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Abstract Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation. We further identified that PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA methylation and transcriptional suppression of SMAD7. Our in vitro and in vivo experiments showed that PHF14 promotes metastasis through binding DNMT3B to suppress SMAD7 expression. Moreover, our data revealed that PHF14 expression correlates with lowered SMAD7 level and shorter survival of LAD patients, and importantly that SMAD7 methylation level of circulating tumor DNA (ctDNA) can potentially be used for prognosis prediction. Together, our present study illustrates a new epigenetic mechanism, mediated by PHF14 and DNMT3B, in the regulation of SMAD7 transcription and TGF-β-driven LAD metastasis, and suggests potential opportunities for LAD prognosis.

In recent years, the emerging highly pathogenic avian influenza (HPAI) A(H5N8) virus has been reported with features of widely spread, an expanding host range, and cross-species transmission, attracting wide attention. The domestic duck plays a major role in the epidemiological cycle of the HPAI H5N8 virus, but little is known concerning innate immune responses during influenza infection in duck species. In this study, we used two wild-bird-origin viruses, H5N8 and H4N6, to conduct duck infection experiments, and detect the load of the two viruses, and retinoic acid-inducible gene I (RIG-I) and interferon β (IFN-β) in the host’s natural immune response. Through comparison, it is found that the expression levels of RIG-I and IFN-β are both fluctuating. The innate immunity starts rapidly within 6 h after infection and is inhibited by the virus to varying degrees. The expression of RIG-I and IFN-β decreased on 1–2 days post-infection (dpi). The HPAI H5N8 virus has a stronger inhibitory effect on RIG-I than the low pathogenic avian influenza (LPAI) H4N6 virus and is the strongest in the lungs. After infection with HPAI H5N8 virus, 2 dpi, viral RNA replicates in large amounts in the lungs. It has been proven that RIG-I and IFN-β play an important role in the innate immune response of ducks to HPAI H5N8 virus infection, especially in the lungs. The main battlefield of RIG-I and IFN-β after infection with the LPAI H4N6 virus is in the rectum. Both viruses have been effectively controlled after 7 dpi. These results will help to understand the transmission mechanisms of avian influenza virus in wild ducks and help effectively prevent and control avian influenza.

Aim: Ovarian cancer is a collaborative malignant tumor of the female reproductive system in clinical research. Some clinical studies have shown that OR3A4, which is a cancer-causing lncRNA, plays a major role in promoting the occurrence and development of a variety of tumors. And we also expressed the view that it expressed in ovarian tissue. However, the function of OR3A4 in ovarian cancer remains unclear.Methods and Results: To further verify the function of lncRNA OR3A4 in ovarian cancer, we established the xenograft model in the zebra fish. In this study, cells transformed with OR3A4 shRNA plasmids were transplanted into the zebra fish, and the cell proliferation and migration ability were significantly reduced compared to the empty vector. While knocking out OR3A4, we further downregulated its expression by siRNA of KLF6. Our study found that the knocked out OR3A4 resulted in a decrease in cell proliferation and migration level, which can be found in the downregulated expression of KLF6. We also verify the relationship between OR3A4 and circulating tumor cells in the zebra fish xenograft model, the results indicate that lncRNA OR3A4 may be involved in the resistance of ovarian cancer to complain.Conclusion: lncRNA OR3A4 promotes the proliferation and metastasis of ovarian cancer through the KLF6 pathway.

Purpose: We found in previous study that metformin could treat sepsis myocarditis in a mouse model. We employed the zebrafish model organism to investigate the effect of metformin on sepsis myocarditis. Methods and Results: Wild-type zebrafish was used to establish a sepsis myocarditis model and combined with image software analysis and cytokine detection, the protective dose of metformin was determined. The results showed that immersion with Escherichia coli could cause 75% mortality in zebrafish and make larvae appear as characteristics of severe sepsis myocarditis. Pretreatment with 10 mM metformin for 3 hours could effectively reduce heart congestion and swelling in zebrafish with sepsis myocarditis and increased the heart rate. It could reduce the mortality and prolong the survival time of zebrafish with sepsis myocarditis; Tg(mpx: EGFP) transgenic zebrafish were adopted to explore the number of neutrophils in zebrafish heart before and after metformin protection, and metformin could maintain the number of neutrophils in zebrafish heart; quantitative real-time reverse transcription–polymerase chain reaction showed that metformin could reduce the expression of pro-inflammatory factors, tumor necrosis factor-α and interleukin (IL)-6, and could promote the anti-inflammatory factor, transforming growth factor-β and IL-10 expression. Conclusion: We established a zebrafish sepsis myocarditis model and applied metformin in advance to provide a protective effect on the zebrafish heart.

