Nature-Inspired Photocatalytic Azo Bond Cleavage with Red Light.

The emerging field of photoredox catalysis in mammalian cells enables spatiotemporal regulation of a wealth of biological processes. However, the selective cleavage of stable covalent bonds driven by low-energy visible light remains a great challenge. Herein, we report that red light excitation of a commercially available dye, abbreviated NMB+, leads to catalytic cleavage of stable azo bonds in both aqueous solutions and hypoxic cells and hence a means to photodeliver drugs or functional molecules. Detailed mechanistic studies reveal that azo bond cleavage is triggered by a previously unknown consecutive two-photon process. The first photon generates a triplet excited state, 3NMB+*, that is reductively quenched by an electron donor to generate a protonated NMBH•+. The NMBH•+ undergoes a disproportionation reaction that yields the initial NMB+ and two-electron-reduced NMBH (i.e., leuco-NMB, abbreviated as LNMB). Interestingly, LNMB forms a charge transfer complex with all four azo substrates that possess an intense absorption band in the red region. A second red photon induces electron transfer from LNMB to the azo substrate, resulting in azo bond cleavage. The charge transfer complex mediated two-photon catalytic mechanism reported herein is reminiscent of the flavin-dependent natural photoenzyme that catalyzes bond cleavage reactions with high-energy photons. The red-light-driven photocatalytic strategy offers a new approach to bioorthogonal azo bond cleavage for photodelivery of drugs or functional molecules.

The fertility tracks of pollen tube in the ovary of Solanum nigrum by three-dimensional reconstruction.

In this paper, we present an enhanced method for automatically capturing a large number of consecutive paraffin sections using a microscope. Leveraging these microstructural images, we employed three-dimensional visualisation and reconstruction techniques to investigate the dispersal growth process of pollen tube bundles upon entering the ovary of Solanum nigrum. Additionally, we explored their behaviour within different ovules and examined the relationship between the germination rate of seeds and the fertilisation process. Our findings reveal that despite the abundance of Solanum nigrum seeds, only a fraction of them is capable of successful germination. The germination rate of seeds is closely related to whether fertilisation of the ovules and pollen tubes is completed. Due to the limited number of pollen tubes entering the ovary, only a portion of the ovules can be fertilised. The proportion of fertilised ovules positively correlates with the germination rate of the seeds. Through three-dimensional reconstruction, we observed a phenomenon of proximity during the pollination process, wherein ovules closer to the pollen tube bundles are more likely to be fertilised. Furthermore, fertilised ovules exhibited significant changes in morphology and embryo sac structure. The number of fertilised ovules directly impacts the germination rate of wild Solanum nigrum seeds. Although all Solanum nigrum ovules have the potential to develop into seeds, most seeds originating from unfertilised ovules are unable to germinate normally, resulting in an incomplete germination rate of seeds and preventing it from reaching 100%.

Synthesis of New Derivatives of Berberine Canagliflozin and Study of Their Antibacterial Activity and Mechanism.

The isoquinoline alkaloid berberine, derived from Coptidis rhizoma, exhibits antibacterial, hypoglycemic, and anti-inflammatory properties. Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. We synthesized compounds B9OC and B9OBU by conjugating canagliflozin and n-butane at the C9 position of berberine, aiming to develop antimicrobial agents for combating bacterial infections worldwide. We utilized clinically prevalent pathogenic bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, to investigate the antibacterial efficacy of B9OC. This was accomplished through the determination of the MIC80 values, analysis of bacterial growth curves, evaluation of biofilm formation using crystal violet staining, assessment of impact on bacterial proteins via SDS-PAGE analysis, and observation of alterations in bacterial morphology utilizing field emission scanning electron microscopy. Meanwhile, the ADMET of compound B9OC was predicted using a computer-aided method. The findings revealed that B9OC exhibited lower minimal inhibitory concentrations against all three bacteria compared to berberine alone or in combination with canagliflozin. The minimal inhibitory concentrations (MICs) of B9OC against the three experimental strains were determined to be 0.035, 0.258, and 0.331 mM. However, B9OBu exhibited a lower level of antimicrobial activity compared to berberine. The compound B9OC exhibits a broad spectrum of antibacterial activity by disrupting the integrity of bacterial cell walls, leading to cellular rupture and the subsequent degradation of intracellular proteins.

