Mechanisms of hormetic effects of ofloxacin on Chlorella pyrenoidosa under environmental-relevant concentration and long-term exposure.

Antibiotics are frequently detected in surface water and pose potential threats to organisms in aquatic ecosystem such as microalgae. The occurrence of biphasic dose responses raised the possibility of stimulation of microalgal biomass by antibiotics at environmental-relevant concentration and caused potential ecological risk such as algal bloom. However, the underlying mechanisms of low concentration-induced hormetic effects are not well understood. In this study, we evaluated the hormesis of ofloxacin on Chlorella pyrenoidosa under environmental-relevant concentration and long-term exposure. Results showed the hormetic effects of ofloxacin on cell density and carbon fixation rate (RC). The predicted maximum promotion was 17.45 % by 16.84 µg/L and 20.08 % by 15.78 µg/L at 21 d, respectively. The predicted maximum concentration of non-effect on cell density and RC at 21 d was 3.24 mg/L and 1.44 mg/L, respectively. Ofloxacin induced the mobilization of pigments and antioxidant enzymes to deal with oxidative stress. PCA analysis revealed Chl-a/Chl-b could act as a more sensitive biomarker under acute exposure while chlorophyll fluorescence parameters were in favor of monitoring long-term implication. The hormesis in increased secretion of extracellular organic matters was regarded as a defensive mechanism and accelerated indirect photodegradation of ofloxacin. Bioremoval was dominant and related to biomass accumulation in the total dissipation while abiotic removal appeared slight contributions. This study provided new insights into the understanding of hormesis of microalgae induced by antibiotics.

ZIF-67-Derived Flexible Sulfur Cathode with Improved Redox Kinetics for High-Performance Li-S Batteries.

Lithium-sulfur (Li-S) batteries have received much attention due to their high energy density and low price. In recent years, alleviating the volume expansion and suppressing the shuttle effect during the charge and discharge processes of Li-S batteries have been widely addressed. However, the slow conversion kinetics from polysulfide (LiPSs) to Li2S2/Li2S still limits the application of Li-S batteries. Therefore, we designed a ZIF-67 grown on cellulose (named ZIF-67@CL) as an electrocatalyst to improve the interconversion kinetics from LiPSs to Li2S2/Li2S for Li-S batteries. Based on the results of adsorption experiments of LiPSs, ZIF-67@CL and CL hosts were immersed in Li2S4 solution to adsorb LiPSs, and the UV-Vis test was conducted on the supernatant after adsorption. The results showed that the ZIF-67@CL had a stronger adsorption for LiPSs compared with the cellulose (CL). Furthermore, in the Li2S nucleation tests, the fabricated cells were galvanostatically discharged to 2.06 V at 0.112 mA and then potentiostatically discharged at 2.05 V. Based on the results of Li2S nucleation tests, the catalytic effect of ZIF-67 was further verified. As a result, the sulfur cathode used a ZIF-67 catalyst (named S/ZIF-67@CL) and delivered an initial capacity of 1346 mAh g-1 at a current density of 0.2 C. Even at a high current density of 2 C, it exhibited a high-capacity performance of 1087 mAh g-1 on the first cycle and maintained a capacity output of 462 mAh g-1 after 150 cycles, with a Coulombic efficiency of over 99.82%.

Bacterial extracellular vesicles: Vital contributors to physiology from bacteria to host.

Bacterial extracellular vesicles (bEVs) represent spherical particles with diameters ranging from 20 to 400 nm filled with multiple parental bacteria-derived components, including proteins, nucleic acids, lipids, and other biomolecules. The production of bEVs facilitates bacteria interacting with their environment and exerting biological functions. It is increasingly evident that the bEVs play integral roles in both bacterial and host physiology, contributing to environmental adaptations to functioning as health promoters for their hosts. This review highlights the current state of knowledge on the composition, biogenesis, and diversity of bEVs and the mechanisms by which different bEVs elicit effects on bacterial physiology and host health. We posit that an in-depth exploration of the mechanistic aspects of bEVs activity is essential to elucidate their health-promoting effects on the host and may facilitate the translation of bEVs into applications as novel natural biological nanomaterials.

Effect of inspiratory muscle training in children with asthma: a systematic review and meta-analysis of randomized controlled trials.

