Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis.

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

Synthesis and Characterization of Bridging-Diazene Diiron Half-Sandwich Complexes: The Role of Sulfur Hydrogen Bonding.

We report two bridging-diazene diiron complexes [Cp*Fe(8-quinolinethiolate)]2(µ-N2H2) (1-N2H2) and [Cp*Fe(1,2-Cy2PC6H4S)]2(µ-N2H2) (2-N2H2), synthesized by the reaction of hydrazine with the corresponding thiolate-based iron half-sandwich complex, [Cp*Fe(8-quinolinethiolate)]2 (1) and Cp*Fe(1,2-Cy2PC6H4S) (2). Crystallographic analysis reveals that the thiolate sites in 1-N2H2 and 2-N2H2 can engage in N-H···S hydrogen bonding with the diazene protons. 1-N2H2 is thermally stable in both solid and solution states, allowing for one-electron oxidation to afford a cationic diazene radical complex [1-N2H2]+ at room temperature. In contrast, 2-N2H2 tends to undergo N2H2/N2 transformation, leading to the formation of a Fe(III)-H species by the loss of N2. In addition to stabilizing HN=NH species through the hydrogen bonding, the thiolate-based ligands also seem to facilitate proton-coupled electron transfer, thereby promoting N-H cleavage.

LAZY4 acts additively with the starch-statolith-dependent gravity-sensing pathway to regulate shoot gravitropism and tiller angle in rice.

Rice tiller angle is a key agronomic trait that has significant effects on the establishment of a high-yield rice population. However, the molecular mechanism underlying the control of rice tiller angle remains to be clarified. Here, we characterized the novel tiller-angle gene LAZY4 (LA4) in rice through map-based cloning. LA4 encodes a C3H2C3-type RING zinc-finger E3 ligase localized in the nucleus, and an in vitro ubiquitination assay revealed that the conserved RING finger domain is essential for its E3 ligase activity. We found that expression of LA4 can be induced by gravistimulation and that loss of LA4 function leads to defective shoot gravitropism caused by impaired asymmetric auxin redistribution upon gravistimulation. Genetic analysis demonstrated that LA4 acts in a distinct pathway from the starch biosynthesis regulators LA2 and LA3, which function in the starch-statolith-dependent pathway. Further genetic analysis showed that LA4 regulates shoot gravitropism and tiller angle by acting upstream of LA1 to mediate lateral auxin transport upon gravistimulation. Our studies reveal that LA4 regulates shoot gravitropism and tiller angle upstream of LA1 through a novel pathway independent of the LA2-LA3-mediated gravity-sensing mechanism, providing new insights into the rice tiller-angle regulatory network.

Engineering sub-organelles of a diploid Saccharomyces cerevisiae to enhance the production of 7-dehydrocholesterol.

7-Dehydrocholesterol (7-DHC) is widely present in various organisms and is an important precursor of vitamin D3. Despite significant improvements in the biosynthesis of 7-DHC, it remains insufficient to meet the industrial demands. In this study, we reported high-level production of 7-DHC in an industrial Saccharomyces cerevisiae leveraging subcellular organelles. Initially, the copy numbers of DHCR24 were increased in combination with sterol transcriptional factor engineering and rebalanced the redox power of the strain. Subsequently, the effects of compartmentalizing the post-squalene pathway in peroxisomes were validated by assembling various pathway modules in this organelle. Furthermore, several peroxisomes engineering was conducted to enhance the production of 7-DHC. Utilizing the peroxisome as a vessel for partial post-squalene pathways, the potential of yeast for 7-dehydrocholesterol production was demonstrated by achieving a 26-fold increase over the initial production level. 7-DHC titer reached 640.77 mg/L in shake flasks and 4.28 g/L in a 10 L bench-top fermentor, the highest titer ever reported. The present work lays solid foundation for large-scale and cost-effective production of 7-DHC for practical applications.

Advancements in gradient bone scaffolds: enhancing bone regeneration in the treatment of various bone disorders.

