Ultrafast distant wound response is essential for whole-body regeneration.

Injury induces systemic responses, but their functions remain elusive. Mechanisms that can rapidly synchronize wound responses through long distances are also mostly unknown. Using planarian flatworms capable of whole-body regeneration, we report that injury induces extracellular signal-regulated kinase (Erk) activity waves to travel at a speed 10-100 times faster than those in other multicellular tissues. This ultrafast propagation requires longitudinal body-wall muscles, elongated cells forming dense parallel tracks running the length of the organism. The morphological properties of muscles allow them to act as superhighways for propagating and disseminating wound signals. Inhibiting Erk propagation prevents tissues distant to the wound from responding and blocks regeneration, which can be rescued by a second injury to distal tissues shortly after the first injury. Our findings provide a mechanism for long-range signal propagation in large, complex tissues to coordinate responses across cell types and highlight the function of feedback between spatially separated tissues during whole-body regeneration.

Expansion spatial transcriptomics.

Capture array-based spatial transcriptomics methods have been widely used to resolve gene expression in tissues; however, their spatial resolution is limited by the density of the array. Here we present expansion spatial transcriptomics to overcome this limitation by clearing and expanding tissue prior to capturing the entire polyadenylated transcriptome with an enhanced protocol. This approach enables us to achieve higher spatial resolution while retaining high library quality, which we demonstrate using mouse brain samples.

Pregnant outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer. / æŠ—ç€ä¸ç‚¹æŠ—ä½“é˜³æ€§æ‚£è€ ä½“å¤–å—ç²¾ç»“å±€åˆ†æž.

OBJECTIVES: To analyze the pregnant outcomes in patients with positive anti-centromere antibody (ACA) receiving in vitro fertilization (IVF) -embryo transfer (ET) and natural conception. METHODS: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received in vitro fertilization-embryo transfer therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnant outcomes were analyzed using self-matching analysis. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. RESULTS: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the double pronuclei rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immunosuppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant difference in miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. CONCLUSIONS: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Milletdb: a multi-omics database to accelerate the research of functional genomics and molecular breeding of millets.

Millets are a class of nutrient-rich coarse cereals with high resistance to abiotic stress; thus, they guarantee food security for people living in areas with extreme climatic conditions and provide stress-related genetic resources for other crops. However, no platform is available to provide a comprehensive and systematic multi-omics analysis for millets, which seriously hinders the mining of stress-related genes and the molecular breeding of millets. Here, a free, web-accessible, user-friendly millets multi-omics database platform (Milletdb, http://milletdb.novogene.com) has been developed. The Milletdb contains six millets and their one related species genomes, graph-based pan-genomics of pearl millet, and stress-related multi-omics data, which enable Milletdb to be the most complete millets multi-omics database available. We stored GWAS (genome-wide association study) results of 20 yield-related trait data obtained under three environmental conditions [field (no stress), early drought and late drought] for 2 years in the database, allowing users to identify stress-related genes that support yield improvement. Milletdb can simplify the functional genomics analysis of millets by providing users with 20 different tools (e.g., 'Gene mapping', 'Co-expression', 'KEGG/GO Enrichment' analysis, etc.). On the Milletdb platform, a gene PMA1G03779.1 was identified through 'GWAS', which has the potential to modulate yield and respond to different environmental stresses. Using the tools provided by Milletdb, we found that the stress-related PLATZs TFs (transcription factors) family expands in 87.5% of millet accessions and contributes to vegetative growth and abiotic stress responses. Milletdb can effectively serve researchers in the mining of key genes, genome editing and molecular breeding of millets.

Synthesis of Polycyclic 3,3'-Biindoles via AgOTf-Catalyzed Nucleophilic Addition and Cycloisomerization.

