on the proliferation, migration, and radiosensitivity of hypoxic NPC cells were assessed by in vitro experiments. NPC cell lines stably overexpressing HIF-1α were established using a lentivirus to investigate the regulation of HIF-1α/VEGF signaling in hypoxic NPC cells by SMJHS. Through a combination of network pharmacological analysis, cellular biofunctional validation, and molecular biochemical experiments, our study found that SMJHS had an anti-proliferative effect on NPC cells cultured under hypoxic conditions, inhibiting their migration and increasing their radiosensitivity. Additionally, SMJHS suppressed the expression of HIF-1α and VEGFA, exhibiting potential as an effective option for improving NPC treatment.

The type III effector NopL interacts with GmREM1a and GmNFR5 to promote symbiosis in soybean.

The establishment of symbiotic interactions between leguminous plants and rhizobia requires complex cellular programming activated by Rhizobium Nod factors (NFs) as well as type III effector (T3E)-mediated symbiotic signaling. However, the mechanisms by which different signals jointly affect symbiosis are still unclear. Here we describe the mechanisms mediating the cross-talk between the broad host range rhizobia Sinorhizobium fredii HH103 T3E Nodulation Outer Protein L (NopL) effector and NF signaling in soybean. NopL physically interacts with the Glycine max Remorin 1a (GmREM1a) and the NFs receptor NFR5 (GmNFR5) and promotes GmNFR5 recruitment by GmREM1a. Furthermore, NopL and NF influence the expression of GmRINRK1, a receptor-like kinase (LRR-RLK) ortholog of the Lotus RINRK1, that mediates NF signaling. Taken together, our work indicates that S. fredii NopL can interact with the NF signaling cascade components to promote the symbiotic interaction in soybean.

Application of the radial artery after angiography in patients undergoing total arterial coronary revascularization.

OBJECTIVE: There is growing evidence supporting the utilization of the radial artery as a secondary arterial graft in coronary artery bypass grafting (CABG) surgery. However, debates continue over the recovery period of the radial artery following angiography. This study aims to evaluate the clinical outcomes and experiences related to the use of the radial artery post-angiography in total arterial coronary revascularization. METHODS: A retrospective analysis was performed on data from patients who underwent total arterial CABG surgery at the University of Hong Kong Shenzhen Hospital from July 1, 2020, to September 30, 2022. Preoperative assessments included ultrasound evaluations of radial artery blood flow, diameter, intimal integrity, and the Allen test. Additionally, pathological examinations of the distal radial artery and coronary artery CT angiography were conducted, along with postoperative follow-up to assess the safety and efficacy of using the radial artery in patients undergoing total arterial CABG. RESULTS: A total of 117 patients, compromising 102 males and 15 females with an average age of 60.0 ± 10.0 years, underwent total arterial CABG. The internal mammary artery was used in situ in 108 cases, while in 4 cases, it was grafted to the ascending aorta due to length limitations. Bilateral radial arteries were utilized in 88 patients, and bilateral internal mammary arteries in 4 patients. Anastomoses of the proximal radial arteries to the proximal ascending aorta included 42 cases using distal T-anastomosis and 4 using sequential grafts. The interval between bypass surgery and coronary angiography ranged from 7 to 14 days. Pathological examination revealed intact intima and continuous elastic membranes with no significant inflammatory infiltration or hyperplastic lumen stenosis in the radial arteries. There were no hospital deaths, 3 cases of perioperative cerebral infarction, 1 secondary thoracotomy for hemorrhage control, 21 instances of intra-aortic balloon pump (IABP) assistance, and 2 cases of poor wound healing that improved following debridement. CT angiography performed 2 weeks post-surgery showed no internal mammary artery occlusions, but 4 radial artery occlusions were noted. CONCLUSION: Ultrasound may be used within 2 weeks post-angiography to assess the recovery of the radial artery in some patients. Radial arteries with intact intima may be considered in conjunction with the internal mammary artery for total arterial coronary CABG. However, long-term outcomes of these grafts require further validation through larger prospective studies.

