Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Phylogeny, adaptive evolution, and taxonomy of Acronema (Apiaceae): evidence from plastid phylogenomics and morphological data.

Introduction: The genus Acronema, belonging to Apiaceae, includes approximately 25 species distributed in the high-altitude Sino-Himalayan region from E Nepal to SW China. This genus is a taxonomically complex genus with often indistinct species boundaries and problematic generic delimitation with Sinocarum and other close genera, largely due to the varied morphological characteristics. Methods: To explore the phylogenetic relationships and clarify the limits of the genus Acronema and its related genera, we reconstructed a reliable phylogenetic framework with high support and resolution based on two molecular datasets (plastome data and ITS sequences) and performed morphological analyses. Results: Both phylogenetic analyses robustly supported that Acronema was a non-monophyletic group that fell into two clades: Acronema Clade and East-Asia Clade. We also newly sequenced and assembled sixteen Acronema complete plastomes and performed comprehensively comparative analyses for this genus. The comparative results showed that the plastome structure, gene number, GC content, codon bias patterns were high similarity, but varied in borders of SC/IR and we identified six different types of SC/IR border. The SC/IR boundaries of Acronema chienii were significantly different from the other Acronema members which was consistent with the type VI pattern in the genus Tongoloa. We also identified twelve potential DNA barcode regions (ccsA, matK, ndhF, ndhG, psaI, psbI, rpl32, rps15, ycf1, ycf3, psaI-ycf4 and psbM-trnD) for species identification in Acronema. The molecular evolution of Acronema was relatively conservative that only one gene (petG) was found to be under positive selection (ω = 1.02489). Discussion: The gene petG is one of the genes involved in the transmission of photosynthetic electron chains during photosynthesis, which plays a crucial role in the process of photosynthesis in plants. This is also a manifestation of the adaptive evolution of plants in high-altitude areas to the environment. In conclusion, our study provides novel insights into the plastome adaptive evolution, phylogeny, and taxonomy of genus Acronema.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Peering through the hedge: Multiple datasets yield insights into the phylogenetic relationships and incongruences in the tribe Lilieae (Liliaceae).

The increasing use of genome-scale data has significantly facilitated phylogenetic analyses, contributing to the dissection of the underlying evolutionary mechanisms that shape phylogenetic incongruences, such as incomplete lineage sorting (ILS) and hybridization. Lilieae, a prominent member of the Liliaceae family, comprises four genera and approximately 260 species, representing 43% of all species within Liliaceae. They possess high ornamental, medicinal and edible values. Yet, no study has explored the validity of various genome-scale data in phylogenetic analyses within this tribe, nor have potential evolutionary mechanisms underlying its phylogenetic incongruences been investigated. Here, transcriptome, Angiosperms353, plastid and mitochondrial data, were collected from 50 to 93 samples of Lilieae, covering all four recognized genera. Multiple datasets were created and used for phylogenetic analyses based on concatenated and coalescent-based methods. Evolutionary rates of different datasets were calculated, and divergence times were estimated. Various approaches, including coalescence simulation, Quartet Sampling (QS), calculation of concordance factors (gCF and sCF), as well as MSCquartets and reticulate network inference, were carried out to infer the phylogenetic discordances and analyze their underlying mechanisms using a reduced 33-taxon dataset. Despite extensive phylogenetic discordances among gene trees, robust phylogenies were inferred from nuclear and plastid data compared to mitochondrial data, with lower synonymous substitution detected in mitochondrial genes than in nuclear and plastid genes. Significant ILS was detected across the phylogeny of Lilieae, with clear evidence of reticulate evolution identified. Divergence time estimation indicated that most of lineages in Lilieae diverged during a narrow time frame (ranging from 5.0 Ma to 10.0 Ma), consistent with the notion of rapid radiation evolution. Our results suggest that integrating transcriptomic and plastid data can serve as cost-effective and efficient tools for phylogenetic inference and evolutionary analysis within Lilieae, and Angiosperms353 data is also a favorable choice. Mitochondrial data are more suitable for phylogenetic analyses at higher taxonomic levels due to their stronger conservation and lower synonymous substitution rates. Significant phylogenetic incongruences detected in Lilieae were caused by both incomplete lineage sorting (ILS) and reticulate evolution, with hybridization and "ghost introgression" likely prevalent in the evolution of Lilieae species. Our findings provide new insights into the phylogeny of Lilieae, enhancing our understanding of the evolution of species in this tribe.