A method for the rapid synthesis of polycyclic 3,3'-biindole derivatives has been developed through AgOTf-catalyzed nucleophilic addition and cycloisomerization processes. The cascade reaction employs readily accessible indoles and their N-2-formylphenyl derivatives and provides functionalized polycyclic 3,3'-biindoles in moderate to good yields under mild conditions. This reaction is highly efficient and takes only several minutes (∼5 min). Notably, the method is also highlighted by a Selectfluor-mediated oxidation reaction that quickly generates the oxindole derivatives.

Electrochemical Cyclization of Alkynyl Enaminones: Controllable Synthesis of Indeno[1,2-c]pyrroles or Indanones.

We report an electrochemical intramolecular [3 + 2] cyclization of alkynyl enaminones in a user-friendly undivided cell under constant current conditions without an oxidant and catalyst, and indeno[1,2-c]pyrrole derivatives could be obtained in good to excellent yields. Notably, preliminary substituent-controlled selective transformation is also achieved under electrocatalysis alone, and indeno[1,2-c]pyrrole (R4 ≠ H) or indanone derivatives (R4 = H) could be prepared directly under electrocatalysis without adding a base and heating process.

Oxamate Attenuates Glycolysis and ER Stress in Silicotic Mice.

Glycolysis and ER stress have been considered important drivers of pulmonary fibrosis. However, it is not clear whether glycolysis and ER stress are interconnected and if those interconnections regulate the development of pulmonary fibrosis. Our previous studies found that the expression of LDHA, a key enzyme involved in glycolysis, was increased in silica-induced macrophages and silicotic models, and it was closely related to silicosis fibrosis by participating in inflammatory response. However, whether pharmacological inhibition of LDHA is beneficial to the amelioration of silicosis fibrosis remains unclear. In this study, we investigated the effects of oxamate, a potent inhibitor of LDHA, on the regulation of glycolysis and ER stress in alveolar macrophages and silicotic mice. We found that silica induced the upregulation of glycolysis and the expression of key enzymes directly involved in ER stress in NR8383 macrophages. However, treatment of the macrophages and silicotic mice with oxamate attenuated glycolysis and ER stress by inhibiting LDHA, causing a decrease in the production of lactate. Therefore, oxamate demonstrated an anti-fibrotic role by reducing glycolysis and ER stress in silicotic mice.

Transient Stabilization Effect of CO2 in the Electrochemical Hydrogenation of Azo Compounds and the Reductive Coupling of α-Ketoesters.

The carbon dioxide (CO2 ) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α-ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.

Key role of exopolysaccharide on di-butyl phthalate adsorbing by Lactobacillus plantarum CGMCC18980.

Plasticizers belong to hormone-like substances existing widely in the environment. According to the Environmental Protection Agency of China, they are considered to be the fourth class of toxic chemicals due to their harmful effects on normal endocrine system in human bodies. In the recent published work of our lab, Lactobacillus plantarum CGMCC18980 (strain P1) could reduce the toxicity of di-butyl phthalate (DBP) in rats effectively. The purpose of this study is to further explore the adsorption mechanism of di-butyl phthalate to L. plantarum CGMCC18980, based on optimizing the adsorption conditions. As a consequence, the adsorption effect of L. plantarum CGMCC18980 attributed to relationships between exopolysaccharide, membrane protein, and the cell wall. Experimental results demonstrated that exopolysaccharide and the cell wall were devoted to DBP binding. An obvious adsorption layer was observed outside of L. plantarum CGMCC18980 through scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) results showed that the functional groups involved in adsorption were mainly C=O, C-N, and C-O, which related to lipids and polysaccharides. Zeta potential analysis indicated that DBP adsorption had no significant relationship with surface charge. These results revealed that exopolysaccharide may be the key factor of strain CGMCC18980 in DBP adsorption. KEY POINTS: • Lactobacillus plantarum CGMCC18980 has the ability to adsorb di-butyl phthalate, reaching to 58.63%. • Exopolysaccharide is considered to play a key role in adsorption process. • Membrane protein, cell wall, and surface charge do not contribute to adsorption.

