Diverse mode operation fiber laser mode-locked by nonlinear multimode interference.

We present an all-fiber passively mode-locked (ML) laser with a nonlinear multimode interference (NLMI)-based saturable absorber (SA) capable of generating five pulse modes. The SA consists of two centrally aligned graded index multimode fiber (GIMF) with different diameters (105-50 µm) and features a widely adjustable transmission with saturable/reverse-saturable absorption. Based on this, dissipative soliton (DS), Q-switched rectangular pulse (QRP), dissipative soliton resonance (DSR), noise-like pulse (NLP) and bright-dark pulse pairs (BDP) are observed at three dispersions without additional filter. The DS has a pulse energy, bandwidth and duration of up to 1.15 nJ, 17.98 nm and ∼2.78 ps. The achievable pulse duration and energy of DSR and NLP are 5.21, 48.06 ns and 4.53, 5.12 nJ, respectively. Furthermore, it is demonstrated that the BDP is superimposed by a chair-case pulse (CP) and a rectangular pulse (RP) belonging to orthogonal polarization states. The versatility, flexibility, simplicity and energy scalability of the large-core hybrid GIMF-SA, make it interesting and highly attractive in ultrafast photonics.

Impact on cytokine accumulation in 35-day preserved whole blood due to resin adsorption.

Blood transfusion in critically ill individuals such as sepsis was associated with higher morbidity and mortality. During storage, various bioactive substances accumulated, may exacerbate the initial immunosuppressive reaction in severely ill patients. The objective of this study is to explore how resin adsorption impacts the accumulation of cytokines and the presence of extracellular microvesicles (EVs) in whole blood. Through comparative analysis and screening, amberchrom CG 300 C was chosen to assess the adsorption efficiency and evaluate the quality of whole blood after adsorption. Subsequently, the supernatants from both the unadsorpted (UA) and adsorpted (A) groups were co-cultured with peripheral blood mononuclear cells (PBMCs) to assess their effects on cellular growth and cytokine concentrations. The findings of our study revealed that resin adsorption effectively eradicated most bioactive components in conserved blood, including IL-8, TGF-ß, sCD40L, sFasL, without affecting the quality of the blood. Furthermore, scanning electron microscopy (SEM) revealed a reduction in extracellular microvesicles following adsorption. Compared to UA, A 's supernatant markedly enhanced PBMC growth (p < 0.01). Additionally, the A's supernatant markedly diminished the emission of pro-inflammatory cytokines, like IL-6. The research revealed that adsorbing resin effectively reduced bioactive substances from preserved whole blood, and did not impact red blood cell quality, proving to be a reliable method for extracting bioactive substances from storage blood. The results could pave the way for creating innovative blood bags and hold clinical significance in lowering the frequency of TRIM among patients who have undergone transfusions.

Endovascular Denervation for the Improvement of Limb Ischemia in Patients with Peripheral Artery Disease: A Randomized Clinical Trial.

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.

The Photothermal Conversion and UV Resistance of Silk Fabrics Being Achieved through Surface Modification with C@SiO2 Nanoparticles.

With the improvement in people's living standards, the development and application of smart textiles are receiving increasing attention. In this study, a carbon nanosurface was successfully coated with a SiO2 layer to form C@SiO2 nanomaterials, which improved the dispersion of carbon nanomaterials in an aqueous solution and enhanced the absorption of light by the carbon nanoparticles. C@SiO2 nanoparticles were coupled on the surface of silk fabric with the silane coupling agent KH570 to form C@SiO2 nanosilk fabric. The silk fabric that was subjected to such surface modification was endowed with a special photothermal function. The results obtained with scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and infrared spectroscopy (FTIR) showed that C@SiO2 nanoparticles were successfully modified on the surface of the silk fabric. In addition, under the irradiation of near-infrared light with a power of 20 W and a wavelength of 808 nm, the C@SiO2 nanosilk fabric experienced rapid warming from 23 °C to 60 °C within 30 s. After subjecting the functional fabric to hundreds of photothermal experiments and multiple washes, the photothermal efficiency remained largely unchanged and proved to be durable and stable. In addition, the thermogravimetric (TG) analysis results showed that the C@SiO2 nanoparticles contributed to the thermal stability of the silk fabric. The UV transmittance results indicated that C@SiO2 nanofabric is UV-resistant. The silk modification method developed in this study is low-cost, efficient, and environmentally friendly. It has some prospects for future applications in the textile industry.

Causal relationship between periodontal disease-related phenotype and knee osteoarthritis: A two-sample mendelian randomization analysis.

