Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles.

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.

[Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability].

OBJECTIVE: To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID). METHODS: Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People's Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis. RESULTS: The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants (MECP2: c.502C>T, MECP2: c.916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants (MECP2: c.1157_1197del/c.925C>T, KDM5C: c.2128A>T, SLC6A8: c.1631C>T) and 6 variants of uncertain significance (KLHL15: c.26G>C, PAK3: c.970A>G/c.1520G>A, GRIA3: c.2153C>G, TAF1: c.2233T>G, HUWE1: c.10301T>A). The PAK3: c.970A>G, GRIA3: c.2153C>G and TAF1: c.2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81:19). Therefore, the PAK3: c.1520G>A variant may underlie its pathogenesis. CONCLUSION: Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Synergistic optimization of triple phase junctions and oxygen vacancies over MnxCd1-xS/Ov-WO3 for boosting photocatalytic hydrogen evolution.

Strengthening the separation of photogenerated charge carriers is crucial for improving the efficiency of photocatalytic hydrogen evolution. Herein, t-Mn0.5Cd0.5S/Ov-WO3 (t-MCSW) triple-phase junctions with rich oxygen vacancies were developed using the calcination-hydrothermal method. The corresponding morphology and structure of the samples were examined by XRD, TEM and XPS. The formation of the S-scheme heterostructure in t-MCSW has also been confirmed with in situ XPS, work function analysis and free radical capture tests. The experimental results demonstrate that t-MCSW-7 exhibited optimal activity (194.2 mmol g-1 h-1), which was about 4 times higher than that of the individual Mn0.5Cd0.5S (t-MCS, 48.8 mmol g-1 h-1). The apparent quantum yield of t-MCSW-7 is 29.14% at 420 nm, and the material exhibits excellent stability after seven cycles of photocatalytic reaction. The excellent photocatalytic activity of t-MCSW-7 is attributed to more efficient separation of charge carriers by triple-phase junctions connected by homojunctions and heterojunctions. Moreover, the existence of oxygen vacancies broadens absorption spectra and accelerates surface charge transfer. The synergistic effect of phase junctions and oxygen vacancies leads to an enhancement of hydrogen evolution activity. This work provides a new idea for preparing efficient photocatalysts.

A Multifunctional Co-Based Metal-Organic Framework as a Platform for Proton Conduction and Ni trophenols Reduction.

The design and development of proton conduction materials for clean energy-related applications is obviously important and highly desired but challenging. An ultrastable cobalt-based metal-organic framework Co-MOF, formulated as [Co2(btzip)2(µ2-OH2)] (namely, LCUH-103, H2btzip = 4, 6-bis(triazol-1-yl)-isophthalic acid) had been successfully synthesized via the hydrothermal method. LCUH-103 exhibits a three-dimensional framework and a one-dimensional microporous channel structure with scu topology based on the binuclear metallic cluster {Co2}. LCUH-103 indicated excellent chemical and thermal stability; peculiarly, it can retain its entire framework in acid and alkali solutions with different pH values for 24 h. The excellent stability is a prerequisite for studying its proton conductivity, and its proton conductivity σ can reach up to 1.25 × 10-3 S·cm-1 at 80 °C and 100% relative humidity (RH). In order to enhance its proton conductivity, the proton-conducting material Im@LCUH-103 had been prepared by encapsulating imidazole molecules into the channels of LCUH-103. Im@LCUH-103 indicated an excellent proton conductivity of 3.18 × 10-2 S·cm-1 at 80 °C and 100% RH, which is 1 order of magnitude higher than that of original LCUH-103. The proton conduction mechanism was systematically studied by various detection means and theoretical calculations. Meanwhile, LCUH-103 is also an excellent carrier for palladium nanoparticles (Pd NPs) via a wetness impregnation strategy, and the nitrophenols (4/3/2-NP) reduction in aqueous solution by Pd@LCUH-103 indicated an outstanding conversion efficiency, high rate constant (k), and exceptional cycling stability. Specifically, the k value of 4-NP reduction by Pd@LCUH-103 is superior to many other reported catalysts, and its k value is as high as 1.34 min-1 and the cycling stability can reach up to 6 cycles. Notably, its turnover frequency (TOF) value is nearly 196.88 times more than that of Pd/C (wt 5%) in the reaction, indicating its excellent stability and catalytic activity.

Two-Dimensional Lanthanide Metal-Organic Frameworks as a Platform for Sensing Pollutant and Nitrophenols Reduction.

