BACKGROUND:SMARCA4-deficient pulmonary neoplasms have emerged as a major focus of lung cancer research in recent years. This subtype is characterized by aggressive behavior and poor prognosis. However, radiotherapy-related studies in this population remain scarce, and evidence is lacking regarding the optimal selection of radiotherapy parameters and the sequencing of combination with immunotherapy. The present study aimed to evaluate the efficacy of radiotherapy in these tumors and to explore the prognostic value of radiotherapy parameters. METHODS:Clinical data of 88 patients with SMARCA4-deficient pulmonary neoplasms were retrospectively analyzed. Patients were divided into a radiotherapy group (n=20) and a non-radiotherapy group (n=68). Overall survival (OS) was compared between groups using the Kaplan-Meier method. Subgroup analyses were performed for radiotherapy site, biological equivalent dose (BED), fractionation mode, and the timing of radiotherapy combined with immunotherapy. RESULTS:The radiotherapy group had a lower proportion of patients aged ≥60 years (25.0% vs 66.2%, P<0.001) and a higher proportion receiving immunotherapy (65.0% vs 33.8%, P=0.013) compared with the non-radiotherapy group. The median OS was not reached in the radiotherapy group, which was significantly superior to that in the non-radiotherapy group (22.9 mon, P=0.048). Among patients receiving radiotherapy, those who also received immunotherapy had a significantly longer median OS than those receiving radiotherapy alone. No statistically significant differences in OS were observed among subgroups stratified by radiotherapy site, BED, fractionation schedule or timing. CONCLUSIONS:Radiotherapy effectively improves OS in SMARCA4-deficient lung tumors, with synergistic potential when combined with immunotherapy. The lack of prognostic impact of radiotherapy parameters supports regimen simplification, while the timing of combined therapy needs refinement. These exploratory results lay a critical foundation for future large‑sample confirmatory studies.

Perfluorobutanesulfonic acid (PFBS), a short-chain per- and polyfluoroalkyl substance (PFAS) introduced as a “safer” alternative to perfluorooctanesulfonic acid (PFOS), is increasingly detected in in drinking water sources and human serum worldwide, yet its neurotoxicological effects during critical visual developmental windows remain poorly characterized. Here, we investigated the effects of PFBS exposure during the critical period on binocular visual development, a sensitive developmental stage essential for establishing binocular vision. C57BL/6J mice were exposed to PFBS (1 mg/kg/day via drinking water) during the critical period (postnatal days 21-35, P21-P35), using in vivo extracellular recordings in primary visual cortex (V1) of mice, we demonstrated that PFBS exposure severely impairs ocular dominance plasticity. These plasticity deficits disrupted binocular integration and resulted in persistent functional impairments in depth perception and visual acuity extending into adulthood (P35 and P60: all p < 0.05), indicating long-lasting alterations in visual processing. Mechanistic investigations revealed that PFBS exposure downregulated brain-derived neurotrophic factor (BDNF)-TrkB signaling, accompanied by reduced glutamatergic receptor expression, elevated GABAergic receptor levels, and decreased dendritic spine density (total spine density: p < 0.01; all spine subtypes: p < 0.05). Importantly, concurrent treatment with 7,8-dihydroxyflavone (DHF), a TrkB agonist, during the critical period largely prevented all PFBS-induced deficits, confirming that disruption of the BDNF-TrkB pathway underlies the observed neurotoxicity and identifying a potential intervention target. These findings provide the electrophysiological evidence that developmental PFBS exposure poses significant risks to visual system maturation through BDNF-TrkB pathway disruption, highlighting the need for environmental regulations addressing short-chain PFAS neurotoxicity. This study underscores that PFBS exposure during sensitive developmental windows may increase the risk of vision impairment and long-term neurological dysfunction.

