Diagnostic value and method of soluble transferrin receptor for suspected coronary artery disease: a case-control study.

Background: Many studies have pointed out that iron overload in the body is a risk factor for coronary atherosclerosis (AS), while there are also studies that show that iron deficiency is associated with coronary AS. There is still no consensus on how iron metabolism affects coronary artery disease (CAD). This study aimed to analyze the relationship between iron metabolism indexes and CAD, investigate the diagnostic value of soluble transferrin receptor (sTfR) in suspected CAD, and establish a diagnostic model. Methods: This was a retrospective study. A total of 268 people with CAD-like symptoms who underwent coronary angiography in the Department of Cardiovascular Medicine, The Second Affiliated Hospital of Anhui Medical University from September 2022 to May 2023 without other chronic diseases or related medication history were included in the study and formed a continuous series including 188 CAD patients and 80 control subjects. Each iron metabolism index was divided into a grade variable according to tertile. The comparison of CAD morbidity between the tertiles and nonlinear correlation test was conducted to investigate the relationship between iron metabolism indexes and CAD risk. We used restricted cubic spline (RCS) to plot the relationship curve between sTfR and CAD risk and to determine the sTfR value corresponding to the minimal odds, according to which we divided the total sample into the "sTfR low level" subgroup and the "sTfR high level" subgroup. Logistic regression analyses were used to establish diagnostic models in both subgroups. The diagnostic efficiency of the indexes and models was compared by receiver operating characteristic (ROC) analysis. Results: There is a "J" shape correlation between sTfR and CAD risk. Age/sTfR ratio [area under the curve (AUC) =0.690, 95% confidence interval (CI): 0.598-0.782, specificity 0.488 and sensitivity 0.842] has the best diagnostic efficiency in the "sTfR low level" subgroup. The diagnostic efficiency of sTfR (AUC =0.701, 95% CI: 0.598-0.803, specificity 0.541 and sensitivity 0.797) in the "sTfR high level" subgroup was higher than that of cardiac troponin I (cTnI) (AUC =0.674, 95% CI: 0.564-0.784, specificity 0.719 and sensitivity 0.653). The specific diagnostic methods were as follows: (I) When sTfR ≤1.087 mg/L, calculate the age/sTfR ratio, which indicates the diagnosis of CAD when the result is >58.595; (II) We can directly make a preliminary clinical diagnosis of CAD when sTfR >1.205 mg/L. Except for the above 2 cases, we can initially rule out a diagnosis of CAD. Conclusions: The iron metabolism index sTfR correlates with CAD morbidity in a "J" shape. With superior diagnostic efficacy than cTnI, sTfR can assist in diagnosing CAD in patients with CAD-like symptoms. In addition, sTfR can provide guidance for the management of body iron levels in CAD patients.

Chikusetsu Saponin IVa liposomes modified with a retro-enantio peptide penetrating the blood-brain barrier to suppress pyroptosis in acute ischemic stroke rats.

BACKGROUND: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application. RESULT: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats. CONCLUSION: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.

High performance TadA-8e derived cytosine and dual base editors with undetectable off-target effects in plants.

Cytosine base editors (CBEs) and adenine base editors (ABEs) enable precise C-to-T and A-to-G edits. Recently, ABE8e, derived from TadA-8e, enhances A-to-G edits in mammalian cells and plants. Interestingly, TadA-8e can also be evolved to confer C-to-T editing. This study compares engineered CBEs derived from TadA-8e in rice and tomato cells, identifying TadCBEa, TadCBEd, and TadCBEd_V106W as efficient CBEs with high purity and a narrow editing window. A dual base editor, TadDE, promotes simultaneous C-to-T and A-to-G editing. Multiplexed base editing with TadCBEa and TadDE is demonstrated in transgenic rice, with no off-target effects detected by whole genome and transcriptome sequencing, indicating high specificity. Finally, two crop engineering applications using TadDE are shown: introducing herbicide resistance alleles in OsALS and creating synonymous mutations in OsSPL14 to resist OsMIR156-mediated degradation. Together, this study presents TadA-8e derived CBEs and a dual base editor as valuable additions to the plant editing toolbox.

