Different source of commercial soy protein isolates: Structural, compositional, and physicochemical characteristics in relation to protein functionalities.

This study aimed to illustrate the relationship among physicochemical properties, subunit composition and protein functionalities in a broad collection of commercial soy protein isolates (SPIs) from China and the EU. The results indicated that SPIs had large variations in glycinin/ß-conglycinin composition, protein denaturation, and water- and oil-binding capacity (WBC and OBC) and solubility. These SPIs could be roughly divided into pre-denatured SPI, partially hydrolyzed SPI, and less modified SPI. The pre-denatured SPI with high surface hydrophobicity and large particle sizes showed reduced WBC and OBC due to increased protein aggregation, and partially hydrolyzed SPI showed high protein solubility owing to the exposure of hydrophilic regions and reduction in molecular size. The processing-induced physicochemical changes played a pivotal role in determining protein functionalities, whereas subunit composition affected protein functionality less. Overall, this study highlighted the obvious difference in raw material quality of commercial SPI, and provided promising methods for SPI categorization.

Tryptophan sulfonate: A new chemical marker for accurate and efficient inspection of sulfur-treated food products.

Sulfur treatment for the pesticidal and antibacterial processing of food products has been criticized since it impairs the quality of treated products. The inspection of sulfur-treated products is thus required to achieve the regulation of sulfur treatment. Sulfite assay is currently available for the inspection, but it bears the disadvantages of inaccurate results and complex experimental procedures. Here we report a new chemical marker, namely tryptophan sulfonate, that can be used for the accurate and efficient inspection of sulfur-treated foods. First, the marker was discovered in sulfur-fumigated ginger, yam, and ginseng by untargeted metabolomics. The marker identity was then elucidated using chromatographic separation, nuclear magnetic resonance analysis and chemical synthesis. Finally, to demonstrate its applicability in the inspection, a tryptophan sulfonate assay was developed to test 50 commercial food samples, and the results indicated that it performed better than the sulfite assay in terms of both accuracy and efficiency.

A wide-range UAC sensor for the classification of hyperuricemia in spot samples.

Hyperuricemia (HUA) has received wide attention as an independent risk factor for various chronic diseases. HUA is usually asymptomatic, and the related damage can be reduced by effective classification and treatment according to uric acid clearance (UAC). UAC is a calculated ratio based on the uric acid level in blood and urine. This important method is not universally used due to the inconvenience of collecting 24-h urine samples in the clinic, and most sensors are limited by the need for wide ranges and for two testing samples. In this study, a pH-sensitive urate oxidase-modified electrochemical sensor with filter membrane was proposed to calculate UAC by detecting uric acid in blood and urine. The results demonstrated that the sensor had high selectivity for uric acid with a detection limit of 0.25 µM in 5 µL spot sample, the wide linear range was 2.5-7000 µM, and the impact of the sample pH was calibrated. The linear correlation of the measurement results between the UAC sensor and clinical instrument was higher than 0.980 for 87 patients. The change in UAC in spot urine may reflect alteration in body-transport mechanisms. Thus, the UAC sensor may open a new window for the management of HUA and broaden its application in point-of-care testing.

A novel and sensitive dual signaling ratiometric electrochemical aptasensor based on nanoporous gold for determination of Ochratoxin A.

Ochratoxin A (OTA) is a toxic pollutant in foods, and its actual detection is crucial. A novel and sensitive dual signaling ratiometric electrochemical aptasensor based on nanoporous gold (NPG) was proposed to determine OTA. NPG, with high specific surface area and conductivity, improved the sensitivity by immobilizing more aptamers. Meanwhile, the dual signaling ratiometric strategy improved the detection reproducibility through self-referencing and built-in correction. NPG and ratiometric strategy multi-amplified the dual signal changes. The sensitivity of OTA was evaluated by the ratio of methylene to ferrocene current values. Under the optimal conditions, the NPG-based aptasensor demonstrated excellent sensitivity with a wide linear range of 1 pg/mL to 2 ng/mL and the limit of detection (LOD) of 0.4 pg/mL for OTA. This developed aptasensor also effectively detected OTA in spiked Cordyceps sinensis and grape juice samples, with recovery values falling in the 98.49-108.0% range.

