A comparison increasing the photodegradation power of a Ag/g-C3N4 /CoNi-LDH nanocomposite: Photocatalytic activity toward water treatment.

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.

Dissolved organic matter characteristics linked to bacterial community succession and nitrogen removal performance in woodchip bioreactors.

Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.

Nitrogen-cycling processes under long-term compound heavy metal(loids) pressure around a gold mine: Stimulation of nitrite reduction.

Mining and tailings deposition can cause serious heavy metal(loids) pollution to the surrounding soil environment. Soil microorganisms adapt their metabolism to such conditions, driving alterations in soil function. This study aims to elucidate the response patterns of nitrogen-cycling microorganisms under long-term heavy metal(loids) exposure. The results showed that the diversity and abundance of nitrogen-cycling microorganisms showed negative feedback to heavy metal(loids) concentrations. Denitrifying microorganisms were shown to be the dominant microorganisms with over 60% of relative abundance and a complex community structure including 27 phyla. Further, the key bacterial species in the denitrification process were calculated using a random forest model, where the top three key species (Pseudomonas stutzei, Sphingobium japonicum and Leifsonia rubra) were found to play a prominent role in nitrite reduction. Functional gene analysis and qPCR revealed that nirK, which is involved in nitrite reduction, significantly accumulated in the most metal-rich soil with the increase of absolute abundance of 63.86%. The experimental results confirmed that the activity of nitrite reductase (Nir) encoded by nirK in the soil was increased at high concentrations of heavy metal(loids). Partial least squares-path model identified three potential modes of nitrite reduction processes being stimulated by heavy metal(loids), the most prominent of which contributed to enhanced nirK abundance and soil Nir activity through positive stimulation of key species. The results provide new insights and preliminary evidence on the stimulation of nitrite reduction processes by heavy metal(loids).

Recent Advances of Light/Hypoxia-Responsive Azobenzene in Nanomedicine Design.

Azobenzene (Azo) and its derivatives are versatile stimuli-responsive molecules. Their reversible photoisomerization and susceptibility to reduction-mediated cleavage make them valuable for various biomedical applications. Upon exposure to the UV light, Azo units undergo a thermodynamically stable trans-to-cis transition, which can be reversed by heating in the dark or irradiation with visible light. Additionally, the N=N bonds in azobenzenes can be cleaved under hypoxic conditions by azoreductase, making azobenzenes useful as hypoxia-responsive linkers. The integration of azobenzenes into nanomedicines holds promise for enhancing therapeutic efficacy, particularly in tumor targeting and controllable drug release. In this Concept paper, recent advances in the design and applications of azobenzene-based nanomedicines are updated, and future development opportunities are also summarized.

The role of m6A-associated membraneless organelles in the RNA metabolism processes and human diseases.

N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.

Cortical and subcortical substrates of working memory in the right hemisphere: A connectome-based lesion-symptom mapping study.

Working Memory (WM) is a cognitive system whose crucial role is to temporarily hold and manipulate information. Early studies suggest that verbal WM is typically associated with left hemisphere (LH) brain regions, while the processing of visuospatial information in WM more specifically depends on the right hemisphere (RH). However, recent evidence suggests a more complex network involving both hemispheres' prefrontal and posterior parietal cortices in these processes. Unfortunately, previous lesion studies often examined only one modality (either verbal, or visuospatial) or one hemisphere, which limits the possible conclusions regarding non-lateralized hemispheric involvement. Using connectome-based lesion-symptom mapping on a large sample of patients with left (LBD) and right (RBD) focal brain damage, we examined whether gray matter damage and white matter disconnections predict deficits of WM updating in an N-back task. Patients were examined with two WM tasks that differed regarding modality (verbal, spatial) and cognitive load (1-back, 2-back). Behavioral outcomes indicated that RBD patients showed significant deficits in WM updating, regardless of task modality or load. This observation was supported by whole-brain voxel-based analysis, revealing associations between WM deficits and gray matter clusters in the RH. Specifically, damage to the right lateral frontal cortex including the brain region homologous to Broca's area was associated with verbal WM deficits, while damage to the right inferior parietal lobe and posterior temporal cortex predicted spatial WM deficits. Additionally, white matter analyses identified severely impacted tracts in the RH, predicting deficits in both verbal and spatial WM. Our findings suggest that the mental manipulation of both verbal and visuospatial information in WM updating relies on the integrity of the RH, irrespective of the specific type of information held in mind.