Response of microbial communities in aquifers with multiple organic solvent contamination: Implications for MNA remedy.

The application of Monitored Natural Attenuation (MNA) technology has been widespread, while there is a paucity of data on groundwater with multiple co-contaminants. This study focused on high permeability, low hydraulic gradient groundwater with co-contamination of benzene, toluene, ethylbenzene, and xylenes (BTEX), chlorinated aliphatic hydrocarbons (CAHs), and chlorinated aromatic hydrocarbons (CPs). The objective was to investigate the responses of microbial communities during natural attenuation processes. Results revealed greater horizontal variation in groundwater microbial community composition compared to vertical variation. The variation was strongly correlated with the total contaminant quantity (r = 0.722, p < 0.001) rather than individual contaminants. BTEX exerted a more significant influence on community diversity than other contaminants. The assembly of groundwater microbial communities was primarily governed by deterministic processes (ßNTI < -2) in high contaminant concentration zones, while stochastic processes (|ßNTI| < 2) dominated in low-concentration zones. Moreover, the microbial interactions shifted at different depths indicating the degradation rate variation in the vertical. This study makes fundamental contribution to the understanding for the effects of groundwater flow and material fields on indigenous microbial communities, which will provide a scientific basis for more precise adoption of microbial stimulation/augmentation to accelerate the rate of contaminant removal.

[Multi Scenario Carbon Peak Prediction and Emission Reduction Path Analysis of Xi'an Hi-tech Zone].

The fifth session of the 13th National People's Congress proposed to be committed to promoting carbon peaking and carbon neutrality, promoting the comprehensive green and low-carbon transformation of the economy and society and achieving high-quality development. As an important scientific and technological innovation and industrial cluster in Shaanxi Province, the economic development of the Xi'an Hi-tech Zone largely relies on energy consumption, making the task of carbon reduction particularly challenging. Firstly, taking the Xi'an Hi-tech Zone as the research object, through systematic accounting of carbon emissions within the park, we analyzed the current carbon emission status of enterprises in different energy types and industries. Then, using the Kaya model, multiple independent carbon peak scenarios were set up to predict the total carbon emissions and peak time under different scenarios. Finally, based on the development characteristics of the Xi'an Hi-tech Zone, we scientifically selected corresponding carbon emission reduction paths and provided reasonable emission reduction suggestions. The results showed that the proportion of carbon emissions consumed by electricity was currently the highest, and the share was increasing yearly. Industrial carbon emissions had always been dominant, and the development of the tertiary industry was becoming increasingly prosperous. In the scenario prediction, the carbon emission factor scenario, energy intensity scenario, and economic level scenario could reach the carbon peak by 2030. Among them, the economic development level had the greatest impact on the peak and time of the future carbon peak in the Xi'an Hi-tech Zone, whereas the industrial structure scenario, energy source structure scenario, and population size scenario had no peak before 2030. The future emission reduction path mainly started from decarbonization of the power sector, stable and high-quality economic development, green upgrading of energy and industrial structure, and building a green transportation system. This can reserve more preparation time for achieving carbon neutrality and provide decision-making reference for the low-carbon development of industrial parks in China.

Expanding plant genome editing scope and profiles with CRISPR-FrCas9 systems targeting palindromic TA sites.

