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Flexoelectricity, the coupling between electric polarization and strain gradients in dielectrics, attracts growing research interest because of its potential to replace/complement piezoelectricity in electromechanical applications. Thanks to the large dielectric permittivity, ferroelectrics exhibit enhanced flexoelectricity and usually serve as the functional ingredient in flexoelectric devices. However, ferroelectric flexoelectricity usually suffers from poor temperature stability, which adversely affects practical applications. In this work, compositional gradients are introduced into Ba1−xSrxTiO3 systems to enhance the temperature stability of flexoelectric behavior. Experimental results show that the drastic variations of flexoelectricity (up to 100 times) from 20 to 120 °C in single component ceramics (such as Ba0.67Sr0.33TiO3 and BaTiO3) can be significantly reduced in graded Ba1−xSrxTiO3 ceramics, in which the flexoelectric coefficient is in the range from 13 to 26 μC/m. The improved stability results from the engineered sequential Curie temperatures of individual layers in graded ceramics and the positive correlation between dielectric constant and flexoelectricity. Our work provides a method to enable the robust performance of flexoelectric devices in an ambient environment with large temperature fluctuations. [ABSTRACT FROM AUTHOR]

Abstract Background The cardiometabolic index (CMI) is a new predictor of obesity-related diseases, but its link to periodontitis is under-researched. This study aims to examine the potential association between the CMI and periodontitis. Methods We conducted a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009–2014) to examine the potential association between CMI and periodontitis. The study utilized a weighted multivariate logistic model to assess the association between TG, HDL-C, TG/HDL-C, obesity indices (BMI, WC, WHtR, CMI), and periodontitis, employing the area under the receiver operating characteristic curves (ROC) to estimate areas under the curve (AUC). Furthermore, generalized smooth curve fitting was conducted to examine the relationship between CMI and periodontitis. Finally, the study incorporated subgroup analysis and interaction tests to examine consistency across different populations. Results TG/HDL-C, WHtR, and CMI were positively associated with periodontitis in the fully adjusted classification model. It was observed that for each unit increase in CMI, there was a corresponding 17.8% increase in the prevalence of periodontitis [1.178 (1.049, 1.322) 0.00562] and 18.7% increase in the prevalence of moderate/severe [1.187 (1.057, 1.334) 0.00376] in the fully adjusted model. When CMI was used as a categorical variable, the adjusted OR for periodontitis prevalence increased significantly with increasing CMI after adjusting for all potential covariates (T3 vs. T1: OR, 1.28 [1.06, 1.55], p 0.05). Further generalized smooth curve fitting and threshold effect models indicated a positive linear correlation between CMI and periodontitis. Moreover, there is no interactive association between TG/HDL-C, WHtR, CMI, and periodontitis. Conclusions This cross-sectional study revealed a positive relationship between CMI and periodontitis. Further prospective studies are warranted to validate our findings.

Abstract Background Cervical ripening is a multifactorial outcome, and the association between cervical ripening and vaginal microbiota remains unexplored in term primiparous women. A new sequencing technology, microbiome 2bRAD sequencing (2bRAD-M) that provides a higher level of species discrimination compared to amplicon sequencing. We applied 2bRAD-M to analyze the vaginal microbiota in a population with variations in cervical ripeness and to explore potential microbiota factors influencing cervical ripening. Methods A total of 30 full-term primigravid women participated in this study, with 15 belonging to the low scoring group of cervical ripeness and 15 to the high scoring group. Clinical information was collected from the participants, and the vaginal microbiota and community structure of both groups were analyzed using 2bRAD-M sequencing. Microbiota diversity and differential analyses were conducted to explore potential factors influencing cervical ripening. Results A total of 605 species were detected. There was no difference in vaginal microbiota diversity between the two groups, and the vaginal microbial composition was structurally similar. In the two groups, Lactobacillus crispatus and Lactobacillus iners were identified as the two pivotal species through random forest analysis. Concurrent, extensive and close connections between species within the two groups were observed in the correlation analysis, influencing the aforementioned two species. Pairwise comparisons showed that Sphingomonas (P = 0.0017) and three others were abundant in high scoring group, while Alloprevotella (P = 0.0014), Tannerella (P = 0.0033), Bacteroides (P = 0.0132), Malassezia (P = 0.0296), Catonella (P = 0.0353) and Pseudomonas (P = 0.0353) and so on showed higher abundance in low scoring group. Linear discriminant analysis effect size identified 29 discriminative feature taxa. Conclusion For the first time, vaginal microbiota was sequenced using 2bRAD-M. With a relatively simple structure, a more stable vaginal microbiota is associated with higher cervical ripeness, and certain microorganisms, such as Sphingomonas, may play a beneficial role in cervical ripening.

