Library-Assisted Evolution in Eukaryotic Cells Yield Adenine Base Editors with Enhanced Editing Specificity.

The current-generation adenine base editor (ABE) ABE8e, which has evolved from the prokaryotic evolution system, exhibits high efficiency in mediating A-to-G conversion and is presumed to be promising for gene therapy. However, its much wider editing window and substantially higher off-target editing activity restricted its applications in precise base editing for therapeutic use. This study uses a library-assisted protein evolution approach using eukaryotic cells to generate ABE variants with improved specificity and reduced off-target editing while maintaining high activity in human cells. The study generated an expanded set of ABEs with efficient editing activities and chose four evolved variants that offered either similar or modestly higher efficiency within a narrower editing window of protospacer position ≈4-7 compared to that of ABE8e in human cells, which would enable minimized bystander editing. Moreover, these variants resulted in reduced off-target editing events when delivered as plasmid or mRNA into human cells. Finally, these variants can install both disease-suppressing mutations and disease-correcting mutations efficiently with minimal undesired bystander editing making them promising approaches for specific therapeutic edits. In summary, the work establishes a mutant-library-assisted protein evolution method in eukaryotic cells and generates alternative ABE variants as efficient tools for precise human genome editing.

Factor structure and reliability of the symptom measurement of post-stroke depression in the rehabilitation stage.

BACKGROUND: The incidence of Post Stroke Depression (PSD) in the Rehabilitation Stage is high, which can bring serious physical and psychological disorders to patients. However, there is still a lack of targeted tools for screening PSD in the rehabilitation stage. Therefore, the aim of this study was to evaluate the factor structure and reliability of a measurement instrument to screen for PSD in the rehabilitation stage. METHODS: A cross-sectional study was conducted on 780 hospitalized stroke patients who were within the rehabilitation stage from May to August 2020. Exploratory factor analysis (EFA) as well as first- and second-order confirmatory factor analysis (CFA) were performed to evaluate the factor structure of the newly developed Symptom Measurement of Post-Stroke Depression in the Rehabilitation Stage (SMPSD-RS). The reliability and validity of the SMPSD-RS were also verified using several statistical methods. RESULTS: EFA extracted a 24-item, five-factor (cognition, sleep, behavior, emotion, and obsession) model that can clinically explain the symptoms of PSD during the rehabilitation stage. A first-order CFA confirmed the EFA model with good model fit indices, and the second-order CFA further confirmed the five-factor structure model and showed acceptable model fit indices. Acceptable reliability and validity were also achieved by the corresponding indicators. CONCLUSION: The SMPSD-RS was proven to have a stable factor structure and was confirmed to be reliable and valid for assessing PSD symptoms in stroke patients during the rehabilitation stage.

Critical review on the environmental behaviors and toxicity of triclosan and its removal technologies.

As a highly effective broad-spectrum antibacterial agent, triclosan (TCS) is widely used in personal care and medical disinfection products, resulting in its widespread occurrence in aquatic and terrestrial environments, and even in the human body. Notably, the use of TCS surged during the COVID-19 outbreak, leading to increasing environmental TCS pollution pressure. From the perspective of environmental health, it is essential to systematically understand the environmental occurrence and behavior of TCS, its toxicological effects on biota and humans, and technologies to remove TCS from the environment. This review comprehensively summarizes the current knowledge regarding the sources and behavior of TCS in surface water, groundwater, and soil systems, focusing on its toxicological effects on aquatic and terrestrial organisms. Effluent from wastewater treatment plants is the primary source of TCS in aquatic systems, whereas sewage application and/or wastewater irrigation are the major sources of TCS in soil. Human exposure pathways to TCS and associated adverse outcomes were also analyzed. Skin and oral mucosal absorption, and dietary intake are important TCS exposure pathways. Reducing or completely degrading TCS in the environment is important for alleviating environmental pollution and protecting public health. Therefore, this paper reviews the removal mechanisms, including adsorption, biotic and abiotic redox reactions, and the influencing factors. In addition, the advantages and disadvantages of the different techniques are compared, and development prospects are proposed. These findings provide a basis for the management and risk assessment of TCS and are beneficial for the application of treatment technology in TCS removal.

Association between friends' hesitancy and personal COVID-19 vaccine hesitancy among Chinese medical staff.

