Coherent beam combining of two all-PM thulium-doped fiber chirped pulse amplifiers.

In this paper, we report a coherent beam combining (CBC) system that involves two thulium-doped all-polarization maintaining (PM) fiber chirped pulse amplifiers. Through phase-locking the two channels via a fiber stretcher by using the stochastic parallel gradient descent (SPGD) algorithm, a maximum average power of 265 W is obtained, with a CBC efficiency of 81% and a residual phase error of λ/17. After de-chirping by a pair of diffraction gratings, the duration of the combined laser pulse is compressed to 690 fs. Taking into account the compression efficiency of 90% and the main peak energy proportion of 91%, the corresponding peak power is calculated to be 4 MW. The laser noise characteristics before and after CBC are examined, and the results indicate that the CBC would degrade the low frequency relative intensity noise (RIN), of which the integration is 1.74% in [100 Hz, 2 MHz] at the maximum combined output power. In addition, the effects of the nonlinear spectrum broadening during chirped pulse amplification on the CBC efficiency are also investigated, showing that a higher extent of pulse stretching is effective in alleviating the spectrum broadening and realizing a higher output power with decent combining efficiency.

Emerging anticancer potential and mechanisms of snake venom toxins: A review.

Animal-derived venom, like snake venom, has been proven to be valuable natural resources for the drug development. Previously, snake venom was mainly investigated in its pharmacological activities in regulating coagulation, vasodilation, and cardiovascular function, and several marketed cardiovascular drugs were successfully developed from snake venom. In recent years, snake venom fractions have been demonstrated with anticancer properties of inducing apoptotic and autophagic cell death, restraining proliferation, suppressing angiogenesis, inhibiting cell adhesion and migration, improving immunity, and so on. A number of active anticancer enzymes and peptides have been identified from snake venom toxins, such as L-amino acid oxidases (LAAOs), phospholipase A2 (PLA2), metalloproteinases (MPs), three-finger toxins (3FTxs), serine proteinases (SPs), disintegrins, C-type lectin-like proteins (CTLPs), cell-penetrating peptides, cysteine-rich secretory proteins (CRISPs). In this review, we focus on summarizing these snake venom-derived anticancer components on their anticancer activities and underlying mechanisms. We will also discuss their potential to be developed as anticancer drugs in the future.

System optimization study of hybrid K-edge/XRF densitometer for uranium-plutonium solution measurement.

In this paper, a comprehensive hybrid K-edge/XRF densitometer (HKED) device model is constructed using MCNP simulation. After the modeling process, a systematic simulation study is conducted to analyze the physical parameters and material selection of KED and XRF. The simulation results reveal that the optimal parameters for the X-ray tube are an X-ray source voltage of 160 kV and a 1 mm Fe filter. The sample should be placed in a vial with an inner diameter of 1.4 cm and an outer diameter of 2 cm. For the KED technique, the determined main parameters are a 1.9 cm Fe filter rod and an inner diameter of 0.08 cm for the collimator. For the XRF technique, the determined main parameters are a 0.01 cm Gd filter and an inner diameter of 0.3 cm for the collimator, with a detector angle of 150°. After selecting appropriate parameters, the average calibration factor Δµ of the KED technique was found to be 3.301 cm2 g-1, with a relative standard deviation (RSD) of 3.36%. Additionally, the comparison between the simulated and calculated values of uranium concentration revealed a minimum measurement error of 0.4%. The minimum detection concentration of KED for uranium solutions is approximately 1 g/L. For plutonium solutions ranging from 0.5 to 20 g/L, linear fitting of the Ka1 net peak area and plutonium concentration showed a coefficient of determination (R2) of 0.999. The detection limit of XRF for plutonium measurement was 2.33✕10-4 g/L. The linear fitting coefficients (R2) of uranium concentration versus K-edge transmission rate and plutonium concentration versus Ka1 net peak area for the hybrid technique in measuring uranium-plutonium mixed solutions are determined as 0.999 and 0.996, respectively, demonstrating the response relationship of the HKED device to uranium and plutonium under different concentrations.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. RESULTS: A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. CONCLUSIONS: We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell-cell communication in the tumor microenvironment.

Nervogenic Acid Derivatives and Phenanthrenes from Liparis nervosa and Their Antimicrobial and Immunosuppressive Activities.

Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5 µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96 µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.

