Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Antibacterial effect of the metal nanocomposite on Escherichia coli.

Ag nanocomposites (NAs) have been found to induce irreversible harm to pathogenic bacteria, however, NAs tend to aggregate easily when used alone. These nanocomposites also show increased toxicity and their underlying antibacterial mechanism is still unknown. In short, practical applications of NA materials face the following obstacles: elucidating the mechanism of antibacterial action, reducing cytotoxicity to body cells, and enhancing antibacterial activity. This study synthesized a core-shell structured ZnFe2O4 @Cu-ZIF-8 @Ag (FUA) nanocomposite with high antibacterial activity and low cytotoxicity. The nanocomposites achieved a 99.99 % antibacterial rate against Escherichia coli (E. coli) and tetracycline-resistant E. coli (T - E. coli), in under 20 min at 100 µg/mL. The nanocomposites were able to inactivate E. coli due to the gradual release of Cu2+, Zn2+, and Ag+ ions, which synergistically form •OH from FUA in an aerobic environment. The presence of •OH has significant effects on the antibacterial activity. The released metal ions combine with •OH to cause damage to the bacterial cell wall, resulting in the leakage of electrolytes and ions. Moreover, in comparison to NA, the toxicity of FUA is considerably reduced. This study is expected to inspire the development of other silver-based nanocomposite materials for the inactivation of drug-resistant bacteria.

Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, including the Vibrio cholerae-infecting ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1), harbor CRISPR-Cas systems to counteract host defenses. Nevertheless, ICP1 Cas8f lacks the helical bundle domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage and how this system accomplishes the interference stage remains unknown. Here, we found that Cas1, a highly conserved component known to exclusively work in the adaptation stage, also mediates the interference stage through connecting Cas2/3 to the DNA-bound CRISPR-associated complex for antiviral defense (Cascade; CRISPR system yersinia, Csy) of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA (double-stranded DNA), Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes reveal the whole process of Cas1-mediated target DNA cleavage by the ICP1 CRISPR-Cas system. Together, these data support an unprecedented model in which Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system and the study also sheds light on a unique model of primed adaptation.

A comparative study on anti-MOG and anti-AQP4 associated optic neuritis following mild COVID-19: insights from a Chinese single-center experience.

Background: Research on the relationship between mild COVID-19 and the subsequent development of isolated optic neuritis (ON) with antibodies specific to myelin oligodendrocyte glycoprotein (MOG-ON) and aquaporin 4 (AQP4-ON) is limited, particularly case-control studies that directly compare these conditions within the same affected population. Methods: A retrospective analysis of initial MOG-ON and AQP4-ON cases during the COVID-19 peak and subsequent months. Patients were classified as possible COVID-19 related ON (PCRON) or non-COVID-19 related ON (NCRON). The study compared epidemiology, comorbidities, and clinical features between these groups. Results: Patients with MOG-ON tended to develop ON symptoms closer in time to a mild COVID-19 infection compared to those with AQP4-ON (6.87 ± 6.25 weeks vs. 11.06 ± 5.84 weeks; p = 0.038), a significantly higher proportion of patients with MON-ON developing symptoms within 6 weeks after COVID-19 compared to those with AQP4-ON (15/23 [65.2%] vs. 5/17 [29.4%]; p = 0.025). Comparing MOG-ON and AQP4-ON patients, MOG-ON patients were more likely to have a recent infection before ON onset (73.1% vs. 30%; p = 0.007) and had better peak and post-treatment visual acuity (p = 0.01; p < 0.001). In contrast, AQP4-ON patients frequently showed comorbid connective tissue diseases (30.0% vs. 0%, p = 0.004) and antinuclear antibody abnormalities (40.0% vs. 7.7%, p = 0.012). Among MOG-ON patients, PCRON had increased rates of atherosclerotic vascular diseases (AVDs) (53.3% vs. 9.1%, p = 0.036), phospholipid antibody abnormalities (60.0% vs. 18.2%, p = 0.04), and bilateral visual impairment (66.7% vs. 9.1%, p = 0.005). Multivariate analysis pinpointed AVDs (OR = 15.21, p = 0.043) and bilateral involvement (OR = 25.15, p = 0.015) as independent factors related to COVID-19 associated MOG-ON, with both being good discriminators for PCRON (AUC = 0.879). No differences were found between the PCRON and NCRON groups in AQP4-ON patients. Conclusion: Mild COVID-19 is more likely associated with MOG-ON than AQP4-ON. MOG-ON that develops within 6 weeks following a COVID-19 infection may be associated with the COVID-19 infection. AVDs may have a synergistic effect on MOG-ON in patients with COVID-19, which warrants further investigation. COVID-19 related MOG-ON often affects both eyes, and acute visual function damage can be severe, but generally has a good prognosis.

