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Programmed cell death (PCD) is a form of cell death distinct from accidental cell death (ACD) and is also referred to as regulated cell death (RCD). Typically, PCD signaling events are precisely regulated by various biomolecules in both spatial and temporal contexts to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS), although the role of PCD extends beyond the CNS. Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases. In this review, we summarize the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Additionally, we examine the key factors involved in these PCD signaling pathways and discuss the potential for their development as therapeutic targets and strategies. Therefore, therapeutic strategies targeting the inhibition or facilitation of PCD signaling pathways offer a promising approach for clinical applications in treating neurodegenerative diseases.

To monitor the biological function of H2S in real time, this investigation demonstrated the design and synthesis of a novel fluorescent probe integrated with cyanine and 2,4-dinitrophenol for the qualitative and quantitative detection of H2S. An NIR sensitive sensor (FS-HS-1) was provided with a straightforward process. Spectroscopy experiments elucidated that FS-HS-1 could selectively detect H2S in a PBS solution (containing 40% acetonitrile) with a 111-fold fluorescence enhancement at 715 nm (ex. 605 nm). The response towards NaHS occurred in less than 2 min, and the detection limit was confirmed to be as low as 4.47 ± 0.11 nmol/L. Furthermore, the probe is capable of monitoring changes in exogenous H2S concentrations within living cells with confocal and 2P imaging.

The innate immune system plays a critical role in the host response against pathogenic microbial infection. However, aberrant activation of the innate immune pathways is a characteristic feature of various diseases. Thus, targeted drugs must be developed based on the understanding of the innate immune signaling pathways. This study demonstrated that an allene small molecule (DWL-4-140) can efficiently and selectively exert regulatory effects on the stimulator of interferon genes (STING), resulting in the downregulation of DNA-induced interferon responses. Mechanistically, DWL-4-140 targeted the cyclized nucleotide-binding domain (CBD) of STING, inhibiting the assembly of the STING multimeric complex and the recruitment of downstream signaling mediators. In addition to downregulating the 10-carboxymethyl-9-acridanone-induced production of inflammatory factors, DWL-4-140 alleviated the pathological features of Trex1 deletion-induced lupus in mice. Thus, this study demonstrated that DWL-4-140 pharmacologically inhibits STING with potential therapeutic applications in auto-inflammatory diseases.

To address the potential biological relationship between reactive inorganic sulfur species (RISSs) and formaldehyde, the novel two-photon ratiometric RISSs probes (PH-RISSs) were synthesized practically with high selectivity and sensitivity toward RISSs and the related two-photon microscopic imaging assay was established which could be employed in the interpretation of the potential interaction between RISSs and formaldehyde. It was disclosed that the level of RISSs would raise toward formaldehyde and this behavior could be prohibited by CSE (cystathionine gamma lyase) inhibitor and reactive oxygen species (ROS) inhibitor, which indicated that formaldehyde could facilitate the metabolism of biothiols by CSE and this motivation of RISSs should be related with ROS intimately. Thus, RISSs might provide the critical biological compensation toward formaldehyde in a short term for living system and this two-photon ratiometric technique could be a practical tool to understand further the detailed interaction between aldehydes and RISSs in living systems.

In recent years, with the continuous progress of China's blast furnace ironmaking technology, the requirements for the grade of ore into the furnace have also increased. At present, the research on high-speed and low-silicon sintering technology has become a great progress in the development of sintering technology. The application of high-speed and low-silicon sintering can further improve the quality of the furnace, and achieve the purposes of iron lifting, silicon reduction, coke reduction and pig iron cost reduction. This technology is also of great significance for improving blast furnace smelting conditions and corresponding technical and economic indicators, and the corresponding state has called for the energy saving and consumption reduction of the ironmaking process. However, with the increase of iron grade in sintered ore, the content of SiO2 decreases, especially when the content of SiO2 is less than 5%, the liquid phase volume decreases during the sintering process, and the problems of insufficient bonding phase are bound to affect the strength and sintered ore, production and quality. Therefore, solving these problems has become an inexhaustible motive force for the continuous innovation and development of high-speed low-silicon sintering technology. This article is mainly a summary of the current development status of high-speed low-silicon sintering technology at home and abroad, as well as corresponding solutions based on actual production problems. At the same time, some ideas for the future development of the technology are becoming intelligent.

