The endosomal sorting complex ESCRT-II mediates the assembly and architecture of ESCRT-III helices.

The endosomal sorting complexes required for transport (ESCRTs) constitute hetero-oligomeric machines that mediate topologically similar membrane-sculpting processes, including cytokinesis, retroviral egress, and multivesicular body (MVB) biogenesis. Although ESCRT-III drives membrane remodeling that creates MVBs, its structure and the mechanism of vesicle formation are unclear. Using electron microscopy, we visualize an ESCRT-II:ESCRT-III supercomplex and propose how it mediates vesicle formation. We define conformational changes that activate ESCRT-III subunit Snf7 and show that it assembles into spiraling ~9 nm protofilaments on lipid monolayers. A high-content flow cytometry assay further demonstrates that mutations halting ESCRT-III assembly block ESCRT function. Strikingly, the addition of Vps24 and Vps2 transforms flat Snf7 spirals into membrane-sculpting helices. Finally, we show that ESCRT-II and ESCRT-III coassemble into ~65 nm diameter rings indicative of a cargo-sequestering supercomplex. We propose that ESCRT-III has distinct architectural stages that are modulated by ESCRT-II to mediate cargo capture and vesicle formation by ordered assembly.

Autism patient-derived SHANK2BY29X mutation affects the development of ALDH1A1 negative dopamine neuron.

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endogenous SHANK2 proteins in an isoform-specific manner. Here, we report a point mutation on SHANK2, which is found in a patient with autism, located on exon of the SHANK2B transcript variant (NM_133266.5), hereby SHANK2BY29X. This mutation results in an early stop codon and an aberrant splicing event that impacts SHANK2 transcript variants distinctly. Induced pluripotent stem cells (iPSCs) carrying this mutation, from the patient or isogenic editing, fail to differentiate into functional dopamine (DA) neurons, which can be rescued by genetic correction. Available SMART-Seq single-cell data from human midbrain reveals the abundance of SHANK2B transcript in the ALDH1A1 negative DA neurons. We then show that SHANK2BY29X mutation primarily affects SHANK2B expression and ALDH1A1 negative DA neurons in vitro during early neuronal developmental stage. Mice knocked in with the identical mutation exhibit autistic-like behavior, decreased occupancy of ALDH1A1 negative DA neurons and decreased dopamine release in ventral tegmental area (VTA). Our study provides novel insights on a SHANK2 mutation derived from autism patient and highlights SHANK2B significance in ALDH1A1 negative DA neuron.

Time trends of 16 modifiable risk factors on the burden of major cancers among the Chinese population.

The cancer burden in China is increasing. We aimed to assess the time trends in the prevalence of 16 modifiable risk factors involved in lifestyle, diet, infection, and air pollution between 1997 and 2025 based on the China Health and Nutrition Survey, the Global Burden of Disease website, and publically available studies. The population attributable fraction (PAF) and its 95% uncertainty interval (UI) from 2007 to 2035 were calculated to quantify the attributable cancer burden in major 12 anatomic sites using the comparative risk assessment method, considering a 10-year lag effect. As a result, 1,559,476 cancer cases (PAF = 54.1%, 95% UI: 36.8%-65.8%) from the 12 anatomic sites were attributable to these modifiable risk factors in 2007, with lung, liver, and gastric cancer raging the top three. It was predicted that by 2035, the attributable cancer cases would reach 1,680,098 (PAF = 44.2%, 95% UI: 29.1%-55.5%), with the top three of lung, liver, and colorectal cancer. Smoking, physical inactivity, insufficient fruit consumption, HBV infection, and Helicobacter pylori infection were the most attributable risk factors in 2007, contributing to 480,352, 233,684, 215,009, 214,455, and 187,305 associated cancer cases, respectively. In 2035, the leading factors for cancer would be smoking, physical inactivity, insufficient fruit intake, HPV infection, and HBV infection, resulting in 427,445, 424,327, 185,144, 156,535, and 154,368 cancer cases, respectively. Intervention strategies should be swiftly established and dynamically altered in response to risk factors like smoking, physical inactivity, poor fruit intake, and infectious factors that may cause a high cancer burden in the Chinese population.