OBJECTIVE: This study aimed to explore the bidirectional causal relationship between periodontal disease-related phenotype (PDRP) and knee osteoarthritis (KOA) in a European population using a two-sample Mendelian Randomization (MR) approach. METHODS: We leveraged publicly available GWAS summary statistics for PDRP (n = 975) and KOA (n = 403,124), assessing their roles as both exposures and outcomes. Our comprehensive MR analysis employed various methods, including inverse variance weighting (IVW), weighted median, Egger regression, simple mode, and weighted mode, to enhance the robustness of our findings. To ensure the reliability of our instrumental variables, we implemented a rigorous screening process based on p-values and F-values, utilized Phenoscanner to investigate potential confounders, and conducted sensitivity analyses. RESULTS: Our analysis identified five SNPs associated with PDRP and three SNPs with KOA, all surpassing the genome-wide significance threshold, as instrumental variables. The IVW method demonstrated a significant causal relationship from PDRP to KOA (beta = 0.013, SE = 0.007, P = 0.035), without evidence of directional pleiotropy (MR-Egger regression intercept = 0.021, P = 0.706). No support was found for reverse causality from KOA to PDRP, as further MR analyses yielded non-significant P-values. Additionally, funnel plots and Cochran's Q test detected no significant heterogeneity or directional pleiotropy, confirming the robustness of our results. In multivariate analysis, when considering smoking, alcohol consumption, BMI collectively no direct causal relationship between KOA and PDRP. Conversely, smoking and higher BMI were independently associated with an increased risk of KOA. CONCLUSION: In conclusion, our analysis revealed no direct causal relationship from KOA to PDRP. However, a causal relationship from PDRP to KOA was observed. Notably, when adjusting for potential confounders like smoking, alcohol intake, and BMI, both the causal connection from PDRP to KOA and the inverse relationship were not substantiated.

Cannabidiol reverts the malignant phenotype of hepatocellular carcinoma cells via the GPR55/TP53/MAPK axis.

Cannabidiol (CBD) has antioxidant and anti-inflammatory activities. However, the anti-tumor effect of CBD on hepatocellular carcinoma (HCC) remains unclear. Here, we investigated whether CBD displays anti-tumorigenic effects in HCC cells and whether it could reduce tumorigenesis and metastases in vivo. First, this study treated HCC cells with different concentrations of CBD, followed by analyzing the changes in the proliferative, apoptotic, migratory and invasive abilities. The effects of CBD on the growth and metastasis of HCC cells in vivo were verified by tumorigenesis and metastasis assays. Subsequently, the target genes of CBD were predicted through the SwissTarget website and the genes differentially expressed in cells after CBD treatment were analyzed by microarray for intersection. The enrichment of the pathways after CBD treatment was analyzed by KEGG enrichment analysis, followed by western blot validation. Finally, rescue assays were used to validate the functions of genes as well as pathways in the growth and metastasis of HCC cells. A significant weakening of the ability of HCC cells to grow and metastasize in vitro and in vivo was observed upon CBD treatment. Mechanistically, CBD reduced GRP55 expression in HCC cells, along with increased TP53 expression and blocked MAPK signaling activation. In CBD-treated cells, the anti-tumor of HCC cells was restored after overexpression of GRP55 or deletion of TP53. CBD inhibits the MAPK signaling activation and increases the TP53 expression by downregulating GRP55 in HCC cells, thereby suppressing the growth and metastasis of HCC cells.

Programmed cell death, from liver Ischemia-Reperfusion injury perspective: An overview.

Liver ischemia-reperfusion injury (LIRI) commonly occurs in liver resection, liver transplantation, shock, and other hemorrhagic conditions, resulting in profound local and systemic effects via associated inflammatory responses and hepatic cell death. Hepatocyte death is a significant component of LIRI and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of programmed cell death (PCD), necroptosis, ferroptosis, pyroptosis, autophagy, NETosis, and parthanatos have been shown to be involved in LIRI. Understanding the mechanisms underlying cell death following LIRI is indispensable to mitigating the widespread effects of LIRI. Here, we review the roles of different PCD and discuss potential therapy in LIRI.

[Retracted] Downregulation of ROS­FIG inhibits cell proliferation, colony­formation, cell cycle progression, migration and invasion, while inducing apoptosis in intrahepatic cholangiocarcinoma cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data shown in Fig. 9 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to International Journal of Molecular Medicine, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 34: 661­668, 2014; 10.3892/ijmm.2014.1823].

Enhancing regenerative medicine: the crucial role of stem cell therapy.

Stem cells offer new therapeutic avenues for the repair and replacement of damaged tissues and organs owing to their self-renewal and multipotent differentiation capabilities. In this paper, we conduct a systematic review of the characteristics of various types of stem cells and offer insights into their potential applications in both cellular and cell-free therapies. In addition, we provide a comprehensive summary of the technical routes of stem cell therapy and discuss in detail current challenges, including safety issues and differentiation control. Although some issues remain, stem cell therapy demonstrates excellent potential in the field of regenerative medicine and provides novel tactics and methodologies for managing a wider spectrum of illnesses and traumas.

Genetic and transcriptome analysis of the smb mutant in Bombyx mori.