Stereocontrol of C–O bond formation from a carbon-based radical is very difficult due to the rapid inversion of the carbon radical. Here the authors present a method to form chiral esters from conjugated dienes with copper and chiral PyBox ligands, likely proceeding via an allylic radical.

One of the main challenges faced in food safety is the accumulation of toxic heavy metals from environmental sources, which can sequentially endanger human health when they are consumed. It is invaluable to establish a practical assay for the determination of heavy metals for food safety. Among the current detection methods, technology based on fluorescent probes, with the advantages of sensitivity, convenience, accuracy, cost, and reliability, has recently shown pluralistic applications in the food industry, which is significant to ensure food safety. Hence, this review systematically presents the recent progress on novel fluorescent probes in determining heavy metals for food safety over the past five years, according to fluorophores and newly emerging sensing cores, which could contribute to broadening the prospects of fluorescent materials and establishing more practical assays for heavy metal determinations.

Pellet quality including chemical composition, physical properties and metallurgical performance of three parts, its quality and mineral composition, properties and structure of the pellets has the close relation, studies show that the mineralogical micro structure and distribution of pellets had significant effects on the metallurgical properties, so the analysis and determination of pellets of mineral composition and micro structure is very important to improve the quality of pellets. Paper to pellets micro mineral as the research object, mainly studies the CNN and PCA two kinds of image processing algorithm, in the heart of the traditional model of CNN structure characteristics obtained by convolution PCA dimension reduction at a time, will be the main features of PCA to extract into the depth of the CNN learning, realize the mineral phase of shallow and deep information of the image to do effective fusion, in a larger extent, reflects the mineralogical characteristics, thus more intuitive response metallurgical properties. The location and alkalinity of the ore phase were identified by the extracted deep fusion feature, and the results were compared with those of the traditional CNN algorithm. It was found that the accuracy of location and alkalinity recognition of PCA and CNN coupling algorithm was 93.82% and 91.26%, respectively, which were higher than the accuracy of traditional CNN algorithm 92.73% and 88.93%, which verified the accuracy of PCA and CNN coupling model and its applicability in mineral phase recognition.

Abstract Gravitational shockwaves are insensitive to higher-curvature corrections in the action. Recent work found that the OPE coefficients of lowest-twist multi-stress-tensor operators, computed holographically in a planar black hole background, are insensitive as well. In this paper, we analyze the relation between these two limits. We explicitly evaluate the two-point function on a shockwave background to all orders in a large central charge expansion. In the geodesic limit, we find that the ANEC exponentiates in the multi-stress-tensor sector. To compare with the black hole limit, we obtain a recursion relation for the lowest-twist products of two stress tensors in a spherical black hole background, letting us efficiently compute their OPE coefficients and prove their insensitivity to higher curvature terms. After resumming the lowest-twist stress-tensors and analytically continuing their contributions to the Regge limit, we find a perfect agreement with the shockwave computation. We also discuss the role of double-trace operators, global degenerate states, and multi-stress-tensor conformal blocks. These holographic results suggest the existence of a larger universal structure in higher-dimensional CFTs.

Abstract First-quantized propagation in quantum gravitational AdS3 backgrounds can be exactly reconstructed using CFT2 data and Virasoro symmetry. We develop methods to compute the bulk-to-boundary propagator in a black hole microstate, ϕ L O L O H O H $$ \left\langle {\phi}_L{\mathcal{O}}_L{\mathcal{O}}_H{\mathcal{O}}_H\right\rangle $$ , at finite central charge. As a first application, we show that the semiclassical theory on the Euclidean BTZ solution sharply disagrees with the exact description, as expected based on the resolution of forbidden thermal singularities, though this effect may appear exponentially small for physical observers.

