An increase of serum CA-125 to two times of nadir level strongly predicts the image-identified relapse of serous ovarian cancer.

Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors.

Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.

30-100 kHz, 2 ns passively Q-switched laser for fast and efficient photoacoustic microscopy.

Actively Q-switched (AQS) fiber laser and solid-state laser (SSL) are widely used for photoacoustic microscopy (PAM). In contrast, passively Q-switched (PQS) SSL not only maintains most of the merits of AQS lasers, but also exhibits unique advantages, including the pulse width (PW), pulse repetition rate (PRR) tunability, wavelength, compactness, and cost. These advantages all benefit the PAM. However, there are few reports demonstrating the performance of PQS-SSL on PA imaging. Here, we demonstrate a compact PQS-SSL for fast and efficient PA imaging. The laser uniquely maintains a constant PW (~2 ns) and pulse energy (~3 µJ) during the PRR variation (30-100 kHz), which is valuable for preserving a stabilized imaging performance at different scanning rates. The PA imaging performance is compared by a resolution target and showcased by whole-body scanning of an embryonic zebrafish in vivo. The performance indicates that PQS-SSL is a promising candidate for PAM.

NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π-π interaction to prepare g-C3N4-loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt-N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g-C3N4-loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage invitro and an OA joint model invivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

Feedback control of heart rate during treadmill exercise based on a two-phase response model.

This work investigated automatic control of heart rate during treadmill exercise. The aim was to theoretically derive a generic feedback design strategy that achieves a constant input sensitivity function for linear, time-invariant plant models, and to empirically test whether a compensator C2 based on a second-order model is more dynamic and has better tracking accuracy than a compensator C1 based on a first-order model. Twenty-three healthy participants were tested using first and second order compensators, C1 and C2, respectively, during 35-minute bouts of constant heart rate treadmill running. It was found that compensator C2 was significantly more accurate, i.e. it had 7% lower mean root-mean-square tracking error (1.98 vs. 2.13 beats per minute, p = 0.026), and significantly more dynamic, i.e. it had 17% higher mean average control signal power (23.4 × 10-4 m2/s2 vs. 20.0 × 10-4 m2/s2, p = 0.011), than C1. This improvement likely stems from the substantially and significantly better fidelity of second-order models, compared to first order models, in line with classical descriptions of the different phases of the cardiac response to exercise. These outcomes, achieved using a treadmill, are consistent with previous observations for the cycle ergometer exercise modality. In summary, whenever heart rate tracking accuracy is of primary importance and a more dynamic control signal is acceptable, the use of a compensator based on a second-order nominal model is recommended.

Comprehensive systematic review and meta-analysis of the association between common genetic variants and autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is neurodevelopmental disorder characterized by stereotyped behavior and deficits in communication and social interactions. To date, numerous studies have investigated the associations between genetic variants and ASD risk. However, the results of these published studies lack a clear consensus. In the present study, we performed a systematic review on the association between genetic variants and ASD risk. Meanwhile, we conducted a meta-analysis on available data to identify the association between the single nucleotide polymorphisms (SNPs) of candidate genes and ASD risk. METHODS: We systematically searched public databases including English and Chinese from their inception to August 1, 2022. Two independent reviewers extracted data and assessed study quality. Odds ratio and 95 % confidence interval were used as effect indexes to evaluate the association between the SNPs of candidate genes and the risk of ASD. Heterogeneity was explored through subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed by using Egger's and Begg's tests for funnel plot asymmetry. In addition, TSA analysis were performed to confirm the study findings. RESULTS: We summarized 84 SNPs of 32 candidate genes from 81 articles included in the study. Subsequently, we analyzed 16 SNPs of eight genes by calculating pooled ORs, and identified eight significant SNPs of contactin associated protein 2 (CNTNAP2), methylentetrahydrofolate reductase (MTHFR), oxytocin receptor (OXTR), and vitamin D receptor (VDR). Results showed that seven SNPs, including the CNTNAP2 rs2710102 (homozygote, heterozygote, dominant and allelic models) and rs7794745 (heterozygote and dominant models), MTHFR C677T (homozygote, heterozygote, dominant, recessive and allelic models) and A1298C (dominant and allelic models), OXTR rs2254298 (homozygote and recessive models), VDR rs731236 (homozygote, dominant, recessive and allelic models) and rs2228570 (homozygote and recessive models), were showed to be correlated with an increased ASD risk. By contrast, the VDR rs7975232 was correlated with a decreased the risk of ASD under the homozygote and allelic models. CONCLUSION: Our study summarized research evidence on the genetic variants of ASD and provides a broad and detailed overview of ASD risk genes. The C677T and A1298C polymorphisms of MTHFR, rs2710102 and rs7794745 polymorphisms of CNTNAP2, rs2254298 polymorphism of OXTR, and rs731236 and rs2228570 polymorphisms of VDR were genetic risk factors. The rs7975232 polymorphism of VDR was a genetic protective factor for ASD. Our study provides novel clues to clinicians and healthcare decision-makers to predict ASD susceptibility.

