Exploring community succession and metabolic changes in corn gluten meal-bran mixed wastes during fermentation.

Addressing the challenge of sustainable agricultural processing waste management is crucial. Protein sources are essential for livestock farming, and one viable solution is the microbial fermentation of agricultural by-products. In this study, the microorganisms utilized for fermentation were Pichia fermentans PFZS and Limmosilactobacillus fermentum LFZS. The results demonstrated that the fermented corn gluten meal-bran mixture (FCBM) effectively degraded high molecular weight proteins, resulting in increases of approximately 23.3%, 367.6%, and 159.3% in crude protein (CP), trichloroacetic acid-soluble protein (TCA-SP), and free amino acid (FAA), respectively. Additionally, there was a significant enhancement in the content of beneficial metabolites, including total phenols, carotenoids, and microorganisms. FCBM also effectively reduced anti-nutritional factors while boosting antioxidant and anti-inflammatory substances, such as dipeptides and tripeptides. The fermentation process was marked by an increase in beneficial endophytes, which was closely correlated with the enhancement of beneficial metabolites. Overall, FCBM provides a theoretical basis for substituting traditional protein resources in animal husbandry.

[Clinical phenotype, genetic characteristics, and creation of immortalized cell lines for patients from a pedigree affected with Hunter syndrome].

OBJECTIVE: To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members. METHODS: A pedigree of six members who had visited Xi'an Children's Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis. RESULTS: The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c.823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein's spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient's immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+PM2_Supporting+PM5+PP1+PP3). CONCLUSION: Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.

Effects of ß-carotene supplementation in the diet of laying breeder hens on the growth performance and liver development of offspring chicks.

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

The biological activity and signaling profile of EGF/EGFR were affected under heat stress conditions in IEC6 cells.

Epidermal growth factor (EGF) is an effective cytoprotective peptide. It is the main nutritional factor involved in the development of the intestinal tract. It has many important biological effects on the intestinal mucosa. After binding to epidermal growth factor receptor (EGFR), it initiates a signal transduction cascade to jointly promote the migration, proliferation, and differentiation of various cell types. Heat stress severely affects the intestinal health of livestock and is becoming increasingly prevalent due to the yearly increase in ambient temperature and intestinal diseases. However, the effect of heat stress on the activity and signaling of EGF/EGFR in intestinal cells is still unclear. Therefore, rat intestinal crypt epithelial cell line (IEC6) was used as a model to explore this issue, and the results showed that EGF/EGFR is internalized into IEC6 cells in a time-dependent manner under physiological conditions. However, the activity of EGF/EGFR was altered under heat stress. Furthermore, we explored the effect of heat stress on EGF/EGFR-activated signaling transduction in IEC6 cells, and the results showed that levels of factors involved in EGFR-mediated intracellular signaling (such as EGFR, signal transducers and activators of transcription 3/protein kinase B, and extracellular regulatory kinase 1/2) were downregulated under heat stress. In summary, this study shows that heat stress could damage the biological activity and intracellular signaling of EGF/EGFR. These findings have scientific importance in the field of animal husbandry; and lay the foundation for the further study of the biological activities of EGF/EGFR in the intestine.

Gonadal Transcriptome Analysis and Sequence Characterization of Sex-Related Genes in Cranoglanis bouderius.

In China, the Cranoglanis bouderius is classified as a national class II-protected animal. The development of C. bouderius populations has been affected by a variety of factors over the past few decades, with severe declines occurring. Considering the likelihood of continued population declines of the C. bouderius in the future, it is critical to investigate the currently unknown characteristics of gonadal differentiation and sex-related genes for C. bouderius conservation. In this study, the Illumina sequencing platform was used to sequence the gonadal transcriptome of the C. bouderius to identify the pathways and genes related to gonadal development and analyze the expression differences in the gonads. A total of 12,002 DEGs were identified, with 7220 being significantly expressed in the ovary and 4782 being significantly expressed in the testis. According to the functional enrichment results, the cell cycle, RNA transport, apoptosis, Wnt signaling pathway, p53 signaling pathway, and prolactin signaling pathway play important roles in sex development in the C. bouderius. Furthermore, the sequence characterization and evolutionary analysis revealed that AMH, DAX1, NANOS1, and AR of the C. bouderius are highly conserved. Specifically, the qRT-PCR results from various tissues showed significant differences in AMH, DAX1, NANOS1, and AR expression levels in the gonads of both sexes of C. bouderius. These analyses indicated that AMH, DAX1, NANOS1, and AR may play important roles in the differentiation and development of C. bouderius gonads. To our best knowledge, this study is the first to analyze the C. bouderius gonadal transcriptome and identify the structures of sex-related genes, laying the foundation for future research.

