Identification of a novel TSC1 gene variant in a patient with atypical vitiligo-like skin lesions: Unveiling the hidden tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC), an autosomal-dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the TSC1 or TSC2 gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences. METHODS: In this study, a single patient presenting with atypical vitiligo-like skin lesions suspected to have TSC was enrolled. Targeted next-generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of TSC1 c.1030-2A>T, located in intron 10, on RNA splicing. RESULTS: A novel TSC1: c.1030-2A>T heterozygosis variant was identified in intron 10. In vitro minigene assay revealed that the c.1030-2A>T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59). CONCLUSION: The detection of this novel pathogenic TSC1 variant in the patient with atypical vitiligo-like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the TSC1 gene and refining the genotype-phenotype map of TSC.

Genetic Variants Associated with Acne Vulgaris.

Acne vulgaris (AV) ranks among the common chronic inflammatory disorders that impact the sebaceous components of hair follicles. Acne vulgaris is characterised by cardinal manifestations such as the presence of pimples, nodules, pustules, and cysts, which have the potential to lead to the development of acne scarring and pigmentation. The phenomenon is influenced by polygenic inheritance or can be ascribed to the interplay between multiple genes and environmental factors. In recent years, some researchers have found that some genes (such as IL, TNF, RETN, CYP family, MMPs and TIMPs genes et al) are associated with acne vulgaris and may affect the progression and prognosis of the disease. The number of reviews addressing acne-associated genetic variants, however, is limited. In that case, we have compiled a list of prevalent genes associated with acne in recent times. This helps us understand acne's genetic basis and lets us step in early for people prone to severe acne, lowering the chance of acne scars.

The Biological Processes of Ferroptosis Involved in Pathogenesis of COVID-19 and Core Ferroptoic Genes Related With the Occurrence and Severity of This Disease.

Background: A worldwide outbreak of coronavirus disease 2019 (COVID-19) has resulted in millions of deaths. Ferroptosis is a form of iron-dependent cell death which is characterized by accumulation of lipid peroxides on cellular membranes, and is related with many physiological and pathophysiological processes of diseases such as cancer, inflammation and infection. However, the role of ferroptosis in COVID-19 has few been studied. Material and Method: Based on the RNA-seq data of 100 COVID-19 cases and 26 Non-COVID-19 cases from GSE157103, we identified ferroptosis related differentially expressed genes (FRDEGs, adj.P-value < .05) using the "Deseq2" R package. By using the "clusterProfiler" R package, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Next, a protein-protein interaction (PPI) network of FRDEGs was constructed and top 30 hub genes were selected by cytoHubba in Cytoscape. Subsequently, we established a prediction model for COVID-19 by utilizing univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) regression. Based on core FRDEGs, COVID-19 patients were identified as two clusters using the "ConsenesusClusterPlus" R package. Finally, the miRNA-mRNA network was built by Targetscan online database and visualized by Cytoscape software. Results: A total of 119 FRDEGs were identified and the GO and KEGG enrichment analyses showed the most important biologic processes are oxidative stress response, MAPK and PI3K-AKT signaling pathway. The top 30 hub genes were selected, and finally, 7 core FRDEGs (JUN, MAPK8, VEGFA, CAV1, XBP1, HMOX1, and HSPB1) were found to be associated with the occurrence of COVID-19. Next, the two patterns of COVID-19 patients had constructed and the cluster A patients were likely to be more severe. Conclusion: Our study suggested that ferroptosis was involved in the pathogenesis of COVID-19 disease and the functions of core FRDEGs may become a new research aspect of this disease.

Evaluation of Effective Crosslinking Density for Pseudo-Semi Interpenetrating Polymer Networks Based on Polyether Glycols Mixture by Dynamic Mechanical Analysis.

