Case report: Whole exome sequencing reveals a novel splicing variant of ANKRD17 gene in a Chinese male juvenile with developmental delay and transient tic disorder.

Background: The Ankyrin Repeat Domain Containing Protein 17 (ANKRD17, OMIM:615929) gene is a protein-coding gene associated with diseases such as Chopra-Amiel-Gordon Syndrome and Non-Specific Syndromic Intellectual Disability. The protein encoded by ANKRD17 gene belongs to the ankyrin repeat-containing protein family, which is one of the most widely existing protein domains that exclusively mediate protein-protein interactions. To date, the research and reports on the ANKRD17 gene are limited. Case presentation: Trio whole exome sequencing (Trio-WES) was conducted on the proband and his unaffected parents to elucidate the genetic etiology in the proband, who was clinically diagnosed with developmental delay and other phenotypes. Subsequently, Sanger sequencing was employed for validation of the identified candidate variant. Furthermore, RNA analysis was utilized to ascertain the impact of the variant on splicing. The WES revealed a novel heterozygous ANKRD17 splicing variant (c.7248 + 1G>A) in the proband, but not detected in his unaffected parents. And the presence of the splicing variant of the ANKRD17 gene was valided by the Sanger sequencing subsequently. And the RNA analysis confirmed that the novel variant was predicted to result in loss of donor splice site, and the analysis at mRNA level confirmed that it leads to exon 32 skipping (r.7100_7278del179) and causes premature termination of translation to the protein (p.D2357fs), therefore is classified as pathogenic. Conclusion: Our study reported a novel splicing variant in ANKRD17 gene, which may be associated with partial eating, frequent urination, and tic syndrome. This finding expands both the phenotypic and genotypic spectrum of ANKRD17 gene. Although there is currently no curative therapy available for ANKRD17 gene variants, a definitive diagnosis of its genetic etiology is significant for genetic counseling and family planning purposes. Furthermore, this is the first reported case of the ANKRD17 gene in China.

Case report: Genetic diagnoses in a pediatric patient with retinoblastoma and comorbid global developmental delay: three distinct entities diagnosed by whole exome sequencing in a single patient.

Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD). Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband. Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.

Energy-Saving Ambient Electrosynthesis of Nylon-6 Precursor Coupled with Electrocatalytic Upcycling of Polyethylene Terephthalate.

Cyclohexanone oxime is an important intermediate in the chemical industry, especially for the manufacture of nylon-6. The traditional cyclohexanone oxime production strongly relies on cyclohexanone-hydroxylamine and cyclohexanone ammoxidation processes, which require harsh reaction conditions and consume considerable amounts of energy. Herein, direct electrosynthesis of cyclohexanone oxime is reported from environmental pollutants nitrite and cyclohexanone with almost 100% yield by using low-cost Cu2Se nanosheets as electrocatalysts. Combination of in situ Fourier transform infrared spectroscopy and theoretical calculations verifies that the p-d orbital hybridization between Cu and Se elements could synergistically optimize the surface electronic structure and enable improved adsorption and formation of the key active N intermediate NH2OH*, thereby enhancing cyclohexanone/nitrite-to-cyclohexanone oxime conversion over the Cu2Se nanosheets. Based on these, an efficient asymmetric co-electrolysis system is further demonstrated by coupling cyclohexanone/nitrite-to-cyclohexanone oxime conversion with the upcycling of polyethylene terephthalate plastics, achieveing energy-saving simultaneously production of value-added products (cyclohexanone oxime and glycolic acid).

Dual Hydrogen Production System: Synergistic Effect of Ru and Ce Over Cu2O Nanotubes Drives Hydrogen Evolution and Formaldehyde Oxidation.

