A systematic review on reporting quality of economic evaluations for negotiated glucose-lowering drugs in China national reimbursement drug list.

BACKGROUND: This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). METHODS: We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal-Wallis test and Mann-Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. RESULTS: We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal-Wallis test and Mann-Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. CONCLUSIONS: There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Three-dimensional porous calcium alginate fluorescence bead-based immunoassay for highly sensitive early diagnosis of breast cancer.

A sensitive biosensor capable of detecting trace concentrations of several cancer biomarkers in clinical samples is critical for early detection of cancer because different cancer biomarkers may be expressed at different stages of cancer. Previous multiplex studies using microarrays or color-coded beads had limited multiplex detection in a single well, and difficulty in optimizing and unifying the incubation parameters for all tests made in different wells had posed challenges to small sample size and lengthened assay time. Herein, we proposed a novel approach to achieve multiplex analysis on a single three-dimensional porous calcium alginate bead. Because of the high surface area to volume ratio of the calcium alginate immuno-bead, the sensitivity and linear dynamic range of the as-proposed multiplex analysis method are significantly improved. Based on the direct sandwich immunoassay principle, dual-capturing antibodies were encapsulated into a single 3D porous calcium alginate bead as a proof-of-concept for multiplexity detection of serum-HER2 and serum-CA125 breast cancer biomarkers. High sensitivity was attained, with LODs of 0.004 ng mL-1 for serum HER2, and 0.005 U mL-1 for serum CA125, both of which are below the clinical cutoff values, enabling for early breast cancer diagnosis. Stability tests revealed that the 3D immuno-beads were stable at 4 °C and room temperature (25 °C) for at least 14 days. Most importantly, the results obtained using the developed system were in good agreement with those obtained using standard methods while analyzing real clinical samples. In addition, the analysis required only approximately 30 min, which was much less time than typical ELISA techniques. When endogenous interferences were introduced, no cross-reactivity was observed. We anticipate this approach to be potentially used in the multiplex assays and biosensors.

Psychometric properties and measurement invariance of Short-Form Life Attitude Inventory for hospital staff.

BACKGROUND: The life attitude of health care workers can deeply influence the quality of care. Examining the performance of the Short-Form Life Attitude Inventory (SF-LAI), this study analyzes the factorial structure, reliability, and invariance of the revised SF-LAI across genders and professions among the staff of a teaching medical center. METHODS: The SF-LAI was developed for university students in Taiwan. From January to February 2019, we administered a cross-sectional survey of life attitudes by distributing the SF-LAI to all staff members of a medical center in Taiwan. The construct validity was evaluated using a confirmatory factor analysis (CFA). Model fit was assessed in terms of the comparative fit index (CFI), Tucker-Lewis index (TFI), standardized root mean square residual (SRMR), and root mean square of error of approximation (RMSEA). Internal consistency was calculated using Cronbach's alpha and McDonald's omega. We also performed the CFA invariance analysis for the SF-LAI-R across genders and professions (physician, nurse and other hospital staff). RESULTS: Of 884 (24.62%) responses, 835 were valid. The participants had a mean age of 47.8 years, and 20.12% were male. In a comparison of multiple CFAs, a second-order model with six factors outperformed other models. The goodness of fit indices revealed the CFI was 0.955, TFI was 0.952, RMSEA was 0.071, and SRMR was 0.038. The Cronbach's alphas, McDonald's omega coefficients for internal consistency were all greater than 0.8. The first and second-order model had metric and scalar invariance across genders and professions. CONCLUSIONS: As health care demands evolve, humanities are becoming more important in medical education. Life attitude of hospital care worker is a crucial indicator of whether one embodies the ideals of a humanistic education. The revised SF-LAI has acceptable structural validity, internal consistency, and invariance across genders and professions among staff members of a teaching medical center.

Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

Long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse. METHODS: This was a retrospective study of patients who underwent Le Fort colpocleisis from January 2007 to August 2018 in our hospital. Follow-up was conducted via outpatient visits or the telephone. Records were reviewed for anatomical recurrence, complications, urinary and intestinal symptoms post-operation, reoperation rate, patient satisfaction, Patient Global Impression of Improvement (PGI-I) score, regret rate etc. RESULTS: A total of 208 patients underwent follow-up. The follow-up time was 60.7 ± 34.18 (12-140) months. There were no intraoperative complications. Postoperative urinary retention occurred in 3.8% of patients (8 out of 208). There was no anatomical recurrence. New or more severe urinary symptoms occurred in 8.7% of patients (18 out of 208); new or more severe intestinal symptoms occurred in 1.9% of patients (4 out of 208). The reoperation rate was 1.44% (3 out of 208). Three cases of reoperation occurred for the following reasons: a case of severe stress urinary incontinence, a case of abscess in the vaginal septum, and a case of uterine malignancy after 2 years of colpocleisis. Patient satisfaction was as follows: 98.6% (205 out of 208) of patients were very satisfied. The PGI-I score was very much improved or improved in 99.5% (207 out of 208) of patients. A total of 0.96% (2 out of 208) of patients regretted undergoing colpocleisis. CONCLUSIONS: The long-term follow-up results showed that Le Fort colpocleisis was a safe and effective surgical procedure associated with high satisfaction. There was a very low regret rate, but the procedure should be taken seriously.

[An integrative metabolomics and network pharmacology method for exploring bioactive components and preliminary pharmacodynamics in medicinal parts of Harrisonia perforata].

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.

Ten tips for foundation doctors when making inpatient referrals to surgical specialties.

Making referrals to another specialty is an underemphasised skill in the undergraduate medical curriculum. As a result, many new foundation doctors find themselves ill-equipped to make effective referrals to other specialties as part of their day-to-day responsibilities. This can often be frustrating to the foundation doctor, the specialist and contribute to critical delays in patient care. Surgical registrars are required to triage patients (for urgent review or even to take to theatre) often under time and high patient volume pressures. As such, it is imperative for foundation doctors to make referrals as efficiently as possible to facilitate surgical specialty decision making and, ultimately, to expedite medical care to patients. In this article, we describe 10 tips for the foundation doctor in making inpatient referrals to surgical specialties.

Combined spectroscopies and molecular docking approach to characterizing the binding interaction between lisinopril and bovine serum albumin.

To further understand the mode of action and pharmacokinetics of lisinopril, the binding interaction of lisinopril with bovine serum albumin (BSA) under imitated physiological conditions (pH 7.4) was investigated using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) and molecular docking methods. The results showed that the fluorescence quenching of BSA near 338 nm resulted from the formation of a lisinopril-BSA complex. The number of binding sites (n) for lisinopril binding on subdomain IIIA (site II) of BSA and the binding constant were ~ 1 and 2.04 × 10(4) M(-1), respectively, at 310 K. The binding of lisinopril to BSA induced a slight change in the conformation of BSA, which retained its α-helical structure. However, the binding of lisinopril with BSA was spontaneous and the main interaction forces involved were van der Waal's force and hydrogen bonding interaction as shown by the negative values of ΔG(0), ΔH(0) and ΔS(0) for the binding of lisinopril with BSA. It was concluded from the molecular docking results that the flexibility of lisinopril also played an important role in increasing the stability of the lisinopril-BSA complex.

A combined spectroscopic and molecular docking approach to characterize binding interaction of megestrol acetate with bovine serum albumin.

The binding interactions between megestrol acetate (MA) and bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) were investigated by fluorescence spectroscopy, circular dichroism and molecular modeling. The results revealed that the intrinsic fluorescence of BSA was quenched by MA due to formation of the MA-BSA complex, which was rationalized in terms of a static quenching procedure. The binding constant (Kb ) and number of binding sites (n) for MA binding to BSA were 2.8 × 10(5) L/mol at 310 K and about 1 respectively. However, the binding of MA with BSA was a spontaneous process due to the negative ∆G(0) in the binding process. The enthalpy change (∆H(0) ) and entropy change (∆S(0) ) were - 124.0 kJ/mol and -295.6 J/mol per K, respectively, indicating that the major interaction forces in the binding process of MA with BSA were van der Waals forces and hydrogen bonding. Based on the results of spectroscopic and molecular docking experiments, it can be deduced that MA inserts into the hydrophobic pocket located in subdomain IIIA (site II) of BSA. The binding of MA to BSA leads to a slight change in conformation of BSA but the BSA retained its secondary structure, while conformation of the MA has significant change after forming MA-BSA complex, suggesting that flexibility of the MA molecule supports the binding interaction of BSA with MA.