Pseudo-semi interpenetrating polymer networks (pseudo-semi IPNs) are a special example of topological isomerism in macromolecules, which have attracted significant attention in recent years with a high potential in a variety of engineering applications of polymeric materials. In this article, pseudo-semi IPNs were synthetized by sequential polymerization of thermoplastic polymers (TPEs) in the presence of thermosetting elastomer (TSEs) with contents of 10, 20, 30, 40 and 50 wt.% in a vacuum oven at 60 °C for about 72 h. In addition, this article describes a method for researching the elastic modulus, effective crosslinking density and physical crosslinking density of TSEs and pseudo-semi IPNs. The inherent interactions and entanglements of pseudo-semi IPNs were discussed by analyzing the changes in elastic modulus and effective crosslinking density at different temperatures. The results show that after the TPE was added to the TSE matrix as a plastic-reinforced material, the ductility increased from 89.6% to 491%, the effective crosslinking density was increased by 100% at high temperatures and the strength of the material matrix was significantly improved. Two physical events take place in our pseudo-semi IPNs as result of energy dissipation and polymeric chains mobility.

Syringocystadenoma Papilliferum and Basal Cell Carcinoma Arising in Nevus Sebaceous.

Nevus sebaceous (NS) is a benign congenital hamartoma with the potential to develop into a secondary benign or malignant skin tumors. Two or more skin tumors rarely arise simultaneously from a single NS lesion. Herein, we report a case of syringocystadenoma papilliferum and basal cell carcinoma arising in an NS, based on dermoscopic, reflectance confocal microscopic, and histopathological findings.

A novel mutation of the NF1 gene in a Chinese family with neurofibromatosis type 1.

BACKGROUND: Mutations in the neurofibromin 1 (NF1) gene are associated with clinical manifestations of neurofibromatosis type 1 (NF1). OBJECTIVE: To clarify the relationship between NF1 variants and disease phenotype. METHODS: Peripheral blood samples were collected from a patient and her relatives and genomic DNA was extracted for next-generation sequencing (NGS) to detect potential variants; the results were validated by Sanger sequencing. RESULTS: A novel frameshift variant c.4508_c.4509delAT (p.Asn1503fsTer26) was detected in exon 34 of the NF1 gene in the patient and her daughter, but not in any other (healthy) family member. This c.4508_c.4509delAT (p.Asn1503fsTer26) frameshift variant of NF1 may underlie NF1 in this family. CONCLUSIONS: This finding expands the spectrum of pathogenic mutations of the NF1 gene, which could aid genetic counseling and prenatal diagnosis.

NEMO Gene Mutations in Two Chinese Females with Incontinentia Pigmenti.

Purpose: To identify the mutations of the NEMO gene in two Chinese females with incontinentia pigmenti. Patients and Methods: Patients were both from Nanchong, Sichuan Province. Genomic DNA was extracted from the peripheral blood of patients and patient 1's father. The mutations of the NEMO gene in patient 1 by GAP polymerase chain reaction and Sanger sequencing and her father were detected. NEMO-specific polymerase chain reaction and Sanger sequencing were used to identify the NEMO gene mutation in patient 2. Results: DNA analysis identified a rare frameshift mutation, c.723_c.724insCAGG(p.A242QfsX15) in exon 5 of the NEMO gene in patient 1 with a family history but not in her healthy father. The common deletion of exons 4-10 of the NEMO gene was found in sporadic patient 2. Conclusion: Our data revealed that the rare frameshift mutation, c.723_c.724insCAGG(p.A242QfsX15) in exon 5 of the NEMO gene in patient 1 and the deletion of exons 4-10 of the NEMO gene in patient 2 could cause the occurrence of IP. Genetic testing is helpful for early diagnosis and genetic counseling for families.

Coexistence of intrinsic room-temperature ferromagnetism and piezoelectricity in monolayer BiCrX3 (X = S, Se, and Te).

