Fat-1, an enzyme encoded by the fat-1 gene, is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in Caenorhabditis elegans. To better investigate whether the expression of Fat-1 will exert a beneficial function in dyslipidemia and metabolic dysfunction-associated fatty liver disease (MAFLD), we established an adeno-associated virus 9 expressing Fat-1. We found that adeno-associated-virus-mediated expression of Fat-1 markedly reduced the levels of plasma triglycerides and total cholesterol but increased high-density lipoprotein levels in male wild-type hamsters on both chow diet and high-fat diet as well as in chow-diet-fed male LDLR^−/− hamsters. Fat-1 ameliorated diet-induced MAFLD in wild-type hamsters by enhancing fatty acid oxidation through the hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent pathway. Mechanistically, Fat-1 increased the levels of multiple lipid derivatives as ligands for PPARα and simultaneously facilitated the nuclear localization of PPARα. Our results provide new insights into the multiple therapeutic potentials of Fat-1 to treat dyslipidemia, MAFLD, and atherosclerosis.

Takeover safety draws increasing attention in the intelligent transportation as the new energy vehicles with cutting-edge autopilot capabilities vigorously blossom on the road. Despite recent studies highlighting the importance of drivers' emotions in takeover safety, the lack of emotion-aware takeover datasets hinders further investigation, thereby constraining potential applications in this field. To this end, we introduce ViE-Take, the first Vision-driven (Vision is used since it constitutes the most cost-effective and user-friendly solution for commercial driver monitor systems) dataset for exploring the Emotional landscape in Takeovers of autonomous driving. ViE-Take enables a comprehensive exploration of the impact of emotions on drivers' takeover performance through 3 key attributes: multi-source emotion elicitation, multi-modal driver data collection, and multi-dimensional emotion annotations. To aid the use of ViE-Take, we provide 4 deep models (corresponding to 4 prevalent learning strategies) for predicting 3 different aspects of drivers' takeover performance (readiness, reaction time, and quality). These models offer benefits for various downstream tasks, such as driver emotion recognition and regulation for automobile manufacturers. Initial analysis and experiments conducted on ViE-Take indicate that (a) emotions have diverse impacts on takeover performance, some of which are counterintuitive; (b) highly expressive social media clips, despite their brevity, prove effective in eliciting emotions (a foundation for emotion regulation); and (c) predicting takeover performance solely through deep learning on vision data not only is feasible but also holds great potential.

The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression. Aging is a well-established primary risk factor for cancer, while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors. Moreover, aging itself disrupts circadian rhythms, leading to physiological changes that may accelerate cancer development. Despite these connections, the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature. In this review, we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development. We discuss how core circadian genes impact tumor risk and prognosis, highlighting the shared hallmarks of cancer and aging such as genomic instability, cellular senescence, and chronic inflammation. Furthermore, we examine the interplay between circadian rhythms and aging, focusing on how this crosstalk contributes to tumorigenesis, tumor proliferation, and apoptosis, as well as the impact on cellular metabolism and genomic stability. By elucidating the common pathways linking aging, circadian rhythms, and cancer, this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies. We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments, including chronotherapy and antiaging interventions, which may offer important benefits in the clinical management of cancer.

Accurately reconstructing the intricate structure of natural organisms is the long-standing goal of 3-dimensional (3D) bioprinting. Projection-based 3D printing boasts the highest resolution-to-manufacturing time ratio among all 3D-printing technologies, rendering it a highly promising technique in this field. However, achieving standardized, high-fidelity, and high-resolution printing of composite structures using bioinks with diverse mechanical properties remains a marked challenge. The root of this challenge lies in the long-standing neglect of multi-material printability research. Multi-material printing is far from a simple physical assembly of different materials; rather, effective control of material interfaces is a crucial factor that governs print quality. The current research gap in this area substantively hinders the widespread application and rapid development of multi-material projection-based 3D bioprinting. To bridge this critical gap, we developed a multi-material projection-based 3D bioprinter capable of simultaneous printing with 6 materials. Building upon this, we established a fundamental framework for multi-material printability research, encompassing its core logic and essential process specifications. Furthermore, we clarified several critical issues, including the cross-linking behavior of multicomponent bioinks, mechanical mismatch and interface strength in soft–hard composite structures, the penetration behavior of viscous bioinks within hydrogel polymer networks, liquid entrapment and adsorption phenomena in porous heterogeneous structures, and error source analysis along with resolution evaluation in multi-material printing. This study offers a solid theoretical foundation and guidance for the quantitative assessment of multi-material projection-based 3D bioprinting, holding promise to advance the field toward higher precision and the reconstruction of more intricate biological structures.