Bone scaffolds are widely employed for treating various bone disorders, including defects, fractures, and accidents. Gradient bone scaffolds present a promising approach by incorporating gradients in shape, porosity, density, and other properties, mimicking the natural human body structure. This design offers several advantages over traditional scaffolds. A key advantage is the enhanced matching of human tissue properties, facilitating cell adhesion and migration. Furthermore, the gradient structure fosters a smooth transition between scaffold and surrounding tissue, minimizing the risk of inflammation or rejection. Mechanical stability is also improved, providing better support for bone regeneration. Additionally, gradient bone scaffolds can integrate drug delivery systems, enabling controlled release of drugs or growth factors to promote specific cellular activities during the healing process. This comprehensive review examines the design aspects of gradient bone scaffolds, encompassing structure and drug delivery capabilities. By optimizing the scaffold's inherent advantages through gradient design, bone regeneration outcomes can be improved. The insights presented in this article contribute to the academic understanding of gradient bone scaffolds and their applications in bone tissue engineering.

A Large-Scale Network Construction and Lightweighting Method for Point Cloud Semantic Segmentation.

To significantly enhance the performance of point cloud semantic segmentation, this manuscript presents a novel method for constructing large-scale networks and offers an effective lightweighting technique. First, a latent point feature processing (LPFP) module is utilized to interconnect base networks such as PointNet++ and Point Transformer. This intermediate module serves both as a feature information transfer and a ground truth supervision function. Furthermore, in order to alleviate the increase in computational costs brought by constructing large-scale networks and better adapt to the demand for terminal deployment, a novel point cloud lightweighting method for semantic segmentation network (PCLN) is proposed to compress the network by transferring multidimensional feature information of large-scale networks. Specifically, at different stages of the large-scale network, the structure and attention information of the point features are selectively transferred to guide the compressed network to train in the direction of the large-scale network. This paper also solves the problem of representing global structure information of large-scale point clouds through feature sampling and aggregation. Extensive experiments on public datasets and real-world data demonstrate that the proposed method can significantly improve the performance of different base networks and outperform the state-of-the-art.

Bimetallic H2 Addition and Intramolecular Caryl-H Activation Mediated by an Iron-Zinc Hydride.

Heteronuclear Fe(µ-H)Zn hydride Cp*Fe(1,2-Cy2PC6H4)HZnEt (3) undergoes reversible intramolecular Caryl-H reductive elimination through coupling of the cyclometalated phosphinoaryl ligand and the hydride, giving rise to a formal Fe(0)-Zn(II) species. Addition of CO intercepts this equilibrium, affording Cp*(Cy2PPh)(CO)Fe-ZnEt that features a dative Fe-Zn bond. Significantly, this system achieves bimetallic H2 addition, as demonstrated by the transformation of the monohydride Fe(µ-H)Zn to a deuterated dihydride Fe-(µ-D)2-Zn upon reaction with D2.

Acute kidney injury prediction model utility in premature myocardial infarction.

The incidence of premature myocardial infarction (PMI) has been rising and acute kidney injury (AKI) occurring in PMI patients severely impacts prognosis. This study aimed to develop and validate a prediction model for AKI specific to PMI patients. The MIMIC-Ⅲ-CV and MIMIC-Ⅳ databases were utilized for model derivation of PMI patients. Single-center data served for external validation. There were 571 and 182 AKI patients in the training set (n = 937) and external validation set (n = 292) cohorts, respectively. Finally, a 7-variable model consisting of: Sequential Organ Failure Assessment (SOFA) score, coronary artery bypass grafting (CABG), ICU stay time, loop diuretics, estimated glomerular filtration rate (eGFR) HCO3- and Albumin was developed, achieving an AUC of 0.85 (95% CI: 0.83-0.88) in the training set. External validation also confirmed model robustness. This model may assist clinicians in the early identification of patients at elevated risk for PMI. Further validation is warranted before clinical application.

Catalytic hydrogenation of olefins by a multifunctional molybdenum-sulfur complex.