High-density probes record from thousands of neurons simultaneously, yet resolving single-neuron identity remains an ill-posed inverse problem. While detailed simulations precisely characterize the biophysical forward process, their utility for interpreting brain signal remains unclear. Here we show that biophysical simulations of population neuronal electrical signals serve as an effective bridge between theory and experiment. By pre-training artificial neural networks exclusively on large-scale synthetic data, we demonstrate robust zero-shot generalization across diverse brain regions, experimental paradigms and species, enabling the accurate inference of single-unit activities and cell-type properties without exposure to real data. Furthermore, uncovering a substantial population of functionally competent but weakly active neurons systematically obscured by conventional heuristics, our framework resolves a long-standing discrepancy regarding ocular dominance in mouse primary visual cortex. These findings establish biophysical simulations as a reference standard, bridging the gap between theoretical understanding and experimental observation through data-driven inference.

The visual system is a complex hierarchical structure that processes diverse visual information to guide cognition and behavior. Elucidating the principles that govern the development and function of the visual system's circuitry is a central goal in visual neuroscience. This review examines connectivity, computation, and plasticity within the early mammalian visual system, focusing on three key structures: the retina, the superior colliculus (SC), and the primary visual cortex (V1). The retina serves as the initial site for visual information processing, culminating in activation of highly selective retinal ganglion cells (RGCs), which convey all visual information to the brain. The SC is a primary retinorecipient region that integrates visual information to guide appropriate behavioral responses, exhibiting visual processing both similar to and distinct from RGCs. Retinal information is also relayed via the thalamus to V1, which extracts detailed visual features through spatial and temporal integration, forming the basis of conscious visual perception. The development of these structures involves a coarse-to-fine maturation of functional networks driven by intrinsic mechanisms, including molecular cues and spontaneous patterns of activity. In addition, experience-dependent plasticity in the SC and V1 allows the visual system to adapt to changes of sensory inputs during development. Recent work has significantly advanced our understanding of the complex neuronal computations executed in these early visual regions and the molecular and circuit mechanisms underlying development and plasticity. This knowledge has significant implications for both basic neuroscience and clinical applications, particularly in the context of visual system disorders.

The visual thalamus serves as a critical hub for feature preprocessing in visual processing pathways. Emerging evidence demonstrates that experience-dependent plasticity can be revealed by monocular deprivation (MD) in the dorsolateral geniculate nucleus (dLGN) of the thalamus. However, whether and how this thalamic plasticity induces changes in multiple receptive field properties and the potential mechanisms remain unclear. Using in vivo electrophysiology, here we show that binocular neurons in the dLGN of 4-day MD mice starting at P28 undergo a significant ocular dominance (OD) shift during the critical period. This OD plasticity could be attributed to the potentiation of ipsilateral eye responses but not to the depression of deprived eye responses, contrasting with conventional observations in the primary visual cortex (V1). The direction and orientation selectivity of ipsilateral eye responses, but not of contralateral eye responses in these neurons, were dramatically reduced. Developmental analysis revealed pre-critical and critical period-associated changes in densities of both GABA positive neurons and GABAA receptor α1 subunit (GABRA1) positive neurons. However, early compensatory inhibition from V1 feedback in P18 MD mice maintained network stability with no changes in OD and feature selectivity. Mechanistically, pharmacological activation of GABAA receptors rescued the MD-induced OD shifts and feature selectivity impairments in critical period MD mice, operating independently of the V1 feedback. Furthermore, under different contrast levels and spatial frequencies, these critical period-associated changes in receptive field properties still indicate alterations in ipsilateral eye responses alone. Together, these findings provide novel insights into the developmental mechanisms of thalamic sensory processing, highlighting the thalamus as an active participant in experience-dependent visual plasticity rather than merely a passive relay station. The identified GABA-mediated plasticity mechanisms offer potential therapeutic targets for visual system disorders.