COVID-19 vaccine hesitancy remains problematic among healthcare workers. Social network influences may shape vaccine decision-making, but few studies have examined this in this critical workforce. We assessed the relationship between friends' COVID-19 vaccination attitudes and personal hesitancy among Chinese healthcare personnel. In December 2022-January 2023, a cross-sectional online survey was conducted at a tertiary hospital in China using WeChat. Of the 1832 healthcare personnel who were invited to answer the structured questionnaire, 613 (33.5%) samples had valid data for data analysis. Logistic regression examined the association between friends' hesitancy and participants' own hesitancy, adjusting for confounders. Of 613 healthcare workers included, 266 (43.4%) were hesitant. Those with hesitant friends had 6.34 times higher adjusted odds of hesitating themselves versus those without hesitant friends (95% CI 2.97-13.52). Strong associations persisted across subgroups. Chinese healthcare workers' COVID-19 vaccination hesitancy was highly influenced by perceived friends' attitudes. Fostering pro-vaccine social norms through trusted peer networks could help promote vaccine acceptance in this critical workforce.

Understanding factors affecting Chinese medical staff's fear of receiving the fourth dose of COVID-19 vaccine: A cross-sectional study in Taizhou.

The study was conducted to assess medical staffs' fear of receiving the fourth dose of the Coronavirus disease 2019 (COVID-19) vaccine. From December 17, 2022, to January 31, 2023, an online survey was conducted to assess the fear among medical staffs regarding the administration of the fourth dose of the COVID-19 vaccine. The participants were exclusively drawn from a tertiary grade hospital in Taizhou. Out of the 1, 832 medical staffs invited to participate in the questionnaire, a total of 613 (33.5%) provided valid responses for subsequent analysis. Among them, 81 (13.8%) expressed fear of receiving the fourth dose of COVID-19. The fear was significantly influenced by these factors: the presence of serious food/drug allergic reactions (OR = 3.84, 95% CI: 1.40-10.52), received booster COVID-19 vaccine (OR = 0.20, 95% CI: 0.11-0.35), opinion on vaccination requirement (OR = 0.20, 95% CI: 0.11-0.35), viewpoint (OR = 0.23, 95% CI: 0.12-0.44) with scores ≥10, and positive attitude toward vaccination (OR = 0.21, 95% CI: 0.13-0.35). Our study revealed that a subset of medical staffs still harbor apprehension toward receiving the fourth dose of the new COVID-19 vaccine. Factors influencing this fear encompass allergic reactions, booster COVID-19 vaccine, as well as opinion, viewpoint, and attitude toward vaccination. Educating medical staffs on these factors may help mitigate their fear.

Emotion regulation in undergraduate nursing students: A latent profile analysis.

BACKGROUND: Current research on emotion regulation of undergraduate nursing students mainly focused on the overall level of emotion regulation and its relationship with other variables, ignoring the individual heterogeneity of emotion regulation of undergraduate nursing students. AIM: By latent profile analysis (LPA), this study aimed to identify different emotion regulation profiles among undergraduate nursing students and to explore demographic and personal factors associated with different emotion regulation profiles. METHOD: This was a cross-sectional study. A total of 578 nursing students were investigated by the demographic questionnaire, the emotion regulation scale, the Connor-Davidson resilience scale-10 item and the core self-evaluations scale. LPA was used to analyze the latent profiles of emotion regulation among undergraduate nursing students. And multiple logistic regression was used to explore the predictors of different profiles. RESULT: Three potential profiles were identified: profile 1-- low suppression and moderate reappraisal group, profile 2-- moderate suppression and high reappraisal group, profile 3-- high suppression and high reappraisal group. Resilience, family monthly income and perception of nursing profession were predictors of different profiles. CONCLUSION: Most nursing students were classified into profile 2 and their emotion regulation was relatively good. However, students in profile 1 were with moderate cognitive reappraisal and students in profile 3 were with high expressive suppression, and their emotion regulation need to be further improved by increasing their cognitive reappraisal and decreasing their expressive suppression. Strategies tails to improve resilience, increase scholarships and change the perception of nursing profession may be effective ways to improve emotion regulation of undergraduate nursing students in different profiles.