Multiplex dependence analysis of China's interprovincial virtual water based on an ecological network.

The interprovincial circulation of goods and services has formed virtual water flows between regions, which can redistribute water resources. Based on previous virtual water trade research, this study further explored the multiple dependencies of virtual water, i.e., direct, indirect, and complete dependence. This study examined the direct, indirect, and complete dependence of virtual water between provinces in China by constructing multilayer dependence networks and identified the key regions and paths of virtual water trade network. The results showed direct dependence was the densest and had the largest overall dependence degree, but indirect dependence was the most stable and orderly. Second, the dominant provinces were Guangxi, Hunan, Sichuan, Xinjiang, and Anhui, referred to as "core‒five‒region," and the flow relevant to them accounted for approximately 30% of the virtual water. The seven provinces of Shanxi, Zhejiang, Shandong, Hubei, Guangdong, Shaanxi, and Gansu depend both directly and indirectly on the "core‒five‒region." Shanxi and Zhejiang have close direct and indirect dependence, with more than one of the "core‒five‒region." Guangdong was the province with the most direct and indirect input of virtual water from the "core‒five‒region." The study provides a scientific basis for multiregional identification for the collaborative management of water resources in China from the perspective of dependence.

Polysaccharide from Boletus aereus ameliorates DSS-induced colitis in mice by regulating the MANF/MUC2 signaling and gut microbiota.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions characterized by disruptions in the colonic mucus barrier and gut microbiota. In this study, a novel soluble polysaccharide obtained from Boletus aereus (BAP) through water extraction was examined for its structure. The protective effects of BAP on colitis were investigated using a DSS-induced mice model. BAP was found to promote the expression of intestinal mucosal and tight junction proteins, restore the compromised mucus barrier, and suppress the activation of inflammatory signaling. Moreover, BAP reshape the gut microbiota and had a positive impact on the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, BAP decreased cytokine levels through the MANF-BATF2 signaling pathway. Correlation analysis revealed that MANF was negatively correlated with the DAI and the level of cytokines. Furthermore, the depletion of gut microbiota using antibiotic partially inhabited the effect of BAP on the activation of MANF and Muc2, indicating the role of gut microbiota in its protective effect against colitis. In conclusion, BAP had an obvious activation on MANF under gut inflammation. This provides new insights into the prospective use of BAP as a functional food to enhance intestinal health.

Epigenetic regulation in cancer.

Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher-order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment.

Pd(II)-Catalyzed ß-C(sp3)-H Alkynylation of Alanine in Di- and Tripeptides with Asn as an Endogenous Directing Group.

The introduction of alkyne moieties into peptides remains in demand as it represents a promising approach for further structural diversification of peptides. Herein, we describe the Pd(II)-catalyzed C(sp3)-H alkynylation of Ala-Asn-embedded di- and tripeptides using Asn as the endogenous lead group. In addition, a key building block for the glycopeptide Tyc4PG-14 and Tyc4PG-15 was produced by our methodology.

Crosstalk between metabolic remodeling and epigenetic reprogramming: A new perspective on pancreatic cancer.

Pancreatic cancer is a highly malignant solid tumor with a poor prognosis and a high mortality rate. Thus, exploring the mechanisms underlying the development and progression of pancreatic cancer is critical for identifying targets for diagnosis and treatment. Two important hallmarks of cancer-metabolic remodeling and epigenetic reprogramming-are interconnected and closely linked to regulate one another, creating a complex interaction landscape that is implicated in tumorigenesis, invasive metastasis, and immune escape. For example, metabolites can be involved in the regulation of epigenetic enzymes as substrates or cofactors, and alterations in epigenetic modifications can in turn regulate the expression of metabolic enzymes. The crosstalk between metabolic remodeling and epigenetic reprogramming in pancreatic cancer has gained considerable attention. Here, we review the emerging data with a focus on the reciprocal regulation of metabolic remodeling and epigenetic reprogramming. We aim to highlight how these mechanisms could be applied to develop better therapeutic strategies.

The study of DIEA three dimensional reconstruction technique based on CTA in preoperative perforator selection.

