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Staged and geometry-adapted support for coal mine roadways under weak rock conditions: a numerical study
Abstract Controlling large deformation and instability of roadways in weak coal seams remains a critical challenge for safe and efficient mining operations. This study carried out an engineering filed observation firstly, and by setting three main roadways as research targets, it then proposed a series of supporting strategies for each of them. Numerical model was established using RockScience Phase2 finite element software to simulate the roadway’s mechanical response across all stages. Results indicated that the staged supporting strategy sequentially mitigated excavation-induced instability, roadway widening increased rib convergence, roadway heightening triggered additional roof sag. Supplementary grouting and rib bolts were testified as effective. Stress redistribution analysis revealed that grouting and bolts transferred concentrated stress from the weak coal seam to the stiff sandy mudstone. Additionally, a comparative analysis of a trapezoidal roadway variant validated the universality of the hybrid ‘liner + grouting’ support, which reduced yielded elements compared to unsupported conditions. This study demonstrates that phased support, tailored to excavation sequence and geological weakness, is an effective solution for roadway stability control, providing theoretical and technical references for similar weak rock mining projects.
Point‐of‐Care Diagnosis of Respiratory Viruses at Single‐Nucleotide Resolution with an Autocatalytic Rolling Circle Amplification System
Abstract Amid the continuing epidemic of respiratory viruses (RVs), clinical diagnostics need scalable technologies that enable point‐of‐care testing of pathogenic viruses with high accuracy and specificity. Here, we propose an autocatalytic rolling circle amplification (A‐RCA) system for the precise identification of RV genomic markers through sequence‐specific target recognition and synergistic catalytic signal amplification. The system, which we incorporated into lateral‐flow strip tests, exploits the cross‐stimulation between deoxyribonuclease (DNAzyme) self‐cleavage reaction and rolling circle amplification (RCA) to exponentially amplify the recognition of virus RNA sequences for the visually perceptible signal transduction. With superior amplification efficiency, this innovative autocatalysis‐driven artificial reaction system facilitates the rapid and robust detection of various viral RNAs, including those of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), influenza A, and influenza B, with single‐nucleotide resolution, offering a portable diagnostic platform for unsupervised self‐examination of different RVs and their mutants. This modular A‐RCA system is adaptable for multiplexed viral RNA profiling in clinical nasopharyngeal swabs and implemented on lateral‐flow strip assays for point‐of‐care (POC) diagnostics. The accessibility and programmability of the A‐RCA system make it a promising candidate for epidemiological surveillance in resource‐limited settings, facilitating the prompt response to emerging RVs and the prevention of viral pandemics.
Effectiveness of village doctors led cognitive behavioral therapy for COPD patients in a randomized controlled trial
Site‐Selective Peptide and Protein Functionalization with Cyclopropenium Cations
Abstract In the realm of organic chemistry, carbocations play a pivotal role as highly reactive intermediates in the synthesis of complex molecules. While cyclase enzymes construct terpenoid natural products through carbocation intermediates, the use of these electrophilic reactive species for peptide and protein bioconjugation in aqueous media remains unexplored. Herein, we disclose the discovery and development of a new chemical modification of peptides and proteins with aromatic cyclopropenium cations, selective at cysteine residues. The bioconjugation is fast, operationally simple, and occurs at low concentration in aqueous media, allowing for the installation of a tetrasubstituted cyclopropene ring with excellent site selectivity. Moreover, the cyclopropenylation is preferential to internal cysteines, thus complementing current methodologies for selective terminal cysteine bioconjugation. These studies further showcased the bioconjugates' utility as radical traps in a thiol–ene process, enabling the formation of cyclopropane‐linked conjugates.