Fermentation-promoting effect of three salt-tolerant Staphylococcus and their co-fermentation flavor characteristics with Zygosaccharomyces rouxii in soy sauce brewing.

Staphylococcus is the dominant genus in the fermentation process of soy sauce, but its effect on the flavor of soy sauce has not been clearly established. In order to investigate the role of this genus in soy sauce fermentation, individual fermentation with Staphylococcus spp. screened from the moromi and their co-fermentation with an ester-producing yeast of Zygosaccharomyces rouxii were designed. Through the analysis of physicochemical properties, organic acid composition, volatile flavor compounds (VFCs) and sensory characteristics during fermentation, Staphylococcus was confirmed as a contributor to the acidity, ester aroma and alcohol aroma of soy sauce. In their co-fermentation with yeast, the ester aroma of soy sauce was further enhanced. Moreover, pathway enrichment analysis and network construction of key VFCs also revealed potential metabolic networks for formation of characteristic flavor compounds in co-fermentation. This work will help optimize the fermentation functional microbiota to obtain better soy sauce flavor.

Macrophage-derived MMP12 promotes fibrosis through sustained damage to endothelial cells.

Macrophages are essential for the maintenance of endothelial cell function. However, the potential impact and mechanisms of crosstalk between macrophages and endothelial cells during silicosis progression remain unexplored. To fill this knowledge gap, a mouse model of silicosis was established. Single cell sequencing, spatial transcriptome sequencing, western blotting, immunofluorescence staining, tube-forming and wound healing assays were used to explore the effects of silicon dioxide on macrophage-endothelial interactions. To investigate the mechanism of macrophage-mediated fibrosis, MMP12 was specifically inactivated using siRNA and pharmacological approaches, and macrophages were depleted using disodium chlorophosphite liposomes. Compared to the normal saline group, the silica dust group showed altered macrophage-endothelial interactions. Matrix metalloproteinase family member MMP12 was identified as a key mediator of the altered function of macrophage-endothelial interactions after silica exposure, which was accompanied by pro-inflammatory macrophage activation and fibrotic progression. By using ablation strategies, macrophage-derived MMP12 was shown to mediate endothelial cell dysfunction by accumulating on the extracellular matrix. During the inflammatory phase of silicosis, MMP12 secreted by pro-inflammatory macrophages caused decreased endothelial cell viability, reduced migration, decreased trans-endothelial resistance and increased permeability; while during the fibrotic phase, macrophage-derived MMP12 sustained endothelial cell injury through accumulation on the extracellular matrix.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy.

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Hepatoprotective efficacy and interventional mechanism of JianPi LiShi YangGan formula in acute-on-chronic liver failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute-on-chronic liver failure (ACLF) progresses rapidly with a high short-term death rate. Although JianPi LiShi YangGan formula (YGF) has been used to treat ACLF by managing inflammatory responses and reducing endotoxemia, hepatocyte injury, and mortality, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to investigate the potential mechanisms underlying the efficacy and protective benefits of YGF in mice with ACLF. MATERIALS AND METHODS: YGF composition was determined using high-performance liquid chromatography coupled with mass spectrometry. We constructed a mouse model of ACLF using carbon tetrachloride, lipopolysaccharide (LPS), and D-galactosamine (D-Gal), as well as an in vitro model of D-Gal/LPS-induced hepatocyte injury. The therapeutic effects of YGF in ACLF mice were verified using hematoxylin-eosin, Sirius red, and Masson staining, and by measuring serum alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokine levels. Mitochondrial damage in hepatocytes was evaluated using electron microscopy, while superoxide anion levels in liver tissue were investigated using dihydroethidium. Transcriptome analysis, immunohistochemistry, western blotting, and immunofluorescence assays were performed to explore the mechanisms underlying the ameliorative effects of YGF against ACLF. RESULTS: In mice with ACLF, YGF therapy partially decreased serum inflammatory cytokine levels, as well as hepatocyte injury and liver fibrosis. The livers of ACLF mice treated with YGF exhibited decreased mitochondrial damage and reactive oxygen species generation, as well as a decreased number of M1 macrophages and increased number of M2 macrophages. Transcriptome analysis revealed that YGF may regulate biological processes such as autophagy, mitophagy, and PI3K/AKT signaling. In ACLF mice, YGF promoted mitophagy and inhibited PI3K/AKT/mTOR pathway activation in hepatocytes. Meanwhile, the autophagy inhibitor 3M-A reduced the capacity of YGF to induce autophagy and protect against hepatocyte injury in vitro. In contrast, the PI3K agonist 740 Y-P suppressed the ability of YGF to control PI3K/AKT/mTOR pathway activation and induce autophagy. CONCLUSIONS: Together, our findings suggest that YGF mediates autophagy, tight junctions, cytokine generation, and other biological processes. In addition, YGF inhibits hepatic inflammatory responses and ameliorates hepatocyte injury in mice with ACLF. Mechanistically, YGF can promote mitophagy to ameliorate acute-on-chronic liver failure by inhibiting the PI3K/AKT/mTOR pathway.