The metaverse enables immersive virtual healthcare environments, presenting opportunities for enhanced care delivery. A key challenge lies in effectively combining multimodal healthcare data and generative artificial intelligence abilities within metaverse-based healthcare applications, which is a problem that needs to be addressed. This paper proposes a novel multimodal learning framework for metaverse healthcare, MMLMH, based on collaborative intra- and intersample representation and adaptive fusion. Our framework introduces a collaborative representation learning approach that captures shared and modality-specific features across text, audio, and visual health data. By combining modality-specific and shared encoders with carefully formulated intrasample and intersample collaboration mechanisms, MMLMH achieves superior feature representation for complex health assessments. The framework's adaptive fusion approach, utilizing attention mechanisms and gated neural networks, demonstrates robust performance across varying noise levels and data quality conditions. Experiments on metaverse healthcare datasets demonstrate MMLMH's superior performance over baseline methods across multiple evaluation metrics. Longitudinal studies and visualization further illustrate MMLMH's adaptability to evolving virtual environments and balanced performance across diagnostic accuracy, patient–system interaction efficacy, and data integration complexity. The proposed framework has a unique advantage in that a similar level of performance is maintained across various patient populations and virtual avatars, which could lead to greater personalization of healthcare experiences in the metaverse. MMLMH's successful functioning in such complicated circumstances suggests that it can combine and process information streams from several sources. They can be successfully utilized in next-generation healthcare delivery through virtual reality.

Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans. Carnitine–acylcarnitine translocase deficiency (CACTD) is a scarce autosomal recessive genetic disease and may result in patients' death due to heart arrest or respiratory insufficiency. However, the reasons and mechanism of CACTD inducing respiratory insufficiency have never been elucidated. Herein, we employed lipidomic techniques to create comprehensive lipidomic maps of entire lungs throughout both prenatal and postnatal developmental stages in mice. We found that the acylcarnitines manifested notable variations and coordinated the expression levels of carnitine–acylcarnitine translocase (Cact) across these lung developmental stages. Cact-null mice were all dead with a symptom of respiratory distress and exhibited failed lung development. Loss of Cact resulted in an accumulation of palmitoyl-carnitine (C16-acylcarnitine) in the lungs and promoted the proliferation of mesenchymal progenitor cells. Mesenchymal cells with elevated C16-acylcarnitine levels displayed minimal changes in energy metabolism but, upon investigation, revealed an interaction with sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (Samhd1), leading to decreased protein abundance and enhanced cell proliferation. Thus, our findings present a mechanism addressing respiratory distress in CACTD, offering a valuable reference point for both the elucidation of pathogenesis and the exploration of treatment strategies for neonatal respiratory distress.

Exosomes (Exos) are emerging as noninvasive biomarkers for diagnosis and progression monitoring of gastric cancer (GC). However, the heterogeneity discrimination and ultrasensitive quantification of Exos presents a considerable analytical challenge, thereby impeding severely their clinical application. Herein, we propose an integrated terahertz metasensing platform for the discrimination of Exos in distinct subtypes of GC in a single step—through the simultaneous evaluation of the category and richness level of Exos membrane proteins. Characterized by dual-sided independent sensing capabilities with enhanced sensitivity (169 and 325 GHz per refractive index unit, respectively), the metasensor functionalized with antibodies simultaneously reflects the content of 2 membrane proteins in the terahertz spectral response. Our approach concurrently completes accurate differentiation and precise quantification of GC-subtype Exos by integrating dual-sided sensing information in merely a single assay. The dual-sided sensing design enhances the reliability of detection results. Moreover, combined with the signal amplification of gold nanoparticles, the platform experimentally demonstrates a superior dynamic response to Exos concentrations spanning from 1 × 10⁴ to 1 × 10⁸ particles/ml, with the limit of detection being 1 × 10⁴ particles/ml. This work provides new insights into multisensing metasurface design and paves the way for precise and personalized cancer treatment through the specific sensing of Exos.

