miR-26a-5p inhibits the proliferation of psoriasis-like keratinocytes in vitro and in vivo by dual interference with the CDC6/CCNE1 axis.

Psoriasis is a chronic inflammatory proliferative dermatological ailment that currently lacks a definitive cure. Employing data mining techniques, this study identified a collection of substantially downregulated miRNAs (top 10). Notably, 32 targets were implicated in both the activation of the IL-17 signaling pathway and cell cycle dysregulation. In silico analysis revealed that one of these miRNAs, miR-26a-5p, is a highly conserved cross-species miRNA. Strikingly, the miR-26a-5p sequences in humans and mice are identical, and mmu-miR-26a-5p was found to target the same 7 cell cycle targets as its human counterpart, hsa-miR-26a-5p. Among these targets, CDC6 and CCNE1 were the most effective targets of miR-26a-5p, which was further validated in vitro using a dual luciferase reporter system and qPCR assay. The therapeutic assessment of miR-26a-5p revealed its remarkable efficacy in inhibiting the proliferation and G1/S transition of keratinocytes (HaCaT and HEKs) in vitro. In vivo experiments corroborated these findings, demonstrating that miR-26a-5p effectively suppressed imiquimod (IMQ)-induced psoriasis-like skin lesions in mice over an 8-day treatment period. Histological analysis via H&E staining revealed that miR-26a-5p treatment resulted in reduced keratinocyte thickness and immune cell infiltration into the spleens of IMQ-treated mice. Mechanistic investigations revealed that miR-26a-5p induced a cascade of downregulated genes associated with the IL-23/IL-17A axis, which is known to be critical in psoriasis pathogenesis, while concomitantly suppressing CDC6 and CCNE1 expression. These findings were corroborated by qPCR and Western blot analyses. Collectively, our study provides compelling evidence supporting the therapeutic potential of miR-26a-5p as a safe and reliable endogenous small nucleic acid for the treatment of psoriasis.

The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions.

Mammalian cytosolic thioredoxin reductase (TrxR1) serves as an antioxidant protein by transferring electrons from NADPH to various substrates. The action of TrxR1 is achieved via reversible changes between NADPH-reduced and non-reduced forms, which involves C-terminal selenolthiol/selenenylsulfide exchanges. TrxR1 may be released into extracellular environment, where TrxR1 is present mainly in the non-reduced form with active-site disulfide and selenenylsulfide bonds. The relationships between extracellular TrxR1 and tumor metastasis or cellular signaling have been discovered, but there are few reports on small-molecule compounds in targeted the non-reduced form of TrxR1. Using eight types of small-molecule thiol-reactive reagents as electrophilic models, we report that the selenenylsulfide bond in the non-reduced form of TrxR1 functions as a selector for the thiol-reactive reagents at pH 7.5. The non-reduced form of TrxR1 is resistant to hydrogen peroxide/oxidized glutathione, but is sensitive to certain electrophilic reagents in different ways. With 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and S-nitrosoglutathione (GSNO), the polarized selenenylsulfide bond breaks, and selenolate anion donates electron to the dynamic covalent bond in DTNB or GSNO, forming TNB-S-Se-TrxR1 complex or ON-Se-TrxR1 complex. The both complexes lose the ability to transfer electrons from NADPH to substrate. For diamide, the non-reduced TrxR1 actually prevents irreversible damage by this oxidant. This is consistent with the regained activity of TrxR1 through removal of diamide via dialysis. Diamide shows effective in the presence of human cytosolic thioredoxin (hTrx1), Cys residue(s) of which is/are preferentially affected by diamide to yield disulfide, hTrx1 dimer and the mixed disulfide between TrxR1-Cys497/Sec498 and hTrx1-Cys73. In human serum samples, the non-reduced form of TrxR1 exists as dithiothreitol-reducible polymer/complexes, which might protect the non-reduced TrxR1 from inactivation by certain electrophilic reagents under oxidative conditions, because cleavage of these disulfides can lead to regain the activity of TrxR1. The details of the selective response of the selenenylsulfide bond to electrophilic reagents may provide new information for designing novel small-molecule inhibitors (drugs) in targeted extracellular/non-reduced TrxR1.

Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome.