Nanocelluloses fine-tuned polyvinylidene fluoride (PVDF) membrane for enhanced separation and antifouling.

To mitigate membrane fouling and address the trade-off between permeability and selectivity, we fabricated nanocellulose (NC) fine-tuned polyvinylidene fluoride (PVDF) porous membranes (NC-PVDFs) using phase inversion method through blending NCs with varied aspect ratios, surface charges and grafted functional groups. NC-PVDF presented rougher surface (increased by at least 18.3 %), higher porosity and crystallinity compared to PVDF membrane. Moreover, cellulose nanocrystals incorporated PVDF (CNC-PVDF) elevated membrane surface charge and hydrophilicity (from 74.3° to 71.7°), while 2,2,6,6-tetramethylpiperidine-1-oxyl-oxidized cellulose nanofibers modified PVDF (TCNF-PVDF) enhanced the porosity (from 25.0 % to 40.3 %) and tensile strength (63.6 % higher than PVDF). For separation performance, NC improved flux, rejection and fouling resistance due to facilitation of phase transition thermokinetics as pore-forming agent and increased hydrophilicity at both interface and pore wall. For water flux, NC-PVDFs (139-228 L·m-2·h-1) resulted in increased permeability compared to bare PVDF. CNC-PVDF membrane exhibited the highest water flux because of improved porosity, roughness and hydrophilicity. For bovine serum albumin (BSA) rejection, the removal rates of all NC-PVDFs were all above 90 %. Notably, TCNF-PVDF exhibited the most remarkable elevation of BSA rejection (95.1 %) owing to size exclusion and charge repulsion in comparison with PVDF.

Cationic fluorescent carbon dots with solution ultra-stability and its rapid/on-site sensing application for HClO.

Carbon dots (CDs) as a remarkable fluorescent nanomaterial have the advantages of easy preparation, good photostability and high sensitivity. However, the poor aqueous solution stability of carbon dots largely limited their practical application due to the characteristic of easily forming precipitation for long time storage. Here, a kind of cationic fluorescent carbon dots CDs-P(Ph)3 was designed by introducing a cationic compound, (4-carboxybutyl) triphenyl phosphonium bromide, to construct an electrostatic shell outside the dots. Such electrostatic shell could highly improve carbon dots stability in an aqueous solution to make CDs-P(Ph)3 stable for long-term storage with negligible aggregation. Meanwhile, the sensitivity of CDs-P(Ph)3 for hypochlorous acid (HClO) was also enhanced on the basis of the electron-withdrawing effect of cationic substituents on the surface of carbon dots. The limit of detection of CDs-P(Ph)3 for HClO was as low as ∼0.32 µM. Additionally, the fluorescence of CDs-P(Ph)3 could be rapid quenched by HClO with a quenching efficiency of more than 80% within 30 s. The excellent stability of CDs-P(Ph)3 in an aqueous solution made it suitable for on-site detecting HClO in real samples, such as tap, well and lake water. Such designed fluorescent nanomaterial would provide a practical application pathway for optical sensing detection in environmental samples.

