The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons.

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals' cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

Effect of collagen sponge combined with epidermal growth factor in repairing maxillofacial head and neck wounds in rats.

Collagen sponge and epidermal growth factor (EGF) promote wound healing. However, the effect of collagen sponge combined with EGF in repairing maxillofacial head and neck wounds remains unclear. The rats were divided into 3 groups, including experimental group 1 (Vaseline gauze+EGF), experimental group 2 (collagen sponge+EGF) with control group (Vaseline+normal saline), and maxillofacial head and neck wounds were simulated. Wound pathological morphology was detected by HE staining; wound EGF, IL-1ß, IL-6 along with TNF-α contents by ELISA and MMP1 level by western blot. At 7 and 14 days after treatment, wound healing rate of two experimental groups was higher than that of control group, and that of experimental group 2 presented higher than that of experimental group 1. Compared with control group, experimental group 1 had significantly fewer inflammatory cells in the wound tissue, local erythrocyte spillage outside the vascular walls, more collagen deposition and more granulation tissue. Compared with experimental group 1, inflammatory cells in wound tissues of experimental group 2 were significantly reduced, the collagen tissues were visible and arranged, and the growth of the wound granulation tissue was obvious. IL-1ß, IL-6 along with TNF-α levels in two experimental groups presented lower than control group, and EGF level was higher. More importantly, in contrast to experimental group 1, IL-1ß, IL-6 along with TNF-α in experimental group 2 presented lower, and EGF level presented higher. At 14 days after treatment, MMP1 level in two experimental groups was lower than control group. In contrast to experimental group 1, MMP1 level in experimental group 2 was lower. In summary, collagen sponge combined with EGF for the first time significantly improved the healing speed of maxillofacial head and neck wounds and reduced the scar left after wound healing.

Effects and underlying mechanism of micro-nano-structured zirconia surfaces on biological behaviors of human gingival fibroblasts under inflammatory conditions.

Zirconia is one of the most commonly used materials for abutments of dental implants, especially in the anterior region. Soft tissue integration to the zirconia abutment surface remains a challenge. Peri-implant soft tissue integration serves as a physiological barrier, attenuating pathogen penetration and preventing peri­implant disease. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but the effects under inflammatory conditions are still unclear. In this study, we established two micro-nano structures on zirconia surfaces using a femtosecond laser, including microgrooves with widths of 30 µm (G3) and 60 µm (G6) and depths of 5 µm, and nanoparticles inside the microgrooves. Polished surfaces were used as controls. HGFs were seeded onto the three groups of zirconia specimens and stimulated with lipopolysaccharide. The HGFs on micro-nano-structured zirconia surfaces exhibited lower inflammatory responses and higher cell adhesion, proliferation, and migration under inflammatory conditions compared with the polished surfaces. Additionally, the G3 group exhibited lower inflammatory responses and higher cell adhesion and migration than the G6 group. The micro-nano-structured zirconia surface exhibited decreased neutrophil infiltration and increased M2-type macrophage polarization in vivo. To explore the molecular mechanism, RNA sequencing and gene silencing were utilized, which revealed two critical target genes regulated by the G3 group. Overall, we proposed an innovative micro-nano-structured zirconia surface that reduced the in vitro and in vivo inflammatory responses and promoted HGF adhesion, migration, and proliferation under inflammatory conditions, in which TRAFD1 and NLRC5 were the underlying key genes. STATEMENT OF SIGNIFICANCE: Zirconia is one of the most commonly used materials for abutments, especially in the anterior region. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but few studies have investigated these effects under inflammatory conditions, and the mechanism remains unclear. In this study, we developed an innovative micro-nano-structured zirconia surface using a femtosecond laser, which reduces the in vitro and in vivo pro-inflammatory responses and promotes HGFs adhesion, migration, and proliferation under inflammatory conditions compared with the polished zirconia surface. The potential underlying mechanism was also investigated. This work has provided some theoretical basis for the micro-nano-structured zirconia surface in potentially reducing the inflammation and enhancing peri­implant soft-tissue integration under inflammatory conditions.

Consideration of non-phase-matched nonlinear effects in the design of quasi-phase-matching crystals for optical parametric oscillators.

