Ip3r-Grp75-Vdac and Relevant Ca2+ Signaling Regulate Dietary Palmitic Acid-Induced De Novo Lipogenesis by Mitochondria-Associated ER Membrane (MAM) Recruiting Seipin in Yellow Catfish.

BACKGROUND: The mitochondria-associated endoplasmic reticulum membrane (MAM) is the central hub for endoplasmic reticulum and mitochondria functional communication. It plays a crucial role in hepatic lipid homeostasis. However, even though MAM has been acknowledged to be rich in enzymes that contribute to lipid biosynthesis, no study has yet investigated the exact role of MAM on hepatic neutral lipid synthesis. OBJECTIVES: To address these gaps, this study investigated the systemic control mechanisms of MAM on neutral lipids synthesis by recruiting seipin, focusing on the role of the inositol trisphosphate receptor-1,4,5(Ip3r)-75 kDa glucose-regulated protein (Grp75)-voltage-dependent anion channel (Vdac) complex and their relevant Ca2+ signaling in this process. METHODS: To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco), were fed 6 different diets containing a range of palmitic acid (PA) concentrations from 0-150 g/kg in vivo for 10 wk. In vitro, experiments were also conducted to intercept the MAM-mediated Ca2+ signaling in isolated hepatocytes by transfecting them with si-mitochondrial calcium uniporter (mcu). Because mcu was placed in the inner mitochondrial membrane (IMM), si-mcu cannot disrupt MAM's structural integrity. RESULTS: 1. Hepatocellular MAM subproteome analysis indicated excessive dietary PA intake enhanced hepatic MAM structure joined by activating Ip3r-Grp75-Vdac complexes. 2. Dietary PA intake induced hepatic neutral lipid accumulation through MAM recruiting Seipin, which activated lipid droplet biogenesis. Our findings also revealed a previously unidentified mechanism whereby MAM-recruited seipin and controlled hepatic lipid homeostasis, depending on Ip3r-Grp75-Vdac-controlled Ca2+ signaling and not only MAM's structural integrity. CONCLUSIONS: These results offer a novel insight into the MAM-recruited seipin in controlling hepatic lipid synthesis in a MAM structural integrity-dependent and Ca2+ signaling-dependent manner, highlighting the critical contribution of MAM in maintaining hepatic neutral lipid homeostasis.

The application of extracorporeal shock wave therapy in the treatment of temporomandibular joint disorders in a preliminary, small sample study.

OBJECTIVE: The aim of this study was to investigate the efficacy of low-intensity, high-frequency shock waves in the treatment of temporomandibular joint disorders. METHODS: Twenty-six patients with temporomandibular joint disorder admitted to the Second Hospital of Shanxi Medical University from August 2022 to December 2022 were selected as study subjects and randomly divided into two groups, A and B, with 13 patients each. In Group A, there were 5 males and 8 females with an average age of 38.85 ± 11.03 years. In Group B, there were 4 males and 9 females with an average age of 39.15 ± 11.16 years. Group A was the control group, which received routine treatment (manual massage + transcutaneous electrical nerve stimulation + ultrashort wave therapy) plus sham shock wave therapy; Group B was the experimental group, which received routine treatment (manual massage + transcutaneous electrical nerve stimulation + ultrashort wave therapy) plus shock wave therapy. The routine treatment was administered once/day, five times per week for a total of 2 weeks of treatment. In addition, shock wave therapy was administered once every 5 days, and the treatment was administered three times. The treatment period was 2 weeks, and the two groups were compared before treatment, at the end of the treatment period, and 4 weeks after treatment. The pain level of the two groups was assessed by the visual analogue scale (VAS) before and after treatment, and the temporomandibular opening index (TOI) before and after treatment was compared between the two groups. VAS and TOI scores were evaluated using the Mann-Whitney U-test, the Kruskal-Wallis H-test and two-way ANOVA. RESULTS: There was no significant difference in the VAS score and temporomandibular opening index between the two groups before treatment (p = .829 and .75, respectively). After 2 weeks of treatment, the VAS score and temporomandibular joint opening index of both groups were significantly improved compared to those before therapy. In addition, the VAS score and temporomandibular joint opening index in the experimental group were significantly better than those in the control group (p < .001 and <.001, respectively). There was a small increase in scores 4 weeks after the treatment compared to just after the treatment period, but the difference was not significant. CONCLUSION: This is a preliminary small sample study that demonstrates the positive effect of using low-intensity, high-frequency shock waves on the treatment of temporomandibular joint disorders and is worthy of clinical promotion.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Multi-omics analysis identifies sex-specific hepatic protein-metabolite networks in yellow catfish (Pelteobagrus fulvidraco) exposed to chronic hypoxia.