Two-dimensional (2D) materials with intrinsic ferromagnetism and piezoelectricity have received growing attention due to their potential applications in nanoscale spintronic devices. However, their applications are highly limited by the low Curie temperatures (TC) and small piezoelectric coefficients. Here, using first-principles calculations, we have successfully predicted that BiCrX3 (X = S, Se, and Te) monolayers simultaneously possess ferromagnetism and piezoelectricity by replacing one layer of Bi atoms with Cr atoms in Bi2X3 monolayers. Our results demonstrate that BiCrX3 monolayers are not only intrinsic ferromagnetic semiconductors with indirect band gaps, adequate TC values of higher than 300 K, and significant out-of-plane magnetic anisotropic energies, but also exhibit appreciable in-plane and out-of-plane piezoelectricity. In particular, the in-plane piezoelectric coefficients of BiCrX3 monolayers with ABCAB configuration are up to 15.16 pm V-1, which is higher than those of traditional three-dimensional piezoelectric materials such as α-quartz. The coexistence of ferromagnetism and piezoelectricity in BiCrX3 monolayers gives them promising applications in spintronics and nano-sized sensors.

Controllable Spin Switching in a Single-Molecule Magnetic Tunneling Junction.

A new type of spin-current filter is proposed that consists of a single-molecule magnet (SMM) coupled to two normal metal electrodes. It is shown that this tunneling junction can generate a highly spin-polarized current, whose spin polarization can be switched by means of magnetic fields and gate voltages applied to the SMM. This spin switching in the SMM tunnel junction arises from spin-selective single-electron resonant tunneling via the lowest unoccupied molecular orbit of the SMM. The electron current spectrum is still spin polarized in the absence of an external magnetic field, which can help to judge whether the molecule's spin state has reached the ground-state doublet [Formula: see text]. This device can be realized with current technologies and may have practical use in spintronics and quantum information.

Magnetic field-controlled spin-dependent thermoelectric current in a single-molecule magnet transistor.

Control of the charge, spin, and heat currents in thermoelectric devices is an interesting research field that is currently experiencing a burst of activity. In this work, a new type of spin-current generator is proposed that consists of a single-molecule magnet sandwiched between a pair of nonmagnetic electrodes. By applying an external magnetic field, this tunneling junction can generate a 100% spin-polarized current via thermoelectric effects, and the flow direction and spin polarization can be changed by adjusting the gate voltage or magnetic field. Moreover, regardless of whether the external magnetic field exists, the thermoelectric current is always highly spin polarized and can be switched by using different gate voltage windows. This molecular electrical device can be realized with current technologies and may have practical use in spin caloritronics and quantum information processing.

Diagnosis and treatment of lymphocutaneous dermatosis caused by Nocardia brasiliensis: a case report.

Cutaneous nocardiosis is a skin disease mainly caused by Nocardia brasiliensis and Nocardia asteroides. Here, we report a rare case of lymphocutaneous dermatosis in an 87-year-old Chinese man infected with Nocardia brasiliensis. An 87-year-old Chinese man presented at our hospital after suffering erythema, nodules, abscesses, ulceration, and pain in the left upper limb for 10 days. The patient was initially misdiagnosed as lymphocutaneous sporotrichosis. The results of gram staining, acid-fast staining, mass spectrograph revealed Nocardia brasiliensis and 16S ribosomal RNA (16S rRNA) sequencing of samples showed that the patient had a Nocardia brasiliensis infection. Anti-infective therapy with sulfamethoxazole combined with amoxicillin clavulanate potassium was administered for 10 days, followed by sulfamethoxazole alone for 20 days. After 30 days of treatment, the abscess was treated with repeated pus extraction, debridement of erosion and ulcer, wet compress of povidone iodine solution and spectrum of multi-source instrument. The redness and swelling had subsided, and purulent secretion and ulceration had decreased. Lymphocutaneous nocardiosis can easily be misdiagnosed as sporotrichosis based on its clinical manifestations. However, mass spectrometry analysis showed Nocardia brasiliensis according to the fingerprint of the bacteria and 16S rRNA sequencing to identify bacterial DNA can assist with making a diagnosis. For patients with Nocardia brasiliensis, sulfamethoxazole combined with amoxicillin clavulanate potassium is an effective anti-infective treatment.

Belowground interactions differ between sympatric desert shrubs under water stress.