PTX3 promotes cementum formation and cementoblast differentiation via HA/ITGB1/FAK/YAP1 signaling pathway.

Cementum is a vital component of periodontium, yet its regeneration remains a challenge. Pentraxin 3 (PTX3) is a multifunctional glycoprotein involved in extracellular matrix remodeling and bone metabolism regulation. However, the role of PTX3 in cementum formation and cementoblast differentiation has not been elucidated. In this study, we initially observed an increase in PTX3 expression during cementum formation and cementoblast differentiation. Then, overexpression of PTX3 significantly enhanced the differentiation ability of cementoblasts. While conversely, PTX3 knockdown exerted an inhibitory effect. Moreover, in Ptx3-deficient mice, we found that cementum formation was hampered. Furthermore, we confirmed the presence of PTX3 within the hyaluronan (HA) matrix, thereby activating the ITGB1/FAK/YAP1 signaling pathway. Notably, inhibiting any component of this signaling pathway partially reduced the ability of PTX3 to promote cementoblast differentiation. In conclusion, our study indicated that PTX3 promotes cementum formation and cementoblast differentiation, which is partially dependent on the HA/ITGB1/FAK/YAP1 signaling pathway. This research will contribute to our understanding of cementum regeneration after destruction.

Passive laser power stabilization in a broadband noise spectrum via a second-harmonic generator.

An extremely conspicuous passive power noise stabilization is the first, to the best of our knowledge, discovered in a cavity-enhanced second-harmonic generation (SHG) process. Differing from the SHG as a buffer reservoir, the stronger strength of the nonlinear interaction pushes the power noise suppression level to a higher value and exhibits a broadband noise reduction performance due to the mechanism of dynamic pump suppression in the SHG process. The noise is suppressed to near shot noise limit (SNL) among the kHz to MHz frequency range, accompanied by a maximum noise reduction of 35 dB. A comprehensive demonstration indicates that the nonlinear interaction has no function on the phase noise of fundamental and harmonic waves. A theoretical model is also established that is consistent well with the experimental results. The methodology is beneficial to multiple optical metrology experiments.

[Resveratrol attenuates neuroinflammation and alleviates emotional dysfunction in mice with sepsis-associated encephalopathy through promoting chaperone-mediated autophagy (CMA)].

Objective To elucidate the role of chaperone-mediated autophagy (CMA) in alleviating emotional dysfunction in mice with sepsis-associated encephalopathy (SAE). Methods The SAE mouse model was established by cecal ligation and perforation (CLP). The severity of sepsis was assessed using the sepsis severity score (MSS). Emotional function in SAE mice was assessed by the open-field test and elevated plus-maze. The expression levels of cognitive heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2A (LAMP2A) and high mobility group box 1 protein B1 (HMGB1) were detected using Western blotting. Co-localization of LAMP2A in the hippocampal neurons was observed by immunofluorescence. The release of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using ELISA. Following 12 hours post-CLP, mice were orally administered resveratrol at a dose of 30 mg/kg once daily until day 14. Results The mortality rate of CLP mice was 45.83% 24 days post CLP, and all surviving mice exhibited emotional disturbances. 24 hours after CLP, a significant decrease in HSC70 and LAMP2A expression in hippocampal neurons was observed, indicating impaired CMA activity. Meanwhile, HMGB1 and inflammatory cytokines (IL-6 and TNF-α) levels increased. After resveratrol treatment, an increase of HSC70 and LAMP2A expression, and a decrease of HMGB1 expression and inflammatory cytokine release were observed, suggesting enhanced CMA activity and reduced neuroinflammation. Behavioral tests showed that emotional dysfunction was improved in SAE mice after resveratrol treatment. Conclusion CMA activity of hippocampal neurons in SAE mice is significantly reduced, leading to emotional dysfunction. Resveratrol can alleviate neuroinflammation and emotional dysfunction in SAE mice by promoting CMA and inhibiting the expression of HMGB1 and the release of inflammatory factors.

Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. METHODS: Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4 (ANGPTL4) phosphorylation. RESULTS: We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive (N+) GC and further demonstrated that a high-fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity-related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase-2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. CONCLUSIONS: Leptin-induced phosphorylation of ANGPTL4 facilitates LPL-mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.

Primary familial brain calcification presenting with parkinsonism and motor complications caused by a novel SLC20A2 variant: a case report.