Hypoxia disrupts the endocrine system of teleosts. The liver plays important roles in the endocrine system, energy storage, and metabolic processes. The aim of this study was to investigate the sex-specific hepatic response of yellow catfish under chronic hypoxia at the multi-omics level. Common hepatic responses in both sexes included the HIF-1 signaling pathway, glycolysis/gluconeogenesis, and steroid biosynthesis. Hypoxia dysregulated primary bile acid biosynthesis, lipid metabolism, and vitellogenin levels in female fish. Endoplasmic reticulum function in females also tended to be disrupted by hypoxia, as evidenced by significantly enriched pathways, including ribosome, protein processing in the endoplasmic reticulum, and RNA degradation. Other pathways, including the TCA cycle, oxidative phosphorylation, and Parkinson's and Huntington's disease, were highly enriched by hypoxia in male fish, suggesting that mitochondrial function was dysregulated. In both sexes of yellow catfish, the cell cycle was arrested and apoptosis was inhibited under chronic hypoxia. Multi-omics suggested that SLC2A5, CD209, LGMN, and NEDD8 served as sex-specific markers in these fish under chronic hypoxia. Our results provide insights into hepatic adaptation to chronic hypoxia and facilitate our understanding of sex-specific responses in fish.

ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients.

Many mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for the SARS-CoV-2 spike protein receptor-binding domain (RBD) is angiotensin-converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have a negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity-ACE2-like abzymes. To explore this hypothesis, we studied patients hospitalized with COVID-19 who had plasma samples available obtained about 7 days after admission. ACE2 is a metalloprotease that requires Zn2+ for activity. However, we found that the plasma from some patients studied could specifically cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using disodium EDTA anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn2+ was added or the plasma was diluted to decrease EDTA concentration. After processing samples by 100 kDa size exclusion columns and protein A/G adsorption, which depleted immunoglobulin by >99.99%, the plasma samples did not cleave the ACE2 substrate peptide. The data suggest that some patients with COVID-19 develop antibodies with abzyme-like activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate many physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure COVID-19 pathogenesis. IMPORTANCE: We provide what we believe to be the first description of angiotensin-converting enzyme 2 (ACE2)-like enzymatic activity associated with immunoglobulin in COVID-19 patients. COVID-19 includes many puzzling clinical features that have unclear pathogenesis, including a hyperinflammatory state, abnormalities of the clotting cascade, and blood pressure instability. We hypothesized that some patients with COVID-19 patients may produce antibodies against SARS-CoV-2 with enzymatic activity, or abzymes, that target important proteolytic regulatory cascades. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein binds ACE2 on the surface of the future host cell. This means that the RBD has a negative molecular image of ACE2. We hypothesized that some antibodies produced against the RBD would have, in turn, a negative molecular image of the RBD sufficiently similar to ACE2 to have ACE2-like catalytic activity. In other words, some anti-RBD antibodies would be ACE2-like abzymes. Abzymes elicited by SARS-CoV-2 infection have the potential to affect host physiology.

Anillin contributes to prostate cancer progression through the regulation of IGF2BP1 to promote c-Myc and MAPK signaling.

Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.

CircUBE3A(2,3,4,5) promotes adenylate-uridylate-rich binding factor 1 nuclear translocation to suppress prostate cancer metastasis.