Water splitting for hydrogen production is limited by high cell voltage and low energy conversion efficiencies due to the slow kinetic process of the oxygen evolution reaction (OER). Here, an electrolytic system is constructed in which the cathode and anode co-release H2 at ultra-low input voltage using formaldehyde oxidation reaction (FOR) instead of OER. The prepared RuCe co-doped Cu2O nanotubes on copper foam (RuCe-Cu2O/CF) are used as electrode materials for the HER-FOR system. A current density of 0.8 A cm-2 is achieved at 0.55 V, and a stable hydrogen production process is realized at both the cathode and anode. Density functional theory (DFT) studies show that the synergistic effect of Ru and Ce drives: i) the d-band center of RuCe-Cu2O/CF away from the Fermi energy level; ii) the energy barrier for the C─H cracking of the H2C(OH)O* intermediate in FOR is lowered, which promotes the formation of H2 from H*, and iii) ΔGH* tends to 0 (-0.1 eV), optimizing the reaction kinetics of HER. This work provides a new design for an efficient catalyst for dual hydrogen production systems from water splitting.

Electrocatalytic Valorization of Nitrate and Polyester Plastic for Simultaneous Production of Ammonia and Glycolic Acid.

Electrochemical upcycling of nitrate and polyester plastic into valuable products is an ideal solution to realize the resource utilization. Here, the co-production of ammonia (NH3) and glycolic acid (GA) via electrochemical upcycling of nitrate and polyethylene terephthalate (PET) plastics over mesoporous Pd3Au film on Ni foam (mPd3Au/NF), which is synthesized by micelle-assisted replacement method, is proposed. The mPd3Au/NF with well-developed mesoporous structure provides abundant active sites and facilitated transfer channels and strong electronic effect. As such, the mPd3Au/NF exhibits high Faraday efficiencies of 97.28% and 95.32% at 0.9 V for the formation of NH3 and GA, respectively. Theoretical results indicate that the synergistic effect of Pd and Au can optimize adsorption energy of key intermediates *NOH and *OCH2-CH2OH on active sites and increase bond energy of C─C band, thereby improving the activity and selectivity for the formation of NH3 and GA. This work proposes a promising strategy for the simultaneous conversation of nitrate and PET plastic into high-value NH3 and GA.

Modulating Hydrogen Adsorption by Unconventional p-d Orbital Hybridization over Porous High-Entropy Alloy Metallene for Efficient Electrosynthesis of Nylon-6 Precursor.

Renewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment-unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx-involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high-entropy alloy PdCuAgBiIn metallene (HEA-PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6 %) and almost 100 % yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d-block metals and p-block metals could regulate the local electronic structure of active sites and induce electron localization of electron-rich Pd sites, which tunes the active hydrogen supply, facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C-N coupling to selectively produce C6H11NO.

Prognostic value of human papillomavirus cell-free DNA in cervical cancer patients: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients. METHODS: Searches were performed in MEDLINE, Embase, and CENTRAL from their inception until 26 November 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients according to the levels of HPV cell-free DNA. Data extraction and study quality assessment were performed independently by two authors. Pooled hazard ratios and 95% confidence intervals were calculated using the inverse-variance method for survival outcomes. RESULTS: Five studies were finally included in this meta-analysis. Blood samples were collected from 167 patients before treatment, with 150 individuals available for analysis at the end of treatment. Furthermore, 82 patients with available samples at 3 months post-treatment were included in the analysis. The pooled results indicated a significant association between positive HPV cell-free DNA at end of treatment and worse progression-free survival in patients with cervical cancer (pooled hazard ratio: 5.49; 95 % confidence interval: 2.85-10.58; I2: 0 %). Similar findings were observed in patients with detectable HPV cell-free DNA at 3 months post-treatment (pooled hazard ratio: 7.86; 95 % confidence interval: 3.32-18.60; I2: 0 %). However, the detection of HPV cell-free DNA before treatment was not significantly associated with progression-free survival (pooled hazard ratio: 0.97; 95 % confidence interval: 0.55-1.71; I2: 0 %). CONCLUSION: Cervical cancer patients testing positive for HPV cell-free DNA at the end of treatment or 3 months post-treatment displayed significantly poorer oncological outcomes compared to those testing negative. Thus, personalized monitoring of HPV cell-free DNA holds promise as a prognostic biomarker for patients with cervical cancer.

Heterointerface-Rich Ni3N/WO3 Hierarchical Nanoarrays for Efficient Glycerol Oxidation-Assisted Alkaline Hydrogen Evolution.