[Isovaleric acidemia due to compound heterozygous variants of IVD gene in a case].

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 µmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION: The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.

[Clinical phenotype and variantal analysis of a pedigree affected with hereditary coagulation factor V deficiency].

OBJECTIVE: To explore the molecular basis for a pedigree affected with coagulation factor V (FV) deficiency. METHODS: Clinical data of the patient and his family members was analyzed. Targeted capture and next-generation sequencing (NGS) and Sanger sequencing were carried out to detect potential variant of the FV gene. RESULTS: The patient presented with jaundice and prolonged prothrombin time (PT) and activated partial thromboplastic time (APTT). V factor activity measured only 0.1% of the normal level, though the patient had no sign of bleeding. A paternal heterozygous variant c.653T>C (p.F218S) and a maternal heterozygous variant c.3642_3643del (p.P1215Rfs*175) were identified in the FV gene of the patient. His elder brother was a heterozygous carrier of the c.653T>C (p.F218S) variant. c.653T>C(p.F218S) was a known pathogenic variant, while the c.3642_3643del (p.P1215Rfs*175) variant was unreported previously. CONCLUSION: Mutations of the FV gene probably underlie the hereditary coagulation factor V deficiency in this patient. NGS combined with Sanger sequencing has detected potential variant with efficiency and provided a reliable basis for clinical and prenatal diagnosis for this family.

Inhibition of osteolysis after local administration of osthole in a TCP particles-induced osteolysis model.

PURPOSE: Wear debris-induced osteolysis and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. However, no effective measures for the prevention and treatment of particles-induced osteolysis currently exist. Here, we investigated the efficacy of local administration of osthole on tricalcium phosphate (TCP) particles-induced osteolysis in a murine calvarial model. METHODS: TCP particles were implanted over the calvaria of ICR mice, and established TCP particles-induced osteolysis model. On days one, four, seven, ten and thirteen post-surgery, osthole (10 mg/kg) or phosphate buffer saline (PBS) were subcutaneously injected into the calvaria of TCP particles-implanted or sham-operated mice. Two weeks later, blood, the periosteum and the calvaria were collected and processed for bone turnover markers, pro-inflammatory cytokine, histomorphometric and molecular analysis. RESULTS: Osthole (10 mg/kg) markedly prevented TCP particles-induced osteoclastogenesis and bone resorption in a mouse calvarial model. Osthole also inhibited the decrease of serum osteocalcin level and calvarial alkaline phosphatase (ALP) activity, and prevented the increase in the activity of tartrate resistant acid phosphatase (TRAP) and cathepsin K in the mouse calvaria. Furthermore, osthole obviously reduced the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) into the periosteum. Western blotting demonstrated TCP particles caused a remarkable endoplasmic reticulum (ER) stress response in the mouse calvaria, which was obviously blocked by osthole treatment. CONCLUSION: These results suggest that local administration of osthole inhibits TCP particles-induced osteolysis in the mouse calvarial in vivo, which may be mediated by inhibition of the ER stress signaling pathway, and it will be developed as a new drug in the prevention and treatment of destructive diseases caused by prosthetic wear particles.

Deficient and excess dietary selenium levels affect growth performance, blood cells apoptosis and liver HSP70 expression in juvenile yellow catfish Pelteobagrus fulvidraco.