Metastatic progression is the primary cause of mortality in prostate cancer (PCa) patients. Although circular RNAs (circRNAs) have been implicated in cancer progression and metastasis, our current understanding of their role in PCa metastasis remains limited. In this study, we identified that circUBE3A(2,3,4,5), which originated from exons 2, 3, 4 and 5 of the human ubiquitin-protein ligase E3A (UBE3A) gene, was specifically downregulated in PCa tissues and correlated with the Gleason score, bone metastasis, and D'Amico risk classification. Through the in vitro and in vivo experiments, we demonstrated that overexpression of circUBE3A(2,3,4,5) inhibited PCa cell migration, invasion, metastasis, and proliferation. Mechanistically, circUBE3A(2,3,4,5) was found to bind to adenylate-uridylate-rich binding factor 1 (AUF1), promoting the translocation of AUF1 into the nucleus. This led to decreased AUF1 in the cytoplasm, resulting in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) mRNA instability and a subsequent reduction at the protein level. The downregulation of MTHFD2 further inhibited vimentin expression, thereby suppressing PCa cell epithelial-mesenchymal transition. Additionally, two pairs of the short-inverted repeats (TSIRs) in flanking introns were identified to synergistically facilitate the generation of circUBE3A(2,3,4,5) and other circRNAs. In summary, TSIRs-induced circUBE3A(2,3,4,5) acts as a suppressor of PCa metastasis by enhancing AUF1 nuclear translocation, reducing MTHFD2, and subsequently inhibiting vimentin expression. This study characterizes circUBE3A(2,3,4,5) as a functional circRNA and proposes it as a highly promising target for preventing PCa metastasis.

Vaccine Strategies to Elicit Mucosal Immunity.

Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines.

A randomized trial of treatment for anterior cruciate ligament reconstruction by radial extracorporeal shock wave therapy.

OBJECTIVE: The aim of this study was to explore the effects of radial extracorporeal shock wave therapy (rESWT) in patients with anterior cruciate ligament(ACL) reconstruction(ACLR). METHODS: We conducted a randomized, controlled trial involving 72 eligible patients with ACL reconstruction in which we compared two strategies: the experimental group was standard rehabilitation plus rESWT and the control group was standard rehabilitation plus sham rESWT. The outcome was the change from baseline to 24 weeks in the average score on Lysholm knee joint score (LKS), range of motion (ROM), visual analogue scale (VAS) and International Knee Literature Committee (IKDC). RESULTS: Of 36 subjects assigned to rehabilitation plus rESWT, 4 lost to follow up. Of 36 assigned to rehabilitation plus sham rESWT, 5 lost to follow up. The LKS, ROM and IKDC scores of the experimental group were markedly increased at 3 and 6 weeks after treatment (P < 0.001), and the VAS was notably decreased (P < 0.001). However, there were no significant differences in the LKS, ROM, IKDC and VAS between the groups at 24 weeks after treatment (P > 0.05). CONCLUSION: The strategy of rehabilitation plus rESWT had better functional outcomes after ACL reconstruction. As such, our study demonstrates that rESWT is essential for patients with ACL reconstruction. Early use of rESWT can improve joint function, pain relief and ability of daily living. rESWT has a positive effect on the overall rehabilitation of patients.

Characterization and expression analysis of seven lipid metabolism-related genes in yellow catfish Pelteobagrus fulvidraco fed high fat and bile acid diet.

SREBPs, such as SREBP1 and SREBP2, were the key transcriptional factors regulating lipid metabolism. The processing of SREBPs involved many genes, such as scap, s1p, s2p, cideb. Here, we deciphered the full-length cDNA sequences of scap, srebp1, srebp2, s1p, s2p, cideb and cidec from yellow catfish Pelteobagrus fulvidraco. Their full-length cDNA sequences ranged from 1587 to 3884 bp, and their ORF length from 1191 to 2979 bp, encoding 396-992 amino acids. Some conservative domains were predicted, including the multiple transmembrane domains in SCAP, the bHLH-ZIP domain in SREBP1 and SREBP2, the ApoB binding region, ER targeting region and LD targeting region in CIDEb, the LD targeting region in the CIDEc, the conserved catalytic site and processing site in S1P, and the transmembrane helix domain in S2P. Their mRNA expression could be observed in the heart, spleen, liver, kidney, brain, muscle, intestine and adipose, but varied with tissues. The changes of their mRNA expression in responses to high-fat (HFD) and bile acid (BA) diets were also investigated in the brain, heart, intestine, kidney and spleen tissues. In the brain, HFD significantly increased the mRNA expression of seven genes (scap, srebp1, srebp2, s1p, s2p, cideb and cidec), and the BA attenuated the increase of scap, srebp1, srebp2, s1p, s2p, cideb and cidec mRNA expression induced by HFD. In the heart, HFD significantly increased the mRNA abundances of six genes (srebp1, srebp2, scap, s2p, cideb and cidec), and BA attenuated the increase of their mRNA abundances induced by HFD. In the intestine, HFD increased the cideb, s1p and s2p mRNA abundances, and BA attenuated the HFD-induced increment of their mRNA abundances. In the kidney, HFD significantly increased the scap, cidec and s1p mRNA expression, and BA diet attenuated the increment of their mRNA expression. In the spleen, HFD treatment increased the scap, srebp2, s1p and s2p mRNA expression, and BA diet attenuated HFD-induced increment of their mRNA expression. Taken together, our study elucidated the characterization, expression profiles and transcriptional response of seven lipid metabolic genes, which would serve as the good basis for the further exploration into their function and regulatory mechanism in fish.