Feasibility of the LvL UP digital lifestyle coaching intervention designed to prevent non-communicable diseases and common mental disorders
Abstract LvL UP is a smartphone-based lifestyle coaching intervention aimed at improving health behaviours, mental well-being, and preventing noncommunicable diseases and common mental disorders. It features a ‘talk and tools’ approach, combining automated health literacy coaching via conversational agent with digital tools such as journaling, life hacks, and slow-paced breathing exercises. An ‘in-the-wild’ mixed-methods study was conducted in Singapore to evaluate LvL UP’s feasibility and acceptability to inform a future definitive trial. The app was available on iOS and Android from March to August 2023 and was promoted through online and offline strategies. Data collection included in-app surveys, usage metrics, and interviews, summarised using descriptive statistics and template analysis. The app was downloaded 307 times. Data from 99 active users were analysed. Most users were female and aged 21–35 years with mild to moderate vulnerabilities in physical activity, diet, and depressive symptoms. Engagement was highest during the first eight days, with 9% remaining engaged for up to 50 days. Users rated technology acceptance highly, finding the app enjoyable, easy to use, and informative. Suggested improvements included streamlined onboarding, fixing bugs, shortening dialogues, and adding rewards. The findings support LvL UP’s feasibility and have informed enhancements for future trials.
Revealing Pathway Complexity in Host–Guest Binding: Allosteric Regulation and Temporal Chiral Inversion During Complexation of Naphtho[2,2]urils
Abstract Studies on pathway complexity in supramolecular polymerization have uncovered intriguing kinetic behaviors, though these are not directly transferable to host–guest systems. Here, we report unprecedented chiral inversion kinetics in a host–guest complexation process, arising from the coupling of sequential binding and conformational interconversion. Naphtho[n,n]urils (NGU[n,n]), constructed by alternating glycoluril and naphthyl units, were synthesized via a one‐pot three‐component condensation, yielding hybrid architectures with well‐defined cavities. In NGU[2,2], the two naphthyl units adopt either S P or R P planar chiral conformations, giving rise to interconvertible racemic and meso conformers. NGU[2,2] binds chiral amino acid derivatives stepwise through hydrogen bonding and cation–dipole interactions, forming 1:1 and 1:2 complexes. Complexation shifts the equilibrium between racemic and meso conformers, inducing a circular dichroism (CD) response. Notably, the transition from the 1:1 to the 1:2 complex triggers an inversion of conformational preference in NGU[2,2], representing a unique case of chiral allosteric regulation. Furthermore, temporal inversion of the CD signal was observed upon mixing NGU[2,2] with the guest, displaying a transient overshoot and sign reversal. This kinetic behavior originates from the interplay between binding dynamics and conformational interconversion, with the meso conformer playing a central role.
Room-temperature photoluminescence in monocarboxylate-protected silver nanoclusters via steric hindrance-induced interfacial structure locking
Chromatin remodeling factor BAF155 coordinates oligodendroglial-neuronal communications linked to regional myelination and autism-like behavioral deficits in mice
Resolving forebrain developmental organisation by analysis of differential growth patterns
Abstract The forebrain is the most complex region of the vertebrate central nervous system, and its developmental organisation is controversial. We fate-mapped the embryonic chick anterior neural tube and built a 4D model of brain growth. We reveal modular patterns of anisotropic growth, ascribed to progenitor regions through multiplex hybridisation chain reaction. Morphogenesis is dominated by directional growth towards the eye, more isometric expansion of the prethalamus and dorsal telencephalon, and anterior movement of ventral cells into the hypothalamus. Comparative gene expression analysis and cell mixing experiments suggest the existence of a contiguous transverse boundary region, encompassing the zona limitans intrathalamica and retromammillary hypothalamus, that divides the anterior and posterior forebrain, and becomes distorted at the base of the zona limitans intrathalamica . Fate conversion experiments indicate that the hypothalamus is topologically tripartite, lying ventral to the telencephalon, prethalamus and zona limitans intrathalamica . Our findings challenge the widely accepted prosomere model of forebrain organisation, do not support a segmented anterior forebrain, and instead suggest a ‘tripartite hypothalamus’ model.
Targeted antisense oligonucleotide treatment rescues developmental alterations in spinal muscular atrophy organoids
HIF-1α-mediated feedback prevents TOR signalling from depleting oxygen supply and triggering stress during normal development
Abstract Growth deceleration before growth termination is a universal feature of growth during development. Transcriptomics analysis reveals that during their two-day period of growth deceleration, wing imaginal discs of Drosophila undergo a progressive metabolic shift from oxidative phosphorylation towards glycolysis. Ultra-sensitive reporters of HIF-1α stability and activity show that imaginal discs become increasingly hypoxic during development in normoxic conditions, suggesting that limiting oxygen supply could underlie growth deceleration. We confirm the expectation that rising levels of HIF-1α dampen TOR signalling activity through transcriptional activation of REDD1. Conversely, excess TOR leads, in a tissue-size-dependent manner, to hypoxia, which boosts HIF-1α levels and activity. Thus, HIF-1α mediates a negative feedback loop whereby TOR signalling triggers hypoxia, which in turn reduces TOR signalling. Abrogation of this feedback by Sima/HIF-1α knockdown leads to cellular stress, which is alleviated by reduced TOR signalling or a modest increase in environmental oxygen. We conclude that Sima/HIF-1α prevents TOR-mediated growth from depleting local oxygen supplies during normal development.