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2-associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment.

Enabling AI-Generated Content for Gadolinium-Free Contrast-Enhanced Breast Magnetic Resonance Imaging.

BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Quercetin encapsulation and release using rapid CO2-responsive rosin-based surfactants in Pickering emulsions.

Emulsion-based delivery systems are extensively employed for encapsulating functional active ingredients, protecting them from degradation, and enhancing bioavailability and release efficiency. Here, a CO2-responsive surfactant synthesized from rosin displays rapid responsiveness to CO2 at room temperature, transitioning reversibly switches between active and inactive states multiple times. The dual tertiary amines on the rosin rigid structure contributes to its CO2 sensitivity. When in its active cationic form, in conjunction with silica nanoparticles, it exhibits desired Pickering emulsification performance across various oil phases. In the Pickering emulsion loaded with quercetin, the encapsulation efficiency and loading efficiency reached 80.50% and 0.69%, respectively, with stability lasting at least 30 days. The system provides robust protection for quercetin against external factors, such as UV and heat, revealing sustained release effects. This study investigated the potential of using rosin-based CO2-responsive surfactants alongside nanoparticles to design stable Pickering emulsion systems for active substance encapsulation and sustained release.

Can Leading by Example Alone Improve Cooperation?

Cooperation is essential for the survival of human society. Understanding the nature of cooperation and its underlying mechanisms is crucial for studying human behavior. This paper investigates the impact of leadership on public cooperation by employing repeated sequential public goods games, as well as by examining whether leading by example (through rewards and punishments) can promote cooperation and organizational success. The leaders were assigned randomly and were given the authority to reward or punish. As a result, (1) the leaders showed a strong tendency toward reciprocity by punishing free riders and rewarding cooperators at their own expense, which enhanced the intrinsic motivation for others to follow their example; and (2) both rewards and punishments were effective in promoting cooperation, but punishment was more effective in sustaining a high level of collaboration. Additionally, leaders preferred using rewards and were more reluctant to use punishments. These findings are crucial for creating organizational structures that foster cooperation.

Histone lactylation facilitates hepatocellular carcinoma progression by upregulating endothelial cell-specific molecule 1 expression.

Hepatocellular carcinoma (HCC) is a common malignant tumor. Histone lactylation, a novel epigenetic modification, plays a crucial role in various cancers. However, the functional role and underlying mechanism of histone lactylation in HCC progression have not yet been investigated. Histone lactylation levels in HCC tissues and cells were assessed using a densitometric kit and western blot analysis. The role of histone lactylation in cell malignant phenotypes was determined through functional assays in vitro, and a xenograft tumor model was established to verify the function of histone lactylation in vivo. ChIP assay was performed to explore the interaction between histone lactylation and endothelial cell-specific molecule 1 (ESM1). Additionally, gain-and-loss-of-function assays were conducted to investigate the regulatory role of ESM1 in HCC pathogenesis. Histone lactylation levels were increased in HCC tissues and cells, and H3K9 lactylation (H3K9la) and H3K56 lactylation (H3K56la) were identified as the histone modification sites. We observed that H3K9la and H3K56la caused abnormal histone lactylation and were associated with poor prognosis. Functionally, histone lactylation was found to promote HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in vitro. However, histone lactylation inhibition with 2-deoxy-d-glucose (2-DG) reduced the malignant phenotypes of HCC cells. In vivo, 2-DG treatment reduced tumor growth and metastasis in the HCC mouse model. Mechanistically, it was revealed that histone lactylation activated ESM1 transcription in HCC cells. ESM1 was expressed at a high level in HCC and exerted a carcinogenic role. Histone lactylation facilitates cell malignant phenotypes, tumor growth, and metastasis by upregulating ESM1 expression in HCC, which reveals the downstream molecular mechanism of histone lactylation and might provide a novel therapeutic target for HCC therapy.

Chirally Selective and Switchable Luminescence from Achiral Quantum Emitters on Suspended Twisted Stacking Metasurfaces.