Choline-mediated hepatic lipid homoeostasis in yellow catfish: unravelling choline's lipotropic and methyl donor functions and significance of ire-1α signalling pathway.

Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline's methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid ß-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.

Moderate replacement of fish oil with palmitic acid-stimulated mitochondrial fusion promotes ß-oxidation by Mfn2 interacting with Cpt1α via its GTPase-domain.

The mitochondrial matrix serves as the principal locale for the process of fatty acids (FAs) ß-oxidation. Preserving the integrity and homeostasis of mitochondria, which is accomplished through ongoing fusion and fission events, is of paramount importance for the effective execution of FAs ß-oxidation. There has been no investigation to date into whether and how mitochondrial fusion directly enhances FAs ß-oxidation. The underlying mechanism of a balanced FAs ratio favoring hepatic lipid homeostasis remains largely unclear. To address such gaps, the present study was conducted to investigate the mechanism through which a balanced dietary FAs ratio enhances hepatic FAs ß-oxidation. The investigation specifically focused on the involvement of Mfn2-mediated mitochondrial fusion in the regulation of Cpt1α in this process. In the present study, the yellow catfish (Pelteobagrus fulvidraco), recognized as a model organism for lipid metabolism, were subjected to eight weeks of in vivo feeding with six distinct diets featuring varying FAs ratios. Additionally, in vitro experiments were conducted to inhibit Mfn2-mediated mitochondrial fusion in isolated hepatocytes, achieved through the transfection of hepatocytes with si-mfn2. Further, deletion mutants for both Mfn2 and Cpt1α were constructed to elucidate the critical regions responsible for the interactions between these two proteins within the system. The key findings were: (1) Substituting palmitic acid (PA) for fish oil (FO) proved to be enhanced in reducing hepatic lipid accumulation. This beneficial effect was primarily attributed to the activation of mitochondrial FAs ß-oxidation; (2) The balanced replacement of PA stimulated Mfn2-mediated mitochondrial fusion by diminishing Mfn2 ubiquitination, thereby enhancing its protein retention within the mitochondria; (3) Mfn2-mediated mitochondrial fusion promoted FAs ß-oxidation through direct interaction between Mfn2 and Cpt1α via its GTPase-domains, which is essential for the maintenance of Cpt1 activity. Notably, the present research results unveil a previously undisclosed mechanism wherein Mfn2-mediated mitochondrial fusion promotes FAs ß-oxidation by directly augmenting the capacity for FA transport into mitochondria (MT), in addition to expanding the mitochondrial matrix. This underscores the pivotal role of mitochondrial fusion in preserving hepatic lipid homeostasis. The present results further confirm that these mechanisms are evolutionarily conserved, extending their relevance from fish to mammals.

Novel Optical Kerr Switching Photonic Device Based on Nonlinear Carbon Material.

In the context of current communication systems, there is an urgent demand for more efficient and higher-speed optical signal processing technologies. Researchers are actively exploring new materials and devices to harness nonlinear optical phenomena, seeking advancements in this field. Nonlinear carbon materials, especially promising 2D materials, have garnered attention for their potential interaction with light and have become integral to the development of all-optical signal processing devices. This study focuses on utilizing a photonic device based on a nonlinear Au/CB composite material for optical Kerr switching. The application of Au/CB as a nonlinear material in the Kerr switch represents a noteworthy advancement, demonstrating its capability to modulate optical signals. By appropriately applying a pump light, the study achieves optical Kerr switching with an extinction ratio of approximately 15 dB in the fully off state of the signal light carrying a 10 GHz analog signal, marking a pioneering achievement in the field to the best of our knowledge. The experimental results, encompassing extinction ratios, signal control, and stability, not only validate the feasibility of this technology but also underscore its potential applicability within optical communication systems. The successful modulation and control of a 10 GHz analog signal showcase the practicality and effectiveness of the Au/CB-based optical Kerr switch. This progress contributes to the continuous evolution of optical Kerr switching, a crucial component in modern optical communication systems. Therefore, we believe that the Au/CB-based optical Kerr switch is an exceptionally promising and stable all-optical signal processing device. As the contemporary communication landscape evolves, the integration of this technology holds the potential to enhance the efficiency and speed of optical signal processing.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer.