Abstract Background Mindfulness-based stress reduction (MBSR) intervention has been widely used to reduce the burden of symptoms in cancer patients, and its effectiveness has been proven. However, the effectiveness of MBSR on depression, anxiety, fatigue, quality of life (QOL), posttraumatic growth (PTG), fear of cancer recurrence (FCR), pain, and sleep in breast cancer patients has not yet been determined. This study aims to determine the role of mindfulness-based stress reduction therapy in patients with breast cancer. Objectives The objective was to systematically review the literature to explore the effect of MBSR on anxiety, depression, QOL, PTG, fatigue, FCR, pain, stress and sleep in breast cancer patients. To explore the effect of 8-week versus 6-week MBSR on the 9 indicators. Data were extracted from the original RCT study at the end of the intervention and three months after baseline to explore whether the effects of the intervention were sustained. Methods We conducted searches on PubMed, Web of Science, Embase, and China National Knowledge Infrastructure from inception to November 2023. Eligible studies included randomized controlled trials of breast cancer patients who received mindfulness stress reduction intervention, reporting outcomes for anxiety, depression, fatigue, QOL, PTG, FCR, pain, stress, and sleep. Two researchers conducted separate reviews of the abstract and full text, extracted data, and independently evaluated the risk of bias using the Cochrane ‘Bias Risk Assessment tool’. The meta-analysis utilized Review Manager 5.4 to conduct the study, and the effect size was determined using the standardized mean difference and its corresponding 95% confidence interval. Results The final analysis included 15 studies with a total of 1937 patients. At the end of the intervention, the interventions with a duration of eight weeks led to a significant reduction in anxiety [SMD=-0.60, 95% CI (-0.78, -0.43), P

Aiming at the problems of insufficient model input information and poor reasoning performance in knowledge-based visual question answering (VQA), this paper constructs a PTCR knowledge-based VQA framework based on large language model (LLM), which consists of four parts: answer candidate generation, targeted image descriptions, autonomous chain of thought (CoT) construction, and prompted LLM inference. The PTCR framework uses LLM to guide multimodal large language models to generate targeted image descriptions, which solves the problem of incomplete coverage of previous image captions. It improves the model??s reasoning ability by guiding LLM to autonomously generate CoT, which provides the thinking process of similar problems during the reasoning process; and it introduces selection rearrangement technology to eliminate LLM??s selection location discrimination during the reasoning process, and reduces the randomness error of the reasoning by means of majority voting. Experimental results show that the accuracy of the CogVLM model enhanced by the PTCR framework is improved by 16.7 percentage points and 13.3 percentage points on the OK-VQA and A-OKVQA datasets. Meanwhile, compared with Prophet, the accuracy of the PTCR framework is improved by 3.4 percentage points and 5.0 percentage points on the OK-VQA and A-OKVQA datasets. The results of ablation experiments demonstrate that the methods used in this paper, such as targeted image descriptions and autonomous chains of thought, are all effective in improving accuracy. It is evident that the PTCR framework has improved the performance of knowledge-based VQA.

The mechanism of contra-rotating propeller's aerodynamic noise is very complicated，and propeller-driven aircraft is not equipped passive noise reduction components such as nacelle liner to absorb noise during sound transmission，the noise generated by propeller will straightforward radiated to the fuselage and surrounding. Therefore，reducing the intensity of propeller noise is the key to the development of low-noise propeller aircraft. In this paper，a "soft blade" module is formed by placing a "small hole and through channel" structure on the suction front edge of spiral blade tip to balance the peak pressure at the leading edge of blade and reduce the load noise. According to the optimal parameters，the conventional propeller and the soft-blade propeller are manufactured，and the radiation noise measurement is carried out on the basis of the counter-rotating propeller aerodynamic noise test system. The results show that the counter-rotating propeller with perforated structure can effectively reduce the noise as well as ensuring the aerodynamic performance. At the 90° pointing angle，which has the most significant effect on the aircraft cabin，the noise reduction at the second-order passing frequency reaches 5 dB.

