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Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003-2004, 2011-2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, Kaplan‒Meier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45-0.83;0.59,0.42-0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32-0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 µg/L), and cardiovascular mortality (range ≤ 129.08 µg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 µg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers.

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Water treatment faces significant challenges due to the increasing complexity of pollutants and the need for more efficient, sustainable treatment methods. However, current adsorbent materials often struggle with issues such as low adsorption capacity, slow kinetics, and poor reusability, limiting their practical application. In this study, we developed a novel hierarchical porous hybrid gel (HPHG) for water treatment to address the limitations of conventional adsorbents. The HPHG features a multi-level porous structure (from 48 ± 28 nm to 4385 ± 823 nm) that significantly enhances its porosity and specific surface area. We systematically investigated the relationship between the material's structure and its adsorption performance. Kinetic studies revealed a tendency towards a pseudo-second-order adsorption model, attributed to the material's unique structural features that facilitate rapid mass exchange channels inside HPHG and provide abundant active sites for pollutant adsorption. Reusability tests demonstrated that the material retained 85.4% of its initial adsorption capacity after five adsorption-desorption cycles, highlighting its potential for practical applications. This study provides valuable insights into structure-performance relationships in advanced water treatment materials, offering a promising approach for designing next-generation adsorbents with superior efficiency and sustainability.

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OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is a growing concern among the elderly population, significantly impacting morbidity and mortality rates. This study aimed to screen and investigate the characteristics and prognosis of early-stage HFpEF in the elderly. METHODS: A total of 1789 community-dwelling individuals aged over 65 from northern Shanghai were enrolled. According to American Heart Association (AHA) guidelines, participants were classified into four groups: HFpEF stage 0, HFpEF stage A, HFpEF stage B and HFpEF stage C. Major endpoints included major adverse cardiovascular events (MACEs), all-cause death and cardiovascular death. RESULTS: After a mean follow-up period of 7.10 ± 1.27 years, 1623 elderly subjects were included [HFpEF stage 0 (10.3%), HFpEF stage A (16.3%), HFpEF stage B (60.6%) and HFpEF stage C (12.8%)]. Patients with HFpEF stage A, HFpEF stage B and HFpEF stage C exhibited more MACEs than those in HFpEF stage 0 (P < 0.01). Patients with HFpEF stage C had a significantly higher cardiovascular (P < 0.001) and all-cause death ratio (P < 0.01). With HFpEF stage 0 as a reference, the increases in MACEs were significantly associated with HFpEF stage A [hazard ratio (HR): 2.97, 95% confidence interval (CI) (1.13, 7.82), P < 0.05], HFpEF stage B [HR: 2.69, 95% CI (1.09, 6.64), P < 0.05] and HFpEF stage C [HR: 4.86, 95% CI (1.88, 12.59), P < 0.01] in the Cox regression analysis. Our finding remains unaltered in the sensitivity analysis, with no interaction for effectiveness. CONCLUSIONS: Compared with those with HFpEF stage 0, patients with HFpEF, whether in stage B or C, exhibit significantly higher cardiovascular and all-cause mortality in the elderly. This study underscores the importance of early-stage HFpEF screening, particularly in older, asymptomatic stage B individuals.

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BACKGROUND: Cervical intraepithelial neoplasia grade 2 (CIN2) is one of the precursor stages before cervical lesions develop into cervical cancer. The spontaneous development of CIN2 is ambiguous. One part of CIN2 lesions will progress to cervical intraepithelial neoplasia grade 3 or worse (CIN3+), another part will regress to cervical intraepithelial neoplasia grade 1 or less (CIN1-), and the last part will persist. Although the guidelines suggest that CIN2 patients with fertility requirements can be treated conservatively to minimize the risk of infertility and obstetric complications, most CIN2 patients undergo surgical treatment to prevent the progression of the disease, which will lead to over-treatment and unnecessary complications. AIM OF REVIEW: The clinical outcome of CIN2 lesions is unpredictable and depends on histopathological examinations. Thus, it is necessary to identify the biomarkers differentiating regression lesions from progression lesions, which is conducive to supporting individualised treatment. The natural history of CIN2 is commonly regulated by the interaction of human papillomavirus (HPV) viral factors (HPV genotype and viral DNA methylation), host factors (p16/Ki-67 status, host gene methylation effects, human leukocyte antigen subtypes and immune microenvironment) and other factors (vaginal microbiota). KEY SCIENTIFIC CONCEPTS OF REVIEW: This review summarized the biomarkers predicting the spontaneous regression of CIN2, which correlated with HPV infection, the (epi)genetic change of host genes and microenvironment change. However, potential biomarkers must be validated with prospective cohort studies, which should be conducted with expanded enrollment, a longer observational period and the tracking of more patients.

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Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.

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Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis.