Structural characteristics of BtKY72 RBD bound to bat ACE2 reveal multiple key residues affecting ACE2 usage of sarbecoviruses.

Two different sarbecoviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, have caused serious challenges to public health. Certain sarbecoviruses utilize angiotensin-converting enzyme 2 (ACE2) as their cellular receptor, whereas some do not, speculatively due to the two deletions in their receptor-binding domain (RBD). However, it remains unclear whether sarbecoviruses with one deletion in the RBD can still bind to ACE2. Here, we showed that two phylogenetically related sarbecoviruses with one deletion, BtKY72 and BM48-31, displayed a different ACE2-usage range. The cryo-electron microscopy structure of BtKY72 RBD bound to bat ACE2 identified a key residue important for the interaction between RBD and ACE2. In addition, we demonstrated that the mutations involving four types of core residues enabled the sarbecoviruses with deletion(s) to bind to human ACE2 (hACE2) and broadened the ACE2 usage of SARS-CoV-2. Our findings help predict the potential hACE2-binding ability to emerge sarbecoviruses and develop pan-sarbecovirus therapeutic agents. IMPORTANCE: Many sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possess the ability to bind to receptor angiotensin-converting enzyme 2 (ACE2) through their receptor-binding domain (RBD). However, certain sarbecoviruses with deletion(s) in the RBD lack this capability. In this study, we investigated two closely related short-deletion sarbecoviruses, BtKY72 and BM48-31, and revealed that BtKY72 exhibited a broader ACE2-binding spectrum compared to BM48-31. Structural analysis of the BtKY72 RBD-bat ACE2 complex identifies a critical residue at position 493 contributing to these differences. Furthermore, we demonstrated that the mutations involving four core residues in the RBD enabled the sarbecoviruses with deletion(s) to bind to human ACE2 and expanded the ACE2 usage spectra of SARS-CoV-2. These findings offer crucial insights for accurately predicting the potential threat of newly emerging sarbecoviruses to human health.

Advanced membrane-based electrode engineering toward efficient and durable water electrolysis and cost-effective seawater electrolysis in membrane electrolyzers.

Researchers have been seeking for the most technically-economical water electrolysis technology for entering the next-stage of industrial amplification for large-scale green hydrogen production. Various membrane-based electrolyzers have been developed to improve electric-efficiency, reduce the use of precious metals, enhance stability, and possibly realize direct seawater electrolysis. While electrode engineering is the key to approaching these goals by bridging the gap between catalysts design and electrolyzers development, nevertheless, as an emerging field, has not yet been systematically analyzed. Herein, this review is organized to comprehensively discuss the recent progresses of electrode engineering that have been made toward advanced membrane-based electrolyzers. For the commercialized or near-commercialized membrane electrolyzer technologies, the electrode material design principles are interpreted and the interface engineering that have been put forward to improve catalytic sites utilization and reduce precious metal loading is summarized. Given the pressing issues of electrolyzer cost reduction and efficiency improvement, the electrode structure engineering toward applying precious metal free electrocatalysts is highlighted and sufficient accessible sites within the thick catalyst layers with rational electrode architectures and effective ions/mass transport interfaces are enabled. In addition, this review also discusses the innovative ways as proposed to break the barriers of current membrane electrolyzers, including the adjustments of electrode reaction environment, and the feasible cell-voltage-breakdown strategies for durable direct seawater electrolysis. Hopefully, this review may provide insightful information of membrane-based electrode engineering and inspire the future development of advanced membrane electrolyzer technologies for cost-effective green hydrogen production.

Tudor-SN promotes cardiomyocyte proliferation and neonatal heart regeneration through regulating the phosphorylation of YAP.

BACKGROUND: The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury. METHODS: The Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN -/-) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo. RESULTS: We previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription. CONCLUSION: Tudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.

Mulberry leaves supplementation alters lipid metabolism and promotes fatty acid ß oxidation in growing mutton sheep.

