Could early life DHA supplementation benefit neurodevelopment? A systematic review and meta-analysis.

Background: Docosahexaenoic acid (DHA) plays a crucial role in the growth and functional development of the infant brain. However, the impact of additional DHA supplementation on neurodevelopment in infants remains controversial in randomized controlled trials. In this systematic review and meta-analysis, we aimed to investigate the effects of prenatal and postnatal DHA supplementation on neurodevelopment. Methods: We systematically searched the MEDLINE, EMBASE, and Cochrane Library electronic databases using a predefined strategy until 8 February 2024. We extracted relevant study characteristics and outcomes related to the nervous system. Two independent reviewers critically evaluated the included studies to assess their validity and risk of bias. Results: A total of 21 studies met our inclusion criteria, one study was removed after quality assessment, and the meta-analysis included 9 randomized controlled trials. The meta-analysis results indicated that there was no statistically significant difference between the DHA supplementation group and the placebo group, as assessed by the Mental Development Index [MDI; mean difference (MD), 0.41; 95% confidence interval (CI), -0.91 to 1.73; p = 0.55]. However, the DHA group had a significantly higher Psychomotor Development Index (PDI) than the placebo group (MD, 1.47; 95% CI, 0.23 to 2.72; p = 0.02). Subgroup analyses based on populations showed that DHA supplementation was superior to placebo for infants in both MDI (language score conversion; MD, 2.05; 95% CI, -0.16 to 4.26; p = 0.07) and PDI (MD, 1.94; 95% CI, 0.23 to 3.65; p = 0.03). Other subgroup analyses indicated no statistical differences between the two groups. The remaining assessments that could not be summarized quantitatively underwent a narrative evaluation. Conclusion: Based on the BSID assessments, DHA supplementation in infants may have potential neurodevelopmental benefits. Because the meta-analysis included few high-quality articles and had some limitations, more relevant articles are needed to address the need for separate DHA supplementation in infants, pregnant women, and lactating mothers. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348100, identifier: CRD42022348100.

Prognostic value of growth differentiation factor-15 in heart failure among whole ejection fraction phenotypes.

AIMS: The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model. METHODS AND RESULTS: This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0 years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P = 0.002) and a higher MAGGIC risk score (P < 0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4 year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.20-1.54; P < 0.001] and HF rehospitalization (HR = 1.75, 95% CI: 1.57-1.95; P < 0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR = 1.73, 95% CI: 1.40-2.14; P < 0.001; HF rehospitalization: HR = 3.37, 95% CI: 2.73-4.15; P < 0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index = 0.021, 95% CI: 0.002-0.041; IDI = 0.011, 95% CI: 0.001-0.025; continuous NRI = 0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index = 0.034, 95% CI: 0.005-0.063; IDI = 0.021, 95% CI: 0.007-0.032; continuous NRI = 0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup. CONCLUSIONS: GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

Sensitivity, Specificity, Positive Rate and Consistency of Two Kits in SARS-CoV-2 Nucleic Acid Detection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was a highly transmissible and pathogenic coronavirus and it emerged in late 2019. SARS-CoV-2 had caused a pandemic of acute respiratory disease and its name was coronavirus disease 2019 (COVID-19). It threatened human health and public safety. This study would analyze and evaluate two different kinds of SARS-CoV-2 nucleic acid detection reagents which could provide value for accurate detection. METHODS: 80 patients were randomly selected in the First Affiliated Hospital of Anhui Medical University in December 2022 and 80 oropharyngeal swabs were collected. Nucleic acid was extracted first, and then two real-time fluorescent quantitative RT-PCR nucleic acid amplification reagents were used to detect ORF1ab and N genes. Statistical software was used to compare and analyze the results. RESULTS: Among 80 patients, 57 were males and 23 were females with an age range of 5 - 90 years with an average age of 65.7 years. Most of the specimens were collected from Department of Infectious Diseases and Department of Respiratory and Critical care. Compared with regent Reference, the sensitivity of regent A and B was 88.3% and 93.3% and the specificity was 90.0% and 95.0%, respectively. The positive rates of the double target genes were 85.0% and 93.3%, the positive rates of ORF1ab gene were 86.7% and 95.0% and the positive rates of N gene were 88.3% and 96.7%, respectively. The Kappa values were all greater than 0.75, indicating high consistency. CONCLUSIONS: Between two nucleic acid detection reagents, reagent B had higher sensitivity and specificity. And the positive rate and consistency of reagent B were also higher than that of reagent A, with statistical significance. For weakly positive specimens with low viral load, it was recommended to use another reagent with higher sensitivity to retest and ensure the accuracy and repeatability of the results.

Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping.

Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic Informational Field Theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Whilst GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in ovis aries related to bone growth (Dataset-1) and to a series of linked metabolic and epigenetic pathways (Dataset-2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked.

Efficacy and safety of tetrandrine in treatment of rheumatoid arthritis: a meta analysis. / æ±‰é˜²å·±ç”²ç´ æ²»ç–—ç±»é£Žæ¹¿å ³èŠ‚ç‚Žæœ‰æ•ˆæ€§å’Œå®‰å ¨æ€§çš„meta分析.

OBJECTIVES: To explore the efficacy and safety of tetrandrine in the treatment of rheumatoid arthritis. METHODS: Randomized controlled studies of tetrandrine in the treatment of rheumatoid arthritis were searched in China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), World Wide Web Database, SinoMed, PubMed, Springer, Web of Science, the Cochrane Central Register of Controlled Trails database. A meta-analysis was conducted using R software version 3.5.3 to evaluate the clinical outcomes, including the total effective rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), visual analog scale (VAS) for pain, disease activity score (DAS), tender joint count (TJC), swollen joint count (SJC), and morning stiffness duration, as well as adverse events of RA patients. RESULTS: A total of 10 articles were included in the study. The meta-analysis indicated that tetrandrine significantly improved the total effective rate (OR=3.27, 95%CI: 2.01-5.37, P<0.01), ESR (SMD=1.12, 95%CI: 0.06-2.19, P<0.05), CRP (SMD=0.75, 95%CI: 0.28-1.22, P<0.01), VAS (SMD=0.55, 95%CI: 0.21-0.89, P<0.01), SJC (SMD=0.85, 95%CI: 0.40-1.31, P<0.01), TJC (SMD=1.16, 95%CI: 0.58-1.74, P<0.01), and morning stiffness (SMD=1.09, 95%CI: 0.68-1.50, P<0.01). However, no statistical significance was found in RF (SMD=1.70, 95%CI: －1.10-4.51, P>0.05) and DAS (SMD=0.26, 95%CI: －0.59-1.11, P>0.05). The overall incidence of adverse events associated with tetrandrine treatment for rheumatoid arthritis was 20% (95%CI: 12%-27%, I2=60%, P<0.05), with mild severity and favorable outcomes. CONCLUSIONS: Tetrandrine is effective in the treatment of RA patients with a mild degree of adverse events.

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation.

Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFß and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFß-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin-proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFß. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

Photoperiodic and lighting treatments for flowering control and its genetic regulation in sugarcane breeding.

Improvement of sugarcane is hampered due to its narrow genetic base, and the difficulty in synchronizing flowering further hinders the exploitation of the genetic potential of available germplasm resources. Therefore, the continuous evaluation and optimization of flowering control and induction techniques are vital for sugarcane improvement. In view of this, the review was conducted to investigate the current understanding of photoperiodic and lighting treatment effects on sugarcane flowering and its genetic regulation. Photoperiod facilities have made a significant contribution to flowering control in sugarcane; however, inductive photoperiods are still unknown for some genotypes, and some intended crosses are still impossible to produce because of unresponsive varieties. The effectiveness of lower red/far-red ratios in promoting sugarcane flowering has been widely understood. Furthermore, there is vast potential for utilizing blue, red, and far-red light wavelengths in the flowering control of sugarcane. In this context, light-emitting diodes (LEDs) remain efficient sources of light. Therefore, the combined use of photoperiod regimes with different light wavelengths and optimization of such treatment combinations might help to control and induce flowering in sugarcane parental clones. In sugarcane, FLOWERING LOCUS T (ScFT) orthologues from ScFT1 to ScFT13 have been identified, and interestingly, ScFT3 has evidently been identified as a floral inducer in sugarcane. However, independent assessments of different FT-like gene family members are recommended to comprehensively understand their role in the regulation of flowering. Similarly, we believe this review provides substantial information that is vital for the manipulation of flowering and exploitation of germplasm resources in sugarcane breeding.