Abstract Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

Justice is an ancient concept that originated from commodity exchange and has been continuously critiqued and discussed in philosophy, ethics, and law to identify potential pathways for societies and institutions. Since the 1960s, justice research led by sociologists and political scientists has identified spatial injustices, attributing them to inherent flaws in economic systems, social order, and legal frameworks. Subsequently, the emphasis on spatial aspects, proposed by Henri Lefebvre's "right to the city" and the spatiality of social justice explored by Marxist geographers, inspired scholars such as Pirie, Soja, and Iveson. These scholars have continuously refined the theoretical framework of spatial justice, prioritizing real-world spatial practices. The essence of spatial justice can be understood through a series of dichotomies: it is both a theoretical critique and a practical methodology, passively influenced by social systems yet spatially proactive, static yet dynamic, and both process and outcome. The essential questions are "seeing spatial justice" and "seeking spatial justice", which involve "describing the justice level of social spatial outcomes" and "exploring the spatial causes and formation processes of injustice." Additionally, the two main research directions are "territorial distribution justice" and "local discrimination." Spatial justice does not imply absolute equality in distribution processes or outcomes; rather, it recognizes differences in human needs that lead to unequal distributions. The principles of spatial justice include both equality and differentiation. Scholars generally agree that the principle of equality should meet basic needs, such as transportation infrastructure, primary education, and healthcare services, which ensure minimum living standards. Based on differentiated needs—determined by factors such as region, identity, environment, contributions, and merits—non-essential material goods, social resources, and environmental assets can be allocated unequally. However, the concept of human needs is inherently subjective and is closely related to age, education, perception, and experience. Evaluating the reasonableness of these needs is complex and challenging. Assessing spatial justice from the perspective of human needs requires addressing two key issues: defining the scope of basic and non-basic needs and establishing assessment standards or indices for multidimensional needs. Although researchers such as Davies and Daniels have long argued that distribution should consider actual social needs rather than just population size, current empirical analyses, such as accessibility and availability studies, remain limited to measuring the ratio of resources to population size. Few studies have explored the characteristics and variances in needs related to residents, service levels, quality, and pricing, remaining distant from real, multidimensional, and differentiated human needs. By summarizing existing theories and methods, this study proposes three areas for future research: (1) research on territorial distribution justice should explore actual demand content beyond population size and establish relevant evaluation indicators; (2) urban spatial practices should adopt justice standards from a human-centric perspective to mitigate unjust socio-spatial outcomes; and (3) the forms and methods of achieving justice should be explored at a global regional scale.

Abstract The engineered TadA variants used in cytosine base editors (CBEs) present distinctive advantages, including a smaller size and fewer off-target effects compared to cytosine base editors that rely on natural deaminases. However, the current TadA variants demonstrate a preference for base editing in DNA with specific motif sequences and possess dual deaminase activity, acting on both cytosine and adenosine in adjacent positions, limiting their application scope. To address these issues, we employ TadA orthologs screening and multi sequence alignment (MSA)-guided protein engineering techniques to create a highly effective cytosine base editor (aTdCBE) without motif and adenosine deaminase activity limitations. Notably, the delivery of aTdCBE to a humanized mouse model of Duchenne muscular dystrophy (DMD) mice achieves robust exon 55 skipping and restoration of dystrophin expression. Our advancement in engineering TadA ortholog for cytosine editing enriches the base editing toolkits for gene-editing therapy and other potential applications.

