Small Conjugated Organic Ligand-Modified Polyoxometalate-Based Hybrid Materials for Boosting Photocatalytic CO2 Reduction.

Photocatalytic carbon dioxide (CO2) reduction to value-added chemicals is a multielectron transfer process, and the crucial step is the synthesis of photocatalysts. The introduction of small conjugated organic ligands can make the catalytic active site of the compound easier to be exposed in the reaction system and fully contact with the substrate, accelerating the photocatalytic reaction process. In this paper, we synthesized two isomorphic compounds, namely, {[Co(mtrz)3·(H2O)2]2·[SiW12O40]}·6H2O (1) and {[Ni(mtrz)3·(H2O)2]2·[SiW12O40]}·6H2O (2) (mtrz = 1-methyl-1,2,4-triazole). We found that compound 1 has a great photocatalytic performance through a series of experiments, with a CO reduction yield of 7364.92 µmol g-1 h-1 and a CO selectivity of 82.5%. Furthermore, the high catalytic activity can be maintained over four cycle experiments. The catalytic mechanism of its photocatalytic system is also elucidated, which provides an idea for realizing efficient catalytic reduction of CO2 to CO.

The Impact of Thermal Treatment Intensity on Proteins, Fatty Acids, Macro/Micro-Nutrients, Flavor, and Heating Markers of Milk-A Comprehensive Review.

Milk thermal treatment, such as pasteurization, high-temperature short-time processing, and the emerging ultra-short-time processing (<0.5 s), are crucial for ensuring milk safety and extending its shelf life. Milk is a nutritive food matrix with various macro/micro-nutrients and other constituents that are possibly affected by thermal treatment for reasons associated with processing strength. Therefore, understanding the relationship between heating strength and milk quality is vital for the dairy industry. This review summarizes the impact of thermal treatment strength on milk's nutritional and sensory properties, the synthesizing of the structural integrity and bioavailability of milk proteins, the profile and stability of fatty acids, the retention of macro/micro-nutrients, as well as the overall flavor profile. Additionally, it examines the formation of heat-induced markers, such as Maillard reaction products, lactulose, furosine, and alkaline phosphatase activity, which serve as indicators of heating intensity. Flavor and heating markers are commonly used to assess the quality of pasteurized milk. By examining former studies, we conclude that ultra-short-time-processing-treated milk is comparable to pasteurized milk in terms of specific parameters (such as whey protein behavior, furosine, and ALP contents). This review aims to better summarize how thermal treatments influence the milk matrix, guiding the dairy industry's development and balancing milk products' safety and nutritional value.

Programmable Chemical Evolution with Natural/non-natural Building Blocks.

Non-natural building blocks (BBs) present a vast reservoir of chemical diversity for molecular recognition and drug discovery. However, leveraging evolutionary principles to efficiently generate bioactive molecules with a larger number of diverse BBs poses challenges within current laboratory evolution systems. Here, we introduce programmable chemical evolution (PCEvo) by integrating chemoinformatic classification and high-throughput array synthesis/screening. PCEvo initiates evolution by constructing a diversely combinatorial library to create ancestral molecules, streamlines the molecular evolution process and identifies high-affinity binders within 2-4 cycles. By employing PCEvo with 108 BBs and exploring >10^17 chemical space, we identify bicyclic peptidomimetic binders against targets SAR-CoV-2 RBD and Claudin18.2, achieving nanomolar affinity. Remarkably, Claudin18.2 binders selectively stain gastric adenocarcinoma cell lines and patient samples. PCEvo achieves expedited evolution in a few rounds, marking a significant advance in utilizing non-natural building blocks for rapid chemical evolution applicable to targets with or without prior structural information and ligand preference.

Layered Co-O Cluster Applied to Photocatalytic CO2 Reduction.

