High-fidelity and high-speed wavefront shaping by leveraging complex media.

High-precision light manipulation is crucial for delivering information through complex media. However, existing spatial light modulation devices face a fundamental speed-fidelity tradeoff. Digital micromirror devices have emerged as a promising candidate for high-speed wavefront shaping but at the cost of compromised fidelity due to the limited control degrees of freedom. Here, we leverage the sparse-to-random transformation through complex media to overcome the dimensionality limitation of spatial light modulation devices. We demonstrate that pattern compression by sparsity-constrained wavefront optimization allows sparse and robust wavefront representations in complex media, improving the projection fidelity without sacrificing frame rate, hardware complexity, or optimization time. Our method is generalizable to different pattern types and complex media, supporting consistent performance with up to 89% and 126% improvements in projection accuracy and speckle suppression, respectively. The proposed optimization framework could enable high-fidelity high-speed wavefront shaping through different scattering media and platforms without changes to the existing holographic setups, facilitating a wide range of physics and real-world applications.

Zinc oxide nanoparticles induces cell death and consequently leading to incomplete neural tube closure through oxidative stress during embryogenesis.

The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn2+ they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn2+ played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.

Genetically Engineered Membrane-Coated Nanoparticles for Enhanced Prostate-Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration-Resistant Prostate Cancer.

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.

Single Atom Ag Bonding Between PF3T Nanocluster and TiO2 Leads the Ultra-Stable Visible-Light-Driven Photocatalytic H2 Production.

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO2 nanoparticle. With an optimized Ag loading (Ag/TiO2 = 0.5 wt%), the Ag atoms will uniformly disperse on TiO2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO2. These characteristics enable the high efficiency of H2 production to 16 580 µmol h-1 g-1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO2@PF3T), the H2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies.

The emerging role of herbal medicines in cancer by interfering with post-translational modification.

SIGNIFICANCE: Herbal medicines demonstrate clinical promise for cancer treatment. Protein post translational modifications (PTMs) regulate tumorigenesis and cancer progression. While PTMs contributing to cancer are well-studied, the precise mechanisms and defined targets of herbal medicines on PTM-associated carcinogenesis remain unclear. Hence, comprehensively understanding how PTMs regulate cancer hallmarks is crucial to elucidate the pharmacological mechanisms of herbal medicines for cancer treatment. RECENT ADVANCES: Advanced development in highly sensitive mass spectrometry (MS)-based techniques has helped utilize PTM-focused studies on cancers. Accumulating evidence has been achieved in laboratory to ascertain the biological mechanism of herbal medicines in cancer therapy. Implication of the strong association between cancer and PTM makes new perspective to comprehend the intricate dialogues between herbal medicines and cellular contexts. CRITICAL ISSUES: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating PTM implicated in cell signaling, apoptosis and transcriptional regulation function, and the possible cellular signaling, have provided important information about the mechanism of many herbal therapies. Continued optimization of proteomic strategies for PTM analysis in herbal medicines are also discussed. FUTURE DIRECTIONS: Rigorous evaluations of herbal medicines and the chemoproteomic strategies are necessary to explore the aberrant regulation of PTM dynamics contributed to the cancer development and herbal associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

A novel semi-flexible coaxial nozzle based on fluid dynamics effects and its self-centering performance study.

Coaxial nozzles are widely used to produce fibers with core-shell structures. However, conventional coaxial nozzles cannot adjust the coaxiality of the inner and outer needles in real-time during the fiber production process, resulting in uneven fiber wall thickness and poor quality. Therefore, we proposed an innovative semi-flexible coaxial nozzle with a dynamic self-centering function. This new design addresses the challenge of ensuring the coaxiality of the inner and outer needles of the coaxial nozzle. First, based on the principles of fluid dynamics and fluid-structure interaction, a self-centering model for a coaxial nozzle is established. Second, the influence of external fluid velocity and inner needle elastic modulus on the centering time and coaxiality error is analyzed by finite element simulation. Finally, the self-centering performance of the coaxial nozzle is verified by observing the coaxial extrusion process online and measuring the wall thickness of the formed hollow fiber. The results showed that the coaxiality error increased with the increase of Young's modulus E and decreased with the increase of flow velocity. The centering time required for the inner needle to achieve force balance decreases with the increase of Young's modulus ( E ) and fluid velocity ( v f ). The nozzle exhibits significant self-centering performance, dynamically reducing the initial coaxiality error from 380 to 60 µm within 26 s. Additionally, it can mitigate the coaxiality error caused by manufacturing and assembly precision, effectively controlling them within 8 µm. Our research provides valuable references and solutions for addressing issues such as uneven fiber wall thickness caused by coaxiality errors.

Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

De novo transcriptome profiling reveals the patterns of gene expression in plum fruits with bud mutations.