Physical activity diminished adverse associations of obesity with lipid metabolism in the population of rural regions of China.

The interactive effects of obesity and physical inactivity on lipid metabolism and prevalent dyslipidemia are scarcely reported in rural regions. 39029 subjects were obtained from the Henan Rural Cohort, and their metabolic equivalents (METs) of physical activity (PA) were computed. Independent associations of the obesity indices and PA with either lipid indices or prevalent dyslipidemia were analyzed by generalized linear models, and additive effects of obesity and PA on prevalent dyslipidemia were further quantified. Each obesity index was positively associated with total cholesterol, triglyceride, low-density lipoprotein or prevalent dyslipidemia but negatively associated with high-density lipoprotein, whereas the opposite association of PA with either each lipid index or prevalent dyslipidemia was observed. Joint association of PA and each obesity index with each lipid index and prevalent dyslipidemia was observed. Furthermore, the association of each obesity index in association with each lipid index was attenuated by increased PA levels.

The association between retinol-binding protein 4 and risk of type 2 diabetes: A systematic review and meta-analysis.

Retinol-binding protein 4 (RBP4) was controversially associated with type 2 diabetes mellitus (T2DM). This meta-analysis aimed at evaluating the association between RBP4 level and T2DM risk. MEDLINE and EMBASE were searched to identify relevant studies up to 3 December 2022. Random effects model was used to pool multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias was estimated by Funnel plot and Egger's test, it was considered to be significant when P < 0.05. Eight studies including 8087 participants were finally included. Compared to those with the lowest level, subjects with the highest level of RBP4 have a higher risk of T2DM (OR = 1.47, 95% CI: 1.16-1.78, P < 0.001, I2 = 86.9%). No publication bias among the included studies was found (t = 0.94, P = 0.377). This meta-analysis indicated that high RBP4 level was associated with increasing risk of T2DM.

Cellulase with Bacillus velezensis improves physicochemical characteristics, microbiota and metabolites of corn germ meal during two-stage co-fermentation.

Corn germ meal (CGM) is one of the major byproducts of corn starch extraction. Although CGM has rich fiber content, it lacks good protein content and amino acid balance, and therefore cannot be fully utilized as animal feed. In this study, we investigated the processing effect of cellulase synergized with Bacillus velezensis on the nutritional value of pretreated CGM (PCGM) in two-stage solid-state fermentation (SSF). High-throughput sequencing technology was used to explore the dynamic changes in microbial diversity. The results showed that compared with four combinations of B. velezensis + Lactiplantibacillus plantarum (PCGM-BL), cellulase + L. plantarum (PCGM-CL),control group (PCGM-CK), and cellulase + B. velezensis + L. plantarum (PCGM-BCL), the fourth combination of PCGM-BCL significantly improved the nutritional characteristics of PCGM. After two-stage SSF (48 h), viable bacterial count and contents of crude protein (CP) and trichloroacetic acid-soluble protein (TCA-SP) all were increased in PCGM-BCL (p < 0.05), while the pH was reduced to 4.38 ± 0.02. In addition, compared with PCGM-BL, the cellulose degradation rate increased from 5.02 to 50.74%, increasing the amounts of short-chain fatty acids (216.61 ± 2.74 to 1727.55 ± 23.00 µg/g) and total amino acids (18.60 to 21.02%) in PCGM-BCL. Furthermore, high-throughput sequencing analysis revealed significant dynamic changes in microbial diversity. In the first stage of PCGM-BCL fermentation, Bacillus was the dominant genus (99.87%), which after 24 h of anaerobic fermentation changed to lactobacillus (37.45%). Kyoto Encylopaedia of Genes and Genomes (KEGG) metabolic pathway analysis revealed that the pathways related to the metabolism of carbohydrates, amino acids, cofactors, and vitamins accounted for more than 10% of the enriched pathways throughout the fermentation period. Concisely, we show that cellulase can effectively improve the nutritional value of PCGM when synergized with B. velezensis in two-stage SSF.

Jumping Interval Training: An Effective Training Method for Enhancing Anaerobic, Aerobic, and Jumping Performances in Aerobic Gymnastics.