A programmable oral bacterial hydrogel for controllable production and release of nanovaccine for tumor immunotherapy.

Oral protein vaccines are mainly used to prevent the infection of intestinal pathogens in clinic due to their high safety and strong compliance. However, it is necessary to design the efficient delivery systems to overcome the harsh gastrointestinal environment in the application process. Here we established a programmable oral bacterial hydrogel system for spatiotemporally controllable production and release of nanovaccines. The system was divided into three parts: (1) Engineered bacteria were encapsulated in chitosan-sodium alginate microcapsules, which offered protection against the extreme acid conditions in the stomach. (2) Microcapsules were dissolved, and then engineered bacteria were released and colonized in the intestine. (3) The release of nanovaccines was controlled periodically by a synchronous lysis genetic circuit for tumor immunotherapy. Compared to control groups, tumor volume of subcutaneous tumor-bearing mice treated with bacterial microgels releasing optimized nanovaccine was almost inhibited by 75% and T cell response was activated at least 2-fold. We believe that this programmable bacterial hydrogel will offer a promising way for the application of oral nanovaccines.

A flexible wearable device coupled with injectable Fe3O4 nanoparticles for capturing circulating tumor cells and triggering their deaths.

Elimination of circulating tumor cells (CTCs) in the blood can be an effective therapeutic approach to disrupt metastasis. Here, a strategy is proposed to implement flexible wearable electronics and injectable nanomaterials to disrupt the hematogenous transport of CTCs. A flexible device containing an origami magnetic membrane is used to attract Fe3O4@Au nanoparticles (NPs) that are surface modified with specific aptamers and intravenously injected into blood vessels, forming an invisible hand and fishing line/bait configuration to specifically capture CTCs through bonding with aptamers. Thereafter, thinned flexible AlGaAs LEDs in the device offer an average fluence of 15.75 mW mm-2 at a skin penetration depth of 1.5 mm, causing a rapid rise of temperature to 48 °C in the NPs and triggering CTC death in 10 min. The flexible device has been demonstrated for intravascular isolation and enrichment of CTCs with a capture efficiency of 72.31% after 10 cycles in a simulated blood circulation system based on a prosthetic upper limb. The fusion of nanomaterials and flexible electronics reveals an emerging field that utilizes wearable and flexible stimulators to activate biological effects offered by nanomaterials, leading to improved therapeutical effects and postoperative outcomes of diseases.

Electrochemical biosensor based on antibody-modified Au nanoparticles for rapid and sensitive analysis of influenza A virus.