In the field of recycling CO2, the photocatalytic CO2 reduction reaction (CO2RR) is a typical example, and researchers have designed a variety of photocatalysts to improve the conversion rate of CO2 over the years. In this paper, two metal-oxygen clusters are designed and formulated as [Co3Zn(OH)6(SO4)]·4H2O (1) and [Ni3Zn(OH)6(SO4)]·4H2O (2). As for compound 1, the main structure is composed of {CoO6} octahedra connected by edge-sharing to form a two-dimensional layer, on which {ZnO4} and {SO4} tetrahedra are supported. More interestingly, compound 1 has outstanding photocatalytic activity, which is mainly attributed to the open-framework structure and the cobalt ions as active sites. Upon catalysis for eight hours, its maximum CO generation rate is 9982.13 µmol g-1 h-1, with a selectivity of 81.8%. Additionally, compound 1 takes on weak antiferromagnetic coupling due to Co(II) ions.

Efficient Visible-Light-Driven Hydrogen Production over Cu-Modified Polyoxotungstate Hybrids.

Hydrogen energy is a renewable and clean source, which makes a great difference in future sustainable energy systems. Visible-light-driven photocatalysis reaction involves harnessing the abundance of sunlight for hydrogen production among many catalytic technologies. However, the fabrication of photocatalysts that have distinctive performance in visible light is still the primary challenge. Herein, two new Cu-modified polyoxotungstate hybrids, {[Cu2(bim)4(H2O)2](HBW12O40)2·(H2bim)2·8H2O} (1) (bim = [1,1'-methylenebis(1H-imidazole)]) and {[Cu2(bim)4(H2O)2](H3PW10Ti2O40)2·(H2bim)2·8H2O} (2), have been successfully isolated by bridging two saturated Keggin polyoxotungstates and copper-azole complexes. Not surprisingly, 2 holds higher reduction activity due to the more negative charge and stronger basicity on the terminal oxygen of Ti═O and bridge oxygen of Ti-O-W. The H2 yield was 17075 µmol g-1 h-1 for 2 in the tunable light-driven H2 production system, which is promising in the field of photocatalysis.

Two 1D Anderson-Type Polyoxometalate-Based Metal-Organic Complexes as Bifunctional Heterogeneous Catalysts for CO2 Photoreduction and Sulfur Oxidation.

Sulfur oxides from the combustion of petrol and excessive emissions of carbon dioxide (CO2) are currently the main causes of environmental pollution. Considerable interest has been paid to solving the challenge, and catalytic reactions seem to be the desired choice. Due to the high density of Lewis acid active sites, polyoxometalates are considered to be the ideal choice for these catalytic reactions. Herein, two captivating polyoxometalate-based metal-organic complexes, formulated as [Co(H2O)2DABT]2[CrMo6(OH)5O19] ({Co-CrMo6}) and [Zn(H2O)2DABT]2[CrMo6(OH)5O19] ({Zn-CrMo6}) (DABT = 3,3'-diamino-5,5'-bis(1H-1,2,4-triazole)) were successfully obtained under hydrothermal conditions. The structural analysis demonstrates that {Co-CrMo6} and {Zn-CrMo6} are isostructural with two different transition metal (Co/Zn) ions based on quadridentate Anderson-type [CrMo6(OH)5O19]4- polyanions. A fan-shaped unit of {Co-CrMo6}/{Zn-CrMo6} is linked to generate a one-dimensional (1D) ladder-like structure. Intriguingly, benefitting from rich Co centers with a suitable energy band structure, {Co-CrMo6} displays better photocatalytic activity than {Zn-CrMo6} for converting CO2 into CO, endowing the CO formation of 1935.3 µmol g-1 h-1 with high selectivity. Meanwhile, {Co-CrMo6} also exhibits a satisfactory removal rate of 99% for oxidizing dibenzothiophene at 50 °C, which suggests that {Co-CrMo6} may be utilized as a potential dual functional material with immense prospects in photocatalytic CO2 reduction and sulfur oxidation for the first time.

BAK1 plays contrasting roles in regulating abscisic acid-induced stomatal closure and abscisic acid-inhibited primary root growth in Arabidopsis.