Glycerol oxidation-assisted water electrolysis has emerged as a cost-effective way of co-producing green hydrogen and HCOOH. Still, preparing highly selective and stable nickel-based metal electrocatalysts remains a challenge. Herein, heterostructure Ni3N/WO3 nanosheet arrays of bifunctional catalysts with large specific surface areas loaded on nickel foam (denoted as Ni3N/WO3/NF) were synthesized. This catalyst was for glycerol oxidation reaction (GOR) and hydrogen evolution reaction (HER) with excellent catalytic performance, a voltage saving of 267 mV compared to oxygen evolution reaction (OER), and a HER overpotential of 104 mV at 100 mA cm-2. The cell voltage in the assembled GOR//HER hybrid electrolysis system reaches 100 mA cm-2 at 1.50 V, 296 mV lower than the potential required for overall water splitting. This work demonstrates that replacing GOR with OER using a cost-effective and highly active Ni-based bifunctional electrocatalyst can make hybrid water electrolysis an energy-efficient, sustainable, and green strategy for hydrogen production.

Intact lung tissue and bronchoalveolar lavage fluid are both suitable for the evaluation of murine lung microbiome in acute lung injury.

BACKGROUND: Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome. METHODS AND RESULTS: To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury. CONCLUSION: This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract.

Interstitial Boron-Modulated Porous Pd Nanotubes for Ammonia Electrosynthesis.

Electrochemical conversion of nitrogen into ammonia at ambient conditions as a sustainable approach has gained significant attention, but it is still extremely challenging to simultaneously obtain a high faradaic efficiency (FE) and NH3 yield. In this work, the interstitial boron-doped porous Pd nanotubes (B-Pd PNTs) are constructed by combining the self-template reduction method with boron doping. Benefiting from distinctive one-dimensional porous nanotube architectonics and the incorporation of the interstitial B atoms, the resulting B-Pd PNTs exhibit high NH3 yield (18.36 µg h-1 mgcat.-1) and FE (21.95%) in neutral conditions, outperforming the Pd/PdO PNTs (10.4 µg h-1 mgcat.-1 and 8.47%). The present study provides an attractive method to enhance the efficiency of the electroreduction of nitrogen into ammonia by incorporating interstitial boron into porous Pd-based catalysts.

Case Report: A Rare Case of Primary Angiosarcoma of the Cervix with a Literature Review.

Primary angiosarcomas are a rare type of soft-tissue sarcomas that originate from endothelial cells. These sarcomas can develop in any part of the body and have a poor prognosis. However, they are commonly found in the skin of elderly white men, particularly on the scalp and head region. Primary angiosarcoma of the cervix is exceptionally rare. To date, only two cases of this disease have been reported worldwide. The diagnosis of the disease is difficult microscopically, requiring immunohistochemistry and genetic testing to distinguish. We report a recent case, in which the lesion was preoperatively considered a high-grade endometrial stromal sarcoma. A 35-year-old woman presented with vaginal bleeding and cervical erosions. A high-grade endometrial stromal sarcoma involving the cervix was considered and a modified radical hysterectomy was performed with bilateral salpingo-oophorectomy and sentinel lymph nodes resection. The gene diagnosis performed by fluorescence in situ hybridization for YWHAE translocation fusion was negative excluding a YWHAE-translocated high-grade endometrial stromal sarcoma. A primary angiosarcoma of the cervix was finally diagnosed. Primary angiosarcoma of the cervix is rare, and gynecologic pathologists do not know it well, so it is easy to be wrongly considered. Immunohistochemistry and genetic testing help confirm the diagnosis.

A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.

BACKGROUND: Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify. METHODS: An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. RESULTS: The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband's sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband's spermatozoa have high DNA fragmentation. CONCLUSIONS: It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.

Synthesis of hierarchical mordenite by solvent-free method for dimethyl ether carbonylation reaction.