Mulberry leaves (MLs) are an unconventional feed with fiber and various active ingredients, and are acknowledged as likely to regulate lipid metabolism, while the molecular mechanism remains undefined. Therefore, our objective was to define the role of MLs on the overall lipid metabolism. We conducted a feeding experiment of three groups on growing mutton sheep fed with dried mulberry leaves (DMLs), with fermented mulberry leaves (FMLs), or without MLs (as control). Analyses of transcriptome and widely target lipids demonstrated the addition of MLs triggered big perturbations in genes and metabolites related to glycerolipid, phospholipid, ether lipid, and sphingolipid metabolism. Additionally, the variations of the above lipids in the treatment of MLs possibly facilitate immunity enhancement of growing mutton sheep via the activation of complement and coagulation cascades. Furthermore, treatments with MLs could expedite proceedings of lipid degradation and fatty acid ß oxidation in mitochondria, thereby to achieve the effect of lipid reduction. Besides, added DMLs also fuel fatty acid ß-oxidation in peroxisomes and own much stronger lipolysis than added FMLs, possibly attributed to high fiber content in DMLs. These findings establish the novel lipid-lowering role and immune protection of MLs, which lays the foundation for the medicinal application of MLs.

Mulberry leaves (MLs) are rich in a wide variety of active ingredients and are also a kind of traditional Chinese medicine with the same origin as medicine and food. Previous studies have found that MLs may regulate lipid metabolism. But the exact mechanism remains unclear. Our study reveals that ML supplement not only alters lipid metabolism including glycerol phospholipid, ether lipid as well as sphingolipid metabolism, which may help to improve immunity but also promote fatty acid degradation as well as ß oxidation to achieve the effect of fat reduction.

Metabolomic and transcriptomic analysis of flavonoids biosynthesis mechanisms in mulberry fruit (Hongguo 2) under exogenous hormone treatments.

The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.

Bimetallic MOFs-Derived NiFe2O4/Fe2O3 Enabled Dendrite-free Lithium Metal Anodes with Ultra-High Area Capacity Based on An Intermittent Lithium Deposition Model.

In practical operating conditions, the lithium deposition behavior is often influenced by multiple coupled factors and there is also a lack of comprehensive and long-term validation for dendrite suppression strategies. Our group previously proposed an intermittent lithiophilic model for high-performance three-dimensional (3D) composite lithium metal anode (LMA), however, the electrodeposition behavior was not discussed. To verify this model, this paper presents a modified 3D carbon cloth (CC) backbone by incorporating NiFe2O4/Fe2O3 (NFFO) nanoparticles derived from bimetallic NiFe-MOFs. Enhanced Li adsorption capacity and lithiophilic modulation were achieved by bimetallic MOFs-derivatives which prompted faster and more homogeneous Li deposition. The intermittent model was further verified in conjunction with the density functional theory (DFT) calculations and electrodeposition behaviors. As a result, the obtained Li-CC@NFFO||Li-CC@NFFO symmetric batteries exhibit prolonged lifespan and low hysteresis voltage even under ultra-high current and capacity conditions (5 mA cm-2, 10 mAh cm-2), what's more, the full battery coupled with a high mass loading (9 mg cm-2) of LiFePO4 cathode can be cycled at a high rate of 5 C, the capacity retention is up to 95.2 % before 700 cycles. This work is of great significance to understand the evolution of lithium dendrites on the 3D intermittent lithiophilic frameworks.

A High-Performance and Durable Direct-Ammonia Symmetrical Solid Oxide Fuel Cell with Nano La0.6Sr0.4Fe0.7Ni0.2Mo0.1O3-δ-Decorated Doped Ceria Electrode.