AIM: To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene. METHODS: Ophthalmological examinations, including slit-lamp biomicroscopy and lacrimal duct probing, and computed tomography dacryocystography (CT-DCG) were performed for all participants. The family pedigree was drawn, genetic features were analyzed, and the genomic DNA of the subjects was extracted. Pathogenic genes were screened via whole exome sequencing (WES) and confirmed using Sanger sequencing. RESULTS: Six patients belonged to this three-generation family, and their clinical manifestations included congenital nasolacrimal duct obstruction, congenital absence of lacrimal puncta and canaliculi, lacrimal fistulae, and limb deformities. This pattern indicates autosomal dominant inheritance. Diagnosis was based on the clinical characteristics of LADD syndrome, which presented in all the patients in this family. A novel frameshift mutation in the FGF10 gene (NM_004465.1), c.234dupC (p.Trp79Leus*15), was identified in all patients via WES. The variant was confirmed by Sanger sequencing and classified as a "pathogenic mutation" according to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines. CONCLUSION: A novel frameshift mutation in the FGF10 gene is found in all patients. This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Estrogen ameliorates sepsis-induced vascular hyporeactivity in thoracic aorta of female rats via permissive effect of GRα expression.

OBJECTIVE: Estrogen is correlated to the lower mortality and disease severity of female than that of male, which indicates the potential therapeutic role of estrogen supplement therapy in sepsis. The structure of Daidzein is similar to that of 17ß estradiol (E2), an estrogen in human body, causing the exogenous Daidzein can interact with estrogen receptor as well as E2 in the body. We aim to explore the therapeutic role of estrogen in sepsis-induced vascular dysfunction. Also, we wonder if estrogen regulates blood pressure via glucocorticoid-mediated vascular reactivity. METHODS: Female SD rats received ovariectomy (OVX) to induce estrogen deficiency. After 12 weeks of administration, cecal ligation and puncture (CLP) was used to establish the in vivo model of sepsis. Lipopolysaccharide (LPS) was used to construct the in vitro model of sepsis in vascular smooth muscle cells (VSMCs). E2 and Daidzein were used for estrogen supplement therapy. RESULTS: E2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E2 and Daidzein promoted glucocorticoid permissive action and increased glucocorticoid receptor α (GRα) expression in thoracic aorta smooth muscle cells. E2 and Daidzein upregulated GRα, and inhibits cytokine production, proliferative phenotype and cell migration in LPS-induced VSMCs. CONCLUSION: Estrogen improved vascular hyporeactivity in thoracic aorta induced by sepsis via permissive effect of GRα expression.

Application of Nonlinear Models Combined with Conventional Laboratory Indicators for the Diagnosis and Differential Diagnosis of Ovarian Cancer.

Existing biomarkers for ovarian cancer lack sensitivity and specificity. We compared the diagnostic efficacy of nonlinear machine learning and linear statistical models for diagnosing ovarian cancer using a combination of conventional laboratory indicators. We divided 901 retrospective samples into an ovarian cancer group and a control group, comprising non-ovarian malignant gynecological tumor (NOMGT), benign gynecological disease (BGD), and healthy control subgroups. Cases were randomly assigned to training and internal validation sets. Two linear (logistic regression (LR) and Fisher's linear discriminant (FLD)) and three nonlinear models (support vector machine (SVM), random forest (RF), and artificial neural network (ANN)) were constructed using 22 conventional laboratory indicators and three demographic characteristics. Model performance was compared. In an independent prospectively recruited validation set, the order of diagnostic efficiency was RF, SVM, ANN, FLD, LR, and carbohydrate antigen 125 (CA125)-only (AUC, accuracy: 0.989, 95.6%; 0.985, 94.4%; 0.974, 93.4%; 0.915, 82.1%; 0.859, 80.1%; and 0.732, 73.0%, respectively). RF maintained satisfactory classification performance for identifying different ovarian cancer stages and for discriminating it from NOMGT-, BGD-, or CA125-positive control. Nonlinear models outperformed linear models, indicating that nonlinear machine learning models can efficiently use conventional laboratory indicators for ovarian cancer diagnosis.

Graphene-containing metal-organic framework nanocomposites for enhanced microwave ablation of salivary adenoid cystic carcinoma.

Salivary adenoid cystic carcinoma (SACC), one of the most common malignant tumors in the head and neck region, is characterized by high postoperative recurrence rate and poor prognosis. Microwave (MW) ablation possesses advantages in preserving SACC patients' facial aesthetics and oral function, but unfortunately, it suffers from low therapeutic efficacy due to the limited MW-thermal efficiency. Moreover, the insufficient thermal ablation may aggravate hypoxic state in tumors, which is deleterious to the treatment of residual tumors and aggressive tumors. Hence, MW ablation has been rarely applied in treating head and neck tumors in recent years. To minimize the unfavorable outcomes and maximize the therapeutic effects of MW ablation, a MW sensitizer coupled with a self-sufficient oxygen nanoagent was employed for the first time in MW ablation to treat head and neck tumors. We prepared a graphene-containing metal-organic framework (ZIF67@Gr-PEG), which exhibited excellent MW thermal conversion ability endowed by the incorporated Gr and showed in situ oxygen generation capacity derived from the ZIF67 matrix. In an animal experiment, ZIF67@Gr-PEG-based MW ablation with a temperature up to 66.1 °C exhibited a high tumor ablation rate. More importantly, insufficient MW ablation-induced high expressions of HIF-1α and VEGF were observed in our experiment, whereas the levels of tumor hypoxia and angiogenesis were efficiently decreased in MW ablation with the assistance of ZIF67@Gr-PEG nanocomposites (NCs). Notably, our strategy for MW ablation not only evidences the great potential of ZIF67@Gr-PEG but also promotes the translation of thermotherapeutic graphene from basic research to clinical practice.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip.