Exploration of molybdenum complexes as homogeneous hydrogenation catalysts has garnered significant attention, but hydrogenation of unactivated olefins under mild conditions are scarce. Here, we report the synthesis of a molybdenum complex, [Cp*Mo(Ph2PC6H4S-CH = CH2)(Py)]+ (2), which exhibits intriguing reactivity toward C2H2 and H2 under ambient pressure. This vinylthioether complex showcases efficient catalytic activity in the hydrogenation of various aromatic and aliphatic alkenes, demonstrating a broad substrate scope without the need for any additives. The catalytic pathway involves an uncommon oxidative addition of H2 to the cationic Mo(II) center, resulting in a Mo(IV) dihydride intermediate. Moreover, complex 2 also shows catalytic activity toward C2H2, leading to the production of polyacetylene and the extension of the vinylthioether ligand into a pendant triene chain.

Design of in vitro biomimetic experimental system and simulation analysis for transvascular transport of nano-preparation.

Recently, the enhanced penetration and retention (EPR) effect of nano-preparations has been questioned. Whether the vascular endothelial cell gap (VECG) is the main transport pathway of nano-preparations has become a hot issue at present. Therefore, we propose an in vitro biomimetic experimental system that demonstrates the transvascular transport of nano-preparation. Based on the tumor growth process, the experimental system was used to simulate the change process of abnormal factors (vascular endothelial cell gap and interstitial fluid pressure (IFP)) in the tumor microenvironment. The influence of change in the abnormal factors on the enhanced penetration and retention effect of nano-preparation was explored, and simulation verification was performed. The results show that when the interstitial fluid pressure is close to the vascular fluid pressure (VFP), the transport of nano-preparation is obstructed, resulting in the disappearance of enhanced penetration and retention effect of the nano-preparation. This indicates that the pressure gradient between vascular fluid pressure and interstitial fluid pressure determines whether the enhanced penetration and retention effect of nano-preparations can exist.

Relationship between social participation and life satisfaction in community-dwelling older adults: Multiple mediating roles of depression and cognitive function.

BACKGROUND: Numerous studies have explored the relationship between social participation, depression, cognitive function, and life satisfaction in community-dwelling older adults. However, the results of these studies were not consistent. Therefore, the in-depth excavation of the complex relationship mechanism between these four variables is limited. This study aims to explore whether depression and cognitive function act as the multiple mediators between social participation and life satisfaction in community-dwelling older adults. METHODS: This study used the meta-analytic structural equation modeling (MASEM) approach. Six databases were comprehensively searched to investigate the relationship between social participation, depression, cognitive function, and life satisfaction in community-dwelling older adults from inception to March 1, 2023. RESULTS: The analysis included 50 articles that reported 66 effect sizes (N = 161,854). The MASEM found the relationship between social participation and life satisfaction was mediated by depression [ß = 0.085, 95 % CI (0.053, 0.126)] and by cognitive function [ß = 0.015, 95 % CI (0.002, 0.033)], respectively. Depression and cognitive function also played multiple mediating roles between social participation and life satisfaction in community-dwelling older adults [ß = 0.005, 95 % CI (0.001, 0.012)]. CONCLUSIONS: There was not only a direct association between social participation and life satisfaction, but also an association through multiple mediating roles of depression and cognitive function in community-dwelling older adults. In the process of using diverse interventions to promote social participation in community-dwelling older adults, more attention should be paid to their psychological status and cognitive function to eliminate intrinsic barriers so as to improve life satisfaction effectively.

Transformation of Acetylene to Ethenylidene, Carbene, Acetylide, Vinyl, and Olefin Groups with Cp*Fe(1,2-Cy2PC6H4S).

Tautomerization of C2H2 at half-sandwich compound Cp*Fe(1,2-Cy2PC6H4S) exclusively produces an iron ethenylidene, Cp*Fe(=C=CH2)(1,2-Cy2PC6H4S) (2). Protonation of the ethenylidene causes nucleophilic attack of the Cα by sulfur, affording a sulfur-tethered carbene complex, [Cp*Fe=C(CH3)SC6H4PCy2]+ (3+). This Fischer-type carbene complex undergoes an unusual isomerization by migrating a hydrogen atom from the ß-CH3 group to the α-C, leading to the formation of an olefin complex [Cp*Fe(η4-CH=CH2SC6H4PCy2]+ (4+). Compound 2 also displays diverse redox reactivities. It transforms to a neutral acetylide ferric complex (5) when reacting with free radical scavengers and to a cationic vinyl complex [Cp*Fe(η3-C(=CH2)SC6H4PCy2]+ (6+) upon 1e- oxidation. The interconversion between the vinyl and acetylide complexes can be realized through protonation/deprotonation reactions.

