Sequential Reductive Dechlorination of Triclosan by Sediment Microbiota Harboring Organohalide-Respiring Dehalococcoidia.

Aquatic ecosystems represent a prominent reservoir of xenobiotic compounds, including triclosan (TCS), a broad-spectrum biocide extensively used in pharmaceuticals and personal care products. As a biogeochemical hotspot, the potential of aquatic sediments for the degradation of TCS remains largely unexplored. Here, we demonstrated anaerobic biotransformation of TCS in a batch microcosm established with freshwater sediment. The initial 43.4 ± 2.2 µM TCS was completely dechlorinated to diclosan, followed by subsequent conversion to 5-chloro-2-phenoxyphenol, a monochlorinated TCS (MCS) congener. Analyses of community profile and population dynamics revealed substrate-specific, temporal-growth of Dehalococcoides and Dehalogenimonas, which are organohalide-respiring bacteria (OHRB) affiliated with class Dehalococcoidia. Dehalococcoides growth was linked to the formation of diclosan but not MCS, yielding 3.6 ± 0.4 × 107 cells per µmol chloride released. A significant increase in Dehalogenimonas cells, from 1.5 ± 0.4 × 104 to 1.5 ± 0.3 × 106 mL-1, only occurred during the reductive dechlorination of diclosan to MCS. Dehalococcoidia OHRB gradually disappeared following consecutive transfers, likely due to the removal of sediment materials with strong adsorption capacity that could alleviate TCS's antimicrobial toxicity. Consequently, a solid-free, functionally stable TCS-dechlorinating consortium was not obtained. Our results provide insights into the microbial determinants controlling the environmental fate of TCS.

Structural insights into transcription activation of the Streptomyces antibiotic regulatory protein, AfsR.

The Streptomyces antibiotic regulatory proteins (SARPs) are ubiquitously distributed transcription activators in Streptomyces and control antibiotics biosynthesis and morphological differentiation. However, the molecular mechanism behind SARP-dependent transcription initiation remains elusive. We here solve the cryo-EM structure of an AfsR-loading RNA polymerase (RNAP)-promoter intermediate complex (AfsR-RPi) including the Streptomyces coelicolor RNAP, a large SARP member AfsR, and its target promoter DNA that retains the upstream portion straight. The structure reveals that one dimeric N-terminal AfsR-SARP domain (AfsR-SARP) specifically engages with the same face of the AfsR-binding sites by the conserved DNA-binding domains (DBDs), replacing σHrdBR4 to bind the suboptimal -35 element, and shortens the spacer between the -10 and -35 elements. Notably, the AfsR-SARPs also recruit RNAP through extensively interacting with its conserved domains (ß flap, σHrdBR4, and αCTD). Thus, these macromolecular snapshots support a general model and provide valuable clues for SARP-dependent transcription activation in Streptomyces.

Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite.

Colorectal cancer is a heterogeneous disease which can be divided into proximal colon cancer, distal colon cancer and rectal cancer according to the anatomical location of the tumor. Each anatomical location of colorectal cancer exhibits distinct characteristics in terms of incidence, clinical manifestations, molecular phenotypes, treatment, and prognosis. Notably, proximal colon cancer differs significantly from cancers of other anatomical subsites. An increasing number of studies have highlighted the presence of unique tumor biological characteristics in proximal colon cancer. Gaining a deeper understanding of these characteristics will facilitate accurate diagnosis and treatment approaches.

Identifying Target Molecule and Trace Amount of the Byproduct by Two-Dimensional Self-Assembly with Different Solution Concentrations.