BACKGROUND: DNA methylation is a part of epigenetic modification, that is closely related to the growth and development of colorectal cancer (CRC). Specific methylated genes and methylated diagnostic models of tumors have become current research focuses. The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC. AIM: To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip. METHODS: The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients (n = 5) and colorectal adenoma patients (n = 5). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma. RESULTS: A total of 1865 methylated CpG sites with significant differences were detected, including 676 hypermethylated sites and 1189 hypomethylated sites. The distribution of these sites covered from the 1st to 22nd chromosomes and are mainly distributed on the gene body and gene promoter region. GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation, molecular binding, transcription factor activity and signal transduction pathway. CONCLUSION: The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

Rapid detection of trace formaldehyde in food based on surface-enhanced Raman scattering coupled with assembled purge trap.

It has been remained a challenge to detect trace formaldehyde in complex samples, such as rice flour and duck blood products. In this study, a purge-trap device was designed and used for volatile target detection, which avoided interference adsorptions on enhanced particle surfaces during subsequent surface-enhanced Raman spectroscopy (SERS) analysis. The device produced a low detection limit for formaldehyde of 1 × 10-4 µg/mL in the concentration ranges of 4 × 10-3-4 µg/mL and 1 × 10-4-3 × 10-3 µg/mL. In the process of the detection of duck blood and rice flour, partial least squares regression (PLSR) was adopted for sample analysis. The formaldehyde concentration was calculated and compared to the actual value from the above model with R2 of 0.97, which indicated high accuracy and stability. These results suggested that the proposed method was reliable and suitable for rapid analysis of trace formaldehyde in real products.

Long noncoding RNA LINC02580 suppresses the invasion-metastasis cascade in hepatocellular carcinoma by targeting SRSF1.

Hepatocellular carcinoma (HCC) is a severe global health problem. There is increasing evidence for the important roles of long noncoding RNAs in tumorigenesis and metastasis in HCC. In this study, we identified and characterized a novel long noncoding RNA, LINC02580, involved in HCC. LINC02580 was highly downregulated in HCC cohorts and was identified as a tumor suppressor. Low LINC02580 expression in patients with HCC was correlated with poor prognosis. Functional assays indicated that LINC02580-deficient cells show enhanced colony formation, migration, and invasion in vitro and promote subcutaneous tumor formation and distant lung metastasis in vivo. With respect to the underlying mechanism, we found that LINC02580 modulates the epithelial-mesenchymal transition (EMT) associated pathway in HCC cells by specifically binding to serine and arginine-rich splicing factor 1 (SRSF1). In summary, our findings illustrated that LINC02580 is a metastasis-suppressing lncRNA in HCC, and provided vital clues of how LINC02580 performs its biological functions. Further, this lncRNA may be a potential target in the prognosis and treatment of HCC.

Urinary Peptides Associated Closely with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common disease of pregnant women, which has a higher incidence in recent years. The purpose of this study is to explore urinary biomarkers that could predict and monitor gestational diabetes mellitus (GDM). Urine samples from 30 normal pregnant women and 78 GDM patients were collected and purified by weak cationic exchange magnetic beads (MB-WCX), then analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The urinary peptide signatures of the two groups were compared by BioExplorer software. The potential ability of the differently expressed peptides to distinguish GDM patients from normal pregnant women was evaluated by receiver operating characteristic (ROC) analysis. At last, the differently expressed peptides were identified by liquid chromatography tandem mass spectrometry (LC-MS). There were four differently expressed peptides (m/z 1000.5, 1117.5, 1142.9, and 2022.9) between two groups, which were identified as fragments of urinary albumin, α2-macroglobulin, human hemopexin, and α1-microglobulin, respectively. The diagnostic efficacy of m/z 1142.9 was better than the other peptides. The area under the curve (AUC) of the m/z 1142.9 was 0.690 (95% CI: 0.583-0.796). The discovery of urinary polypeptides provides the possibility for the early prediction of GDM and the monitoring of glucose metabolism in GDM patients by a noninvasive method.