The mechanisms that balance plant growth and stress responses are poorly understood, but they appear to involve abscisic acid (ABA) signaling mediated by protein kinases. Here, to explore these mechanisms, we examined the responses of Arabidopsis thaliana protein kinase mutants to ABA treatment. We found that mutants of BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) were hypersensitive to the effects of ABA on both seed germination and primary root growth. The kinase OPEN STOMATA 1 (OST1) was more highly activated by ABA in bak1 mutant than the wild type. BAK1 was not activated by ABA treatment in the dominant negative mutant abi1-1 or the pyr1 pyl4 pyl5 pyl8 quadruple mutant, but it was more highly activated by this treatment in the abi1-2 abi2-2 hab1-1 loss-of-function triple mutant than the wild type. BAK1 phosphorylates OST1 T146 and inhibits its activity. Genetic analyses suggested that BAK1 acts at or upstream of core components in the ABA signaling pathway, including PYLs, PP2Cs, and SnRK2s, during seed germination and primary root growth. Although the upstream brassinosteroid (BR) signaling components BAK1 and BR INSENSITIVE 1 (BRI1) positively regulate ABA-induced stomatal closure, mutations affecting downstream components of BR signaling, including BRASSINOSTEROID-SIGNALING KINASEs (BSKs) and BRASSINOSTEROID-INSENSITIVE 2 (BIN2), did not affect ABA-mediated stomatal movement. Thus, our study uncovered an important role of BAK1 in negatively regulating ABA signaling during seed germination and primary root growth, but positively modulating ABA-induced stomatal closure, thus optimizing the plant growth under drought stress.

A reduced polyoxometalate-encapsulated organo cobalt modified phosphate framework for improving photocatalytic reduction of CO2.

A reduced polyoxometalate-based organo-metallophosphate (MOPO) framework formulated as [Co4(PO4)(C7H8N4)6](PWVI10WV2O40) (Co-PO4-PW12) with an ultra-high CO production rate of 13 676 µmol g-1 h-1 has been presented through photocatalytic CO2 reduction investigations.

Thermo-responsive composite nanoparticles based on hydroxybutyl chitosan oligosaccharide: Fabrication, stimulus release and cancer therapy.

Designing thermo-responsive nanocarriers based on biopolymers is fascinating and challenging for cancer therapy. In this study, thermo-responsive composite nanoparticles (CNPs) were prepared using hydroxybutyl chitosan oligosaccharide (HBCOS) and sodium caseinate (SC) via electrostatic interactions and covalent crosslinking. The temperature-responsive behaviors of CNPs were induced by the breakage of hydrogen bonds and the shrinkage of chains in nanoparticles. The CNPs exhibited concentration-independent thermo-responsive behavior, non-adsorption aggregation, and non-hemolysis, suggesting excellent stability and thermo-sensitivity. The initial release rate and final amount of DOX released from CNPs at 42 °C were higher than that at 37 °C, showing a thermo-responsive release, which was also more prominent at lower pH. The release of DOX from CNPs followed first order kinetics based on Fickian diffusion. In vitro cytotoxicity assays confirmed the thermo-responsive antitumor activity of DOX-loaded CNPs as the HT-29 cell viability incubated with DOX-loaded CNPs at 42 °C was significantly lower than that at 37 °C. Cellular uptake experiments proved that DOX-loaded CNPs accumulated in the cytoplasm after being endocytosed and promoted DOX release by increasing environment temperature. This study generated stable thermo-sensitive CNPs based on biopolymers, which can be used as potential nanocarriers for the controlled release of anticancer drugs for cancer therapy.

Racial and Ethnic Disparities in Receipt of General Anesthesia for Cesarean Delivery.

