Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale.

Serotonin influences many aspects of animal behavior. But how serotonin acts on its diverse receptors across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. Comprehensive genetic analyses identify three core serotonin receptors (MOD-1, SER-4, and LGC-50) that induce slow locomotion upon serotonin release and others (SER-1, SER-5, and SER-7) that interact with them to modulate this behavior. SER-4 induces behavioral responses to sudden increases in serotonin release, whereas MOD-1 induces responses to persistent release. Whole-brain imaging reveals widespread serotonin-associated brain dynamics, spanning many behavioral networks. We map all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict which neurons show serotonin-associated activity. These results reveal how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

Brain-wide representations of behavior spanning multiple timescales and states in C. elegans.

Changes in an animal's behavior and internal state are accompanied by widespread changes in activity across its brain. However, how neurons across the brain encode behavior and how this is impacted by state is poorly understood. We recorded brain-wide activity and the diverse motor programs of freely moving C. elegans and built probabilistic models that explain how each neuron encodes quantitative behavioral features. By determining the identities of the recorded neurons, we created an atlas of how the defined neuron classes in the C. elegans connectome encode behavior. Many neuron classes have conjunctive representations of multiple behaviors. Moreover, although many neurons encode current motor actions, others integrate recent actions. Changes in behavioral state are accompanied by widespread changes in how neurons encode behavior, and we identify these flexible nodes in the connectome. Our results provide a global map of how the cell types across an animal's brain encode its behavior.

Autonomous navigation of stratospheric balloons using reinforcement learning.

Efficiently navigating a superpressure balloon in the stratosphere1 requires the integration of a multitude of cues, such as wind speed and solar elevation, and the process is complicated by forecast errors and sparse wind measurements. Coupled with the need to make decisions in real time, these factors rule out the use of conventional control techniques2,3. Here we describe the use of reinforcement learning4,5 to create a high-performing flight controller. Our algorithm uses data augmentation6,7 and a self-correcting design to overcome the key technical challenge of reinforcement learning from imperfect data, which has proved to be a major obstacle to its application to physical systems8. We deployed our controller to station Loon superpressure balloons at multiple locations across the globe, including a 39-day controlled experiment over the Pacific Ocean. Analyses show that the controller outperforms Loon's previous algorithm and is robust to the natural diversity in stratospheric winds. These results demonstrate that reinforcement learning is an effective solution to real-world autonomous control problems in which neither conventional methods nor human intervention suffice, offering clues about what may be needed to create artificially intelligent agents that continuously interact with real, dynamic environments.

Immunophilin FKB20-2 participates in oligomerization of Photosystem I in Chlamydomonas.

PSI is a sophisticated photosynthesis protein complex that fuels the light reaction of photosynthesis in algae and vascular plants. While the structure and function of PSI have been studied extensively, the dynamic regulation on PSI oligomerization and high light response is less understood. In this work, we characterized a high light-responsive immunophilin gene FKB20-2 (FK506-binding protein 20-2) required for PSI oligomerization and high light tolerance in Chlamydomonas (Chlamydomonas reinhardtii). Biochemical assays and 77-K fluorescence measurement showed that loss of FKB20-2 led to the reduced accumulation of PSI core subunits and abnormal oligomerization of PSI complexes and, particularly, reduced PSI intermediate complexes in fkb20-2. It is noteworthy that the abnormal PSI oligomerization was observed in fkb20-2 even under dark and dim light growth conditions. Coimmunoprecipitation, MS, and yeast 2-hybrid assay revealed that FKB20-2 directly interacted with the low molecular weight PSI subunit PsaG, which might be involved in the dynamic regulation of PSI-light-harvesting complex I supercomplexes. Moreover, abnormal PSI oligomerization caused accelerated photodamage to PSII in fkb20-2 under high light stress. Together, we demonstrated that immunophilin FKB20-2 affects PSI oligomerization probably by interacting with PsaG and plays pivotal roles during Chlamydomonas tolerance to high light.

Grandmaster level in StarCraft II using multi-agent reinforcement learning.