Metal-ion-controlled hydrogel dressing with enhanced adhesive and antibacterial properties for accelerated wound healing.

In order to improve the wound repair environment, this research has successfully developed a new multifunctional hydrogel dressing, which has strong adaptability and can accelerate wound healing. Pioneering the development of metal-ion-controlled hydrogel dressings, this research integrates dopamine and imidazole double crosslinked networks with metal-ion coordination. The resulting hydrogel dressing exhibits a notable antibacterial effect and exceptional mechanical properties, withstanding pressures of up to 12 kPa, tensions of 25 kPa, and maintaining skin adhesion at 6 kPa. Furthermore, the dressing can self-heal within only 7-8 s post-injection. Impressively, the hydrogel achieves complete biodegradation within a short timeframe (37 h). Notably, the use of various metal ions facilitates painless peeling during the degradation period, perfectly aligning with the requirements of an ideal wound dressing. This study has made significant progress in the fields of trauma repair and materials, providing strong solutions for dealing with harsh post-traumatic environments.

Loss of GCN5L1 exacerbates damage in alcoholic liver disease through ferroptosis activation.

BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD. RESULTS: Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol-induced ferroptosis. GCN5L1-modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure. CONCLUSION: Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol-induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol-induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.

Economic Evaluation of COVID-19 Immunization Strategies: A Systematic Review and Narrative Synthesis.

OBJECTIVES: This study aimed to systematically assess global economic evaluation studies on COVID-19 vaccination, offer valuable insights for future economic evaluations, and assist policymakers in making evidence-based decisions regarding the implementation of COVID-19 vaccination. METHODS: Searches were performed from January 2020 to September 2023 across seven English databases (PubMed, Web of Science, MEDLINE, EBSCO, KCL-Korean Journal Dataset, SciELO Citation Index, and Derwent Innovations Index) and three Chinese databases (Wanfang Data, China Science and Technology Journal, and CNKI). Rigorous inclusion and exclusion criteria were applied. Data were extracted from eligible studies using a standardized data collection form, with the reporting quality of these studies assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). RESULTS: Of the 40 studies included in the final review, the overall reporting quality was good, evidenced by a mean score of 22.6 (ranging from 10.5 to 28). Given the significant heterogeneity in fundamental aspects among the studies reviewed, a narrative synthesis was conducted. Most of these studies adopted a health system or societal perspective. They predominantly utilized a composite model, merging dynamic and static methods, within short to medium-term time horizons to simulate various vaccination strategies. The research strategies varied among studies, investigating different doses, dosages, brands, mechanisms, efficacies, vaccination coverage rates, deployment speeds, and priority target groups. Three pivotal parameters notably influenced the evaluation results: the vaccine's effectiveness, its cost, and the basic reproductive number (R0). Despite variations in model structures, baseline parameters, and assumptions utilized, all studies identified a general trend that COVID-19 vaccination is cost-effective compared to no vaccination or intervention. CONCLUSIONS: The current review confirmed that COVID-19 vaccination is a cost-effective alternative in preventing and controlling COVID-19. In addition, it highlights the profound impact of variables such as dose size, target population, vaccine efficacy, speed of vaccination, and diversity of vaccine brands and mechanisms on cost effectiveness, and also proposes practical and effective strategies for improving COVID-19 vaccination campaigns from the perspective of economic evaluation.

The survival after thyroidectomy versus lobectomy in multifocal papillary thyroid microcarcinoma patients.

