The environmental toxicant cadmium (Cd) can be absorbed by the human body via dermal exposure, yet its influence on skin microbiota remains largely uncharacterized. Staphylococcus epidermidis, a key component of the cutaneous microecosystem, maintains host skin health. This study investigated the interaction between environmentally relevant Cd concentrations and this commensal bacterium, assessing S. epidermidis’ potential barrier function in Cd–skin crosstalk. Exposure to 0.001 mg/L Cd (estimated urban skin exposure level) for 24 h did not significantly inhibit bacterial growth. However, when Cd concentration exceeded 1 mg/L (estimated highly polluted or occupational exposure level), growth inhibition exhibited a dose‑dependent pattern. This isolate exhibited substantial Cd removal capacity, with a maximal removal rate of 94.4

Background Currently, an important lipid marker for assessing the risk of chronic inflammation and metabolic disorders is considered to be the non-HDL cholesterol to HDL cholesterol ratio (NHHR). This study aimed to examine the association between NHHR and the inflammatory biomarker alpha-1 acid glycoprotein (AGP) and assess the potential of NHHR as an inflammatory marker for chronic inflammation. Methods This cross-sectional analysis used serum samples from adult women participating in the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. The NHHR was treated as the independent variable, with AGP as the dependent variable. Multivariate linear regression was used to analyze the association between NHHR and AGP. Nonlinear associations were examined using spline regression and threshold effect analysis. Furthermore, subgroup and sensitivity evaluations were performed to evaluate the reliability of the findings. Results The analysis included 3,027 adult women, revealing a significant positive correlation between NHHR and AGP levels. Each incremental increase in NHHR was correlated with a 0.605 mg/dL increase in square-root-transformed AGP levels, as found in the fully adjusted model. Nonlinear analysis revealed a threshold effect at a critical value of 3.167, suggesting that the relationship between the NHHR and AGP was more pronounced below this threshold. Further subgrouping and sensitivity analyses confirmed that the connection between NHHR and AGP was consistent across most of the population. Conclusions For the first time, this research reveals a direct relationship between NHHR and AGP, and also shows that a novel biomarker that can assess chronic inflammation is NHHR. These findings underscore the critical importance of regular monitoring of NHHR and AGP levels to enhance health management, particularly in the realm of chronic disease prevention and intervention strategies.

In recent years, nitric oxide (NO) has been widely studied as a non-drug resistant antimicrobial agent, but the issue of low NO loading capacity as well as premature leakage during transportation limit its further application. Herein, we have developed a BNN6-loading molybdenum disulfide (MoS2) nanoflowers denoted PEG-MoS2-BNN6 with near-infrared light-triggered NO release and hyperthermia properties to realize the antibacterial and antifungal capability. The PEG-MoS2-BNN6 was synthesized by grafting polyethylene glycol (PEG) to MoS2 nanoflowers and the NO donor BNN6 was subsequently loaded via hydrophobic interaction. The incorporation of PEG can effectively improve the biocompatibility of MoS2. Moreover, BNN6 achieves a high payload thanks to the layered nanoflower structure of PEG-MoS2. Under the 808 ​nm laser irradiation for 10 ​min, the obtained PEG-MoS2-BNN6 could not only generate heat locally for low-temperature photothermal therapy (PTT) but also activate the decomposition of BNN6 to release NO. Notably, the simultaneously generated NO and gentle hyperthermia could trigger great antimicrobial effects against both S. aureus and Candida albicans, which effectively solved the limitations of monotherapy. Overall, this nanoplatform with low-temperature PTT/NO synergistic effects provides a new strategy to solve bacterial and fungal infections, which is promising in biomedical application in the future.

The present study describes the first prenatally diagnosed 46,XX testicular disorders of sex development (46,XX testicular DSD) case with DMD gene mutation by integrated analyses in a Chinese pedigree. Chromosome karyotype G-banding analysis of the proband showed a 46,XX karyotype, but B-ultrasound analysis demonstrated the existence of scrotum, testis and penis which inferred a male sexual differentiation. Aneuploidy and copy number variation (CNV) detection by low-coverage single-end whole genome sequencing (WGS) revealed a de novo SRY (sex-determining region Y) gene positive fragment of 224.34 kb length (chrY:2,649,472-2,873,810) which explained the gonadal/genital-chromosomal inconsistency in the proband. Additionally, targeted-region-capture-based DMD gene sequencing and Sanger verification confirmed a widely reported pathogenic heterozygous nonsense mutation (NM_004006, c.9100C>T, p.Arg3034Ter) in the dystrophin-coding gene named DMD. This study emphasizes that integrated analyses of the imaging results, cytogenetics, and molecular features can play an important role in prenatal diagnosis. It requires the combination of more detection techniques with higher resolution than karyotyping to determine the genetic and biological sex of fetuses in prenatal diagnosis. To conclusively determine both the biological and genetic sex of the fetus at the time of prenatal diagnosis particularly in cases that involve X-linked conditions is of vital importance, which would crucially influence the decision-making regarding abortions. This study will help in prenatal diagnosis of DMD in future, also providing a new perspective that enables the genetic diagnosis of sex reversal in pregnancy. Moreover, genetic counseling/analysis for early diagnosis and pre-symptom interventions are warranted.

