Development of a Reliable GADSAH Model for Differentiating AFP-negative Hepatic Benign and Malignant Occupying Lesions.

Purpose: Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention. Patients and Methods: A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results: We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set. Conclusion: The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.

Development and application of a new biological nano-selenium fermentation broth based on Bacillus subtilis SE201412.

In order to improve the functionality and additional value of agricultural products, this study developing nano-selenium fermentation broth and established a new application strategy of bio-nano-selenium by screening and identifying selenium-rich microorganisms. We isolated a new strain from tobacco waste and named it Bacillus subtilis SE201412 (GenBank accession no. OP854680), which could aerobically grow under the condition of 66,000 mg L-1 selenite concentration, and could convert 99.19% of selenite into biological nano-selenium (BioSeNPs) within 18 h. Using strain SE201412, we industrially produced the different concentrations of fermentation broth containing 5000-3000 mg L-1 pure selenium for commercial use. The synthesized selenium nanoparticles (SeNPs) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). TEM and SEM results showed that SeNPs were distributed outside cells. NTA assay of fermentation broth indicated that the nanoparticles were spherical with an average particle size of 126 ± 0.5 nm. Toxicity test revealed that the median lethal dose (LD50) of the fermentation broth to mice was 2710 mg kg-1, indicating its low toxicity and high safety. In addition, we applied BioSeNP fermentation broth to rice and wheat through field experiments. The results showed that the application of fermentation broth significantly increased the total selenium content and organic selenium percentage in rice and wheat grains. Our findings provide valuable reference for the development of BioSeNPs with extensive application prospects.

Genome-wide investigation of the AP2/ERF gene family in ginger: evolution and expression profiling during development and abiotic stresses.

BACKGROUND: AP2/ERF transcription factors (TFs) constitute one of the largest TF families in plants, which play crucial roles in plant metabolism, growth, and development as well as biotic and abiotic stresses responses. Although the AP2/ERF family has been thoroughly identified in many plant species and several AP2/ERF TFs have been functionally characterized, little is known about this family in ginger (Zingiber officinale Roscoe), an important affinal drug and diet vegetable. Recent completion of the ginger genome sequencing provides an opportunity to investigate the expression profiles of AP2/ERF genes in ginger on a genome-wide basis. RESULTS: A total of 163 AP2/ERF genes were obtained in the Z.officinale genome and renamed according to the chromosomal distribution of the ZoAP2/ERF genes. Phylogenetic analysis divided them into three subfamilies, of which 35 belonged to the AP2 subfamily, 120 to ERF, three to RAV, and five to Sololist, respectively, which is in accordance with the number of conserved domains and gene structure analysis. A total of 10 motifs were detected in ZoAP2/ERF genes, and some of the unique motifs were found to be important for the function of ZoAP2/ERF genes. The chromosomal localization, gene structure, and conserved protein motif analyses, as well as the characterization of gene duplication events provided deep insight into the evolutionary features of these ZoAP2/ERF genes. The expression profiles derived from the RNA-seq data and quantitative reserve transcription (qRT-PCR) analysis of ZoAP2/ERFs during development and responses to abiotic stresses were investigated in ginger. CONCLUSION: A comprehensive analysis of the AP2/ERF gene expression patterns in various tissues by RNA-seq and qRT-PCR showed that they played an important role in the growth and development of ginger, and genes that might regulate rhizome and flower development were preliminary identified. In additionally, the ZoAP2/ERF family genes that responded to abiotic stresses were also identified. This study is the first time to identify the ZoAP2/ERF family, which contributes to research on evolutionary characteristics and better understanding the molecular basis for development and abiotic stress response, as well as further functional characterization of ZoAP2/ERF genes with an aim of ginger crop improvement.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Hyaluronic acid bioinspired polymers for the regulation of cell chondrogenic and osteogenic differentiation.

As the simplest glycosaminoglycan (GAG) in extracellular matrix, hyaluronic acid (HA) takes part in several important biological processes, such as regulating cell proliferation, differentiation, and migration. In this work, a series of HA-inspired polymers with different saccharide and carboxylate units (HA-analogue polymers) are synthesized by free radical polymerization, and characterized using Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC) and nuclear magnetic resonance spectrometer (NMR), Moreover, cell experiments demonstrate that HA-analogue polymers with a certain proportion of saccharide and carboxylate (PM1G1) units shows a positive effect on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, HA-analogue polymers have prominent cartilage inductive capacity in chondrogenic induction medium (CIM) and brilliant bone inductive capacity in osteogenic induction medium (OIM) toward BMSCs. Therefore, it is confirmed that the HA-analogue polymers can effectively mimic the functions of HA and have broad potential application prospects in the biomedical and clinical fields.

Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg).