Enhanced removal performance of magnesium-modified biochar for cadmium in wastewaters: Role of active functional groups, processes, and mechanisms.

In this study, a series of biochar products with different active functional groups were developed by one-pot coprecipitation method, including magnesium-modified biochar (MgBC) and functional group-grafted MgBC (Cys@MgBC, Try@MgBC, and Glu@MgBC), for effective adsorption of cadmium (Cd(II)) from wastewaters. These biochars exhibited excellent removal performance for Cd(II), particularly Cys@MgBC, whose maximum Cd(II) adsorption capacity reached 223.7 mg g-1. The highly active and weakly crystalline Mg could adsorb Cd(II) through precipitation and ion exchange, which was further promoted by the introduced functional groups through complexation and precipitation. After 120 d of natural process, the immobilization efficiency of Cd(II) by Cys@MgBC, Try@MgBC, and Glu@MgBC was still maintained at 98.7%, 95.2%, and 82.7% respectively. This study proposes and clarifies the complexation mechanism of functional group-grafted Mg-modified biochar for heavy metals, providing new insights into the practical application of these biochars.

Feasibility and optimization of a novel upflow denitrification reactor using denitrifying granular sludge for nitric acid pickling wastewater treatment.

Stainless steel is highly valued for its superior resistance to corrosion. However, the pickling process involved in stainless steel production generates abundant NO3--N, causing health and environmental risks. To address this issue, this study proposed a novel solution utilizing an up-flow denitrification reactor and denitrifying granular sludge for treating NO3--N pickling wastewater under high NO3--N loading. It was found that, the denitrifying granular sludge exhibited stable denitrification performance with the highest denitrification rate of 2.79 gN/(gVSS·d) and average removal rates of NO3--N and TN of 99.94% and 99.31%, respectively, under optimal operating conditions of pH 6-9, temperature 35 °C, C/N ratio 3.5, hydraulic retention time (HRT) 11.1 h and ascending flow rate 2.75 m/h. This process reduced carbon source usage by 12.5-41.7% as compared to traditional denitrification methods. These findings demonstrate the efficacy of combining granular sludge and an up-flow denitrification reactor for treating nitric acid pickling wastewater.

Therapeutic adenine base editing of human hematopoietic stem cells.

In ß-thalassemia, either γ-globin induction to form fetal hemoglobin (α2γ2) or ß-globin repair to restore adult hemoglobin (α2ß2) could be therapeutic. ABE8e, a recently evolved adenine base editor variant, can achieve efficient adenine conversion, yet its application in patient-derived hematopoietic stem cells needs further exploration. Here, we purified ABE8e for ribonucleoprotein electroporation of ß-thalassemia patient CD34+ hematopoietic stem and progenitor cells to introduce nucleotide substitutions that upregulate γ-globin expression in the BCL11A enhancer or in the HBG promoter. We observed highly efficient on-target adenine base edits at these two regulatory regions, resulting in robust γ-globin induction. Moreover, we developed ABE8e-SpRY, a near-PAMless ABE variant, and successfully applied ABE8e-SpRY RNP to directly correct HbE and IVS II-654 mutations in patient-derived CD34+ HSPCs. Finally, durable therapeutic editing was produced in self-renewing repopulating human HSCs as assayed in primary and secondary recipients. Together, these results support the potential of ABE-mediated base editing in HSCs to treat inherited monogenic blood disorders.

The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy.

Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy. Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome. Results: Of the 111 evaluable patients, the low ALI group (<32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p < 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035-0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients. Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.

Determinants of the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine in Taizhou, China.

The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis. Four hundred thirty-seven medical staff (85.0%) were willing to have their children receive vaccine boosters. After adjustments for confounding factors, the opinion ('Do you think your child needs a booster vaccination against COVID-19?') (yes vs. no, OR = 6.91, 95% CI: 3.29-14.54), the viewpoint ('What are your thoughts the effectiveness of COVID-19 vaccine boosters for children?' (≥12 vs. <12, OR = 13.81, 95% CI: 4.03-), and the attitude ('Your attitude to whether your child is boosting the Covid-19 vaccine?') (yes vs. no, OR = 4.66, 95% CI: 2.30-9.44) were significantly associated with their willingness to have their children receive a COVID-19 vaccine booster. A moderate percentage of the respondents expressed willingness to have their children receive booster vaccines. The findings implied that factors affecting medical staffs' willingness to vaccinate their children with a COVID-19 vaccine booster included viewpoint, opinion, and attitudes.

CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric ß0/ß0 transfusion-dependent ß-thalassemia.

Gene editing to disrupt the GATA1-binding site at the +58 BCL11A erythroid enhancer could induce γ-globin expression, which is a promising therapeutic strategy to alleviate ß-hemoglobinopathy caused by HBB gene mutation. In the present study, we report the preliminary results of an ongoing phase 1/2 trial (NCT04211480) evaluating safety and efficacy of gene editing therapy in children with blood transfusion-dependent ß-thalassemia (TDT). We transplanted BCL11A enhancer-edited, autologous, hematopoietic stem and progenitor cells into two children, one carrying the ß0/ß0 genotype, classified as the most severe type of TDT. Primary endpoints included engraftment, overall survival and incidence of adverse events (AEs). Both patients were clinically well with multilineage engraftment, and all AEs to date were considered unrelated to gene editing and resolved after treatment. Secondary endpoints included achieving transfusion independence, editing rate in bone marrow cells and change in hemoglobin (Hb) concentration. Both patients achieved transfusion independence for >18 months after treatment, and their Hb increased from 8.2 and 10.8 g dl-1 at screening to 15.0 and 14.0 g dl-1 at the last visit, respectively, with 85.46% and 89.48% editing persistence in bone marrow cells. Exploratory analysis of single-cell transcriptome and indel patterns in edited peripheral blood mononuclear cells showed no notable side effects of the therapy.

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression.

Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression-like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein-positive (GFAP+ ) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine-positive (BrdU+ ) and BrdU+ /GFAP+ cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT-PCR. We found that running exercise reversed CUS-induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT-1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression.

Parental hesitancy towards vaccinating their children with a booster dose against COVID-19: Real-world evidence from Taizhou, China.

INTRODUCTION: Parental vaccine-hesitancy can lead to delays or refusal to vaccinate children despite the availability of vaccines. This is a population-based, cross-sectional study investigating whether parents in China are hesitant to vaccinate their children with a COVID-19 vaccine booster. METHODS: Parents in Taizhou, China, responded to a self-reported online questionnaire on their hesitancy to vaccinate their children with a COVID-19 vaccine booster. Of the 1252 parents who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid data for data analysis. RESULTS: A total of 41.8% of participants were hesitant to give their children a COVID-19 vaccine booster. After adjusting for confounders, parental gender (female vs. male parent, OR=0.56 95% CI: 0.32-0.87), parental opinion (yes vs. no, OR=0.17, 95% CI: 0.09-0.30), parental attitudes (yes vs. no, OR=0.28, 95% CI: 0.16-0.50), the presence of people around them who are generally hesitant to receive COVID-19 booster vaccines for children (yes vs. no, OR=0.14, 95%CI: 0.08-0.23), the individual hesitancy of people around them to administer booster COVID-19 vaccines to children (yes vs. no, OR=0.02, 95%CI: 0.02-0.22), and parents' hesitancy to receive a booster vaccine for their children showed significant correlation. The disparity of factors related to booster vaccine-hesitancy for children between fathers and mothers was also found. CONCLUSIONS: We found that a moderate proportion of parents reported that they were hesitant to give their children a COVID-19 vaccine booster. The results suggest that an in-depth, dynamic assessment and further health education planning are necessary to reduce Chinese parents' hesitancy to vaccinate their children.

Strong Adsorption of Phosphorus by ZnAl-LDO-Activated Banana Biochar: An Analysis of Adsorption Efficiency, Thermodynamics, and Internal Mechanisms.