BACKGROUND: The extent of thyroid surgery for multifocal papillary thyroid microcarcinoma (PTMC) remains controversial. Studies on the optimal surgical approach for a multifocal PTMC are scarce. This study aimed to compare the effectiveness of thyroidectomy and lobectomy for the treatment of multifocal PTMC. METHODS: A population-based retrospective cohort of patients with multifocal PTMC was analyzed using the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017, and divided into two groups (thyroidectomy, lobectomy) based on the surgical approach. The clinicopathologic features and survival outcomes were compared between the two groups. Cox proportional hazards regression analysis to explore prognostic factors of survival. Propensity score matching (PSM) was used to balance covariates. RESULTS: Overall, a total of 9387 multifocal PTMC patients were included in the study. Among them, 8,107 (86.36%) patients received thyroidectomy, and 1280 (13.64%) patients underwent lobectomy. Compared to patients in the thyroidectomy group, patients in the lobectomy group were diagnosed with older age (50.47 years vs. 49.32 years, p = 0.003), a higher proportion of males (20.47% vs. 14.99%, p < 0.001), larger tumors (6.22 mm vs. 4.97 mm, p < 0.001), and more frequently underwent radiotherapy (35.40% vs. 10.16%, p < 0.001). Multivariate Cox regression analysis revealed that age was the only independent prognostic factor for thyroid cancer-specific survival (TCSS), and the determinants of overall survival (OS) were age and gender. Unadjusted survival analysis revealed no difference between the two treatment groups in TCSS (p = 0.598) and OS (p = 0.126). After 1:1 Propensity Score Matching (PSM), there was still no difference in TCSS (p = 0.368) or OS (p = 0.388). The stratified analysis revealed that for patients aged under or above 55, thyroidectomy was not associated with superior BCSS or OS (p > 0.05). CONCLUSIONS: Thyroidectomy was not associated with improved survival compared to thyroid lobectomy for patients with multifocal PTMC.

Serum albumin and cardiovascular disease: a Mendelian randomization study.

BACKGROUND: An increasing body of evidence suggests that serum albumin levels play a role in cardiovascular diseases. However, the specific causal relationship between serum albumin levels and cardiovascular disease remains partially unknown. METHODS: Mendelian randomization (MR) was employed in this study to examine potential causal relationships between instrumental variables and cardiovascular diseases. Specifically, we utilized genetic variants of serum albumin levels within the reference range as our instrumental variables. To acquire data on genetic associations with cardiovascular diseases, we sourced information from renowned genome-wide association studies such as UK BioBank, EMBL-EBI, and FinnGen. Notably, our study leveraged summary statistics from large cohorts that have been previously described. RESULTS: We explored the association between serum albumin levels and various conditions, including heart failure (HF), venous thromboembolism (VTE), stroke, atrial fibrillation (AF), coronary artery disease (CAD), type 2 diabetes (T2DM), and pulmonary heart disease (PHD). Genetically predicted serum albumin levels were associated with PHD (odds ratio = 0.737, 95% CI = 0.622 - 0.874, P < 0.001), AF (odds ratio = 0.922, 95% CI = 0.870 - 0.977, P = 0.006), VTE (odds ratio = 0.993, 95% CI = 0.991 - 0.995, P < 0.001), and Stroke (odds ratio = 0.997, 95% CI = 0.995 - 0.999, P = 0.002). However, genetically predicted serum albumin level traits were not associated with HF, CAD and T2DM. CONCLUSION: Our study demonstrates a significant association between serum albumin levels and cardiovascular disease, underscoring the crucial role of low serum albumin as a predictive factor in patients with cardiovascular disease.

Minimal alveolar concentration of sevoflurane in combination with remimazolam in adults during laryngeal mask insertion: an up-down sequential allocation study.

