Pulse buildup dynamics in a self-starting Mamyshev oscillator.

The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.

[Genetic analysis of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 due to variant of PIGN gene].

OBJECTIVE: To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). METHODS: Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c.963G>A (p.Q321=) and c.994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c.963G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PM3), whilst the c.994A>T was classified as a variant of uncertain significance (PM2_Supporting+PP3). CONCLUSION: Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Danggui-Shaoyao-San Promotes Amyloid-ß Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder currently without satisfactory therapeutic treatments. Triggering receptors expressed on a myeloid cells-2 (Trem2) gene mutation has been reported as a powerful AD risk factor that induces Trem2 gene deletion aggravated microglia disfunction and Amyloid-ß (Aß) aggregation in the brain. The traditional Chinese medicine (TCM) formula Danggui-Shaoyao-San (DSS) has shown therapeutic effect on alleviating the symptoms of AD. However, the neuroprotective effect and underlying mechanism of DSS against AD is still far from fully understood. METHODS: Double-label immunofluorescence and Western blotting were employed to evaluate the different polarization states of mouse BV2 microglial (BV2) cells after lipopolysaccharide (LPS) or interleukin (IL)-4 treatment. Trem2 over-expression lentiviral vector and Trem2 siRNA were used respectively to evaluate the effect of Trem2 on microglia polarization via detecting the proteins expression of iNOS and arginase1 (Arg1) by Western blotting while the Aß-scavenging capacity of BV2 cells was assessed by flow cytometry. Cell counting kit-8 (CCK8) assay was performed to assess the effect of DSS on the viability of BV2 cells. Flow cytometry was used to investigate the effect of DSS on the Aß-scavenging capacity of BV2 cells treated with corresponding concentration of DSS-containing serum. Protein of Trem2 and the gene expression of the M1 or M2 phenotype in BV2 cells treated with DSS after Trem2 over-expression or silence were detected by Western blot and RT-qPCR, respectively. RESULTS: In vitro experiments. DSS exhibited anti-inflammatory and neuroprotective functions. It was found that Trem2 had an effect on inducing a shift of M1 microglia towards the M2 phenotype and enhanced the Aß-scavenging capacity of BV2 cells, further that DSS administration relieved inflammation by engulfing Aß through the activities of Trem2. Importantly, DSS treatment effectively increased the Aß-scavenging capacity of BV2 cells through accelerating the shift of M1 microglia towards an M2 phenotype via increasing Trem2 expression. CONCLUSIONS: Results demonstrated that DSS promoted the clearance of Aß through the regulation of microglia polarization via increased expression of Trem2 in BV2 cells.

Generation of different mode-locked states in a Yb-doped fiber laser based on nonlinear multimode interference.

We demonstrated an ultrafast Yb-doped fiber laser with a single mode fiber-graded index multimode fiber-single mode fiber (SMF-GIMF-SMF) structure based saturable absorber. The GIMF was placed in the groove of an in-line fiber polarization controller to adjust its birefringence, enabling the SMF-GIMF-SMF structure to realize efficient saturable absorption based on nonlinear multimode interference without strict length restriction. By adjusting two intra-cavity polarization controllers, stable dissipation solitons and noise-like pulses were achieved in the 1030 nm waveband with pulse durations of 10.67 ps and 276 fs, respectively. We also realized Q-switched mode-locked pulses in the same fiber laser cavity. By the dispersive Fourier transform method, the real-time spectral evolution in the buildup process of the Q-switched mode-locked state was captured, which showed that the continuous-wave in this laser could gradually evolved into the stable Q-switched mode-locked pulses through unstable self-pulsation, relaxation oscillation and rogue Q-switching stage. To the best of our knowledge, our work reveals the buildup dynamics of the Q-switched mode-locked operation in a fiber laser for the first time. And we also studied the real-time spectral evolution of the stable Q-switched mode-locked pulses, which exhibited periodic breathing property.

A role for LSH in facilitating DNA methylation by DNMT1 through enhancing UHRF1 chromatin association.

LSH, a SNF2 family DNA helicase, is a key regulator of DNA methylation in mammals. How LSH facilitates DNA methylation is not well defined. While previous studies with mouse embryonic stem cells (mESc) and fibroblasts (MEFs) derived from Lsh knockout mice have revealed a role of Lsh in de novo DNA methylation by Dnmt3a/3b, here we report that LSH contributes to DNA methylation in various cell lines primarily by promoting DNA methylation by DNMT1. We show that loss of LSH has a much bigger effect in DNA methylation than loss of DNMT3A and DNMT3B. Mechanistically, we demonstrate that LSH interacts with UHRF1 but not DNMT1 and facilitates UHRF1 chromatin association and UHRF1-catalyzed histone H3 ubiquitination in an ATPase activity-dependent manner, which in turn promotes DNMT1 recruitment to replication fork and DNA methylation. Notably, UHRF1 also enhances LSH association with the replication fork. Thus, our study identifies LSH as an essential factor for DNA methylation by DNMT1 and provides novel insight into how a feed-forward loop between LSH and UHRF1 facilitates DNMT1-mediated maintenance of DNA methylation in chromatin.