Bud mutation is a common technique for plant breeding and can provide a large number of breeding materials. Through traditional breeding methods, we obtained a plum plant with bud mutations (named "By") from an original plum variety (named "B"). The ripening period of "By" fruit was longer than that of "B" fruit, and its taste was better. In order to understand the characteristics of these plum varieties, we used transcriptome analysis and compared the gene expression patterns in fruits from the two cultivars. Subsequently, we identified the biological processes regulated by the differentially expressed genes (DEGs). Gene ontology (GO) analysis revealed that these DEGs were highly enriched for "single-organism cellular process" and "transferase activity". KEGG analysis demonstrated that the main pathways affected by the bud mutations were plant hormone signal transduction, starch and sucrose metabolism. The IAA, CKX, ARF, and SnRK2 genes were identified as the key regulators of plant hormone signal transduction. Meanwhile, TPP, the beta-glucosidase (EC3.2.1.21) gene, and UGT72E were identified as candidate DEGs affecting secondary metabolite synthesis. The transcriptome sequencing (RNA-seq) data were also validated using RT-qPCR experiments. The transcriptome analysis demonstrated that plant hormones play a significant role in extending the maturity period of plum fruit, with IAA, CKX, ARF, and SnRK2 serving as the key regulators of this process. Further, TPP, beta-glucosidase (EC3.2.1.21), and UGT72E appeared to mediate the synthesis of various soluble secondary metabolites, contributing to the aroma of plum fruits. The expression of BAG6 was upregulated in "B" as the fruit matured, but it was downregulated in "By". This indicated that "B" may have stronger resistance, especially fungal resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01472-3.

Evaluating three internal fixation techniques for Pauwels III femoral neck fractures via finite element analysis.

The selection of implants for fixing unstable femoral neck fractures (FNF) remains contentious. This study employs finite element analysis to examine the biomechanics of treating Pauwels type III femoral neck fractures using cannulated compression screws (3CS), biplane double-supported screw fixation (BDSF), and the femoral neck system (FNS). A three-dimensional model of the proximal femur was developed using computed tomography scans. Fracture models of the femoral neck were created with 3CS, BDSF, and FNS fixations. Von Mises stress on the proximal femur, fracture ends, internal fixators, and model displacements were assessed and compared across the three fixation methods (3CS, BDSF, and FNS) during the heel strike of normal walking. The maximum Von Mises stress in the proximal fragment was significantly higher with 3CS fixation compared to BDSF and FNS fixations (120.45 MPa vs. 82.44 MPa and 84.54 MPa, respectively). Regarding Von Mises stress distribution at the fracture ends, the highest stress in the 3CS group was 57.32 MPa, while BDSF and FNS groups showed 51.39 MPa and 49.23 MPa, respectively. Concerning implant stress, the FNS model exhibited greater Von Mises stress compared to the 3CS and BDSF models (236.67 MPa vs. 134.86 MPa and 140.69 MPa, respectively). Moreover, BDSF displayed slightly lower total displacement than 3CS fixation (7.19 mm vs. 7.66 mm), but slightly higher displacement than FNS (7.19 mm vs. 7.03 mm). This study concludes that BDSF outperforms 3CS fixation in terms of biomechanical efficacy and demonstrates similar performance to the FNS approach. As a result, BDSF stands as a dependable alternative for treating Pauwels type III femoral neck fractures.

Metatranscriptomics-guided genome-scale metabolic reconstruction reveals the carbon flux and trophic interaction in methanogenic communities.

BACKGROUND: Despite rapid advances in genomic-resolved metagenomics and remarkable explosion of metagenome-assembled genomes (MAGs), the function of uncultivated anaerobic lineages and their interactions in carbon mineralization remain largely uncertain, which has profound implications in biotechnology and biogeochemistry. RESULTS: In this study, we combined long-read sequencing and metatranscriptomics-guided metabolic reconstruction to provide a genome-wide perspective of carbon mineralization flow from polymers to methane in an anaerobic bioreactor. Our results showed that incorporating long reads resulted in a substantial improvement in the quality of metagenomic assemblies, enabling the effective recovery of 132 high-quality genomes meeting stringent criteria of minimum information about a metagenome-assembled genome (MIMAG). In addition, hybrid assembly obtained 51% more prokaryotic genes in comparison to the short-read-only assembly. Metatranscriptomics-guided metabolic reconstruction unveiled the remarkable metabolic flexibility of several novel Bacteroidales-affiliated bacteria and populations from Mesotoga sp. in scavenging amino acids and sugars. In addition to recovering two circular genomes of previously known but fragmented syntrophic bacteria, two newly identified bacteria within Syntrophales were found to be highly engaged in fatty acid oxidation through syntrophic relationships with dominant methanogens Methanoregulaceae bin.74 and Methanothrix sp. bin.206. The activity of bin.206 preferring acetate as substrate exceeded that of bin.74 with increasing loading, reinforcing the substrate determinantal role. CONCLUSION: Overall, our study uncovered some key active anaerobic lineages and their metabolic functions in this complex anaerobic ecosystem, offering a framework for understanding carbon transformations in anaerobic digestion. These findings advance the understanding of metabolic activities and trophic interactions between anaerobic guilds, providing foundational insights into carbon flux within both engineered and natural ecosystems. Video Abstract.