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods: Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results: Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions: Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Information Leakage Rate of Optical Code Division Multiple Access Network Using Wiretap Code.

Secrecy capacity is usually employed as the performance metric of the physical layer security in fiber-optic wiretap channels. However, secrecy capacity can only qualitatively evaluate the physical layer security, and it cannot quantitatively evaluate the physical layer security of an imperfect security system. Furthermore, secrecy capacity cannot quantitatively evaluate the amount of information leakage to the eavesdropper. Based on the channel model of an optical CDMA network using wiretap code, the information leakage rate is analyzed to evaluate the physical layer security. The numerical results show that the information leakage rate can quantitatively evaluate the physical layer security of an optical CDMA wiretap channel, and it is related to transmission distance, eavesdropping position, confidential information rate and optical code.

Distributed optical synthetic aperture position-transformed method with high-frequency domain coverage.

Realizing an ultrahigh-equivalent aperture for space-based direct optical detection using a distributed optical synthetic aperture (DOSA) system with a very low filling ratio is challenging. This study proposes a position-transformation method for DOSA systems with high-frequency domain coverage called High-Frequency domain-Covering discrete Archimedean Spiral Arrays (HFCASA). The study shows that Golay3 HFCASA with a filling ratio of 0.0675% can greatly improve frequency domain coverage and fulfill the resolution requirements of a 200 m aperture telescope. HFCASA provides the theoretical basis for the future deep-space exploration of DOSA.

Effects of Different Dietary Zinc (Zn) Sources on Growth Performance, Zn Metabolism, and Intestinal Health of Grass Carp.

This research was conducted to investigate the effects of four dietary zinc (Zn) sources on growth performance, Zn metabolism, antioxidant capacity, endoplasmic reticulum (ER) stress, and tight junctions in the intestine of grass carp Ctenopharyngodon idella. Four Zn sources consisted of Zn dioxide nanoparticles (ZnO NPs), Zn sulfate heptahydrate (ZnSO4·7H2O), Zn lactate (Zn-Lac), and Zn glycine chelate (Zn-Gly), respectively. Grass carp with an initial body weight of 3.54 g/fish were fed one of four experimental diets for 8 weeks. Compared to inorganic Zn (ZnSO4·7H2O), grass carp fed the ZnO NPs and Zn-Gly diets exhibited better growth performance. Furthermore, grass carp fed the organic Zn (Zn-Lac and Zn-Gly) diets displayed enhanced Zn transport activity, improved intestinal histology, and increased intestinal tight junction-related genes expression compared to other groups. In comparison to other Zn sources, dietary ZnO NPs caused increased Zn deposition and damaged antioxidation capacity by suppressing antioxidant enzymatic activities and related gene expression in the intestine. Grass cap fed the ZnO NPs diet also exhibited lower mRNA abundance of endoplasmic reticulum (ER) stress- and tight junction-associated genes. According to the above findings, it can be concluded that dietary organic Zn addition (Zn-Lac and Zn-Gly) is more beneficial for intestinal health in grass carp compared to inorganic and nanoform Zn sources. These findings provide valuable insights into the application of organic Zn sources, specifically Zn-Lac and Zn-Gly, in the diets for grass carp and potentially for other fish species.

Characterization of fifteen key genes involved in iron metabolism and their responses to dietary iron sources in yellow catfish Pelteobagrus fulvidraco.