Balanced branched-chain amino acids modulate meat quality by adjusting muscle fiber type conversion and intramuscular fat deposition in finishing pigs.

BACKGROUND: Pork is an important food for humans and improving the quality of pork is closely related to human health. This study was designed to investigate the effects of balanced branched-chain amino acid (BCAA)-supplemented protein-restricted diets on meat quality, muscle fiber types, and intramuscular fat (IMF) in finishing pigs. RESULTS: The results showed that, compared with the normal protein diet (160 g kg-1 crude protein), the reduced-protein diet (120 g kg-1 crude protein) supplemented with BCAAs to the ratio of 2:1:2 not only had higher average daily gain (P < 0.05) and carcass weight (P < 0.05) but also improved meat tenderness and juiciness by decreasing shear force (P < 0.05) and increasing water-holding capacity (P < 0.05). In particular, this treatment showed higher (P < 0.05) levels of phospho-acetyl-CoA carboxylase (P-ACC) and peroxisome proliferation-activated receptor-γ (PPARγ), and lower (P < 0.05) levels of P-adenosine 5'-monophosphate (AMP)-activated protein kinase (P-AMPK), increasing the composition of IMF and MyHC I (P < 0.05) in the longissimus dorsi muscle (LDM). In terms of health, this group increased eicosapentaenoic acid (EPA) (P < 0.01) and desirable hypocholesterolemic fatty acids (DHFA) (P < 0.05), and decreased atherogenicity (AI) (P < 0.01) and hypercholesterolemic saturated fatty acids (HSFA) (P < 0.05). CONCLUSION: Our findings suggest a novel role for a balanced BCAA-supplemented restricted protein (RP) diet in the epigenetic regulation of more tender and healthier pork by increasing IMF deposition and fiber type conversion, providing a cross-regulatory molecular basis for revealing the nutritional regulation network of meat quality. © 2021 Society of Chemical Industry.

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.

Preparation of a novel magnetorheological fluid for high temperatures.

Magnetorheological fluids, especially those in high-power magnetorheological devices, inevitably work at high temperatures because of the wall slip, energized coils and frictions between particles. In order to prepare a magnetorheological fluid for high temperatures, this work investigates the properties of three main components (soft magnetic particles, surfactants and base carrier fluids) for a magnetorheological fluid at high temperatures. On this basis, a novel magnetorheological fluid for high temperatures is prepared. Its sedimentation stability, viscosity and shear yield stress are investigated at high temperatures. The results show that the novel magnetorheological fluid has acceptable sedimentation, suitable viscosity and stable shear yield stress at high temperatures. The novel magnetorheological fluid for high temperatures can be applied to most magnetorheological devices, especially high-power magnetorheological devices.

SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1.

Faithful inheritance of DNA methylation across cell division requires DNMT1 and its accessory factor UHRF1. However, how this axis is regulated to ensure DNA methylation homeostasis remains poorly understood. Here we show that SET8, a cell-cycle-regulated protein methyltransferase, controls protein stability of both UHRF1 and DNMT1 through methylation-mediated, ubiquitin-dependent degradation and consequently prevents excessive DNA methylation. SET8 methylates UHRF1 at lysine 385 and this modification leads to ubiquitination and degradation of UHRF1. In contrast, LSD1 stabilizes both UHRF1 and DNMT1 by demethylation. Importantly, SET8 and LSD1 oppositely regulate global DNA methylation and do so most likely through regulating the level of UHRF1 than DNMT1. Finally, we show that UHRF1 downregulation in G2/M by SET8 has a role in suppressing DNMT1-mediated methylation on post-replicated DNA. Altogether, our study reveals a novel role of SET8 in promoting DNA methylation homeostasis and identifies UHRF1 as the hub for tuning DNA methylation through dynamic protein methylation.

Mode-locked and Q-switched mode-locked fiber laser based on a ferroferric-oxide nanoparticles saturable absorber.

We demonstrated an ultrafast erbium-doped fiber laser (EDFL) based on ferroferric-oxide (Fe3O4) nanoparticles as a saturable absorber (SA). The investigated SA was based on magnetic fluid deposited on the end face of a fiber ferrule connector. When the SA was inserted into an EDFL cavity, a stable 2.93 ps mode-locked pulse can be achieved by adjusting the intra-cavity polarization controller. The pulse had a central wavelength of 1572.39 nm and a 3 dB bandwidth of 1.39 nm. We also obtained Q-switched mode-locked pulses at 1593.4 nm. The repetition frequency and the temporal width of the Q-switched pulse envelope varied with the pump power. When the pump power reached 225 mW, the maximum average output power and the pulse envelope energy were up to 4.51 mW and 235.5 nJ. To the best of our knowledge, this is the first time that mode-locked and Q-switched mode-locked pulses have been obtained in a fiber laser based on Fe3O4 nanoparticles.