Cardiovascular diseases constitute a marked threat to global health, and the emergence of spatial omics technologies has revolutionized cardiovascular research. This review explores the application of spatial omics, including spatial transcriptomics, spatial proteomics, spatial metabolomics, spatial genomics, and spatial epigenomics, providing more insight into the molecular and cellular foundations of cardiovascular disease and highlighting the critical contributions of spatial omics to cardiovascular science, and discusses future prospects, including technological advancements, integration of multi-omics, and clinical applications. These developments should contribute to the understanding of cardiovascular diseases and guide the progress of precision medicine, targeted therapies, and personalized treatments.

Since the scarcity of bandwidth resources has become increasingly critical in modern communication systems, orbital angular momentum (OAM) with a higher degree of freedom in information modulation has become a promising solution to alleviate the shortage of spectrum resources. Consequently, the integration of OAM with millimeter-wave technology has emerged as a focal point in next-generation communication research. Recently, programmable metasurfaces have gained considerable attention as essential devices for OAM generation due to real-time tunability, but their profiles are relatively high as a result of the external feed source. This paper proposes a conformal radiation-type programmable metasurface operating in the millimeter-wave band. By employing a series–parallel hybrid feed network to replace conventional external feed sources, the overall profile of the metasurface system can be reduced to less than 0.1λ. Furthermore, the proposed innovation design could also achieve a conformal cross-shaped architecture, which is ultraportable and very effective in integrating with the front ends of satellites or aircraft and eliminating issues such as feed source blockage as well as energy spillover losses in conventional metasurfaces. The proposed metasurface could achieve a realized gain of 22.54 dB with an aperture efficiency of 21.75%, thus generating high-purity OAM waves with topological charges of l = 0, l = +1, l = +2, and l = +3. Additionally, by incorporating beam scanning techniques, OAM waves could be deflected to accommodate scenarios with moving receivers, demonstrating substantial potential for future high-speed wireless communication applications.

Robo-pigeons, a novel class of hybrid robotic systems developed using brain–computer interface technology, hold marked promise for search and rescue missions due to their superior load-bearing capacity and sustained flight performance. However, current research remains largely confined to laboratory environments, and precise control of their flight behavior, especially flight altitude regulation, in a large-scale spatial range outdoors continues to pose a challenge. Herein, we focus on overcoming this limitation by using electrical stimulation of the locus coeruleus (LoC) nucleus to regulate outdoor flight altitude. We investigated the effects of varying stimulation parameters, including stimulation frequency (SF), interstimulus interval (ISI), and stimulation cycles (SC), on the flight altitude of robo-pigeons. The findings indicate that SF functions as a pivotal switch controlling the ascending and descending flight modes of the robo-pigeons. Specifically, 60 Hz stimulation effectively induced an average ascending flight of 12.241 m with an 87.72% success rate, while 80 Hz resulted in an average descending flight of 15.655 m with a 90.52% success rate. SF below 40 Hz did not affect flight altitude change, whereas over 100 Hz caused unstable flights. The number of SC was directly correlated with the magnitude of altitude change, enabling quantitative control of flight behavior. Importantly, electrical stimulation of the LoC nucleus had no significant effects on flight direction. This study is the first to establish that targeted variation of electrical stimulation parameters within the LoC nucleus can achieve precise altitude control in robo-pigeons, providing new insights for advancing the control of flight animal–robot systems in real-world applications.

