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BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p

Abstract Background Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. Results DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). Conclusions Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

Salvia penghuana, a new species from Guizhou Province of southwestern China, is described and illustrated. Morphologically, Salvia penghuana is similar to S. filicifolia, but can be easily distinguished from the latter by ovate-lanceolate bracts, purple corolla, and foot-shaped fused lower arms of connective. In addition, S. penhuana is morphologically similar to S. cavaleriei, but differs by having 3–4-pinnate leave, ovate-lanceolate bracts, puberulent calyx, and longer upper arms of connective. Based on the fibril root, small calyx and corolla, and completely reduced posterior thecae, S. penghuana should be placed in section Sobiso of subg. Glutinaria.

The integration of TiCN particles into superalloy composites for laser powder bed fusion (LPBF) and the construction of Triply Periodic Minimal Surface (TPMS) lattice structures have been understudied. This research systematically examines the microstructure and mechanical properties of LPBF-processed 10 vol% micron sized TiCN particle reinforced Inconel 718 (IN718) composites. The compressive behavior of the resultant TPMS lattice structures, derived from the TiCN-IN718 composite, was scrutinized through a combination of experimental testing and Finite Element (FE) simulation. The micro-sized TiCN reinforcement is demonstrated to notably augment the hardness, tensile strength, and wear resistance of the LPBFed TiCN-IN718 composite. Furthermore, the application of homogenization-solution-aging (HSA) heat treatment is shown to provide additional enhancements to the composite's mechanical behavior. Both the TiCN reinforcement and the HSA heat treatment are identified as pivotal factors influencing the compressive response of the TPMS lattice structures. Experimental findings indicate that the HSA-treated D-structure attains the highest compressive strength, reaching 122 MPa, outperforming both the G- and P-structures. During quasi-static compression testing, the D- and G-structures undergo a layer-by-layer collapse, while the P-structure exhibits tilt shear band behavior. The congruence between FE simulation results and experimental data substantiates the simulation's reliability and its capacity to accurately evaluate the mechanical behavior of TPMS lattice structures.

Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain, indispensable for neuronal growth, synaptic development, neuronal repair, and hippocampal neuroplasticity. Among its genetic variants, the BDNF Val66Met polymorphism is widespread in the population and has been associated with the onset and aggravation of diverse pathologies, including metabolic conditions like obesity and diabetes, cardiovascular ailments, cancer, and an array of psychiatric disorders. Psychiatric disorders constitute a broad category of mental health issues that influence mood, cognition, and behavior. Despite advances in research and treatment, challenges persist that hinder our understanding and effective intervention of these multifaceted conditions. Achieving and maintaining stable body weight is pivotal for overall health and well-being, and the relationship between psychiatric conditions and body weight is notably intricate and reciprocal. Both weight gain and loss have been linked to varying mental health challenges, making the disentanglement of this relationship critical for crafting holistic treatment strategies. The BDNF Val66Met polymorphism's connection to weight fluctuation in psychiatric patients has garnered attention. This review investigated the effects and underlying mechanisms by which the BDNF Val66Met polymorphism moderates body weight among individuals with psychiatric disorders. It posits the polymorphism as a potential biomarker, offering prospects for improved monitoring and therapeutic approaches for mental illnesses.

Abstract Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.

Background Amino acids are not only the main form of N in rice, but also are vital for its growth and development. These processes are facilitated by amino acid transporters within the plant. Despite their significance, only a few AAP amino acid transporters have been reported. Results In this study, we observed that there were differences in the expression of amino acid transporter OsAAP7 among 521 wild cultivated rice varieties, and it directly negatively correlated with tillering and grain yield per plant. We revealed that OsAAP7 protein was localized to the endoplasmic reticulum and had absorption and transport affinity for amino acids such as phenylalanine (Phe), lysine (Lys), leucine (Leu), and arginine (Arg) using subcellular localization, yeast substrate testing, fluorescent amino acid uptake, and amino acid content determination. Further hydroponic studies showed that exogenous application of amino acids Phe, Lys and Arg inhibited the growth of axillary buds in the overexpression lines, and promoted the elongation of axillary buds in the mutant lines. Finally, RNA-seq analysis showed that the expression patterns of genes related to nitrogen, auxin and cytokinin pathways were changed in axillary buds of OsAAP7 transgenic plants. Conclusions This study revealed the gene function of OsAAP7, and found that blocking of amino acid transporter OsAAP7 with CRISPR/Cas9 technology promoted tillering and yield by determining basic and neutral amino acids accumulation in rice.