The discharge of harmful and toxic pollutants in water is destroying the ecosystem balance and human being health at an alarming rate. Therefore, the detection and removal of water pollutants by using stable and efficient materials are significant but challenging. Herein, three novel lanthanide metal-organic frameworks (Ln-MOFs), [La(L)(DMF)2(H2O)2]·H2O (LCUH-104), [Nd(L)(DMF)2(H2O)2]·H2O (LCUH-105), and [Pr(L)(DMF)2(H2O)2]·H2O (LCUH-106) [H3L = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid (H3TZI)] were solvothermally constructed and structurally characterized. In the three Ln-MOFs, dinuclear metallic clusters {Ln2} were connected by deprotonated tetrazol-containing dicarboxylate TZI3- to obtain a 2D layered framework with a point symbol of {42·84}·{46}. Their excellent chemical and thermal stabilities were beneficial to carry out fluorescence sensing and achieve the catalytic nitrophenols (NPs) reduction. Especially, the incorporation of the nitrogen-rich tetrazole ring into their 2D layered frameworks enables the fabrication of Pd nanocatalysts (Pd NPs@LCUH-104/105/106) and have dramatically enhanced catalytic activity by using the unique metal-support interactions between three Ln-MOFs and the encapsulating palladium nanoparticles (Pd NPs). Specifically, the reduction of NPs (2-NP, 3-NP, and 4-NP) in aqueous solution by Pd NPs@LCUH-104 exhibits exceptional conversion efficiency, remarkable rate constants (k), and outstanding cycling stability. The catalytic rate of Pd NPs@LCUH-104 for 4-NP is nearly 8.5 times more than that of Pd/C (wt 5%) and its turnover frequency value is 0.051 s-1, which indicate its excellent catalytic activity. Meanwhile, LCUH-105, as a multifunctional fluorescence sensor, exhibited excellent fluorescence detection of norfloxacin (NFX) (turn on) and Cr2O72- (turn off) with high selectivity and sensitivity at a low concentration, and the corresponding fluorescence enhancement/quenching mechanism has also been systematically investigated through various detection means and theoretical calculations.

Conformationally confined three-armed supramolecular folding for boosting near-infrared biological imaging.

Herein, a triphenylamine derivative (TP-3PY) possessing 4-(4-bromophenyl)pyridine (PY) as an electron-accepting group and tris[p-(4-pyridylvinyl)phenyl]amine (TPA) with large two-photon absorption cross-sections as an electron-donating group was obtained, and showed intense absorption in the visible light region (λmax = 509 nm) and weak near-infrared (NIR) fluorescence emission at 750 nm. After complexation with cucurbit[8]uril (CB[8]), TP-3PY showed bright NIR fluorescence emission at 727 nm and phosphorescence emission at 800 nm. When the supramolecular assembly (TP-3PY⊂CB[8]) further interacted with dodecyl-modified sulfonatocalix[4]arene (SC4AD), the fluorescence and phosphorescence emissions were further enhanced at 710 and 734 nm, respectively. However, only the fluorescence emission of TP-3PY was enhanced in the presence of cucurbit[7]uril (CB[7]) and SC4AD. More interestingly, the photoluminescence of TP-3PY⊂CB[8]@SC4AD and TP-3PY⊂CB[7]@SC4AD assemblies could be excited by both visible (510 nm) and NIR light (930 nm). Finally, these ternary supramolecular assemblies with bright NIR light emission were applied to lysosome imaging of tumor cells and real-time biological imaging of mice.

Treating relapsed/refractory mature T- and NK-cell neoplasms with tislelizumab: a multicenter open-label phase 2 study.

Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2 study evaluated the efficacy and safety of the programmed cell death protein 1 inhibitor tislelizumab in these patients. Seventy-seven patients were treated with 200 mg tislelizumab every 3 weeks. Twenty-two patients with extranodal NK-/T-cell lymphomas were enrolled in cohort 1; 44 patients with peripheral T-cell lymphoma (PTCL) were enrolled in cohort 2 (21 patients had PTCL not otherwise specified, 11 patients had angioimmunoblastic T-cell lymphoma, and 12 patients had anaplastic large-cell lymphoma). Cohort 3 comprised 11 patients with cutaneous T-cell lymphoma, of which 8 patients had mycosis fungoides (MF) and 3 had Sézary syndrome. Of the 77 patients, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% received ≥3 prior systemic regimens. Promising efficacy was observed in cohort 3 (median follow-up [FU], 16.6 months; overall response rate [ORR], 45.5%; complete response [CR], 9.1%; median duration of response [DOR], 11.3 months; median progression-free survival, 16.8 months; median overall survival, not reached). Modest efficacy was observed in cohort 1 (median FU, 8.4 months; ORR, 31.8%; CR, 18.2%; median DOR, not reached) and cohort 2 (median FU, 9.3 months; ORR, 20.5%; CR, 9.1%; median DOR, 8.2 months). Most treatment-related adverse events were grade 1 or 2, and the safety profile was consistent with the known safety profile of tislelizumab. In conclusion, tislelizumab was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions. This trial was registered at www.clinicaltrials.gov as #NCT03493451.

Functionalized 2D defect g-C3N4 for artificial photosynthesis of H2O2 and synchronizing tetracycline fluorescence detection and degradation.

Artificial photosynthesis of H2O2 is a clean production technology, which brings the synergistic effect to photodegradation of pollutants. Inspired by defect engineering, 2D defective carbon nitride (g-C3N4) photocatalyst was obtained via potassium ion assisted synthesis. Defective g-C3N4 is protonated and applied to photosynthesis of H2O2, H2O2 concentration produced reached 477.7 µM, which was approximately 5.27 times that by pristine g-C3N4. Additionally, defective g-C3N4 materials are borrowed to synchronizing tetracycline (TC) fluorescence detection and degradation, suggesting the catalyst existed bifunctional characteristics of TC detection and degradation. Meanwhile, metal impregnation engineering (molybdenum) was borrowed enhancing the electron-trapping ability in local region of defective g-C3N4, which takes advantages to the efficient degradation of TC. Furthermore, optical and electrical properties of photocatalysts were investigated in details by advanced material characterization testing. This work provides potential applications in the field of artificial photosynthesis and pollution degradation.

Pd sub-nanolayer on Au core for enhanced catalytic hydrogenation reduction of oxyanions pollutants: Synergistic effect of Pd and Au.

Oxyanion pollutants in industrial wasterwater, such as (Cr(VI)), BrO3- (Br(V)) and SeO32- (Se(IV)) have detrimental or toxic effects on individual health when their concentrations accumulated to a certain level. The conversion of these oxyanions into harmless/industrial-valuable products or removal from wastewater is of significance. Herein, we designed Pd sub-nanolayer on Au core catalysts supported on Al2O3 (sub-Pd-Au/Al2O3) for highly effective catalytic hydrogenation reduction of oxyanions under ambient conditions. The sub-Pd(0.049)-Au(0.927)/Al2O3 catalyst exhibited the highest catalytic activity and TOF value for Cr(VI), Br(V) and Se(IV) reduction, respectively, by optimizing the Pd loading amount. The synergistic effect between Pd sub-nanolayer and Au core enhanced catalytic activity by regulating the Pd dispersion and site property, according to thorough characterizations that included high-angle annular dark-field transmission electron microscopy (HAADF-TEM) image, in-situ CO-IR adsorption, CO chemisorption, and X-ray photoelectron spectroscopy (XPS). This work might provide some new lights on design of highly efficient catalysts for the elimination of oxyanion pollutants.

Six Sets of Aromatic Polyketides Differing in Size and Shape Derive from a Single Biosynthetic Gene Cluster.

One new aromatic polyketide, prealnumycin B (1), and four known aromatic polyketides, K1115A (2), 1,6-dihydroxy-8-propylanthraquinone (DHPA, 3), phaeochromycin B (4), and (R)-7-acetyl-3,6-dihydroxy-8-propyl-3,4dihydronaphthalen-1(2H)-one (5), were isolated from the marine-derived Streptomyces sundarbansensis SCSIO NS01; these compounds represent four sets of aromatic polyketides differing in size and shape. A type II polyketide synthase (PKS) cluster, als, was identified by complete genome sequencing and was shown, by in vivo gene inactivation experiments in the wild-type (WT) NS01 strain and heterologous expression experiments, to encode the biosynthesis of compounds 1-5. Moreover, heterologous expression of the als cluster afforded three additional aromatic polyketides representing two different carbon skeletons, the new phaeochromycin L (6) and two known aromatic polyketides, phaeochromycins D (7) and E (8). These findings expand our knowledge of type II PKS machineries and their versatility in generating structurally diverse aromatic polyketides and highlight the power of type II PKSs in accessing new polyketides via ectopic expression in heterologous hosts.