Zn-Al layered bimetallic composites were prepared by ethanol strengthening and co-precipitation using banana straw as a raw material. A high-efficiency phosphorus adsorbent (ZnAl-LDO-BC) was obtained by calcination at a high temperature. The kinetics and thermodynamics of phosphorus adsorption on ZnAl-LDO-BC were then studied. The results showed that the adsorption process of ZnAl-LDO-BC corresponds with the pseudo-second-order (PSO) kinetic equation and the Langmuir model. The theoretical maximum adsorption capacity of ZnAl-LDO-BC is 111.11 mg/g (at 45 °C, 500 mg/L phosphorus initial concentration). The influence of anions on phosphorus adsorption decreased in strength in the following order: CO3 2- > SO4 2- > NO3 -. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) were used to characterize the adsorption of phosphorus on ZnAl-LDO-BC and showed that ZnAl-LDO-BC can efficiently adsorb phosphorus. The adsorption mechanism utilizes both O-H and C-H on the surface of ZnAl-LDO-BC for the adsorption of PO4 3-, forming Zn3(PO4)2·4H2O via complexation precipitation; additionally, biochar surface adsorption and interlayer adsorption are indispensable forms of phosphate adsorption. With the systematic study of phosphorus adsorption by ZnAl-LDO-BC, a novel green technology was developed for addressing phosphorus pollution.

Fabrication and Characterization of Novel ZnAl-Layered Double Hydroxide for the Superadsorption of Organic Contaminants from Wastewater.

An imidazole ester skeleton (zeolitic imidazolate framework (ZIF)) was grown on the surface of a ZnAl-layered double hydroxide (ZnAl-LDH) material to form a porous composite (ZIF-ZnAl-LDH). To understand the adsorption characteristics of the two materials, the effects of pH, adsorption time, and adsorption concentration on the adsorption of Congo red (CR) solution were investigated comprehensively. In addition, ZnAl-LDH and ZIF-ZnAl-LDH were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and X-ray photoelectron spectroscopy (XPS). The results clearly showed that ZnAl-LDH had a lamellar structure with a diameter of approximately 200-500 nm and ZIF-ZnAl-LDH had a regular three-dimensional hexagonal structure. The kinetics and thermodynamics of the CR adsorption by ZnAl-LDH and ZIF-ZnAl-LDH can be described using pseudo-second-order (PSO) and Langmuir models, respectively. The highest value of adsorption capacity obtained from the Langmuir equation was equal to 625.00 and 909.09 mg/g for these two compounds, respectively. The values of the standard Gibbs free energy (ΔG°), entropy (ΔS°), and enthalpy (ΔH°) obtained for these adsorption processes prove that the adsorption of CR by ZnAl-LDH and ZIF-ZnAl-LDH is a spontaneous endothermic process. Furthermore, through the analysis of the characterization results, it is concluded that the adsorption mechanisms of ZnAl-LDH and ZIF-ZnAl-LDH on CR are mainly dominated by electrostatic action, functional group action, surface pore adsorption, and anion exchange.

Wenxin Granule Ameliorates Hypoxia/Reoxygenation-Induced Oxidative Stress in Mitochondria via the PKC-δ/NOX2/ROS Pathway in H9c2 Cells.

Myocardial infarction and following reperfusion therapy-induced myocardial ischemia/reperfusion (I/R) injury have been recognized as an important subject of cardiovascular disease with high mortality. As the antiarrhythmic agent, Wenxin Granule (WXG) is widely used to arrhythmia and heart failure. In our pilot study, we found the antioxidative potential of WXG in the treatment of myocardial I/R. This study is aimed at investigating whether WXG could treat cardiomyocyte hypoxia/reoxygenation (H/R) injury by inhibiting oxidative stress in mitochondria. The H9c2 cardiomyocyte cell line was subject to H/R stimuli to mimic I/R injury in vitro. WXG was added to the culture medium 24 h before H/R exposing as pretreatment. Protein kinase C-δ (PKC-δ) inhibitor rottlerin or PKC-δ lentivirus vectors were conducted on H9c2 cells to downregulate or overexpress PKC-δ protein. Then, the cell viability, oxidative stress levels, intracellular and mitochondrial ROS levels, mitochondrial function, and apoptosis index were analyzed. In addition, PKC-δ protein expression in each group was verified by western blot analysis. Compared with the control group, the PKC-δ protein level was significantly increased in the H/R group, which was remarkably improved by WXG or rottlerin. PKC-δ lentivirus vector-mediated PKC-δ overexpression was not reduced by WXG. WXG significantly improved H/R-induced cell injury, lower levels of SOD and GSH/GSSG ratio, higher levels of MDA, intracellular and mitochondrial ROS content, mitochondrial membrane potential and ATP loss, mitochondrial permeability transition pore opening, NOX2 activation, cytochrome C release, Bax/Bcl-2 ratio and cleaved caspase-3 increasing, and cell apoptosis. Similar findings were obtained from rottlerin treatment. However, the protective effects of WXG were abolished by PKC-δ overexpression, indicating that PKC-δ was a potential target of WXG treatment. Our findings demonstrated a novel mechanism by which WXG attenuated oxidative stress and mitochondrial dysfunction of H9c2 cells induced by H/R stimulation via inhibitory regulation of PKC-δ/NOX2/ROS signaling.