Cerebral small vessel disease (SVD) involves ischemic white matter damage and choroid plexus (CP) dysfunction for cerebrospinal fluid (CSF) production. Given the vascular and CSF links between the eye and brain, this study explored whether retinal vascular morphology can indicate cerebrovascular injury and CP dysfunction in SVD. We assessed SVD burden using imaging phenotypes like white matter hyperintensities (WMH), perivascular spaces, lacunes, and microbleeds. Cerebrovascular injury was quantified by WMH volume and peak width of skeletonized mean diffusivity (PSMD), while CP volume measured its dysfunction. Retinal vascular markers were derived from fundus images, with associations analyzed using generalized linear models and Pearson correlations. Path analysis quantified contributions of cerebrovascular injury and CP volume to retinal changes. Support vector machine models were developed to predict SVD severity using retinal and demographic data. Among 815 participants, 578 underwent ocular imaging. Increased SVD burden markedly correlated with both cerebral and retinal biomarkers, with retinal alterations equally influenced by cerebrovascular damage and CP enlargement. Machine learning models showed robust predictive power for severe SVD burden (AUC was 0.82), PSMD (0.81), WMH volume (0.77), and CP volume (0.80). These findings suggest that retinal imaging could serve as a cost-effective, noninvasive tool for SVD screening based on vascular and CSF connections.

Cell therapy is a promising strategy for acute liver failure (ALF), while its therapeutic efficacy is often limited by cell loss and poor arrangement. Here, inspired by liver microunits, we propose a novel spatially ordered multicellular lobules for the ALF treatment by using a microfluidic continuous spinning technology. The microfluidics with multiple microchannels was constructed by assembling parallel capillaries. Sodium alginate (Alg) solution encapsulating human umbilical vein endothelial cells (HUVECs), hepatocytes, and mesenchymal stem cells (MSCs) are introduced into the middle channel and the 6 parallel outer channels of the microfluidics, respectively. Simultaneously, Ca²⁺-loaded solutions are pumped through the innermost and outermost channels, forming a hollow microfiber with hepatocytes and MSCs alternately surrounding the HUVECs. These microfibers could highly resemble the cord-like structure of liver lobules, bringing about outstanding liver-like functions. We have demonstrated that in ALF rats, our biomimetic lobules can effectively suppress excessive inflammatory responses, decrease cell necrosis, and promote regenerative pathways, leading to satisfied therapeutic efficacy. These findings underscore the potential of spatially ordered multicellular microfibers in treating related diseases and improving traditional clinical methods.

Gain-of-function mutations of Notch2 cause the rare autosomal dominant disorder known as Hajdu–Cheney syndrome (HCS). Most patients with HCS develop congenital heart disease; however, the precise mechanisms remain elusive. Here, a murine model expressing the human Notch2 intracellular domain (hN2ICD) in cardiomyocytes (hN2ICD-Tg^CM) was generated and the mice spontaneously developed ventricular diastolic dysfunction with preserved ejection fraction and cardiac hypertrophy. Ectopic hN2ICD expression promoted cardiomyocyte hypertrophy by suppressing adenylosuccinate lyase (ADSL)-mediated adenosine 5′-monophosphate (AMP) generation, which further enhanced the activation of the mammalian target of rapamycin complex 1 pathway by reducing AMP-activated kinase activity. Hairy and enhancer of split 1 silencing abrogated hN2ICD-induced cardiomyocyte hypertrophy by increasing Adsl transcription. Importantly, pharmacological activation of AMP-activated kinase ameliorated cardiac hypertrophy and dysfunction in hN2ICD-Tg^CM mice. The frameshift mutation in Notch2 exon 34 (c.6426dupT), which causes early-onset HCS, induces AC16 human cardiomyocyte hypertrophy through suppressing ADSL-mediated AMP generation. Thus, targeting Notch2-mediated purine nucleotide metabolism may be an attractive therapeutic approach to heart failure treatment.

Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria—Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite—propionic acid—alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.