BACKGROUND: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative-hypnotic. The combination of remimazolam and sevoflurane does not increase respiratory sensitivity, produce bronchospasm, or cause other adverse conditions. We aimed to observe the effects of different remimazolam doses on the minimum alveolar concentration (MAC) of sevoflurane at end-expiration during laryngeal mask insertion and evaluate the effect of sex on the efficacy of the combination of remimazolam on the suppression of laryngeal mask insertion in adult patients. METHODS: We included 240 patients undergoing laparoscopic surgery under general anesthesia with elective placement of a laryngeal mask (120 males and 120 females). The patients were randomly divided into four groups according to sex: a control group (randomization for female patients, RF0; randomization for male patients, RM0) and three remimazolam groups (RF1, RM1 / RM2, RF2 / RM3, RF3), with 30 patients in each group. Induction was established by vital capacity rapid inhalation induction (VCRII), using 8% sevoflurane and 100% oxygen (6 L/min) in all patients. The (RF1, RM1), (RM2, RF2), and (RM3, RF3) groups were continuously injected with remimazolam at doses of 1, 1.5, and 2.0 mg/kg/h, respectively, while the (RM0, RF0) group was injected with an equal volume of normal saline. The end-expiratory concentration of sevoflurane was adjusted to a preset value after the patient's eyelash reflex disappeared. After the end-expiratory concentration of sevoflurane was kept stable for at least 15 min, the laryngeal mask was placed, and the patient's physical response to the mask placement was observed immediately and within 30 s of placement. The MAC of sevoflurane was measured using the up-and-down sequential method of Dixon. RESULTS: The calculated MAC of end-expiratory sevoflurane during laryngeal mask insertion in adult females was (2.94 ± 0.18)%, (2.69 ± 0.16)%, (2.32 ± 0.16)% and (1.83 ± 0.15)% in groups RF0, RF1, RF2 and RF3; (2.98 ± 0.18)%, (2.80 ± 0.19)%, (2.54 ± 0.15)% and (2.15 ± 0.15)% in male groups RM0, RM1, RM2 and RM3, respectively. The MAC values were significantly lower in the (RF1-RF3, RM1-RM3) group when compared to the (RF0, RM0) group. There was no significant difference between (RF0, RF1) and (RM0, RM1), but the MAC value of the RF2-RF3 group was significantly lower than that of the RM2-RM3 group. CONCLUSIONS: Remimazolam can effectively reduce end-expiratory sevoflurane MAC values during laryngeal mask placement in adults. When remimazolam was measured above 1.5 mg/kg/h, the effect of inhibiting laryngeal mask implantation in female patients was stronger than that in male patients. Remimazolam at a dose of 1-2 mg/kg/h combined with sevoflurane induction can be safely and effectively used in these patients.

Silver-infused lysine crosslinked hydrogel with oxidized regenerated cellulose for prospective advanced wound dressings.

The study aimed to develop a multifunctional wound dressing with enhanced antibacterial properties and wound healing promotion. The synthesis process involved preparing oxidized regenerated cellulose (ORC) following a modified procedure, synthesizing chitosan/silver nanoparticles (CS/Ag NPs) via an in-situ reduction method, and subsequently preparing ORC/CS/Lys@Ag NPs hydrogels. Characterization techniques including FTIR, XRD, SEM, and EDS were employed to analyze functional groups, lattice structure, morphology, and elemental composition. Gelation time, swelling behavior, water retention, mechanical properties, viscosity, self-healing capacity, rheological behavior, oxygen permeability, in vitro degradation, release of Ag+, and antibacterial properties were evaluated using various experimental methods. Results indicated that the novel wound dressing has the capability to evenly distribute Ag NPs to effectively counteract bacteria. It can maintain moist conditions for 86 h, resist a sturdy mechanical pressure of 11.3 KPa, and degrade by 11.045 % ± 0.429 within 8 h. Combining its efficient gas exchange abilities, self-repairing function, and biocompatibility, almost full recovery was observed in injured mouse skin within 13 days, highlighting its promising clinical utility.

Neofunctionalization of an OMT cluster dominates polymethoxyflavone biosynthesis associated with the domestication of citrus.

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.

Optimization of Antioxidant Activity of Compounds Generated during Ginseng Extract Fermentation Supplemented with Lactobacillus.