The aim of this study was to compare the effects of jumping interval training (JIT) and running high-intensity interval training (HIIT) on the aerobic, anaerobic and jumping performances of youth female aerobic gymnasts. A randomized controlled study was conducted over an 8-week period, involving 73 youth female athletes (16.2 ± 1.3 years old) of aerobic gymnastics. The study comprised two experimental groups (JIT and HIIT) and a control group. Participants in the experimental groups engaged in two additional training sessions per week alongside their regular training regimen, while the control group followed their usual training routine. Before and after the intervention period, gymnasts were assessed for their performance in the countermovement jump test (CMJ), the specific aerobic gymnastics anaerobic test (SAGAT) and the 20-m multistage fitness test. Significant interactions time × group were found in SAGAT (p < 0.001; = 0.495), CMJ (p < 0.001; = 0.338) and 20-m multistage fitness test (p < 0.001; = 0.500). The time × group analysis post-intervention revealed significantly lower scores in SAGAT for the control group compared to the JIT (p = 0.003) and HIIT (p = 0.034). Additionally, significantly higher scores were observed for the JIT group in the CMJ test compared to the HIIT (p = 0.020) and control (p = 0.028) groups following the intervention. Finally, the 20 m multistage fitness test post-intervention revealed significantly lower scores for the control group compared to JIT (p < 0.001) and HIIT (p < 0.001). Both JIT and HIIT are recommended training strategies to adopt in aerobic gymnastics for significantly improving the aerobic and anaerobic performances of athletes. However, JIT may be particularly relevant to use as it offers additional benefits in improving vertical jumping performances.

Simulation and an experimental study on the optical performance of a Wolter-I focusing mirror based on a 3D ray tracing algorithm.

The nested Wolter-I type focusing mirror is widely used in the field of X-ray astronomy. The thin-shell mirrors produced by the electroforming replication method will introduce various shape errors during the fabricating and assembling process. This study introduces a non-analytical 3D geometrical ray tracing algorithm capable of predicting optical performance for large mirror deformations. The algorithm's implementation involves error reconstruction, light source and ray simulation, and optical performance calculation. Experimental and simulation validation underscores the algorithm's precision and effectiveness. The results also indicate that edge deformation can seriously affect imaging contrast which is generally considered to be determined only by surface scattering. Applying the 3D ray tracing algorithm, a range of low-frequency fabrication and assembly errors are simulated, such as absolute radius, taper, roundness, edge effects, mirror posture, and hoisting deformation errors, and their effects on imaging quality are analyzed and discussed.

Weizmannia coagulans JA845 improves atherosclerosis induced by vitamin D3 and high-fat diet in rats through modulating lipid metabolism, oxidative stress, and endothelial vascular injury.

AIMS: Probiotics have been proved to be strongly linked to the occurrence and progression of atherosclerosis. This study aimed to investigate the improved effects and mechanisms underlying a potential probiotic, Weizmannia coagulans JA845, on atherosclerosis. METHODS AND RESULTS: Male Sprague-Dawley rats supported on a high-fat diet with vitamin D3 supplementation were subjected to W. coagulans JA845 treatment. W. coagulans JA845 obviously alleviated histological abnormalities of the abdominal aorta. After 6 weeks of W. coagulans JA845 administration, levels of TG, TC, LDL, ox-LDL, ROS, and MDA in the JA845 group decreased significantly, and those of HDL, GSH-Px, and SOD were markedly elevated. Treatment with W. coagulans JA845 also inhibited the secretion of ICAM-1 and VCAM-1 and regulated the plasma NO and eNOS content. In brief, administration of W. coagulans JA845 promoted the expression of the SIRT3/SOD2/FOXO3A pathway, inhibited the lipid metabolism pathway, SREBP-1c/FAS/DGAT2, and suppressed the JNK2/P38 MAPK/VEGF pathway implicated in endothelial injury. CONCLUSIONS: These results indicated W. coagulans JA845 improved atherosclerosis by regulating lipid metabolism, antioxidative stress, and protecting against endothelial injury.

Analysis of the Potassium-Solubilizing Priestia megaterium Strain NK851 and Its Potassium Feldspar-Binding Proteins.