A clinical warning in the treatment of chlorfenapyr poisoning.

Chlorfenapyr, an arylpyrrole-based insecticide, disrupts mitochondrial oxidative phosphorylation to deprive the target organism of energy. Chlorfenapyr poisoning in humans causes distinct clinical signs such as hyperhidrosis, malignant hyperthermia, rhabdomyolysis, and delayed neurological symptoms that worsen over time and can be fatal. When treating acute chlorfenapyr poisoning, physicians must consider the latent period and not assume that a patient is safe after an initial response to treatment. It is important to take measures before sudden, fatal symptoms appear. This paper presents three cases of chlorfenapyr poisoning as a warning for physicians to understand its clinical course and treatment.

Lewis Base-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Chlorosilanes en Route to Si-Stereogenic Silylethers.

Enantiopure Si-stereogenic organosilanes are highly valued in the fields of organic synthesis, development of advanced materials, and drug discovery. However, they are not naturally occurring, and their synthesis has been largely confined to resolution of racemic silanes or desymmetrization of symmetric silanes. In contrast, the dynamic kinetic asymmetric transformation (DYKAT) of racemic organosilanes offers a mechanistically distinct approach and would broaden the accessibility of Si-stereogenic silanes in an enantioconvergent manner. In this study, we report a Lewis base-catalyzed DYKAT of racemic chlorosilanes. The chiral isothiourea catalyst, (S)-benzotetramisole, facilitates silyletherification with phenols, yielding (R)-silylethers in good yields with high enantioselectivity (27 examples, up to 86% yield, up to 98:2 er). Kinetic analysis, control experiments, and DFT calculations suggest that a two-catalyst-bound pentacoordinate silicate is responsible for the Si-configurational epimerization of the ion-paired tetracoordinated silicon intermediates.

MXene-Based Skin-Like Hydrogel Sensor and Machine Learning-Assisted Handwriting Recognition.

Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.

Smartphone-assisted fluorescent sensor for the visualization and quantitative detection of doxycycline and L-arginine.

A novel smartphone-assisted fluorescent sensor based on europium/zirconium metal-organic framework (Eu0.5/Zr0.5-MOF) was developed for the fast and sensitive determination of doxycycline (DOX) and L-arginine (Arg). After the addition of DOX, the fluorescence of Eu0.5/Zr0.5-MOF was quenched owing to the inner filter effect (IFE). When Arg was introduced into the Eu0.5/Zr0.5-MOF@DOX complex system, the fluorescence was recovered because the interaction between Arg and Eu0.5/Zr0.5-MOF@DOX weakened the IFE. Moreover, the Eu0.5/Zr0.5-MOF produced continuous fluorescence color changes for the visual measurement of DOX and Arg. The fluorescent probe for DOX and Arg offered broad linear ranges of 0.05-80 and 0.1-60 µg/mL, respectively, with detection limits as low as 2.07 and 67.5 ng/mL. The proposed method was successfully applied to monitor DOX in eggs and Arg in human serum. This work provides a powerful platform for the real-time and visual analysis of DOX and Arg in food and biological samples.

Fatigue Analysis of Composite Bolted Joints under Random and Constant Amplitude Fatigue Loadings.

This paper attempts to analyze the random fatigue life and failure modes of joints using two calculation methods. Three kinds of tests were carried out, which were the static test, constant amplitude fatigue test and the random fatigue test, and four kinds of joints were designed. After the static test, the joint was subjected to a constant amplitude fatigue test by selecting different percentages of load according to the static strength. In order to predict the random fatigue life more precisely, two calculation methods were carried out, which were the linear cumulative damage method and the equivalent loading finite element method. Based on the linear cumulative damage hypothesis, the fatigue life of the joint was established as a function of the load amplitude, and then, the random life prediction was calculated by the amplitude distribution of the random loading. Another method was the equivalent loading method, which was to obtain the equivalent constant amplitude fatigue loading of the random loading spectrum. The finite element model was established based on the stiffness and strength degradation rule. The equivalent random life and fatigue failure modes of the joint were modeled. The two life prediction methods show good agreement with the fatigue experimental result, and all prediction results were included in a scatter band of the factor of 2.

