Helical hollow channel waveguide in YAG fabricated by femtosecond laser enhanced wet etching.

Three-dimensional optical waveguides with hollow channels have many advantages, such as strong mode confinement and excellent dispersion control ability. Femtosecond laser enhanced wet etching is widely used to fabricate hollow channel waveguides in transparent dielectric materials. We propose a method for fabricating hollow channel waveguides in YAG using femtosecond laser enhanced wet etching with a simpler fabrication process and shorter etching time compared with the previous work. After 90 h of etching, a series of helical hollow channel waveguides with a length of 5 mm and a radius of 32 µm were successfully fabricated. At a pitch of 3 µm, the waveguide exhibited a loss (including coupling loss and transmission loss) as low as 0.68 dB at 1030 nm. The helical hollow channel waveguide also exhibited exceptional isotropic light confinement capability and remarkable supercontinuum-generating properties. Moreover, helical hollow channel waveguides with a radius of 2 µm were successfully fabricated. According to simulations, waveguides of such size can effectively control dispersion. Our work presents, to our knowledge, a novel approach to fabricating hollow channel waveguides with arbitrary lengths using femtosecond laser-enhanced wet etching.

[Anti-pyroptosis effect of Albiziae Cortex-Tribuli Fructus combination on hepatic stellate cell line LX2: based on network pharmacology].

Based on network pharmacology, molecular docking, and in vitro experimental verification, this study aims to explore the effect of Albiziae Cortex-Tribuli Fructus combination on HSC-LX2 pyroptosis. Specifically, the targets of Albiziae Cortex, Tribuli Fructus, and hepatic fibrosis were retrieved from an online database and CNKI, and "drug-component-target" network and "drug-component-target-disease" network were constructed. Protein-protein interaction(PPI) network was established based on STRING. Metascape was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and the mechanism of Albiziae Cortex-Tribuli Fructus combination against liver fibrosis was predicted. Molecular docking was used to verify some of the results of network pharmacology, and in vitro experiment was carried out to further verify the above conclusions. According to the results of network pharmacological analysis, 25 active components and 439 targets of Albiziae Cortex-Tribuli Fructus combination and 152 anti-liver fibrosis targets were screened out, including nucleotide-binding oligomerization domain and leucine-rich-repeat-and pyrin-domain-containing 3(NLRP3) and caspase-1. The key targets were involved in 194 KEGG pathways in which the NOD-like receptor signaling pathway topped. The binding common targets were related to pyroptosis. The results of in vitro experiment showed that the pair-containing serum reduced the proliferation rate of HSC-LX2 and the content of reactive oxygen species(ROS), interleukin-18(IL-18), and interleukin-1ß(IL-1ß)(P<0.05). Western blot and qRT-PCR suggested that the protein and gene expression of NLRP3, caspase-1, α-smooth muscle actin(α-SMA), and gasdermin D(GSDMD) in HSC-LX2 increased after AngⅡ stimulation, and the expression decreased after the intervention of pair-containing serum(P<0.05). In summary, the pair-containing serum can inhibit the classic pathway of pyroptosis, which may be the anti-liver fibrosis mechanism. This is consistent with the predicted results of network pharmacology.

Expression levels and activation status of Yap splicing isoforms determine self-renewal and differentiation potential of embryonic stem cells.

Yap is the key effector of Hippo signaling; however, its role in embryonic stem cells (ESCs) remains controversial. Here, we identify two Yap splicing isoforms (Yap472 and Yap488), which show equal expression levels but heterogeneous distribution in ESCs. Knockout (KO) of both isoforms reduces ESC self-renewal, accelerates pluripotency exit, but arrests terminal differentiation, while overexpression of each isoform leads to the reverse phenotype. The effect of both Yap isoforms on self-renewal is Teads-dependent and mediated by c-Myc. Nonetheless, different isoforms are found to affect overlapping yet distinct genes, and confer different developmental potential to Yap-KO cells, with Yap472 exerting a more pronounced biological effect and being more essential for neuroectoderm differentiation. Constitutive activation of Yaps, particularly Yap472, dramatically upregulates p53 and Cdx2, inducing trophectoderm trans-differentiation even under self-renewal conditions. These findings reveal the combined roles of different Yap splicing isoforms and mechanisms in regulating self-renewal efficiency and differentiation potential of ESCs.

Transcriptome analysis reveals potential key immune genes of Hong Kong oyster (Crassostrea hongkongensis) against Vibrio parahaemolyticus infection.