Scanning tunneling microscopy (STM) is a powerful way to realize the recognition of self-assembled nanostructures on the atomic scale. In this article, dihexadecyl 6,9-bis((4-(hexadecyloxy)phenyl)ethynyl) phenanthro[9,10-c]thiophene-1,3-dicarboxylate (D-PT) and dihexadecyl 6-bromo-9-((4-(hexadecyloxy) phenyl)ethynyl)phenanthrol[9,10-c]thiophene-1,3-dicarboxylate (S-BrPT) with different substituents were chosen as the target system. D-PT with four side chains as the target molecule and S-BrPT with three side chains and a bromine substituent as the byproduct were mixed in a molar concentration ratio of 20:1. The effect of solution concentration on the molecular self-assembly of the mixture was investigated by STM at the hexadecane/HOPG interface. At high concentrations, only D-PT molecules formed a dimer pattern resulting from the intermolecular van der Waals force and self-adaption. Further diluting the solution, D-PT formed the coexisting dimer and linear structures, in which the linear pattern was formed via solvent coadsorption. At low concentrations, S-BrPT molecules forming N-shaped dimers appeared and filled the linear structure fabricated by D-PT molecules. With further decrease in the concentration, S-BrPT molecules formed N-shaped dimers covering almost half of the surface area, resulting from the C-Br···π and Br···H-C bonds. At very low concentrations, S-BrPT molecules formed N-shaped dimers to arrange the matrix architecture due to the coadsorption of more hexadecane molecules. Density functional theory (DFT) calculations demonstrated that the stronger intermolecular C-Br···π and Br···H-C bonds were significant factors in determining the formation of N-shaped dimers and the stability of this nanostructure. This work enriches the diversity of self-assembled motifs and provides a strategy to characterize different symmetric molecules with trace amounts in a mixed system by STM.

An Axially Chiral Quinoline-2-Carboxylic Acid-Cu Catalyst for Enantioselective Synthesis of C2- and C1-Symmetric BINOLs.

The in situ dimeric coordination of two chiral ligands bearing quinoline-2-carboxylic acid units and substituted BINOL backbones with a copper ion generates a new chiral catalyst for oxidative homo- and cross-coupling of various 2-naphthols, enabling enantioselective synthesis of a broad range of highly useful diversely substituted C2- and C1-symmetric BINOLs in up to 96% yield with good to excellent enantioselectivities (up to 98:2 e.r.).

Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review.

Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety. Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019). Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.

The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.

An Integrated Approach Using Network Pharmacology and Experimental Validation to Reveal the Therapeutic Mechanism of Weifuchun in Treating Gastric Cancer.

Gastric cancer (GC) is a prevalent malignancy affecting the gastrointestinal tract. Weifuchun (WFC), a Chinese herbal prescription comprising red ginseng, Isodon amethystoides, and Fructus aurantii, is widely used in China for various chronic stomach disorders. However, its therapeutic role and mechanisms in treating GC remain unexplored. In a randomized, controlled, single-blind trial involving postoperative stages II and III GC patients, we compared adjuvant chemotherapy plus WFC (chemo plus WFC group) to adjuvant chemotherapy alone (chemo group) over 6 months. We assessed recurrence and metastasis rates and used systematic pharmacology to predict WFC's active components, screen target genes, and construct network interaction maps, were validated through in vitro experiments. The combined therapy significantly reduced 2-year recurrence and metastasis rates. We identified 67 active ingredients, 211 drug target proteins, 1539 disease targets, 105 shared targets, and 188 signaling pathways associated with WFC. WFC impacted cell apoptosis, proliferation, and the inflammatory response, with top tumor-related signaling pathways involving 5'-adenosine monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinase, nuclear factor kappa-B (NFKB), and apoptosis. In vitro, WFC inhibited proliferation and migration while inducing apoptosis in GC cells, reduced VEGFA, TNFa, and IL6 expressions. Immunocytochemistry showed increased p-AMPK staining, and molecular analysis revealed decreased NFKB and phosphorylation of extracellular-regulated protein kinase 1/2 (ERK1/2) levels, increased p-AMPK and BAX protein levels in WFC-treated cells, effects reversed by Compound C. WFC's antitumor effects involve AMPK-dependent ERK1/2 and NFKB pathways, regulating proliferation, migration, and apoptosis in GC cells.

A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.

Jellyfish-inspired Polyurea Ionogel with Mechanical Robustness, Self-Healing, and Fluorescence Enabled by Hyperbranched Cluster Aggregates.