We investigated the effects of deficient and excess dietary selenium (Se) on growth, blood cells apoptosis and liver heat shock protein 70 (HSP70) expression in juvenile yellow catfish (Pelteobagrus fulvidraco). After 8 weeks, yellow catfish (initial weight: 2.12 ± 0.01 g) fed isonitrogenous and isolipid diets containing <0.05 (deficient dietary Se) or 6.5 (excess dietary Se) mg Se/kg displayed a significantly lower weight gain ratio (WGR) than those fed a diet containing 0.23 (normal dietary Se) mg Se/kg. As dietary Se levels increased, liver Se concentration, glutathione peroxidase activity and the hepatosomatic index increased significantly. Plasma glucose concentration was highest in the normal treatment compared with the excess dietary Se treatment. Both deficient and excess dietary Se lead to increased reactive oxygen species (ROS) production and apoptosis ratio in blood cells, whereas only excess dietary Se increased their cytoplasmic free-Ca(2+) (CF-Ca(2+)) concentration. Excess dietary Se also resulted in the highest level of HSP70 expression, thereby possibly providing a protective mechanism against oxidative stress. These results indicate that both deficient and excess dietary Se restrained the growth of juvenile yellow catfish and caused oxidative stress. The overproduction of ROS may act as a signal molecule mediate apoptosis when dietary Se deficiency. Both ROS and CF-Ca(2+) were recorded when dietary Se excess, suggesting that Ca(2+) may be activated by Se and play a major role during Se-induced oxidative stress and cell apoptosis.

Female specific association between NNMT gene and schizophrenia in a Han Chinese population.

Accumulating evidence has shown that alterations in one carbon metabolism might play an important role in the pathogenesis of schizophrenia (SZ). Nicotinamide-N-methyltransferase (NNMT) is one of the key enzymes of one-carbon metabolism. To examine whether NNMT gene was associated with SZ in Han Chinese population, we selected seven single nucleotide polymorphisms (SNPs) in NNMT gene, and investigated its association with SZ from a cohort of 42 SZ patients and 86 healthy controls by Mass-ARRAY technology. Statistical analyses revealed that one (rs694539) of the SNPs in the female subgroup showed significant difference between SZ patients and controls both in genotypic (p= 0.0170) and allelic frequencies (p = 0.0059). We also found that the frequency of haplotype 'A G G C T C T' in the female patients was significantly higher than in controls (p=0.0015). Our results suggest that NNMT rs694539 may have a role in the etiology of SZ in a Han Chinese female population.

Nutritional supplementation of breeding hens may promote embryonic development through the growth hormone-insulin like growth factor axis.

The late stage of embryo development is a crucial period of metabolic changes, with rapid organ development requiring a substantial supply of nutrients. During this phase, maternal nutritional levels play a vital role in the growth, development, and metabolism of the offspring. In this study, we added 2 doses of ß-carotene (ßc) (120 mg/kg and 240 mg/kg) to the daily diet of Hailan Brown laying hens to investigate the impact of maternal nutritional enrichment on embryo development. Maternal nutrition supplementation significantly increased the expression of chicken embryo liver index, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF) in serum. At the same time, the expression of GH/growth hormone receptor (GHR), IGF-1 mRNA, and Proliferating Cell Nuclear Antigen (PCNA) protein in the liver was upregulated, indicating that maternal nutrition intervention may promote chicken embryo liver development through the GH-IGF-1 axis. Transcriptome sequencing results showed that differential genes in liver after maternal nutritional supplementation with ß-carotene were enriched in pathways related to cell proliferation and metabolism. Consequently, we postulated that maternal ß-carotene supplementation might operate via the GH-IGF-1 axis to regulate the expression of genes involved in growth and development, thereby promoting liver development. These results contribute to formulating more effective poultry feeding strategies to promote offspring growth and development.

Causality orientations and spontaneous mental contrasting.

Mental contrasting is a motivational behavior change strategy necessary for strong goal commitment. Meanwhile, general causality orientations are motivational patterns that represent individuals' motivation for behavior change and the reason for their goal commitment. The current study explored whether causality orientations predict spontaneous mental contrasting in Chinese university students. Study 1 investigated whether academic autonomy, control, and amotivated orientations correlate with spontaneous mental contrasting about an important academic goal. The findings of Study 1 reveal that autonomy orientation did not correlate with mental contrasting, whereas control and amotivated orientations were negatively correlated with mental contrasting. Study 2 investigated whether priming autonomy and control orientations, in addition to the neutral condition, would induce spontaneous mental contrasting about an academic goal related to the students' research topic. The results of Study 2 revealed that the autonomy condition orientation did not differ significantly from the controlled orientation condition. However, when compared to the neutral condition, the autonomy condition significantly predicted mental contrasting, whereas the controlled orientation condition did not show any significant difference. In Study 2, the autonomy-oriented participants generated more spontaneous mental contrast than the control orientation and neutral conditions. The findings show that controlled and amotivated orientations predicted negative mental contrasting. As a result, controlled and amotivated students must learn how to use mental contrasting to achieve high levels of goal commitment and achievement. Lastly, the study discussed its implications, limitations, and suggestions for future research.