Dynamic control of circularly polarized photoluminescence has aroused great interest in quantum optics and nanophotonics. Chiral plasmonic metasurfaces enable the manipulation of the polarization state via plasmon-photon coupling. However, current plasmonic light-emitting metasurfaces for effective deterministic modulation of spin-dependent emission at near-infrared wavelengths are underexplored in terms of dissymmetry and tunability. Here, we demonstrate a microfluidic hybrid emitting system of a suspended twisted stacking metasurface coated with PbS quantum dots. The suspended metasurface is fabricated with a single step of electron beam exposure, exhibiting a strong optical chirality of 309° µm-1 with a thickness of less than λ/10 at key spectral locations. With significant chiral-selective interactions, enhanced photoluminescence is achieved with strong dissymmetry in circular polarization. The dissymmetry factor of the induced circularly polarized emission can reach 1.54. More importantly, altering the refractive index of the surrounding medium at the bottom surface of the metasurface can effectively manipulate the chiroptical responses of the hybrid system, hence leading to chirality-reversed emission. This active hybrid emitting system could be a resultful platform for chirality-switchable light emission from achiral quantum emitters, holding great potential for anticounterfeiting, biosensing, light sources, imaging, and displays.

Mechanism Switch in Surface-Enhanced Raman Scattering: The Role of Nanoparticle Dimensions.

Surface-enhanced Raman scattering (SERS) is renowned for amplifying Raman signals, with electromagnetic mechanism (EM) enhancement arising from localized surface plasmon resonances and chemical mechanism (CM) enhancement as a result of charge transfer interactions. Despite the conventional emphasis on EM as a result of plasmonic effects, recent findings highlight the significance of CM when noble metals appear as smaller entities. However, the threshold size of the noble metal clusters/particles corresponding to the switch in SERS mechanisms is not clear at present. In this work, the VSe2-xOx/Au composites with different Au sizes are employed, in which a clear view of the SERS mechanism switch is observed at the Au size range of 16-21 nm. Our findings not only provide insight into the impact of noble metal size on SERS efficiency but also offer quantitative data to assist researchers in making informed judgments when analyzing SERS mechanisms.

Genome-Wide Identification and Characterization of U-Box Gene Family Members and Analysis of Their Expression Patterns in Phaseolus vulgaris L. under Cold Stress.

The common bean (Phaseolus vulgaris L.) is an economically important food crop grown worldwide; however, its production is affected by various environmental stresses, including cold, heat, and drought stress. The plant U-box (PUB) protein family participates in various biological processes and stress responses, but the gene function and expression patterns of its members in the common bean remain unclear. Here, we systematically identified 63 U-box genes, including 8 tandem genes and 55 non-tandem genes, in the common bean. These PvPUB genes were unevenly distributed across 11 chromosomes, with chromosome 2 holding the most members of the PUB family, containing 10 PUB genes. The analysis of the phylogenetic tree classified the 63 PUB genes into three groups. Moreover, transcriptome analysis based on cold-tolerant and cold-sensitive varieties identified 4 differentially expressed PvPUB genes, suggesting their roles in cold tolerance. Taken together, this study serves as a valuable resource for exploring the functional aspects of the common bean U-box gene family and offers crucial theoretical support for the development of new cold-tolerant common bean varieties.

CircPGM5 regulates Foxo3a phosphorylation via MiR-21-5p/MAPK10 axis to inhibit bladder cancer progression.

Bladder cancer (BC) is one of the most prevalent malignant tumors worldwide, and the incidence is especially higher in males. Extensive evidence has demonstrated the pivotal role of circular RNAs (circRNAs) in BC progression. However, the exact regulatory mechanism of circRNAs in BC remains incompletely elucidated and warrants further exploration. This study screened a novel circRNA-circPGM5 from thousands of circRNAs by high-throughput sequencing. We found that circPGM5, originating from the PGM5 gene, was significantly lower expressed in BC tissues. Quantitative real-time PCR (qRT-PCR) verified that circPGM5 showed relatively low expression in 50 pairs of BC tissues and EJ and T24 cells. Notably, circPGM5 expression was correlated with stage, grade, and lymphatic metastasis of BC. Through RNA-FISH assay, we confirmed that circPGM5 predominantly localized in the cytoplasm. Functionally, overexpression of circPGM5 inhibited the proliferation, migration, and invasion of BC cells in vitro. Remarkably, circPGM5 demonstrated markedly significant tumor growth and metastasis suppression in vivo. Mechanistically, we discovered that circPGM5 upregulated the mitogen-activated protein kinase 10 (MAPK10) expression by influencing the oncogenic miR-21-5p activity through miR-21-5p absorption. This modulation of MAPK10 impacted the phosphorylation of the tumor suppressor Foxo3a in BC. In conclusion, our findings uncovered the tumor-suppressing role of circPGM5 in BC via the miR-21-5p/MAPK10/Foxo3a axis.

Anneal-free ultra-low loss silicon nitride integrated photonics.