Dark solitons in the exploding pulsation of the bright dissipative soliton in ultrafast fiber lasers.

Soliton explosion is an extremely pulsating behavior of the bright dissipative soliton (DS) in ultrafast lasers. By numerical simulation, we find that the dark soliton (DAS) can coexist with the bright soliton during the exploding process. The collapsed temporal structure of the exploding soliton is induced by the DASs. We reveal the birthing, evolving, and decaying of the DASs inside the bright DS. The time-frequency analysis of the exploding soliton helps us better understand the temporal and spectral structures of the exploding soliton, which might be useful for real-time spectroscopy of the coexisting dark and bright solitons during the soliton explosion.

A Novel CD40L Mutation Associated with X-Linked Hyper IgM Syndrome in a Chinese Family.

Background: Mutations in CD40 ligand gene (CD40L) affecting immunoglobulin class-switch recombination and somatic hypermutation can result in X-Linked Hyper IgM Syndrome (HIGM1, XHIGM), a kind of rare serious primary immunodeficiency disease (PID) characterized by the deficiency of IgG, IgA and IgE and normal or increased serum concentrations of IgM. The objective of this study is to explain genotype-phenotype correlation and highlight the mutation responsible for a Chinese male patient with XHIGM.Methods: Whole exome sequencing (WES) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutation in the XHIGM family.Results: The results of the sequencing revealed that a new causative mutation in CD40L (c.714delT in exon 5, p.F238Lfs*4) which leads to the change in amino acids (translation terminates at the third position after the frameshift mutation) appeared in the proband. As his mother in the family was carrier with this heterozygous mutation, the hemizygous mutation in this patient came from his mother indicating that genetic mode of XHIGM is X-linked recessive inheritance.Conclusion: This study broadens our knowledge of the mutation in CD40L and lays a solid foundation for prenatal diagnosis and genetic counseling for the XHIGM family.

Elucidation of distinct fluorescence and room-temperature phosphorescence of organic polymorphs from benzophenone-borate derivatives.

The development of organic room-temperature phosphorescence (RTP) is accompanied by opportunities and challenges. RTP from crystal polymorphism has aroused much attention, due to the significant different photophysical characteristics and intermolecular packings found in the same molecule with different crystal phases. Herein, we report three organic molecules BP-o-BO, BP-m-BO, and BP-p-BO, in which two crystal polymorphisms of BP-p-BO are successfully cultivated with different emission properties. BP-p-BO-A exhibits bright cyan photoluminescence (PL) with a quantum yield of 11.3% and a distinct RTP with a lifetime of 17.1 ms, which is much higher than the deep blue PL of BP-p-BO-B (6.9%) and the corresponding RTP lifetime of 3.3 ms. Crystal structure analyses indicate that the different emission properties can be ascribed to the different intermolecular packing, further demonstrating the essential role of molecular packing in the designing of RTP materials.

Polymorphisms of TGF-ß1 and TGF-ß3 in Chinese women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-ß (TGF-ß) superfamily play key roles in the homeostasis of pancreatic ß-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-ß1, TGF-ß3 and the risk to GDM in Chinese women. METHODS: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-ß1 (rs4803455) and TGF-ß3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. RESULTS: An increased frequency of TGF-ß3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-ß1 rs4803455 and TGF-ß3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). CONCLUSIONS: The AA and AG genotype of TGF-ß3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

Comparative study of alleviation effects of DMTU and PCIB on root growth inhibition in two tall fescue varieties under cadmium stress.

In plants, tolerance to cadmium (Cd) stress is closely related to indole-3-acetic acid (IAA) and hydrogen peroxide (H2O2). However, it is unclear whether Cd-resistant and -sensitive varieties respond differently to Cd stress. In this study, the effects of dimethylthiourea (DMTU, a H2O2 scavenger) and p-chlorophenoxy isobutyric acid (PCIB, an IAA signaling inhibitor) on root growth, endogenous hormones and antioxidant system were investigated to decipher how DMTU and PCIB treatments alleviate the inhibition of root elongation in Cd-resistant (Commander) and -sensitive (Crossfire III) tall fescue varieties under Cd stress. Both varieties subjected to 10 µM Cd treatments for 12 h presented a substantial decrease in root elongation coupled with a reduction in brassinosteroid (BR) and zeatin riboside (ZR) contents, but the changes in IAA and abscisic acid (ABA) contents under Cd stress were opposite in the two varieties. In addition, the H2O2 content and antioxidant enzyme activities significantly increased in both varieties. However, pretreatment with PCIB or DMTU mitigated the inhibition of root elongation caused by Cd, accompanied by the significant changes of aforementioned physiological parameters. PCIB significantly reduced the IAA content in 'Commander', while DMTU significantly increased the IAA content in 'Crossfire III' and effectively relieved the inhibition of root elongation. But both treatments decreased the Cd-induced H2O2 accumulation. These results indicated that DMTU or PCIB can alleviate the Cd-inhibited root elongation in two varieties whose resistance differed under Cd stress, but they presented differences in the response of hormones, especially IAA, which may be due to the different adaptation mechanisms of two varieties in response to Cd stress.