Precise determination of reaction conditions for accurate quantification in digital PCR by real-time fluorescence monitoring within microwells.

Real-time digital polymerase chain reaction (qdPCR) provides enhanced precision in the field of molecular diagnostics by integrating absolute quantification with process information. However, the optimal reaction conditions are traditionally determined through multiple iterative of experiments. Therefore, we proposed a novel approach to precisely determine the optimal reaction conditions for qdPCR using a standard process, employing real-time fluorescence monitoring within microwells. The temperature-sensitive fluorophore intensity presented the real temperature of each microwell. This enabled us to determine the optimal denaturation and annealing time for qdPCR based on the corresponding critical temperatures derived from the melting curves and amplification efficiency, respectively. To confirm this method, we developed an ultrathin laminated chip (UTL chip) and chose a target that need to be absolutely quantitative. The UTL chip was designed using a fluid‒solid‒thermal coupling simulation model and exhibited a faster thermal response than a commercial dPCR chip. By leveraging our precise determination of reaction conditions and utilizing the UTL chip, 40 cycles of amplification were achieved within 18 min. This was accomplished by precisely controlling the denaturation temperature at 2 s and the annealing temperature at 10 s. Furthermore, the absolutely quantitative of DNA showed good correlation (R2 > 0.999) with the concentration gradient detection using the optimal reaction conditions with the UTL chip for qdPCR. Our proposed method can significantly improve the accuracy and efficiency of determining qdPCR conditions, which holds great promise for application in molecular diagnostics.

Characterization of summertime single aerosol particles in Chengdu (China): Interannual evolution and impact of COVID-19 lockdown.

To investigate the interannual evolution of air pollution in summer and the impact of the COVID-19 lockdown on local pollution in Chengdu, China, single aerosol particles were continuously measured in three summer periods: the regular period in 2020 (RP2020); the regular period in 2022 (RP2022); and the lockdown period in 2022 (LP2022). It was found that, from RP2020 to RP2022, the mass concentrations of PM2.5, PM10, SO2 and NO2 decreased by 25.6 %, 24.7 %, 28.8 % and 38.5 %, respectively, while the concentration of O3 increased by 11.0 %. Affected by regional transport, there was no significant decrease in the concentrations of various pollutants during LP2022. All single aerosol particles could be classified into seven categories: vehicle emissions (VE), dust, biomass burning (BB), coal combustion (CC), K mixed with sulfate (KSO4), K mixed with nitrate (KNO3) and K mixed with sulfate and nitrate (KSN) particles. From RP2020 to RP2022, the contributions of BB and CC particles decreased by 12.1 % and 0.9 %, respectively, while VE and dust particles increased by 3.6 % and 2.5 %, respectively; and compared to RP2022, the contributions of VE, dust and CC particles in LP2022 decreased by 22.2 %, 11.0 % and 12.7 %, respectively. The high PM2.5 pollution events in RP2020 and RP2022 were mainly caused by combustion sources (BB and CC, 51.6 %) and VE (38.3 %) particles, respectively, while the pollution event in LP2022 was contributed by BB (27.0 %) and secondary inorganic (KSO4, KNO3 and KSN, 60.2 %) particles. The formation mechanisms of different pollution events were further validated by WRF-Chem results. Although the potential source areas of particles showed a shrinking trend from RP2020 to RP2022, regional transport still caused high PM2.5 pollution events during LP2022. Photochemical processes dominated the formation of KSO4 particles, while the KNO3 and KSN particles were mainly generated by liquid-phase reactions, and this effect increased year by year.