Plant diseases caused by vegetable viruses are an important threat to global food security, presenting a major challenge for the development of antiviral agrochemicals. Functional proteins of plant viruses play a crucial role in the viral life cycle, and targeted inhibition of these proteins has emerged as a promising strategy. However, the current discovery of antiviral small molecules is hampered by the limitations of synthetic approaches and the narrow range of targets. Herein, we report a practical application of organocatalysis for serving pesticide discovery that bears a unique molecular basis. An N-heterocyclic carbene-modulated reaction is first designed to asymmetrically functionalize diverse natural phenols with phthalides. Our designed method is capable of producing a series of new phthalidyl ethers under mild conditions with good yields, enantioselectivity, and functional group tolerance. Among these, compound (R)-3w exhibits excellent and enantioselectivity-preferred curative activity against potato virus Y (PVY). Mechanistically, it is proposed that (R)-3w interacts with the nuclear inclusion body A (Nia) protein of PVY at the His150 residue. This binding impairs Nia's function to cleavage polyprotein, thereby inhibiting formation of viral replication complex. The study provides insights into advancing synthetic protocol to facilitate agrochemical discovery, and our identified (R)-3w may serve as a potential lead for future research and development PVY-Nia inhibitors.

Agglutinate particles, an important component resulting from micrometeoroids impacts, account for about 13.4% to 84.7% of the volume of lunar regolith depending on its maturity. They are crucial in the soil's evolution and the migration of volatile substances. Here, we examined a representative agglutinate particle from Chang′e-5 samples and modeled how volatiles move through its porous framework. Our analysis revealed that the agglutinate's surface features a patchy distribution of smooth, open pores, as shown by both surface and 3-dimensional structural assessments. By integrating elemental distribution data, we propose that the formation of these smooth, open pores is primarily due to the flow of gaseous volatiles, byproducts of intricate physiochemical reactions occurring in the lunar surface layer during impacts by micrometeoroids. Numerical models of volatile transport in the porous agglutinate have been developed for different flow regimes. These models demonstrate that under the intense conditions of impacts, the transport of volatiles occurs at a remarkably high velocity. Consequently, it is improbable that water would accumulate within the porous structure of lunar soil agglutinates. Nevertheless, understanding this process is valuable for gaining a deeper understanding of the lunar regolith's development and for potential future endeavors in extracting water from the lunar surface.

Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel. Then, T cells were infused and fully contacted with these tumor spheroids under biomimetic flow conditions provided by herringbone-patterned microgrooves arrays. We found that the tamed tumor-reactive T cells could be fully activated and a rapid clonal proliferation was realized during the cultivation. In addition, these tumor-reactive T cells exhibited a specific and powerful tumor-killing capability in vitro. Thus, the suggested dynamic microfluidic chips with staged structure-transformable properties realize both the producible formation of tumor spheroids and the recapitulation of tumor-immune crosstalk to expand tumor-reactive T cells. These features indicate that the dynamic and reproducible tumor immunology-on-a-chip has potential in the preparation of therapeutic T cell products for clinical cancer immunotherapy.

Twisted nylon actuators (TNAs) are widely recognized in soft robotics for their excellent load-to-weight ratio and cost-effectiveness. However, their limitations in deformation and output force restrict their ability to support more advanced applications. Here, we report 3 performance-enhancing strategies inspired by the construction process of chromosome, which are validated through 3 novel types of TNAs. First, we design a dual-level helical structure, demonstrating remarkable improvements in the deformation (60.2% vertically and approximately 100% horizontally) and energy storage capability (launching a miniature basketball to 131 cm in height). Second, we present a parallel-twisted method, where the output force of TNAs reaches 11.0 N, achieving 12.1% contraction under a load of 15 N (10,000 times its weight). Additionally, we construct the dual-level helical structure based on parallel-twisted TNAs, resulting in a 439.7% improvement in load capability. We have adopted TNAs for several applications: (a) two bionic elbows capable of rotating and shooting a miniature basketball over 130 cm; (b) a robot that can rapidly jump over 30 cm; and (c) a soft finger that achieves contracting (15.3% contraction under 2 kg load), precise bending (tracking errors less than 2.0%), and twisting motions. This work presents approaches for fabricating high-performance soft actuators and explores the potential applications of these actuators for driving soft robots with multifunctional capabilities.