Three-combination probiotics therapy in children with salmonella and rotavirus gastroenteritis.

GOALS: Quantitative Vesikari scales and qualitative severe diarrhea (Vesikari scale ≥11) assessments were used to grade the Salmonella-induced and rotavirus-induced gastroenteritis severity. A significant reduction in severe diarrhea (Vesikari score ≥11) was used to evaluate the efficacy of three-combination probiotics (BIO-THREE). BACKGROUND: Several studies have shown that rotavirus and Salmonella infections are the leading causes of infectious gastroenteritis. Although probiotics have been effective in some studies, the use of 3-combination formulation probiotics is rare. STUDY: This single-center, open-label, randomized, controlled trial included 159 patients (age range, 3 mo to 14 y) hospitalized with infectious gastroenteritis between February 2009 and October 2010. RESULTS: Patients were grouped according to the pathogen identified (48, Salmonella; 42, rotavirus; and 69, unknown origin). The total diarrhea duration was significantly shorter for children who received BIO-THREE (P<0.0001). After BIO-THREE administration, there were significantly less intervention group patients with severe diarrhea at intervention day 3. Vesikari scale or diarrhea frequency results did not reveal significant differences between groups (except for day 5 in patients with rotavirus), and there were no significant changes in other clinical parameters or the length of hospital stay. CONCLUSIONS: Seven-day BIO-THREE administration demonstrated high efficacy and safety in infants and children with severe gastroenteritis. The incidence of severe gastroenteritis was significantly reduced in the rotavirus origin and BIO-THREE intervention groups.

Perinatal factors in patent ductus arteriosus in very low-birthweight infants.

BACKGROUND: The relationship between hemoglobin and patent ductus arteriosus (PDA) has not been discussed before. The aim of this study was to assess the influence of hemoglobin and perinatal factors on PDA in very low-birthweight (VLBW) infants. METHODS: Using data from the Premature Baby Foundation of Taiwan (PBFA), the characteristics, perinatal factors, and hemoglobin of VLBW infants with and without PDA and treatment were compared. RESULTS: Between January 2008 and December 2010, 89 VLBW infants were admitted to hospital. The overall survival rate was 87.6%. Twelve infants were excluded. Compared to those without PDA, the 34 infants with PDA received oral indomethacin or surgery, had smaller mean gestational age (GA; 27.93 ± 1.818 weeks, P = 0.000003), lower mean birthweight (BW; 1031 ± 259 g, P = 0.0001), significantly lower Apgar score at 5 min, more severe respiratory distress syndrome (RDS; grade 3 or 4), greater use of surfactants, and lower mean hemoglobin (P = 0.018) after birth than those without PDA. Compared to those with indomethacin, the seven infants with surgery had lower mean GA (26.43 ± 1.718 weeks, P = 0.011), significantly lower Apgar scores at 1 min, but higher platelet count (P = 0.002) after birth, and more red blood cell transfusions (P = 0.039). CONCLUSIONS: Smaller GA, lower BW, lower Apgar score at 5 min, more severe RDS, greater use of surfactants, and lower hemoglobin after birth place VLBW infants at greater risk of PDA. Proper prenatal care, and prevention of premature labor and delivery may be the most important preventative factors. The appropriate hemoglobin level for PDA closure requires further investigation.

Characterization of intermolecular interaction between cyanidin-3-glucoside and bovine serum albumin: spectroscopic and molecular docking methods.