Plastid phylogenomics contributes to the taxonomic revision of taxa within the genus Sanicula L. and acceptance of two new members of the genus.

Introduction: The genus Sanicula L. is a taxonomically complicated taxa within Apiaceae, as its high variability in morphology. Although taxonomists have performed several taxonomic revisions for this genus, the interspecific relationships and species boundaries have not been satisfactorily resolved, especially for those endemic to China. This study mainly focused on S. giraldii var. ovicalycina, S. tienmuensis var. pauciflora, and S. orthacantha var. stolonifera and also described two new members of the genus. Methods: We newly sequenced sixteen plastomes from nine Sanicula species. Combined with eleven plastomes previously reported by us and one plastome downloaded, we performed a comprehensively plastid phylogenomics analysis of 21 Sanicula taxa. Results and Discussion: The comparative results showed that 21 Sanicula plastomes in their structure and features were highly conserved and further justified that two new species were indeed members of Sanicula. Nevertheless, eleven mutation hotspot regions were still identified. Phylogenetic analyses based on plastome data and the ITS sequences strongly supported that these three varieties were clearly distant from three type varieties. The results implied that these three varieties should be considered as three independent species, which were further justified by their multiple morphological characters. Therefore, revising these three varieties into three independent species was reasonable and convincing. Moreover, we also identified and described two new Sanicula species (S. hanyuanensis and S. langaoensis) from Sichuan and Shanxi, China, respectively. Based on their distinct morphological characteristics and molecular phylogenetic analysis, two new species were included in Sanicula. In summary, our study impelled the revisions of Sanicula members and improved the taxonomic system of the genus.

2-Methyl-4'-(methylthio)-2-morpholinopropiophenone: A commercial photoinitiator being used as a new psychoactive substance.

Synthetic cathinones, which are novel psychoactive substances, have caused major social problems worldwide. A substance called 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP), which is employed as a commercial industrial photoinitiator for triggering polymerization, has a basic cathinone backbone; however, few reports regarding MMMP have been published. In the current study, three potential metabolites of MMMP-namely hydroxy-MMMP (HO-MMMP), HO-MMMP-sulfoxide (HO-MMMP-SO), and HO-MMMP-sulfone (HO-MMMP-SO2)-were successfully synthesized, and MMMP and these three potential metabolites were used as standards to establish an analytic method based on liquid chromatography-tandem mass spectrometry for the quantitative analysis of urine. This analytic method and related parameters-including dynamic range, limit of quantification, selectivity, precision, accuracy, carryover effect, matrix effect, interference, and dilution integrity-were optimized and validated. Forty urine samples from 1,691 individuals who abused drugs were determined to contain MMMP, HO-MMMP, HO-MMMP-SO, or HO-MMMP-SO2; the results of this study indicate that approximately 2.37 % of drug abusers in Taiwan consumed MMMP in 2023. These 40 urine samples were analyzed to investigate the metabolism of MMMP in humans. The results indicate that HO-MMMP-SO is the main metabolite in human urine. This study recommends HO-MMMP-SO with a concentration of 2 ng/mL as a target and cutoff value, respectively, for identifying individuals who have consumed MMMP.

Attenuating bone loss in osteoporosis: the potential of corylin (CL) as a therapeutic agent.

The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have been developed in recent years to mitigate bone resorption and enhance bone density. Nonetheless, the efficacy and safety of these pharmaceutical interventions remain constrained. Corylin (CL), a naturally occurring compound derived from the anti-osteoporosis plant Psoralea corylifolia L., has exhibited promising potential in impeding osteoclast differentiation. This study aims to evaluate the effect and molecular mechanisms of CL regulating osteoclast differentiation in vitro and its potential as a therapeutic agent for osteoporosis treatment in vivo. Our investigation revealed that CL effectively inhibits osteoclast formation and their bone resorption capacity by downregulating the transcription factors NFATc1 and c-fos, consequently resulting in the downregulation of genes associated with bone resorption. Furthermore, it has been observed that CL can effectively mitigate the migration and fusion of pre-osteoclast, while also attenuating the activation of mitochondrial mass and function. The results obtained from an in vivo study have demonstrated that CL is capable of attenuating the bone loss induced by ovariectomy (OVX). Based on these significant findings, it is proposed that CL exhibits considerable potential as a novel drug strategy for inhibiting osteoclast differentiation, thereby offering a promising approach for the treatment of osteoporosis.