Ionogels are promising for soft iontronics, with their network structure playing a pivotal role in determining their performance and potential applications. However, simultaneously achieving mechanical toughness, low hysteresis, self-healing, and fluorescence using existing network structures is challenging. Drawing inspiration from jellyfish, we propose a novel hierarchical crosslinking network structure design for in situ formation of hyperbranched cluster aggregates (HCA) to fabricate polyurea ionogels to overcome these challenges. Leveraging the disparate reactivity of isocyanate groups, we induce the in situ formation of HCA through competing reactions, enhancing toughness and imparting the clustering-triggered emission of ionogel. This synergy between supramolecular interactions in the network and plasticizing effect in ionic liquid leads to reduced hysteresis of the ionogel. Furthermore, the incorporation of NCO-terminated prepolymer with dynamic oxime-urethane bonds (NPU) enables self-healing and enhances stretchability. Our investigations highlight the significant influence of HCA on ionogel performance, showcasing mechanical robustness including high strength (3.5 MPa), exceptional toughness (5.5 MJ m-3), resistance to puncture, and low hysteresis, self-healing, as well as fluorescence, surpassing conventional dynamic crosslinking approaches. This network design strategy is versatile and can meet the various demands of flexible electronics applications.

Associations between gut microbiota and chronic sinusitis: A bidirectional Mendelian randomization study.

BACKGROUND: Studies have indicated a close association between dysbiosis of the gut microbiota and chronic sinusitis. However, the causal relationship between the gut microbiota and the risk of chronic sinusitis remains unclear. METHODS: Using genome-wide association study (GWAS) data for the gut microbiota and chronic sinusitis, we conducted a two-sample Mendelian randomization (MR) study to determine the potential causal relationship between the microbiota and chronic sinusitis. We employed the inverse variance-weighted (IVW) method as the primary analytical approach to estimate the effect. Additionally, sensitivity, heterogeneity, and pleiotropy analyses were conducted to evaluate the robustness of the results. Reverse MR analysis was also applied to investigate potential reverse causality. RESULTS: Through MR analysis, we identified 17 gut microbiota classifications that are closely associated with chronic sinusitis. However, after Bonferroni multiple correction, only class Bacilli (odds ratio: 0.785, 95% confidence interval: 0.677-0.911, p = .001, false discovery rate = 0.023) maintained a significant causal negative relationship with chronic sinusitis. Sensitivity analysis did not reveal any evidence of heterogeneity or horizontal pleiotropy. Reverse MR analysis found five gut microbiota classifications that are significantly associated with chronic sinusitis, but they were no longer significant after Bonferroni multiple correction. There was no evidence to suggest a reverse causal relationship between chronic sinusitis and class Bacilli. CONCLUSION: Specific gut microbiota predicted by genetics exhibit a potential causal relationship with chronic sinusitis, and class Bacilli may have a protective effect on chronic sinusitis.

A Lu3Sc2Ga3O12: Eu3+ red-emitting phosphor with excellent optical properties and thermal stability was obtained by partially replacing Lu3+ with Gd3+ / Y3.

A novel red phosphor Lu3(1-x)Sc2Ga3O12: xEu3+(0 ≤ x ≤ 0.3) was successfully prepared by high temperature solid state method. The Lu2.4Sc2Ga3O12: 0.2Eu3+ phosphor shows strong high internal quantum efficiency and thermal stability with values of 64.79 % and 87.0 %, respectively. Based on Lu2.4Sc2Ga3O12: 0.2Eu3+ phosphor, the partial replacement of Lu3+ ions in the host by Gd3+ / Y3+ ions changes the local crystal field environment of Eu3+ ions, resulting in wonderful changes in the luminous center, and the luminous intensity at 593 nm is increased by 3.66 and 3.54 times, respectively. The decay time of Eu3+ ions is analyzed from the perspective of dynamics, and the reasons for the enhancement of luminescence after partial replacement of Lu3+ ions are discussed in detail from two aspects of phosphor structure and crystal field effect around Eu3+ ions. In addition, with the substitution of Gd3+ / Y3+ ions, the thermal stability of the sample is 90.3 %/89.4 % with excellent low thermal quenching. The thermal quenching mechanism is described by combining Debye temperature and activation energy. The sample also has a high internal quantum efficiency IQE=79.03 % / 78.24 %. Finally, under the excitation of 365 nm chip, the phosphors of Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Gd3+ and Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Y3+ synthesized R-LED device has extremely high color rendering index, Ra is 78.23/77.15 and color temperature is 1640.38 K/1642.97 K. The experimental results show that the Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Gd3+ / Y3+ phosphors prepared has a wide application prospect in w-LED devices.