CRISPR-Cas9 is widely used for genome editing, but its PAM sequence requirements limit its efficiency. In this study, we explore Faecalibaculum rodentium Cas9 (FrCas9) for plant genome editing, especially in rice. FrCas9 recognizes a concise 5'-NNTA-3' PAM, targeting more abundant palindromic TA sites in plant genomes than the 5'-NGG-3' PAM sites of the most popular SpCas9. FrCas9 shows cleavage activities at all tested 5'-NNTA-3' PAM sites with editing outcomes sharing the same characteristics of a typical CRISPR-Cas9 system. FrCas9 induces high-efficiency targeted mutagenesis in stable rice lines, readily generating biallelic mutants with expected phenotypes. We augment FrCas9's ability to generate larger deletions through fusion with the exonuclease, TREX2. TREX2-FrCas9 generates much larger deletions than FrCas9 without compromise in editing efficiency. We demonstrate TREX2-FrCas9 as an efficient tool for genetic knockout of a microRNA gene. Furthermore, FrCas9-derived cytosine base editors (CBEs) and adenine base editors (ABE) are developed to produce targeted C-to-T and A-to-G base edits in rice plants. Whole-genome sequencing-based off-target analysis suggests that FrCas9 is a highly specific nuclease. Expression of TREX2-FrCas9 in plants, however, causes detectable guide RNA-independent off-target mutations, mostly as single nucleotide variants (SNVs). Together, we have established an efficient CRISPR-FrCas9 system for targeted mutagenesis, large deletions, C-to-T base editing, and A-to-G base editing in plants. The simple palindromic TA motif in the PAM makes the CRISPR-FrCas9 system a promising tool for genome editing in plants with an expanded targeting scope.

The correlation between subendocardial viability ratio and the degree of coronary artery stenosis in patients with coronary heart disease and its predictive value for the incidence of short-term cardiovascular events.

OBJECTIVES: This study aimed to analyze the ability of subendocardial viability ratio (SEVR) to predict the degree of coronary artery stenosis and the relationship between SEVR and the incidence of short-term cardiovascular endpoint events. METHOD: The indexes of 243 patients with chest pain were collected.. Binary logistic regression analyses were performed using the dichotomous outcome of high and non-high SYNTAX scores. Receiver operating characteristic curves were employed to comparatively analyze the diagnostic efficiencies of the indices and models. A survival analysis combined with the Cox regression analysis was performed using the Kaplan-Meier method to understand the relationship between the SEVR and the incidence of cardiovascular events within 1 year in patients with coronary heart disease (CHD). RESULTS: SEVR was significantly lower (P < 0.05) in the high-stenosis group than control and low-stenosis groups. The diagnostic efficacy of SEVR [area under the curve (AUC) = 0.861] was better than those of age (AUC = 0.745), ABI (AUC = 0.739), and AIx@HR75 (AUC = 0.659). The cutoff SEVR was 1.105. In patients with confirmed CHD who had been discharged from the hospital for 1 year, only SEVR affected survival outcomes (hazard ratio = 0.010; 95% confidence interval: 0.001-0.418; P = 0.016). CONCLUSION: A significant decrease in SEVR predicted severe coronary artery stenosis, with a cutoff value of 1.105 and an accuracy of 0.861. In patients with CHD, the lower the SEVR, the higher was the rate of cardiovascular events at 1 year after hospital discharge.

Structure-guided engineered urethanase from Candida parapsilosis with pH and ethanol tolerance to efficiently degrade ethyl carbamate in Chinese rice wine.

Urethane hydrolase can degrade the carcinogen ethyl carbamate (EC) in fermented food, but its stability and activity limit its application. In this study, a mutant G246A and a double mutant N194V/G246A with improved cpUH activity and stability of Candida parapsilosis were obtained by site-directed mutagenesis. The catalytic efficiency (Kcat/Km) of mutant G246A and double mutant N194V/G246A are 1.95 times and 1.88 times higher than that of WT, respectively. In addition, compared with WT, the thermal stability and pH stability of mutant G246A and double mutant N194V/G246A were enhanced. The ability of mutant G246A and double mutant N194V/G246A to degrade EC in rice wine was also stronger than that of WT. The mutation increased the stability of the enzyme, as evidenced by decreased root mean square deviation (RMSD) and increased hydrogen bonds between the enzyme and substrate by molecular dynamics simulation and molecular docking analysis. The molecule modification of new cpUH promotes the industrial process of EC degradation.

