Fabrication of novel glutathione-Fe3O4-loaded/activated carbon encapsulated sand bionanocomposites for enhanced removal of Diethyl phthalate from aqueous environment in a vertical flow reactor.

The extensive use of plasticizers in various industries has made Diethyl phthalate (DEP), a serious threat to the environment and ecological water security, owing to its complex-structure and low-biodegradability. Thus, the present study aimed to design a sustainable sand-coated nano glutathione (GSH) -Fe3O4-loaded/activated carbon (AC) bionanocomposite (AC-GSH-Fe3O4@sand bionanocomposite) for effective removal of DEP from water. Characterization results suggested bionanocomposites' rough and irregular texture due to the uneven distribution of AC and Fe3O4 nanoparticles over the sand. The XRD spectra indicated high crystallinity of bionanocomposites, while the FTIR spectra confirmed the presence of all individual components, i.e., GSH, AC, Fe3O4, and sand. EDX-mapping, AFM, and TGA further verified its elemental composition, topographical changes and thermal stability. The influence of pH (3, 7, 9), bed height (2, 4, 6) cm, and flow rate (2.5, 3.5, 4.5) mL min-1 were studied in a dynamic system with an initial DEP concentration of 50 mg L-1 to investigate the removal behavior of the bionanocomposites. The best DEP removal efficiency (90.18 %) was achieved over 28-hours at pH 9, bed-height-4 cm, and flow-rate-3.5 mL min-1, with an optimum qmax-200.25 mg g-1 as determined through Thomas-model. Breakthrough curves were predicted using various column models, and the corresponding parameters essential for column-reactor process design were calculated. The high reusability up to the 10th cycle (≥ 83.32%) and the effective treatment in complex matrices (tap-water: 90.11 %, river-water: 89.72 %, wastewater: 83.83%) demonstrated bionanocomposites' prominent sustainability. Additionally, the production cost at 6.64 USD per Kg, underscores its potentiality for industrial application. Phytotoxicity assessment on mung-bean revealed better root (5.02 ± 0.27) cm and shoot (17.64 ± 0.35) cm growth in the bionanocomposite-treated DEP samples over the untreated samples. Thus, AC-GSH-Fe3O4@sand bionanocomposites could be considered a highly-sustainable, low-cost technique for the effective removal of DEP and other phthalate-esters from contaminated matrices.

PROTAC'ing the androgen receptor and other emerging therapeutics in prostate cancer.

INTRODUCTION: The androgen receptor (AR) is a critical driver of prostate cancer progression and the advent of androgen receptor pathway inhibitors (ARPIs) has transformed the treatment landscape of metastatic prostate cancer. However, resistance to ARPIs eventually develops via mutations in AR, AR overexpression, and alternative AR signaling which have required novel approaches to target effectively. AREAS COVERED: The mechanism of action and early clinical results of proteolysis targeting chimera (PROTAC) agents targeting AR are reviewed. Preclinical and early clinical data for other emerging AR-targeting therapeutics, including dual anti-androgen receptor inhibitors (DAARIs) and anitens that target the N-terminal domain (NTD) of AR, were also identified through literature search for agents which may circumvent resistance through AR splice variants and AR LBD mutations. The literature search utilized PubMed to identify articles that were relevant to this review from 2000 - 2024. EXPERT OPINION: PROTACs, DAARIs, and anitens represent novel and promising AR-targeting therapeutics that may become an important part of prostate cancer treatment in the future. Elucidating mechanisms of resistance, including ability of these agents to target full length AR, may yield further insights into maximal therapeutic efficacy aimed at silencing AR signaling.

Complement C3a/C3aR and C5a/C5aR deposits accelerate the progression of advanced IgA nephropathy to end-stage renal disease.

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732-0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079-9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

The Potential of the lncRNAs ADAMTSL4-AS1, AC067931 and SOCS2-AS1 in Peripheral Blood Mononuclear Cells as Novel Diagnostic Biomarkers for Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.

Crosstalk between epitranscriptomic and epigenomic modifications and its implication in human diseases.