microRNA-663a (miR-663a) was reported to be highly expressed in cancers. However, its roles in melanoma progression remain unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to measure miR-663a expression level in melanoma cell lines and normal cells. Cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were conducted to analyze biological roles of miR-663a in melanoma. Luciferase activity reporter assay was conducted to validate the connection of miR-663a and Four and a half LIM domain (FHL) protein 3 (FHL3) in melanoma. Our results showed miR-663a expression level was significantly increased in melanoma cells compared with normal cells. Silencing miR-663a expression suppresses melanoma cell proliferation, migration, and invasionin vitro. Moreover, FHL3 was validated as a functional target of miR-663a. Knockdown of FHL3 partially rescued the inhibitory effects of miR-663a inhibitor on melanoma cell behaviors. Together, our work provided evidence that miR-663a functions as an oncogenic miRNA in melanoma.

Thalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment.

Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.

The absorption of nutrients and disease resistance are two indispensable physiological processes in plants; however, it is still largely unknown whether there is cross-talk between their molecular signaling pathways. In this study, we identified the rice OsPT8 protein, which is a member of the phosphate transporters (PTs) Pht1 family and also plays a role in rice disease resistance. The transcriptional level of OsPT8 is suppressed after infection with rice pathogens and treatment with pathogen-associated molecular patterns (PAMPs). Overexpression of OsPT8 suppresses rice disease resistance against the pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae. Accordingly, the transcription level of resistance related genes, such as PAL and PBZ1, is inhibited in plants overexpressing OsPT8 (OsPT8-OX) after inoculation with these pathogens. In OsPT8-OX plants, PAMPs-triggered immunity (PTI) response genes, such as OsRac1 and SGT1, are suppressed during treatment with PAMPs chitin or flg22. Moreover, the typical response of PTI is suppressed after chitin or flg22 treatment. We also identified OsPT8 as an interactor of a rice mitogen-activated protein kinase BWMK1, which is a regulator of disease resistance. Under low phosphate (Pi) conditions, the OsPT8-OX plants display better agronomic traits than the control plants. However, the differences in development between OsPT8-OX and the control plants are reduced upon the increase of Pi concentration. These results demonstrate that OsPT8 regulates the transduction of Pi signaling for development and negatively regulates rice immunity.

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype-genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.

Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder, manifested with neurofibromas and Cafe´-au-lait spots. Germline mutations in NF1 gene are associated with Neurofibromatosis type 1. NF1 gene encodes neurofibromin, a RAS-specific GTPase activating protein. In our study, we present a clinical molecular study of four Chinese probands with NF1 from four unrelated families, showing extreme phenotypic variation with rare phenotype. In family 1, the proband is a 16 months old girl with multiple café-au-lait spots throughout her whole body. In family 2, the proband is a 6 months old girl with several café-au-lait spots mostly in her trunk and in lower limbs. In family 3, the proband is a 4 months old boy with several café-au-lait spots, tibial pseudarthrosis, and chronic iron deficiency anemia. In family 4, the proband is a 14 years old boy with multiple café-au-lait spots of variable sizes. Targeted exome capture based next generation sequencing and Sanger sequencing identified a novel mutation and three previously reported mutations in these four probands. These four mutations in NF1 gene were causing disease phenotypes in these four probands and was absent in unaffected family members and in healthy controls. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), these four mutations, are classified as "likely pathogenic". Our result expands the mutational spectrum of the NF1 gene associated with neurofibromatosis type1.

Herein we demonstrate that Se-containing phycocyanin (Se–PC) purified from Se-enriched cultures of Nostoc sp. could reverse paraquat (PQ)-induced DNA cell apoptosis through inhibition of superoxide overproduction in human kidney cells.

Aim:To evaluate the serum levels of interleukin6(IL-6)and explore the role of IL-6 in the onset and development of systemic lupus erythematosus (SLE).Methods:Thirty SLE patients were se-lected as the SLE group.Meanwhile,SLEDAI of all SLE patients were recorded.While 29 healthy people were selected as the control group.An ELISA kit was used to quantify the level of IL-6 in peripheral blood of all patients.Results:The level of IL-6 in peripheral blood of SLE group (9.636 ±3.852 pg/mL)was significantly higher than that of NC group (4.433 ±1 .143 pg/mL)(P <0.05).In the correla-tion analysis,our results showed the IL-6 level of the peripheral blood was related to the SLEDAI score in SLE patients (r =0.671 )with a P value less than 0.05.The sensitivity and specificity of peripheral blood IL-6 in diagnosing SLE was 86.7% and 86.2% respectively at a cut-off value of 5.865 pg/mL. Conclusion:Peripheral IL-6 level of SLE patients not only was associated with the pathogenesis of SLE, but also affect the development of SLE disease.Measure serum cytokine can be used to guide the clinical treatment of SLE.