Background: Asthma is a common chronic respiratory disease in children. Alongside pharmacological interventions, inspiratory muscle training (IMT) emerges as a complementary therapeutic approach for asthma management. However, the extent of its efficacy in pediatric populations remains uncertain when compared to its benefits in adults. This systematic review aims to evaluate the effectiveness of IMT with threshold loading in children with asthma. Methods: Randomized controlled trials (RCTs) evaluating the efficacy of inspiratory muscle training in pediatric asthma patients were identified through June 2023 across various literature databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAL), Web of Science, China Knowledge Resource Integrated Database (CNKI), Wei Pu Database, Wan Fang Database, and Chinese Biomedical Database (CBM). These trials compared inspiratory muscle training against sham inspiratory muscle training and conventional care. Eligible studies were assessed in terms of risk of bias and quality of evidence. Where feasible, data were pooled and subjected to meta-analysis, with results reported as mean differences (MDs) and 95% confidence intervals (CIs). Results: Six trials involving 333 patients were included in the analysis. IMT demonstrated significant improvements in maximum inspiratory pressure (MIP) (MD 25.36, 95% CI 2.47-48.26, P = 0.03), maximum expiratory pressure (MEP) (MD 14.72, 95% CI 4.21-25.24, P = 0.006), forced vital capacity in percent predicted values [FVC(% pred)] (MD 3.90, 95% CI 1.86-5.93, P = 0.0002), forced expiratory volume in the first second in percent predicted values [FEV1(% pred)] (MD 4.96, 95% CI 2.60-7.32, P < 0.0001), ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) (MD 4.94, 95% CI 2.66-7.21, P < 0.0001), and asthma control test (ACT) (MD = 1.86, 95% CI: 0.96-2.75, P < 0.0001). Conclusions: Findings from randomized controlled trials indicate that inspiratory muscle training enhances respiratory muscle strength and pulmonary function in pediatric asthma patients. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449918, identifier: CRD42023449918.

Analysis of affordability differences for rare diseases in China: a comparison across disease types and regions.

BACKGROUND: China has implemented policies to make rare diseases more affordable. While previous studies evaluated overall affordability, few have examined affordability differences across regions and disease types. Given the vastness of China and varying medical policies across cities, this study assesses the affordability of rare diseases based on China's First List of Rare Diseases (CFLRD), National Reimbursement Drug List (NRDL), and outpatient chronic and special disease policies in each prefecture. METHOD: Six rare diseases were selected and the average annual treatment cost of all relevant drugs in NRDL was calculated for each disease. Based on the WHO/HAI standardized approach, the study analyzed 289 cities with outpatient chronic and special disease policies, measured the security levels by the actual reimbursement ratio of Basic Medical Insurance (BMI) and affordability by the ratio of individual expenses after reimbursement to the annual disposable income of urban residents in the province. The security levels and affordability differences across disease types and provinces were analyzed using the Mann-Whitney U test and the K-W test. RESULT: The affordability of rare diseases varied significantly on the disease types and annual treatment cost. Diseases with an annual treatment cost below 100 000 yuan are affordable to all prefectures even with low reimbursement rates, while those with a higher treatment cost were not affordable in at least 80% of prefectures even though the reimbursement ratio is high. The affordability of the same disease varies significantly across provinces and municipalities. Outpatient chronic and special diseases insurance and critical illness insurance, and the inconsistencies between them, result in regional differences. CONCLUSION: Although China has made progress in improving the affordability of rare diseases, significant differences persist between cities and diseases. The study suggests the optimization of the BMI system and explores independent funds and innovative insurance models to enhance the affordability of rare diseases, particularly those with extremely high treatment costs.

Clinical significance of serum high sensitive C-reactive protein/albumin ratio in primary prostate biopsy.