Carbon- and Nitrogen-Based Complexes as Photocatalysts for Prebiotic and Oxygen Chemistry during Earth Evolution.

Sunlight has long served as primary energy source on our planet, shaping the behavior of living organisms. Extensive research has been dedicated to unraveling the evolutionary pathways involved. When the formation of Earth atmosphere, it primarily consisted of small gas molecules, which are considered crucial for the emergence of life. Recent demonstrations have shown that these molecules can also be transformed into semiconductors, with the potential to harness solar energy and catalyze chemical reactions as photocatalysts. Building upon this research, this minireview focuses on the potential revolutionary impact of photocatalysis on Earth. Initially, it examines key reactions, such as the formation of prebiotic molecules and the oxygen evolution reaction via water oxidation. Additionally, various C-N complexes in photocatalysts are explored, showcasing their roles in catalyzing chemical reactions. The conclusion and outlook provide a potential pathway for the evolution of Earth, shedding light on the significance of metal-free photocatalysts in development of Earth.

Efficient Semitransparent Solar Cells Enabled by Introducing N-Ethylbenzylamine Additives into Thin Layer of Halide Perovskites.

Semitransparent perovskite solar cells (ST-PSCs) have opened up new applications in tandem devices and building-integrated photovoltaics. Decreasing the thickness of the perovskite film makes it feasible to fabricate semitransparent perovskite layers. However, the formation of high-quality thin perovskite films has been a challenge during the film manufacturing process since the crystallization dynamics of thinner (<200 nm) films are different from that of thick films. In this article, we demonstrate a feasible method to fabricate a thinner layer of highly crystalline perovskites with low defect density for efficient ST-PSCs by introducing N-Ethylbenzylamine (EBA) to modify halide perovskites through Lewis acid-base interaction. As a result, a semitransparent solar cell based on EBA-treated perovskite with a film thickness of only ∼190 nm exhibits a high power conversion efficiency (PCE) of 14.77%, an average visible transmittance (AVT) of 13.2%, and an excellent light utilization efficiency (LUE) of 1.95%, which is the highest value in the ST-PSCs with Au as the electrode. Our findings highlight the effectiveness of the EBA additive in improving the photovoltaic performance of ST-PSCs, offering valuable insights into developing efficient and transparent photovoltaic technologies.

Electrical Contacts in Monolayer MoSi2N4 Transistors.

The latest synthesized monolayer (ML) MoSi2N4 material exhibits stability in ambient conditions, suitable bandgap, and high mobilities. Its potential as a next-generation transistor channel material has been demonstrated through quantum transport simulations. However, in practical two-dimensional (2D) material transistors, the electrical contacts formed by the channel and the electrode must be optimized, as they are crucial for determining the efficiency of carrier injection. We employed the density functional theory (DFT) combined with the nonequilibrium Green's function (NEGF) method to systematically explore the vertical and horizontal interfaces between the typical metal electrodes and the ML MoSi2N4. The DFT+NEGF method incorporates the coupling between the electrode and the channel, which is crucial for quantum transport. Among these metals, Sc and Ti form n-type Ohmic contacts with zero tunneling barriers at both vertical and horizontal interfaces with ML MoSi2N4, making them optimal for contact metals. In-ML MoSi2N4 contacts display zero Schottky barriers but a 3.11 eV tunneling barrier. Cu and Au establish n-type Schottky contacts, while Pt forms a p-type contact. The Fermi pinning factors of the metal-ML MoSi2N4 contacts for both electrons and holes are above 0.51, much higher than the typical 2D semiconductors. Moreover, there is a strong positive correlation between the Fermi pinning factor and the band gap, with a Spearman rank correlation coefficient of 0.897 and a p-value below 0.001. Our work provides insight into the contact optimization for the ML MoSi2N4 transistors and highlights the promising potential of ML MoSi2N4 as the channel material for the next-generation FETs.