Desulfurization and upgrade of pyrolytic oil and gas during waste tires pyrolysis: The role of metal oxides.

Pyrolysis can effectively convert waste tires into high-value products. However, the sulfur-containing compounds in pyrolysis oil and gas would significantly reduce the environmental and economic feasibility of this technology. Here, the desulfurization and upgrade of waste tire pyrolysis oil and gas were performed by adding different metal oxides (Fe2O3, CuO, and CaO). Results showed that Fe2O3 exhibited the highest removal efficiency of 87.7 % for the sulfur-containing gas at 600 °C with an outstanding removal efficiency of 99.5 % for H2S. CuO and CaO were slightly inferior to Fe2O3, with desulfurization efficiencies of 75.9 % and 45.2 % in the gas when added at 5 %. Fe2O3 also demonstrated a notable efficacy in eliminating benzothiophene, the most abundant sulfur compound in pyrolysis oil, with a removal efficiency of 78.1 %. Molecular dynamics simulations and experiments showed that the desulfurization mechanism of Fe2O3 involved the bonding of Fe-S, the breakage of C-S, dehydrogenation and oxygen migration process, which promoted the conversion of Fe2O3 to FeO, FeS and Fe2(SO4)3. Meanwhile, Fe2O3 enhanced the cyclization and dehydrogenation reaction, facilitating the upgrade of oil and gas (monocyclic aromatics to 57.4 % and H2 to 22.3 %). This study may be helpful for the clean and high-value conversion of waste tires.

Time delays between physiological signals in interpreting the body's responses to intermittent hypoxia in obstructive sleep apnea.

Objective.Intermittent hypoxia, the primary pathology of obstructive sleep apnea (OSA), causes cardiovascular responses resulting in changes in hemodynamic parameters such as stroke volume (SV), blood pressure (BP), and heart rate (HR). However, previous studies have produced very different conclusions, such as suggesting that SV increases or decreases during apnea. A key reason for drawing contrary conclusions from similar measurements may be due to ignoring the time delay in acquiring response signals. By analyzing the signals collected during hypoxia, we aim to establish criteria for determining the delay time between the onset of apnea and the onset of physiological parameter response.Approach.We monitored oxygen saturation (SpO2), transcutaneous oxygen pressure (TcPO2), and hemodynamic parameters SV, HR, and BP, during sleep in 66 patients with different OSA severity to observe body's response to hypoxia and determine the delay time of above parameters. Data were analyzed using the Kruskal-Wallis test, Quade test, and Spearman test.Main results.We found that simultaneous acquisition of various parameters inevitably involved varying degrees of response delay (7.12-25.60 s). The delay time of hemodynamic parameters was significantly shorter than that of SpO2and TcPO2(p< 0.01). OSA severity affected the response delay of SpO2, TcPO2, SV, mean BP, and HR (p< 0.05). SV delay time was negatively correlated with the apnea-hypopnea index (r= -0.4831,p< 0.0001).Significance.The real body response should be determined after removing the effect of delay time, which is the key to solve the problem of drawing contradictory conclusions from similar studies. The methods and important findings presented in this study provide key information for revealing the true response of the cardiovascular system during hypoxia, indicating the importance of proper signal analysis for correctly interpreting the cardiovascular hemodynamic response phenomena and exploring their physiological and pathophysiological mechanisms.

Protocol for embedded 3D printing of heart tissues using thiol-norbornene collagen.

Here, we present a protocol for 3D printing heart tissues using thiol-norbornene photoclick collagen (NorCol). We describe steps for synthesizing NorCol, preparing bioink and the support bath, and cell-laden printing. We then detail procedures for the loading of C2C12 cells into NorCol, ensuring structural integrity and cell viability after printing. This protocol is adaptable to various cell lines and allows for the printing of diverse complex structures, which can be used in drug screening and disease modeling.