Assembly of Two Self-Interpenetrating Metal-Organic Frameworks Based on a Trigonal Ligand: Syntheses, Crystal Structures, and Properties.

Two self-interpenetrating metal-organic frameworks (MOFs) 1 and 2 were designed and constructed through the coordination self-assembly of transition metal nodes and a trigonal ligand. They both exhibit interesting three-dimensional constructions with the 1 + 2 self-locked mode. Because of the outstanding moisture susceptibility and luminescence property, MOF 1 has a potential detectability toward nitrofurantoin (NFT) in water. More importantly, MOF 1 can efficiently monitor NFT in bovine serum. Taking into account of Lewis basic sites in the skeleton, MOF 2 can be implemented as an outstanding heterogeneous catalyst for the Knoevenagel reaction. Furthermore, they both reveal excellent circularity and an application effect for five cycles.

Phase transitions in mutualistic communities under invasion.

Predicting the outcome of species invasion in ecosystems is challenging due to the non-equilibrium nature of the transitions that occur during invasion events. This limits the accuracy of classical ecological models that are typically fit to equilibrium conditions. Here, we address this limitation by solving for the transition dynamics of a cross-feeding community along an analytically tractable manifold defined by the system carrying capacity. We find that continuous changes in invader characteristics and environmental conditions induce discontinuous transitions in the invasion outcomes, resembling phase transitions in physical systems. These sharp transitions are emergent properties of species-resource interactions and relate directly to the extent of overlap in the growth strategy of competing species, with first and second order transitions resulting from complete and partial overlap, respectively. Moreover, we demonstrate that these phase transitions can be modulated by environmental variations to organize species in space.

Horizontal gene transfer can help maintain the equilibrium of microbial communities.

Horizontal gene transfer and species coexistence are two focal points in the study of microbial communities. Yet, the evolutionary advantage of horizontal gene transfer has not been well understood and is constantly being debated. Here we propose a simple population dynamics model based on frequency-dependent genotype interactions to evaluate the influence of horizontal gene transfer on microbial communities. In particular, we examine the structural stability of coexistence (i.e., the capability of the system to maintain species coexistence in response to small changes in parameters), as well as the robustness (defined as the maximal degree of perturbation the system can sustain around a stable coexistence steady state) of microbial communities. We find that both structural stability of coexistence and robustness of the microbial community are strongly affected by the gene transfer rate and direction. An optimal gene flux can stabilize the ecosystem, helping it recover from disturbance and maintain the species coexistence.

Phase Transition and Second Harmonic Generation in Thiophosphates Ag2Cd(P2S6) and AgCd3(PS4)S2 Containing Two Second-Order Jahn-Teller Distorted Cations.

Two new phases in the Ag-Cd-P-S system containing two second-order Jahn-Teller (SOJT) distorted d10 cations (Cd2+ and Ag+), namely, Ag2Cd(P2S6) (1) and AgCd3(PS4)S2 (2), are obtained via medium-temperature solid-state synthesis. Compound 1 exhibits a two-dimensional layered structure and undergoes a first-order structural phase transition at approximately 280 °C. This outcome can be ascribed to the significant mismatch in the expansion coefficients between Cd-S (Ag-S) and P-P (P-S) bonds evaluated through bond valence theory. The three-dimensional non-centrosymmetric (NCS) framework of 2 is constructed by two types of tetrahedral layers consisting of corner-shared CdS4, AgS4, and PS4 tetrahedra. Compound 2 exhibits second harmonic generation (SHG) intensity of 0.45 times that of commercial AgGaS2 (AGS) at a laser irradiation of 1.85 µm and an optical band gap of 2.56 eV, and no intrinsic vibrational absorption of chemical bonds is observed in the range of 2.5-18.2 µm. Both phase transition in 1 and SHG properties in 2 are closely related to the SOJT distorted d10 cations and diverse phosphorus-sulfur polyanions (PaSb)n-, which together can easily result in NCS distorted structures and interesting properties.