Purpose: Interferon regulatory factor 4 (IRF4) is identified as a transcriptional factor and plays an important role in the immune response in mammals; however, there are few reports about the function of zebrafish IRF4. Methods: We first amplified the coding sequence of irf4a from the testis of zebrafish. Besides, the fragments of irf4a , P2A , EGFP , and Tol2 vector were added for homologous recombination. By sequencing, we can get the Tol2-ef1α-irf4a-EGFP recombinant plasmid and it was microinjected into zebrafish embryos. Fluorescence observation was proceeded at days 3 post fertilization; F0 generations expressing green fluorescence in multiple tissues throughout the body were screened as the founder and raised them to sexual maturity. After mating with WT zebrafish to generate F1 offspring, polymerase chain reaction was used to identify whether irf4a was integrated into the zebrafish genome. Conclusion: We obtained the systematic overexpressed irf4a transgenic zebrafish with green fluorescence labeled in spine, eyes, heart, brain, and other tissues. The transgenic zebrafish will be used as a tool for the role of IRF4a in the immune response to the inflammation preconditioning in the future study.

The hoist system of electric mining shovel (EMS) always encounters excessive vibration in present work. However, the shortage of suitable dynamic model has been the bottleneck of reducing vibration. In order to analyze the vibration of the EMS hoist system, a coupled dynamic model is proposed using the hierarchical modeling method, which contains couplings of bolt, bear, coupling, rope, and gear mesh. The components were equivalent to mass elements with several nodes corresponding to their structure. Considered helical gears and motors, a dynamic gear transmission model with couplings of bending, torsion, and axes was developed. Based on the dynamic model, the modal characteristics were calculated, and the vibration modes were classified to five types. Under the ripple drive torque simulated by Simulink, the dynamic characteristics of the hoist system in time domain and frequency domain were obtained using numerical integration with the Runge–Kutta method in Matlab. At last, the model validity was verified by contrasting the responses under actual test and the model. The dynamic model and study results can provide support for dynamic characteristic evaluation and dynamic optimization of the EMS hoist system.

Climate change and anthropogenic activities have significantly contributed to the degradation of wet meadows on the Qinghai-Tibet Plateau (QTP). Soil nitrogen (N) availability is a crucial determinant of the productivity of wet meadow vegetation. Furthermore, soil microbial nitrogen functional genes (NFGs) are critical in the transformation of soil N. Nevertheless, the dynamics of NFGs in response to vegetation degradation, as well as the underlying drivers, remain poorly understood. In this study, wet meadows at varying levels of vegetation degradation on the QTP, categorized as non-degraded (ND), slightly degraded (SD), moderately degraded (MD), and heavily degraded (HD), were examined. Soil samples from depths of 0 to 10 cm and 10 to 20 cm were collected during different growth cycles (June 2020, August 2020, and May 2021). The analysis focused on NFGs involved in organic nitrogen fixation (nifH), archaeal and bacterial ammonia oxidation (amoA-AOA and amoA-AOB, respectively), and nitrite reduction (nirK), utilizing real-time fluorescence quantitative PCR. Our findings indicate a significant decline in the abundance of NFGs with intensified vegetation degradation, exhibiting notable spatial and temporal fluctuations. Specifically, the relative NFGs followed the pattern: nirK > amoA-AOA > amoA-AOB > nifH. Redundancy analysis revealed that vegetation cover was the primary regulator of NFGs abundance, accounting for 56.1%-57% of the variation. Additionally, soil total nitrogen, pH, and total phosphorus content were responsible for 38.5%, 28.2%, and 7% of the variability in NFGs, respectively. The (amoA-AOA + amoA-AOB + nirK) ratios associated with effective N transformation indicated that the vegetation degradation process moderately increased the nitrification potential. IMPORTANCE Our research investigates how the degradation of meadows affects the tiny organisms in soil that help plants use nitrogen, which is essential for their growth. In the Qinghai-Tibet Plateau, a region known for its unique ecosystems, we found that as meadows deteriorate--due to climate change and human activities--the number of these beneficial organisms significantly decreases. This decline could reduce soil fertility, impacting plant life and the overall health of the ecosystem. Understanding these changes helps us grasp how environmental pressures influence soil and plant health. Such knowledge is crucial for developing strategies to preserve these vulnerable ecosystems and ensure they continue to sustain biodiversity and provide resources for local communities. [ABSTRACT FROM AUTHOR]