Femtosecond optical parametric oscillators (OPOs) are widely used in ultrafast nonlinear frequency conversion and quantum information. However, conventional OPOs based on quasi-phase-matching (QPM) crystals have many parasitic non-phase-matched processes which decrease the conversion efficiency. Here, we propose nine-wave coupled equations (NWCEs) to simulate all phase-matched and non-phase-matched interactions in QPM crystals to improve conventional three-wave coupled equations (TWCEs), especially for the situation of high intensity ultrashort pulses and complexly structured crystals. We discuss how to design the poling period of QPM crystal to maximize the conversion efficiency of signal light for a given OPO system. The simulation reveals that the OPO based on chirped periodically poled lithium niobate (CPPLN) with a certain chirp rate has higher signal wave conversion efficiency than that of a PPLN, and demonstrates that NWCEs illustrate more details of the pulse evolution in the OPO cavity. Starting from a CPPLN, an aperiodically poled lithium niobate (APPLN) design is available by modifying the domain lengths of the crystal and optimizing the OPO output power via dynamical optimization algorithm. The results show that by using a properly designed APPLN crystal, a 1600 nm OPO, when pumped by a femtosecond laser with 1030 nm central wavelength, 150 femtosecond pulse duration and 5 GW/cm2 power intensity at the focus, can achieve very efficient output with a signal light conversion efficiency of 50.6%, which is higher than that of PPLN (25.2%) and CPPLN (40.2%). The scheme in this paper will provide a reference for the design of nonlinear QPM crystals of OPOs and will help to understand the complex nonlinear dynamical behavior in OPO cavities.

Liprin-α proteins are master regulators of human presynapse assembly.

The formation of mammalian synapses entails the precise alignment of presynaptic release sites with postsynaptic receptors but how nascent cell-cell contacts translate into assembly of presynaptic specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that in mammalian synapses, liprin-α proteins directly link trans-synaptic initial contacts to downstream steps. Here we show that, in human neurons lacking all four liprin-α isoforms, nascent synaptic contacts are formed but recruitment of active zone components and accumulation of synaptic vesicles is blocked, resulting in 'empty' boutons and loss of synaptic transmission. Interactions with presynaptic cell adhesion molecules of either the LAR-RPTP family or neurexins via CASK are required to localize liprin-α to nascent synaptic sites. Liprin-α subsequently recruits presynaptic components via a direct interaction with ELKS proteins. Thus, assembly of human presynaptic terminals is governed by a hierarchical sequence of events in which the recruitment of liprin-α proteins by presynaptic cell adhesion molecules is a critical initial step.

Numerical investigation of effective nonlinear coefficient model for coupled third harmonic generation.

In this paper, the optimal solution of effective nonlinear coefficient of quasi-phase-matching (QPM) crystals for coupled third harmonic generation (CTHG) was numerically investigated. The effective nonlinear coefficient of CTHG was converted to an Ising model for optimizing domain distributions of aperiodically poled lithium niobate (APPLN) crystals with lengths as 0.5 mm and 1 mm, and fundamental wavelengths ranging from 1000 nm to 6000 nm. A method for reconstructing crystal domain poling weight curve of coupled nonlinear processes was also proposed, which demonstrated the optimal conversion ratio between two coupled nonlinear processes at each place along the crystal. In addition, by applying the semidefinite programming, the upper bound on the effective nonlinear coefficients deff for different fundamental wavelengths were calculated. The research can be extended to any coupled dual χ(2) process and will help us to understand better the dynamics of coupled nonlinear interactions based on QPM crystals.

Clinical Study of Rh-bFGF Combined With Collagen Sponge in the Treatment of Maxillofacial Deep â ¡ Degree Burn.

OBJECTIVES: To observe the clinical effect of recombinant human alkaline fibroblast growth factor (rh-bFGF) combined with collagen sponge in the treatment of maxillofacial deepⅡ degree burn. METHODS: From January 2019 to January 2022, 96 patients with maxillofacial deep Ⅱ degree burns were randomly divided into a control group (N=48) and an observation group (N=48). The observation group was treated with rh-bFGF and collagen sponge after debridement, whereas the control group was treated with silver sulfadiazine ointment after debridement. The healing rate and healing time of the wounds were observed, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, epidermal growth factor (EGF), endothelial growth factor growth factor (VEGF), and metalloproteinase tissue inhibitor 1 (TIMP-1) were measured. Vancouver Scar Scale (VSS) was used to evaluate the local scar at 6 months after wound healing in both groups. RESULTS: On the 10th, 14th, and 21st day of treatment, the wound healing rate in the observation group was higher than that in the control group (P<0.05), the wound healing time in the observation group was lower than that in the control group (P<0.05), and on the 14th day of treatment, the levels of TNF-α and IL-6 in the observation group were lower than those in the control group (P<0.05). The levels of IL-10 in the observation group were higher than those in the control group (P<0.05). The levels of EGF, VEGF, and TIMP-1 in the observation group were higher than those in the control group (P<0.05), and the scores of VSS in the observation group were lower than those in the control group (P<0.05). CONCLUSIONS: Rh-bFGF combined with collagen sponge can decrease the levels of TNF-α and IL-6 and increase the levels of IL-10, which can control the inflammation effectively, at the same time, it can increase the level of EGF, VEGF, and TIMP-1, promote wound healing, and reduce scar hyperplasia. The treatment protocol is simple, safe, effective, and suitable for clinical application.