Importance: General anesthesia for cesarean delivery is associated with increased maternal morbidity, and Black and Hispanic pregnant patients have higher rates of general anesthesia use compared with their non-Hispanic White counterparts. It is unknown whether risk factors and indications for general anesthesia differ among patients of differing race and ethnicity. Objective: To evaluate differences in general anesthesia use for cesarean delivery and the indication for the general anesthetic by race and ethnicity. Design, Setting, and Participants: In this retrospective, cross-sectional, single-center study, electronic medical records for all 35 117 patients who underwent cesarean delivery at Northwestern Medicine's Prentice Women's Hospital from January 1, 2007, to March 2, 2018, were queried for maternal demographics, clinical characteristics, obstetric and anesthetic data, the indication for cesarean delivery, and the indication for general anesthesia when used. Data analysis occurred in August 2023. Exposure: Cesarean delivery. Main Outcomes and Measures: The rate of general anesthesia for cesarean delivery by race and ethnicity. Results: Of the 35 117 patients (median age, 33 years [IQR, 30-36 years]) who underwent cesarean delivery, 1147 (3.3%) received general anesthesia; the rates of general anesthesia were 2.5% for Asian patients (61 of 2422), 5.0% for Black patients (194 of 3895), 3.7% for Hispanic patients (197 of 5305), 2.8% for non-Hispanic White patients (542 of 19 479), and 3.8% (153 of 4016) for all other groups (including those who declined to provide race and ethnicity information) (P < .001). A total of 19 933 pregnant patients (56.8%) were in labor at the time of their cesarean delivery. Of those, 16 363 (82.1%) had neuraxial labor analgesia in situ. Among those who had an epidural catheter in situ, there were no racial or ethnic differences in the rates of general anesthesia use vs neuraxial analgesia use (Asian patients, 34 of 503 [6.8%] vs 1289 of 15 860 [8.1%]; Black patients, 78 of 503 [15.5%] vs 1925 of 15 860 [12.1%]; Hispanic patients, 80 of 503 [15.9%] vs 2415 of 15 860 [15.2%]; non-Hispanic White patients, 255 of 503 [50.7%] vs 8285 of 15 860 [52.2%]; and patients of other race or ethnicity, 56 of 503 [11.1%] vs 1946 of 15 860 [12.3%]; P = .16). Indications for cesarean delivery and for general anesthesia were not different when stratified by race and ethnicity. Conclusions and Relevance: Racial disparities in rates of general anesthesia continue to exist; however, this study suggests that, for laboring patients who had labor epidural catheters in situ, no disparity by race or ethnicity existed. Future studies should address whether disparities in care that occur prior to neuraxial catheter placement are associated with higher rates of general anesthesia among patients from ethnic and racial minority groups.

Antioxidant Lipid Supplement on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis.

The efficacy of functional lipids with antioxidant properties in reducing cardiovascular risk has not been consistent. Randomized controlled trials (RCTs) reporting estimates for the effects of antioxidant functional lipid supplementations on cardiometabolic risk factors were searched up to 1 May 2024. Overall, antioxidant lipid supplementations, compared with placebo, had favorable effects on systolic blood pressure (lycopene: -1.95 [-3.54, -0.36] mmHg), low-density lipoprotein cholesterol (n6 fatty acid: -0.39 [-0.71, -0.06] mmol/L; astaxanthin: -0.11 [-0.21, -0.01] mmol/L), high-density lipoprotein cholesterol (n3 fatty acid: 0.20 [0.13, 0.27] mmol/L; n6 fatty acid: 0.08 [0.01, 0.14] mmol/L; astaxanthin: 0.13 [0.05, 0.21] mmol/L), total cholesterol (n6 fatty acid: -0.24 [-0.37, -0.11] mmol/L; astaxanthin: -0.22 [-0.32, -0.12] mmol/L; beta-carotene: -0.13 [-0.23, -0.04] mmol/L), triglyceride (n3 fatty acid: -0.37 [-0.47, -0.28] mmol/L; astaxanthin: -0.46 [-0.83, -0.10] mmol/L), and fasting blood insulin (astaxanthin: -2.66 [-3.98, -1.34] pmol/L). The benefits of antioxidant lipid supplementations appeared to be most evident in blood pressure and blood lipids in participants with different cardiometabolic health statuses. Notably, n9 fatty acid increased triglyceride and hemoglobin A1C in the total population, which increases CVD risk. Antioxidant lipid supplementations ameliorate cardiometabolic risk factors, while their effect may depend on type and cardiometabolic health status. Long-term RCTs are needed to corroborate risk-benefit ratios across different antioxidant functional lipid supplementation settings.