An electrochemical aptasensor for ATP based on a configuration-switchable tetrahedral DNA nanostructure.

A novel electrochemical aptasensor for ATP was developed based on an aptamer-embedded configuration-switchable tetrahedral DNA nanostructure (TDN) and the formation of a G-quadruplex. This unique TDN was formed through the self-assembly of four specially designed single-stranded DNA (ssDNA) sequences (S1, S2, S3 and S4). The TDN was immobilized on the surface of a Au electrode through the thiol groups at the 5'-end of S1, S2 and S3. Five edges of the TDN were designed to form a double helix to preserve the structural robustness of the tetrahedron, while the ATP aptamer embedded sequence (S3) was designed to be located at the rest edge. The two terminals of S4 at the same edge were composed of two split G-quadruplex-forming sequences, which were non-complementary to the aptamer. This edge offered the configuration-switchable characteristic of the TDN. In the absence of ATP, the TDN remained in a relaxed state, and the G-quadruplex cannot form due to the large distance between the split G-quadruplex-forming sequences. However, in the presence of ATP, the aptamer combined with ATP and shortened the distance between the split sequences, resulting in the taut state of the TDN and the formation of a G-quadruplex at the edge. After the addition of hemin, the differential pulse voltammograms (DPVs) were used to quantify ATP. The sensor revealed a dynamic response range from 0.1 nM to 1 µM, with a detection limit of 50 pM. In addition, the specificity and practicability in real samples were also verified, indicating its potential applications.

Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases.

BACKGROUND: Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with the MMACHC c.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention. METHODS: We assessed 149 cblC patients caused by MMACHC c.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019. RESULTS: Two patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group. CONCLUSIONS: Most cblC patients caused by MMACHC c.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.

Preparation of polyethylene glycol-polyacrylic acid block copolymer micelles with pH/hypoxic dual-responsive for tumor chemoradiotherapy.

Block copolymers of poly(ethylene glycol)-poly(acrylic acid) linked with metronidazole (MN-PAA-PEG) were prepared via carbodiimide and esterification methods, and self-assembled into core-shell micelles as nano radiosensitizers and carriers of doxorubicin (DOX) delivery. These DOX/MN-PAA-PEG micelles exhibited good pH value and hypoxia dual-responsive properties via analyzing the change of micelle size and drug‒release behavior under hypoxia humor condition. The results of the cell test indicated that DOX was efficiently delivered by DOX/MN-PAA-PEG micelles into the cell nuclei. Compared to 22.4 % of their DOX release under pH 7.4, the rate of DOX release from DOX/MN-PAA-PEG micelles under reducing condition (pH 5.0) was up to 55.9 %. DOX-loaded micelles under 600 MU electron radiation and hypoxia induced the rapidest apoptosis of the tumor-cells, indicating the synergistic effect of their radiotherapy and chemotherapy from the prepared micelles. In vivo investigation and fluorescence imaging revealed that MN-PAA-PEG possessed no toxicity on main organs, and DOX/MN-PAA-PEG micelles were mainly accumulated in the tumor site at 10 h of post-injection, suggesting their good passive tumor-targeted effect. These results suggested that DOX/MN-PAA-PEG micelles were promising candidates for chemoradiotherapy on tumor.

Screening and analysis of small molecular peptides in urine of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common clinical disease with complicated clinical process and harmful effects on pregnant women and fetus. The purpose of this study is to use the convenient urine samples in combination with glucose levels to detect or predict GDM. In this study, urine samples of non-pregnant women, normal pregnant women and GDM patients were collected. The peptides in urine were enriched by weak cationic exchange magnetic beads (MB-WCX) and analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). 46 polypeptide peaks with statistical difference (P < 0.01) were screened out by using Bioexplorer analysis software. The level of molecules with mass-to-charge ratio of 1079.2, 1290.6 and 1500.7 was higher in the GDM group than the other two groups. Through the analysis of differential molecules by liquid chromatography tandem mass spectrometry (LC-MS), the above molecules were identified as coagulation factor IX, TBC1 family member 5 isoform a [Homo sapiens] (TBC1D5a) and immunoglobulin kappa constant. The discovery of polypeptides provides the research basis for further primary screening and assistant diagnosis of GDM through urine samples.

A cautionary tale of cross-contamination among plasmids from commercial suppliers.