Embedded cooling pipe system is regarded as the primary means in mass concrete to control the temperature. The effects of three factors are investigated on the thermal field of mass concrete by the combination of measurement, theoretical analyze and numerical simulation in this paper, including cooling pipe spacing, pipe diameter and pipe arrangement. The results demonstrate that the peak temperature is reduced by the increase in both of the pipe distance and pipe diameter. The peak temperature is measured to decrease from 1 °C to 3 °C on the monitoring points, with additional 0.5 m of pipe spacing or 10 mm of pipe diameter. The serious influence is conducted by the pipe diameter on the temperature difference, and the selection of cooling pipe diameter is considered to balance multiple problems in the project necessarily. The serpentine arrangement is more widely used for better cooling and construction in the comparison of the circular arrangement. The results on the optimization of cooling system are utilized for the project to control the hydration heat accurately and reduce or even prevent the generation of cracks.

Feedback-insensitive Quantum Dot (QD) comb lasers hold significant promise for integrated dense wavelength division multiplexing photonic systems due to their ability to generate multiple wavelengths and operate without bulky isolators, facilitating the development of high-density and large-scale photonic integrated circuits. In this study, we investigated the optical feedback (OFB) influence of the InAs/GaAs QD comb laser from various perspectives. Our findings reveal that the comb laser exhibits a stable locking region with consistent optical spectra across a range of OFB strengths (−45 to −10 dB). Furthermore, under a high OFB strength of −10 dB, there is a notable 40 dB suppression of relative intensity noise in the low-frequency range (below 1 GHz). Transmission experiments demonstrate clear eye openings at 25 Gbps using a bit pattern of 231-1 pseudorandom binary sequence. Remarkably, the bit error rates decrease by five orders of magnitude under −10 dB OFB. These results indicate the ultra-robustness of 100 GHz grid QD comb laser, which exhibits great transmission enhancement under a strong OFB of −10 dB.

Purpose: To investigate the effect of Sprouty2 (SPRY2) on sevoflurane (SEV) induced nerve injury in rats and its potential signaling pathway. Methods: Male Sprague-Dawley rats were divided into sham and SEV groups containing six rats per group. Neurological injury assessment and H & E staining were performed to evaluate the degree of nerve injury in the rats, while quantitative polymerase chain reaction (qPCR) and immunoblot assays were performed to confirm the expression levels of SPRY2 in hippocampus tissues. Morris water maze tests were performed to determine the degree of cognitive deficit in rats. TUNEL and immunoblot assays were performed to evaluate the effects of SPRY2 on the apoptosis of hippocampus tissues. Results: The SPRY2 expression was elevated in sevoflurane-induced hippocampus injury (p < 0.001). Ablation of SPRY2 inhibited sevoflurane-induced hippocampal neuron apoptosis (p < 0.001). In addition, depletion of SPRY2 promoted hippocampal neuron activity and decreased apoptosis (p < 0.001). Knockdown of SPRY2 promoted ERK signaling pathway, thereby protecting against sevoflurane-induced nerve injury and cognitive deficit in the rats (p < 0.001). Conclusion: Sevoflurane induces cognitive dysfunction and upregulates SPRY2 expression in brain tissues in rats. The SPRY2 knockdown improves SEV-induced neural injuries and cognitive deficits, inhibits hippocampal neuron apoptosis, and enhances its activity. Meanwhile, SPRY2 depletion protects SEV-induced nerve injury via the ERK pathway. Thus, Sprouty2 could serve as a promising drug target for the treatment of SEV-induced cognitive dysfunctions. [ABSTRACT FROM AUTHOR]