Phelan-McDermid syndrome is a neurodevelopmental disorder caused by the terminal deletion of chromosome 22 (22q13) followed by the loss of function of the SHANK3 gene. Various terminal deletions of chromosome 22q13 are associated with Phelan-McDermid with a spectrum of phenotypic severity. Here, we have done a clinical molecular study of a Chinese proband with Phelan-McDermid syndrome. Both the proband and her younger brother are associated with this syndrome while their parents are phenotypically normal. We used a karyotype in order to detect the genotype of the proband and her younger brother. We have also used whole genome low-coverage paired-end next generation sequencing to determine whether the parent is the carrier of translocation with terminal 22q13 deletions. We found that both proband and her younger brother are comprises of a novel deletion of 22q13.31q13.33, harboring genes were associated with several clinical phenotype such as severity of speech delay, neonatal hypotonia, delayed in age of walking, male genital anomalies, dysplastic toenails, large and fleshy hands, macrocephaly, short stature, facial asymmetry, and atypical reflexes. Probands and her younger brother inherited this translocation from their mother whereas their father is genotypically normal. In conclusion, our present study expands the deletion spectrum and report a novel deletion associated with Phelan-McDermid syndrome.

We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for beta-thalassemia (beta-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C>T; codon 17 (A>T), HBB: c.52A>T; -28 (A>G), HBB: c.-78A>G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing beta-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for beta-thal.

AIM: To investigate the protective effect of sodium selenite ( Na2 SeO3 ) on human keratinocytes under ultraviolet-B (UVB) irradiation.METHODS: The cultured HaCaT cells were divided into 4 groups: (1) normal control group;(2) Na2 SeO3 group:pretreated with Na2 SeO3 at doses of 10 nmol/L, 50 nmol/L, 100 nmol/L, 200 nmol/L and 1 μmol/L for 24 h;(3) UVB group: irradiated with UVB at doses of 300, 600 and 900 J/m2; (4) Na2SeO3 +UVB group:after pretreated with Na2SeO3 for 24 h, irradiated with UVB at doses of 300, 600 and 900 J/m2.The cell pro-liferation was detected by MTT assay .The apoptotic rates of HaCaT cells treated with UVB at dose of 300 J/m2 were as-sessed by flow cytometry .RESULTS:Compared with normal control group , the cell proliferation activity in UVB group de-creased significantly ( P<0.05 ) .The cell activity was inversely correlated with the irradiation intensity .No significant difference of the cell activity between Na 2 SeO3 group and normal control group was observed .The cell proliferation in Na2SeO3 +UVB group was higher than that in UVB group significantly (P<0.05).Na2SeO3 at concentration of 100 nmol/L showed the strongest activity to promote cell proliferation .After 300 J/m2 UVB irradiation, the apoptotic rate in Na2SeO3+UVB group decreased significantly ( P<0.05) compared with UVB group .The inhibitory effect of Na 2 SeO3 at concentra-tion of 100 nmol/L on apoptosis was the strongest .CONCLUSION: The damage of human keratinocytes by UVB irradia-tion is in a dose-dependent manner .The photoprotection performance of Na 2 SeO3 reduces the damage of human keratino-cytes induced by UVB irradiation .

The rice MAPK gene BWMK1 is transcriptionally activated by fungal pathogen infection and wounding and acts as a positive regulator in plant disease resistance signaling.To further understand the BWMK1-mediated molecular signaling regulating pathways,a yeast two-hybrid system using BWMK1 as a bait was used to screen BWMK1 interacting proteins,and 7 BWMK1 interacting protein encoding genes BWIP1-BWIP7 were isolated,BWIP1-BWIP7 were located on 12,2,3,10,6,4,5 chromosomes,respectively.Homologous coding proteins were found for each isolated gene except BWIP2 and BWIP7,which indicated that BWIP1,3,4,5 and 6 respectively coded for 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase,myo-inositol phosphate synthease,putative phosphate transporter,WD-40 repeat containing protein and N-acetyl glutamate kinase 2.

Phosphorus (Pi) is one of the major nutrients for higher plant growth and development. Recent studies show that OsPHR2, OsSPX1, OsmiR399, OsPHO, OsIPS1, OsIPS2, OsSIZ1 and pht1 family have been involved in the phosphate-related signal transduction and regulation pathways. OsPHR2 and OsSPX1 have the similar function with the homologous genes in Arabidopsis thaliana, overexpression of OsPHR2 and suppression of OsSPX1 are resulted in severe signs of toxicity caused by the over-accumulation of Pi. The majority of the plants PTs belong to the Pht1 family. Recent study advances of Phosphate-Signaling Pathway in rice were reviewed.