To cope with the easy transmissibility of the avian influenza A virus subtype H1N1, a biosensor was developed for rapid and highly sensitive electrochemical immunoassay. Based on the principle of specific binding between antibody and virus molecules, the active molecule-antibody-adapter structure was formed on the surface of an Au NP substrate electrode; it included a highly specific surface area and good electrochemical activity for selective amplification detection of the H1N1 virus. The electrochemical test results showed that the BSA/H1N1 Ab/Glu/Cys/Au NPs/CP electrode was used for the electrochemical detection of the H1N1 virus with a sensitivity of 92.1 µA (pg/mL)-1 cm2, LOD of 0.25 pg/ml, linear ranges of 0.25-5 pg/mL, and linearity of (R 2 = 0.9846). A convenient H1N1 antibody-based electrochemical electrode for the molecular detection of the H1N1 virus will be of great use in the field of epidemic prevention and raw poultry protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11581-023-04944-w.

[Construction of "lock-key" biological living material based on double engineered bacteria and its application on intestinal retention in vivo].

At present, the research of biological living materials mainly focuses on applications in vitro, such as using a single bacterial strain to produce biofilm and water plastics. However, due to the small volume of a single strain, it is easy to escape when used in vivo, resulting in poor retention. In order to solve this problem, this study used the surface display system (Neae) of Escherichia coli to display SpyTag and SpyCatcher on the surface of two strains, respectively, and constructed a double bacteria "lock-key" type biological living material production system. Through this force, the two strains are cross-linked in situ to form a grid-like aggregate, which can stay in the intestinal tract for a longer time. The in vitro experiment results showed that the two strains would deposit after mixing for several minutes. In addition, confocal imaging and microfluidic platform results further proved the adhesion effect of the dual bacteria system in the flow state. Finally, in order to verify the feasibility of the dual bacteria system in vivo, mice were orally administrated by bacteria A (p15A-Neae-SpyTag/sfGFP) and bacteria B (p15A-Neae-SpyCatcher/mCherry) for three consecutive days, and then intestinal tissues were collected for frozen section staining. The in vivo results showed that the two bacteria system could be more detained in the intestinal tract of mice compared with the non-combined strains, which laid a foundation for further application of biological living materials in vivo.

A red light-controlled probiotic bio-system for in-situ gut-brain axis regulation.

Microbes regulate brain function through the gut-brain axis, deriving the technology to modulate the gut-brain axis in situ by engineered probiotics. Optogenetics offers precise and flexible strategies for controlling the functions of probiotics in situ. However, the poor penetration of most frequently used short wavelength light has limited the application of optogenetic probiotics in the gut. Herein, a red-light optogenetic gut probiotic was applied for drug production and delivery and regulation of the host behaviors. Firstly, a Red-light Optogenetic E. coli Nissle 1917 strain (ROEN) that could respond to red light and release drug product by light-controlled lysis was constructed. The remaining optical power of red light after 3 cm tissue was still able to initiate gene expression of ROEN and produce about approximately 3-fold induction efficiency. To give full play to the in vivo potential of ROEN, its responsive ability of the penetrated red light was tested, and its encapsulation was realized by PH-sensitive alginate microcapsules for further oral administration. The function of ROEN for gut-brain regulation was realized by releasing Exendin-4 fused with anti-neonatal Fc receptor affibody. Neuroprotection and behavioral regulation effects were evaluated in the Parkinson's disease mouse model, after orally administration of ROEN delivering Exendin-4 under optogenetic control in the murine gut. The red-light optogenetic probiotic might be a perspective platform for in situ drug delivery and gut-brain axis regulation.

Hydrogel-Encapsulated Engineered Microbial Consortium as a Photoautotrophic "Living Material" for Promoting Skin Wound Healing.

Genetically modified engineered microorganisms have been encapsulated in hydrogels and used as "living materials" for the treatment of skin diseases. However, their applications are often limited by the epidermal dry, nutrient-poor environment and cannot maintain functions stably for an expected sufficient time. To solve this problem, a photoautotrophic "living material" containing an engineered microbial consortium was designed and fabricated. The engineered microbial consortium comprised Synechococcus elongatus PCC7942 for producing sucrose by photosynthesis and another heterotrophic engineered bacterium (Escherichia coli or Lactococcus lactis) that can utilize sucrose for the growth and secretion of functional biomolecules. These engineered microorganisms in the "living material" were proved to function stably for a longer time than only individual microbes. Subsequently, CXCL12-secreting engineered L. lactis was used to construct the "living material", and its effect on promoting wound healing was verified in a full-thickness rat-skin defect model. The wounds treated by our hydrogel-encapsulated engineered microbial consortium (HeEMC) healed faster, with a wound area ratio of only 13.2% at day 14, compared to the remaining 62.6, 51.4, and 40.8% of the control, PEGDA, and PEGDA/CS groups, respectively. In conclusion, we established an efficient living material HeEMC to offer promising applications in the treatment of skin diseases.