Spike sorting is an essential process in neural recording, which identifies and separates electrical signals from individual neurons recorded by electrodes in the brain, enabling researchers to study how specific neurons communicate and process information. Although there exist a number of spike sorting methods which have contributed to significant neuroscientific breakthroughs, many are heuristically designed, making it challenging to verify their correctness due to the difficulty of obtaining ground truth labels from real-world neural recordings. In this work, we explore a data-driven, deep learning-based approach. We begin by creating a large-scale dataset through electrophysiology simulations using biologically realistic computational models. We then present SimSort, a pretraining framework for spike sorting. Trained solely on simulated data, SimSort demonstrates zero-shot generalizability to real-world spike sorting tasks, yielding consistent improvements over existing methods across multiple benchmarks. These results highlight the potential of simulation-driven pretraining to enhance the robustness and scalability of spike sorting in experimental neuroscience.

Eye opening represents a critical milestone in postnatal visual development, triggering experience-dependent plasticity that refines neural circuits across visual pathways. While synaptic maturation in the thalamocortical system has been extensively studied, how eye opening shapes synaptic development in the superior colliculus (SC) - a major subcortical hub mediating rapid orienting and motion detection - remains poorly understood. Here, we combine electrophysiological, biochemical, and ultrastructural approaches to investigate experience-promoted synaptic development in the mouse SC following eye opening. We show that eye opening enhances spontaneous AMPAR-mediated synaptic transmission, increasing both the frequency and amplitude of currents. This functional potentiation is accompanied by elevated expression of GluR1, GluR2, and the postsynaptic density protein 95. Structural analyses further reveal enlargement of postsynaptic densities, increased presynaptic vesicle number, and elevated dendritic spine density without altering spine subtype distribution. Our findings demonstrate that eye opening primes robust functional and structural maturation of SC synapses through AMPAR-mediated mechanisms, highlighting the SC as a key site of experience-dependent plasticity with distinct developmental mechanisms in the subcortical visual pathway.

The balance between memory specificity and generalization is essential for animals’ adaptive behaviours in diverse contexts, and is controlled by thalamus and hippocampus. Yet, whether and how thalamo-hippocampal circuitry regulates this balance remains elusive. Using single-neuron projectome analysis, we found that dorsal and ventral subregions of ventral CA1 (vCA1d and vCA1v) received inputs from two distinct neuronal populations in the nucleus of reuniens (NRe vCA1d and NRe vCA1v neurons), respectively. Cell type-specific trans-synaptic retrograde tracing and circuit-barcoded single-cell RNA sequencing of NRe vCA1d and NRe vCA1v neurons uncovered distinct presynaptic inputs as well as gene expression patterns underlying their different intrinsic excitabilities and spike waveforms. Using single-unit recording, circuit specific chemogenetic inhibitions, and miniscope Ca 2+ imaging, we found that NRe vCA1d (but not NRe vCA1v ) neurons and downstream vCA1d neurons exhibited reduced contextual discriminability, promoting memory generalization after threat learning. These results demonstrate that the NRe-vCA1d circuit regulates memory precision by promoting memory generalization over specificity.

The mitochondrial proton motive force (pmf) is a critical driver of cellular energy production and influences various cellular processes. Dysregulation of pmf is implicated in a range of diseases, including neurodegenerative diseases, mitochondrial diseases, cancer and aging-related pathologies. Currently, an efficient strategy to rescue ATP production and mitigate reactive oxygen species (ROS) generation under conditions of energy deprivation is lacking. Here, we engineered a light-sensitive, mitochondria-targeting proton-pumping rhodopsin (PPR), mt-EcGAPR, capable of generating an efficient pmf for ATP synthesis while simultaneously mitigating reactive oxygen species (ROS) generation during stress and decreasing DNA double-strand breaks (DSBs). Owing to its transparency to visible light, eye is the ideal candidate for the noninvasive application of mt-EcGAPR in the treatment of mitochondria-related retinal degenerative diseases. Using a silicone oil-induced ocular hypertension glaucoma mouse model, we demonstrate that ambient light activation of mt-EcGAPR significantly increased ATP production, suppressed ROS accumulation, and protected retinal ganglion cells (RGCs) from degeneration. Mechanistically, mt-EcGAPR inhibited endoplasmic reticulum (ER) stress-ATF6-gasdermin D (GSDMD)-mediated pyroptosis, thereby preserving retinal structure and function. This intervention ultimately led to improved visual acuity in glaucomatous eyes of mice. Collectively, our findings establish mt-EcGAPR as a promising therapeutic strategy for glaucoma and potentially other neurodegenerative diseases associated with mitochondrial dysfunction and impaired bioenergetics.