Preoperative selection of perforator is one of the key steps for successful surgery. The purpose of this study is to simulate the selection process of the perforator of the flap using the 3D models of the deep inferior epigastric artery (DIEA). A retrospective study was performed of women who underwent deep inferior epigastric perforator flap breast reconstruction from January 2011 to July 2021. Construct 3D models of the DIEA using computerized tomography angiography images, and then computational fluid dynamics simulations were performed. Correlation and regression analyses were used to analyze the geometric and hemodynamic parameters. Statistical analysis suggested that the outlet flow was positively correlated with the inlet area (r = 0.338, p = 0.000), outlet area (r = 0.840, p = 0.000), the average radius of the perforator (r = 0.592, p = 0.000), and negatively correlated with the length of perforator(r = -0.210, p = 0.024). The results of linear regression analysis showed that the outlet area (p = 0.000), the average radius (p = 0.000), and the length (p = 0.044) of the perforator were the influencing factors on outlet flow. In multiple perforators analysis, there was a significant difference in the total outlet flow among single perforator, double perforators, and triple perforators (p = 0.002). The successful implementation of this experiment provides a new approach for the selection of dominant perforators in the future.

Kirschner Wire Prying and Leverage Technique: a new closed reduction method in treatment of pediatric "Irreducible Supracondylar Humerus Fractures".

BACKGROUND: This study employs an innovative closed reduction approach to treat pediatric "Irreducible Supracondylar Humerus Fractures" with the goal of demonstrating its practical application compared to conventional methods. METHODS: This study sampled 146 surgically treated cases of "Irreducible Supracondylar Humerus Fractures" in our department. After applying inclusion and exclusion criteria, 120 children were selected and divided into two groups based on treatment methods. Group 1 underwent Closed Reduction and Percutaneous Pinning (CRPP), while Group 2 received treatment using the Kirschner Wire Prying and Leverage Technique alongside CRPP. The relevant data to the study were collected and assessed during the follow-up period. RESULTS: Results indicate that Group 2 demonstrated significantly shorter operative times and fewer instances of intraoperative fluoroscopy compared to Group 1. Furthermore, the percentage of cases requiring open reduction was notably higher in Group 1 than in Group 2. The analysis also identified age, BMI, time from injury to surgery, and the initial deviation of the distal fragment as independent risk factors associated with the failure of closed reduction. The integration of CRPP with the Kirschner Wire Prying and Leverage Technique emerges as a safe and effective strategy for managing "Irreducible Supracondylar Humerus Fractures." This innovative approach not only reduces operative time and intraoperative fluoroscopy needs but also diminishes the reliance on open reduction without compromising safety.

Layer-based Simulation for Three-Dimensional Fluid Flow in Spherical Coordinates.

Fluid flows in spherical coordinates have raised the interest of the graphics community in recent years. The majority of existing works focus on 2D manifold flows on a spherical shell, and there are still many unresolved problems for 3D simulations in spherical coordinates, such as boundary conditions for arbitrary obstacles and flexible artistic controls. In this paper, we propose a practical spherical-coordinate simulator for flow motions in 3D domains. Based on a layer-by-layer structure and a boundary-aware pressure solving scheme, we are able to recover horizontal and vertical flow motions in the presence of arbitrary terrain shapes within a spherical shell of finite thickness. Our proposed method straightforwardly builds on the conventions of previous 2D-manifold spherical-coordinate simulations and provides flexible artistic control strategies for art design.

Insight into microbial adaptability in continuous flow anaerobic ammonium oxidation process for low-strength sewage treatment.

Organic matter concentration is a critical factor influencing the adaptability of anaerobic ammonium oxidation (anammox) bacteria to low-strength sewage treatment. To address this challenge and achieve stable anammox activity, a micro-aeration partial nitrification-anammox process was developed for continuous-flow municipal sewage treatment. Under limited ammonium conditions, the effective utilization of organics in denitrification promoted the stable accumulation of nitrite and enhanced anammox activity. This, in turn, led to enhanced nitrogen removal efficiency, reaching approximately 87.7%. During the start-up phase, the protein content of extracellular polymeric substances (EPS) increased. This enhanced EPS intensified the inhibitory effect of denitrifying bacteria (DNB) on nitrite-oxidizing bacteria through competition for nitrite, thereby facilitating the proliferation of anammox bacteria (AnAOB). Additionally, several types of DNB capable of utilizing slowly biodegradable organics contributed to the adaptability of AnAOB. These findings provide valuable insights for ensuring efficient anammox performance and robust nitrogen removal in the treatment of low-strength sewage.