Potassium-solubilizing bacteria are an important microbial group that play a critical role in releasing mineral potassium from potassium-containing minerals, e.g., potassium feldspar. Their application may reduce eutrophication caused by overused potassium fertilizers and facilitate plants to utilize environmental potassium. In this study, a high-efficiency potassium-solubilizing bacterium, named NK851, was isolated from the Astragalus sinicus rhizosphere soil. This bacterium can grow in the medium with potassium feldspar as the sole potassium source, releasing 157 mg/L and 222 mg/L potassium after 3 days and 5 days of incubation, respectively. 16S rDNA sequencing and cluster analysis showed that this strain belongs to Priestia megaterium. Genome sequencing further revealed that this strain has a genome length of 5,305,142 bp, encoding 5473 genes. Among them, abundant genes are related to potassium decomposition and utilization, e.g., the genes involved in adherence to mineral potassium, potassium release, and intracellular trafficking. Moreover, the strong potassium-releasing capacity of NK851 is not attributed to the acidic pH but is attributed to the extracellular potassium feldspar-binding proteins, such as the elongation factor TU and the enolase that contains potassium feldspar-binding cavities. This study provides new information for exploration of the bacterium-mediated potassium solubilization mechanisms.

Transformation of Ginsenosides by Lactiplantibacillus plantarum MB11 Fermentation: Minor Ginsenosides Conversion and Enhancement of Anti-Colorectal Cancer Activity.

The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.

Lycorine inhibits the proliferation of neuroblastoma neuro-2a cells by inducing G2/M phase cell cycle arrest and apoptosis.

Lycorine, a benzylphenanthridine-type alkaloid extracted form Amarillidaceae genera, exhibits an efficacy against various types of cancer. Nonetheless, the impact of lycorine treatment on neuroblastoma has not yet been investigated. Here we utilized a combinatorial strategy to explore and to understand the effect of lycorine on neuroblastoma Neuro-2a cells. Our results indicated that lycorine inhibits the Neuro-2a cells proliferation by promoting cell apoptosis. In addition, wound healing assay revealed that lycorine inhibits the Neuo-2a cells migration. Comparative transcriptome analysis showed that lycorine has the potential to affect cycle pathway. Flow cytometry analysis confirmed that lycorine arrested the Neuro-2a cell cycle at G2/M phase. Furthermore, we detected that the protein expression of Cyclin A, Cyclin B1 and Cyclin E were decreased, whereas protein of p53, Tgfß3, Gadd45ß, Gadd45γ, p21 and p27 were increased after treatment with lycorine. Collectively, we propose that lycorine might be a valuable candidate therapeutic agent in combating neuroblastoma.

Visible Light Generation of a Microsecond Long-Lived Potent Reducing Agent.

Photoexcitation of molecular radicals can produce strong reducing agents; however, the limited lifetimes of the doublet excited states preclude many applications. Herein, we propose and demonstrate a general strategy to translate a highly energetic electron from a doublet excited state to a ZrO2 insulator, thereby increasing the lifetime by about 6 orders of magnitude while maintaining a reducing potential less than -2.4 V vs SCE. Specifically, red light excitation of a salicylic acid modified perylene diimide radical anion PDI•- anchored to a ZrO2 insulator yields a ZrO2(e-)|PDI charge separated state with an ∼10 µs lifetime in 23% yield. The ZrO2(e-)s were shown to drive CO2 → CO reduction with a Re catalyst present in micromolar concentrations. More broadly, this strategy provides new opportunities to reduce important reagents and catalysts at low concentrations through diffusional electron transfer.

Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl3 induced mouse model of Alzheimer's disease via modulating gut microbiota and PI3K/Akt/GSK-3ß signaling pathway.

Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer's disease (AD) in D-galactose (D-gal) and AlCl3-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3ß pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.

Fermentation of NaHCO3-treated corn germ meal by Bacillus velezensis CL-4 promotes lignocellulose degradation and nutrient utilization.