Abstract Background In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. Methods This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60–65 Gy in 25–28 fractions to primary lesions and positive lymph nodes; 50–50.4 Gy in 25–28 fractions to the pelvis) or intensity-modulated radiotherapy (50–50.4 Gy in 25–28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. Discussion Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. Trial registration The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Abstract Expression profiling in spatially defined regions is crucial for systematically understanding tissue complexity. Here, we report a method of photo-irradiation for in-situ barcoding hybridization and ligation sequencing, named PBHL-seq, which allows targeted expression profiling from the photo-irradiated region of interest in intact fresh frozen and formalin fixation and paraffin embedding (FFPE) tissue samples. PBHL-seq uses photo-caged oligodeoxynucleotides for in situ reverse transcription followed by spatially targeted barcoding of cDNAs to create spatially indexed transcriptomes of photo-illuminated regions. We recover thousands of differentially enriched transcripts from different regions by applying PBHL-seq to OCT-embedded tissue (E14.5 mouse embryo and mouse brain) and FFPE mouse embryo (E15.5). We also apply PBHL-seq to the subcellular microstructures (cytoplasm and nucleus, respectively) and detect thousands of differential expression genes. Thus, PBHL-seq provides an accessible workflow for expression profiles from the region of interest in frozen and FFPE tissue at subcellular resolution with areas expandable to centimeter scale, while preserving the sample intact for downstream analysis to promote the development of transcriptomics.

Abstract Background The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). Methods and results In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. Conclusions Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC. Graphical abstract

Abstract Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at −402 mA cm−2 and a high activity up to −1 A cm−2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at −100 mA cm−2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

Abstract The electrochemical oxygen reduction reaction (ORR) to produce hydrogen peroxide (H2O2) is appealing due to its sustainability. However, its efficiency is compromised by the competing 4e− ORR pathway. In this work, we report a hierarchical carbon nanosheet array electrode with a single-atom Ni catalyst synthesized using organic molecule-intercalated layered double hydroxides as precursors. The electrode exhibits excellent 2e− ORR performance under alkaline conditions and achieves H2O2 yield rates of 0.73 mol gcat −1 h−1 in the H-cell and 5.48 mol gcat −1 h−1 in the flow cell, outperforming most reported catalysts. The experimental results show that the Ni atoms selectively adsorb O2, while carbon nanosheets generate reactive hydrogen species, synergistically enhancing H2O2 production. Furthermore, a coupling reaction system integrating the 2e− ORR with ethylene glycol oxidation significantly enhances H2O2 yield rate to 7.30 mol gcat −1 h−1 while producing valuable glycolic acid. Moreover, we convert alkaline electrolyte containing H2O2 directly into the downstream product sodium perborate to reduce the separation cost further. Techno-economic analysis validates the economic viability of this system.

The extrinsic black tooth stain (EBS) is commonly found in primary dentition. Patients cannot clean the EBS; this can only be done by professional scaling and debridement. It also has a tendency to reform, which significantly compromises children's aesthetics and even affects their quality of life. However, there is no conclusive evidence on the etiology of the EBS. The associations between the EBS and related oral microbial features is one of the research hot topics. No literature review summarized these research progresses in this area. Therefore, we reviewed the literature on the microbiology of the EBS since 1931 and reported as the following 5 aspects: molecular biotechnology, morphological structure and physiochemical characteristics, microbial etiology hypothesis and core microbial characteristics. The EBS is a special dental plaque mainly composed of Gram-positive bacilli and cocci with scattered calcium deposits that acquired salivary pellicle activates. Early studies showed that the Actinomyces was the main pathogenic bacteria. With advances in biological research techniques, the ‘core microbiome’ was proposed. The potential pathogenic genera were Actinomyces, Prevotella nigrescens, Pseudotropinibacterium, Leptotrichia, Neisseria and Rothia. However, the pathogenic species of the above genera were still unclear. Currently, it is believed that the EBS consists of iron compounds or black substances that oral bacterial metabolism produces or that the bacterial metabolites formed after chemical reactions in the micro-ecological environment.

Infections with vancomycin-resistant Enterococcus (VRE) have been increasingly reported, especially in immunocompromised patients. Bacteriophages (phages) are often considered as potential therapeutic candidates in treating infectious diseases. To search for therapeutic phages as antimicrobial agents for the treatment of Enterococcus faecium infections, eight E. faecium phages were isolated from the environments. One of these, phage φEc-ZZ2, which was capable of eliciting efficient lysis of E. faecium, was selected for analysis. Transmission electron microscopy revealed its resemblance to members of the family Siphoviridae, with a tail 200 nm long and an icosahedral head 45 nm in diameter. Phage φEc-ZZ2 exhibited rapid adsorption (> 99% adsorbed in 10 min), a short latency period of 20 min and a large burst size of 180 PFU/cell. Host range determination shows that φEc-ZZ2 has a relatively broader host range (specificity for 54.5% of tested E. faecium strains). Furthermore, when φEc-ZZ2 alone was incubated at different pH, the phage was stable over a wide pH range (5 to 9). These characteristics of φEc-ZZ2 will provide useful information for further research on the interaction between Enterococcus phages and their hosts. Moreover, in consideration of its pH stability and broader host range, φEc-ZZ2 may be a good candidate as a therapeutic/disinfectant agent to control nosocomial infections caused by E. faecium.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