SLAM medical imaging enabled by pre-chirp and gain jointly managed Yb-fiber laser.

We demonstrate a pre-chirp and gain jointly managed Yb-fiber laser that drives simultaneous label-free autofluorescence-multiharmonic (SLAM) medical imaging. We show that a gain managed Yb-fiber amplifier produces high-quality compressed pulses when the seeding pulses exhibit proper negative pre-chirp. The resulting laser source can generate 43-MHz, 34-fs pulses centered at 1110 nm with more than 90-nJ energy. We apply this ultrafast source to SLAM imaging of cellular and extracellular components in various human tissues of intestinal adenocarcinoma, lung adenocarcinoma, and liver.

Autoinhibition and activation of myosin VI revealed by its cryo-EM structure.

Myosin VI is the only molecular motor that moves towards the minus end along actin filaments. Numerous cellular processes require myosin VI and tight regulations of the motor's activity. Defects in myosin VI activity are known to cause genetic diseases such as deafness and cardiomyopathy. However, the molecular mechanisms underlying the activity regulation of myosin VI remain elusive. Here, we determined the high-resolution cryo-electron microscopic structure of myosin VI in its autoinhibited state. Our structure reveals that autoinhibited myosin VI adopts a compact, monomeric conformation via extensive interactions between the head and tail domains, orchestrated by an elongated single-α-helix region resembling a "spine". This autoinhibited structure effectively blocks cargo binding sites and represses the motor's ATPase activity. Certain cargo adaptors such as GIPC can release multiple inhibitory interactions and promote motor activity, pointing to a cargo-mediated activation of the processive motor. Moreover, our structural findings allow rationalization of disease-associated mutations in myosin VI. Beyond the activity regulation mechanisms of myosin VI, our study also sheds lights on how activities of other myosin motors such as myosin VII and X might be regulated.

Time-resolved ARPES with tunable 12-21.6 eV XUV at 400 kHz repetition rate.

Time-resolved and angle-resolved photoemission spectroscopy (trARPES) is a powerful method to detect the non-equilibrium electronic structure in solid systems. In this study, we report a trARPES apparatus with tunable photon energy selectively among 12, 16.8, and 21.6 eV at a repetition rate of 400 kHz. The energy and temporal resolutions of the three harmonics are determined as 104/111/157 meV and 276/190/154 fs, respectively. The photon flux on the sample is estimated to be 1010-1011 photons/s by using a photodiode. Finally, the performance of this setup is verified by both equilibrium and non-equilibrium ARPES measurements on topological materials Zr2Te2P and Bi2Se3. Meanwhile, the importance of the tunability of the extreme ultraviolet (XUV) source is highlighted by comparing experimental results measured with the three different photon energies.

Trend and heterogeneity in forced vital capacity among Chinese students during 1985-2019: results from Chinese National Survey on Students' Constitution and Health.

BACKGROUND: Forced vital capacity (FVC) reflects respiratory health, but the long-term trend and heterogeneity in FVC of Chinese students were understudied. METHODS: Data were from Chinese National Survey on Students' Constitution and Health 1985-2019. Super Imposition by Translation and Rotation model was used to draw FVC growth curves. Sex-, region-, and nationality-heterogeneity in FVC was evaluated. Spearman correlation and generalized additive model was used to reveal influencing factors for FVC. RESULTS: Compared to 1985, age at peak FVC velocity was 1.09, 3.17, 0.74, and 1.87 years earlier for urban male, urban female, rural male, and rural female in 2019, respectively. Peak FVC velocity first decreased and then increased during 1985-2019, only male rebounded to larger than 1985 level. FVC declined from 1985 to 2005 and then raised. Males consistently had higher FVC than females, with disparities increasing in the 13-15 age group. Urban students also had higher FVC than rural students. In 2019, FVC difference between 30 Chinese provinces and the national average showed four scenarios: consistently above national average; less than national average until age 18, then above; greater than national average until age 18, then this advantage reversed; less than national average in almost all the age. Most Chinese ethnic minority students had lower FVC levels compared to Han students. Spearman correlation and generalized additive model showed that age, sex, and height were the leading influencing factors of FVC, followed by socioeconomic and environmental factors. CONCLUSIONS: Chinese students experienced advanced FVC spurt, and there was sex-, region- and nationality-heterogeneity in FVC. Routine measurement of FVC is necessary in less developed areas of China.