Chemical Reaction Modulated Low-Dimensional Phase Toward Highly Efficient Sky-Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6% (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.

Deletion of Bmal1 in aggrecan-expressing cells leads to mouse temporomandibular joint osteoarthritis.

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Kinetic Monte Carlo simulations on electroforming in nanomanipulated conductive bridge random access memory devices.

Conductive bridge random access memory (CBRAM) devices exhibit great potential as the next-generation nonvolatile memory devices. However, they suffer from two major disadvantages, namely relatively high power consumption and large cycle-to-cycle and device-to-device variations, which hinder their more extensive commercialization. To learn how to enhance their device performance, kinetic Monte Carlo (KMC) simulations were employed to illustrate the variation of electroforming processes in nanomanipulated CBRAM devices by introducing an ion-blocking layer with scalable nanopores and tuning the microstructures of dielectric layers. Both the size of nanopores and the inhomogeneity of dielectric layers have significant impacts on the forming processes of conductive filaments. The dielectric layer with a high-content loose texture plus the scalable nanopore-containing ion-blocking layer leads to the formation of size-controlled and uniform filaments, which remarkably contributes to miniaturizable and stable CBRAM devices. Our study provides insights into nanomanipulation strategies to realize high-performance CBRAM devices, still awaiting future experimental confirmation.

Recent research progress on tumour-specific responsive hydrogels.

Most existing hydrogels, even recently developed injectable hydrogels that undergo a reversible sol-gel phase transition in response to external stimuli, are designed to gel immediately before or after implantation/injection to prevent the free diffusion of materials and drugs; however, the property of immediate gelation leads to a very weak tumour-targeting ability, limiting their application in anticancer therapy. Therefore, the development of tumour-specific responsive hydrogels for anticancer therapy is imperative because tumour-specific responses improve their tumour-targeting efficacy, increase therapeutic effects, and decrease toxicity and side effects. In this review, we introduce the following three types of tumour-responsive hydrogels: (1) hydrogels that gel specifically at the tumour site; (2) hydrogels that decompose specifically at the tumour site; and (3) hydrogels that react specifically with tumours. For each type, their compositions, the mechanisms of tumour-specific responsiveness and their applications in anticancer treatment are comprehensively discussed.

Enhanced sludge granulation and stable performance of an anammox expanded granular sludge bed (EGSB) reactor through the utilization of hydroxyapatite (HAP) particles.

The reuse of hydroxyapatite particles (HAPs) as a granulation activator for anammox sludge was explored to address the remaining issues of time-consuming and unstable granular structure in anammox granulation. During the granulation, nitrogen removal capacity from 2.8 to 13.7 gN/L/d was obtained within 193 days, accompanied by an enhancement in bio-activity from 0.23 to 0.52 gN/gVSS/d. HAPs and anammox microorganisms coupled well to aggregate into granules for denser biomass, higher settleability, and stronger mechanical properties, which effectively improved the biomass retention capacity and structural strength of the sludge system. A skeleton structure formed by the HAPs was characterized during the transformation of the granules, playing a crucial role in strengthening the stability of the sludge. The intermediate processes of granulation were thus clarified to propose an evolutionary pathway for anammox-HAP granules. The pre-addition of HAPs is conducive to achieving faster anammox granulation and rapid process start-up for high-strength wastewater treatment.

Investigating the impact of poverty on mental illness in the UK Biobank using Mendelian randomization.

It is unclear whether poverty and mental illness are causally related. Using UK Biobank and Psychiatric Genomic Consortium data, we examined evidence of causal links between poverty and nine mental illnesses (attention deficit and hyperactivity disorder (ADHD), anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia). We applied genomic structural equation modelling to derive a poverty common factor from household income, occupational income and social deprivation. Then, using Mendelian randomization, we found evidence that schizophrenia and ADHD causally contribute to poverty, while poverty contributes to major depressive disorder and schizophrenia but decreases the risk of anorexia nervosa. Poverty may also contribute to ADHD, albeit with uncertainty due to unbalanced pleiotropy. The effects of poverty were reduced by approximately 30% when we adjusted for cognitive ability. Further investigations of the bidirectional relationships between poverty and mental illness are warranted, as they may inform efforts to improve mental health for all.

Targeting hTERT Promoter G-Quadruplex DNA Structures with Small-Molecule Ligand to Downregulate hTERT Expression for Triple-Negative Breast Cancer Therapy.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.