Colossal Barocaloric Effect near Ambient Temperature in 1-Dodecanol under a Low Pressure.

Solid-state refrigeration based on the barocaloric effect is an effective alternative to traditional vapor compression refrigeration. Here 1-dodecanol has been studied due to its large latent heat at a solid-liquid phase transition point around room temperature. The transition temperature will vary with the applied hydrostatic pressure, exhibiting with a sensitivity of 0.14 K MPa-1, which indicates its potential for refrigeration. A pressure of 40 MPa can result in a large isothermal entropy change of 520 J kg-1 K-1 (equivalent to that obtained in vapor compression refrigeration) at 297 K. A large adiabatic temperature change of >20 K in 1-dodecanol was acquired by direct measurement. A wide temperature window of ∼50 K (288-337 K) can be obtained in 1-dodecanol, which demonstrates broad application prospects. These discoveries offer promising prospects for barocaloric cooling and high-efficiency refrigeration technologies relying on solid-liquid phase transitions.

A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH.

Time-restricted feeding (TRF) is a potent dietary intervention for improving metabolic diseases, including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH). However, the mechanism of this efficacy has remained elusive. Here, we show that TRF improves MASLD, which is associated with a significant enrichment of Ruminococcus torques (R. torques). Mechanistically, R. torques suppresses the intestinal HIF-2α-ceramide pathway via the production of 2-hydroxy-4-methylpentanoic acid (HMP). We identify rtMor as a 4-methyl-2-oxopentanoate reductase that synthesizes HMP in R. torques. Finally, we show that either the colonization of R. torques or oral HMP supplementation can ameliorate inflammation and fibrosis in a MASH mouse model. These findings identify R. torques and HMP as potential TRF mimetics for the treatment of metabolic disorders.

Dion-Jacobson-Phase 2D Sn-Based Perovskite Comprising a High Dipole Moment of π-Conjugated Short-Chain Organic Spacers for High-Performance Solar Cell Applications.

The stability issue of Sn-based perovskite solar cells (PSCs) is expected to be resolved by involving a two-dimensional (2D) layered structure. However, Sn-based 2D PSCs, especially Dion-Jacobson (DJ)-phase ones with potentially good stability, have rarely been reported. Herein, superior DJ-phase Sn 2D perovskites with 3-aminobenzylamine (3ABA2+) or 4-aminobenzylamine (4ABA2+) π-conjugated short-chain ligands are reported to fabricate efficient 2D lead-free PSCs. Notably, the high dipole moment of the 3ABAI2 organic spacer is approved to possess faster charge transfer for forming (3ABA)FA4Sn5I16 2D perovskite with an extremely low exciton binding energy (only 84 meV). In combination with a diacetate partial substitution and methylamine iodide/bromide (MAI/MABr) post-treatment strategy to delay crystallization and improve compactness and coverage of the perovskite film, a record power conversion efficiency (PCE) of 6.81% and stability of 840 h (less than 5% degradation in a N2 atmosphere for unencapsulated devices) are acquired in eventual (3ABA)FA4Sn5I16 2D PSCs, which are among the highest PCE and the longest stability of Sn-based 2D PSCs reported to date. Our work provides a prospective molecule design and film preparation strategy of 2D Sn perovskites toward nontoxic high-performance tin-based PSCs, which pushes the almost stagnant research forward.

High χ P2PFBEMA-b-P2VP Block Copolymers Forming 6-8 nm Domains for Semiconductor Lithography.