Clinical Study of Damage Control Surgery in the Management of Odontogenic Cervical Necrotizing Fasciitis with Septic Shock.

Objective: To evaluate the clinical efficacy of damage control surgery (DCS) in the treatment of odontogenic cervical Necrotizing Fasciitis (CNF) complicated with septic shock. Methods: From January 2019 to January 2022, 8 cases with odontogenic cervical Necrotizing Fasciitis (CNF) complicated with septic shock were selected. According to the concept of damage control surgery (DCS), they were treated with incision and decompression, debridement and sealing vacuum suction (VSD) at the early stage, anti-shock, anti-infection, life support. At the later stage, the patients were treated by skin autograft combined with early rehabilitation. Results: In 8 cases, shock was corrected in a short time, lac decreased rapidly, infection index including white blood cell (WBC), C-reactive protein (CRP), thrombocytocrit (PCT) decreased rapidly, organ function including blood urea nitrogen (BUN), total bilirubin (Tbil), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (Alb), creatine kinase (CK) was improved effectively, P < .05. The wounds of all the patients were effectively closed and cured. The average days of hospitalization were 21-42 days (27.00±3.20 days). No recurrence was found in the follow-up of 6 months. Conclusion: Odontogenic cervical Necrotizing fasciitis with septic shock progresses rapidly. Damage control surgery can effectively control infection, correct shock and avoid further deterioration of organ function. This scheme has unique advantages, which can make the wound repaired in time and improve the success rate of treatment. It is worth popularizing in clinic.

KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation.

Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-ß, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.

High power optical frequency comb with 10-19 frequency instability.

Optical frequency combs with more than 10 W have paved the way for extreme ultraviolet combs generation by interaction with inert gases, leading to extreme nonlinear spectroscopy and the ultraviolet nuclear clock. Recently, the demand for an ultra-long-distance time and frequency space transfer via optical dual-comb proposes a new challenge for high power frequency comb in respect of power scaling and optical frequency stability. Here we present a frequency comb based on fiber chirped pulse amplification (CPA), which can offer more than 20 W output power. We further characterize the amplifier branch noise contribution by comparing two methods of locking to an optical reference and measure the out-of-loop frequency instability by heterodyning two identical high-power combs. Thanks to the low noise CPA, reasonable locking method, and optical path-controlled amplifiers, the out-of-loop beat note between two combs demonstrates the unprecedented frequency stability of 4.35 × 10-17 at 1s and 6.54 × 10-19 at 1000 s.

Self-started Kerr-lens mode-locked thin-disk oscillator.

Kerr-lens mode-locking (KLM) has been widely used in thin-disk oscillators to generate high-power femtosecond pulses. Here we demonstrate a Kerr-lens mode-locked Yb:YAG thin-disk oscillator that can be self-started under two configurations. The first can deliver 13-W, 235-fs pulses at a repetition rate of 103 MHz; the second delivers 49 W at a repetition rate of 46.5 MHz, whose corresponding pulse energy of 1.05 µJ is, to the best of our knowledge, the highest energy ever obtained in self-started Kerr-lens mode-locked oscillators. A new method to initiate KLM in the form of optical perturbation in a thin-disk oscillator has also been demonstrated.

Kerr-lens mode-locked femtosecond Yb:CALYO oscillator with more than 20-W average power.

We report on the demonstration of a pure Kerr-lens mode-locked Yb:CALYO laser which can directly deliver sub-200 fs pulses with more than 20-W average power. With an incident pump power of 89 W, 153-fs pulses were generated with an average power of 21.5 W at a repetition rate of 77.9 MHz. The corresponding peak power and single pulse energy were 1.6 MW and 0.27 µJ, respectively. The stable operation of the mode-locking was confirmed by very small fluctuations in both spectrum and output power recorded over an hour. Second harmonic generation (SHG) was conducted with 59% conversion efficiency, which indicated that the high-power mode-locking pulses are of good quality. Stable Kerr-lens mode-locking (KLM) with 156-fs pulse duration and 27.2-W average power was also achieved with 109-W pump power. To the best of our knowledge, this is the highest average output power ever reported from a femtosecond mode-locked bulk oscillator.