Crosstalk between N6-methyladenosine (m6A) and epigenomes is crucial for gene regulation, but its regulatory directionality and disease significance remain unclear. Here, we utilize quantitative trait loci (QTLs) as genetic instruments to delineate directional maps of crosstalk between m6A and two epigenomic traits, DNA methylation (DNAme) and H3K27ac. We identify 47 m6A-to-H3K27ac and 4,733 m6A-to-DNAme and, in the reverse direction, 106 H3K27ac-to-m6A and 61,775 DNAme-to-m6A regulatory loci, with differential genomic location preference observed for different regulatory directions. Integrating these maps with complex diseases, we prioritize 20 genome-wide association study (GWAS) loci for neuroticism, depression, and narcolepsy in brain; 1,767 variants for asthma and expiratory flow traits in lung; and 249 for coronary artery disease, blood pressure, and pulse rate in muscle. This study establishes disease regulatory paths, such as rs3768410-DNAme-m6A-asthma and rs56104944-m6A-DNAme-hypertension, uncovering locus-specific crosstalk between m6A and epigenomic layers and offering insights into regulatory circuits underlying human diseases.

The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma.

INTRODUCTION: Cancer is the major cause of morbidity and mortality worldwide. Current treatments for both solid and hematological tumors are associated with severe adverse effects and drug resistance, necessitating the development of novel selective antineoplastic drugs. METHODS: The present study describes the antitumor activity of the imidazacridine derivative 5-acridin-9-ylmethylidene-2-thioxoimidazolidin-4-one (LPSF/AC05) in breast cancer, leuke-mia, and lymphoma cells. Cytotoxicity assays were performed in PBMC and in breast cancer, leukemia, and lymphoma cell lines using the MTT method. Changes in cell cycle progression and apoptosis were assessed using flow cytometry. Moreover, topoisomerase II inhibition as-says were performed. LPSF/AC05 exhibited cytotoxicity in six of the nine cell lines tested. RESULTS: The best results for leukemia and lymphoma were observed in the Toledo, Jurkat, and Raji cell lines (IC50 = 27.18, 31.04, and 33.36 M, respectively). For breast cancer, the best re-sults were observed in the triple-negative cell line MDA-MB-231 (IC50 = 27.54 µM). The compound showed excellent selectivity, with no toxicity to normal human cells (IC50 > 100M; selectivity index > 3). Cell death was primarily induced by apoptosis in all cell lines. Furthermore, LPSF/AC05 treatmentinduced cell cycle arrest at the G0/G1 phase in leuke-mia/lymphoma and at the G2/M phase in breast cancer. CONCLUSION: Finally, topoisomerase II was inhibited. These results indicate the potential ap-plication of LPSF/AC05 in cancer therapy.

Molecular mechanism of HDAC6-mediated pyroptosis in neurological function recovery after cardiopulmonary resuscitation in rats.

Brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is the leading cause of neurological dysfunction and death. This study aimed to explore the mechanism of histone deacetylase 6 (HDAC6) in neurofunctional recovery following CA/CPR in rats. A rat model was established by CA/CPR treatment. Adenovirus-packaged sh-HDAC6 was injected into the tail vein. To evaluate the neurofunction of rats, survival time, neurofunctional scores, serum NSE/S100B, and brain water content were measured and Morris water maze test was performed. HDAC6, microRNA (miR)-138-5p, Nod-like receptor protein 3 (NLRP3), and pyroptotic factors levels were determined by real-time quantitative polymerase chain reaction or Western blot assay. HDAC6 and H3K9ac enrichment on miR-138-5p promoter were examined by chromatin immunoprecipitation. miR-138-5p-NLRP3 binding was analyzed by dual-luciferase reporter assay. NLRP3 inflammasome was activated with nigericin sodium salt. After CPR treatment, HDAC6 was highly expressed, while miR-138-5p was downregulated. HDAC6 downregulation improved neurofunction and reduced pyroptosis. HDAC6 enrichment on the miR-138-5p promoter deacetylated H3K9ac, inhibiting miR-138-5p, and promoting NLRP3-mediated pyroptosis. Downregulating miR-138-5p partially reversed the protective effect of HDAC6 inhibition after CPR. In Conclusion, HDAC6 enrichment on miR-138-5p promoter deacetylated H3K9ac, inhibiting miR-138-5p expression and promoting NLRP3-mediated pyroptosis, worsening neurological dysfunction in rats after CPR.

3D C-arm navigated suture button implantation for AC joint dislocations - the pilot study.