A case report of human infection with avian influenza H10N3 with a complex respiratory disease history.

BACKGROUND: On March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3. CASE PRESENTATION: A 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People's Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient's respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6-99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022). CONCLUSIONS: According to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin.

Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes.

BACKGROUND: Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. METHODS: An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. RESULTS: GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05). CONCLUSIONS: GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Insights into RNA N6-methyladenosine and programmed cell death in atherosclerosis.

N6-methyladenosine (m6A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m6A modification has gained increasing attention in the development of atherosclerosis and has become a research hotspot in recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, plays a pivotal role in atherosclerosis pathogenesis. In this review, we delve into the intricate interplay between m6A modification and diverse PCD pathways, shedding light on their complex association during the onset and progression of atherosclerosis. Clarifying the relationship between m6A and PCD in atherosclerosis is of great significance to provide novel strategies for cardiovascular disease treatment.

Predictive value of combining urinary N-acetyl-ß-D-glucosaminidase and serum homocysteine for contrast-induced nephropathy in patients after percutaneous coronary intervention.

Background: Contrast-induced nephropathy (CIN) can lead to serious complications following percutaneous coronary intervention (PCI). Urine N-Acetyl-ß-D-glucosaminidase (uNAG) and serum homocysteine (sHCY) are both potential predictors for CIN detection, but their combination has not been explored. We aimed to combine uNAG and sHCY as predictors for the early detection of CIN and for prognosis prediction in patients after PCI. Methods: A total of 232 consecutive patients who underwent PCI at a university hospital were recruited for this study. According to the European Society of Urology and Reproduction (ESUR) criterion, CIN is defined as an elevation of serum creatinine (sCr) by ≥25% or ≥0.5 mg/dl from baseline within 48 h. We assessed the use of individual biomarkers (uNAG and sHCY) measured around PCI and their combinations for CIN detection and prognosis prediction. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to evaluate the predictive efficiency of potential predictors. Results: In total, 54 (23.28%) patients developed CIN. Concentrations of uNAG and sHCY increased significantly in CIN subjects (p < 0.05) than non-CIN. CIN could be predicted by uNAG and sHCY but not by creatinine at an early stage. At pre-PCI, 0, 12, 24, and 48 h after PCI, the AUC-ROC value of uNAG in calculating total CIN was 0.594, 0.603, 0.685, 0.657, and 0.648, respectively. The AUC-ROC value of sHCY in calculating total CIN was 0.685, 0.726, 0.771, 0.755, and 0.821, respectively. The panel of uNAG plus sHCY detected CIN with significantly higher accuracy than either individual biomarker alone and earlier than sCr. For detecting total CIN, this panel yielded AUC-ROCs of 0.693, 0.754, 0.826, 0.796, and 0.844 at pre-PCI, 0, 12, 24, and 48 h after PCI, respectively, which were superior to those of the individual biomarkers. For predicting the incidence of major adverse cardiovascular events (MACE) within 30 days to 12 months, the AUC-ROC values for uNAG and sHCY measured before discharge were 0.637 and 0.826, respectively. The combined panel yielded an AUC-ROC of 0.832. The combined detection did not significantly enhance the predictive capability for MACE in patients with CIN. The CIN group and the non-CIN group showed no significant difference in the Coronary Heart Disease Intensive Care Unit (CCU) stay time, hospital stay time, demand for renal replacement therapy, CCU mortality rate, and in-hospital mortality rate. Conclusions: The uNAG and sHCY panel demonstrated better sensitivity and specificity for predicting the diagnosis and prognosis of CIN in patients after PCI, earlier than sCr. The combination of these biomarkers revealed a significantly superior discriminative performance for CIN detection and prognosis compared to using uNAG or sHCY alone.