Bacterial pathogens are a major cause of infectious diseases in aquatic animals. The abuse of antibiotics in the aquatic industry has led to the proliferation of antibiotic resistance. It is therefore essential to develop more effective and safer strategies to increase the efficacy and extend the life span of the antibiotics used in aquaculture. In this study, we show that six aquaculture bacterial pathogens (i.e., Aeromonas hydrophila, Vibrio alginolyticus, Edwardsiella tarda, Streptococcus iniae, Vibrio harveyi, and Vibrio fluvialis) in the stationary phase can be rapidly killed after immersion in gentamicin- or neomycin-containing, ion-free solutions for a few minutes. Such hypoionic shock treatment enhances the bacterial uptake of gentamicin in an ATP-dependent manner. Importantly, we demonstrate, as a proof of concept, that gentamicin under hypoionic shock conditions can effectively kill A. hydrophila in vivo in a skin infection model of zebrafish (Danio rerio), completely curing the infected fish. Given that pathogenic bacteria generally adhere to the skin surface and gills of aquatic animals, our strategy is of potential significance for bacterial infection control, especially for small-scale economic fish farming and ornamental fish farming. Further, the combined treatment can be completed within 5 min with a relatively small volume of solution, thus minimizing the amount of residual antibiotics in both animals and the environment.

The S-shaped hydrofoil is often used in the design of reversible machinery due to its centrally symmetrical camber line. The objective of this paper is to study the influence of cloud cavitation on the flow structure and the unsteady characteristics of lift and drag around an S-shaped hydrofoil via experimental tests and numerical simulations. In the experimental component, the tests were carried out in a cavitation tunnel and a high-speed camera was used to record the cavitation details around the S-shaped hydrofoil with different cavitation numbers. The experimental results show that sheet cavitation gradually transforms into cloud cavitation with a decrease in the inlet cavitation number, the maximum cavity length increases faster after the occurrence of cloud cavitation, and the shedding cycle time of cloud cavitation gradually increases with a decrease in the inlet cavitation number. In the numerical component, the numerical results are in good agreement with the experimental data. The numerical results show that the movement of the re-entrant jet is the main factor for the formation of the cloud cavitation around the S-shaped hydrofoil. The shedding cloud cavity induces the U-shaped vortex structure around the S-shaped hydrofoil, and it produces a higher vorticity distribution around the cavity. The periodic motion of cloud cavity causes the unsteady fluctuation of the lift–drag coefficient of the S-shaped hydrofoil, and because of the unique pressure distribution characteristics of the S-shaped hydrofoil, the lift and drag coefficient appeared as two peaks in one typical cycle of cloud cavitation.

Summary: Numerous mammalian cells contain abundant Zn2+ in their secretory granules, yet available Zn2+ sensors lack the desired specificity and sensitivity for imaging granular Zn2+. We developed a fluorescent zinc granule indicator, ZIGIR, that possesses numerous desired properties for live cell imaging, including >100-fold fluorescence enhancement, membrane permeability, and selective enrichment to acidic granules. The combined advantages endow ZIGIR with superior sensitivity and specificity for imaging granular Zn2+. ZIGIR enables separation of heterogenous β cells based on their insulin content and sorting of mouse islets into pure α cells and β cells. In human islets, ZIGIR facilitates sorting of endocrine cells into highly enriched α cells and β cells, reveals unexpectedly high Zn2+ activity in the somatostatin granule of some δ cells, and uncovers variation in the glucagon content among human α cells. We expect broad applications of ZIGIR for studying Zn2+ biology and Zn2+-rich secretory granules and for engineering β cells with high insulin content for treating diabetes.

Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. As a single-chain ATP-independent nuclear proteasome activator, proteasome activator 200 (PA200) associates with 20S core particle to form proteasome complex that catalyzes polyubiquitin-independent degradation of acetylated histones, thus playing a pivotal role in DNA repair and spermatogenesis. Here, we present cryo-electron microscopy (cryo-EM) structures of the human PA200-20S complex and PA200 at 2.72 Å and 3.75 Å, respectively. PA200 exhibits a dome-like architecture that caps 20S and uses its C-terminal YYA (Tyr-Tyr-Ala) to induce the α-ring rearrangements and partial opening of the 20S gate. Our structural data also indicate that PA200 has two openings formed by numerous positively charged residues that respectively bind (5,6)-bisdiphosphoinositol tetrakisphosphate (5,6[PP]2-InsP4) and inositol hexakisphosphate (InsP6) and are likely to be the gates that lead unfolded proteins through PA200 and into the 20S. Besides, our structural analysis of PA200 found that the bromodomain (BRD)-like (BRDL) domain of PA200 shows considerable sequence variation in comparison to other human BRDs, as it contains only 82 residues because of a short ZA loop, and cannot be classified into any of the eight typical human BRD families. Taken together, the results obtained from this study provide important insights into human PA200-induced 20S gate opening for substrate degradation and the opportunities to explore the mechanism for its recognition of H4 histone in acetylation-mediated proteasomal degradation.

Abstract We investigate the quantum null energy condition (QNEC) in holographic CFTs, focusing on half-spaces and particular classes of states. We present direct, and in certain cases nonperturbative, calculations for both the diagonal and off-diagonal variational derivatives of entanglement entropy. In d ≥ 3, we find that the QNEC is saturated. We compute relations between the off-diagonal variation of entanglement, boundary relative entropy, and the bulk stress tensor. Strong subadditivity then leads to energy conditions in the bulk. In d = 2, we find that the QNEC is in general not saturated when the Ryu-Takayanagi surface intersects bulk matter. Moreover, when bulk matter is present the QNEC can imply new bulk energy conditions. For a simple class of states, we derive an example that is stronger than the bulk averaged null energy condition and reduces to it in certain limits.

Abstract We recently used Virasoro symmetry considerations to propose an exact formula for a bulk proto-field ϕ in AdS3. In this paper we study the propagator 〈ϕϕ〉. We show that many techniques from the study of conformal blocks can be generalized to compute it, including the semiclassical monodromy method and both forms of the Zamolodchikov recursion relations. When the results from recursion are expanded at large central charge, they match gravitational perturbation theory for a free scalar field coupled to gravity in our chosen gauge. We find that although the propagator is finite and well-defined at long distances, its perturbative expansion in GN=32c $$ {G}_N=\frac{3}{2c} $$ exhibits UV/IR mixing effects. If we nevertheless interpret 〈ϕϕ〉 as a probe of bulk locality, then when GNmϕ≪1 $$ {G}_{N{m}_{\phi }}\ll 1 $$ locality breaks down at the new short-distance scale σ∗∼GNRAdS34 $$ {\sigma}_{\ast}\sim \sqrt[4]{G_N{R}_{\mathrm{AdS}}^3} $$. For ϕ with very large bulk mass, or at small central charge, bulk locality fails at the AdS length scale. In all cases, locality ‘breakdown’ manifests as singularities or branch cuts at spacelike separation arising from non-perturbative quantum gravitational effects.

Abstract We use conformal symmetry to define an AdS3 proto-field ϕ as an exact linear combination of Virasoro descendants of a CFT2 primary operator O $$ \mathcal{O} $$. We find that both symmetry considerations and a gravitational Wilson line formalism lead to the same results. The operator ϕ has many desirable properties; in particular it has correlators that agree with gravitational perturbation theory when expanded at large c, and that automatically take the correct form in all vacuum AdS3 geometries, including BTZ black hole backgrounds. In the future it should be possible to use ϕ to probe bulk locality and black hole horizons at a non-perturbative level.