Remarkably efficient Pt/CeO2-Al2O3 catalyst for catalytic hydrodeiodination of monoiodoacetic acid: Synergistic effect of Al2O3 and CeO2.

Monoiodoacetic acid (MIAA) is one of the highly toxic halogenated disinfection by-products, which is formed during water disinfection processes. Catalytic hydrogenation with supported noble metal catalyst is a green and effective technique for the transformation of halogenated pollutant, but its activity still needs to be identified. In this study, Pt nanoparticles were supported on CeO2 modified γ-Al2O3 (Pt/CeO2-Al2O3) by chemical deposition method and the synergistic effect of Al2O3 and CeO2 on catalytic hydrodeiodination (HDI) of MIAA was systematically studied. Characterizations revealed that Pt dispersion could be improved by the introduced CeO2 through the formation of Ce-O-Pt bond and MIAA adsorption could be facilitated by high Zeta potential of Al2O3 component. Furthermore, optimal Ptn+/Pt0 could be obtained by adjusting CeO2 deposition amount on Al2O3, which could effectively facilitate the activation of C-I bond. Therefore, Pt/CeO2-Al2O3 exhibited remarkable catalytic activities and TOF values compared with those of Pt/CeO2 and Pt/Al2O3. Through detailed kinetic experiments and characterization, the extraordinary catalytic performance of Pt/CeO2-Al2O3 can be attributed to the abundant Pt sites as well as the synergistic effect between CeO2 and Al2O3.

Series of Dual Functional Two-Dimensional RE-OFs for Nitrophenol Reduction and Dye Separation.

The rational design and preparation of stable and multifunctional metal-organic frameworks (MOFs) with excellent catalysis and adsorption properties are desirable but are great challenges. The nitrophenol (NP) reduction to aminophenols (APs) by using the catalyst Pd@MOFs is an effective strategy, which has attracted extensive attention in recent years. Here, we report four stable isostructural two-dimensional (2D) rare earth metal-organic frameworks [RE4(AAPA)6(DMA)2 (H2O)4][DMA]3[H2O]8 (namely LCUH-101, RE = Eu, Gd, Tb, Y; AAPA2- = 5-[(anthracen-9-yl-methyl)-amino]-1,3-isophthalate), which feature a 2D layer structure with sql topology of point symbol {44·62} and exhibit excellent chemical stability and thermostability. The as-synthesized Pd@LCUH-101 was utilized for the catalytic reduction of 2/3/4-nitrophenol, which indicates high catalytic activity and recyclability attributed to the synergistic effect between Pd nanoparticles and the 2D layered structure. Of note, the turnover frequency (TOF), the reaction rate constant (k), and the activation energy (Ea) of Pd@LCUH-101 (Eu) in the reduction of 4-NP, respectively, are 1.09 s-1, 2.17 min-1, and 50.2 kJ·mol-1, which show that it has superior catalytic activity. Remarkably, LCUH-101 (Eu, Gd, Tb, and Y) are multifunctional MOFs that can effectively absorb and separate mixed dyes. The appropriate interlayer spacing enables them to efficiently adsorb methylene blue (MB) and rhodamine B (RhB) in aqueous solution, with adsorption capacities of 0.97 and 0.41 g·g-1, respectively, which is one of the highest values among those of the reported MOF-based adsorbers. Meanwhile, LCUH-101 (Eu) can be used for the separation of the dye mixture MB/MO and RhB/MO, and the excellent reusability enables LCUH-101 (Eu) to be used as chromatographic column filters to quickly separate and recover dyes. Therefore, this work provides a new strategy for the exploitation of stable and efficient catalysts for NP reduction and adsorbents for dyes.

Seven drimane-type sesquiterpenoids from an earwig-associated Aspergillus sp.

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC50 value of 12.88 ± 0.11 µmol·L-1.

Adaptive-back-stepping-based controller design for double-pendulum rotary cranes.

The operating process of rotary crane is often very complicated and there are many unpredictable conditions, such as the condition of the load sway around the hook, which will undoubtedly make the sway characteristics analysis of the system and the controller design become more difficult. In addition, for the purpose of decreasing the complexity of controller design, traditional control methods often perform model linearization processing operation, which can reduce the robustness of the system to a certain extent (when the parameters of the crane are unknown or there are external disturbances, the control capability of traditional control methods will be largely degraded). Based on the above, this paper first uses kinematic analysis to derive rotary crane model, and then proposes a nonlinear controller based on adaptive back-stepping method to achieve pendulum elimination and boom positioning. Then the stability of the system is proved by Lyapunov Lemmas. Finally, the performance of the system is verified by comparing the experimental results of different methods.