Hong Kong oyster (Crassostrea hongkongensis) is one of the main species of economic shellfish cultivated in the coastal areas of southern China. The cultivation of this shellfish may be adversely impacted by Vibrio parahaemolyticus, a harmful pathogenic bacterium for many mariculture species, as it usually exists on the surface of Hong Kong oysters. Although previous studies have discovered that oysters rely on non-specific immune system to fight pathogen invasion, the genes corresponding to the complex immune system against Vibrio is still not fully elucidated. Therefore, we conducted a transcriptome analysis on the gill from Hong Kong oysters at two time points (i.e., 12 h and 24 h after V. parahaemolyticus or PBS challenge) to identify potential immune genes against V. parahaemolyticus infection. A total of 61779 unigenes with the average length of 1221 bp were obtained, and the annotation information of 39917 unigenes were obtained from Nr, SwissProt, KEGG and COG/KOG. After a pairwise comparison between V. parahaemolyticus or PBS challenge at the two time points, three groups of differentially expressed genes induced by V. parahaemolyticus were captured and analyzed. GO and KEGG analyses showed that multiple immune-related genes played an important role in pathogen infection, including HSP70, PCDP3 and TLR4. Furthermore, genes annotation indicated that LITAF, TNFSF10, Duox2 and big defensin family are also involved in immune regulation. Our study provides a reference for further exploration the molecular mechanism that defenses the pathogen infection regarding the identified immune-related genes in Hong Kong oysters.

IBD: An Interpretable Backdoor-Detection Method via Multivariate Interactions.

Recent work has shown that deep neural networks are vulnerable to backdoor attacks. In comparison with the success of backdoor-attack methods, existing backdoor-defense methods face a lack of theoretical foundations and interpretable solutions. Most defense methods are based on experience with the characteristics of previous attacks, but fail to defend against new attacks. In this paper, we propose IBD, an interpretable backdoor-detection method via multivariate interactions. Using information theory techniques, IBD reveals how the backdoor works from the perspective of multivariate interactions of features. Based on the interpretable theorem, IBD enables defenders to detect backdoor models and poisoned examples without introducing additional information about the specific attack method. Experiments on widely used datasets and models show that IBD achieves a 78% increase in average in detection accuracy and an order-of-magnitude reduction in time cost compared with existing backdoor-detection methods.

Effects of hot and humid environments on thermoregulation and aerobic endurance capacity of Laser sailors.

Objectives: The purpose was to investigate the effects of hot and humid environments on thermoregulation and aerobic endurance capacity and whether high skin temperature serves as a more important thermoregulatory factor affecting aerobic exercise capacity. Methods: A randomized cross-over design was applied to this study, in which nine Laser sailors performed the 6 km rowing test (6 km test) in both a warm (ambient temperature: 23 ± 1.4 °C; relative humidity: 60.5 ± 0.7%; wind speed: 0 km/h; WARM) and hot environment (ambient temperature: 31.8 ± 1.1 °C; relative humidity: 63.5 ± 4.9%; wind speed: 3.5 ± 0.7 km/h; HOT). Results: The time for completing 6 km test of HOT group was significantly longer than that of WARM group (P = 0.0014). Mean power of 3-4 km, 4-5 km and 5-6 km were significant lower in HOT group (P = 0.014, P = 0.02, P = 0.003). Gastrointestinal temperature and skin temperature were significantly higher in HOT group during the 6 km test (P = 0.016, P = 0.04). Heat storage at 5 min and 15 min of HOT group were significantly higher than that of WARM group (P = 0.0036; P = 0.0018). Heart rate and physiological strain index of HOT group were significantly higher than that of WARM group during the 6 km test (P = 0.01, P < 0.01). Conclusion: When skin temperature and core temperature both increased, high skin temperature may be the more important thermoregulatory factor that affected the aerobic endurance performance in hot and humid environments. The high skin temperature narrowed the core to skin temperature gradient and skin to ambient temperature gradient, which may result in greater accumulation of heat storage. The greater heat storage led to the lower muscle power output, which contributed to the reduction of the heat production.

Physical fitness characteristics and performance in single-handed dinghy and 470 classes sailors.