Synergetic Electrostatic and Steric Effects in α-FAPbI3 Single Crystals For X-Ray Detection and Imaging.

It is still challenging to stabilize α-FAPbI3 perovskite for high performance optoelectrical devices. Herein, a novel strategy is proposed utilizing the synergetic electrostatic and steric effect to stabilize the α-FAPbI3 phase and suppress the ion migration. Dimethylamine (DMA+) cations are chosen as the dopant to fabricate FA0.96DMA0.04PbI3 single crystals (SCs). DFT calculations reveal that DMA+ cations can improve the stability of α-FAPbI3 phase in both thermodynamics (lower Gibbs free energy) and kinetics (higher defect formation and migration energy). The resulting SCs exhibit an environmental stability over 100 days and an extraordinary low dark current drift of 3.7 × 10-7 nA cm-1 s-1 V-1, comparable to 2D perovskite SCs. The X-ray detectors have also achieved the-state-of-the-art performance in X-ray detection and imaging. This work demonstrates the significance of electrostatic and steric effects in improving the phase and operational stability of perovskites.

BST2 promotes gastric cancer metastasis under the regulation of HOXD9 and PABPC1.

Gastric cancer (GC) constitutes substantial cancer mortality worldwide. Several cancer types aberrantly express bone marrow stromal cell antigen 2 (BST2), yet its functional and underlying mechanisms in GC progression remain unknown. In our study, RNA sequencing data revealed that BST2 was transcriptionally activated by homeobox D9 (HOXD9). BST2 was significantly upregulated in GC tissues and promoted epithelial-mesenchymal transition and metastasis of GC. BST2 knockdown reversed HOXD9's oncogenic effect on GC metastasis. Moreover, BST2 messenger RNA stability could be enhanced by poly(A) binding protein cytoplasmic 1 (PABPC1) through the interaction between BST2 3'-UTR and PABPC1 in GC cells. PABPC1 promoted GC metastasis, which BST2 silencing attenuated in vitro and in vivo. In addition, positive correlations among HOXD9, BST2, and PABPC1 were established in clinical samples. Taken together, increased expression of BST2 induced by HOXD9 synergizing with PABPC1 promoted GC cell migration and invasion capacity.

Relationship between triglyceride-glucose index baselines and trajectories with incident cardiovascular diseases in the elderly population.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants. METHODS: After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes. RESULTS: During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19-1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10-1.25) and 1.25 (1.15-1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs. CONCLUSION: Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.

Aptamer-Modified Nb2C Multifunctional Nanomedicine for Targeted Photothermal/Chemotherapy Combined Therapy of Tumor.

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

Pathogenesis of cardiovascular diseases: effects of mitochondrial CF6 on endothelial cell function.

Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.

Post-diagnostic lifestyle and mortality of cancer survivors: Results from a prospective cohort study.

OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

Ethyl 3-aminobenzo[b]thiophene-2-carboxylate Derived Ratiometric Schiff Base Fluorescent Sensor for the Recognition of In3+ and Pb2.

An ethyl 3-aminobenzo[b]thiophene-2-carboxylate derived ratiometric Schiff base fluorescent sensor R was devised and synthesized. R exhibited a highly sensitive and selective ratiometric response to In3+ in DMF/H2O tris buffer solution. R exhibited a colorimetric/fluorescent dual-channel response to In3+. More importantly, R can distinguish In3+ from Ga3+ and Al3+ in less than 5 min. R exhibited a good linear correlation with the concentration of In3+ in the 5-25 µM range and the limit of detection for In3+ was found to be 8.36 × 10-9 M. According to the job`s plot and MS spectra, R formed a complex with In3+ at 1:2 with a complexation constant of 8.24 × 109 M2. Based on Gaussian theory calculations, the response mechanism of R to In3+ can be explained by photo-induced electron transfer (PET) and intramolecular charge transfer (ICT) mechanisms. In addition, R can be used for the detection of indium in tap water with satisfactory recoveries. Meanwhile, R displayed a linear relationship to micromolar concentrations (0-50 µM) of Pb2+ and recognized Pb2+ in a ratiometric response with a detection limit of 8.3 × 10-9 M.