Development and validation of a simple and rapid UPLC-MS/MS method for loganin and its application in pharmacokinetic and tissue distribution studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc. is a medicinal and edible homolog in traditional Chinese medicine. Loganin, an iridoid glycoside, is one of the main active components of Cornus officinalis Sieb. et Zucc. Loganin has been demonstrated to improve depression-like behavior and may be a potential antidepressant candidate. However, the pharmacokinetic characteristics and tissue distribution of loganin, especially in the brain region, are still unclear. AIM OF THE STUDY: This study aims to investigate the pharmacokinetic characteristics and tissue distribution after oral administration of loganin in rats. MATERIALS AND METHODS: A simple, rapid and reproducible UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. The samples were prepared by acetonitrile precipitation with chloramphenicol as internal standard (IS). Loganin was separated by gradient elution on ACQUITY UPLC®BEH C18 (2.1 × 50 mm, 1.7 µm) using multiple reactions monitoring (MRM) mode. Concentration-time data was subjected to pharmacokinetic analysis. The pharmacokinetic parameters of loganin in rat plasma were analyzed by compartment model using DAS 2.0 software. RESULTS: The established UPLC-MS/MS method was accurate and reliable with a good linearity (R2 > 0.99) in the respective concentration range, satisfying the quantitative requirements. This method was successfully used to study the pharmacokinetics and tissue distribution after oral administration of loganin in rats. The peak time (Tmax) of oral administration was about 40 min, and the half-life (t1/2) was about 50 min, indicating that loganin was quickly absorbed and eliminated in rats. Oral bioavailability was 5.50%. The dose correlation results showed that AUC had a poor correlation with dose, while Cmax had a good correlation with dose. In tissues, loganin (35 mg/kg) was highly distributed in the stomach, small intestine, kidney, liver and lung. When the dose was 70 mg/kg, loganin had significant distribution in the cortex. CONCLUSION: In this study, a simple and sensitive UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. Loganin was absorbed quickly, eliminated quickly, and had low bioavailability. The distribution of loganin in the cortex was higher than that in the hippocampus. We hope that our results can provide a reference for loganin to become a new antidepressant.

Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis.

Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called "exosomeMMP19 (ExoMMP19)", was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called "exosome therapeutics (ExoTx)", was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.

The protective effect of Schisandra chinensis (Turcz.) Baill. polysaccharide on DSS-induced ulcerative colitis in mice via the modulation of gut microbiota and inhibition of NF-κB activation.

BACKGROUND: Schisandra chinensis (Turcz.) Baill, a fruit utilized in traditional Chinese medicine (TCM), has a long history of medical application. It has been used to treat diseases of the gastrointestinal tract. Schisandra chinensis (Turcz.) Baill polysaccharide (SACP) is an important biologically active ingredient that has been shown to have a variety of beneficial effects including immune regulation and anti-oxidative properties. Ulcerative colitis (UC) is a complicated gastrointestinal inflammatory disease. We explore the protective effect of SACP against UC. RESULTS: Schisandra chinensis (Turcz.) Baill polysaccharide significantly reduced the disease activity index (DAI) and levels of myeloperoxidase(MPO) and malondialdehyde (MDA) in colonic tissue. It also alleviated weight loss and histopathological damage of mice. The expression of MUC2 and occludin proteins was increased and the barrier function of the colonic mucosa was enhanced by SACP treatment. NF-κB pathway activation was also inhibited and the production of pro-inflammatory cytokines was decreased whereas anti-inflammatory cytokines were increased. 16SrDNA sequencing of fecal flora showed that SACP increased the abundance of Muribaculaceaeunclassified, LachnospiraceaeNK4A136group and reduced the abundance of Bacteroides and Erysipelatoclostridium. CONCLUSION: Schisandra chinensis (Turcz.) Baill polysaccharide can protect against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis in mice. © 2023 Society of Chemical Industry.

Study on mechanism of cellulose nanocrystals on hydrophobic phthalocyanine green in aqueous phase.

Phthalocyanine green is a hydrophobic pigment with excellent properties, which is usually dispersed in the organic phase. However, most organic phases are volatile and harmful to the environment and organisms. Therefore, phthalocyanine green dispersed in the aqueous phase has development potential. In this work, cellulose nanocrystals (CNCs) were used as dispersant and stabilizer to disperse phthalocyanine green in the aqueous phase. Phthalocyanine green was added to CNCs colloid to prepare phthalocyanine green suspensions with good dispersibility and stability. The particle size, zeta potential, absorbance and microstructure of the phthalocyanine green suspensions were tested and analyzed. The results showed that CNCs had good dispersibility and stability to phthalocyanine green due to charge repulsion and steric hindrance. The phthalocyanine green suspensions were nano-sized and had well compatibility with different types of coating forming substances. The coatings of the mixture had good water resistance, adhesion and mechanical properties. The suspensions had the application property and could be mixed with coating forming substances to prepare coating materials. As a renewable and easily degraded biomass resource, CNCs are expected to become a new dispersant and stabilizer for pigment.