The intermolecular interaction between cyanidin-3-glucoside (Cy-3-G) and bovine serum albumin (BSA) was investigated using fluorescence, circular dichroism and molecular docking methods. The experimental results revealed that the fluorescence quenching of BSA at 338 nm by Cy-3-G resulted from the formation of Cy-3-G-BSA complex. The number of binding sites (n) for Cy-3-G binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding Cy-3-G to BSA, Cy-3-G is closer to the Tyr residue than the Trp residue, the secondary structure of BSA almost not change, the binding process of Cy-3-G with BSA is spontaneous, and Cy-3-G can be inserted into the hydrophobic cavity of BSA (site II') in the binding process of Cy-3-G with BSA. Moreover, based on the sign and magnitude of the enthalpy and entropy changes (ΔH(0) = - 29.64 kcal/mol and ΔS(0) = - 69.51 cal/mol K) and the molecular docking results, it can be suggested that the main interaction forces of Cy-3-G with BSA are Van der Waals and hydrogen bonding interactions.

Educators' implicit perspectives on wisdom: a comparison between interpersonal and intrapersonal perspectives.

This research aimed to investigate educators' implicit perspectives on wisdom in order to compare interpersonal and intrapersonal perspectives and to help identify similarities or differences between these two theoretical perspectives. A total of 56 educators in Taiwan were interviewed individually. We utilised the grounded theory method to analyse the qualitative data. Results showed that both interpersonal and intrapersonal perspectives converged on four core components of wisdom: intrapsychic integration, actions in service of problem solving and ideal implementation, positive results and feedback and adjustments. The interpersonal perspective referred to external characteristics, and admiration and influence, whereas the intrapersonal perspective included greater detail about intrapsychic integration and action strategies than did the interpersonal perspective. We close with a discussion both of how wisdom appears to span across different fields and how the present results might feed into the teaching of wisdom in schools.

Scalable and Flexible Multi-Layer Prismatic Photonic Metamaterial Film for Efficient Daytime Radiative Cooling.

To maintain a comfortable indoor living environment in low latitude or tropical regions, humans consume significant amounts of electrical energy in air conditioning, leading to substantial CO2 emissions. Passive daytime radiative cooling (PDRC) allows objects to cool down during the daytime without any energy consumption by dissipating heat through the atmospheric transparency window (8-13 µm) to outer space, which has garnered significant attention. However, the practical applications of common PDRC materials are hindered by their poor optical selectivity and high-reflective silver backing. Additionally, the availability of artificial photon emitters with complex structures and excellent performance is also limited by their high cost. Herein, a novel multilayer prismatic photonic metamaterial film without any silver reflector, easily scalable and produced by a roll-to-roll method is demonstrated, which exhibits ≈96.4% sunlight reflectance (0.3-2.5 µm) and ≈97.2% emissivity in mid-infrared (IR) (8-13 µm). At an average solar intensity of ≈920 W m-2, it is on average 6.8 °C below ambient temperature during the day and theoretically yields a radiative cooling power of 88.9 W m-2. Furthermore, the film exhibits excellent hydrophobicity, superior flexibility, and robust mechanical strength, providing an attractive and viable pathway for practical applications addressing the pressing challenges of climate and energy issues.

Effect of remimazolam on electroencephalogram burst suppression in elderly patients undergoing cardiac surgery: Protocol for a randomized controlled noninferiority trial.

Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).

Moving dynamics of a nanorobot with three DNA legs on nanopore-based tracks.

DNA nanorobots have garnered increasing attention in recent years due to their unique advantages of modularity and algorithm simplicity. To accomplish specific tasks in complex environments, various walking strategies are required for the DNA legs of the nanorobot. In this paper, we employ computational simulations to investigate a well-designed DNA-legged nanorobot moving along a nanopore-based track on a planar membrane. The nanorobot consists of a large nanoparticle as the robot core and three single-stranded DNAs (ssDNAs) as the robot legs. The nanopores linearly embedded in the membrane serve as the toeholds for the robot legs. A charge gradient along the pore distribution mainly powers the activation of the nanorobot. The nanorobot can move in two modes: a walking mode, where the robot legs sequentially enter the nanopores, and a jumping mode, where the robot legs may skip a nanopore to reach the next one. Moreover, we observe that the moving dynamics of the nanorobot on the nanopore-based tracks depends on pore-pore distance, pore charge gradient, external voltage, and leg length.