Outcomes of Chengdu Pediatric Emergency Triage Criteria: A Retrospective Study of 198,628 Pediatric Patient Records.

BACKGROUND The Chengdu pediatric emergency triage criteria were developed at our hospital and consist of 4 triage levels: immediate treatment (level 1), treatment within 10 min (level 2), treatment within 30 min (level 3), and treatment within 240 min (level 4). This study aimed to evaluate outcomes from the levels 1 to 4 of this triage criteria. MATERIAL AND METHODS A self-designed survey form was used to collect pediatric Emergency Department (ED) patients' general data, including age, sex, and chief concern, and clinical data, including triage level, whether the patient had died, and whether the patient was admitted to our hospital. A total of 198,628 patient records that were triaged during January to May 2022 using Chengdu pediatric emergency triage criteria were included in this retrospective study. The numbers of patients triaged to levels 1, 2, 3, and 4 were 128, 1164, 14,560, and 182,776, respectively. RESULTS Statistically significant differences were found in waiting time for treatment, hospital admission rates, admission conversion rates, and case mix index at admission under different triage levels. The higher the triage priority level, the shorter the waiting time for ED treatment, higher the hospital admission and admission conversion rates, and higher case mix index value. CONCLUSIONS The Chengdu pediatric emergency triage criteria developed and applied within our hospital appears to be characterized by good clinical validity. Equipped with this triage criteria, triage nurses are more capable of determining the severity and emergency of the pediatric ED patients' health conditions and effectively triaging the patients.

Post-discharge nutritional management for patients with coronary heart disease and frailty: a qualitative study.

BACKGROUND: Frail elderly patients experience physiological function and reserve depletion, leading to imbalances in their internal environment, which increases the risk of coronary heart disease recurrence and malnutrition. However, the majority of these patients, who primarily have a low level of education and lack self-management skills, face difficulties actively dealing with obstacles during the transition period after their discharge from hospitalization. Therefore, it is necessary to understand and discuss in depth the nutrition management experience of discharged elderly patients with coronary heart disease and frailty (ages 65-80 years old) and to analyze the promoting and hindering factors that affect scientific diet behavior during the discharge transition period. METHODS: Fifteen elderly patients with coronary heart disease and frailty who had been discharged from the hospital for 6 months were interviewed using a semistructured method. The directed content analysis approach to descriptive research was used to extract topics from the interview content. RESULTS: All participants discussed the problems in health nutrition management experience of discharged. Five topics and ten subtopics were extracted, such as ①Weak perceptions and behaviors towards healthy eating (personal habit solidification, negative attitudes towards nutrition management), ②Lack of objective factors for independently adjusting dietary conditions (reliance on subjective feelings, times of appetite change), ③Personal hindrance factors (memory impairment, deficiencies in self-nutrition management), ④Expected external support (assistance care support, ways to obtain nutritional information), ⑤Lack of continuous nutrition management (interruption of professional guidance, avoidance of medical treatment behavior). CONCLUSIONS: Nutrition management after discharge places a burden on elderly patients with coronary heart disease and frailty. According to the patients' physical conditions, we should develop a diet support system that is coordinated by individuals, families and society.

Monitoring SF6 Gas Leakage Based on a Customized Binocular System.