Solid oxide fuel cells (SOFCs) offer a significant advantage over other fuel cells in terms of flexibility in the choice of fuel. Ammonia stands out as an excellent fuel choice for SOFCs due to its easy transportation and storage, carbon-free nature and mature synthesis technology. For direct-ammonia SOFCs (DA-SOFCs), the development of anode catalysts that have efficient catalytic activity for both NH3 decomposition and H2 oxidation reactions is of great significance. Herein, we develop a Mo-doped La0.6Sr0.4Fe0.8Ni0.2O3-δ (La0.6Sr0.4Fe0.7Ni0.2Mo0.1O3-δ, LSFNM) material, and explore its potential as a symmetrical electrode for DA-SOFCs. After reduction, the main cubic perovskite phase of LSFNM remained unchanged, but some FeNi3 alloy nanoparticles and a small amount of SrLaFeO4 oxide phase were generated. Such reduced LSFNM exhibits excellent catalytic activity for ammonia decomposition due to the presence of FeNi3 alloy nanoparticles, ensuring that it can be used as an anode for DA-SOFCs. In addition, LSFNM shows high oxygen reduction reactivity, indicating that it can also be a cathode for DA-SOFCs. Consequently, a direct-ammonia symmetrical SOFC (DA-SSOFC) with the LSFNM-infiltrated doped ceria (LSFNM-SDCi) electrode delivers a superior peak power density (PPD) of 487 mW cm-2 at 800 °C when NH3 fuel is utilised. More importantly, because Mo doping greatly enhances the reduction stability of the material, the DA-SSOFC with the LSFN-MSDCi electrode exhibits strong operational stability without significant degradation for over 400 h at 700 °C.

Differential surface modification mechanism of chalcopyrite and pyrite by Thiobacillus ferrooxidans and its response to bioflotation.

Mineral processing encounters the challenge of separating chalcopyrite and pyrite, with the conventional high alkali process characterized by issues such as large dosages of reagents, complex procedures, and environmental pollution. This study addresses this challenge by isolating and enriching Thiobacillus ferrooxidans (T·f) from acidic mine drainage, employing it as a biosurfactant. The modification mechanism of T·f was thoroughly analyzed. Fe dissolution through biological oxidation formed a passivation layer (jarosite [KFe3(SO4)2(OH)6], elemental sulfur (S0), and metal sulfides (Cu/Fe-S) on the surface of minerals. Metal oxides, hydroxides, and sulfates were detected on the surface of two minerals, but the difference was that elemental sulfur (S0) and copper sulfide (Cu-S) were detected on the surface of chalcopyrite. elucidating the fundamental reason for the significant difference in surface hydrophobicity between chalcopyrite and pyrite. T·f has been successfully used as a biosurfactant to achieve copper-sulfur separation.

Influence of Imbibition Fracturing Fluid on the Original Water and Methane Occurrence in Actual Coalbed Methane Reservoirs Using the Integrated Device of Displacement and Low-Field Nuclear Magnetic Resonance.

The original water in the coal rock pores plays a controlling role in the occurrence of gas. Furthermore, during the hydraulic fracturing process, pressurized fracturing fluid with a higher pressure than the original pore pressure in the fractures drives the fracturing fluid to infiltrate into the coal rock pores, thereby altering the occurrence pattern of gas and water in the original pores. However, due to the limitations of the indoor simulation device, a systematic conclusion on the impact of the original pore water and imbibition fracturing fluid on coalbed methane reservoirs has not yet been formed. In this paper, an integrated device combining displacement and low-field nuclear magnetic resonance was employed using underground cylindrical coal rock samples as experimental subjects. Experimental conditions were maintained at a temperature of 30 °C, a confining pressure of 23 MPa, and an approximate reservoir pressure of 15 MPa. The initial water saturation levels were altered to 0, 27.88, and 42.18% to replicate the conditions of a coalbed methane reservoir at a depth of approximately 1200 m. Fracturing fluid with a pressure of 18 MPa was injected into the experimental samples to simulate the impact of the fracturing fluid on the original reservoir during hydraulic fracturing. This allowed for a realistic assessment of the influence of initial water saturation and fracturing fluid absorption on the coalbed methane recovery rate in the reservoir. The experimental results indicate that the imbibition process promotes the desorption of adsorbed gas, and the desorption amount of adsorbed gas increases with the increase in the original water saturation. This will result in an increase in the gas pressure within the pore system. The conditions of this experiment, in comparison to the previous ones, more closely resemble real reservoir conditions. This enables a realistic assessment of how the presence of the original water content and the absorption of the fracturing fluid affect gas occurrence within the reservoir.