PURPOSE: The surgical treatment of acute traumatic AC joint dislocations is still a subject of scientific debate in the literature. The arthroscopically assisted stabilization procedure with a suture button system has been successfully established and is widely used in daily practice. It is minimally invasive and allows the anatomical reconstruction of the torn coracoclavicular ligaments in one step with a permanent implant that does not have to be removed in a second operation. This clinical pilot study is the first to describe the new method of navigated suture button implantation with the future aim of further reducing surgical invasiveness and further increasing surgical precision. MATERIALS AND METHODS: 10 patients with a Rockwood 3b/5 injury could be included in the prospective study (DRKS00031855) within 5 months according to inclusion and exclusion criteria. Surgical stabilization was performed with a suture button system via a navigated coracoclavicular drill tunnel. Demographic and radiological data as well as information on health and shoulder function were collected from patient records, X-rays, DVT scan and 3 questionnaires (DASH, NHS and Eq. 5D) at the preoperative, intraoperative and postoperative (discharge, 6 weeks and 3 months) time points. RESULTS: All operations could be performed within 8.8 days (± 6.81) after trauma. The average operation time was 50.3 min (± 8.81). The mean distance of the drill hole in the clavicle to the AC joint was 26.6 mm (± 2.63). The radiologically measured vertical coracoclavicular distance was 38.8 mm (± 6.16) at discharge and 41.11 mm (± 7.51) at 3 months. This loss of reduction was not statistically significant. In contrast, the DASH, NHS and Eq. 5D results showed significant improvement from discharge to 3 months postoperatively. CONCLUSION: Image-guided 3D C-arm navigated AC joint suture button stabilization is feasible in everyday surgical practice. It may be possible to achieve a further reduction in invasiveness while at the same time increasing the accuracy of implant positioning. Further clinical studies with a larger number of patients and a longer follow-up period are necessary to enable a comparison with conventional methods.

Design and implementation of an innovative single-phase direct AC-AC bipolar voltage buck converter with enhanced control topology.

Direct AC-AC converters are strong candidates in the power converting system to regulate grid voltage against the perturbation in the line voltage and to acquire frequency regulation at discrete step levels in variable speed drivers for industrial systems. All such applications require the inverted and non-inverted form of the input voltage across the output with voltage-regulating capabilities. The required value of the output frequency is gained with the proper arrangement of the number of positive and negative pulses of the input voltage across the output terminals. The period of each such pulse for low-frequency operation is almost the same as the half period of the input grid or utility voltage. These output pulses are generated by converting the positive and negative input half cycles in noninverting and inverting forms as per requirement. There is no control complication to generate control signals used to adjust the load frequency as the operating period of the switching devices is normally greater than the period of the source voltage. However, high-frequency pulse width modulated (PWM) control signals are used to regulate the output voltage. The size of the inductor and capacitor is inversely related to the value of the switching frequency. Similarly, the ripple contents of voltage and currents in these filtering components are also inversely linked with PWM frequency. These constraints motivate the circuit designer to select high PWM frequency. However, the alignment of the high-frequency control input with the variation in the input source voltage is a big challenge for a design engineer as the switching period of a high-frequency signal normally lies in the microsecond. It is also required to operate some high-frequency devices for various half cycles of the source voltage, creating control complications as the polarities of the half cycles are continuously changing. This requires at least the generation of two high-frequency signals for different intervals. The interruption of the filtering inductor current is a big source of high voltage surges in circuits where the high-frequency transistors operate in a complementary way. This may be due to internal defects in the switching transistors or some unnecessary inherent delay in their control signals. In this research work, a simplified AC-AC converter is developed that does not need alignment of high-frequency control with the polarity of the source voltage. With this approach, high-frequency signals can be generated with the help of any analog or digital control system. By applying this technique, only one high-frequency control signal is generated and applied in AC circuits, as in a DC converter, without applying a highly sensitive polarity sensing circuit. So, controlling complications is drastically simplified. The circuit and configuration always avoid the current interruption problem of filtering the inductor. The proposed control and circuit topology are tested both in computer-based simulation and practically developed circuits. The results obtained from these platforms endorse the effectiveness and validation of the proposed work.

Low dose of dexamethasone combined with netupitant and palonosetron in preventing nausea and vomiting in breast cancer patients induced by anthracycline drugs.