Electrocatalytic Interconversions of CO2 and Formate on a Versatile Iron-Thiolate Platform.

Exploring bidirectional CO2/HCO2- catalysis holds significant potential in constructing integrated (photo)electrochemical formate fuel cells for energy storage and applications. Herein, we report selective CO2/HCO2- electrochemical interconversion by exploiting the flexible coordination modes and rich redox properties of a versatile iron-thiolate platform, Cp*Fe(II)L (L = 1,2-Ph2PC6H4S-). Upon oxidation, this iron complex undergoes formate binding to generate a diferric formate complex, [(L-)2Fe(III)(µ-HCO2)Fe(III)]+, which exhibits remarkable electrocatalytic performance for the HCO2--to-CO2 transformation with a maximum turnover frequency (TOFmax) ∼103 s-1 and a Faraday efficiency (FE) ∼92(±4)%. Conversely, this iron system also allows for reduction at -1.85 V (vs Fc+/0) and exhibits an impressive FE ∼93 (±3)% for the CO2-to-HCO2- conversion. Mechanism studies revealed that the HCO2--to-CO2 electrocatalysis passes through dicationic [(L2)-•Fe(III)(µ-HCO2)Fe(III)]2+ generated by unconventional oxidation of the diferric formate species taking place at ligand L, while the CO2-to-HCO2- reduction involves a critical intermediate of [Fe(II)-H]- that was independently synthesized and structurally characterized.

Lemniscular carbon nanohoops with contiguous conjugation from planar chiral [2.2]paracyclophane: influence of the regioselective synthesis on topological chirality.

We report herein the regioselective synthesis of all-carbon lemniscular nanohoops bis-po-CC and bis-pm-TC by the rational control of ring closures at the different positions of planar chiral tetrasubstituted [2.2]paracyclophane. Topological analyses reveal that bis-pm-TC is topologically chiral while bis-po-CC is topologically achiral. X-ray crystal analysis demonstrates that bis-pm-TC adopts a lemniscular conformation with a contiguous conjugation. CD and CPL measurements further reveal that the chiroptical properties of bis-pm-TC are obviously different from those of bis-po-CC due to their different topological chiralities.

Molecular Characterization and Function of the Nogo-66 Receptor (NgR1) Gene in the Chinese Tree Shrew.

BACKGROUND: Nogo-66 receptor (NgR1) is a glycosylphosphatidylinositol-linked cell surface receptor with high affinity for Nogo-66. The binding of Nogo-66 to NgR1 plays a key role in inhibiting neurite growth, limiting synaptic plasticity and mediating Mammalian Reovirus (MRV) infection. The Chinese tree shrew (Tupaia belangeri chinensis) is, a new and valuable experimental animal that is widely used in biomedical research. Although susceptible to MRV, little is known about tree shrew NgR1 and its role in MRV infection. METHODS: In this study, we cloned NgR1 form the Chinese tree shrew by RACE technology and analyzed its characteristics, spatial structure and its tissue expression. We also examined the expression pattern of NgR1 in the response of tree shrew primary nerve cells (tNC) to MRV1/TS/2011 infection. RESULTS: Tree shrew NgR1 was found to have a closer relationship to human NgR1 (90.34%) than to mouse NgR1. Similar to the protein structure of human NgR1, the tree shrew NgR1 has the same leucine-rich repeat (LRR) domain structure that is capped by C-terminal and N-terminal cysteine-rich modules. The tree shrew NgR1 mRNAs were predominantly detected in the central nervous system (CNS), and tree shrew NgR1 can mediate infection by MRV1/TS/2011. CONCLUSIONS: Taken together, these results help to elucidate the function of NgR1 and provide a basis for using the tree shrew as an animal model for studies of the nervous system and infectious diseases.

Advances in Mechanical Properties of Hydrogels for Cartilage Tissue Defect Repair.