Objective: The purpose of this study was to investigate the clinical significance of serum high sensitive C-reactive protein/albumin ratio in primary prostate biopsy. Methods: Retrospective analysis was done on the clinical data of 1679 patients who had their first transrectal or perineal prostate biopsy at our situation from 2010 to 2018. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) were the pathologic diagnoses in 819 and 860 cases, respectively. A comparison was made between the HAR differences between PCa and BPH patients as well as the positive prostate biopsy rate differences between groups with increased and normal HAR. The results of the prostate biopsy were examined using logistic regression, and a model for predicting prostate cancer was created. The receiver characteristic curve (ROC) was used to determine the model's prediction effectiveness. The clinical models integrated into HAR were evaluated for their potential to increase classification efficacy using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). According to the Gleason score (GS) categorization system, prostate cancer patients were separated into low, middle, and high GS groups. The differences in HAR between the various groups were then compared. The prevalence of high GSPCa and metastatic PCa in normal populations and the prevalence of higher HAR in prostate cancer patients were compared using the chi-square test. Result: Patients with PCa had a median HAR (upper quartile to lower quartile) of 0.0379 (10-3), patients with BPH had a median HAR (0.0137 (10-3)), and the difference was statistically significant (p<0.05). Patients with increased HAR and the normal group, respectively, had positive prostate biopsy rates of 52% (435/839)and 46% (384/840), and the difference was statistically significant (p<0.05). Logistic regression analysis showed that HAR (OR=3.391, 95%CI 2.082 ~ 4.977, P < 0.05), PSA density (PSAD) (OR=7.248, 95%CI 5.005 ~ 10.495, P < 0.05) and age (OR=1.076, 95%CI 1.056 ~ 1.096, P < 0.05) was an independent predictor of prostate biopsy results. Two prediction models are built: a clinical model based on age and PSAD, and a prediction model that adds HAR to the clinical model. The two models' ROC had area under the curves (AUC) of 0.814 (95%CI 0.78-0.83) and 0.815 (95%CI 0.79-0.84), respectively. When compared to a single blood total PSA (tPSA) with an AUC of 0.746 (95%CI 0.718-0.774), they were all superior. Nevertheless, there was no statistically significant difference (p<0.05) between the two models. We assessed the prediction model integrated into HAR's capacity to increase classification efficiency using NRI and IDI, and we discovered that NRI>0, IDI>0, and the difference was statistically significant (P>0.05).There was a statistically significant difference in HAR between various GS groups for individuals who had prostate cancer as a consequence of biopsy (p<0.05). The incidence of high GS and metastatic patients was statistically significantly greater (p<0.05) in the HAR elevated group (90.1%and 39.3%, respectively) than in the HAR normal group (84.4% and 12.0%). Conclusion: Prostate biopsy results that were positive were impacted by HAR, an independent factor that increased with the rate of PCa discovery. Patients with elevated HAR had a greater risk of high GS as well as metastatic PCa among those with recently diagnosed prostate cancer through prostate biopsy.

All-in-one Janus covalent organic frameworks separator as fast Li nucleator and polysulfides catalyzer in lithium-sulfur batteries.

The shuttle effect, sluggish conversion kinetics, and uncontrollable lithium dendrites seriously hinder the practical application of lithium-sulfur (Li-S) batteries. Among many modified materials, covalent organic frameworks (COFs) stand out for their excellent ability to inhibit the shuttle effect, while their role in promoting lithium nucleation and catalyzing the conversion of sulfur species has been largely ignored. In this study, an integrated COF separator (TpPa@2400) is developed as a rapid lithium nucleator and sulfur species catalyst in fast-charging Li-S batteries. According to the adsorption energy and Bader charge results, Li atoms preferentially adsorb onto the surface of the TpPa@2400 separator, and the larger Bader charge value (0.52 |e|) of the TpPa@2400 separator also signifies faster lithium transport, promoting the nucleation of Li ions. Furthermore, density functional theory (DFT) theoretically demonstrates that the TpPa@2400 separator exhibits lower free energy for sulfur species interconversion. As a result, the TpPa@2400 separator enables the Li-Li symmetric cell with an extended cycle life of 6000 h at a current density/capacity of 10 mA cm-2/10 mAh cm-2. The Li-S battery assembled using the TpPa@2400 separator delivers a high capacity of 1636.4 mAh/g at 0.1C and a rapid sulfur species conversion capacity of 513.8 mAh/g at 2C.

Integrated Analysis of Gut Microbiome and Adipose Transcriptome Reveals Beneficial Effects of Resistant Dextrin from Wheat Starch on Insulin Resistance in Kunming Mice.