Many real-world applications require artificial agents to compete and coordinate with other agents in complex environments. As a stepping stone to this goal, the domain of StarCraft has emerged as an important challenge for artificial intelligence research, owing to its iconic and enduring status among the most difficult professional esports and its relevance to the real world in terms of its raw complexity and multi-agent challenges. Over the course of a decade and numerous competitions1-3, the strongest agents have simplified important aspects of the game, utilized superhuman capabilities, or employed hand-crafted sub-systems4. Despite these advantages, no previous agent has come close to matching the overall skill of top StarCraft players. We chose to address the challenge of StarCraft using general-purpose learning methods that are in principle applicable to other complex domains: a multi-agent reinforcement learning algorithm that uses data from both human and agent games within a diverse league of continually adapting strategies and counter-strategies, each represented by deep neural networks5,6. We evaluated our agent, AlphaStar, in the full game of StarCraft II, through a series of online games against human players. AlphaStar was rated at Grandmaster level for all three StarCraft races and above 99.8% of officially ranked human players.

Unveiling Spatiotemporal Diffusion of Hot Carriers Influenced by Spatial Nonuniform Hot Phonon Bottleneck Effect in Monolayer MoS2.

The exceptional semiconducting properties of two-dimensional (2D) transition metal dichalcogenides (TMDs) have made them highly promising for the development of future electronic and optoelectronic devices. Extensive studies of TMDs are partly associated with their ability to generate 2D-confined hot carriers above the conduction band edges, enabling potential applications that rely on such transient excited states. In this work, room-temperature spatiotemporal hot carrier dynamics in monolayer MoS2 is studied by transient absorption microscopy (TAM), featuring an initial ultrafast expansion followed by a rapid negative diffusion, and ultimately a slow long-term expansion of the band edge C-excitons. We provide direct experimental evidence to identify the abnormal negative diffusion process as a spatial contraction of the hot carriers resulting from spatial variation in the hot phonon bottleneck effect due to the Gaussian intensity distribution of the pump laser beam.

Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

On-Chip Topological Photonic Crystal Nanobeam Filters.

We present an on-chip filter with a broad tailorable working wavelength and a single-mode operation. This is realized through the application of topological photonic crystal nanobeam filters employing synthesis parameter dimensions. By introducing the translation of air holes as a new synthetic parameter dimension, we obtained nanobeams with tunable Zak phases. Leveraging the bulk-edge correspondence, we identify the existence of topological cavity modes and establish a correlation between the cavity's interface morphology and working wavelength. Through experiments, we demonstrate filters with adjustable filtering wavelengths ranging from 1301 to 1570 nm. Our work illustrates the use of the synthetic translation dimension in the design of on-chip filters, and it holds potential for applications in other devices such as microcavities.

NAMPT regulates mitochondria function and lipid metabolism during porcine oocyte maturation.

Oocyte maturation defect can lead to maternal reproduction disorder. NAMPT is a rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, which can regulate a variety of cellular metabolic processes including glucose metabolism and DNA damage repair. However, the function of NAMPT in porcine oocytes remains unknown. In this study, we showed that NAMPT involved into multiple cellular events during oocyte maturation. NAMPT expressed during all stages of porcine oocyte meiosis, and inhibition of NAMPT activity caused the cumulus expansion and polar body extrusion defects. Mitochondrial dysfunction was observed in NAMPT-deficient porcine oocytes, which showed decreased membrane potential, ATP and mitochondrial DNA content, increased oxidative stress level and apoptosis. We also found that NAMPT was essential for spindle organization and chromosome arrangement based on Ac-tubulin. Moreover, lack of NAMPT activity caused the increase of lipid droplet and affected the imbalance of lipogenesis and lipolysis. In conclusion, our study indicated that lack of NAMPT activity affected porcine oocyte maturation through its effects on mitochondria function, spindle assembly and lipid metabolism.

The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.

Dual-Enhancement Electrochemiluminescence Device for Ultratrace Uranium Visualized Monitoring in Fish, Hair, and Nail Samples.

Uranium is a nuclear fuel but also a hazardous contaminant due to its radioactivity and chemical toxicity. To prevent and mitigate its potential threat, the accurate monitoring of ultratrace uranium (orders of magnitude of pg g-1) in practical environmental samples has become an important scientific problem. To meet this challenge, we developed an efficient electrochemiluminescence (ECL) UO22+ detection device by a novel dual-enhancement mechanism. In detail, poly[(9,9-dioctylfuor-enyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1,3}-thiadiazole)] polymer dots (Pdots) are modified by the UO22+ DNA aptamer, and rhodamine B (RhB) is combined with dsDNA to quench the ECL signal via a resonance energy transfer (RET) process. UO22+ can cut off the DNA aptamer to release RhB, which generates an ECL enhancement process, and then, UO22+ continuously combines with the DNA chain, inducing another ECL enhancement by the RET process from UO22+ to Pdots. This device achieves an ultralow detection limit (12 pg L-1) and a wide linear range (113 pg L-1-11.3 mg L-1), which can successfully give accurate determination results to the ultratrace uranium in biosamples (<1 pg g-1) to monitor the uranium simulation of fish. This work presents an efficient strategy for ultratrace uranium determination in the environment, highlighting its significance in public health and environmental fields.