Cathepsin B degrades RbcL during freezing-induced programmed cell death in Arabidopsis.

KEY MESSAGE: Cathepsin B plays an important role that degrades the Rubisco large subunit RbcL in freezing stress. Programmed cell death (PCD) has been well documented in both development and in response to environmental stresses in plants, however, PCD induced by freezing stress and its molecular mechanisms remain poorly understood. In the present study, we characterized freezing-induced PCD and explored its mechanisms in Arabidopsis. PCD induced by freezing stress was similar to that induced by other stresses and senescence in Arabidopsis plants with cold acclimation. Inhibitor treatment assays and immunoblotting indicated that cathepsin B mainly contributed to increased caspase-3-like activity during freezing-induced PCD. Cathepsin B was involved in freezing-induced PCD and degraded the large subunit, RbcL, of Rubisco. Our results demonstrate an essential regulatory mechanism of cathepsin B for Rubisco degradation in freezing-induced PCD, improving our understanding of freezing-induced cell death and nitrogen and carbohydrate remobilisation in plants.

Natural attenuation of BTEX and chlorobenzenes in a formerly contaminated pesticide site in China: Examining kinetics, mechanisms, and isotopes analysis.

Groundwater contamination from abandoned pesticide sites is a prevalent issue in China. To address this problem, natural attenuation (NA) of pollutants has been increasingly employed as a management strategy for abandoned pesticide sites. However, limited studies have focused on the long-term NA process of co-existing organic pollutants in abandoned pesticide sites by an integrated approach. In this study, the NA of benzene, toluene, ethylbenzene, and xylene (BTEX), and chlorobenzenes (CBs) in groundwater of a retired industry in China was systematically investigated during the monitoring period from June 2016 to December 2021. The findings revealed that concentrations of BTEX and CBs were effectively reduced, and their NA followed first-order kinetics with different rate constants. The sulfate-reducing bacteria, nitrate-reducing bacteria, fermenting bacteria, aromatic hydrocarbon metabolizing bacteria, and reductive dechlorinating bacteria were detected in groundwater. It was observed that distinct environmental parameters played a role in shaping both overall and key bacterial communities. ORP (14.72%) and BTEX (12.89%) were the main drivers for variations of the whole and key functional microbial community, respectively. Moreover, BTEX accelerated reductive dechlorination. Furthermore, BTEX and CBs exhibited significant enrichment of 13C, ranging from +2.9 to +27.3‰, demonstrating their significance in situ biodegradation. This study provides a scientific basis for site management.

Core and bridge symptoms of demoralization in Chinese female cancer patients: a network analysis.

Objective: In this study, we explore the core and bridge symptoms of demoralization in female cancer patients in China, and provide a basis for precise psychological intervention among female cancer patients. Methods: This study used a cross-sectional survey. Participants were recruited from three third-class hospitals in Jiangsu Province from June 2022 to June 2023 using the convenience sampling method. The severity of each symptom of demoralization was investigated in female cancer patients using the Demoralization Scale (DS). Network analysis was performed using the R language to identify core and bridge symptoms in the network and further explore some characteristic edge connections in the network. Results: The network structure model of demoralization had strong accuracy and stability. In the network, the symptoms with the highest strength centrality were "Discouragement" (C3, strength=2.19), "No self-worth" (A3, strength=1.21), "Don't want to live" (A5, strength=1.20), "Hopeless" (D4, strength=0.81), and "Vulnerability" (B3, strength=0.74), respectively. The bridge strength analysis identified "Hopeless" (D4, bridge strength=0.92), "Discouragement" (C3, bridge strength=0.85), "No self-worth" (A3, bridge strength=0.75), "Poor spirits" (E2, bridge strength=0.71), and "Vulnerability" (B3, bridge strength=0.69) as the bridge symptoms. The strongest edge connections of all dimensions were "No self-worth" and "Worthless" (A3-E6, edge weighting=0.27), "Poor spirits" and "Loss of emotional control" (E2-D1, edge weighting=0.22), "Discouragement" and "Vulnerability" (C3-B3, edge weighting=0.14), and "Hopeless" and "No meaning of survival" (D4-A4, edge weighting=0.12). Conclusion: "Discouragement (C3)", "No self-worth (A3)", "Hopeless (D4)", and "Vulnerability (B3)" are both core symptoms and bridge symptoms. These symptoms can not only trigger a patient's demoralization but also stimulate more severe symptom clusters through interactions. The early recognition of and intervention regarding these symptoms could be important for the prevention and treatment of demoralization among female cancer patients.