The purpose of this study was to investigate the differences in the physical fitness characteristics of Chinese single-handed dinghy and 470 sailors, predict the single-handed dinghy sailors' physical factors on the performance by equation to guide the training. The sample of this study consisted of one hundred and sixty-seven Chinese sailors who participated in the 2020 China National Sailing Championships, K Independent Samples Test was used to analyze the differences of different classes sailors, and the performance of Laser and Laser Radial sailors were analyzed by step multivariate linear regression. The results showed that the 470 helmsmen are shorter, lighter and have a lower BMI, 470 crew are similar in height to the single-handed dinghy sailors, but lower in weight and BMI. Laser sailors have better strength and flexibility than the ones of male 470. There is no significant difference in the physical fitness characteristics between the Laser Radial sailors and the female 470 crew, they both had better upper and lower body strength than female 470 helmsmen. The regression equation is possible to explain 65.5% of the performance of the sailors in Laser = 90.963-1.33 × sailing experience-0.461 × bench press-0.018 × cycling peak power out; The regression equation is possible to explain 76.7% of the performance of the sailors in Laser Radial = 27.433-0.391 × sailing experience+0.351 × vertical jump-0.329 × pull-up-0.027 × cycling peak power out. Performance in laser and Laser Radial sailors will be determined by the technique and tactics (sailing experience) as well as physical fitness.

Identification, subcellular localization, and functional comparison of novel Yap splicing isoforms in mouse embryonic stem cells.

Hippo signaling pathway is involved in many biological processes including the fate decision of embryonic stem cells (ESCs). Yes-associated protein (Yap) function as a key effector of Hippo pathway, but its role in ESCs is still controversial. So far, only two isoforms of Yap have been identified and they have both overlapping and distinct functions. Here, we identify six novel isoforms of mouse Yap, bringing the total number of isoforms to eight. According to the differences in the first exon, they are divided into two subtypes (a and b). Isoform-a and isoform-b exhibit different subcellular localizations. Moreover, isoform-a can fully reverse the impaired self-renewal phenotype induced by Yap knockout (KO). Upon overexpression, isoform-a moderately promotes mESCs self-renewal and markedly delays differentiation. On the contrary, no significant pro-self-renewal phenotype is observed when isoform-b overexpressed in wildtype (WT) mESCs or re-expressed in Yap KO cell lines. These finding not only help to clarify the role of Yap in mESCs, but also lay the foundation for advancing functional researches of Yap in other processes.

Identification and functional comparison of Bcl2 splicing isoforms in mouse embryonic stem cells.

Embryonic stem cells (ESCs) provide an ideal model for investigating developmental processes and are great sources for developing regenerative medicine. Harnessing apoptosis facilitates accurate recapitulation of signalling events during embryogenesis and allows efficient expansion of the ESCs during differentiation. Bcl2, a key regulator of intrinsic anti-apoptotic pathway, encodes two splicing isoforms. However, the identification and functional comparison of Bcl2 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we provide the evidence that both Bcl2 splicing variants are expressed in mESCs. Despite the structural difference, they have similar subcellular localisation. Both Bcl2α and Bcl2ß enhance differentiation efficiency of the ESCs and effectively improve the survival and growth of ESCs under serum-free conditions. However, the functional effect of Bcl2α was more potent than that of Bcl2ß. Moreover, only Bcl2α could maintain the long-term expansion and pluripotency of ESCs cultured in serum-free medium. Taken together, our results demonstrate previously unknown functional differences in Bcl2 alternative splicing isoforms in ESCs, and lay the foundation for future efforts to engineer ESCs for regenerative medicine.

Novel alternative splicing variants of Klf4 display different capacities for self-renewal and pluripotency in mouse embryonic stem cells.

Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely while maintaining pluripotency. Krüppel-like factor (Klf) 4 is an important member of the Klf family that is known to play a key role in pluripotency and somatic cell reprogramming. However, the identification and functional comparison of Klf4 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we identified three novel alternative splicing variants of Klf4 in mESCs-mKlf4-108, mKlf4-375 and mKlf4-1482-that are distinct from the previously known mKlf4-1449. mKlf4-1449 and mKlf4-1482 may stimulate the growth of ESCs, while mKlf4-108 can only promote the growth of ESCs in LIFlow/serum conditions. In addition, both mKlf4-1449 and mKlf4-1482 can inhibit the differentiation of mESCs. However, the ability of mKlf4-1482 to promote self-renewal and inhibit differentiation is not as strong as that of mKlf4-1449. In contrast, both mKlf4-108 and mKlf4-375 may have the ability to induce endodermal differentiation. Taken together, we have identified for the first time the existence of alternative splicing variants of mKlf4 and have revealed their different roles, which provide new insights into the contribution of Klf4 to the self-renewal and pluripotency of mouse ESCs.