The role of RNA modifications in hepatocellular carcinoma: functional mechanism and potential applications.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.

Macrophage manufacturing and engineering with 5'-Cap1 and N1-methylpseudouridine-modified mRNA.

Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophages facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage-manufacturing process and indicate that macrophages can be engineered by versatile mRNA technology to achieve therapeutic goals.

Curcumin chitosan microspheres regulate Th17/Treg balance via IGF2BP1- mediated m6A modification of LRP5 in ulcerative colitis.

Objectives: Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper 17 (Th17)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th17/Treg cell balance. Materials and Methods: The UC mouse model was established by administering 3% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th17/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF2BP1 in Th17/Treg balance. Results: We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th17 cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp3 but suppressed RORγt and interleukin-10 mRNA expression. PCR array of RNA modification-related genes revealed that the m6A binding protein IGF2BP1 was a key molecule in CCM regulation of Th17/Treg balance. IGF2BP1 overexpression dramatically repressed the CCM-induced balance of Th17/Treg cell differentiation. Mechanically, IGF2BP1 targeted LRP5 and regulated LRP5 through m6A modification. Furthermore, the silencing of LRP5 canceled the suppressive effect of IGF2BP1 on Th17/Treg cell percentage. Conclusion: CCM modulated the Th17/Treg balance through IGF2BP1-mediated m6A modification, thereby alleviating UC, and providing new ideas for the treatment of UC.

Two birds with one stone: Bimetallic ZnCo2S4 polyhedral nanoparticles decorated porous N-doped carbon nanofiber membranes for free-standing flexible anodes and microwave absorption.

Cost-efficient material with an ingenious design is important in the engineering applications of flexible energy storage and electromagnetic (EM) protection. In this study, bimetallic ZnCo2S4 (ZCS) polyhedral nanoparticles homogenously embedded in the surface of porous N-doped carbon nanofiber membranes (ZCS@PCNFM) have been fabricated by electrospinning technique combined with carbonization and hydrothermal processes. As a self-assembled electrode for lithium-ion batteries (LIBs), the bimetallic ZCS nanoparticles possess rich redox reactions, good electrical conductivity, and pseudocapacitive properties, while the three-dimensional (3D) multiaperture architecture of the nanofiber film not only shortens the transfer spacing of lithium ions and electrons but also effectively tolerates the volume variation during lithiation and delithiation cycles. Benefiting from the above merits, the ZCS@PCNFM electrode exhibits good cycle performance (662.3 mA h/g at 100 mA/g after 100 cycles), superior rate capacity (401.3 mA h/g at 1 A/g) and an extremely high initial specific capacity of 1152.2 mAh/g at 100 mA/g. Meanwhile, depending on the hierarchical nanostructure and multi-component heterogeneous interface effects constructed by 3D inlaid architecture, the ZCS@PCNFM nanocomposite exhibits fascinating microwave absorption (MA) characteristics with a superhigh reflection loss (RL) of -49.7 dB at a filling content of only 20 wt% and corresponding effective absorption bandwidth (EAB, RL<-10 dB) of 5.2 GHz ranging from 12.8 to 18.0 GHz at 2.2 mm.

Design, synthesis, characterization, and biological activities of novel Ag(I)-NHC complexes based on 1,3-dioxane ligand.