BACKGROUND: To study the effects of various courses of dexamethasone (DEX) combined with 5-HT3 receptor antagonists (RA) and NK-1 RA in suppressing high-grade nausea and vomiting (CINV) caused by anthracycline and cyclophosphamide chemotherapy regimens (AC or EC) in breast cancer (BC) patients. PATIENTS AND METHODS: A prospective study was performed with 252 BC patients who received AC between January, 2019 and June, 2022 in our hospital. Patients were randomly separated into control Group (N = 130) who received DEX 12 mg on day 1 and 8 mg per dose on day 2-4 and observation group (N = 122) treated with DEX 5 mg per dose on days 1-4. The response was monitored. Primary study endpoint was complete resolution (CR) of patients nausea or vomiting; secondary study endpoints included acute CR and delayed CR; and complete control (CC), acute CC, delayed CC, and safety. RESULTS: All patients underwent six rounds of chemotherapy, and no difference was found in the clinical data. CR of acute/delayed phase was (94.3%/88.5%, P > 0.05), (89.3%/90.8%, P > 0.05); total CR was (80.3%/81.5%, P > 0.05); CC was (56.6%/59.2%, P > 0.05), (64.8%/67.7%, P > 0.05); total CR was (48.4%/53.1%, P > 0.05). CONCLUSIONS: The preventive antiemetic effects of NEPA, a fixed-dose combination of netupitant and palonosetron combined with DEX 5 mg per dose on days 1-4, can be similar to DEX 12 mg on day 1 and 8 mg per dose on days 2-4, low-dose hormone with better safety, which is beneficial.

A 3 MHz Low-Error Adaptive Howland Current Source for High-Frequency Bioimpedance Applications.

Bioimpedance is a diagnostic sensing method used in medical applications, ranging from body composition assessment to detecting skin cancer. Commonly, discrete-component (and at times integrated) circuit variants of the Howland Current Source (HCS) topology are employed for injection of an AC current. Ideally, its amplitude should remain within 1% of its nominal value across a frequency range, and that nominal value should be programmable. However, the method's applicability and accuracy are hindered due to the current amplitude diminishing at frequencies above 100 kHz, with very few designs accomplishing 1 MHz, and only at a single nominal amplitude. This paper presents the design and implementation of an adaptive current source for bioimpedance applications employing automatic gain control (AGC). The "Adaptive Howland Current Source" (AHCS) was experimentally tested, and the results indicate that the design can achieve less than 1% amplitude error for both 1 mA and 100 µA currents for bandwidths up to 3 MHz. Simulations also indicate that the system can be designed to achieve up to 19% noise reduction relative to the most common HCS design. AHCS addresses the need for high bandwidth AC current sources in bioimpedance spectroscopy, offering automatic output current compensation without constant recalibration. The novel structure of AHCS proves crucial in applications requiring higher ß-dispersion frequencies exceeding 1 MHz, where greater penetration depths and better cell status assessment can be achieved, e.g., in the detection of skin or breast cancer.

Reactivity of Resorcinol on Pt(511) Single-Crystal Surface and Its Effect on the Kinetics of Underpotentially Deposited Hydrogen and Hydrogen Evolution Reaction in 0.1 M NaOH Electrolyte.

This article presents cyclic voltammetry, Tafel polarization, and ac. impedance spectroscopy examinations of resorcinol (RC) ion reactivity on Pt(511) single-crystal plane and the effect of surface-electrosorbed RC ions on the kinetics of UPD H (underpotentially deposited hydrogen) and HER (hydrogen evolution reaction) processes in 0.1 M NaOH solution. Obtained data delivered a proof for the RC ion surface adsorption and its later electroreduction over the potential range characteristic for the UPD H. A favourable role of platinum-adsorbed resorcinol anions on the kinetics of the UPD H and HER processes is also discussed. The above was explained via the recorded capacitance and charge-transfer resistance parameters (the presence of resorcinol at 1.5 × 10-3 M in 0.1 M NaOH caused significant reduction in the resistance parameter values by 3.9 and 2.6 times, correspondingly, for the UPD of H at 50 mV and the HER process, examined at -50 mV vs. RHE) along with the charge transients, produced by injecting small amounts of RC-based 0.1 M NaOH solution to initially RC-free base electrolyte on the Pt(511) electrode plane (a large cathodic charge-transient density of -90 µC cm-2 was recorded at the electrode potential of 50 mV).

AC-ModNet: Molecular Reverse Design Network Based on Attribute Classification.