Abstract We analytically solve the conformal bootstrap equations in the Regge limit for large N conformal field theories. For theories with a parametrically large gap, the amplitude is dominated by spin-2 exchanges and we show how the crossing equations naturally lead to the construction of AdS exchange Witten diagrams. We also show how this is encoded in the anomalous dimensions of double-trace operators of large spin and large twist. We use the chaos bound to prove that the anomalous dimensions are negative. Extending these results to correlators containing two scalars and two conserved currents, we show how to reproduce the CEMZ constraint that the three-point function between two currents and one stress tensor only contains the structure given by Einstein-Maxwell theory in AdS, up to small corrections. Finally, we consider the case where operators of unbounded spin contribute to the Regge amplitude, whose net effect is captured by summing the leading Regge trajectory. We compute the resulting anomalous dimensions and corrections to OPE coefficients in the crossed channel and use the chaos bound to show that both are negative.

Abstract We chart the breakdown of semiclassical gravity by analyzing the Virasoro conformal blocks to high numerical precision, focusing on the heavy-light limit correspond-ing to a light probe propagating in a BTZ black hole background. In the Lorentzian regime, we find empirically that the initial exponential time-dependence of the blocks transitions to a universal t − 3 2 $$ t-\frac{3}{2} $$ power-law decay. For the vacuum block the transition occurs at t ≈ π c 6 h L $$ t\approx \frac{\uppi c}{6{h}_L} $$ , confirming analytic predictions. In the Euclidean regime, due to Stokes phenomena the naive semiclassical approximation fails completely in a finite region enclosing the ‘forbidden singularities’. We emphasize that limitations on the reconstruction of a local bulk should ultimately stem from distinctions between semiclassical and exact correlators.

Abstract The numerical conformal bootstrap is used to study mixed correlators in N $$ \mathcal{N} $$ = 1 superconformal field theories (SCFTs) in d = 4 spacetime dimensions. Systems of fourpoint functions involving scalar chiral and real operators are analyzed, including the case where the scalar real operator is the zero component of a global conserved current multiplet. New results on superconformal blocks as well as universal constraints on the space of 4D N $$ \mathcal{N} $$ = 1 SCFTs with chiral operators are presented. At the level of precision used, the conditions under which the putative “minimal” 4D N $$ \mathcal{N} $$ = 1 SCFT may be isolated into a disconnected allowed region remain elusive. Nevertheless, new features of the bounds are found that provide further evidence for the presence of a special solution to crossing symmetry corresponding to the “minimal” 4D N $$ \mathcal{N} $$ = 1 SCFT.

Abstract Aspects of black hole thermodynamics and information loss can be derived as a consequence of Virasoro symmetry. To bolster the connection between Virasoro conformal blocks and AdS3 quantum gravity, we study sl(2) Chern-Simons Wilson line networks and revisit the idea that they compute a variety of CFT2 observables, including Virasoro OPE blocks, exactly. We verify this in the semiclassical large central charge limit and to low orders in a perturbative 1/c expansion. Wilson lines connecting the boundary to points in the bulk play a natural role in bulk reconstruction. Because quantum gravity in AdS3 is rigidly fixed by Virasoro symmetry, we argue that sl(2) Wilson lines provide building blocks for background independent bulk reconstruction. In particular, we show explicitly that they automatically ‘know’ about the uniformizing coordinates appropriate to any background state.

Abstract One can obtain exact information about Virasoro conformal blocks by analytically continuing the correlators of degenerate operators. We argued in recent work that this technique can be used to explicitly resolve information loss problems in AdS3/CFT2. In this paper we use the technique to perform calculations in the small 1/c ∝ G N expansion: (1) we prove the all-orders resummation of logarithmic factors ∝ 1 c log z $$ \propto \frac{1}{c} \log\;z $$ in the Lorentzian regime, demonstrating that 1/c corrections directly shift Lyapunov exponents associated with chaos, as claimed in prior work, (2) we perform another all-orders resummation in the limit of large c with fixed cz, interpolating between the early onset of chaos and late time behavior, (3) we explicitly compute the Virasoro vacuum block to order 1/c 2 and 1/c 3 with external dimensions fixed, corresponding to 2 and 3 loop calculations in AdS3, and (4) we derive the heavy-light vacuum blocks in theories with N $$ \mathcal{N} $$ = 1, 2 superconformal symmetry.