The Antioxidant Dendrobium officinale Polysaccharide Modulates Host Metabolism and Gut Microbiota to Alleviate High-Fat Diet-Induced Atherosclerosis in ApoE-/- Mice.

BACKGROUND: The discovery of traditional plants' medicinal and nutritional properties has opened up new avenues for developing pharmaceutical and dietary strategies to prevent atherosclerosis. However, the effect of the antioxidant Dendrobium officinale polysaccharide (DOP) on atherosclerosis is still not elucidated. PURPOSE: This study aims to investigate the inhibitory effect and the potential mechanism of DOP on high-fat diet-induced atherosclerosis in Apolipoprotein E knockout (ApoE-/-) mice. STUDY DESIGN AND METHODS: The identification of DOP was measured by high-performance gel permeation chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). We used high-fat diet (HFD)-induced atherosclerosis in ApoE-/- mice as an animal model. In the DOP intervention stage, the DOP group was treated by gavage with 200 µL of 200 mg/kg DOP at regular times each day and continued for eight weeks. We detected changes in serum lipid profiles, inflammatory factors, anti-inflammatory factors, and antioxidant capacity to investigate the effect of the DOP on host metabolism. We also determined microbial composition using 16S rRNA gene sequencing to investigate whether the DOP could improve the structure of the gut microbiota in atherosclerotic mice. RESULTS: DOP effectively inhibited histopathological deterioration in atherosclerotic mice and significantly reduced serum lipid levels, inflammatory factors, and malondialdehyde (F/B) production. Additionally, the levels of anti-inflammatory factors and the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased after DOP intervention. Furthermore, we found that DOP restructures the gut microbiota composition by decreasing the Firmicutes/Bacteroidota (F/B) ratio. The Spearman's correlation analysis indicated that serum lipid profiles, antioxidant activity, and pro-/anti-inflammatory factors were associated with Firmicutes, Bacteroidota, Allobaculum, and Coriobacteriaceae_UCG-002. CONCLUSIONS: This study suggests that DOP has the potential to be developed as a food prebiotic for the treatment of atherosclerosis in the future.

The Combination of Lactoferrin and Creatine Ameliorates Muscle Decay in a Sarcopenia Murine Model.

BACKGROUND: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. METHOD: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. RESULT: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM-receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. CONCLUSIONS: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.

New insights into the milk quality at varying altitudes in China.

Introducing Holstein cows on Qinghai-Tibetan Plateau is a potential solution to enhance local milk production. However, the relationship between milk quality and altitude in China remains unknown. Therefore, the components and plasmin (PL) system of raw milk from different altitudes (sea level, 1600, 2700, and 3800 m) were investigated. The daily milk production of Holstein cows and PL activity decreased as the altitude increased. However, the components content of raw milk, plasminogen (PLG)/PL ratio, activities of PLG and plasmin activator (PA) increased with altitude. The pasteurization resulted a significant decrease in PA activity of all milk and a significant increase in PL activity in milk collected at higher altitudes (2700 and 3800 m), suggesting the pasteurization was unsuitable for preserving milk at higher altitudes. This study offered references for the production and storage of milk after introducing Holstein cows on Qinghai-Tibetan Plateau.

Photoaffinity labeling coupled with proteomics identify PDI-ADAM17 module is targeted by (-)-vinigrol to induce TNFR1 shedding and ameliorate rheumatoid arthritis in mice.