Deep generative models are becoming a tool of choice for exploring the molecular space. One important application area of deep generative models is the reverse design of drug compounds for given attributes (solubility, ease of synthesis, etc.). Although there are many generative models, these models cannot generate specific intervals of attributes. This paper proposes a AC-ModNet model that effectively combines VAE with AC-GAN to generate molecular structures in specific attribute intervals. The AC-ModNet is trained and evaluated using the open 250K ZINC dataset. In comparison with related models, our method performs best in the FCD and Frag model evaluation indicators. Moreover, we prove the AC-ModNet created molecules have potential application value in drug design by comparing and analyzing them with medical records in the PubChem database. The results of this paper will provide a new method for machine learning drug reverse design.

Evaluation of CHD5, H3K9me3, and H4K12ac in Human Testes with Spermatogenic Maturation Arrest: A Cross-Sectional Study.

BACKGROUND: Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specifically in chromatin remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3 lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type. MATERIALS AND METHODS: The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3 was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro- Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05. RESULTS: We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval (CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells. CONCLUSION: The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results, indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.

Extracellular putrescine can augment the epithelial-mesenchymal transition of gastric cancer cells by promoting MAL2 expression by elevating H3K27ac in its promoter region.

Dysregulation of polyamine metabolism has been associated with the development of many cancers. However, little information has been reported about the associations between elevated extracellular putrescine and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. In this study, the influence of extracellular putrescine on the malignant behavior and EMT of the AGS and MKN-28 cells was investigated, followed by RNA sequencing profiling of transcriptomic alterations and CUT&Tag sequencing capturing H3K27ac variations across the global genome using extracellular putrescine. Our results demonstrated that the administration of extracellular putrescine significantly promoted the proliferation, migration, invasion, and expression of N-cadherin in GC cells. We also observed elevated H3K27ac in MKN-28 cells but not in AGS cells when extracellular putrescine was used. A combination of transcriptomic alterations and genome-wide variations of H3K27ac highlighted the upregulated MAL2 and H3K27ac in its promoter region. Knockdown and overexpression of MAL2 were found to inhibit and promote EMT, respectively, in AGS and MKN-28 cells. We demonstrated that extracellular putrescine could upregulate MAL2 expression by elevating H3K27ac in its promoter region, thus triggering augmented EMT in GC cells.

Ac2-26 Reduced Lung Injury After Cardiopulmonary Bypass via the AKT1/GSK3ß/eNOS Pathway.

INTRODUCTION: Cardiopulmonary bypass (CPB) leads to severe inflammation and lung injury. Our previous study showed that Ac2-26 (an active n-terminal peptide of Annexin A1) can reduce acute lung injury. The aim of this study was to evaluate the effect of Ac2-26 on lung injury in CPB rats. METHODS: Forty rats were randomly divided into the sham, CPB, Ac, Ac/serine/threonine kinase 1 (AKT1), and Ac/ glycogen synthase kinase (GSK)-3ß groups. The rats in the sham group only received anesthesia, intubation, and cannulation. The rats in the other 4 groups received the standard CPB procedure. The rats in the CPB, Ac, Ac/AKT1, and Ac/GSK3ß groups were immediately injected with saline, Ac2-26 (1 mg/kg), Ac2-26 combined with short hairpin RNA (AKT1), or Ac2-26 combined with a GSK3ß inhibitor after CPB. At 12 h after the end of CPB, the PaO2/ fraction of inspired oxygen ratio, wet/dry weight ratio and protein content in the bronchoalveolar lavage fluid (BALF) were recorded. The numbers of macrophages and neutrophils in the BALF and blood were determined. Cytokine levels in the blood and BALF were investigated. Lung tissue histology and apoptosis were estimated. The expression of nuclear factor kappa- B, AKT1, GSK3ß, endothelial nitric oxide synthase and apoptosis-related proteins was analyzed. The survival of all the rats was recorded. RESULTS: Compared with the rats in the sham group, all the parameters examined worsened in the rats that received CPB. Compared with those in the CPB group, Ac2-26 significantly improved pulmonary capillary permeability, reduced cytokine levels, and decreased histological scores and apoptosis. The protective effect of Ac2-26 on lung injury was significantly reversed by AKT1 short hairpin RNA or a GSK3ß inhibitor. CONCLUSIONS: Ac2-26 significantly reduced lung injury and inflammation after CPB. The protective effect of Ac2-26 mainly depended on the AKT1/GSK3ß/endothelial nitric oxide synthase pathway.

Silence of Aminopeptidase N 2 gene reveals the trade-offs for acquiring Cry1Ac resistance in Plutella xylostella.