The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications.

DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse immune cells and stromal components, creating a complex landscape that can either promote or inhibit tumor progression. In the TIME, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. DNA methylation regulates immune cell differentiation, immune responses, and TIME composition Targeting DNA methylation in TIME offers various potential avenues for enhancing immune cytotoxicity and reducing immunosuppression. Recent studies have demonstrated that modification of DNA methylation patterns can promote immune cell infiltration and function. However, challenges persist in understanding the precise mechanisms underlying DNA methylation in the TIME, developing selective epigenetic therapies, and effectively integrating these therapies with other antitumor strategies. In conclusion, DNA methylation of both tumor cells and immune cells interacts with the TIME, and thus affects clinical efficacy. The regulation of DNA methylation within the TIME holds significant promise for the advancement of tumor immunotherapy. Addressing these challenges is crucial for harnessing the full potential of epigenetic interventions to enhance antitumor immune responses and improve patient outcomes.

Grafting seedling rootstock strengthens tolerance to drought stress in polyploid mulberry (Morus alba L.).

The economically adaptable mulberry (Morus alba L.) has a long history of grafting in China, yet the physiological mechanisms and advantages in drought tolerance remain unexplored. In our study, we investigated the responses of self-rooted 2X (diploid), 3X (triploid), and 4X (tetraploid) plants, as well as polyploid plants grafted onto diploid seedling rootstocks (2X/2X, 3X/2X, and 4X/2X) under drought stress. We found that self-rooted diploid plants exhibited the most severe phenotypic damage, lowest water retention, photosynthetic capacity, and the least effective osmotic stress adjustment compared to tetraploid and triploid plants. However, grafted diploid and triploid plants showed effective mitigation of drought-induced damage, with higher relative water content and improved soil water retention. Grafted plants also improved the photosystem response to drought stress through elevated photosynthetic potential, closed stomatal aperture, and faster recovery of chlorophyll biosynthesis in the leaves. Additionally, grafted plants altered osmotic protective compound levels, including starch, soluble sugar, and proline content, thereby enhancing drought resistance. Absolute quantification PCR indicated that the expression levels of proline synthesis-related genes in grafted plants were not influenced after drought stress, whereas they were significantly increased in self-rooted plants. Consequently, our findings support that self-rooted triploid and tetraploid mulberries exhibited superior drought resistance compared to diploid plants. Moreover, grafting onto seedling rootstocks enhanced tolerance against drought stress in diploid and triploid mulberry, but not in tetraploid. Our study provides valuable insights for a comprehensive analysis of physiological effects in response to drought stress between stem-roots and seedling rootstocks.

Flexible silicon solar cells with high power-to-weight ratios.

Silicon solar cells are a mainstay of commercialized photovoltaics, and further improving the power conversion efficiency of large-area and flexible cells remains an important research objective1,2. Here we report a combined approach to improving the power conversion efficiency of silicon heterojunction solar cells, while at the same time rendering them flexible. We use low-damage continuous-plasma chemical vapour deposition to prevent epitaxy, self-restoring nanocrystalline sowing and vertical growth to develop doped contacts, and contact-free laser transfer printing to deposit low-shading grid lines. High-performance cells of various thicknesses (55-130 µm) are fabricated, with certified efficiencies of 26.06% (57 µm), 26.19% (74 µm), 26.50% (84 µm), 26.56% (106 µm) and 26.81% (125 µm). The wafer thinning not only lowers the weight and cost, but also facilitates the charge migration and separation. It is found that the 57-µm flexible and thin solar cell shows the highest power-to-weight ratio (1.9 W g-1) and open-circuit voltage (761 mV) compared to the thick ones. All of the solar cells characterized have an area of 274.4 cm2, and the cell components ensure reliability in potential-induced degradation and light-induced degradation ageing tests. This technological progress provides a practical basis for the commercialization of flexible, lightweight, low-cost and highly efficient solar cells, and the ability to bend or roll up crystalline silicon solar cells for travel is anticipated.