Series of TM-OFs as a Platform for Efficient Catalysis and Multifunctional Luminescence Sensing.

Three novel porous transition-metal-organic frameworks (TM-OFs), formulated as [Co3(DCPN)2(µ2-OH2)4(H2O)4](DMF)2 (1), [Cd3(DCPN)2(µ2-OH2)4(H2O)4](DMF)2 (2), and [CdK(DCPN)(DMA)] (3), have been successfully prepared via solvothermal conditions based on a 5-(3',6'-dicarboxylic phenyl) nicotinic carboxylic acid (H3DCPN) ligand. 1 and 2 both have the same porous 3D network structure with the point symbol of {410·614·84}·{45·6}2 based on trinuclear ({Co3} or {Cd3}) clusters, indicating a one-dimensional porous channel, and possess excellent water and thermal stability; 3 also displays a porous 3D network structure with a 4-connected sra topology based on the heteronuclear metal cluster {CdK}. Complex 1 can be used to load Pd nanoparticles (Pd NPs) via a wetness impregnation strategy to obtain Pd@1. The reduction of nitrophenols (2-NP, 3-NP, 4-NP) by Pd@1 in aqueous solution shows outstanding conversion, excellent rate constants (k), and remarkable cycling stability due to the synergistic effect of complex 1 and Pd NPs. Luminescence sensing tests confirmed that 2 is a reliable multifunctional chemical sensor with high selectivity and sensitivity for low concentrations of Fe3+, Cr2O72-, CPFX, and NFX. Specifically, 2 shows a fluorescence enhancement behavior toward fluoroquinolone antibiotics (CPFX and NFX), which has not been reported previously in the literature. Moreover, the rational mechanism of fluorescence sensing was also systematically investigated by various detection means and theoretical calculations.

Halo- and Thiocarbazomycins from Coral- and Coral Reef Sands-Derived Actinomycetes.

Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A-B (1-2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A-C (5-7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.

Bacterial Quorum-Sensing Signal DSF Inhibits LPS-Induced Inflammations by Suppressing Toll-like Receptor Signaling and Preventing Lysosome-Mediated Apoptosis in Zebrafish.

Bacteria and their eukaryotic hosts have co-evolved for millions of years, and the former can intercept eukaryotic signaling systems for the successful colonization of the host. The diffusible signal factor (DSF) family represents a type of quorum-sensing signals found in diverse Gram-negative bacterial pathogens. Recent evidence shows that the DSF is involved in interkingdom communications between the bacterial pathogen and the host plant. In this study, we explored the anti-inflammatory effect of the DSF and its underlying molecular mechanism in a zebrafish model. We found that the DSF treatment exhibited a strong protective effect on the inflammatory response of zebrafish induced by lipopolysaccharide (LPS). In the LPS-induced inflammation zebrafish model, the DSF could significantly ameliorate the intestinal pathological injury, reduce abnormal migration and the aggregation of inflammatory cells, inhibit the excessive production of inflammatory mediator reactive oxygen species (ROS) content, and prevent apoptosis. Through an RNA-Seq analysis, a total of 938 differentially expressed genes (DEGs) was screened between LPS and LPS + DSF treatment zebrafish embryos. A further bioinformatics analysis and validation revealed that the DSF might inhibit the LPS-induced zebrafish inflammatory response by preventing the activation of signaling in the Toll-like receptor pathway, attenuating the expression of pro-inflammatory cytokines and chemokines, and regulating the activation of the caspase cascade through restoring the expression of lysosomal cathepsins and apoptosis signaling. This study, for the first time, demonstrates the anti-inflammatory role and a potential pharmaceutical application of the bacterial signal DSF. These findings also suggest that the interkingdom communication between DSF-producing bacteria and zebrafish might occur in nature.

Series of Stable Anionic Lanthanide Metal-Organic Frameworks as a Platform for Pollutant Separation and Efficient Nanoparticle Catalysis.