We leveraged the potential of high χ-low N block copolymer (BCP), namely, poly[2-(perfluorobutyl) ethyl methacrylate]-block-poly(2-vinylpyridine) (P2PFBEMA-b-P2VP), and demonstrated its utility in next-generation nanomanufacturing. By combining molecular dynamics simulations with experiments, the χ value was calculated to be as high as 0.4 (at 150 °C), surpassing similar structures. Highly ordered features suitable for application were observed, ranging in periods from 19.0 nm down to 12.1 nm, with feature sizes as small as 6 nm. Transmission electron microscopy images of the BCP solutions indicated that preformed micelles in the solution facilitated the self-assembly process of the thin film. In addition, the vertical or parallel orientation of the cylindrical structure was determined by manipulating the solvent, substrate, and annealing conditions. Finally, guided by a wide topographical template, nearly defect-free directed self-assembly (DSA) lines with a resolution of 8 nm were achieved, highlighting its potential practical application in DSA lithography technology.

Metal-organic framework (MOF)-based materials for pyroptosis-mediated cancer therapy.

Pyroptosis is regarded as a promising strategy to modulate tumor immune microenvironments for anticancer therapy. Although pyroptosis inducers have been extensively explored in the biomedical field, their drug resistance, off-targeting capacity, and adverse effects do not fulfill the growing demands of therapy. Nowadays, metal-organic frameworks (MOFs) with unique structures and facile synthesis/functionalization characteristics have shown great potential in anticancer therapy. The flexible choices of metal ions and ligands endow MOFs with inherent anti-cancer efficiency, whereas the porous structures in MOFs make them ideal vehicles for delivering various chemodrug-based pyroptosis inducers. In this review, we provide the latest advances in MOF-based materials to evoke pyroptosis and give a brief but comprehensive review of the different types of MOFs for pyroptosis-mediated cancer therapy. Finally, we also discuss the current challenges of MOF-based pyroptosis inducers and their future prospects in this field.

Biomimetic NO Scavenging Hyaluronic Acid Nanoparticles Enable Targeted Delivery of MTX and Integrated Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.

Natural mineral colloids facilitated transport of EE2 in saturated porous media: Effects of humic acid and conjugate form.

Steroid estrogens have posed significant ecological risks to aquatic organisms due to their potent endocrine-disrupting effects. The role of natural mineral colloids in facilitating the transport of hydrophobic organic pollutants in the environment has been confirmed, but the control mechanisms of colloids on 17α-Ethinylestradiol (EE2) migration in the subsurface environment are often still not well understood. This study combined the batch sorption equilibrium experiments and dynamic transport simulations to reveal the interface interactions and co-transport characteristics between illite colloids and EE2 at both macroscopic and microscopic levels. The existing form changes of EE2 and the influence of coexisting humic acid (HA) during transport in porous media were also specifically investigated. The batch experiments demonstrated that the primary mechanisms governing EE2 sorption onto illite colloids involved surface sorption and hydrogen bonding. The coexistence of HA could load onto the surface of illite colloids, thereby enhancing the colloidal sorption capacity for EE2. Transport experiments demonstrated that the migratory ability of EE2 in silty clay was limited, but illite colloids could significantly promote its penetration, with the peak penetration content (Ct/C0) increasing from 0.64 to 0.77. In the absence of HA, EE2 primarily transported in a dissolved form, accounting for 62.86% of the total concentrations. When HA concentrations were increased to 10 mg/L and 20 mg/L, the proportion of colloidal conjugate EE2 in the effluents reached 52.13% and 54.49%, respectively. The enhanced transport of EE2 by HA was primarily attributed to the improved migration ability of illite colloids and the increased proportion of illite-EE2 conjugate, resulting in a maximum Ct/C0 value of 0.94. The validity of these results was further confirmed by employing calculations based on the Derjaguin-Landau-Verwey-Overbeek and Colloidal Filtration Theory. This study provides new insights of understanding the transport of EE2 in subsurface environment.