Background: Fucoxanthin (FX), a xanthophyll pigment which occurs in marine brown algae with remarkable biological properties, has been proven to be safe for consumption by animals. Although FX has various pharmacological effects including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid, in vivo protective effect against sepsis has not been reported. In this study, we aimed at evaluation the efficacy of the FX in a model of sepsis mouse.Methods: FX was successfully isolated from Conticribra weissflogii ND-8 for the first time. The FX was identified by thin-layer chromatography (TLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and nuclear magnetic resonance (NMR). Animals were randomly divided into 9 groups, including Sham group (mouse received an intraperitoneal injection of normal saline 1.0 ml/kg), FX-treated (0.1–1.0 ml/kg), Lipopolysaccharide (LPS)-treated (20 mg/kg), FX+LPS-treated (0.1–10.0 mg/kg and 20 mg/kg, respectively), and urinastatin groups (104 U/kg). Nuclear factor (NF)-κB activation could be potential treatment for sepsis. NF-κB signaling components were determined by western-blotting. IL-6, IL-1β, TNF-α production, and NF-κB activation were evaluated by ELISA and immunofluorescent staining in vitro.Results: FX was found to decrease the expression of inflammatory cytokines including IL-6, IL-1β, and TNF-α, in a prophylactic manner in the LPS-induced sepsis mouse model. Meanwhile, FX significantly inhibits phosphorylation of the NF-κB signaling pathway induced by LPS at the cellular level and reduces the nuclear translocation of NF-κB. The IC50 for suppressing the expression of NF-κB was 11.08 ± 0.78 μM in the THP1-Lucia™ NF-κB cells. Furthermore, FX also inhibits the expression of inflammatory factors in a dose-dependent manner with the IC50 inhibition of IL-6 production was 2.19 ± 0.70 μM in Raw267.4 macrophage cells. It is likely that the molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as fucoxanthin, are interesting subjects to be used for treating sepsis.

Abstract Background Theaceae, comprising 300 + species, holds significance in biodiversity, economics, and culture, notably including the globally consumed tea plant. Stewartia gemmata, a species of the earliest diverging tribe Stewartieae, is critical to offer insights into Theaceae's origin and evolutionary history. Result We sequenced the complete organelle genomes of Stewartia gemmata using short/long reads sequencing technologies. The chloroplast genome (158,406 bp) exhibited a quadripartite structure including the large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs); 114 genes encoded 80 proteins, 30 tRNAs, and four rRNAs. The mitochondrial genome (681,203 bp) exhibited alternative conformations alongside a monocyclic structure: 61 genes encoding 38 proteins, 20 tRNAs, three rRNAs, and RNA editing-impacting genes, including ATP6, RPL16, COX2, NAD4L, NAD5, NAD7, and RPS1. Comparative analyses revealed frequent recombination events and apparent rRNA gene gains and losses in the mitochondrial genome of Theaceae. In organelle genomes, the protein-coding genes exhibited a strong A/U bias at codon endings; ENC-GC3 analysis implies selection-driven codon bias. Transposable elements might facilitate interorganelle sequence transfer. Phylogenetic analysis confirmed Stewartieae's early divergence within Theaceae, shedding light on organelle genome characteristics and evolution in Theaceae. Conclusions We studied the detailed characterization of organelle genomes, including genome structure, composition, and repeated sequences, along with the identification of lateral gene transfer (LGT) events and complexities. The discovery of a large number of repetitive sequences and simple sequence repeats (SSRs) has led to new insights into molecular phylogenetic markers. Decoding the Stewartia gemmata organellar genome provides valuable genomic resources for further studies in tea plant phylogenomics and evolutionary biology.