Prussian blue and Prussian blue analogs are widely used in sodium-ion batteries (SIBs). In this study, we upcycle the degraded Prussian blue directly into layered materials for SIBs through thermal treatment. Prussian blue thermally decomposes to form metal oxides, which then recrystallize into layered metal oxides with metal–nitrogen bond on their surface under suitable temperature conditions. This transformation method is similar to solid-state synthesis, allowing for the pre-addition of necessary components before material conversion to optimize the composition and integrity of the target materials. Based on in situ x-ray diffraction observations of the crystal structure changes of Prussian blue at different temperatures, we demonstrate 1,000 °C as the optimal temperature for converting to layered materials. These materials exhibit an initial discharge capacity of 122.3 mAh g⁻¹ and good rate and cycling stability. We hope that this research will promote the sustainable development of the SIB industry.

Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity. The “brain–skin axis” theory suggests that abnormalities in the brain and nervous system can lead to skin degeneration because abnormal mental states, like chronic stress, can have negative physiological and functional effects on the skin through a variety of processes, resulting in delayed wound healing and accelerated skin aging. However, it remains unclear whether maintaining a youthful brain has beneficial effects on aged skin healing. In light of this, we identified youthful brain-derived extracellular vesicles (YBEVs) and created a composite GelMA hydrogel material that encourages scarless wound healing in aged skin. We found that YBEVs reduce the expression of senescence, senescence-associated secretory phenotypes, and inflammation-associated proteins, and even restore dysfunction in senescent cells. Furthermore, by encouraging collagen deposition, angiogenesis, epidermal and dermal regeneration, and folliculogenesis, we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats. The pro-repairing speed and effect of this composite hydrogel even matched that of young rats. Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs, some of which may play a role in the regulation of skin energy intake, particularly through oxidative phosphorylation and mitochondrial function. In conclusion, the findings suggest that maintaining a youthful brain could potentially alleviate skin aging, and the proposed YBEVs-GelMA hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.

The stages of transcription initiation and elongation are critical in the regulation of HIV-1 gene expression. Recent single-molecule imaging in living cells has shown that HIV-1 transcription occurs across multiple time scales and plays a key role in the control of latency. However, the molecular mechanisms of HIV-1 transcription remain poorly understood due to the lack of a unified modeling framework and advanced computational methods for analyzing HIV-1 imaging data. Here, we present a general stochastic model that characterizes HIV-1 transcription dynamics and computes the distributions of initiation times and nascent RNA counts. Our results show that coordination between initiation and elongation modulates transcription dynamics and that leveraging initiation-time data enhances model identification. Meanwhile, we develop a statistical inference method that integrates initiation-time data and nascent RNA data. Our results show that incorporating initiation-time data allows for accurate inference of the initiation rate and elongation time, with these parameter estimates being independent of the models used. When applied to HIV-1 transcription data in living cells, our theory and inference methods confirm the dual role of Tat in HIV-1 transcriptional regulation. In addition, the optimal predictive model indicates that Tat induces viral reactivation and latency exit by altering the number of silent states of the promoter. Our approach may provide the potential to improve current HIV-1 cure strategies.

Pre-trained large language models (LLMs) exhibit powerful capabilities for generating natural text. Evolutionary algorithms (EAs) can discover diverse solutions to complex real-world problems. Motivated by the common collective and directionality of text generation and evolution, this paper first illustrates the conceptual parallels between LLMs and EAs at a micro level, which includes multiple one-to-one key characteristics: token representation and individual representation, position encoding and fitness shaping, position embedding and selection, Transformers block and reproduction, and model training and parameter adaptation. These parallels highlight potential opportunities for technical advancements in both LLMs and EAs. Subsequently, we analyze existing interdisciplinary research from a macro perspective to uncover critical challenges, with a particular focus on evolutionary fine-tuning and LLM-enhanced EAs. These analyses not only provide insights into the evolutionary mechanisms behind LLMs but also offer potential directions for enhancing the capabilities of artificial agents.