Herein, a series of new Ag(I)-NHC complexes containing 1,3-dioxane group were synthesized by the direct reaction of Ag2O and benzimidazolium salts in light-free conditions. All Ag(I)-NHC complexes were spectrally characterized using 1H, 13C NMR, FT-IR, LC-MS, and elemental analysis. Additionally, the structures of compounds 1a and 1e were elucidated by the single X-ray diffraction techniques. Further, the synthesized Ag(I)-NHC complexes were evaluated for cytotoxicity study on the L-929 cells and the anticancer activity against the HCT 116 and MCF-7 cancer cell lines. Notably, 1a showed significant anticancer activity against HCT 116 with an IC50 of 6.37 ± 0.92 µg/mL compared to cisplatin (IC50 = 36.75 ± 1.76 µg/mL). 1c (IC50 = 3.21 ± 1.96 µg/mL) and 1e (IC50 = 3.72 ± 1.12 µg/mL) exhibited significant anticancer activity against MCF-7 cells and was similar to cisplatin (IC50 = 32.17 ± 2.85 µg/mL). Meanwhile, 1a and 1e displayed the highest selectivity index. Most importantly, the cell viability test showed that 1e induced neglectable cytotoxicity (IC50 = 36.38 ± 2.27 µg/mL) toward L-929 and was similar to cisplatin (IC50 = 36.11 ± 2.09 µg/mL). The anticancer activities of Ag(I)-NHC complexes vary depending on the substituent group of the silver complex and the cell line type. Moreover, the inhibitory mechanism of 1e was not dependent on caspase-associated apoptosis initiated by the lysosomal-mitochondrial pathway. Taken together, we conclude that this work provides a simple and rapid protocol for the synthesis of Ag(I)-NHC complexes and the featured Ag(I)-NHC complexes have an anticancer drug potential for biomedical applications.

Improved N-phenylpyrrolamide inhibitors of DNA gyrase as antibacterial agents for high-priority bacterial strains.

In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC50 values against Escherichia coli DNA gyrase, and in addition, compound 7c also inhibits E. coli topoisomerase IV in the nanomolar concentration range, making it a promising candidate for the development of potent dual inhibitors for these enzymes. All tested compounds show high selectivity towards the human isoform DNA topoisomerase IIα. Compounds 6a, 6d, 6e and 6f show MIC values between 0.031 and 0.0625 µg/mL against vancomycin-intermediate S. aureus (VISA) and Enterococcus faecalis strains. Compound 6g shows an inhibitory effect against the methicillin-resistant S. aureus strain (MRSA) with a MIC of 0.0625 µg/mL and against the E. faecalis strain with a MIC of 0.125 µg/mL. In a time-kill assay, compound 6d showed a dose-dependent bactericidal effect on the MRSA strain and achieved bactericidal activity at 8 × MIC after 8 h. The duration of the post-antibiotic effect (PAE) on the MRSA strain for compound 6d was 2 h, which corresponds to the PAE duration for ciprofloxacin. The compounds were not cytotoxic at effective concentrations, as determined in an MTS assay on the MCF-7 breast cancer cell line.

Design, synthesis, and in vitro biological evaluation of meta-sulfonamidobenzamide-based antibacterial LpxH inhibitors.

New antibacterial compounds are urgently needed, especially for infections caused by the top-priority Gram-negative bacteria that are increasingly difficult to treat. Lipid A is a key component of the Gram-negative outer membrane and the LpxH enzyme plays an important role in its biosynthesis, making it a promising antibacterial target. Inspired by previously reported ortho-N-methyl-sulfonamidobenzamide-based LpxH inhibitors, novel benzamide substitutions were explored in this work to assess their in vitro activity. Our findings reveal that maintaining wild-type antibacterial activity necessitates removal of the N-methyl group when shifting the ortho-N-methyl-sulfonamide to the meta-position. This discovery led to the synthesis of meta-sulfonamidobenzamide analogs with potent antibacterial activity and enzyme inhibition. Moreover, we demonstrate that modifying the benzamide scaffold can alter blocking of the cardiac voltage-gated potassium ion channel hERG. Furthermore, two LpxH-bound X-ray structures show how the enzyme-ligand interactions of the meta-sulfonamidobenzamide analogs differ from those of the previously reported ortho analogs. Overall, our study has identified meta-sulfonamidobenzamide derivatives as promising LpxH inhibitors with the potential for optimization in future antibacterial hit-to-lead programs.