Intentions Recognition of EEG Signals with High Arousal Degree for Complex Task.

This paper presents a novel electroencephalography (EEG) evoked paradigm based on neurological rehabilitation. By implementing a conceptual model "cup-and-ball" system, EEG signals in manipulating the dynamic constrained objects are generated. Based on the operational EEG signals, a method is proposed to recognize different mental intentions. Under the manipulating task with a high arousal level, common spatial patterns (CSP) is used to extract and optimize features of the EEG signals from ten participants. Quadratic discriminant analysis (QDA) is implemented on EEG signals in different dimensions to identify different EEG patterns. The cross-validation is used to make classifier adaptive to a given data set. The receiver operating characteristic (ROC) curves are presented to illustrate recognition performance. The classification effect of QDA is verified by paired t-test (P < 0.001). Based on the proposed method, the average accuracy of mental intentions is 0.9857 ± 0.0191 and the area under the ROC curve (AUC) is 0.9665 ± 0.0291. The performance of QDA is also compared with the other three classifiers such as the support vector machine (SVM), the decision tree (DT) and the k-nearest neighborhood (k-NN) rule. The results suggest that the proposed method is very competitive with other methods.

Stable and low-threshold random fiber laser via Anderson localization.

We report a stable and low-threshold Er-doped random fiber laser (RFL) based on a femtosecond-laser-inscribed random-distributed-grating array (RDGA) as the random feedback. The RDGA had a reflectivity of 93.5%, and its properties were numerically analyzed based on the transfer matrix method. The threshold of the laser was significantly reduced to 5.7 mW, and the linewidth was ~0.4 pm near the threshold as the Anderson localization effect existing in the RDGA significantly improved the laser quality factor (4 × 106). In addition, we propose a method to select RFL lasing modes by stretching a fiber grating filter used in the cavity with different axial strains. The center wavelength hardly drifted and the maximum jitter value of the peak power was less than 0.12 dB over 1 hour for the selected three lasing modes, which indicated that our laser operation was quite stable.

Pulsating soliton with broadened Kelly sidebands in an ultrafast fiber laser.

We experimentally observed a novel pulsating soliton state with broadened Kelly sidebands in an ultrafast laser. Through simulations, we found that the synchronized and unsynchronized resonant dispersive waves coexisted in the laser. The incoherent interaction between the unsynchronized dispersive waves and soliton resulted in oscillation of the intensity and central wavelength of the soliton. The frequencies of the Kelly sidebands oscillated with the soliton, resulting in their spectral broadening when measured by an optical spectrum analyzer. The numerical results agreed qualitatively well with the experiments. Our results are novel and useful for understanding the chaotic dynamics and designing of the ultrafast fiber laser.

Multiple Luminescence Responses towards Mechanical Stimulus and Photo-Induction: The Key Role of the Stuck Packing Mode and Tunable Intermolecular Interactions.

Organic luminescence with different forms continues to be one of the most active research fields in science and technology. Herein, an ultra-simple organic molecule (TPA-B), which exhibits both mechanoluminescence (ML) and photo-induced room-temperature phosphorescence (RTP) in the crystalline state, provides an opportunity to reveal the internal mechanism of ML and the dynamic process of photo-induced RTP in the same molecule. Through the detailed investigation of photophysical properties together with crystal structures, the key role of molecular packing and intermolecular interactions was highlighted in the luminescence response by mechanical and light stimulus, affording efficient strategies to design potential smart functional materials with multiple luminescence properties.

Mechanoluminescence or Room-Temperature Phosphorescence: Molecular Packing-Dependent Emission Response.

Mechanoluminescence (ML) and room-temperature photophosphorescence (RTP) were achieved in polymorphisms of a triphenylamine derivative with ortho-substitution. This molecular packing-dependent emission afforded crucial information to deeply understand the intrinsic mechanism of different emission forms and the possible packing-function relationship. With the incorporation of solid-state 13 C NMR spectra of single crystals, as well as the analysis of crystal structures, the preferred packing modes for ML and/or RTP were investigated in detail, which can guide the reasonable design of organic molecules with special light-emission properties.