More than 600 mutations have been discovered in the history of silkworm domestication. It is important to study the formation mechanism of these mutations to further understand the life and development process of silkworms and agricultural pest control. The silkworm mutant smb was isolated from silkworm strain NCV, and transcriptome analysis was performed on the silkworm mutant. 796 differentially expressed genes (DEGs) were detected at 48 h of the second instar stage with 669 genes significantly upregulated and 127 genes significantly downregulated. During the GO enrichment analysis, it was found that the enrichment of biological processes was mainly concentrated in proteolysis, carbohydrate metabolism, aminoglycan metabolism, organic substance metabolism, protein metabolism and so on. Based on the analysis of KEGG pathways, it revealed that the pathways enriched in lysosomes, AMPK signaling, fatty acid metabolism, PPAR signaling, galactose metabolism, and protein digestion and absorption were the most significant. Through these most significantly enriched GO terms and KEGG pathways, DEGs consistent with the phenotypic characteristics of the smb mutant were identified, including small body size, slow development, and successive death after the fourth instar. These results provided experimental evidence for the potential formation mechanism of smb mutants.

The Mitogenomic Characterization and Phylogenetic Analysis of the Plant Pathogen Phyllosticta yuccae.

Phyllosticta yuccae is an important plant pathogen causing leaf spot disease in Yucca gigantea Lem. It is imperative to note that the amount of information available about the mitogenome of this subject is severely limited. This must be addressed immediately, as it is crucial to our understanding and progress in this field. To better understand the mitogenomic characteristics of P. yuccae, we conducted its sequencing by MGISEQ. Afterwards, the mitogenome was assembled and annotated. The mitogenomic characteristics and phylogenetic placement of the P. yuccae strain KUMCC 6213 were analyzed. The study revealed that the mitogenome of P. yuccae is a circular DNA molecule, consisting of 178,540 base pairs. It contains a total of 64 genes, including 14 protein-coding genes (PCGs), 26 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and 22 open reading frame genes (ORF), accounting for 80.98% of the total size. Repetitive sequences accounted for 15.42% of the mitogenome. The analysis of codon usage indicated that the codon UUA was the most commonly utilized, whereas the amino acid Leu was the most frequently employed. A comparative analysis of mitogenomes between P. yuccae and Macrophomina phaseolina (Tassi) Goid. showed notable variations in the position and size of gene clusters, with cox1, nad4, and nad4L genes exhibiting relatively low conservation. Phylogenetic analysis based on the 14 PCGs revealed that P. yuccae has the closest genetic relationship with M. phaseolina (Botryosphaeriaceae, Botryosphaeriales). This study first reports the mitogenome of P. yuccae and validates its phylogenetic placement. The findings enhance the knowledge of mitogenomes in Botryosphaeriales, offering novel perspectives on the genetics and evolution of the plant pathogen P. yuccae. This is crucial for the accurate prevention and management of leaf spot disease in Y. gigantea.

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

OBJECTIVE: Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. METHODS: Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. RESULTS: CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. CONCLUSIONS: The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

The Prognostic Value of Serum Calcium Levels in Elderly Dilated Cardiomyopathy Patients.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Advantages of computed tomography-based navigation in clipping distal anterior cerebral artery aneurysms: a retrospective cohort study.

Background: The occurrence rate of distal anterior cerebral artery (DACA) aneurysms is relatively low, primarily due to their deep-seated location, which makes surgical clamping challenging. The objective of this study was to investigate the efficacy and safety of computed tomography (CT) navigation-assisted clipping of DACA aneurysms compared to traditional clipping without navigation. Methods: A retrospective cohort study involving retrospective data collection was performed. The retrospective analysis was conducted on 139 patients with ruptured DACA aneurysms who underwent clipping. From January 2013 to November 2021, 164 patients were retrieved at the Department of Neurosurgery, Renmin Hospital of Wuhan University. The inclusion criteria were patients diagnosed with DACA aneurysms via CT angiography (CTA) or digital subtraction angiography (DSA), those with complete clinical data, and those who underwent craniotomy for aneurysm clipping. Meanwhile, the exclusion criteria were as follows: aneurysm recurrence, traumatic brain injury or surgery history, blood disorders or recent anticoagulant use, and severe organ dysfunction. Data on gender, age, Hunt-Hess grade, Fisher grade, modified Rankin Scale (mRS) score, aneurysm location, hospitalization time, aneurysm found time (the duration from incision to aneurysm discovery), and intraoperative bleeding volume were collected from medical records and neurosurgical databases. Patients were followed up in the clinic or by telephone in May 2022. All patients were divided into a navigation group or a traditional group for statistical analysis. Results: No statistically significant differences were observed in age, sex, Fisher grade, Hunt-Hess grade, hospitalization time, or aneurysm site between the navigation group and traditional group (P>0.05). Intraoperative blood loss was lower in the navigation group than in the traditional group {370 [280-460] vs. 430 [310-610] mL, P=0.045}. Patients in the traditional group had a shorter aneurysm found time than did those in the navigation group {49 [42-53] vs. 79 [63-84] min, P<0.001}. There was no significant difference in the mRS score at hospital discharge (P=0.336) or follow-up (P=0.157) between the two groups. Conclusions: CT neuronavigation-assisted microsurgery for clipping DACA aneurysms may improve surgical accuracy, shorten the time to locate aneurysms, and reduce intraoperative blood loss. Although no significant difference in prognosis was observed, this technique shows promise as a safe and effective alternative to traditional clipping without navigation.