Amplitude of low-frequency fluctuation (ALFF) may be associated with cognitive impairment in schizophrenia: a correlation study.

BACKGROUND: Cognitive impairments are prominent in schizophrenia (SZ). Imaging studies have demonstrated that functional changes of several areas of the brain exist in SZ patients. The relationships between these two indexes are largely unexplored in SZ. The MATRICS Consensus Cognitive Battery (MCCB) was used to measure cognitive impairment in multi-dimensional cognitive fields of SZ patients. This study was conducted to explore the relationship between cognitive functional impairment and the amplitude of low-frequency fluctuation (ALFF) in SZ patients. METHOD: A total of 104 participants (44 SZ patients and 60 age- and gender-matched healthy controls (HC)) were recruited for this study. The MCCB was used to assess cognitive function of the participants, while brain activity was assessed using the ALFF. The relationship between the MCCB and the ALFF was investigated by using a correlation analysis. RESULTS: There were significant differences between SZ patients and HC in MCCB total and domain scores as well as in ALFF results. The reduction of ALFF in the bilateral postcentral gyri and paracentral lobule in SZ patients has a negative correlation with the MCCB sub-test of symbol coding. CONCLUSION: These findings suggest that the reduction of ALFF in bilateral postcentral gyri and paracentral lobule may be related to cognitive impairment in SZ patients.

Exploring the interplay between core and mood symptoms in schizophrenia: A network analysis.

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder characterized by positive symptoms, negative symptoms, cognitive deficits, and co-occurring mood symptoms. Network analysis offers a novel approach to investigate the intricate relationships between these symptom dimensions, potentially informing personalized treatment strategies. METHODS: A cross-sectional study was conducted from November 2019 to October 2021, involving 1285 inpatients with schizophrenia in Liaoning Province, China. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA-14), and Montreal Cognitive Assessment (MoCA). Network analysis was conducted to investigate the network structure, central symptoms, and bridge symptoms. RESULTS: The network analysis uncovered profound interconnectivity between core symptoms and the anxiety-depression community. Central symptoms, such as psychic anxiety, poor rapport, delusions, and attention, were identified as potential therapeutic targets. Bridge symptoms, including insomnia, depressed mood, anxiety-somatic, conceptual disorganization, and stereotyped thinking, emerged as key nodes facilitating interactions between symptom communities. The stability and reliability of the networks were confirmed through bootstrapping procedures. DISCUSSION: The findings highlight the complex interplay between schizophrenia symptoms, emphasizing the importance of targeting affective symptoms and cognitive impairment in treatment. The identification of central and bridge symptoms suggests potential pathways for personalized interventions aimed at disrupting self-reinforcing symptom cycles. The study underscores the need for a transdiagnostic, personalized approach to schizophrenia treatment.

[Research progress on risk prediction of cardiac arrest].

Cardiac arrest (CA) is a serious cardiac event, which has a high incidence and low survival rate at home and abroad. In order to predict the risk of CA in advance, a large number of studies have been conducted by relevant researchers. This paper mainly summarizes the characteristics and research status of the existing analysis and prediction of CA from three aspects: the risk prediction factors of CA, the evaluation index of risk prediction of CA and the early warning scoring system of CA. We hope it can help medical staff to understand the current progress in this field, and provide new ways and methods for predicting the risk of CA.

Integration of Network Pharmacology and Experimental Validation to Explore Jixueteng - Yinyanghuo Herb Pair Alleviate Cisplatin-Induced Myelosuppression.

Jixueteng, the vine of the bush Spatholobus suberectus Dunn., is widely used to treat irregular menstruation and arthralgia. Yinyanghuo, the aboveground part of the plant Epimedium brevicornum Maxim., has the function of warming the kidney to invigorate yang. This research aimed to investigate the effects and mechanisms of the Jixueteng and Yinyanghuo herbal pair (JYHP) on cisplatin-induced myelosuppression in a mice model. Firstly, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) screened 15 effective compounds of JYHP decoction. Network pharmacology enriched 10 genes which may play a role by inhibiting the apoptosis of bone marrow (BM) cells. Then, a myelosuppression C57BL/6 mice model was induced by intraperitoneal (i.p.) injection of cis-Diaminodichloroplatinum (cisplatin, CDDP) and followed by the intragastric (i.g.) administration of JYHP decoction. The efficacy was evaluated by blood cell count, reticulocyte count, and histopathological analysis of bone marrow and spleen. Through the vivo experiments, we found the timing of JYHP administration affected the effect of drug administration, JYHP had a better therapeutical effect rather than a preventive effect. JYHP obviously recovered the hematopoietic function of bone marrow from the peripheral blood cell test and pathological staining. Flow cytometry data showed JYHP decreased the apoptosis rate of BM cells and the western blotting showed JYHP downregulated the cleaved Caspase-3/Caspase-3 ratios through RAS/MEK/ERK pathway. In conclusion, JYHP alleviated CDDP-induced myelosuppression by inhibiting the apoptosis of BM cells through RAS/MEK/ERK pathway and the optimal timing of JYHP administration was after CDDP administration.