Microsphere lens array embedded microfluidic chip for SERS detection with simultaneous enhancement of sensitivity and stability.

Surface enhanced Raman spectroscopy (SERS) utilizes the fingerprint features of molecular vibrations to identify and detect substances. However, in traditional single focus excitation scenarios, its signal collection efficiency of the objective is restricted. Furthermore, the uneven distribution of samples on the SERS substrate would result in poor signal stability, while the excitation power is limited to avoid sample damage. SERS detection system always requires precise adjustment of focal length and spot size, making it difficult for point-of-care testing applications. Here, we proposed a SERS microfluidic chip with barium titanate microspheres array (BTMA) embedded using vacuum self-assembled hot-pressing method for SERS detection with simultaneous enhancement of sensitivity and stability. Due to photonic nano-jets and directional antenna effects, high index microspheres are perfect micro-lens for effective light focusing and signal collecting. The BTMA can not only disperse excitation beam into an array of focal points covering the target uniformly with very low signal fluctuation, but enlarge the power threshold for higher signal intensity. We conducted a proof-of-principle experiment on chip for the detection of bacteria with immuno-magnetic tags and immuno-SERS tags. Together with magnetic and ultrasonic operations, the target bacteria in the flow were evenly congregated on the focal plane of BTMA. It demonstrated a limit of detection of 5 cells/mL, excellent signal reproducibility (error∼4.84%), and excellent position tolerance of 500 µm in X-Y plane (error∼5.375%). It can be seen that BTMA-SERS microfluidic chip can effectively solve the contradiction between sensitivity and stability in SERS detection.

Strength and Failure Analysis of Fiber-Wound Composite Gas Cylinder via Numerical Simulation.

Based on the classical grid theory and related regulations, a structure model of a fiber-wound composite gas cylinder was designed in this paper. Based on the design results, a finite element model of a fully wound composite cylinder of an aluminum alloy inner liner with a working pressure of 35 MPa was established based on the ABAQUS software, and its stress distribution under working pressure and minimum burst pressure was analyzed. According to engineering experience, the pressure tolerance of composite cylinders can be improved by proper autofrettage pressure before working pressure, so the influence of autofrettage pressure was analyzed in this paper. The optimum autofrettage pressure was selected by setting the autofrettage gradient, and damage analysis was carried out on the cylinder with nominal working pressure of 35 MPa based on the Hashin failure criterion. The results show the initial damage sequence: matrix stretching occurs before the fiber stretching, and the damage generally starts from the spiral-wound layer. The tensile damage first appears in the transition section between the head and the barrel body, and the damage of the spiral-wound layer develops from the inner layer of the wound layer to the outer layer, while the damage of the circumferentially wound layer develops from the outer layer to the inner layer.

Phylogeny and Taxonomic Revision of the Genus Melanosciadium (Apiaceae), Based on Plastid Genomes and Morphological Evidence.

Melanosciadium is considered a monotypic genus and is also endemic to the southwest of China. No detailed phylogenetic studies or plastid genomes have been identified in Melanosciadium. In this study, the plastid genome sequence and nrDNA sequence were used for the phylogenetic analysis of Melanosciadium and its related groups. Angelica tsinlingensis was previously considered a synonym of Hansenia forbesii. Similarly, Ligusticum angelicifolium was previously thought to be the genus Angelica or Ligusticopsis. Through field observations and morphological evidence, we believe that the two species are more similar to M. pimpinelloideum in leaves, umbel rays, and fruits. Meanwhile, we found a new species from Anhui Province (eastern China) that is similar to M. pimpinelloideum and have named it M. Jinzhaiensis. We sequenced and assembled the complete plastid genomes of these species and another three Angelica species. The genome comparison results show that M. pimpinelloideum, A. tsinlingensis, Ligusticum angelicifolium, and M. jinzhaiensis have similarities to each other in the plastid genome size, gene number, and length of the LSC and IR regions; the plastid genomes of these species are distinct from those of the Angelica species. In addition, we reconstruct the phylogenetic relationships using both plastid genome sequences and nrDNA sequences. The phylogenetic analysis revealed that A. tsinlingensis, M. pimpinelloideum, L. angelicifolium, and M. jinzhaiensis are closely related to each other and form a monophyletic group with strong support within the Selineae clade. Consequently, A. tsinlingensis and L. angelicifolium should be classified as members of the genus Melanosciadium, and suitable taxonomical treatments have been proposed. Meanwhile, a comprehensive description of the new species, M. jinzhaiensis, is presented, encompassing its habitat environment and detailed morphological traits.