Ochratoxin A (OTA) causes intestinal aging damage through the NLRP3 signaling pathway mediated by calcium overload and oxidative stress.

Ochratoxin A (OTA) is a widespread environmental toxin that poses a serious threat to human and animal health. OTA has been shown to cause cellular and tissue damage and is a global public health problem. However, the effects of OTA on gastrointestinal aging have not been reported. The aim of this study was to investigate the effects of OTA on intestinal aging in vitro and in vivo. In vitro experiments showed that OTA induced cellular inflammation through calcium overload and oxidative stress, significantly up-regulated the expression of P16, P21, and P53 proteins, markedly increased senescence-associated ß-galactosidase activity (SA-ß-gal) positive cells, and obviously decreased the expression of proliferating cell nuclear antigen (PCNA) proteins, which led to intestinal cell senescence. Meanwhile, we found that treatment with ß-carotene ameliorated OTA-induced intestinal cell senescence. Consistent with the results of the in vitro experiments, in vivo studies showed that the intestinal aging of mice fed OTA was significantly higher than that of the control group. In conclusion, OTA may induce intestinal aging through calcium overload, oxidative stress and inflammation. This study lays a foundation for further research on the toxicological effects of OTA.

Hexabromocyclododecane (HBCD) exposure induced premature testicular aging via NCOA4/Fe2+/ROS mediation.

Hexabromocyclododecane (HBCD) has been detected in animals and humans blood. As an environment contamination, HBCD damages tissues and organs in animals and humans and produces cytotoxicity. In current study, we explored the effect of HBCD on premature testicular aging in vivo and in vitro. In vivo, C57 mice (8-week-old) were used as model to estimate the effect of HBCD on premature testicular aging. The results showed that testes were premature aging through measuring several aging-related markers (such as p16INK4a, hereafter p16; p21CIP, hereafter p21) in response to HBCD exposure for 20 weeks. In addition, HBCD exposure can cause oxidative stress and inflammation. Further, mouse spermatogonial cells (GC-1spg cells) were premature senescence after HBCD exposure by the evaluation of cellular senescence marker molecules. Hence, GC-1spg cell line was applied for cell model to investigate the molecule mechanism by which HBCD cause premature testicular aging., Through eliminating Fe2+ in senescent GC-1spg cells, cellular senescence was greatly alleviated. Thus, Fe2+ was identified as the key driver molecule in HBCD-induced premature cellular senescence. Next, we found that elevated iron levels in HBCD-triggered senescent GC-1spg cells were due to Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Furthermore, our results revealed that HBCD-induced senescence was caused by Fe2+ mediated oxidative stress. In summary, HBCD-induced premature testicular aging is dependent on NCOA4/Fe2+/ROS signaling molecule. The current study lays the foundation for further exploration of the effects of HBCD on reproductive toxicology.

WS2 with Controllable Layer Number Grown Directly on W Film.

As a layered material with single/multi-atom thickness, two-dimensional transition metal sulfide WS2 has attracted extensive attention in the field of science for its excellent physical, chemical, optical, and electrical properties. The photoelectric properties of WS2 are even more promising than graphene. However, there are many existing preparation methods for WS2, but few reports on its direct growth on tungsten films. Therefore, this paper studies its preparation method and proposes an innovative two-dimensional material preparation method to grow large-sized WS2 with higher quality on metal film. In this experiment, it was found that the reaction temperature could regulate the growth direction of WS2. When the temperature was below 950 °C, the film showed horizontal growth, while when the temperature was above 1000 °C, the film showed vertical growth. At the same time, through Raman and band gap measurements, it is found that the different thicknesses of precursor film will lead to a difference in the number of layers of WS2. The number of layers of WS2 can be controlled by adjusting the thickness of the precursor.

IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage.

Calcium ions (Ca2+) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca2+ levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca2+ ([Ca2+]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. The results of the Duolink II in situ proximity ligation assay (PLA) revealed a weakened pairwise interaction between IP3R1-GRP75 and VDAC1 and a significantly increased interaction between GRP75 and VDAC1 after IP3R1 interference, resulting in the accumulation of large amounts of [Ca2+]m. These changes led to mitochondrial oxidative stress, increased the levels of reactive oxygen species (ROS) and reduced ATP production, which hindered the maturation and late development of porcine oocytes and induced apoptosis. Nevertheless, after treat with [Ca2+]m chelating agent ruthenium red (RR) or ROS scavenger N-acetylcysteine (NAC), the oocytes developmental abnormalities, oxidative stress and apoptosis caused by Ca2+ overload were improved. In conclusion, our results indicated IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage.

A Novel Homozygous Deletion Including Exon 1 of FA2H Gene Causes Spastic Paraplegia-35: Genetic and Lipidomics Analysis of the Patients.

BACKGROUND: Fatty acid 2-hydroxylase (FA2H) is encoded by the FA2H gene, with mutations therein leading to the neurodegenerative condition, spastic paraplegia-35 (SPG35). We aim to elucidate the genetic underpinnings of a nonconsanguineous Chinese family diagnosed with SPG35 by examining the clinical manifestations, scrutinizing genetic variants, and establishing the role of FA2H mutation in lipid metabolism. METHODS: Using next-generation sequencing analysis to identify the pathogenic gene in this pedigree and family cosegregation verification. The use of lipidomics of patient pedigree peripheral blood mononuclear cells further substantiated alterations in lipid metabolism attributable to the FA2H exon 1 deletion. RESULTS: The proband exhibited gait disturbance from age 5 years; he developed further clinical manifestations such as scissor gait and dystonia. His younger sister also presented with a spastic gait from the same age. We identified a homozygous deletion in the region of FA2H exon 1, spanning from chr16:74807867 to chr16: 74810391 in the patients. Lipidomic analysis revealed significant differences in 102 metabolites compared with healthy controls, with 62 metabolites increased and 40 metabolites decreased. We specifically zeroed in on 19 different sphingolipid metabolites, which comprised ceramides, ganglioside, etc., with only three of these sphingolipids previously reported. CONCLUSIONS: This is the first study of lipid metabolism in the blood of patients with SPG35. The results broaden our understanding of the SPG35 gene spectrum, offering insights for future molecular mechanism research and laying groundwork for determining metabolic markers.

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement.

Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease. Case Description: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery. Conclusions: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.

Inflammatory factors gene polymorphism in recurrent oral ulceration.

BACKGROUND: Some inflammatory factors play an important role in recurrent oral ulceration (ROU). The genetics mechanism of expression level of inflammatory factors is not clear in ROU, but from genetics the expression level of inflammatory factors at least partly depend on the gene polymorphisms. Therfore, we decided to investigate inflammatory factors gene polymorphism and its association with the susceptibility of recurrent oral ulceration in Chinese. METHODS: Genomic DNA was obtained from 42 subjects with recurrent oral ulceration, 86 subjects of healthy control individuals.Genotypes and alleles of 10 genes and 17 polymorphisms sites were analyzed by Mass-ARRAY Analyzer method. Then, the differences in distribution of each genotype and allele were compared. RESULTS: The statistical differences in distribution of TNF-α (rs1800629 and rs1800630) genotype and allele were observed among the groups with recurrent oral ulceration and healthy control individuals (P < 0.01), while VEGFA (rs1570360, rs833061, and rs2010963), EGF (rs4444903), TNF (rs361525), IL10 (rs1800896, rs1800872), IL2 (rs2069762), IL4 (rs2243250), Fas (rs1800682, rs2234767), IL12A (rs2243115, rs568408), IL12B (rs3212227), and IFNG (rs2430561) showed no statistical differences of genotype and allele in controls as compared to those in patients. CONCLUSIONS: This study suggests that the TNF-α (rs1800629 and rs1800630) genotype is an indicator for the susceptibility of recurrent oral ulceration.