Various biological agents have been developed to target tumor necrosis factor alpha (TNF-α) and its receptor TNFR1 for the rheumatoid arthritis (RA) treatment, whereas small molecules modulating such cytokine receptors are rarely reported in comparison to the biologicals. Here, by revealing the mechanism of action of vinigrol, a diterpenoid natural product, we show that inhibition of the protein disulfide isomerase (PDI, PDIA1) by small molecules activates A disintegrin and metalloprotease 17 (ADAM17) and then leads to the TNFR1 shedding on mouse and human cell membranes. This small-molecule-induced receptor shedding not only effectively blocks the inflammatory response caused by TNF-α in cells, but also reduces the arthritic score and joint damage in the collagen-induced arthritis mouse model. Our study indicates that targeting the PDI-ADAM17 signaling module to regulate the shedding of cytokine receptors by the chemical approach constitutes a promising strategy for alleviating RA.

Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling.

Microplastics (MPs) are environmental pollutants and can be inhaled by humans to threaten health. The lung tissue, responsible for the gas exchange between the body and the environment, is vulnerable to MPs exposure. However, from the perspective of cellular senescence, the effect of MPs on lung cells and tissues has not yet been deeply dissected. In this study, we reported that all the four typical MPs exhibited the significant biological effects in term of inducing senescence of human lung derived cells A549 and BEAS-2B in vitro. We further found that polyvinyl chloride (PVC) increased the reactive oxygen species (ROS) level in A549 cells and that PVC-induced senescent characteristics could be largely reversed by antioxidant treatment. Importantly, intratracheal instillation of PVC MPs in mice could effectively impair their physical function, induce the increased systemic inflammation level, cause the accumulation of senescent cells. Our study demonstrates that MPs induce senescence in human lung epithelial cells and mouse lungs by activating ROS signaling, and provides new insight into the potential pathogenesis of MPs on lung diseases.

Gambogic acid exhibits promising anticancer activity by inhibiting the pentose phosphate pathway in lung cancer mouse model.

BACKGROUND: The pentose phosphate pathway (PPP) plays a crucial role in the material and energy metabolism in cancer cells. Targeting 6-phosphogluconate dehydrogenase (6PGD), the rate-limiting enzyme in the PPP metabolic process, to inhibit cellular metabolism is an effective anticancer strategy. In our previous study, we have preliminarily demonstrated that gambogic acid (GA) induced cancer cell death by inhibiting 6PGD and suppressing PPP at the cellular level. However, it is unclear whether GA could suppress cancer cell growth by inhibiting PPP pathway in mouse model. PURPOSE: This study aimed to confirm that GA as a covalent inhibitor of 6PGD protein and to validate that GA suppresses cancer cell growth by inhibiting the PPP pathway in a mouse model. METHODS: Cell viability was detected by CCK-8 assays as well as flow cytometry. The protein targets of GA were identified using a chemical probe and activity-based protein profiling (ABPP) technology. The target validation was performed by in-gel fluorescence assay, the Cellular Thermal Shift Assay (CETSA). A lung cancer mouse model was constructed to test the anticancer activity of GA. RNA sequencing was performed to analyze the global effect of GA on gene expression. RESULTS: The chemical probe of GA exhibited high biological activity in vitro. 6PGD was identified as one of the binding proteins of GA by ABPP. Our findings revealed a direct interaction between GA and 6PGD. We also found that the anti-cancer activity of GA depended on reactive oxygen species (ROS), as evidenced by experiments on cells with 6PGD knocked down. More importantly, GA could effectively reduce the production of the two major metabolites of the PPP in lung tissue and inhibit cancer cell growth in the mouse model. Finally, RNA sequencing data suggested that GA treatment significantly regulated apoptosis and hypoxia-related physiological processes. CONCLUSION: These results demonstrated that GA was a covalent inhibitor of 6PGD protein. GA effectively suppressed cancer cell growth by inhibiting the PPP pathway without causing significant side effects in the mouse model. Our study provides in vivo evidence that elucidates the anticancer mechanism of GA, which involves the inhibition of 6PGD and modulation of cellular metabolic processes.

A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer.

The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.

Surface chemistry of graphene tailoring the activity of digestive enzymes by modulating interfacial molecular interactions.