Sodium bicarbonate pretreatment and solid-state fermentation (SSF) were used to maximize the nutritional value of corn germ meal (CGM) by inoculating it with Bacillus velezensis CL-4 (isolated from chicken cecal contents and capable of degrading lignocellulose). Based on genome sequencing, B. velezensis CL-4 has a 4,063,558 bp ring chromosome and 46.27% GC content. Furthermore, genes associated with degradation of lignocellulose degradation were detected. Pretreatment of CGM (PCGM) with sodium bicarbonate (optimized to 0.06 g/mL) neutralized low pH. Fermented and pretreated CGM (FPCGM) contained more crude protein (CP), soluble protein of trichloroacetic acid (TCA-SP), and total amino acids (aa) than CGM and PCGM. Degradation rates of cellulose and hemicellulose were reduced by 21.33 and 71.35%, respectively, after 48 h fermentation. Based on electron microscopy, FPCGM destroys the surface structure and adds small debris of the CGM substrate, due to lignocellulose breakdown. Furthermore, 2-oxoadipic acid and dimethyl sulfone were the most important metabolites during pretreatment. Concentrations of adenosine, cytidine, guanosine, S-methyl-5'-thioadenosine, and adenine decreased significantly after 48 h fermentation, whereas concentrations of probiotics, enzymes, and fatty acids (including palmitic, 16-hydroxypalmitic, and linoleic acids) were significantly improved after fermentation. In conclusion, the novel pretreatment of CGM provided a proof of concept for using B. velezensis CL-4 to degrade lignocellulose components, improve nutritional characteristics of CGM, and expand CGM lignocellulosic biological feed production. KEY POINTS: • Sodium bicarbonate (baking soda) can be used as an economical and green additive to pretreat corn germ meal; • Fermentation with B. velezensis degrades the cellulose and hemicellulose component of corn germ meal and improves its feed quality; • As a novel qualified presumption of safety (QPS) strain, B. velezensis should have broad potential applications in food and feed industries.

Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling.

Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial-mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients' survival.

Synthesis of Berberine and Canagliflozin Chimera and Investigation into New Antibacterial Activity and Mechanisms.

Berberine is an isoquinoline alkaloid isolated from Chinese herbal medicines such as Coptis chinensis. It has many pharmacological actions, such as antibacterial, hypoglycemic, anti-inflammatory, and so on. However, due to the low lipophilicity of berberine, it is difficult to penetrate the bacterial cell membrane and also difficult to be absorbed orally and usually needs a relatively high dose to achieve the ideal effect. The purpose of this study is to transform the structure of berberine in order to improve the bioavailability of berberine and reduce the dosage. Moreover, we introduce a pharmacophore named Canagliflozin, a hypoglycemic drug (which was also found to have potential anti-bacterial activity) into BBR to see whether this new compound has more existed activities. We at first connected berberine with Canagliflozin, to form a new compound (BC) and see whether BC has synergic effects. We use microbroth dilution method to determine the minimum inhibitory concentration of BC, determine the bacterial growth with the enzyme labeling instrument, observe the formation of bacterial biofilm with crystal violet staining method, observe the bacterial morphology with field emission scanning electron microscope, and determine the intracellular protein with SDS-PAGE. The above indicators reflect the damage of BC to bacteria. New compound BC was successfully obtained by chemical synthesis. The minimal inhibitory concentration of compound BC on three bacteria was significantly better than that of berberine and canagliflozin alone and the combination of berberine and canagliflozin. Moreover, compound BC has obvious destructive effect on bacterial morphology and biofilm, and the compound also has destructive effect on intracellular proteins. Therefore, new compound BC has broad-spectrum antibacterial activity and the inhibitory effect of BC might play a role by destroying the integrity of biofilm and the intracellular protein of bacteria. In conclusion, we create a new molecular entity of berberine and Canagliflozin chimera and open up a new prospect for berberine derivatives in the treatment of bacterial infection.

Study of the Lithium Storage Mechanism of N-Doped Carbon-Modified Cu2 S Electrodes for Lithium-Ion Batteries.