The visual cortex is an essential part of the brain for processing visual information. It exhibits structural and functional plasticity, which is crucial for adapting to complex visual environments. The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period, which involves numerous cellular and molecular events. While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity, recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved. Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.

AbstractBackgroundThoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood.MethodsPatients were identified from a Chinese cancer center (FUSCC) (2005–2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000–2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed.ResultsTotally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy.ConclusionsLACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.

P URPOSE . This study investigates alterations in intrinsically photosensitive retinal ganglion cells (ipRGCs) and dopaminergic amacrine cells (DACs) in lid suture myopia (LSM) rats. M ETHODS . LSM was induced in rats by suturing the right eyes for 4 weeks. Double immunofluorescence staining of ipRGCs and DACs in whole-mount retinas was performed to analyze changes in the density and morphology of control, LSM, and fellow eyes. Real-time quantitative PCR and Western blotting were used to detect related genes and protein expression levels. R ESULTS . Significant myopia was induced in the lid-sutured eye, but the fellow eye was not different to control. Decreased ipRGC density with paradoxically increased overall melanopsin expression and enlarged dendritic beads was observed in both the LSM and fellow eyes of the LSM rat retinas. In contrast, DAC changes occurred only in the LSM eyes, with reduced DAC density and tyrosine hydroxylase (TH) expression, sparser dendritic processes, and fewer varicosities. Interestingly, contacts between ipRGCs and DACs in the inner plexiform layer (IPL) and the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and vesicular monoamine transporter protein 2 (VMAT2) mRNA were decreased in the LSM eyes. C ONCLUSIONS . The ipRGCs and DACs in LSM rat retinas undergo multiple alterations in density, morphology, and related molecule expressions. However, the ipRGC changes alone appear not to be required for the development of myopia, given that myopia is only induced in the lid-sutured eye, and they are unlikely alone to drive the DAC changes. Reduced contacts between ipRGCs and DACs in the LSM eyes may be the structural foundation for the impaired signaling between them. PACAP and VMAT2, strongly associated with ipRGCs and DACs, may play important roles in LSM through complex mechanisms.

Abnormal visual experience during the critical period can cause deficits in visual function, such as amblyopia. High magnesium (Mg2+) supplementary can restore ocular dominance (OD) plasticity, which promotes the recovery of amblyopic eye acuity in adults. However, it remains unsolved whether Mg2+ could recover binocular vision in amblyopic adults and what the molecular mechanism is for the recovery. We found that in addition to the recovery of OD plasticity, binocular integration can be restored under the treatment of high Mg2+ in amblyopic mice. Behaviorally, Mg2+-treated amblyopic mice showed better depth perception. Moreover, the effect of high Mg2+ can be suppressed with transient receptor potential melastatin-like 7 (TRPM7) knockdown. Collectively, our results demonstrate that high Mg2+ could restore binocular visual functions from amblyopia. TRPM7 is required for the restoration of plasticity in the visual cortex after high Mg2+ treatment, which can provide possible clinical applications for future research and treatment of amblyopia.