Sulfur hexafluoride (SF6) gas is extensively utilized as an insulating and arc-quenching medium in the circuit breakers and isolating switches of electrical equipment. It effectively isolates the circuits from the atmosphere and promptly extinguishes arcs. Therefore, the issue of SF6 gas leakage poses a significant threat to the related application fields, and the detection of SF6 gas leakage becomes extremely important. Infrared imaging detection offers advantages including non-contact, high precision, and visualization. However, most existing infrared detection systems are equipped with only one filter to detect SF6 gas. The images captured contain background noise and system noise, making these systems vulnerable to interference from such noises. To address these issues, we propose a method for monitoring SF6 gas leakage based on a customized binocular imaging (CBI) system. The CBI system has two filters, greatly reducing the interference of system noise and background noise. The first filter features the absorption resonant peak of SF6 gas. The second filter is used to record background noise and system noise. One aspect to note is that, in order to avoid the interference of other gases, the central wavelength of this second filter should keep away from the absorption resonant peaks of those gases. Accordingly, the central wavelengths of our customized filters were determined as 10,630 nm and 8370 nm, respectively. Then, two cameras of the same type were separately assembled with a customized filter, and the CBI prototype was accomplished. Finally, we utilized the difference method using two infrared images captured by the CBI system, to monitor the SF6 gas leakage. The results demonstrate that our developed system achieves a high accuracy of over 99.8% in detecting SF6 gas. Furthermore, the CBI system supports a plug-and-play customization to detect various gases for different scenarios.

The Simultaneous Efficient Recovery of Ammonia Nitrogen and Phosphate Resources in the Form of Struvite: Optimization and Potential Applications for the Electrochemical Reduction of NO3.

In response to the need for improvement in the utilization of ammonium-rich solutions after the electrochemical reduction of nitrate (NO3--RR), this study combined phosphorus-containing wastewater and adopted the electrochemical precipitation method for the preparation of struvite (MAP) to simultaneously recover nitrogen and phosphorus resources. At a current density of 5 mA·cm-2 and an initial solution pH of 7.0, the recovery efficiencies for nitrogen and phosphorus can reach 47.15% and 88.66%, respectively. Under various experimental conditions, the generated struvite (MgNH4PO4·6H2O) exhibits a typical long prismatic structure. In solutions containing nitrate and nitrite, the coexisting ions have no significant effect on the final product, struvite. Finally, the characterization of the precipitate product by X-ray diffraction (XRD) revealed that its main component is struvite, with a high purity reaching 93.24%. Overall, this system can effectively recover ammonium nitrogen from the NO3--RR solution system after nitrate reduction, with certain application prospects for the recovery of ammonium nitrogen and phosphate.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Bipolar membrane electrodialysis integrated with in-situ CO2 absorption for simulated seawater concentrate utilization, carbon storage and production of sodium carbonate.

In the context of carbon capture, utilization, and storage, the high-value utilization of carbon storage presents a significant challenge. To address this challenge, this study employed the bipolar membrane electrodialysis integrated with carbon utilization technology to prepare Na2CO3 products using simulated seawater concentrate, achieving simultaneous saline wastewater utilization, carbon storage and high-value production of Na2CO3. The effects of various factors, including concentration of simulated seawater concentrate, current density, CO2 aeration rate, and circulating flow rate of alkali chamber, on the quality of Na2CO3 product, carbon sequestration rate, and energy consumption were investigated. Under the optimal condition, the CO32- concentration in the alkaline chamber reached a maximum of 0.817 mol/L with 98 mol% purity. The resulting carbon fixation rate was 70.50%, with energy consumption for carbon sequestration and product production of 5.7 kWhr/m3 CO2 and 1237.8 kWhr/ton Na2CO3, respectively. This coupling design provides a triple-win outcome promoting waste reduction and efficient utilization of resources.

Stress Dissipation Driven by Multi-Interface Built-In Electric Fields and Desert-Rose-Like Structure for Ultrafast and Superior Long-Term Sodium Ion Storage.

The kinetics and durability of conversion-based anodes greatly depend on the intrinsic stress regulating ability of the electrode materials, which has been significantly neglected. Herein, a stress dissipation strategy driven by multi-interface built-in electric fields (BEFs) and architected structure, is innovatively proposed to design ultrafast and long-term sodium ion storage anodes. Binary Mo/Fe sulfide heterostructured nanorods with multi-interface BEFs and staggered cantilever configuration are fabricated to prove our concept. Multi-physics simulations and experimental results confirm that the inner stress in multiple directions can be dissipated by the multi-interface BEFs at the micro-scale, and by the staggered cantilever structure at the macro-scale, respectively. As a result, our designed heterostructured nanorods anode exhibits superb rate capability (332.8 mAh g-1 at 10.0 A g-1 ) and durable cyclic stability over 900 cycles at 5.0 A g-1 , outperforming other metal chalcogenides. This proposed stress dissipation strategy offers a new insight for developing stable structures for conversion-based anodes.