Owing to their high specific capacity and abundant reserve, Cux S compounds are promising electrode materials for lithium-ion batteries (LIBs). Carbon compositing could stabilize the Cux S structure and repress capacity fading during the electrochemical cycling, but the corresponding Li+ storage mechanism and stabilization effect should be further clarified. In this study, nanoscale Cu2 S was synthesized by CuS co-precipitation and thermal reduction with polyelectrolytes. High-temperature synchrotron radiation diffraction was used to monitor the thermal reduction process. During the first cycle, the conversion mechanism upon lithium storage in the Cu2 S/carbon was elucidated by operando synchrotron radiation diffraction and in situ X-ray absorption spectroscopy. The N-doped carbon-composited Cu2 S (Cu2 S/C) exhibits an initial discharge capacity of 425 mAh g-1 at 0.1 A g-1 , with a higher, long-term capacity of 523 mAh g-1 at 0.1 A g-1 after 200 cycles; in contrast, the bare CuS electrode exhibits 123 mAh g-1 after 200 cycles. Multiple-scan cyclic voltammetry proves that extra Li+ storage can mainly be ascribed to the contribution of the capacitive storage.

Assembling BH3-mimic peptide into a nanocluster to target intracellular Bcl2 towards the apoptosis induction of cancer cell.

Bcl-2, an anti-apoptotic protein, is always overexpressed in tumor cells to suppress the pro-apoptotic function of Bax, thereby prolonging the life of the tumor. However, BH3 proteins could directly activate Bax via antagonizing Bcl-2 to induce apoptosis in response to the stimulation. Thus, mimicking BH3 proteins with a peptide is a potential strategy for anti-cancer therapy. Unfortunately, clinical translation of BH3-mimic peptide is hindered by its inefficacious cellular internalization and proteolysis resistance. Herein, we translated a BH3-mimic peptide into a peptide-auric spheroidal nanocluster (BH3-AuNp), in which polymeric BH3-Auric precursors [Au1+-S-BH3]narein situself-assembled on the surface of gold nanoparticles by a one-pot synthesis. Expectedly, this strategy could improve the anti-proteolytic ability and cytomembrane penetrability of the BH3 peptide. As a result, BH3-AuNp successfully induced the apoptosis of two cancer cell lines by an order of magnitude compared to BH3. This therapeutic and feasible peptide nano-engineering strategy will help peptides overcome the pharmaceutical obstacles, awaken its biological functions, and possibly revive the research about peptide-derived nanomedicine.

The effect of low-dose ketamine on postoperative quality of recovery in patients undergoing breast cancer surgery: A randomised, placebo-controlled trial.

BACKGROUND: Low-dose ketamine has been proved to reduce opioid consumption, prevent depressant action and improve postoperative analgesia. Women undergoing mastectomy experience may not only have persistent postoperative pain syndromes but also emotional problems. However, the effect of intraoperative infusion of low-dose ketamine on postoperative quality of recovery among these patients has not yet been fully studied. METHODS: In this prospective, randomised, single-centre trial, 100 patients planned for modified radical mastectomy were randomly assigned to one of two groups: control group (group C) or ketamine group (group K) at a ratio of 1:1. Group K received the bolus dose of 0.5 mg/kg ketamine and followed by 0.25 mg·kg-1 ·h-1 after the compliment of anaesthesia induction until the end of the surgery, whilst group C received an equivalent dose and regiment of normal saline was group K. The primary outcome was to assess the effects of low-dose ketamine on postoperative quality of recovery using the 40-Item Quality of Recovery (QoR-40) scale on a postoperative day 1 (POD1). The secondary outcome was to assess the numeric rating scale (NRS) at 4, 24 and 48 h after the operation, identity-consequence fatigue scale (ICFS) scores at 3 and 7 days after the operation, hospital anxiety and depression scale (HADS) scores at 2 days and 3 months, as well as chronic pain at 3 months. In a post hoc analysis, the 5 subsections of the QoR-40 scores were also analysed. RESULTS: A total of 100 subjects were randomised. The primary outcome of QoR-40 scores on POD1 was available in 97 patients (49 in group C and 48 in group K). Global QoR-40 scores were not significantly different between group C and group K (169.8 ± 10.7 vs. 172.7 ± 7.5, 95% CI -1.35 (-5.50, 2.80), p = .519). In a post hoc analysis, pain scores were significantly higher in group K than in group C (29.8 ± 3.8 vs. 31.7 ± 2.1, 95% CI -1.81 (-3.00, -0.62), p = .003). The secondary outcomes, including NRS, ICFS scores, HADS scores and chronic pain had no difference between groups (p value for each >.15). CONCLUSION: Intraoperative low-dose ketamine infusion did not improve the overall quality of recovery on POD 1 in patients undergoing breast cancer surgery.