ABSTRACT: The earlobes of chickens exhibit a range of colors, but there has been relatively little research on the formation of structural blue earlobes. Previous results showed that the structural color earlobes were related to the interplay between melanin and collagen in light reflection. To investigate the metabolic differences in these earlobe colors, we conducted nontargeted liquid chromatograph mass spectrometer (LC-MS) for metabolomic sequencing on structural blue (Green and Blue groups) and nonstructural color (Black group) earlobes tissue of Jiangshan black-bone chickens. The content detection in earlobe tissues of different groups shows that there were significant differences in melanin and collagen content between the Black and Green group. The metabolome identified a total of 6,102 mass spectroscopic peaks and ultimately identified 919 annotated metabolites. Variable importance in the projection (VIP) analysis identified the common differential expressed metabolites (DMs) “Tyr Thr Ala Glu” among the 3 groups. By combining those DMs with differentially expressed genes (DEGs) in our previous transcriptome data from the same sample, and associated with KEGG pathway analysis, multiple pathways related to melanogenesis and collagen metabolism were enriched across the 3 groups. By analyzing the metabolites and genes in these pathways, as well as the interaction network diagram of DEGs, we identified some key genes, Wnt Family Member 6 (WNT6), Transcription Factor 7 (TCF7), Proopiomelanocortin (POMC) and Calcium/Calmodulin Dependent Protein Kinase II Alpha (CAMK2A), and some key DMs like DG (11M3/9M5/0:0) and gentisic acid. The differential gene expression and metabolic levels affect the production of melanin and collagen, leading to differences in the content in melanin and the thickness of the collagen layer between earlobe colors, while the thickness of the collagen layer could affect light scattering, ultimately resulting in different colored earlobes in Jiangshan black-bone chickens.

Objective: Whether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. Methods: Overall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. Results: After propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). Conclusion: Patients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) represents a particularly aggressive subtype of gastric carcinoma characterized by elevated rates of vascular invasion, lymphatic dissemination, hepatic metastasis, and an unfavorable clinical outcome. Treatment strategies for AFPGC have historically lacked specificity. Herein, a case is presented involving AFPGC in which the patient exhibited a notable response to combined anti-PD-1 antibody immunotherapy and SOX chemotherapy, potentially achieving a cure. This report marks the first application of this regimen in neoadjuvant therapy for AFP gastric cancer, followed by radical resection and postoperative adjuvant therapy.Case summaryA 62-year-old male patient presented with persistent upper abdominal distension and discomfort lasting over 2 months. Initial investigations revealed markedly elevated serum alpha-fetoprotein (AFP) levels, and subsequent pathological examination confirmed the diagnosis of AFPGC via gastroscopy. Due to the patient’s condition, surgical resection was initially deemed unfeasible. Therefore, a chemo-immunotherapy regimen consisting of SOX chemotherapy and the PD-1 inhibitor tislelizumab was administered for 3 cycles. Following this, successful laparoscopic radical gastrectomy was performed. The treatment protocol was continued with an additional 3 cycles postoperatively. At the time of this case report, the patient maintained a good quality of life with no evidence of disease recurrence or adverse events.ConclusionThe present report highlights a case of AFPGC where significant therapeutic success was achieved through a combined regimen of chemotherapy and immunotherapy, both before and after surgery. The use of anti-PD-1 antibody (tislelizumab) in combination with SOX regimen (S-1 and oxaliplatin) demonstrated effective treatment of AFPGC, potentially offering a curative approach. This approach represents a promising targeted therapy option for patients with AFPGC.

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion This study identified OTUB2 as a novel regulator of intestinal inflammation.