Many researchers have switched to purchasing their desired plasmids from commercial suppliers to save time and resources, as we did for 17 high-risk human papillomavirus plasmids. To our surprise, they were shown to be cross-contaminated with one another. Comparison between the production schedule and the pattern of contaminations proved that this contamination occurred during the production process, which was also shown for another two sets of commercial plasmids. Our experience indicates that the absolute purity of plasmids obtained from external sources cannot be guaranteed. Extreme caution should be exercised, especially when such plasmids are used for human gene therapies and DNA vaccines, where even a minute amount of contamination may pose significant risks to patients.

Switchable DNA tweezer and G-quadruplex nanostructures for ultrasensitive voltammetric determination of the K-ras gene fragment.

Voltammetric detection of the K-ras gene fragment was accomplished through the combined application of (a) a switchable DNA nanostructure, (b) the use of hairpin probe and exonuclease III (Exo III)-assisted signal amplification, (c) a split G-quadruplex, and (d) by exploiting the redox activity of DNAzyme. Three assistant oligonucleotides were designed to construct a DNA tweezer on a gold electrode. It is in "open state" in the absence of K-ras DNA. Then, a hairpin probe was introduced, whose stem-loop structure can be opened through hybridization with the K-ras DNA. Exo III is added which hydrolyzes the complementary region of the hairpin sequence to release a single-stranded rest fragment. The ssDNA hybridizes with the DNA tweezer on the electrode which thereby is switched to the "closed state". This leads to the formation of G-quadruplex due to the shortened distance of the split G-quadruplex-forming sequences in the tweezer. The voltammetric signal of the G-quadruplex-hemin complex, with a peak near -0.3 V vs. Ag/AgCl, is used as the signal output. Under the optimal conditions, the current response in differential pulse voltammetry (DPV) increases linearly with the concentration of K-ras DNA in the range of 0.01-1000 pM, and the detection limit is 2.4 fM. The assay can clearly discriminate K-ras DNA from a single-base mutation. The method has excellent selectivity and was applied to the determination of K-ras DNA in (spiked) serum samples. Graphical abstractSchematic representation of a method for the determination of the K-ras gene fragment through a combination of switchable DNA tweezer, split G-quadruplex, and exonuclease III (ExoIII)-assisted target recycling signal amplification.

Facile synthesis of urchin-like LaWO4Cl assemblies and their near-infrared photothermal conversion.

The construction of the hierarchical nanostructures of inorganic materials with high stability has attracted great attention for photothermal therapy. In this paper, we presented the preparation of urchin-like LaWO4Cl nanostructures assembled with nanoribbons via a facile solvothermal reaction. X-ray diffraction (XRD) analysis confirmed the formation of good crystalline urchin-like LaWO4Cl assemblies. Energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) revealed the element composition of the prepared urchin-like nanostructures. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigations showed that the urchin-like LaWO4Cl assemblies were composed of single crystalline nanoribbons with diameters less than 10 nm. When excited with an 808 nm near-infrared (NIR) laser at the power density of 1.91 W cm-2 for 5 min, the temperature quickly increased to 52 °C. The in vitro cytotoxicity of urchin-like LaWO4Cl was tested with human cervical cancer cells (HeLa), revealing excellent biocompatibility. More importantly, the photothermal treatment with urchin-like LaWO4Cl displayed great therapeutic efficacy in vitro. Thus, urchin-like LaWO4Cl would be a new promising NIR light-driven photothermal agent, which can also pave a new way for the material design of PTT agents.

Genetic Analysis in Fetal Skeletal Dysplasias by Trio Whole-Exome Sequencing.

Skeletal dysplasias (SDs) comprise a series of severe congenital disorders that have strong clinical heterogeneity and usually attribute to diverse genetic variations. The pathogenesis of more than half of SDs remains unclear. Additionally, the clinical manifestations of fetal SDs are ambiguous, which poses a big challenge for accurate diagnosis. In this study, eight unrelated families with fetal SD were recruited and subjected to sequential tests including chromosomal karyotyping, chromosomal microarray analysis (CMA), and trio whole-exome sequencing (WES). Sanger sequencing and quantitative fluorescence PCR (QF-PCR) were performed as affirmative experiments. In six families, a total of six pathogenic/likely pathogenic variations were identified in four genes including SLC26A2, FGFR3, FLNB, and TMEM38B. These variations caused disorders following autosomal dominant or autosomal recessive inheritance patterns, respectively. The results provided reliable evidence for the subsequent genetic counseling and reproductive options to these families. With its advantage in variation calling and interpreting, trio WES is a promising strategy for the investigation of fetal SDs in cases with normal karyotyping and CMA results. It has considerable prospects to be utilized in prenatal diagnosis.