Alternating copolymers are crucial for diverse applications. While dispersity ( Ð , also known as molecular weight distribution, MWD) influences the properties of polymers, achieving low dispersities in alternating copolymers poses a notable challenge via free radical polymerizations (FRPs). In this work, we demonstrated an unexpected discovery that dispersities are affected by the participation of charge transfer complexes (CTCs) formed between monomer pairs during free radical alternating copolymerization, which have inspired the successful synthesis of various alternating copolymers with low dispersities (>30 examples, Ð =1.13–1.39) under visible-light irradiation. The synthetic method is compatible with binary, ternary and quaternary alternating copolymerizations and is expandable for both fluorinated and non-fluorinated monomer pairs. DFT calculations combined with model experiments indicated that CTC-absent reaction exhibits higher propagation rates and affords fewer radical terminations, which could contribute to low dispersities. Based on the integration of Monte Carlo simulation and Bayesian optimization, we established the relationship map between FRP parameter space and dispersity, further suggested the correlation between low dispersities and higher propagation rates. Our research sheds light on dispersity control via FRPs and creates a novel platform to investigate polymer dispersity through machine learning.

Organocatalyzed photo-controlled radical polymerizations (photo-CRPs) have gained increasing interest in tailoring polymers with spatiotemporal regulation. In this work, we have developed an organocatalyzed photo-CRP with various sulfonyl chlorides as initiators by using disulfides as chain transfer agents. In contrast to well-established metal-catalyzed CRPs from sulfonyl initiators, this method not only enables controlled synthesis of polymers without demanding a transition-metal catalyst at room temperature, but also facilitates "ON/OFF" temporal control using LED light as an external trigger. Proton nuclear magnetic resonance and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopies have evidenced the chemical structure of polymers with both sulfonyl and trithiocarbonate terminals. Chain extensions with different macro-initiators and monomers have been successfully conducted to yield block copolymers, suggesting the good chain-end fidelity of polymers obtained in this reaction. We believe that this method represents an attractive metal-free approach to obtain tailored polymers with readily available sulfonyl chlorides as alternative initiators driven by light.

Organocatalyzed reversible-deactivation radical polymerizations (RDRPs) are attractive for many applications. Here, we developed photoredox-mediated RDRP by activating (hetero)aryl sulfonyl chloride (ArSO2 Cl) initiators with pyridines and designing a novel bis(phenothiazine)arene catalyst. The in situ formed sulfonyl pyridinium intermediates effectively promote controlled chain-growth from ArSO2 Cl, enabling access to various well-defined polymers with high initiation efficiencies and controlled dispersities under mild conditions. This versatile method allows "ON/OFF" temporal control, chain-extension, facile synthesis of different polymer brushes via organocatalyzed grafting reactions from linear chains. Time-resolved fluorescence decay studies and calculations support the reaction mechanism. This work provides a transition-metal-free RDRP to tailor polymers with readily available aromatic initiators, and will promote the design of polymerization leveraged from photoredox catalysis.

Fluoroalkenes are feedstocks in the manufacture of high-performance fluoropolymers with various applications. However, the synthesis of well-defined fluoropolymers typically requires harsh conditions and high-pressure techniques to handle gaseous fluoroalkenes. Here, we report the combination of a redox-relay pathway and thermally activated delayed fluorescence (TADF) catalysis to enable controlled copolymerizations of various fluoroalkenes, under ambient conditions. Using this method, a broad scope of main-chain fluoropolymers is prepared with excellent selectivity at low organocatalyst dosages (loadings down to 5 ppm). In addition, polymers with various sequences (for example, diblock and triblock) and topologies (either brush or branched) are synthesized by integration with different agents and synthetic protocols. Mechanistic studies reveal that the rationally designed organic TADF catalyst displays the unique characteristics of redox-relay-based electron transfer, a long lifetime of delayed fluorescence and fine-tuned electronic properties. This work provides an informative concept for precise polymer synthesis and may inspire advanced applications in fluoropolymer engineering. Controlled radical polymerization of fluorinated monomers typically synthesizes fluoropolymers of limited molecular weights with poor control. Now the controlled copolymerization of various fluoroalkenes under ambient conditions is reported by combining a redox-relay pathway and thermally activated delayed fluorescence catalysis.