This study theoretically investigates the impact of external carrier noise from pumping sources on the optical noise of epitaxial quantum dot (QD) lasers on silicon. The findings indicate that the spectral linewidth and relative intensity noise (RIN) of silicon-based QD lasers using a quiet pump are significantly reduced. At 5.5 times the threshold current, the spectral linewidth decreases from 337.2 kHz to 213.2 kHz, and the RIN decreases from −141.3 dB Hz ^−1 to −168.8 dB Hz ^−1 . This reduction is attributed to the lower external carrier noise level of the quiet pump, which also suppresses the spectral linewidth rebroadening effect at a high bias current. Moreover, when external optical injection locking is applied, the spectral linewidth further decreases to 24 kHz at an injection ratio of −70 dB and to 1.8 mHz at 0 dB. The RIN also slightly decreases to −172.4 dB Hz ^−1 with an injection ratio of 10. These results demonstrate that using a quiet pump is an effective and manageable strategy for significantly reducing both the spectral linewidth and RIN of QD lasers, thereby facilitating their application in next-generation photonic integrated circuits, continuous-variable quantum key distribution, quantum computing and ultra-precise quantum sensing.

BackgroundPosterior chamber phakic intraocular implantable collamer lens (ICL) implantation is an effective surgical option for the management of myopia. Over the past few years, the number of ICL surgeries has significantly increased. Postoperative inflammation and endophthalmitis are among the most serious complications after successful ICL surgery. Sometimes, when the blepharospasm is removed at the end of surgery, a small amount of the ocular surface fluid will flow into the anterior chamber, which can lead to an increased risk of infection and inflammation. However, little attention has been paid to this phenomenon.PurposeWe conducted a retrospective study to compare the incidence of extraocular fluid inflow into the eye through the clear corneal incision (CCI) at two different positions (superior and temporal sides).MethodsA total of 116 patients with myopia underwent superior CCI ICL implantation (n = 58) or temporal CCI ICL implantation (n = 58) at our hospital from October to December 2021. The incidence of conjunctival sac fluid entering the anterior chamber after eyelid fixative was removed was compared in both groups.ResultsBoth groups were well matched in all parameters. Ocular surface fluid inflow into the anterior chamber was significantly higher in the superior CCI group (25/58, 47.1%) than in the temporal CCI group (1/58, 1.7%) (p

Quantum dot are one of the best practical examples of nanotechnologies. Owing to the discrete energy levels, quantum dot lasers output unique features like thermal stability, feedback insensitivity and spectral purity.

BackgroundTakayasu’s arteritis (TA) is a rare, chronic granulomatous large-vessel vasculitis that can lead to ocular ischemia. Ocular outcomes after therapeutic management in TA remain largely unknown. We herein conduct a case-based systematic review to address the current treatment options in this particular cohort.MethodsPubMed, Medline, and EMBASE databases were searched pertaining to ocular outcomes after systemic treatment in TA. Studies reporting ocular examinations before and after treatment in TA patients with ocular ischemia were included. Clinical characteristics, therapies, ocular outcomes, and complications were recorded.ResultsA 29-year-old woman with newly diagnosed TA showed dramatic regression of Takayasu’s retinopathy (TR) following balloon angioplasty. Optical coherence tomography angiography (OCTA) was used as a novel strategy for subsequent follow-up. A total of 117 eyes of 66 patients with a median age of 27 years were included for systematic review. TR was the most common ocular manifestation. Oral steroids were prescribed in nearly all patients (n = 65), followed by the use of methotrexate and antiplatelet therapy. Of the patients, 65.8% and 34.2% underwent open surgery and endovascular procedure, respectively. The median follow-up period was 12 weeks (interquartile range 8–33.5). Surgical therapy showed better ocular improvement (including visual and imaging responses) in both acute and chronic vision loss, along with fewer complications than medical therapy alone. In the surgical group, the visual prognosis was significantly better in patients with initial visual acuity better than 20/200 (p = 0.03) and those who underwent surgery before stage III TR (p = 0.01). Ocular outcomes were equivalent in the two surgical approaches.ConclusionClinicians should be familiar with ophthalmic manifestations of this potentially treatable complication in TA. Compared with medical therapy alone, surgical intervention might be a better choice for both acute and chronic vision loss. Surgery is best recommended before the onset of irreversible ischemia to the globe. A combined regimen (oral steroids, immunosuppressants, and antiplatelet drugs) might be effective for those with surgical contradictions or reluctance to an invasive procedure. Physicians should be aware of the importance of ocular examinations, including OCTA, during the diagnosis and follow-up in TA.