BACKGROUND: Iron is an essential metal element for organisms, whose metabolism is regulated by many genes and also dietary iron sources. However, the characterization, distribution and the responses of iron metabolism-related genes to different iron sources were not clear in fish. METHODS: The full-length cDNA sequences of fifteen iron metabolism-relevant genes (tf, tfr1, hp, fpn1, ho1, ho2, tfr2, hjv, hepcidin, fth, ftl, ftm, irp1, irp2 and hif2α.) were obtained via 3' and 5' RACE PCR from yellow catfish, a widely distributed freshwater teleost in China and other Asian countries. Their molecular characterizations were analyzed via the bioinformatic methods. Real-time quantitative PCR was used to explore their mRNA distribution in nine tissues. Their mRNA expression responses in four tissues (heart, brain, kidney and gill) were explored in yellow catfish fed diets with five iron sources, including ferrous sulfate (FeSO4), ferrous bisglycinate (Fe-Gly), ferrous chloride (FeCl2), ferric citrate (Fe-CA) and ferric oxide nanoparticles (Fe2O3NPs). RESULTS: Compared with mammals and other teleost, these members shared similar domains. Their mRNAs were expressed in nine tested tissues, but mRNA levels varied. Yellow catfish fed the diets containing Fe-Gly and Fe2O3NPs had higher iron contents in heart, brain, kidney and gill. Meantime, different dietary iron sources addition affected their mRNA expression differentially in brain, heart, kidney and gill. It should be pointed out that only three biological replicate tanks were used in the present feeding treatment, and more biological replicate tanks (more than five) should be emphasized in further researches. CONCLUSION: Taken together, our study identified fifteen iron metabolism-relevant genes, explored their mRNA expression in nine tissues, and their mRNA expression in the responses to different dietary iron sources in four tissues, indicating their important regulatory function in iron metabolism and homeostasis.

TiN/Ti3C2 heterojunction-based photonic device for optical Kerr switch.

As one of the new nanomaterials, TiN/Ti3C2 shows excellent optoelectronic characteristics, thus it has been widely used in many applications, such as biomedicine, optical sensors, image processing, and optical switching. With the advancement of communication capabilities and communication networks, optical fiber communication has put a higher demand on signal processing. In order to overcome the limitations of the electronic transfer rate bottleneck, the concept of all-optical signal processing has been proposed. Utilizing the excellent optical nonlinear effect of the TiN/Ti3C2 heterojunction-coated microfiber (THM), a novel THM-based optical Kerr switch has been proposed. Injecting a strong control light and a signal light into the device simultaneously, and controlling the state of turn on or off of the control light, can adjust the intensity of the signal light. Based on this, the amplitude modulation of the signal light can be achieved. With a control light power of 200 mW, the maximum extinction ratio of the signal light reaches 27 dB. We believe that this type of compact device can demonstrate great potential for integration with current high-speed fiber communication networks, providing a possible method for all-optical signal processing through nonlinear effects, and has broad prospects in the field of all-optical signal processing, robots, and high-speed communication.

Novel mechanism for zinc inducing hepatic lipolysis via the HDAC3-mediated deacetylation of ß-catenin at lysine 311.

Zinc (Zn) is a multipurpose trace element indispensable for vertebrates and possesses essential regulatory roles in lipid metabolism, but the fundamental mechanism remains largely unknown. In the current study, we found that a high-Zn diet significantly increased hepatic Zn content and influenced the expression of Zn transport-relevant genes. Dietary Zn addition facilitated lipolysis, inhibited lipogenesis, and controlled ß-catenin signal; Zn also promoted T-cell factor 7-like 2 (TCF7L2) to interact with ß-catenin and regulating its transcriptional activity, thereby inducing lipolysis and inhibiting lipogenesis; Zn-induced lipid degradation was mediated by histone deacetylase 3 (HDAC3) which was responsible for ß-catenin deacetylation and the regulation of ß-catenin signal under the Zn treatment. Mechanistically, Zn promoted lipid degradation via stimulating HDAC3-mediated deacetylation of ß-catenin at lysine 311 (K311), which enhanced the interaction between ß-catenin and TCF7L2 and then transcriptionally inhibited fatty acid synthase (FAS), 2-acylglycerol O-acyltransferase 2 (MOGAT2), and sterol regulatory element-binding protein 1 (SREBP1) expression, but elevated the mRNA abundance of adipose triglyceride lipase (ATGL), hormone-sensitive lipase a (HSLA) and carnitine palmitoyltransferase 1a1b (CPT1A1B). Overall, our research reveals a novel mechanism into the important roles of HDAC3/ß-catenin pathway in Zn promoting lipolysis and inhibiting lipogenesis, and highlights the essential roles of K311 deacetylation in ß-catenin actions and lipolytic metabolism, and accordingly provides novel insight into the prevention and treatment of steatosis in the vertebrates.