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Background: There is growing evidence of an association between inflammatory skin diseases and chronic kidney disease, but the association between inflammatory skin diseases and IgA nephropathy has rarely been studied. Thus, bi-directional Mendelian randomization was employed to explore the causality between inflammatory skin diseases (including atopic dermatitis, acne and psoriasis) and IgA nephropathy. Methods: The selection of instrumental variables for inflammatory skin diseases and IgA nephropathy were based on genome-wide association studies. Following the heterogeneity and pleiotropy tests, the bidirectional causality was evaluated by inverse variance weighted along with four other approaches. Three atopic dermatitis-related datasets were obtained from the GEO database and then combined. In the combined dataset, the expression of galactose-deficient IgA1-associated genes (including GALNT2, GALNT12, C1GALT1, C1GALT1C1 and ST6GALNAC2) were compared between atopic dermatitis patients and healthy controls. Results: Atopic dermatitis was associated with an increased risk of IgA nephropathy (OR = 1.054, 95% CI = 1.014-1.095, p = 0.007). However, acne and psoriasis showed no significant causal relationship with IgA nephropathy (OR = 0.988, 95% CI = 0.948-1.031, p = 0.583; OR = 0.996, 95% CI = 0.966-1.028, p = 0.821). In the combined microarray dataset, the expression levels of GALNT12 and C1GALT1C1 in atopic dermatitis patients were significantly lower compared with controls (p = 2.3e-9; p = 0.00067), which may contribute to an increase in aberrant IgA1 synthesis. Conclusion: Among inflammatory skin diseases, atopic dermatitis was found to increase the risk of IgA nephropathy, which may result from the decrease of GALNT12 and C1GALT1C1 expression and the increase of aberrant IgA1 production. Therefore, active management of atopic dermatitis may help prevent the occurrence and progression of IgA nephropathy.

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BACKGROUND: Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests. RESULTS: Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased. CONCLUSIONS: The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.

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Reservoir nearshore areas are influenced by both terrestrial and aquatic ecosystems, making them sensitive regions to water quality changes. The analysis of basin landscape hydrological features provides limited insight into the spatial heterogeneity of eutrophication in these areas. The complex characteristics of shoreline morphology and their impact on eutrophication are often overlooked. To comprehensively analyze the complex relationships between shoreline morphology and landscape hydrological features, with eutrophication, this study uses Danjiangkou Reservoir as a case study. Utilizing Landsat 8 OLI remote sensing data from 2013 to 2022, combined with a semi-analytical approach, the spatial distribution of the Trophic State Index (TSI) during flood discharge periods (FDPs) and water storage periods (WSPs) was obtained. Using Extreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP), explained the relationships between landscape composition, landscape configuration, hydrological topography, shoreline morphology, and TSI, identified key factors at different spatial scales and validated their reliability. The results showed that: (1) There is significant spatial heterogeneity in the TSI distribution of Danjiangkou Reservoir. The eutrophication levels are significant in the shoreline and bay areas, with a tendency to extend inward only during the WSPs. (2) The importance of landscape composition, landscape configuration, hydrological topography, and shoreline morphology to TSI variations during the FDPs are 25.12 %, 29.6 %, 23.09 %, and 22.19 % respectively. Besides shoreline distance, the Landscape Shape Index (LSI) and Hypsometric Integral (HI) are the two most significant environmental variables overall during the FDPs. Forest and grassland areas become the most influential factors during the WSPs. The influence of landscape patterns and hydrological topography on TSI varies at different spatial scales. At the 200 m riparian buffer zone, the increase in cropland and impervious areas significantly elevates eutrophication levels. (3) Morphology complexity, shows a noticeable threshold effect on TSI, with complex shoreline morphology increasing the risk of eutrophication.

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The cellular thermal shift assay (CETSA) and isothermal dose-response fingerprint assay (ITDRF CETSA) have been introduced as powerful tools for investigating target engagement by measuring ligand-triggered thermodynamic stabilization of cellular target proteins. Yet, these techniques have rarely been used to evaluate the thermal stability of RNA-binding proteins (RBPs) when exposed to ligands. Here, we present an adjusted approach using CETSA and ITDRFCETSA to determine the interaction between enasidenib and RBM45. Our assay is sensitive and time-efficient and can potentially be adapted for studying the interactions of RBM45 protein with other potential candidates. Key features • This protocol builds upon the method developed by Molina et al. and extends its application to new protein classes, such as RBPs.

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Non-alcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease globally. It initiates with simple steatosis (NAFL) and can progress to the more severe condition of non-alcoholic steatohepatitis (NASH). NASH often advances to end-stage liver diseases such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Notably, the transition from NASH to end-stage liver diseases is irreversible, and the precise mechanisms driving this progression are not yet fully understood. Consequently, there is a critical need for the development of effective therapies to arrest or reverse this progression. This review provides a comprehensive overview of the pathogenesis of NASH, examines the current therapeutic targets and pharmacological treatments, and offers insights for future drug discovery and development strategies for NASH therapy.