Melanin-like nanoparticles alleviate ischemia-reperfusion injury in the kidney by scavenging reactive oxygen species and inhibiting ferroptosis.

Kidney transplantation is essential for patients with end-stage renal disease; however, ischemia-reperfusion injury (IRI) during transplantation can lead to acute kidney damage and compromise survival. Recent studies have reported that antiferroptotic agents may be a potential therapeutic strategy, by reducing production of reactive oxygen species (ROS). Therefore, we constructed rutin-loaded polydopamine nanoparticles (PEG-PDA@rutin NPs, referred to as PPR NPs) to eliminate ROS resulting from IRI. Physicochemical characterization showed that the PPR NPs were ∼100 nm spherical particles with good ROS scavenging ability. Notably, PPR NPs could effectively enter lipopolysaccharide (LPS)-treated renal tubular cells, then polydopamine (PDA) released rutin to eliminate ROS, repair mitochondria, and suppress ferroptosis. Furthermore, in vivo imaging revealed that PPR NPs efficiently accumulated in the kidneys after IRI and effectively protected against IRI damage. In conclusion, PPR NPs demonstrated an excellent ability to eliminate ROS, suppress ferroptosis, and protect kidneys from IRI.

I prefer what you can see: The role of visual perspective-taking on the gaze-liking effect.

Individuals' gaze on an object usually leads others to prefer that object, which is called the gaze-liking effect. However, it is still unclear whether this effect is driven by social factors (i.e., visual perspective-taking) or the domain-general processing (i.e., attention cueing). This research explored the mechanism of the gaze-liking effect by manipulating the objects' visibility to an avatar in six online one-shot experiments. The results showed that participants' affective evaluation for the object was modulated by the avatar's visual perspective. Specifically, the visible object to the avatar received a higher rating of liking degree. However, when the avatar was replaced with a non-social stimulus, the experimental effect was absent. Furthermore, the gaze-liking effect was robust while controlling for confounding factors such as the distance between the object and the avatar or type of stimuli. These findings provided convincing evidence that the gaze-liking effect involves a process of the other's visual experience and is not merely a by-product of the gaze-cueing effect.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals: publisher's note.

This publisher's note corrects an error in Appl. Opt.63, 1411 (2024)APOPAI0003-693510.1364/AO.512229.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals.

Because of the high efficiency of frequency conversion and beam-target coupling, a fourth harmonic (4ω) laser has a splendid application prospect in a high-power laser facility. The polarization smoothing (PS) crystal is preferably after the frequency conversion crystal to flexibly obtain the best uniformity illumination of the target. However, as a high irradiance 4ω laser beam propagates through the PS crystal, the transverse stimulated Raman scattering (TSRS) effect of the PS crystal will be stronger, resulting in significant energy dissipation and crystal damage. This paper proposes a novel, to the best of our knowledge, fourth harmonic generation (FHG) scheme based on an orthogonal cascade of the DKDP crystals. This orthogonal cascaded FHG (OC-FHG) scheme employs two cascaded FHG crystals with orthogonal optical axes, and the PS crystal is in the middle. The PS crystal can rotate the polarization direction of the 2ω laser by 90°, while the polarization direction of the 4ω laser is maintained to a great extent. This OC-FHG scheme realizes the FHG by two steps, and the laser intensity at the PS crystal cuts down nearly 50%. The output intensity of the 4ω laser can be increased from 1.8G W/c m 2 to about 3.6G W/c m 2 under the condition of effectively inhibiting the TSRS effect. Meanwhile, the output 4ω laser contains two orthogonal polarized beams realizing in-beam polarization smoothing instantaneously. In addition, the novel FHG scheme can also have a high conversion efficiency and bandwidth tolerance.