Systemic chronic inflammation is recognized as a significant contributor to the development of obesity-related insulin resistance. Previous studies have revealed the physiological benefits of resistant dextrin (RD), including obesity reduction, lower fasting glucose levels, and anti-inflammation. The present study investigated the effects of RD intervention on insulin resistance (IR) in Kunming mice, expounding the mechanisms through the gut microbiome and transcriptome of white adipose. In this eight-week study, we investigated changes in tissue weight, glucose-lipid metabolism levels, serum inflammation levels, and lesions of epididymal white adipose tissue (eWAT) evaluated via Hematoxylin and Eosin (H&E) staining. Moreover, we analyzed the gut microbiota composition and transcriptome of eWAT to assess the potential protective effects of RD intervention. Compared with a high-fat, high-sugar diet (HFHSD) group, the RD intervention significantly enhanced glucose homeostasis (e.g., AUC-OGTT, HOMA-IR, p < 0.001), and reduced lipid metabolism (e.g., TG, LDL-C, p < 0.001) and serum inflammation levels (e.g., IL-1ß, IL-6, p < 0.001). The RD intervention also led to changes in the gut microbiota composition, with an increase in the abundance of probiotics (e.g., Parabacteroides, Faecalibaculum, and Muribaculum, p < 0.05) and a decrease in harmful bacteria (Colidextribacter, p < 0.05). Moreover, the RD intervention had a noticeable effect on the gene transcription profile of eWAT, and KEGG enrichment analysis revealed that differential genes were enriched in PI3K/AKT, AMPK, in glucose-lipid metabolism, and in the regulation of lipolysis in adipocytes signaling pathways. The findings demonstrated that RD not only ameliorated IR, but also remodeled the gut microbiota and modified the transcriptome profile of eWAT.

Carbon-Coated Tin-Titanate derived SnO2/TiO2 nanowires as High-Performance anode for Lithium-Ion batteries.

Tin dioxide (SnO2) is a promising alternative material to graphite anode, but the large volume change induced electrode pulverization issue has limited its application in lithium-ion batteries (LIBs). In contrast, titanium dioxide (TiO2) anode shows high structure stability upon lithium insertion/extraction, but with low specific capacity. To overcome their inherent disadvantages, combination of SnO2 with TiO2 and highly conductive carbon material is an effective way. Herein, we report a facile fabrication method of carbon-coated SnO2/TiO2 nanowires (SnO2/TiO2@C) using tin titanate nanowires as precursor, which are prepared by reacting SnCl2·2H2O with layered sodium titanate (Na2Ti3O7) nanowires in the aqueous solution though the ion exchange between Sn2+ and Na+. After annealing under argon atmosphere, the hydrothermally carbon-coated tin-titanate nanowires decompose, forming a unique hybrid structure, where ultrafine SnO2 nanoparticles are uniformly embedded within the TiO2 substrate with carbon coating. Consequently, the SnO2/TiO2@C nanowires demonstrate excellent lithium storage capacity with high pseudocapacitance contribution, excellent reversible capacity, and long-term cycling stability (673.7/510.5 mAh/g at 0.5/1.0 A/g after 250/800 cycles), owing to the unique hybrid structure, as the well-dispersion of ultra-small SnO2 within TiO2 nanowire substrate with simultaneous carbon coating efficiently suppresses the volume changes of SnO2, provides abundant reactive sites for lithium storage, and enhances the electrical conductivity with shortened ion transport distance.

High Fischer Ratio Oligopeptides of Gluten Alleviate Alcohol-Induced Liver Damage by Regulating Lipid Metabolism and Oxidative Stress in Rats.

High Fischer ratio oligopeptides (HFOs) exhibit diverse biological activities, including anti-inflammatory and antioxidant properties. HFOs from gluten origin were prepared through fermentation and enzymatic hydrolysis and then characterized using free amino acid analysis and scanning electron microscopy (SEM). Following intervention, the levels of serum total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic malondialdehyde (MDA) in the rats significantly decreased (p < 0.05). Simultaneously, there was an increasing trend in superoxide dismutase (SOD) levels, and glutathione (GSH) levels were significantly elevated (p < 0.05). The mRNA expression levels of alcohol metabolism-related genes (ADH4, ALDH2, and CYP2E1) exhibited a significant increase (p < 0.05). Histological examination revealed a reduction in liver damage. The findings indicate that high Fischer ratio oligopeptides, prepared through enzymatic and fermentation methods, significantly improve lipid levels, ameliorate lipid metabolism disorders, and mitigate oxidative stress, and exhibit a discernible alleviating effect on alcoholic liver injury in rats.