Thiophosphates Containing Ag+ and Lone-Pair Cations with Interchiral Double Helix Show Both Ionic Conductivity and Phase Transition.

Quaternary metal thiophosphates containing second-order Jahn-Teller distorted d10 Ag+ and lone-pair cations, Ag3Bi(PS4)2 (1), Ag7Sn(PS4)3 (2), and Ag7Pb(PS4)3 (3), were obtained by solid-state synthesis. The structural frameworks of 2 and 3 feature an infinite 1-D interchiral double helix ∞1(Ag3P2S11), which is rare in inorganic compounds. Compound 3 undergoes a significant first-order structural phase transition from monoclinic to hexagonal at ∼204 °C. This can be ascribed to the significant mismatch in the expansion coefficients between Pb-S (Ag-S) and P-S bonds evaluated by bond valence theory. The three compounds are Ag+ ionic conductors, and Ag+ ion migration pathways are proposed by calculating maps of low bond valence mismatch. Moreover, the optical properties of the three compounds were studied, and electronic structure calculations were performed. The combination of second-order Jahn-Teller distorted d10 cation and lone-pair cation provides a new strategy to explore new metal thiophosphates with interesting structures and promising properties.

Syntheses, Structures, and Nonlinear Optical Properties of Two Sulfides Na2In2MS6 (M = Si, Ge).

The first two new Na-containing sulfides Na2In2MS6 (M = Si (1), Ge (2)) in the Na2Q-B2Q3-CQ2 (B = Ga, In; C = Si, Ge, Sn; Q = S, Se) system were prepared for the first time through conventional high-temperature solid-state reaction. They are isostructural with space group Cc (No. 9) in monoclinic phases and feature three-dimensional frameworks built by the (∞)¹[In2MS6]²â» (M = Si, Ge) chains through corner-sharing InS4 tetrahedra and MS4 (M = Si, Ge) tetrahedra, with Na⁺ cation located in the cavities. They display moderate second harmonic generation (SHG) conversion efficiencies compared with commercial AgGaS2, with phase-matching behavior at 1800 nm and laser-induced damage thresholds 6.9 and 4.0 times higher than that of AgGaS2, respectively. Therefore, the output SHG intensities of 1 and 2 will be ∼4.3 and 4.0 times larger than that of AgGaS2, when the intensity of incident laser increased to close the damage energy of 1 and 2, indicating their potential for high-power nonlinear optical application.

Syntheses, structures, and nonlinear-optical properties of metal sulfides Ba2Ga8MS16 (M = Si, Ge).

Two new metal sulfides, Ba(2)Ga(8)MS(16) (M = Si, Ge), have been synthesized by high-temperature solid-state reactions. They are isostructural and crystallize in the noncentrosymmetric space group P6(3)mc (No. 186) with a = 10.866(5) Å, c = 11.919(8) Å, and z = 2 for Ba(2)Ga(8)SiS(16) (1) and a = 10.886(8) Å, c = 11.915(3) Å, and z = 2 for Ba(2)Ga(8)GeS(16) (2). Their three-dimensional frameworks are constructed by corner-sharing mixed (Ga/M)S(4) (M = Si, Ge) and pure GaS(4) tetrahedra, with Ba(2+) cations filling in the tunnels. Compounds 1 and 2 are transparent over 0.42-20 µm and have wide band gaps of around 3.4 and 3.0 eV, respectively. Polycrystalline 2 displays strong nonlinear second-harmonic-generation (SHG) intensities that are comparable to that of the benchmark AgGaS(2) (AGS) with phase-matching behavior at a laser irradiation of 1950 nm. Of particular interest, compound 2 also possesses a high powder laser-induced damage threshold of ∼22 times that of AGS. The alternate stacking of the mixed (Ga/M)S(4) (M = Si, Ge) tetrahedral layer with the pure GaS(4) tetrahedral layer along the c axis and the alignment of these two types of tetrahedra in the same direction may be responsible for the large SHG signals observed.

Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death.

Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases.

Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway.

Oxidative damage induced granulosa cells (GCs) apoptosis was considered as a significant cause of compromised follicle quality, antioxidants therapy has emerged as a potential method for improving endometriosis pregnancy outcomes. Here, we found that GCs from endometriosis patients show increased oxidative stress level. Methyl 3,4-dihydroxybenzoate (MDHB), a small molecule compound that is extracted from natural plants, reversed tert-butyl hydroperoxide (TBHP) induced GCs oxidative damage. Therefore, the aim of this study was to assess the protective effect of MDHB for GCs and its potential mechanisms. TUNEL staining and immunoblotting of cleaved caspase-3/7/9 showed MDHB attenuated TBHP induced GCs apoptosis. Mechanistically, MDHB treatment decreased cellular and mitochondria ROS production, improved the mitochondrial function by rescuing the mitochondrial membrane potential (MMP) and ATP production. Meanwhile, MDHB protein upregulated the expression of vital antioxidant transcriptional factor Nrf2 and antioxidant enzymes SOD1, NQO1 and GCLC to inhibited oxidative stress state, further beneficial to oocytes and embryos quality. Therefore, MDHB may represent a potential drug candidate in protecting granulosa cells in endometriosis, which can improve pregnancy outcomes for endometriosis-associated infertility.

DYT-TOR1A dystonia: an update on pathogenesis and treatment.

DYT-TOR1A dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal movements. It is a severe genetic form of dystonia caused by mutations in the TOR1A gene. TorsinA is a member of the AAA + family of adenosine triphosphatases (ATPases) involved in a variety of cellular functions, including protein folding, lipid metabolism, cytoskeletal organization, and nucleocytoskeletal coupling. Almost all patients with TOR1A-related dystonia harbor the same mutation, an in-frame GAG deletion (ΔGAG) in the last of its 5 exons. This recurrent variant results in the deletion of one of two tandem glutamic acid residues (i.e., E302/303) in a protein named torsinA [torsinA(△E)]. Although the mutation is hereditary, not all carriers will develop DYT-TOR1A dystonia, indicating the involvement of other factors in the disease process. The current understanding of the pathophysiology of DYT-TOR1A dystonia involves multiple factors, including abnormal protein folding, signaling between neurons and glial cells, and dysfunction of the protein quality control system. As there are currently no curative treatments for DYT-TOR1A dystonia, progress in research provides insight into its pathogenesis, leading to potential therapeutic and preventative strategies. This review summarizes the latest research advances in the pathogenesis, diagnosis, and treatment of DYT-TOR1A dystonia.

Fluorescence Polarization Assay Based on a New Recognition Motif QepA for the One-Step Detection of Fluoroquinolones in Eggs.

A recognition motif is vital in determining the specificity and sensitivity of the fluorescence polarization assay (FPA) for detecting chemical contaminants in food. Four candidates (Gyrase, GyrBA, TopIV, and QepA) were prepared for this study. The applicability of QepA was confirmed through DNA cleavage assay, inhibition effects, and mechanism investigations using molecular docking, compared to other counterparts. Finally, a novel FPA based on QepA and a CIP-FITC tracer for the detection of fluoroquinolones (FQs) in eggs was developed. The limits of detection (LODs) for eight fluoroquinolones ranged from 2.2 to 5.1 ng g-1, with enrofloxacin, danofloxacin, and difloxacin meeting the maximum residue limits (MRLs). The spiked recoveries ranged from 65.8 to 103.6% with coefficients of variation (CVs) of 5.4-12.8%. Therefore, a new recognition motif for FQs that did not belong to conventional antibodies was identified, and QepA-based FPA could be a potential tool for rapid, homogeneous, and sensitive monitoring of the residue of FQs in eggs.