As a kind of novel functional material, graphene-related nanomaterials (GRMs) have great potentials in industrial and biomedical applications. Meanwhile, the production and wide application of GRMs will increase the risk of unintended or intentional oral exposure to human beings, attracting safety concerns about their biological fates and toxicological effects. The normal enzymatic activity of digestive enzymes is essential for the proper functioning of the gastrointestinal tract system. However, whether and how orally entered GRMs and their surface groups affect digestive enzymes' activity are still scarce. In this paper, we systematically studied the effects of graphene oxide (GO), graphene modified with hydroxyl groups (OH-G), carboxyl groups (COOH-G), and amino groups (NH2-G) on enzymatic activity of three typical digestive enzymes (pepsin, trypsin, and α-pancreatic amylase). The results showed that the activity of trypsin and α-pancreatic amylase could be greatly changed after GRMs incubation in a surface chemistry dependent manner, while the activity of pepsin was not affected. To elucidate the mechanisms at the molecular level, the interactions between trypsin and GRMs were studied by spectrometry, thermophoresis, and computational simulation approaches, and the key roles of surface chemistry of GRMs in tailoring the activity of trypsin were finally figured out. GO allosterically inhibited trypsin's activity in the non-competitive manner because of the conformation transition induced by the intensive interactions. COOH-G could effectively hamper enzymatic activity of trypsin in the competitive manner by blocking the active catalytic pocket. As for NH2-G and OH-G, they had little impact on the activity of trypsin due to the weak binding affinity or limited conformational change. Our findings not only indicate surface chemistry plays an important role in tailoring the effects of GRMs on the activity of digestive enzymes but also provide new insights for understanding the oral safety of nanomaterials from daily products and the environment.

Personalized smart voice-based electronic prescription for remote at-home feedback management in cardiovascular disease rehabilitation: a multi-center randomized controlled trial.

Objective: To investigate the quality and efficacy of remote at-home rehabilitation for patients with cardiovascular disease (CVD) using personalized smart voice-based electronic prescription, and further explore the standardized health management mode of remote family cardiac rehabilitation. Trial design: A multicenter, randomized (1:1), non-blind, parallel controlled study. Methods: A total of 171 patients with CVD who were admitted to 18 medical institutions in China from April 2021 to October 2022 were randomly divided into a treatment group (86 cases) and a control group (85 cases) in a non-blinded experiment, based on the sequence of enrollment. The control group received routine at-home rehabilitation training, and the treatment group received remote feedback-based at-home cardiac rehabilitation management based on routine at-home rehabilitation training. The primary outcome was the difference in VO2peak (mL/min/kg) after 12 weeks. A linear mixed model was developed with follow-up as the dependent variable. Age and baseline data were utilized as covariates, whereas hospital and patient characteristics were adjusted as random-effect variables. As the linear mixed model can accommodate missing data under the assumption of random missing data, there was no substitute missing value for quantitative data. Results: A total of 171 participants, with 86 in the experimental group and 85 in the control group, were included in the main analysis. The analysis, which used linear mixing model, revealed significant differences in cardiopulmonary function indexes (VO2/kg peak, VO2peak, AT, METs, and maximum resistance) at different follow-up time (0, 4, and 12 weeks) in the experimental group (p < 0.05). In the control group, there was no significant difference in cardiopulmonary values at different follow-up time (0, 4, and 12 weeks; p > 0.05). VO2/kg peak (LS mean 1.49, 95%CI 0.09-2.89, p = 0.037) and other indicators of cardiopulmonary function (p < 0.05) were significantly different between the experimental group and the control group at week 12. The results were comparable in the complete case analysis. Conclusion: The remote home cardiac rehabilitation management mode using personalized smart voice-based electronic prescription provides several benefits to patients, including improvements in muscle strength, endurance, cardiopulmonary function, and aerobic metabolism. It also helps reduce risk factors for cardiovascular disease and enhances patients' self-management abilities and treatment compliance.Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2100044063.