Deep Mutational Scanning of FDX1 Identifies Key Structural Determinants of Lipoylation and Cuproptosis
Abstract Cuproptosis is a recently described form of regulated cell death triggered by ionophore-induced copper (Cu) overload in mitochondria. It is critically dependent on ferredoxin 1 (FDX1), a mitochondrial iron-sulfur cluster containing protein that acts as an electron shuttle. FDX1 reduces ionophore-bound Cu(II) to Cu(I), thereby triggering its release, and promotes mitochondrial protein lipoylation, which is directly targeted by the released copper to drive cell death. Despite the pivotal role of FDX1 in cuproptosis, the structural determinants underlying its distinct functions remain unclear. To address this, we performed deep mutational scanning on FDX1 and find that two conserved solvent-exposed residues, D136 and D139, on alpha helix 3 are essential for both cuproptosis and lipoylation. Charge-reversal mutations at these positions abolish FDX1’s ability to induce cuproptosis and support lipoylation in cells, despite retaining full enzymatic activity in vitro. Guided by structural and genomic analyses, we further identify dihydrolipoamide dehydrogenase (DLD), the E3 subunit of lipoylated complexes as an alternative FDX1 reductase both in cells and in vitro. Together, these findings establish the acidic alpha helix 3 of FDX1 as a critical interface for its upstream regulation and suggest that FDX1’s roles in cuproptosis and in lipoylation are both structurally and functionally linked.
Vibrissae-inspired vision-based magnetic-actuated whisker
Autophagic extracellular vesicles (AEVs) are distinct from exosomes and play crucial roles in viral infections
Late-stage adenine N6-alkylation of nucleos(t)ides and oligonucleotides via photoredox and copper co-catalytic decarboxylative C(sp3)–N coupling
Breaking dense integration limits: inverse-designed lithium niobate multimode photonic circuits
Restoration of PKM1 improves functional maturation of human stem-cell derived-β cell by regulating PEP metabolism
Epitaxial growth of wafer-scale 2D superconductor single crystals by metal-organic chemical vapor deposition
Effectiveness of nirmatrelvir/ritonavir and molnupiravir in reducing the risk of short-term and long-term cardiovascular complications of COVID-19: a target trial emulation study
Abstract While treatment with nirmatrelvir/ritonavir or molnupiravir is effective in lowering the rate of severe COVID-19, the effectiveness of these antivirals in reducing the risk of cardiovascular outcomes, especially among the hospitalized population, remains largely unknown. In this study, we assessed the real-world effectiveness of nirmatrelvir/ritonavir and molnupiravir on short- and long-term cardiovascular complications of COVID-19 using a target trial emulation design. Two target trials of COVID-19 antivirals were emulated by using a territory-wide, population-based, retrospective cohort of hospitalized patients in Hong Kong. Nine cardiovascular outcomes were evaluated in both short-term (day 0–21) and long-term (day 22–365) post-SARS-CoV-2 infection. Compared with the control group, the use of nirmatrelvir/ritonavir was associated with a significantly lower one-year risk of cardiovascular mortality, composite cardiovascular complications, major adverse cardiac events, cerebrovascular disorders, dysrhythmia, ischemic heart disease, and other cardiac disorders following infection. Molnupiravir use was associated with a short-term risk reduction in cardiovascular complications, but only a marginal risk reduction in long-term cardiovascular mortality among other complications. This study demonstrated the effectiveness of nirmatrelvir/ritonavir in reducing the risks of short- and long-term cardiovascular complications following a SARS-CoV-2 infection among the hospitalized population. Our findings suggested health-related benefits of prescribing nirmatrelvir/ritonavir over molnupiravir against severe cardiovascular post-acute sequelae of COVID-19 in the long term.