Smartphone recognition-based immune microparticles for rapid on-site visual data-sharing detection of Newcastle disease virus.

Since the last century, animal viruses have posed great threats to the health of humans and the farming industry. Therefore, virus control is of great urgency, and regular, timely, and accurate detection is essential to it. Here, we designed a rapid on-site visual data-sharing detection method for the Newcastle disease virus with smartphone recognition-based immune microparticles. The detection method we developed includes three major modules: preparation of virus detection vectors, sample detection, and smartphone image analysis with data upload. First, the hydrogel microparticles containing active carboxyl were manufactured, which coated nucleocapsid protein of NDV. Then, HRP enzyme-labeled anti-NP nanobody was used to compete with the NDV antibody in the serum for color reaction. Then the rough detection results were visible to the human eyes according to the different shades of color of the hydrogel microparticles. Next, the smartphone application was used to analyze the image to determine the accurate detection results according to the gray value of the hydrogel microparticles. Meanwhile, the result was automatically uploaded to the homemade cloud system. The total detection time was less than 50 min, even without trained personnel, which is shorter than conventional detection methods. According to experimental results, this detection method has high sensitivity and accuracy. And especially, it uploads the detection information via a cloud platform to realize data sharing, which plays an early warning function. We anticipate that this rapid on-site visual data-sharing detection method can promote the development of virus self-checking at home.

Upconversion Optogenetic Engineered Bacteria System for Time-Resolved Imaging Diagnosis and Light-Controlled Cancer Therapy.

Engineering bacteria can achieve targeted and controllable cancer therapy using synthetic biology technology and the characteristics of tumor microenvironment. Besides, the accurate tumor diagnosis and visualization of the treatment process are also vital for bacterial therapy. In this paper, a light control engineered bacteria system based on upconversion nanoparticles (UCNP)-mediated time-resolved imaging (TRI) was constructed for colorectal cancer theranostic and therapy. UCNP with different luminous lifetimes were separately modified with the tumor targeting molecule (folic acid) or anaerobic bacteria (Nissle 1917, EcN) to realize the co-localization of tumor tissues, thus improving the diagnostic accuracy based on TRI. In addition, blue light was used to induce engineered bacteria (EcN-pDawn-φx174E/TRAIL) lysis and the release of tumor apoptosis-related inducing ligand (TRAIL), thus triggering tumor cell death. In vitro and in vivo results indicated that this system could achieve accurate tumor diagnosis and light-controlled cancer therapy. EcN-pDawn-φx174E/TRAIL with blue light irradiation could inhibit 53% of tumor growth in comparison to that without blue light irradiation (11.8%). We expect that this engineered bacteria system provides a new technology for intelligent bacterial therapy and the construction of cancer theranostics.

Social defeat drives hyperexcitation of the piriform cortex to induce learning and memory impairment but not mood-related disorders in mice.

Clinical studies have shown that social defeat is an important cause of mood-related disorders, accompanied by learning and memory impairment in humans. The mechanism of mood-related disorders has been widely studied. However, the specific neural network involved in learning and memory impairment caused by social defeat remains unclear. In this study, behavioral test results showed that the mice induced both learning and memory impairments and mood-related disorders after exposure to chronic social defeat stress (CSDS). c-Fos immunofluorescence and fiber photometry recording confirmed that CaMKIIα expressing neurons of the piriform cortex (PC) were selectively activated by exposure to CSDS. Next, chemogenetics and optogenetics were performed to activate PC CaMKIIα expressing neurons, which showed learning and memory impairment but not mood-related disorders. Furthermore, chemogenetic inhibition of PC CaMKIIα expressing neurons significantly alleviated learning and memory impairment induced by exposure to CSDS but did not relieve mood-related disorders. Therefore, our data suggest that the overactivation of PC CaMKIIα expressing neurons mediates CSDS-induced learning and memory impairment, but not mood-related disorders, and provides a potential therapeutic target for learning and memory impairment induced by social defeat.