Heterogeneous and monolithic integration of the versatile low-loss silicon nitride platform with low-temperature materials such as silicon electronics and photonics, III-V compound semiconductors, lithium niobate, organics, and glasses has been inhibited by the need for high-temperature annealing as well as the need for different process flows for thin and thick waveguides. New techniques are needed to maintain the state-of-the-art losses, nonlinear properties, and CMOS-compatible processes while enabling this next generation of 3D silicon nitride integration. We report a significant advance in silicon nitride integrated photonics, demonstrating the lowest losses to date for an anneal-free process at a maximum temperature 250 °C, with the same deuterated silane based fabrication flow, for nitride and oxide, for an order of magnitude range in nitride thickness without requiring stress mitigation or polishing. We report record low anneal-free losses for both nitride core and oxide cladding, enabling 1.77 dB m-1 loss and 14.9 million Q for 80 nm nitride core waveguides, more than half an order magnitude lower loss than previously reported sub 300 °C process. For 800 nm-thick nitride, we achieve as good as 8.66 dB m-1 loss and 4.03 million Q, the highest reported Q for a low temperature processed resonator with equivalent device area, with a median of loss and Q of 13.9 dB m-1 and 2.59 million each respectively. We demonstrate laser stabilization with over 4 orders of magnitude frequency noise reduction using a thin nitride reference cavity, and using a thick nitride micro-resonator we demonstrate OPO, over two octave supercontinuum generation, and four-wave mixing and parametric gain with the lowest reported optical parametric oscillation threshold per unit resonator length. These results represent a significant step towards a uniform ultra-low loss silicon nitride homogeneous and heterogeneous platform for both thin and thick waveguides capable of linear and nonlinear photonic circuits and integration with low-temperature materials and processes.

Timing of immunotherapeutic strategies for first-episode Isolated Anti-Myelin Oligodendrocyte Glycoprotein-IgG Associated Optic Neuritis: A single-centre retrospective study.

Background: There is no consensus on the timing of immunotherapeutic strategies for the first-episode anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) associated disorders (MOGAD) presenting with isolated optic neuritis (ON). Objective: To investigate the optimal timing of intravenous methylprednisolone therapy (IVMP) and necessity of immunosuppressive therapy for the first-episode isolated MOG-IgG associated ON (iMOG-ON). Methods: Adult patients with the first-episode iMOG-ON were enrolled. Primary outcomes were best-corrected visual acuity (BCVA) at last follow-up (i.e. final BCVA) and relapse, and their predictors were assessed by multivariate analysis. Results: 62 patients were included. Logistic regression analysis revealed BCVA at the time of IVMP (odds ratio: 0.463 (95 % confidence interval (CI) 0.310-0.714) was a factor predictive of regaining a final BCVA of 0.0 logMAR vision, and its Youden optimal criterion was <0.175 logMAR by plotting the receiver operating characteristic curve. The time-dependent cox proportional hazards model exhibited MMF therapy was not associated with a high likelihood of relapse-free survival (HR = 1.099, 95 % CI 0.892-1.354, P = 0.376) after adjusting for age of onset, gender, and baseline MOG serum titers. Similar analysis exhibited evidently negative association between high MOG-IgG serum titers at baseline and relapse-free survival after adjusting for age of onset, gender, and MMF therapy (HR = 0.339, 95 % CI 0.155-0.741, P = 0.007). Conclusions: During the first episode of iMOG-ON, the optimal timing of IVMP may be a short timeframe before visual acuity decreasing to 0.175 logMAR, and MMF therapy may not be recommended for patients with low MOG-IgG serum titers. Further long-term follow-up studies are required to validate these findings.

Exploring the poverty-reduction benefits of agricultural machinery socialization services in China: Implications for the sustainable development of farmers.

Sustainable development is crucial for alleviating poverty among farmers. In this study, we examined the impact, and the mechanism underlying this impact, of the adoption of agricultural machinery services by farmers on their relative poverty from a multidimensional poverty perspective by employing the logit and ordered logit models and the Karlson-Holm-Breen (KHB) method. These results indicate that adopting agricultural machinery services can significantly reduce the probability of relative poverty among farmers, thereby expediting the sustainability of rural development. However, this poverty-reduction effect varies based on age and sex. The adoption of agricultural machinery services mainly reduces poverty by increasing farmers' human capital. Training in employment skills and non-agricultural work experience are the main transmission mechanisms. Therefore, the socialization of agricultural machinery services can be used as an effective policy tool to reduce relative poverty in developing countries, promote sustained improvements in farmers' incomes, and achieve sustainability in rural development.