Understanding the relationships among species is central to ecological research; however, many knowledge gaps remain regarding how desert plant species interact. In the present study, we assessed the effect of rainfall on the belowground interactions and root morphology of two desert shrubs, Reaumuria soongorica (Tamaricaceae) and Salsola passerina (Chenopodiaceae), from three communities with similar landforms and soil environments. The roots of both R. soongorica and S. passerina were deeper when grown together than grown singly. Interestingly, the belowground biomass of R. soongorica was higher, but the belowground biomass of S. passerina was lower when grown together than when grown alone. This suggests that S. passerina benefitted from the association with R. soongorica. When grown together under conditions of low rainfall, the roots of R. soongorica were deeper than those of S. passerina, which suggests that R. soongorica is more robust than S. passerina when subjected to periods of decreased rainfall. We concluded that the symbiotic relationship between these two shrub species can lead to deeper roots and that the plants are affected by rainfall availability. Combined with the output results of climate change models, we speculated that the distribution area of these two species will expand to the west, which has important implications on how the interactions of other desert species may change in response to climate variability.

[Genetic diagnosis of a patient with long-time misdiagnosis of epilepsy].

OBJECTIVE: To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy. METHODS: Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents. CONCLUSION: The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.

A case report and review of lymphocutaneous nocardiosis caused by Nocardia brasiliensis reported in China.

Primary cutaneous nocardiosis caused by Nocardia brasiliensis is an uncommon disease. The present authors report a Chinese woman presented with lymphocutaneous nocardiosis caused by N. brasiliensis. The lesion begin with her right hand after an unknown insect sting and evolved rapidly and formed painful erythema and two subcutaneous nodules and abscesses on her right forearm in 5 days. N. brasiliensis was isolated from pustule and identified by gene sequencing. The patient received 2 weeks of combination therapy contained infusion of amoxilin potassioum clavinet and oral TMP/SMX and followed by a single therapy of oral TMP/SMX for 1 month and got a marked improvement. The present authors reviewed a case of lymphocutaneous nocardiosis caused by N. brasiliensis reported in China.

Prolonged dry periods between rainfall events shorten the growth period of the resurrection plant Reaumuria soongorica.

The resurrection plant Reaumuria soongorica is widespread across Asia, southern Europe, and North Africa and is considered to be a constructive keystone species in desert ecosystems, but the impacts of climate change on this species in desert ecosystems are unclear. Here, the morphological responses of R. soongorica to changes in rainfall quantity (30% reduction and 30% increase in rainfall quantity) and interval (50% longer drought interval between rainfall events) were tested. Stage-specific changes in growth were monitored by sampling at the beginning, middle, and end of the growing season. Reduced rainfall decreased the aboveground and total biomass, while additional precipitation generally advanced R. soongorica growth and biomass accumulation. An increased interval between rainfall events resulted in an increase in root biomass in the middle of the growing season, followed by a decrease toward the end. The response to the combination of increased rainfall quantity and interval was similar to the response to increased interval alone, suggesting that the effects of changes in rainfall patterns exert a greater influence than increased rainfall quantity. Thus, despite the short duration of this experiment, consequences of changes in rainfall regime on seedling growth were observed. In particular, a prolonged rainfall interval shortened the growth period, suggesting that climate change-induced rainfall variability may have significant effects on the structure and functioning of desert ecosystems.

Human CAFs promote lymphangiogenesis in ovarian cancer via the Hh-VEGF-C signaling axis.