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Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (α-Syn) aggregates. However, the molecular mechanisms regulating α-Syn aggregation and neuronal degeneration remain poorly understood. The peptidase M20 domain containing 1 (PM20D1) gene lies within the PARK16 locus genetically linked to PD. Single nucleotide polymorphisms regulating PM20D1 expression are associated with changed risk of PD. Dopamine (DA) metabolism and DA metabolites have been reported to regulate α-Syn pathology. Here we report that PM20D1 catalyzes the conversion of DA to N-arachidonoyl dopamine (NADA), which interacts with α-Syn and inhibits its aggregation. Simultaneously, NADA competes with α-Syn fibrils to regulate TRPV4-mediated calcium influx and downstream phosphatases, thus alleviating α-Syn phosphorylation. The expression of PM20D1 decreases during aging. Overexpression of PM20D1 or the administration of NADA in a mouse model of synucleinopathy alleviated α-Syn pathology, dopaminergic neurodegeneration, and motor impairments. These observations support the protective effect of the PM20D1-NADA pathway against the progression of α-Syn pathology in PD.

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Objectives: Neuroblastoma (NB), a pediatric malignancy of the peripheral nervous system, is characterized by epigenetic and transcriptional (EP-TF) anomalies. This study aimed to develop an EP-TF clinical prognostic model for NB using CRISPR-Cas9 knockout screening. Results: An integrative analysis was conducted using CRISPR-Cas9 screening in vitro and in vivo with public NB datasets to identify 35 EP-TF genes that exhibited the highest expression in NB and were highly dependent on cancer viability. After univariate analysis, 27 of these 35 genes were included in the least absolute shrinkage and selection operator screen. We established and biologically validated a prognostic EP-TF model encompassing RUVBL1, LARP7, GTF3C4, THAP10, SUPT16H, TIGD1, SUV39H2, TAF1A, SMAD9, and FEM1B across diverse NB cohorts. MYCN serves a potential upstream regulator of EP-TF genes. The high-risk subtype exhibited traits associated with the malignant cell cycle, MYCN-linked signaling and chromatin remodeling, all of which are correlated with poor prognosis and immunosuppression. MEK inhibitors have emerged as promising therapeutic agents for targeting most EP-TF risk genes in NB. Conclusion: Our novel prognostic model shows significant potential for predicting and evaluating the overall survival of NB patients, offering insights into therapeutic targets.

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BACKGROUND: This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. METHODS: In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. RESULTS: According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P < 0.05). Furthermore, AI assistance significantly improved the performance of junior radiologists in the diagnosis of thyroid nodules, and their diagnostic performance was comparable to that of senior radiologists when pathological results were taken as the gold standard (all p > 0.05). CONCLUSIONS: The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

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BACKGROUND: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

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BACKGROUND: We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES). METHODS: Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. RESULTS: Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis. CONCLUSIONS: Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants. IMPACT: We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices.

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Archwire bending is the key to orthodontic treatment, and multi-time bendings are inevitable during manual and robotic automated bending. The purpose of this paper is to quantitatively evaluate the mechanical effects of the different preparation modes and to compare the mechanical properties of the orthodontic loops in one and multiple bends. Three types of typical stainless steel orthodontic loops (vertical loop, T-loop, and L-loop) were used to quantify the mechanical effect of patterns for preparation by experimental comparison between loops with different bending times by using an orthodontic force tester (OFT). The results were statistically analyzed by t-test. The fracture test of the stainless steel archwire was also carried out, and the bending times at fracture were recorded. Results of the tests indicate that one-time and multi-time bending have a significant mechanical effect on orthodontic appliances. Multi-time bending causes significant mechanical decreases and can damage the appliances.

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V-H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V-H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V-H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

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AIM: Rhodojaponin VI (R-VI) is the key compound of Rhododendron molle G. Don (Ericaceae) (RM) with effective clinical application in rheumatoid arthritis and chronic glomerulonephritis. In our study, we tried to explore the effect of R-VI on the rat model of membranous nephropathy. METHODS: The rat model of passive heymann nephritis (PHN) was established by injecting sheep anti-rat Fx1A serum at a single dose through the tail. The rats were orally administered R-VI (0.02 mg/kg) or FK506 (1 mg/kg) 1 day before PHN induction, which was kept for 4 weeks. Urine and blood samples as well as kidney tissue were collected for analysis. C5b-9-induced human podocyte cell (HPC) was employed for experiments in vitro. RESULTS: R-VI could alleviate glomerulonephritis progression and podocyte injury in PHN rats, as indicated by the decreased proteinuria and the elevated level of albumin, accompanied with reduced immune deposits, reversed podocyte injury in the kidneys. Furthermore, R-VI suppressed murine double minute 2 (MDM2) expression without the alteration in the protein level of p53 and decreased Notch1 expression independent of Numb regulation. Pre-treatment with R-VI in C5b-9-induced HPC blocked MDM2/Notch1 signalling pathway. CONCLUSION: Thus, R-VI ameliorates podocyte injury in rats with PHN, which was probably related with MDM2/Notch1 signalling pathway.

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