Preparation of Densified Fine-Grain High-Frequency MnZn Ferrite Using the Cold Sintering Process.

The densified MnZn ferrite ceramics were prepared using the cold sintering process under pressure, with an acetate ethanol solution used as the transient solvent. The effects of the transient solvent, the pressure and annealing temperature on the density, and the micromorphology and magnetic properties of the sintered MnZn ferrites were studied. The densified MnZn ferrite was obtained using the cold sintering process and its relative density reached up to 85.4%. The transient solvent and high pressure are essential to the cold sintering process for MnZn ferrite. The annealing treatment is indispensable in obtaining the sample with the higher density. The relative density was further increased to 97.2% for the sample annealed at 950 °C for 6 h. The increase in the annealing temperature reduces the power loss at high frequencies.

Self-Monitoring Theranostic Nanomaterials: Emerging Visual Agents for Real-Time Monitoring of Tumor Treatment Processes.

Self-monitoring in tumor therapy is a concept that allows for real-time monitoring of the location and state of applied nanomaterials. This monitoring relies on dynamic signals, such as wave or magnetic signals, which vary in response to changes in the location and state of nanomaterials. Dynamic changes in nanomaterials can be monitored using dynamic signals, making it possible to determine and control the treatment process. Theranostic nanomaterials, which possess unique physical and chemical properties, have recently been explored as a viable option for self-monitoring. With the help of self-monitoring, theranostic nanomaterials can guide themselves to achieve region-selective treatment with higher controllability and safety. In this review, self-monitoring theranostic nanomaterials will be introduced in three parts according to their roles during therapy: tumor accumulation, tumor therapy, and metabolism. The limitations and future challenges of current self-monitoring theranostic nanomaterials will also be discussed.

Redox Homeostasis Disruptors Based on Metal-Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis.

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis and cuproptosis for synergistic chemo/chemodynamic therapy. The Cu-GA NPs are biodegraded in response to the highly expressed glutathione (GSH) in tumor cells, resulting in the simultaneous release of Cu+ and GA. The intracellular GSH content is dramatically reduced by the released GA, rendering the tumor cells incapable of scavenging reactive oxygen species (ROS) and more susceptible to cuproptosis. Meanwhile, ROS levels within the tumor cells are significantly increased by the Fenton-like reaction of released Cu+ , which disrupts redox homeostasis and achieves apoptosis-related chemodynamic therapy. Moreover, massive accumulation of Cu+ in the tumor cells further induces aggregation of lipoylated dihydrolipoamide S-acetyltransferase and downregulation of iron-sulfur cluster protein, activating cuproptosis to enhance the antitumor efficacy of Cu-GA NPs. The experiments in vivo further demonstrate that Cu-GA NPs exhibited the excellent biosafety and superior antitumor capacity, which can efficiently inhibit the growth of tumors due to the activation by the tumor specific GSH and hydrogen peroxide. These Cu-based metal-phenolic network NPs provide a potential strategy to build up efficient and safe cancer therapy.

Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway.

A new ent-abietane diterpenoid, named Euphejolkinolide A (1), was isolated from the whole plant of Euphorbia peplus L. Its structure, including absolute configurations, was determined by spectroscopic analyses and was corroborated by single-crystal X-ray diffraction analysis. This new compound was assessed for its activity to induce lysosome biogenesis through Lyso-Tracker Red staining, in which compound 1 could significantly induce lysosome biogenesis. In addition, quantitative real-time PCR (qRT-PCR) analysis demonstrated a direct correlation between the observed lysosome biogenesis and the transcriptional activation of the lysosomal genes after treatment with the compound 1. Moreover, compound 1 promoted autophagic flux by upregulating LC3-II and downregulating SQSTM1 in both human microglia cells and U251 cells, which is required for cellular homeostasis. Further results suggested 1 induced lysosome biogenesis and autophagy which was mediated by TFEB (transcription factor EB). The structure activity relationships (SAR) analysis suggested that the carbony1 at C-7 in 1 might be a key active group. Overall, the current data suggested that 1 could be a potential compound for lysosome disorder therapy by induction of autophagy.