Sodium taurocholate cotransporting polypeptide (NTCP), a carrier protein encoded by solute carrier family 10 member 1 (SLC10A1), is expressed in the basolateral membrane of hepatocytes, where it is responsible for the uptake of bile acids from plasma into hepatocytes. The first patient with NTCP deficiency was described in 2015. A limited number of such patients have been reported in the literature and their genotypic and phenotypic features require further investigation. The current study investigated 4 patients with NTCP deficiency from two unrelated families. The patients were subjected to SLC10A1 genetic analysis and it was revealed that all patients were compound heterozygous for the c.800C>T (p.Ser267Phe) and c.595A>C (p.Ser199Arg) SLC10A1 variants. To the best of the authors' knowledge, the latter variant had not been previously reported. Further analysis in 50 healthy individuals did not identify carriers. The c.595A>C (p.Ser199Arg) variant exhibited co­segregation with hypercholanemia and exhibited a relatively conserved amino acid when compared with homologous peptides. Moreover, SWISS­MODEL prediction revealed that the mutation affected the conformation of the NTCP molecule. The 4 patients demonstrated varying degrees of hypercholanemia while a downward trend in the plasma levels of total bile acids (TBA) in 2 pediatric patients and occasionally normal TBA level in an adult case were observed. The results indicated an autosomal recessive trait for NTCP deficiency, supported the primary role of NTCP in the uptake of bile acids from plasma and suggested that hepatic uptake of bile acids may occur by means other than NTCP uptake. Moreover, the novel missense variant c.595A>C(p.Ser199Arg) enriched the SLC10A1 mutation spectrum and may serve as a new genetic marker for the molecular diagnosis and genetic counseling of NTCP deficiency.

Advances in biomolecule inspired polymeric material decorated interfaces for biological applications.

With the development of surface modification technology, interface properties have great effects on the interaction between biomedical materials and cells and biomolecules, which significantly affects the biocompatibility and functionality of materials. As an orderly and perfect system, biological organisms in nature effectively integrate all kinds of bio-interfaces with physiological functions, which shed light on the importance of biomolecules in organisms. It gives birth to a bio-inspiration strategy to design and fabricate smart materials with specific functionalities, e.g. osteogenic and chondrocytic induced materials inspired by bone sialoprotein and chondroitin sulfate. Through this mimicking approach, various functional materials were utilized to decorate the interfaces and further optimize the performance of biomedical materials, which would widely expand their applications. In this review, followed by a summary and brief introduction of surface modification methods, we highlight recent advances in the fabrication of functional polymeric materials inspired by a range of biomolecules for decorating interfaces. Then, the other applications of biomolecule inspired materials including tissue engineering, diagnosis and treatment of diseases and physiological function regulation are presented and the future outlook is discussed as well.

Prevalence, Characteristics, and Outcome of Cow's Milk Protein Allergy in Chinese Infants: A Population-Based Survey.

BACKGROUND: Cow's milk protein allergy (CMPA) is commonly seen in children. There have been no reports of the true prevalence of CMPA in Chinese infants. The aim of this population-based study is to determine the prevalence, clinical characteristics, and outcome of CMPA in Chinese infants. METHODS: We carried out a prospective survey in 7 participating hospitals throughout southern China. We included infants ≤12 months of age during the survey. For those suspected of CMPA, oral food challenge with cow's milk protein (CMP) was performed. A follow-up telephone interview was conducted at 12 months after the diagnosis to assess the clinical outcome of CMPA. RESULTS: A total of 9910 questionnaire surveys were distributed and 7364 (74.3%) were returned. The eligible survey number of surveys was 6768 (91.9%). A total of 182 infants was confirmed with CMPA, including 13 with anaphylactic reactions, 28 with clinical symptoms and serum immunoglobulin E (sIgE) >3.5 IU/mL, and 141 with positive CMP challenge test. The prevalence of CMPA was 2.69%. Infants with confirmed CMPA had significantly stronger family history of either 1 or both parents with food allergy, higher Cesarean section rate, and lower rate of breastfeeding, compared with those without CMPA. At 12-month telephone follow-up of 176 CMPA infants, 136 infants (77.3%) had become tolerant to CMP. CONCLUSIONS: The prevalence of CMPA was 2.69%. CMPA infants had a strong family history of food allergy and atopy. Both Cesarean delivery and formula feeding were risk factors for CMPA. At 12-month follow-up, the majority of CMPA infants had become tolerant to CMP.

[Influence of cow's milk protein allergy on the diagnosis of functional gastrointestinal diseases based on the Rome IV standard in infants and young children].

OBJECTIVE: To study the influence of cow's milk protein allergy (CMPA) on the diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV standard in infants and young children. METHODS: A total of 84 children aged 1 month to 3 years who were diagnosed with CMPA were enrolled as the case group, and 84 infants and young children who underwent physical examination and had no CMPA were enrolled as the control group. The pediatricians specializing in gastroenterology asked parents using a questionnaire for the diagnosis of FGID based on the Rome IV standard to assess clinical symptoms and to diagnose FGID. RESULTS: The case group had a significantly higher incidence rate of a family history of allergies than the control group (P<0.05). In the case group, 38 (45%) met the Rome IV standard for the diagnosis of FGID, while in the control group, 13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID, the case group had significantly higher diagnostic rates of reflex, functional diarrhea, difficult defecation, and functional constipation than the control group (P<0.05). The children who were diagnosed with FIGD in the control group were given conventional treatment, and those in the case group were asked to avoid the intake of cow's milk protein in addition to the conventional treatment. After 3 months of treatment, the case group had a significantly higher response rate to the treatment than the control group (P<0.05). CONCLUSIONS: In infants and young children, CMPA has great influence on the diagnosis of FGID based on the Rome IV standard. The possibility of CMPA should be considered during the diagnosis of FGID.

SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China.

BACKGROUND: The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet. METHODS AND RESULTS: By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. A large NICCD cohort of 116 Chinese cases was also established, and the 4 high-frequency mutations contributed a much larger proportion of the mutated alleles in the patients from south China than in those from the north (χ(2) = 14.93, P<0.01), with the latitude of 30°N as the geographic dividing line in mainland China. CONCLUSIONS: This paper further enriched the SLC25A13 variation spectrum worldwide, and formed a substantial contribution to the in-depth understanding of the genotypic feature of Chinese CD patients.