Expanding the ubiquitin code in pancreatic cancer.

The ubiquitin-proteasome system (UPS) is a fundamental regulatory mechanism in cells, vital for maintaining cellular homeostasis, compiling signaling transduction, and determining cell fates. These biological processes require the coordinated signal cascades of UPS members, including ubiquitin ligases, ubiquitin-conjugating enzymes, deubiquitinases, and proteasomes, to ubiquitination and de-ubiquitination on substrates. Recent studies indicate that ubiquitination code rewriting is particularly prominent in pancreatic cancer. High frequency mutation or aberrant hyperexpression of UPS members dysregulates ferroptosis, tumor microenvironment, and metabolic rewiring processes and contribute to tumor growth, metastasis, immune evasion, and acquired drug resistance. We conduct an in-depth overview of ubiquitination process in pancreatic cancer, highlighting the role of ubiquitin code in tumor-promoting and tumor-suppressor pathways. Furthermore, we review current UPS modulators and analyze the potential of UPS modulators as cancer therapy.

Research on digital transformation strategy of the energy industry based on differential game under the dual-carbon background in China.

Digital transformation of the energy industry is at the vanguard of promoting green and low-carbon development of energy, and the transformation and upgrading of the energy industry is a critical path to achieve the goal of "dual carbon." The study takes energy enterprises, digital technology providers, and local governments in China as the research objects, then by constructing a three-party dynamic differential game model, four scenarios are considered respectively. The optimal digitization effort, digitization level, carbon emission reduction expectations, and optimal benefits of each subject are studied. The results show that: (1) Government subsidies function as an effective regulating mechanism, helping regulate the profit distribution of energy enterprises. With government subsidies, cost-sharing contracts can improve the profits of energy enterprises and digital service providers and enhance industry digitization and carbon emission reduction to some extent. (2) When there are government subsidies, the optimal digitalization efforts of energy enterprises and the optimal subsidy coefficient of government under the three decisions are independent of time. The extent to which subsidies improve system members' income is correlated to its game structure and status. (3) In the centralized decision-making state, digitalization level, product emission reduction, and total system profit are higher than in the decentralized decision-making state, which can better help the overall revenue system composed of energy enterprises, digital service providers, and local governments to achieve economic and environmental optimization at the same time and reach the Pareto optimal state. (4) With government subsidies and after the introduction of contracts, when certain conditions are met, the followers' optimal digital effort level, product emission reduction, digitization level, demand and profits of each member are all improved except for the leader's optimal effort level, Pareto improvement of profits of all participating members in the system is realized.

Exploring the dynamic changes in hydrogen bond structure of water and heavy water under external perturbation of DMF.

The Raman spectra of DMF-water/heavy water binary solutions at different volume ratios are measured to investigate the hydrogen bond structure between N, N-dimethylformamide (DMF) and water/heavy water. It was observed that when VDMF below 40 %, DMF reinforces the hydrogen bond among water molecules through the substitution of a small amount of water molecules within the tetrahedral structure. However, a similar enhancement phenomenon is not observed in heavy water. When VDMF is less than 60 %, the hydrogen bonds among DMF and heavy water molecules affect the symmetry of OD covalent bond. Furthermore, as VDMF exceeds 40 %/60 %, the tetrahedral structures of water and heavy water are gradually replaced by DMF·3H2O/3D2O, DMF·2H2O/2D2O, and DMF·H2O/D2O clusters. The transition point of hydrogen bond structure in DMF- aqueous solution moved to VDMF = 15 % under the influence of under the influence of dynamic high pressure caused by pulsed laser beam. This study provides valuable insights into the microstructure of water/heavy water clusters.