Cancer-associated fibroblasts (CAFs) play a pivotal role in the development and progression of many human cancers. Recent studies have shown that Hedgehog (Hh) signalling modulates the stromal microenvironment and prepares a suitable niche for tumour metastasis. However, the detailed molecular mechanisms underlying CAF-mediated lymphangiogenesis have not been fully elucidated. Therefore, our goal is to illustrate whether Hh ligands can activate Hh signalling in CAFs in a paracrine fashion and elucidate the effect of CAFs on lymphangiogenesis. We determined here that Sonic Hedgehog (SHH) secreted by ovarian cancer (OC) cells activated Hh signalling in CAFs and promoted the proliferation of CAFs. Moreover, we co-injected SHH-overexpressing OC cells and CAFs in a xenograft model and found that the CAFs accelerated tumourigenesis and lymphangiogenesis in OC. Mechanistically, we found that SHH secreted by the OC cells induced VEGF-C expression in CAFs. Inhibition of Hh signalling in CAFs decreased VEGF-C expression and diminished the positive role of CAFs in supporting tumourigenesis and lymphangiogenesis in a murine xenograft model. Our results demonstrate that CAFs constitute a supportive niche for cancer lymphangiogenesis via the Hh/VEGF-C signalling axis and provide evidence for the clinical application of Hh inhibitors in the treatment of OC.

[Analysis of SLC39A4 gene mutation in a patient with acrodermatitis enteropathica].

OBJECTIVE: To detect pathogenic mutation of the SLC39A4 gene in a male patient with acrodermatitis enteropathica (AE). METHODS: Peripheral venous blood sample and clinical data from the patient and his parents were collected. One hundred unrelated healthy individuals were recruited as controls. All coding exons and flanking exon-intron sequences of the SLC39A4 gene were analyzed by PCR and direct sequencing. RESULTS: The results revealed that the patient and his mother have both carried a novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) in exon 6. A novel nonsense mutation c.958C to T (p.Q320X) in exon 5 was also detected in the patient and his father and grandmother. This novel mutation was not detected in the unaffected family members and 100 unrelated healthy controls. CONCLUSION: The novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) derived from the mother and nonsense mutation c.958C to T (p.Q320X) of the SLC39A4 gene derived from the father may underlie the disease in the patient.

[Analysis of TSC gene mutations in five patients with tuberous sclerosis complex].

OBJECTIVE: To identify pathogenic mutations of TSC1 and TSC2 genes in two familial and one sporadic cases with tuberous sclerosis complex (TSC). METHODS: For five patients and their family members, potential mutations of the TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: For one family, a novel missense mutation c.1964C>T (p.S655F) was detected in the exon 19 of the TSC2 gene. For the sporadic patient, a repeat substitution with deletion mutation c.5238-5255delCATCAAGCGGCTCCGCCA (p.His1746GlnfsX56) was detected in the exon 40 of the TSC2 gene, which led to a stop codon TGA after the 56th amino acids. No mutation was found in another family. CONCLUSION: The missense mutation c.1964C>T(P.S655F) and the substitution with deletion mutation 5238-5255delCATCAAGCGGCTCCGCCA(p.His1746GlnfsX56) of the TSC2 gene probably underlie the disease in the first family and the sporadic case.

Porous CuO nanotubes/graphene with sandwich architecture as high-performance anodes for lithium-ion batteries.

Constructing a porous conductive framework represents a promising strategy for designing high-performance anodes for Li-ion batteries. Here, porous CuO nanotubes/graphene with hierarchical architectures were fabricated by simple annealing of copper nanowires/graphene hybrids synthesized by a microwave-assisted process. In these nanoarchitectures, the embedded porous CuO nanotubes can prevent restacking of the graphene sheets, whereas graphene can increase the electrical conductivity of CuO. Moreover, these two components constitute a sandwich-like interlaced framework that favors ion diffusion, as well as promoting better electron transport. As a result, the as-prepared nanohybrid exhibits a high specific capacity of 725 mA h g-1 and a capacity retention of ∼81% after 250 cycles, as well as outstanding rate performance in comparison to those of bare CuO or a CuO-CNT (carbon nanotubes) hybrid.

[Two novel mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria].

OBJECTIVE: To identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria(DSH). METHODS: Clinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing. RESULTS: A novel frame-shift mutation c.2638delG (p.Asp880ThrfsX15) from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c.2867C>A (p.Ser956X) was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls. CONCLUSION: The frame-shift mutation c.2638delG (p.Asp880ThrfsX15) and the nonsense mutation c.2867C>A (p.Ser956X) in the ADAR1 gene probably underlie the DSH in our patients.