Spermatogonial stem cells (SSCs) are essential for initiating and maintaining normal spermatogenesis, and notably, they have important applications in both reproduction and regenerative medicine. Nevertheless, the molecular mechanisms controlling the fate determinations of human SSCs remain elusive. In this study, we identified a selective expression of APBB1 in dormant human SSCs. We demonstrated for the first time that APBB1 interacted with KAT5, which led to the suppression of GDF15 expression and consequent inhibition of human SSC proliferation. Intriguingly, Apbb1^−/− mice assumed the disrupted spermatogenesis and markedly reduced fertility. SSC transplantation assays revealed that Apbb1 silencing enhanced SSC colonization and impeded their differentiation, which resulted in the impaired spermatogenesis. Notably, 4 deleterious APBB1 mutation sites were identified in 2,047 patients with non-obstructive azoospermia (NOA), and patients with the c.1940C>G mutation had a similar testicular phenotype with Apbb1^−/− mice. Additionally, we observed lower expression levels of APBB1 in NOA patients with spermatogenic arrest than in obstructive azoospermia patients with normal spermatogenesis. Collectively, our findings highlight an essential role of APBB1/KAT5/GDF15 in governing human SSC fate decisions and maintaining normal spermatogenesis and underscore them as therapeutic targets for treating male infertility.

The emergence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) severely compromises conventional β-lactam antibiotics efficacy and poses an extensive global health challenge. Given the close relationship between docosahexaenoic acid (DHA) and metabolic alterations, this study aimed to reveal the novel function of DHA to potentiate β-lactam antibiotics activity through a lipid peroxidation mechanism. Additionally, DHA exhibited significant inhibitory effects on the catalytic function of β-lactamase through interactions with active residues. Herein, the dual-faceted mechanisms of perturbation of lipid metabolism and β-lactamase catalytic inhibition achieved the potentiated antibacterial efficacy of β-lactam antibiotics in combination with DHA against MRSA. Furthermore, to enhance the pharmacodynamic performance and stability of DHA, amoxicillin and DHA co-loaded nanoemulsions (Amo/DHA-NEs) were prepared via high-energy emulsification. Intriguingly, we found that Amo/DHA-NEs effectively rescued MRSA-induced infections in the murine infection models, as evidenced by the superior bacterial clearance and mitigated inflammation. Collectively, this work reveals a potentially exploitable link between DHA-driven metabolic reprogramming and β-lactams resistance, and we propose combination therapies of DHA and β-lactams targeting the emerging threat of MRSA infections.

Room-temperature (RT) terahertz (THz) detection finds widespread applications in security inspection, communication, biomedical imaging, and scientific research. However, the state-of-the-art detection strategies are still limited by issues such as low sensitivity, narrow response range, slow response speed, complex fabrication techniques, and difficulties in scaling up to large arrays. Here, we present a high-sensitivity, broadband-response, and high-speed RT THz detection strategy by utilizing a deep subwavelength metal–semiconductor–metal (MSM) structure. The spontaneously formed 2-dimensional electron gas (2DEG) at the CdTe/PbTe interface provides a superior transport channel characterized by high carrier concentration, low scattering, and high mobility. The synergy of the electromagnetic induced well effect formed in the MSM structure, and the efficient and rapid transport capabilities of the 2DEG channel give rise to an impressive performance improvement. The proposed 2DEG photodetector exhibits a broad frequency range from 22 to 519 GHz, an ultralow noise equivalent power of 3.0 × 10⁻¹⁴ W Hz^−1/2 at 166 GHz, and a short response time of 6.7 μs. This work provides an effective route for the development of high-performance RT THz detection strategies, paving the way for enhanced THz technology applications.