Numerous factors, such as degeneration and accidents, frequently cause cartilage deterioration. Owing to the absence of blood vessels and nerves in cartilage tissue, the ability of cartilage tissue to heal itself after an injury is relatively low. Hydrogels are beneficial for cartilage tissue engineering owing to their cartilage-like structure and advantageous properties. Due to the disruption of its mechanical structure, the bearing capacity and shock absorption of cartilage are diminished. The tissue should possess excellent mechanical properties to ensure the efficacy of cartilage tissue repair. This paper discusses the application of hydrogels in the fields of cartilage repair, the mechanical properties of hydrogels used for cartilage repair, and the materials used for hydrogels in cartilage tissue engineering. In addition, the challenges faced by hydrogels and future research directions are discussed.

LAZY3 interacts with LAZY2 to regulate tiller angle by modulating shoot gravity perception in rice.

Starch biosynthesis in gravity-sensing tissues of rice shoot determines the magnitude of rice shoot gravitropism and thus tiller angle. However, the molecular mechanism underlying starch biosynthesis in rice gravity-sensing tissues is still unclear. We characterized a novel tiller angle gene LAZY3 (LA3) in rice through map-based cloning. Biochemical, molecular and genetic studies further demonstrated the essential roles of LA3 in gravity perception of rice shoot and tiller angle control. The shoot gravitropism and lateral auxin transport were defective in la3 mutant upon gravistimulation. We showed that LA3 encodes a chloroplast-localized tryptophan-rich protein associated with starch granules via Tryptophan-rich region (TRR) domain. Moreover, LA3 could interact with the starch biosynthesis regulator LA2, determining starch granule formation in shoot gravity-sensing tissues. LA3 and LA2 negatively regulate tiller angle in the same pathway acting upstream of LA1 to mediate asymmetric distribution of auxin. Our study defined LA3 as an indispensable factor of starch biosynthesis in rice gravity-sensing tissues that greatly broadens current understanding in the molecular mechanisms underlying the starch granule formation in gravity-sensing tissues, and provides new insights into the regulatory mechanism of shoot gravitropism and rice tiller angle.

Novel coatings for the continuous repair of human bone defects.

Bone defects are the second most common tissue grafts after blood. However, bone grafts face several problems, such as bone scaffolds, which have low bioactivity and are prone to corrosion. Much of the current research on bone scaffolds is focused on the mechanical aspects such as structure and strength. Surface modification of the bone scaffold is carried out in terms of the mechanical structure or structural design of the bone scaffold with reference to a bionic structure. However, with the development of mechanical designs, materials science, and medicine, many studies have reported that promoting bone growth by modifying the structure of the scaffold or coating is not possible. Therefore, the application of a bioactive coating to the surface of the bone scaffold is particularly important to generate a synergistic effect between the structure and active coating. In this article, we present several perspectives to improve the bioactivity of bone scaffolds, including corrosion resistance, loading of bioactive coatings or drugs on bone scaffolds, improved adhesion to the surface of the bone scaffolds, immune response modulation, and drawing on bionic structures during manufacturing.

Recyclable Carbon Cloth-Supported ZnO@Ag3PO4 Core-Shell Structure for Photocatalytic Degradation of Organic Dye.

The extensive use of organic dyes in industry has caused serious environmental problems, and photocatalysis is a potential solution to water pollution by organic dyes. The practical application of powdery photocatalysts is usually limited by the rapid recombination of charge carriers and difficulty in recycling. In this study, recyclable carbon cloth-supported ZnO@Ag3PO4 composite with a core-shell structure was successfully prepared by solvothermal treatment and subsequent impregnation-deposition. The as-prepared carbon cloth-supported ZnO@Ag3PO4 composite showed an improved photocatalytic activity and stability for the degradation of rhodamine B (RhB), a model organic dye, under visible light irradiation. The decomposition ratio of RhB reached 87.1% after exposure to visible light for 100 min, corresponding to a reaction rate constant that was 4.8 and 15.9 times that of carbon cloth-supported Ag3PO4 or ZnO alone. The enhanced performance of the composite can be attributed to the effectively inhibited recombination of photoinduced electron-hole pairs by the S-scheme heterojunction. The carbon fibers further promoted the transfer of charges. Moreover, the carbon cloth-supported ZnO@Ag3PO4 can be easily separated from the solution and repeatedly used, demonstrating a fair recyclability and potential in practical applications.