Cognitive function and cardiovascular health in the elderly: network analysis based on hypertension, diabetes, cerebrovascular disease, and coronary heart disease.

Introduction: Cognitive decline in the elderly population is a growing concern, and vascular factors, such as hypertension, diabetes, cerebrovascular disease, and coronary heart disease, have been associated with cognitive impairments. This study aims to provide deeper insights into the structure of cognitive function networks under these different vascular factors and explore their potential associations with specific cognitive domains. Methods: Cognitive function was assessed using a modified Chinese version of the mini-mental state examination (MMSE) scale, and intensity centrality and side weights were estimated by network modeling. The network structure of cognitive function was compared across subgroups by including vascular factors as subgroup variables while controlling for comorbidities and confounders. Results: The results revealed that cerebrovascular disease and coronary heart disease had a more significant impact on cognitive function. Cerebrovascular disease was associated with weaker centrality in memory and spatial orientation, and a sparser cognitive network structure. Coronary heart disease was associated with weaker centrality in memory, repetition, executive function, recall, attention, and calculation, as well as a sparser cognitive network structure. The NCT analyses further highlighted significant differences between the cerebrovascular disease and coronary heart disease groups compared to controls in terms of overall network structure and connection strength. Conclusion: Our findings suggest that specific cognitive domains may be more vulnerable to impairments in patients with cerebrovascular disease and coronary heart disease. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations, inform personalized cognitive intervention strategies, and provide a better understanding of the potential mechanisms underlying cognitive decline in patients with vascular diseases.

Environmental Microplastic Exposure Changes Gut Microbiota in Chickens.

As novel environmental contaminants, MPs exist widely in the environment and accumulate in organisms, which has become a global ecological problem. MP perturbations of organismal physiology and behavior have been extensively recorded in aquatic animals, but the potential effects of MPs on poultry are not well characterized. Here, we explored the adverse effects of MP exposure on the growth performance and gut microbiota of chickens. Results showed that the growth performance of chickens decreased significantly during MP exposure. Additionally, Firmicutes, Bacteroidota, and Proteobacteria were found to be dominant in the gut microbiota of MP-exposed chickens, regardless of health status. Although the types of dominant bacteria did not change, the abundances of some bacteria and the structure of the gut microbiota changed significantly. Compared with the controls, the alpha diversity of gut microbiota in chickens exposed to MPs showed a significant decrease. The results of comparative analyses of bacteria between groups showed that the levels of 1 phyla (Proteobacteria) and 18 genera dramatically decreased, whereas the levels of 1 phyla (Cyanobacteria) and 12 genera dramatically increased, during MP exposure. In summary, this study provides evidence that exposure to MPs has a significant impact on the growth performance and gut microbial composition and structure of chickens, leading to a gut microbial imbalance. This may raise widespread public concern about the health threat caused by MP contamination, which is relevant to the maintenance of environmental quality and protection of poultry health.

Identification and functional comparison of novel alternatively spliced isoforms of human YAP.

As a key effector of the Hippo pathway, yes-associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein-coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo-YAP signaling pathway.

A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs.

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.

Comparative expression analysis of TEADs and their splice variants in mouse embryonic stem cells.

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles in embryonic stem cell (ESC) renewal and differentiation. Four TEAD transcription factors (Tead1, Tead2, Tead3 and Tead4) and their various splice variants have been discovered in mice, but the expression pattern of them during pluripotency state transition is unclear. Here, we investigated the expression of TEADs and their splice variants in mouse ESCs at different pluripotent/differentiating states and adult mouse tissues. Our results preliminarily revealed the diversity and heterogeneity of TEAD family, which is helpful for understanding their overlapping and distinctive functions. Furthermore, a novel splice variant of Tead1 was identified and named Tead1 isoform 4.