N-terminal acetyltransferase 6 facilitates enterovirus 71 replication by regulating PI4KB expression and replication organelle biogenesis.

Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease in children under 5 years old, which can result in severe neurological complications and even death. Due to limited treatments for EV71 infection, the identification of novel host factors and elucidation of mechanisms involved will help to counter this viral infection. N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71 infection with genome-wide CRISPR/Cas9 screening. NAT6 facilitates EV71 viral replication depending on its acetyltransferase activity but has little effect on viral release. In addition, NAT6 is also required for Echovirus 7 and coxsackievirus B5 infection, suggesting it might be a pan-enterovirus host factor. We further demonstrated that NAT6 is required for Golgi integrity and viral replication organelle (RO) biogenesis. NAT6 knockout significantly inhibited phosphatidylinositol 4-kinase IIIß (PI4KB) expression and PI4P production, both of which are key host factors for enterovirus infection and RO biogenesis. Further mechanism studies confirmed that NAT6 formed a complex with its substrate actin and one of the PI4KB recruiters-acyl-coenzyme A binding domain containing 3 (ACBD3). Through modulating actin dynamics, NAT6 maintained the integrity of the Golgi and the stability of ACBD3, thereby enhancing EV71 infection. Collectively, these results uncovered a novel mechanism of N-acetyltransferase supporting EV71 infection.IMPORTANCEEnterovirus 71 (EV71) is an important pathogen for children under the age of five, and currently, no effective treatment is available. Elucidating the mechanism of novel host factors supporting viral infection will reveal potential antiviral targets and aid antiviral development. Here, we demonstrated that a novel N-acetyltransferase, NAT6, is an essential host factor for EV71 replication. NAT6 could promote viral replication organelle (RO) formation to enhance viral replication. The formation of enterovirus ROs requires numerous host factors, including acyl-coenzyme A binding domain containing 3 (ACBD3) and phosphatidylinositol 4-kinase IIIß (PI4KB). NAT6 could stabilize the PI4KB recruiter, ACBD3, by inhibiting the autophagy degradation pathway. This study provides a fresh insight into the relationship between N-acetyltransferase and viral infection.

Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review.

Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.

Luteoloside inhibits Aß1-42 fibrillogenesis, disintegrates preformed fibrils, and alleviates amyloid-induced cytotoxicity.

Abnormal aggregation and fibrillogenesis of amyloid-ß protein (Aß) can cause Alzheimer's disease (AD). Thus, the discovery of effective drugs that inhibit Aß fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating Aß aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on Aß1-42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-ß-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of Aß1-42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of Aß1-42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with Aß1-42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of Aß, and promote further exploration of the therapeutic strategy against AD.

Design, synthesis, and evaluation of VHL-based EZH2 degraders for breast cancer.

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2. We developed a potent and effective EZH2 degrader P4, which effectively induced EZH2 protein degradation and inhibited breast cancer cell growth. Further studies showed that P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G0/G1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. Therefore, P4 is a potential anticancer molecule for breast cancer treatment.

Cathelicidin peptide analogues inhibit EV71 infection through blocking viral entry and uncoating.

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.