Ginseng holds high medicinal and cosmetic value, with stem and leaf extracts garnering attention for their abundant bioactive ingredients. Meanwhile, fermentation can enhance the effectiveness of cosmetics. The aim of this study was to optimize ginseng fermentation to produce functional cosmetics. Ginseng stem and leaf extracts were fermented with five different strains of lactic acid bacteria. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical (·OH), and superoxide anion (O2·-) scavenging activities as indicators, the fermentation process was optimized via response surface methodology. Finally, validation of the antioxidant activity of the optimized fermentation broth was performed using human skin cells (HaCaT and BJ cells). Based on the antioxidant potency composite comprehensive index, Lactiplantibacillus plantarum 1.140 was selected, and the optimized parameters were a fermentation time of 35.50 h, an inoculum size of 2.45%, and a temperature of 28.20 °C. Optimized fermentation boosted antioxidant activity: DPPH scavenging activity increased by 25.00%, ·OH by 94.00%, and O2·- by 73.00%. Only the rare ginsenoside Rg5 showed a substantial rise in content among the 11 ginsenosides examined after fermentation. Furthermore, the flavonoid content and ·OH scavenging activity were significantly negatively correlated (r = -1.00, p < 0.05), while the Rh1 content and O2·- scavenging activity were significantly positively correlated (r = 0.998, p < 0.05). Both the 0.06% (v/v) and 0.25% (v/v) concentrations of the optimized broth significantly promoted cell proliferation, and notable protective effects against oxidative damage were observed in HaCaT cells when the broth was at 0.06%. Collectively, we demonstrated that ginseng fermentation extract effectively eliminates free radicals, preventing and repairing cellular oxidative damage. This study has identified new options for the use of fermented ginseng in functional cosmetics.

Extensive Genetic Diversity and Epidemiological Patterns of Factor H-Binding Protein Variants among Neisseria meningitidis in China.

Factor H-binding protein (fHbp) is a virulence factor expressed by Neisseria meningitidis (N. meningitidis), the primary causative agent of invasive meningococcal disease (IMD) in humans. fHbp is utilized as the main component in vaccines to provide protection against IMD caused by serogroup B N. meningitidis. In order to comprehensively investigate the genetic diversity and epidemiological patterns of fHbp variants within isolates of Chinese N. meningitidis, we utilized the NEIS0349 locus, which encompasses the complete coding sequences of fHbp. This enabled us to identify allelic variants of fHbp with enhanced resolution. A total of 109 fHbp variants were identified in 1013 Chinese N. meningitidis isolates. We reconstructed a phylogenetic tree and analyzed the epidemiological characteristics of each variant. Considering both temporal and geographical distribution patterns, only four fHbp variants (v2.16, v2.18, v2.404, and v2.21) exhibited persistent nationwide prevalence during the previous decade (2011-2021). These variants were highly prevalent in both serogroup B strains from patients and healthy individuals, suggesting their potential as suitable vaccine candidates for nationwide implementation against IMD caused by serogroup B strains. Our study emphasizes the significance of conducting continuous surveillance of meningococcal strains to monitor the genetic diversity of fHbp for the purpose of vaccine development.

Correlation analysis of disulfidptosis-related gene signatures with clinical prognosis and immunotherapy response in sarcoma.

Disulfidptosis, a newly discovered type of programmed cell death, could be a mechanism of cell death controlled by SLC7A11. This could be closely associated with tumor development and advancement. Nevertheless, the biological mechanism behind disulfidptosis-related genes (DRGs) in sarcoma (SARC) is uncertain. This study identified three valuable genes (SLC7A11, RPN1, GYS1) associated with disulfidptosis in sarcoma (SARC) and developed a prognostic model. The multiple databases and RT-qPCR data confirmed the upregulated expression of prognostic DRGs in SARC. The TCGA internal and ICGC external validation cohorts were utilized to validate the predictive model capacity. Our analysis of DRG riskscores revealed that the low-risk group exhibited a more favorable prognosis than the high-risk group. Furthermore, we observed a significant association between DRG riskscores and different clinical features, immune cell infiltration, immune therapeutic sensitivity, drug sensitivity, and RNA modification regulators. In addition, two external independent immunetherapy datasets and clinical tissue samples were collected, validating the value of the DRGs risk model in predicting immunotherapy response. Finally, the SLC7A11/hsa-miR-29c-3p/LINC00511, and RPN1/hsa-miR-143-3p/LINC00511 regulatory axes were constructed. This study provided DRG riskscore signatures to predict prognosis and response to immunotherapy in SARC, guiding personalized treatment decisions.

A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in IBC patients, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for crosstalk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.