Self-Enhanced Electrochemiluminesence of Dye-Doped Polymer Dots for Coreactant-Free Visualized Detection of Iodide Ions.

The monitoring of radioactive iodide levels is of great significance in environmental science and cancer radiotherapy. In this work, a high-throughput, radiation-resistant, and visualized electrochemiluminescence (ECL) strategy was developed for detection of iodide ions. Herein, the hydrophobic ruthenium derivative (Ru(bpy)3[B(C6F5)4]2) (bpy = bipyridyl) was doped in tertiary amine-coupled polymer dots (N-PFO Pdots) to synthesize self-enhanced Pdots (Ru@Pdots), which showed extremely high ECL intensity in absence of coreactant. Due to the efficient ECL resonance energy transfer between Ru(bpy)3[B(C6F5)4]2 and N-PFO, the Ru@Pdots exhibited 18 times higher ECL intensity compared with bare N-PFO Pdots. Besides, Ru@Pdots also showed 220-times higher ECL intensity compared with Ru(bpy)3[B(C6F5)4]2 doped coreactant-dependent Pdots (Ru@PFO Pdots). Using Ru@Pdots as ECL emitters, an ECL imaging array was designed for iodide ion detection, which exhibited a detection range of 0.8 nM-4 µM and a limit of detection of 0.1 nM. In this strategy, iodide ions were oxidized as iodide free radicals on the surface of the electrode, which could further consume the nitrogen radical of Ru@Pdots and effectively quench the ECL signal. This method also showed good specificity, radiation-resistant performance, and accuracy in actual seawater sample testing, which indicated its value in marine environmental monitoring, nuclear security, and cancer radiotherapy.

CysModDB: a comprehensive platform with the integration of manually curated resources and analysis tools for cysteine posttranslational modifications.

The unique chemical reactivity of cysteine residues results in various posttranslational modifications (PTMs), which are implicated in regulating a range of fundamental biological processes. With the advent of chemical proteomics technology, thousands of cysteine PTM (CysPTM) sites have been identified from multiple species. A few CysPTM-based databases have been developed, but they mainly focus on data collection rather than various annotations and analytical integration. Here, we present a platform-dubbed CysModDB, integrated with the comprehensive CysPTM resources and analysis tools. CysModDB contains five parts: (1) 70 536 experimentally verified CysPTM sites with annotations of sample origin and enrichment techniques, (2) 21 654 modified proteins annotated with functional regions and structure information, (3) cross-references to external databases such as the protein-protein interactions database, (4) online computational tools for predicting CysPTM sites and (5) integrated analysis tools such as gene enrichment and investigation of sequence features. These parts are integrated using a customized graphic browser and a Basket. The browser uses graphs to represent the distribution of modified sites with different CysPTM types on protein sequences and mapping these sites to the protein structures and functional regions, which assists in exploring cross-talks between the modified sites and their potential effect on protein functions. The Basket connects proteins and CysPTM sites to the analysis tools. In summary, CysModDB is an integrated platform to facilitate the CysPTM research, freely accessible via https://cysmoddb.bioinfogo.org/.

Flexible fabrication of core/shell nanoparticles for tailored infrared emissivity on aluminum via femtosecond laser self-deposition.

A metal surface with controllable infrared emissivity has a wide range of applications. However, a flexible and simple fabrication method is needed. Here, a controllable femtosecond laser self-deposition technology was developed to fabricate Al@AlOx core/shell micropillars (MPs) with diverse size distribution on the aluminum surface in a single-step operation under ambient conditions. By establishing a deterministic relationship between pulse-repetition frequency (PRF) and particle size distribution (PSD), we achieved continuous control of the infrared emissivity of the surface by lower PRF, ranging from low (0.31) to high (0.93). Additionally, by using higher PRF, we attained dual-band emissivity control, featuring high emissivity in the range of 10-14 µm and near-continuous change in the range of 2.5-10 µm.

Realizing high-efficiency third harmonic generation via accidental bound states in the continuum.