Physiological-biochemical responses and transcriptomic analysis reveal the effects and mechanisms of sulfamethoxazole on the carbon fixation function of Chlorella pyrenoidosa.

The occurrence of sulfamethoxazole (SMX) is characterized by low concentration and pseudo-persistence. However, the toxic effects and mechanisms of SMX, especially for low concentration and long-term exposure, are still not clear. This study investigated the effects and mechanisms of SMX on carbon fixation-related biological processes of Chlorella pyrenoidosa at population, physiological-biochemical, and transcriptional levels. Results showed that 1-1000 µg/L SMX significantly inhibited the dry weight and carbon fixation rate of C. pyrenoidosa during 21 d. The upregulation of superoxide dismutase (SOD) and catalase (CAT) activities, as well as the accumulation of malondialdehyde (MDA) demonstrated that SMX posed oxidative damage to C. pyrenoidosa. SMX inhibited the activity of carbonic anhydrase (CA), and consequently stimulated the activity of Rubisco. Principal component analysis (PCA) revealed that SMX concentration was positively correlated with Rubisco and CAT while exposure time was negatively correlated with CA. Transcriptional analysis showed that the synthesis of chlorophyll-a was stabilized by regulating the diversion of protoporphyrin IX and the chlorophyll cycle. Meanwhile, multiple CO2 compensation mechanisms, including photorespiratory, C4-like CO2 compensation and purine metabolism pathways were triggered in response to the CO2 requirements of Rubisco. This study provides a scientific basis for the comprehensive assessment of the ecological risk of SMX.

An advanced strategy for quality evaluation of Xinyi Biyan Pill by UPLC-DAD fingerprinting combined with multi-components UPLC-MS/MS analysis.

Xinyi Biyan Pill (XBP) is a classical Chinese patent medicine and widely used to treat acute and chronic or allergic rhinitis in clinical practice. This study aimed to establish and validate a comprehensive strategy combining ultra-performance liquid chromatography with diode array detector (UPLC-DAD) fingerprinting and multi-component quantification for quality evaluation of XBP. In the fingerprint analysis, 32 peaks were selected as common peaks and used to evaluate the similarity of 12 batches of XBP. In addition, 141 compounds of XBP were identified or preliminarily characterized in both positive and negative ion modes by coupling with an advanced hybrid linear ion trap (LTQ)-Orbitrap mass spectrometer. Moreover, a rapid quantitative method based on UPLC tandem mass spectrometry (UPLC-MS/MS) has been optimized and validated for simultaneous determination of 10 chemical markers within 15 min, and applied to analyzing 12 batches of XBP. The proposed comprehensive strategy combining UPLC-DAD fingerprinting and multi-component UPLC-MS/MS quantification exhibited satisfactory results with high efficiency, accuracy and reliability, which can be used as a reference for overall quality consistency evaluation of Chinese herbal formulations.

Suppressing Dendrite Growth with Eco-Friendly Sodium Lignosulfonate Additive in Quasi-Solid-State Li Metal Battery.

The application of lithium metal batteries is limited by the drawbacks of safety problems and Li dendrite formation. Quasi-solid-state electrolytes (QSSEs) are the most promising alternatives to commercial liquid electrolytes due to their high safety and great compatibility with electrodes. However, Li dendrite formation and the slow Li+ diffusion in QSSEs severely hinder uniform Li deposition, thus leading to Li dendrite growth and short circuits. Herein, an eco-friendly and low-cost sodium lignosulfonate (LSS)-assisted PVDF-based QSSE is proposed to induce uniform Li deposition and inhibit Li dendrite growth. Li symmetric cells with 5%-LSS QSSE possess a high Li+ transfer number of 0.79, and they exhibit a long cycle life of 1000 h at a current density/areal capacity of 1 mA cm-2/5 mAh cm-2. Moreover, due to the fast electrochemical dynamics endowed by the improved compatibility of the electrodes and fast Li+ diffusion, the LFP/5%-LSS/Li full cells still maintain a high capacity of 110 mAh g-1 after 250 cycles at 6C. This work provides a novel and promising choice that uses eco-friendly LSS as an additive to PVDF-based QSSE in Li metal batteries.

pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy.

Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.16%), electric neutrality, strong hydrophobicity, and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH. These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.

Rational design of hollow Ti2Nb10O29 nanospheres towards High-Performance pseudocapacitive Lithium-Ion storage.

Ti2Nb10O29, as one of the most promising anode materials for lithium-ion batteries (LIBs), possesses excellent structural stability during lithiation/delithiation cycling and higher theoretical capacity. However, Ti2Nb10O29 faces some challenges, such as insufficient ion diffusion coefficient and poor electronic conductivity. To overcome these problems, this study investigates the effect of applying nanostructure engineering on Ti2Nb10O29 and the lithium storage behaviors. We successfully synthesized hollow Ti2Nb10O29 nanospheres (h-TNO NSs) via solvothermal method using phenolic resin nanospheres as the template. The effects of using a template or not and the annealing atmospheres on the microstructures of the as-prepared Ti2Nb10O29 are investigated. Different nanostructures (porous Ti2Nb10O29 nanoaggregates (p-TNO NAs) without a template and core-shelled Ti2Nb10O29@C nanospheres (cs-TNO@C NSs)) were formed through annealing in Ar. When examined as anodes for LIBs, the h-TNO NSs electrode with hollow spherical structure displayed a better lithium storage performance. Compared to its counterparts, p-TNO NAs and cs-TNO@C NSs, h-TNO NSs electrode exhibited a higher reversible capacity of 282.5 mAh g-1 at 1C, capacity retention of 79.5% (i.e., 224.6 mAh g-1) after 200 cycles, and a higher rate capacity of 173.1 mAh g-1 at 10C after 600 cycles. The excellent electrochemical performance of h-TNO NSs is attributed to the novel structure. The hollow nanospheres with cavities and thin shells not only exposed more active sites and improved ion diffusion, but also buffered the volume variation upon cycling and facilitated electrolyte penetration. This consequently enhanced the lithium storage performance of the electrode and its high pseudocapacitive contribution (90% at 1.0 mV s-1).

SlSAMS1 enhances salt tolerance through regulation DNA methylation of SlGI in tomato.

S-adenosylmethionine (SAM), which is synthesized from methionine and ATP catalyzed by S-adenosylmethionine synthetase (SAMS), is an important methyl donor in plants. SAMS and DNA methylation play an important role in the plant response to abiotic stresses. Previous studies have shown that SAMS improves salt tolerance in tomato plants, but it is not clear whether the DNA methylation pathway mediates SAMS-induced salt tolerance. This study confirmed that SlSAMS1-overexpressing plants exhibited improved salt tolerance. Through whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing (RNA-seq) analysis, the study screened the circadian rhythm pathway and identified the gene SlGI in this pathway, which was regulated by SlSAMS1. The gene body region of SlGI, the core gene of the circadian rhythm pathway, was hypermethylated in SlSAMS1-overexpressing plants, and its expression level was significantly increased. Furthermore, the SlGI-overexpressing plants showed higher salt tolerance, less reduction in plant height and fresh weight, lower electrolyte leakage, malondialdehyde and H2O2 content, and higher antioxidant enzyme activity compared to wild type plants. Therefore, SlSAMS1-overexpressing plants regulated significant changes in CHG-type methylation sites of the SlGI gene body and its expression levels, leading to an enhanced salt tolerance of tomato plants.

Discovery of Indole-Piperazine Hybrid Structures as Potent Selective Class I Histone Deacetylases Inhibitors.

Histone deacetylases (HDACs) are important targets in cancer treatment, and the development of selective and broad-spectrum HDACs inhibitors (HDACis) is urgent. In this research, a series of aroylpiperazine hybrid derivatives were designed and synthesized. Among these, indole-piperazine hybrids 6a (IC50 = 205 nM) and 6b (IC50 = 280 nM) showed submicromolar activity against HDAC1. Moreover, 6a showed a preferable affinity toward class I HDACs, especially for HDAC1-3. In vitro, 6a exhibited better antiproliferative activities against K562 and HCT116 cell lines than chidamide.