Eight new stable porous lanthanide metal-organic frameworks (Ln-OFs), namely, [Ln2(BPTC)2][(CH3)2NH2]2 [Ln = Ho (1), Eu (2), Gd (3), Dy (4), Er (5), Tm (6), Yb (7), Lu (8)], were prepared by 3,3',5,5'-biphenyltetracarboxylic acid (H4BPTC) and lanthanide ions by solvothermal reactions. Complexes 1-8 show a three-dimensional (3D) 6,6-connected network {412·63}·{48·66·8} topology based on binuclear (Ln2) clusters and feature a one-dimensional curving porous channel occupied by exchangeable dimethylamine cations ([(CH3)2NH2]+) in the 3D anionic frameworks. The occupied [(CH3)2NH2]+ in the anionic channels exhibited excellent ion-exchange ability, which is favorable to Pd2+ and cationic dye adsorption. Consequently, 1-8 were used to load Pd nanoparticles to catalyze the reduction of nitrophenols and adsorb and desorb methyl blue (MB). The catalytic reaction efficiencies of Pd@1-8 were higher than that of Pd/C (5 wt %) in the hydrogenation reaction of p-nitrophenol (p-NP). Moreover, Pd@1 exhibited good cycle stability and achieved nearly 100% p-NP conversion after eight cycles. Meanwhile, compound 1 also exhibited a high adsorption ability of MB, possessing an adsorption capacity of 1.41 g·g-1 (second only to 1.49 g·g-1 reported in the literature) selectively over rhodamine B (RhB) and methyl orange (MO) in aqueous solutions. Remarkably, the skeleton of 1 remained stable after four adsorption-desorption cycles of MB in aqueous solution.

Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies.

Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor evaluated in multiple B-cell malignancy studies. We constructed a pooled safety analysis to better understand zanubrutinib-associated treatment-emergent adverse events (TEAEs) and identify treatment-limiting toxicities. Data were pooled from 6 studies (N = 779). Assessments included type, incidence, severity, and outcome of TEAEs. Median age was 65 years; 20% were ≥75 years old. Most patients had Waldenström macroglobulinemia (33%), chronic lymphocytic leukemia/small lymphocytic lymphoma (29%), or mantle-cell lymphoma (19%). Median treatment duration was 26 months (range, 0.1-65); 16% of patients were treated for ≥3 years. Common nonhematologic TEAEs were upper respiratory tract infection (URI, 39%), rash (27%), bruising (25%), musculoskeletal pain (24%), diarrhea (23%), cough (21%), pneumonia (21%), urinary tract infection (UTI), and fatigue (15% each). Most common grade ≥3 TEAEs were pneumonia (11%), hypertension (5%), URI, UTI, sepsis, diarrhea, and musculoskeletal pain (2% each). Atrial fibrillation and major hemorrhage occurred in 3% and 4% of patients, respectively. Atrial fibrillation, hypertension, and diarrhea occurred at lower rates than those reported historically for ibrutinib. Grade ≥3 adverse events included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%).Treatment discontinuations and dose reductions for adverse events occurred in 10% and 8% of patients, respectively. Thirty-nine patients (4%) had fatal TEAEs, including pneumonia (n = 9), sepsis (n = 4), unspecified cause (n = 4), and multiple organ dysfunction syndrome (n = 5). This analysis demonstrates that zanubrutinib is generally well tolerated with a safety profile consistent with known BTK inhibitor toxicities; these were manageable and mostly reversible.

Zhaoshumycins A and B, Two Unprecedented Antimycin-Type Depsipeptides Produced by the Marine-Derived Streptomyces sp. ITBB-ZKa6.

Marine actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the marine-derived Streptomyces sp. ITBB-ZKa6, from Zhaoshu island, Hainan, led to the discovery of two unique antimycin-type depsipeptides, zhaoshumycins A (1) and B (2), along with the isolation of the four known neoantimycins A (3), F (4), D (5), and E (6). The structures of the new compounds 1 and 2 were elucidated on the basis of the analysis of diverse spectroscopic data and biogenetic consideration. Zhaoshumycins A (1) and B (2) represent a new class of depsipeptides, featuring two neoantimycin monomers (only neoantimycin D or neoantimycins D and E) linked to a 1,4-disubstituted benzene ring via an imino group. Initial toxicity tests of 1-6 in MCF7 human breast cancer cells revealed that compounds 5 and 6 possess weak cytotoxic activity. Further structure-activity relationship analysis suggested the importance of the NH2 group at C-34 in 5 and 6 for cytotoxicity in MCF7 cells.