Bacillus thuringiensis (Bt) is widely used as a biopesticide worldwide. To date, at least eight pest species have been found to be resistant to Bt in the field. As the first pest that was reported having resistance to Bt in the field, considerable research has been done on the mechanisms of Bt resistance in Plutella xylostella. However, whether the acquisition of Bt resistance by P. xylostella comes at a fitness cost is also a valuable question. In this study, Aminopeptidase-N 2 (APN2), a Cry toxin receptor gene of P. xylostella, was knocked down by RNA interference, resulting in improved resistance to Cry1Ac. It was also found that larval mortality of APN2 knockdown P. xylostella was significantly higher than that of the control, while the pupation rate, pupal weight, eclosion rate, fecundity (egg/female), hatchability, and female adult longevity were significantly lower in APN2 knockdown P. xylostella than in the control. These results illustrate that if Cry1Ac resistance was obtained only through the reduction of APN2 expression, P. xylostella would need to incur some fitness costs for it.

Effects of soil moisture and an AC-electric field on the phytoremediation of the Cd-contaminated soil.

Phytoremediation enhanced by electric field has been considered a green and low-cost technology for remediating heavy metal-contaminated soils. Soil moisture is a main environmental factor that affects Cd availability in the soil. However, the effects of soil moisture and AC-electric field on the remediation efficiency of willow (Salix spp.) and S. Alfredii interplanted together remain unclear. In the present study, we designed four treatments (60% soil field capacity, 60% soil field capacity + 0.5 V·cm-1 AC, 100% soil field capacity, 100% soil field capacity + 0.5 V·cm-1 AC) to explore the impacts of soil moisture and AC-electric field on soil Cd availability and Cd accumulation in plants. The results showed that the application of an AC-electric field significantly increased soil Cd availability by 20.9% and 10.8% under both 60% and 100% soil field capacity, respectively. Both high water with and without AC-electric field treatments reduced the proportion of acid-extractable and reducible Cd of soil but increased the proportion of residual Cd. Compared with the control, an AC-electric field with 60% soil field capacity significantly enhanced the biomass of S. Alfredii shoots by 31.2% and increased Cd accumulation in willow leaves and S. Alfredii shoots by 14.6% and 32.3%, respectively. In addition, the biomass production of willow was significantly enhanced but the uptake of Cd by willow was dramatically decreased under an AC-electric field with high water treatment. Therefore, these results suggest that the AC-electric field combined with 60% soil field capacity may be a more promising remediation technique to clean up the Cd-contaminated soil.

Sensing the squeeze: nuclear mechanotransduction in health and disease.

The nucleus not only is a repository for DNA but also a center of cellular and nuclear mechanotransduction. From nuclear deformation to the interplay between mechanosensing components and genetic control, the nucleus is poised at the nexus of mechanical forces and cellular function. Understanding the stresses acting on the nucleus, its mechanical properties, and their effects on gene expression is therefore crucial to appreciate its mechanosensitive function. In this review, we examine many elements of nuclear mechanotransduction, and discuss the repercussions on the health of cells and states of illness. By describing the processes that underlie nuclear mechanosensation and analyzing its effects on gene regulation, the review endeavors to open new avenues for studying nuclear mechanics in physiology and diseases.

Application of Optimization Response Surface for the Adsorption of Methylene Blue Dye onto Zinc-coated Activated Carbon.

The activated carbon was produced in the first phase of this investigation by chemically activating hazelnut shell waste with H3PO4. Composite materials were obtained by coating the activated carbon with zinc oxide, whose BET surface area was calculated as 1278 m2 g-1. ZnO-doped ZnO/AC composite was synthesized as an adsorbent for its possible application in the elimination of organic dyestuff MB, and its removal efficiency was investigated. Morphological properties of ZnO/AC were characterized using analytical methods such as XRD, SEM, and BET. The adsorption system and its parameters were investigated and modeled using the response surface method of batch adsorption experiments. The experimental design consisted of three levels of pH (3, 6.5, and 10), initial MB concentration (50, 100, and 150 mg L-1), dosage (0.1, 0.3, and 0.5 g 100 mL-1), and contact time (5, 50, and 95 min). The results from the RSM suggested that the MB removal efficiency was 98.7% under the optimum conditions of the experimental factors. The R2 value, which expresses the significance of the model, was determined as 99.05%. Adsorption studies showed that the equilibrium data fit well with the Langmuir isotherm model compared to Freundlich. The maximum adsorption capacity was calculated as 270.70 mg g-1.