[Reform of biology experiment teaching in the context of "Strengthening Basic Disciplines Program"-taking the course of comprehensive biology design as an example].

Talent training is the core of future national competition. "Strengthening Basic Disciplines Program" is an important initiative exploring the training mode for top-notch creative talents in basic disciplines, and an important measure to meet the needs for fostering future talents. The students enrolled in the "Strengthening Basic Disciplines Program" often have excellent grades and strong motivation, which puts forward new requirements and new goals for the talents training mode. Among them, the teaching reform under the background of "Strengthening Basic Disciplines Program" is imperative. The science, technology, engineering, arts, mathematics (STEAM) education concept is an interdisciplinary comprehensive educational philosophy that happens to coincide with the philosophy of the "Strengthening Basic Disciplines Program". In view of this, the School of Life Sciences of Tianjin University has explored and practiced the reform of biology experimental teaching based on the objective of fostering biology talents in the context of "Strengthening Basic Disciplines Plan" and the STEAM education concept, by taking the course of comprehensive biology design as an example.

Recent advances in cellular optogenetics for photomedicine.

Since the successful introduction of exogenous photosensitive proteins, channelrhodopsin, to neurons, optogenetics has enabled substantial understanding of profound brain function by selectively manipulating neural circuits. In an optogenetic system, optical stimulation can be precisely delivered to brain tissue to achieve regulation of cellular electrical activity with unprecedented spatio-temporal resolution in living organisms. In recent years, the development of various optical actuators and novel light-delivery techniques has greatly expanded the scope of optogenetics, enabling the control of other signal pathways in non-neuronal cells for different biomedical applications, such as phototherapy and immunotherapy. This review focuses on the recent advances in optogenetic regulation of cellular activities for photomedicine. We discuss emerging optogenetic tools and light-delivery platforms, along with a survey of optogenetic execution in mammalian and microbial cells.

Hydrogel microcapsules containing engineered bacteria for sustained production and release of protein drugs.

Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug factory.

Phosphorylation of Spastin Promotes the Surface Delivery and Synaptic Function of AMPA Receptors.

Synaptic plasticity is essential for cognitive functions such as learning and memory. One of the mechanisms involved in synaptic plasticity is the dynamic delivery of AMPA receptors (AMPARs) in and out of synapses. Mutations of SPAST, which encodes SPASTIN, a microtubule-severing protein, are considered the most common cause of hereditary spastic paraparesis (HSP). In some cases, patients with HSP also manifest cognitive impairment. In addition, mice with Spastin depletion exhibit working and associative memory deficits and reduced AMPAR levels. However, the exact effect and molecular mechanism of Spastin on AMPARs trafficking has remained unclear. Here, we report that Spastin interacts with AMPAR, and phosphorylation of Spastin enhances its interaction with AMPAR subunit GluA2. Further study shows that phosphorylation of Spastin can increase AMPAR GluA2 surface expression and the amplitude and frequency of miniature excitatory synaptic currents (mEPSC) in cultured hippocampal neurons. Moreover, phosphorylation of Spastin at Ser210 is crucial for GluA2 surface expression. Phosphorylation of Spastin K353A, which obliterates microtubule-severing activity, also promotes AMPAR GluA2 subunit trafficking to the surface and increases the amplitude and frequency of mEPSCs in cultured neurons. Taken together, our data demonstrate that Spastin phosphorylation promotes the surface delivery of the AMPAR GluA2 subunit independent of microtubule dynamics.