Abstract Introduction Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. Aim We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. Subjects and methods 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. Results The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P 0 0.05 ). Conclusion Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. Trial registration NCT02958111, date of registration 04-11-2016.

Carex duanensis Z.C.Lu, Y.F.Lu & X.F.Jin, a new species in limestone areas of Guangxi, China, was discovered and described. The morphology showed that C. duanensis is similar to C. calcicola, but differs in having culms central, leaf blades 3–5.5 mm wide, bracts longer than spikes, utricles 4–5 mm long, shorter, and nutlets abruptly contracted into an erect beak at apex. SEM microphotographs of utricles and nutlets are provided for the new and related species, C. calcicola.

Abstract Hafnium‐oxide‐based ferroelectrics have garnered considerable research interest, primarily for their robust ferroelectricity at the nanoscale and their high compatibility with complementary metal‐oxide‐semiconductors processes. However, the impact of electrodes on the ferroelectric properties of hafnium‐oxide layer, particularly that of top electrodes, is not yet fully understood even in the simplest capacitor geometry. In this study, the La0.67Sr0.33MnO3/Hf0.5Zr0.5O2 (LSMO/HZO) epitaxial heterostructure is utilized as a model system to conduct a systematic comparative study on ferroelectricity between the LSMO/HZO (H‐LS) bilayer and LSMO/HZO/LSMO (LS‐H‐LS) trilayer samples. In comparison to the H‐LS sample, the LS‐H‐LS sample exhibits a more uniform polar domain configuration and larger ferroelectric polarization. Moreover, the LS‐H‐LS sample exhibits significant improvements in leakage, endurance, and retention. These substantial enhancements in ferroelectricity are likely due to interfacial stress imposed by the LSMO capping layer and its capacity to accommodate extra oxygen vacancies. These results underscore the pivotal role of oxide‐based top electrodes in determining the ferroelectricity of hafnium‐oxide‐based heterostructures, providing crucial insights for optimizing the performance of innovative ferroelectric devices.

Sodium houttuyfonate (SH), derived from the widely utilized natural herb Houttuynia cordata, exhibits an effective therapeutic effect on various diseases, including bacterial and fungal infections, especially the respiratory tract infection. Therefore, the anti-microbial mechanisms of SH may be different from the single-target action mechanism of conventional antibiotics, and further research is needed to clarify this. Firstly, we discovered that SH can effectively intervene in mouse lung infections by reducing bacterial load and acute inflammation response related to pneumonia caused by Pseudomonas aeruginosa. Interestingly, our results confirmed that SH has surface activity and can directly induce changes in the cell wall the shedding of surface lipopolysaccharide (LPS). Additionally, we found that SH-induced shedding of LPS can induce M1 polarization of macrophages in the early stage, leading to the production of corresponding polarization effector molecules. Subsequently, we discovered that SH-induced M1 polarization cells can effectively phagocytose and kill bacterial cells. The protein expression results indicated that SH can enhance the expression of M1 polarization pathway of TLR4/MyD88/NF-κB during the initial phase of macrophage and pathogen interaction. In summary, our results imply that SH could directly induce the shedding of P. aeruginosa LPS in a surfactant-like manner. Afterwards, the SH induced abscisic LPS can initiate the TLR4/MyD88/NF-κB immune pathway to trigger the M1 polarization of macrophages, which might intervene the P. aeruginosa-caused acute lung infection at early stage. Based on these findings, we attempted to coin the term ''immune feedback eradication mechanism against pathogen of natural product'' to describe this potent antimicrobial mechanism of SH.

IntroductionMajor depressive disorder is a condition involving microbiota–gut–brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.MethodsIn the present study, Wistar–Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.ResultsWistar–Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota–gut–brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic–pituitary–adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.ConclusionThe depressive phenotype of Wistar–Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota–gut–brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.

BackgroundChimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL.MethodsRelevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity.ResultsFifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05).ConclusionA high MTV at baseline is associated with a poor survival of NHL patients after CAR-T.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY (INPLASY202450069).

Circular RNAs (circRNAs) are involved in several neurological disorders; however, the mechanisms underlying their involvement remain to be clarified. We attempted to explore the expression profiles of circRNAs and their potential functions and mechanisms in the pathogenesis of intracerebral hemorrhage (ICH) in Northern Chinese males. The microarray results showed that 50 circRNAs were significantly upregulated, while 194 circRNAs were significantly downregulated in ICH patients compared with healthy controls (p