Structural basis of ELKS/Rab6B interaction and its role in vesicle capturing enhanced by liquid-liquid phase separation.

ELKS proteins play a key role in organizing intracellular vesicle trafficking and targeting in both neurons and non-neuronal cells. While it is known that ELKS interacts with the vesicular traffic regulator, the Rab6 GTPase, the molecular basis governing ELKS-mediated trafficking of Rab6-coated vesicles, has remained unclear. In this study, we solved the Rab6B structure in complex with the Rab6-binding domain of ELKS1, revealing that a C-terminal segment of ELKS1 forms a helical hairpin to recognize Rab6B through a unique binding mode. We further showed that liquid-liquid phase separation (LLPS) of ELKS1 allows it to compete with other Rab6 effectors for binding to Rab6B and accumulate Rab6B-coated liposomes to the protein condensate formed by ELKS1. We also found that the ELKS1 condensate recruits Rab6B-coated vesicles to vesicle-releasing sites and promotes vesicle exocytosis. Together, our structural, biochemical, and cellular analyses suggest that ELKS1, via the LLPS-enhanced interaction with Rab6, captures Rab6-coated vesicles from the cargo transport machine for efficient vesicle release at exocytotic sites. These findings shed new light on the understanding of spatiotemporal regulation of vesicle trafficking through the interplay between membranous structures and membraneless condensates.

High average power amplification of femtosecond pulses based on the Yb:CaYAlO4 crystal.

In this paper, we demonstrated the direct amplification of femtosecond pulses with the Yb:CaYAlO4 crystal for the first time. A compact and simple two-stage amplifier delivered amplified pulses with the average powers of 55.4 W for σ-polarization and 39.4 W for π-polarization at the center wavelengthes of 1032 nm and 1030 nm, corresponding to 28.3% and 16.3% optical-to-optical efficiencies, respectively. These are to the best of our knowledge the highest value achieved with a Yb:CaYAlO4 amplifier. Upon using a compressor consisting of prisms and GTI mirrors, a pulse duration of 166-fs was measured. Thanks to the good thermal management, the beam quality (M2) parameters <1.3 along each axis were maintained in each stage.

High-flux wavelength tunable XUV source in the 12-40.8†eV photon energy range with adjustable energy and time resolution for Tr-ARPES applications.

High-order harmonic generation (HHG) has a broad spectrum covering vacuum ultraviolet to extreme ultraviolet (XUV) bands, which is useful for applications involving material analyses at different information depths. Such an HHG light source is perfect for time- and angle-resolved photoemission spectroscopy. Here, we demonstrate a high-photon flux HHG source driven by a two-color field. Applying a fused silica compression stage to reduce the driving pulse width, we obtained a high XUV photon flux of 2 × 1012 phs/s @21.6 eV on target. We designed a classical diffraction mounted (CDM) grating monochromator that can achieve a wide range of photon energy from 12 to 40.8 eV, while the time resolution is improved by reducing the pulse front tilt after the harmonic selection. We designed a spatial filtering method to adjust the time resolution using the CDM monochromator and significantly reduced the pulse front tilt of the XUV pulses. We also demonstrate a detailed prediction of the energy resolution broadening which is caused by the space charge effect.

Acellular allogenic dermis combined with VSD for repair of abdominal wall defect: a case series.

OBJECTIVE: To explore the clinical application of acellular allogenic dermis combined with VSD in repairing abdominal wall defect combined with abdominal infection. METHODS: Clinical data of 5 cases of abdominal cavity infection with abdominal wall defect admitted in the Burn Department of Quanzhou First Hospital from January 2019 to January 2022 were collected for this study. The abdominal cavity was closed temporarily after debridement and VSD in the early stage, and the abdominal wall defect was repaired by acellular allogeneic dermis combined with autologous split-thickness skin graft in the second stage. The changes of infection indexes (WBC, CRP, PCT, Lac) before and after treatment and the clinical therapeutic effect were observed. RESULTS: In the 5 observed cases, the infection index decreased significantly, the intra-abdominal pressure was normal, and there was no abdominal wall hernia, intestinal adhesion, intestinal obstruction or any other complications. The wound of abdominal wall defect achieved stage 1 healing, the local scar tissue only has slight proliferation, and the appearance was satisfying. There was no recurrence in 6 months follow-up. CONCLUSION: Early use of VSD can effectively control abdominal infection and reduce the occurrence of intestinal fistula or other complications. In the later stage of treatment, acellular allogenic dermis combined with autologous split-thickness skin graft can effectively repair abdominal wall defect.