The bound states in the continuum (BICs) have attracted much attention in designing metasurface due to their high Q-factor and effectiveness in suppressing radiational loss. Here we report on the realization of the third harmonic generation (THG) at a near-ultraviolet wavelength (343 nm) via accidental BICs in a metasurface. The absolute conversion efficiency of the THG reaches 1.13 × 10-5 at a lower peak pump intensity of 0.7 GW/cm2. This approach allows the generation of an unprecedentedly high nonlinear conversion efficiency with simple structures.

Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases.

Neurons are the primary cells responsible for information processing in the central nervous system (CNS). However, they are vulnerable to damage and insult in a variety of neurological disorders. As the most abundant glial cells in the brain, astrocytes provide crucial support to neurons and participate in synapse formation, synaptic transmission, neurotransmitter recycling, regulation of metabolic processes, and the maintenance of the blood-brain barrier integrity. Though astrocytes play a significant role in the manifestation of injury and disease, they do not work in isolation. Cellular interactions between astrocytes and neurons are essential for maintaining the homeostasis of the CNS under both physiological and pathological conditions. In this review, we explore the diverse interactions between astrocytes and neurons under physiological conditions, including the exchange of neurotrophic factors, gliotransmitters, and energy substrates, and different CNS diseases such as Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. This review sheds light on the contribution of astrocyte-neuron crosstalk to the progression of neurological diseases to provide potential therapeutic targets for the treatment of neurological diseases.

Superparamagnetic Iron Oxide-Erastin-Polyethylene Glycol Nanotherapeutic Platform: A Ferroptosis-Based Approach for the Integrated Diagnosis and Treatment of Nasopharyngeal Cancer.

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)-erastin-polyethylene glycol (PEG) nanoparticles prepared by loading SPIO-PEG nanoparticles with erastin on ferroptosis. SPIO-erastin-PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO-erastin-PEG were measured as (-37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T2-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO-erastin-PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO-erastin-PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO-erastin-PEG have been demonstrated in 5-8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO-erastin-PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.

Base-Promoted Ring-Opening Hydroxylation of Cyclic Sulfonium Salts.

Herein, we reported a general strategy for the synthesis of sulfur-containing primary alcohol derivatives by base-promoted ring-opening hydroxylation of cyclic sulfonium salts. A variety of sulfonium salts were successfully transformed into the desired hydroxylated products in moderate to excellent yields with good functional group tolerance. Moreover, the one-pot synthesis, scale-up reaction, and late-stage functionalization of complex molecules demonstrated the practicability of this synthetic protocol in the field of synthetic chemistry.

Epidemiological characteristics of human metapneumovirus among children in Nanjing, China.

PURPOSE: The objective of this study was to examine the molecular epidemiology and clinical characteristics of HMPV infection among children with ARIs in Nanjing. METHODS: The respiratory samples were collected from 2078 children (≤ 14 years) with acute respiratory infections and were tested for HMPV using real-time RT-PCR. Amplification and sequencing of the HMPV G gene were followed by phylogenetic analysis using MEGA 7.0. RESULT: The detection rate of HMPV among children was 4.7% (97/2078), with a concentration in those under 5 years of age. Notably, the peak season for HMPV prevalence was observed in winter. Among the 97 HMPV-positive samples, 51.5% (50/97) were available for characterization of the HMPV G protein gene. Phylogenetic analysis indicated that the sequenced HMPV strains were classified into three sublineages: A2c111nt - dup (84.0%), B1 (2.0%), and B2 (14.0%). CONCLUSION: There was an incidence of HMPV among hospitalized children during 2021-2022 in Nanjing with A2c111nt - dup being the dominant strain. This study demonstrated the molecular epidemiological characteristics of HMPV among children with respiratory infections in Nanjing, China.

Synthesis of alkynyl sulfides via base-promoted nucleophilic ring-opening of α-bromostyrene sulfonium salt.

An efficient method for the synthesis of alkynyl sulfides via a C(sp3)-S bond cleavage of α-bromostyrene sulfonium salts has been developed. This base-promoted nucleophilic ring-opening pathway allows the preparation of diverse alkynyl sulfide compounds using tetramethylene sulfoxide as the sulfur source. The reaction proceeds with good functional group tolerance and could be applied to the late-stage functionalization of bioactive molecules and drugs. Furthermore, the synthetic utility of this method was demonstrated by a one-pot synthesis, scale-up reaction and further modification of various alkynyl sulfide products.