A tumor-targeted and enzyme-responsive gold nanorod-based nanoplatform with facilitated endo-lysosomal escape for synergetic photothermal therapy and protein therapy.

To tackle the obstacles related to tumor targeting and overcome the limitations of single treatment models, we have developed a nanoplatform that is both tumor-targeted and enzyme-responsive. This nanoplatform integrates photothermal gold nanorods (AuNRs) and protein drugs into a single system. This nanosystem, known as AuNRs@HA-mPEG-Deta-LA, was fabricated by modifying gold nanorods (AuNRs) with a polymeric ligand called hyaluronic acid-grafted-(mPEG/diethylenetriamine-conjugated-lipoic acid). The purpose of this fabrication was to load cytochrome c (CC) and utilize it for the synergetic protein-photothermal therapy of cancer. The resulting nanoplatform exhibited a high efficiency in loading proteins and demonstrated excellent stability in different biological environments. Additionally, CC-loaded AuNRs@HA-mPEG-Deta-LA not only enabled localized hyperthermia for photothermal therapy (PTT) with laser irradiation but also facilitated the release of CC under the action of hyaluronidase, an enzyme known to be overexpressed in tumor cells. The confocal imaging results demonstrated that the presence of a specific polymeric ligand on this nanoparticle enhances the internalization of CD44-positive cancer cells, accelerates endo/lysosomal escape, and facilitates the controlled release of CC within the cells. Furthermore, the results of the MTT assay also showed that AuNRs@HA-mPEG-Deta-LA as a protein nanocarrier demonstrated excellent biocompatibility. Importantly, this synergistic therapeutic strategy effectively induced apoptosis in A549 cancer cells by increasing the intracellular concentration of CC and utilizing the photothermal conversion of AuNRs, which was observed to be more effective compared to using only protein therapy or PTT. Therefore, this study showcased a nanoplatform based on AuNRs that has great potential for tumor-targeted protein delivery in combination with PTT in cancer treatment.

Anti-inflammatory activity of Boletus aereus polysaccharides: Involvement of digestion and gut microbiota fermentation.

Boletus aereus, an edible mushroom, has gained popularity as a medicinal and functional food. This study aimed to investigate the digestive characteristics of B. aereus polysaccharide (BAP) and its effects on gut microbiota. In vitro digestion results indicated partial degradation of BAP. Furthermore, the digested BAP displayed significantly enhanced antioxidant ability. The 16S rRNA sequencing data revealed that BAP positively influenced the abundance of Phascolarctobacterium, Prevotella, and Bifidobacterium in the gut microbiota. Additionally, BAP promoted the production of short-chain fatty acids (SCFAs). Metabolites of BAP utilized by the gut microbiota effectively reduced the concentration of TNF-α, IL-1ß, and NO in an LPS-stimulated RAW 264.7 cell inflammation model. Mantel tests demonstrated a strong correlation among fermentation indicators, gut microbiome composition, SCFAs, and inflammatory cytokines. Overall, this research revealed the underlying digestive and fermentation mechanisms of BAP and provided new insights into the usage of edible mushroom polysaccharides in functional food.

Visible-light-driven photocatalytic carboxylation to aromatic carboxylic acids with CO2.

(Hetero)aromatic carboxylic acids and their derivatives attract attention due to their role in the synthesis of several biologically active molecules, active pharmaceutical ingredients, polymers, etc. Carbon dioxide (CO2) is a prime C1 source for the synthesis of aromatic carboxylic acids because of its nontoxicity, nonflammability, abundance and renewability. Owing to the thermodynamic and chemical inertness of CO2, traditional carboxylation to aromatic carboxylic acids with CO2 is always performed under harsh reaction conditions or using stoichiometric metallic reductants. Visible-light-driven carboxylation with CO2 provides an environmentally benign, mild, and high-efficiency route for the production of aromatic carboxylic acids. This review comprehensively introduces the visible-light-driven preparation of aromatic carboxylic acids through a visible-light-driven oxidative addition and reductive elimination mechanism, binding of aryl (radical) anions which are produced by photoinduced electron transfer (PET) to CO2, binding of carbon dioxide anion radicals (CO2˙-) which are formed by PET to aryl compounds, radical coupling between CO2˙- and aryl radicals, and other mechanisms. Finally, this review provides a summary and the future work direction. This article offers a theoretical guidance for efficient synthesis of aromatic carboxylic acids via photocatalysis.