BackgroundNear-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment technology that combines the advantages of optical technology and immunotherapy to provide a highly effective, precise, and low side-effect treatment approach. The aim of this study is to visualize the scientific results and research trends of NIR-PIT based on bibliometric analysis methods.MethodsThe Web of Science Core Collection (WoSCC) database was searched in August 2024 for relevant publications in the field of NIR-PIT. Data were analyzed using mainly CiteSpace and R software for bibliometric and visual analysis of the country/region, authors, journals, references and keywords of the publications in the field.ResultsA total of 245 publications were retrieved, including articles (n = 173, 70.61%) and reviews (n = 72, 29.39%). The annual and cumulative number of publications increased every year. The highest number of publications was from the United States (149, 60.82%), followed by Japan (70, 28.57%) and China (33, 13.47%). The research institution with the highest number of publications was National Institutes of Health (NIH)-USA (114, 46.53%). Kobayashi H (109) was involved in the highest number of publications, Mitsunaga M (211) was the most frequently cited in total. CANCERS (17) was the most frequently published journal, and NAT MED (220) was the most frequently co-cited journal. The top 10 keywords include near-infrared photoimmunotherapy (166), photodynamic therapy (61), monoclonal antibody (58), in vivo (50), cancer (46), expression (31), breast cancer (27), enhanced permeability (24), antibody (23), growth factor receptor (16). Cluster analysis based on the co-occurrence of keywords resulted in 13 clusters, which identified the current research hotspots and future trends of NIR-PIT in cancer treatment.ConclusionThis study systematically investigated the research hotspots and development trends of NIR-PIT in cancer treatment through bibliometric and visual analysis. As an emerging strategy, the research on the application of NIR-PIT in cancer treatment has significantly increased in recent years, mainly focusing on the targeting, immune activation mechanism, and treatment efficacy in solid tumors has received extensive attention. Future studies may focus on improving the efficacy and safety of NIR-PIT in cancer treatment, as well as developing novel photosensitizers and combination therapeutic regimens, and exploring the efficacy of its application in a wide range of solid tumors, which will provide an important reference and guidance for the application of NIR-PIT in clinical translation.

ObjectivePatient education is an important part of ankylosing spondylitis (AS) management. Effective patient education should be targeted at specific priorities and needs of the patients. However, the educational needs of patients with AS in China have not been systematically explored. The purpose of this study was to assess the level of educational needs and analyze associated factors in patients with AS in China.MethodsThis multicenter cross-sectional study was conducted at five hospitals in China. The Chinese version of the Educational Needs Assessment Tool (ENAT) was used to measure educational needs. Disease activity and physical function were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Multiple linear regression analysis was used to identify the predictors of educational needs.ResultsThis study included 163 patients with AS. The mean ENAT score was 86.25 (31.64). Patients wanted to know more about the arthritis process, self-help measures, and treatments. Multiple linear regression analysis indicated that younger age, being female, higher disease activity, and no family history of AS (p

BackgroundOrnithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations.MethodsWe presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein.ResultsWhole-exome sequencing detected an OTC variant [NM_000531: c.622 (exon6) G > A, p.A208T]. Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure.ConclusionThis study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

IntroductionDeaf students have more difficulties with emotion regulation due to their hearing loss. They are suffering higher socio-emotional risk than the hearing person. But there are few studies explored the neural mechanisms of impaired emotion regulation in the deaf college students.MethodsThirty hearing college students and 27 deaf college students completed the emotion regulation task while recording ERP data and subjective emotion intensity.ResultsBehavioral results found that deaf college students had higher emotional experience intensity compared to healthy controls. The ERP results showed the deaf college students had lower LPP amplitudes both using reappraisal and suppression strategies. Moreover, the LPP of expression suppression was associated with the increase of depression scores among deaf college students.DiscussionDeaf college students may have impaired emotion regulation so that they are more accustomed to using expression suppression strategies to regulate their negative emotions which lead to high risk to be depression.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.

C27H24O4, orthorhombic, P212121 (no. 19), a = 5.694(2) Å, b = 8.957(2) Å, c = 40.662(8) Å, V = 2073.7(10) Å3, Z = 4, Rgt (F) = 0.0339, wRref (F 2) = 0.0837, T = 100(2) K