Purpose: This network meta-analysis was conducted to obtain the relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion (RVO) by summarizing all available evidences.Methods: PubMed, Embase, and Cochrane Library databases were searched for all relevant randomized controlled trials. The outcomes were estimated through a network meta-analysis, including the mean change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness (CRT).Results: We identified 15 randomized controlled trials (RCTs) involving 3,431 patients with RVO in our study. Different therapeutic regimens were compared including three anti-vascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, and aflibercept), ranibizumab with laser, dexamethasone intravitreal implant, and laser. For branch RVO, ranibizumab 0.5 mg monthly [weighted mean difference (WMD) = 11, 95% confidence intervals (CrI) 3.6 to 19], ranibizumab 0.5 mg 3 + pro re nata (WMD = 9.4, 95% CrI 0.43–18) is most effective in terms of changes of BCVA and 15 letters or more of BCVA improvement. For central RVO, three anti-VEGF regimens can improve visual acuity and there is no significant difference of efficacy among ranibizumab, bevacizumab and aflibercept (p > 0.05). Ranibizumab 0.5 mg monthly could achieve additional efficacy in CRT reduction in eyes with branch RVO or central RVO (WMD = -130, 95% CrI -400 to 140 or WMD = -280, 95% CrI -590 to 16)). Dexamethasone intravitreal implant (WMD = 1.7, 95% CrI -4.2 to 7.1 or WMD = 0.38, 95% CrI -9.8 to 8.8)) did not show a significant improvement in visual acuity at the end of 6 months follow-up in eyes with branch RVO or central RVO.Conclusion: In summary, this network meta-analysis demonstrated several anti-VEGF agents had equivalent effects on mean visual acuity changes and anatomical recovery in 6 months in eyes with branch or central RVO. Only one injection of dexamethasone intravitreal implant in 6 months could not maintain the visual benefit. Patients and clinicians could choose pharmacotherapies with further consideration toward personal factors.

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.

ObjectivesThe objective of this study was to assess the reliability of online information, as provided by three major search engines in China, about the usage of antiepileptic drugs (AEDs) during pregnancy.MethodOver eight weeks, six physicians conducted a literature search on six computers and six smartphones at a frequency of once per week. During each web search on each computer and smartphone, three major search engines in China were used, namely, Baidu, Sogou and 360. The search terms used were a combination of words, including one AED name (valproate/oxcarbazepine/levetiracetam/lamotrigine) and one Chinese word ("huaiyun" or "renshen", which means pregnancy in Chinese). The top ten websites retrieved from each search were recorded. After the content of each website was evaluated, the sites were categorized into 9 types. Meanwhile, commercial advertisements on each web page were also registered.ResultsA total of 16,411 search results were assessed. After excluding the redundant web pages, 4840 search results were included in the data analysis. Only 12.05% of the search results were reliable, 47.75% were partly reliable, and 40.21% were unreliable. A total of 4139 (85.52%) webpages contained commercial advertisements. The results from a multivariate analysis suggested that websites with no advertisements and professional websites have an independent positive impact on reliability.ConclusionOverall, little information on AED usage during pregnancy provided by major search engines in China was reliable.Practice implicationsAccurate and professional online information for female patients with epilepsy should be provided through major efforts by the government, search engine companies, professional websites and epilepsy physicians.