Carbon superstructure-supported half-metallic V2O3 nanospheres for high-efficiency photorechargeable zinc ion batteries.

Photorechargeable zinc ion batteries (PZIBs), which can directly harvest and store solar energy, are promising technologies for the development of a renewable energy society. However, the incompatibility requirement between narrow band gap and wide coverage has raised severe challenges for high-efficiency dual-functional photocathodes. Herein, half-metallic vanadium (III) oxide (V2O3) was first reported as a dual-functional photocathode for PZIBs. Theoretical and experimental results revealed its unique photoelectrical and zinc ion storage properties for capturing and storing solar energy. To this end, a synergistic protective etching strategy was developed to construct carbon superstructure-supported V2O3 nanospheres (V2O3@CSs). The half-metallic characteristics of V2O3, combined with the three-dimensional superstructure assembled by ultrathin carbon nanosheets, established rapid charge transfer networks and robust framework for efficient and stable solar-energy storage. Consequently, the V2O3@CSs photocathode delivered record zinc ion storage properties, including a photo-assisted discharge capacities of 463 mAh∙g-1 at 2.0 A∙g-1 and long-term cycling stability over 3000 cycles. Notably, the PZIBs assembled using V2O3@CSs photocathodes could be photorecharged without an external circuit, exhibiting a high photo conversion efficiency (0.354%) and photorecharge voltage (1.0 V). This study offered a promising direction for the direct capture and storage of solar energy.

Chemoenzymatic Measurement of LacNAc in Single-Cell Multiomics Reveals It as a Cell-Surface Indicator of Glycolytic Activity of CD8+ T Cells.

Despite the rich information about the physiological state of a cell encoded in the dynamic changes of cell-surface glycans, chemical methods to capture specific glycan epitopes at the single-cell level are quite limited. Here, we report a chemoenzymatic method for the single-cell detection of N-acetyllactosamine (LacNAc) by labeling LacNAc with a specific DNA barcode. The chemoenzymatic labeling does not alter the transcriptional status of immune cells and is compatible with multiple scRNA-seq platforms. Integrated analysis of LacNAc and the transcriptome of T cells at the single-cell level reveals that the amount of cell-surface LacNAc is significantly upregulated in activated CD8+ T cells but maintained at basal levels in resting CD8+ T cells (i.e., naive and central memory T cells). Further analysis confirms that LacNAc levels are positively correlated with the glycolytic activity of CD8+ T cells during differentiation. Taken together, our study demonstrates the feasibility of the chemoenzymatic detection of cell-surface glycan in single-cell RNA sequencing-based multiomics with TCR sequence and cell-surface epitope information (i.e., scTCR and CITE-seq), and provides a new way to characterize the biological role of glycan in diverse physiological states.

Age-related impairment in fear memory extinction is restored by ketamine in middle-aged mice.

Posttraumatic stress disorder (PTSD), a disabling and chronic condition after exposure to an extreme traumatic event, affects approximately 8% of the population worldwide. However, the underlying mechanisms of PTSD are not clear. The ability to manage fear memories is critical for PTSD. Differences in stress responsiveness and coping strategies by age represent an important starting point for the understanding and prevention of PTSD. However, we do not know whether the ability to cope with fear memories is decreased in middle-aged mice. To investigate this, we compared fear memory extinction among different age groups of mice. We found that middle-aged mice exhibited impaired fear memory extinction, which was accompanied by sustained enhanced long-term potentiation (LTP) induction in the extinction process. Most interestingly, ketamine treatment restored the impaired fear memory extinction in middle-aged mice. Moreover, ketamine could ameliorate the increased LTP during the extinction process through a presynaptic mechanism. Altogether, our results indicated that middle-aged mice were unable to extinguish fear memories, which could be treated with ketamine via presynaptic-mediated synaptic plasticity in middle-aged mice, suggesting that ketamine administration may be a new strategy for the treatment of PTSD.