High-Efficiency Removal of Cr(VI) from Wastewater by Mg-Loaded Biochars: Adsorption Process and Removal Mechanism.

Biochars were produced with magnesium chloride as an additive for the sorption of hexavalent chromium dissolved in water using five types of straw (from taro, corn, cassava, Chinese fir, and banana) and one type of shell (Camellia oleifera) as the raw materials. The removal of hexavalent chromium by the six biochars mainly occurred within 60 min and then gradually stabilized. The kinetics of the adsorption process were second order, the Langmuir model was followed, and the adsorption of Cr(VI) by the six biochars was characterized by Langmuir monolayer chemisorption on a heterogeneous surface. Banana straw biochar (BSB) had the best performance, which perhaps benefitted from its special structure and best adsorption effect on Cr(VI), and the theoretical adsorption capacity was calculated as 125.00 mg/g. For the mechanism analysis, Mg-loaded biochars were characterized before and after adsorption by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy/energy dispersive spectroscopy (SEM-EDS). The adsorption mechanism differed from the adsorption process of conventional magnetic biochar, and biochar interactions with Cr(VI) were controlled mainly by electrostatic attraction, complexation, and functional group bonding. In summary, the six Mg-loaded biochars exhibit great potential advantages in removing Cr(VI) from wastewater and have promising potential for practical use, especially BSB, which shows super-high adsorption performance.

Cyclic Tripeptide-based Potent and Selective Human SIRT5 Inhibitors.

BACKGROUND: SIRT5 is one of the seven members (SIRT1-7) of the mammalian sirtuin family of protein acyl-lysine deacylase enzymes. In recent years, important regulatory roles of SIRT5 in (patho)physiological conditions (e.g. metabolism and cancer) have been increasingly demonstrated. For a better biological understanding and therapeutic exploitation of the SIRT5- catalyzed deacylation reaction, more effort on identifying potent and selective SIRT5 inhibitors beyond those currently known would be rewarding. OBJECTIVE: In the current study, we would like to see if it would be possible to develop potent and selective SIRT5 inhibitory lead compounds with a novel structural scaffold than those of the currently known potent and selective SIRT5 inhibitors. METHODS: In the current study, six N-terminus-to-side chain cyclic tripeptides (i.e. 8-13) each harboring the thiourea-type catalytic mechanism-based SIRT5 inhibitory warhead Nε-carboxyethylthiocarbamoyl- lysine as the central residue were designed, synthesized by the Nα-9- fluorenylmethoxycarbonyl (Fmoc) chemistry-based solid phase peptide synthesis (SPPS) on the Rink amide 4-methylbenzhydrylamine (MBHA) resin, purified by the semi-preparative reversedphase high performance liquid chromatography (RP-HPLC), characterized by the high-resolution mass spectrometry (HRMS); and were evaluated by the in vitro sirtuin inhibition assay and the in vitro proteolysis assay. RESULTS: Among the cyclic tripeptides 8-13, we found that 10 exhibited a potent (IC50 ~2.2 µM) and selective (≥60-fold over the SIRT1/2/3/6-catalyzed deacylation reactions) inhibition against the SIRT5-catalyzed desuccinylation reaction. Moreover, 10 was found to exhibit a ~42.3-fold stronger SIRT5 inhibition and a greater proteolytic stability than its linear counterpart 14. CONCLUSION: With a novel and modular structural scaffold as compared with those of all the currently reported potent and selective SIRT5 inhibitors, 10 could be also a useful and feasible lead compound for the quest for superior SIRT5 inhibitors as potential chemical/pharmacological probes of SIRT5 and therapeutics for human diseases in which SIRT5 desuccinylase activity is upregulated.