A series of hierarchical mordenite (MOR) catalysts were synthesized by adding soft templates via the solvent-free method. The influence of different kinds of soft templates on the structure, morphology and acid sites of mordenite were systematically characterized. The characterization results revealed that the addition of soft templates could successfully introduce hierarchical structure into the system while maintaining good crystallinity. The specific surface area and pore volume became larger. Surfactants could also affect the amount and distribution of acid sites, which in turn would affect the dimethyl ether carbonylation activity. Compared with cationic and nonionic surfactants, the addition of anionic surfactants such as sodium dodecyl benzene sulfonate could result in more Al species to preferentially enter into the 8 member ring, thus enhancing the amount of active sites for the carbonylation reaction while weakening the strength. Meanwhile, the addition of sodium dodecyl benzene sulfonate could also reduce the number of strong acid sites in the 12 member ring and obviously improve the carbonylation performance.

Amorphous/crystalline RhFeP metallene for hydrazine-assisted water splitting.

Replacing the slow oxygen evolution reaction with favorable hydrazine oxidation reaction (HzOR) is a green and efficient way to produce hydrogen. In this work, we synthesize amorphous/crystalline RhFeP metallene via phase engineering and heteroatom doping. RhFeP metallene has good catalytic activity and stability for HER and HzOR, and only an ultralow voltage of 18 mV is required to achieve 10 mA cm-2in a two-electrode hydrazine-assisted water splitting system. The superior result is mainly ascribed to the co-doping of Fe and P and the formation of amorphous/crystalline RhFeP metallene with abundant phase boundaries, thereby adjusting electronic structure and increasing active sites.

Overall Spontaneous Water Splitting for Calcium Bismuthate Ca(BiO2)2: Flexible-Electronic-Controlled Band Edge Position and Adsorption-Site-Modulated Bond Strength.

Eco-friendly photocatalysts for water splitting, highly efficient in oxygen/hydrogen evolution reactions, hold great promise for the storage of inexhaustible solar energy and address environmental challenges. However, current common photocatalysts rarely exhibit both H2 and O2 production performances unless some regulatory measures, such as strain engineering, are implemented. Additionally, the extensive utilization of flexible electronics remains constrained by their high Young's modulus. Herein, on the basis of density functional theory calculations, we identify a novel spontaneous oxygen-producing two-dimensional Ca(BiO2)2 material, which can efficiently regulate the electronic structures of the surface active sites, optimize the reaction pathways, reduce the reaction energy barriers, and boost the overall water-splitting activity through biaxial strain modulation. In detail, an unstrained Ca(BiO2)2 monolayer not only possesses a suitable band gap value (2.02 eV) to fulfill the photocatalytic water-splitting band edge relationships but also holds favorable transport properties, excellent optical absorption across the visible light spectrum, and spontaneous oxygen production under neutral conditions. More excitingly, under application of a 7% biaxial tensile strain modulation with an ideal biaxial strength of 32.35 GPa nm, the Ca(BiO2)2 monolayer not only maintains its structural integrity but also exhibits a completely spontaneous reaction for photocatalytic hydrogen precipitation with superior optical absorption. This can primarily be attributed to the substantial reduction of the potential barrier through strain engineering as well as the weakening of bond energy resulting from changes of the adsorption site as calculated by crystal orbital Hamiltonian population analysis. This flexible stretchable electronic modulated the photocatalyst behavior and bond energy of O-Bi and O-Ca interactions, offering outstanding potential for photocatalytic water spontaneous oxygen and hydrogen evolution among all of the reported metal oxides, and is more likely to become a promising candidate for future flexible electronic devices.

UCHL-3 as a potential biomarker of ovarian cancer.

OBJECTIVE: This study explored promising prognostic and immune therapeutic candidate biomarkers for OC and determined the expression, prognostic value, and immune effects of UCHL3. METHODS: UCHL3 expression and clinical data were investigated using bioinformatic analysis. CCK8 and transwell assays were conducted to evaluate the impact of UCHL3 on proliferation and migration, and the effects of UCHL3 were further validated in a mouse model. Univariate and least absolute shrinkage and selection operator regression analyses were performed to construct a novel UCHL3-related prognostic risk model. Gene set enrichment analysis (GSEA) and immune analysis were performed to identify the significantly involved functions of UCHL3. Finally, bioinformatic analysis and immunohistochemistry were performed to explore the effect of UCHL3 on chemotherapy. RESULTS: UCHL3 expression was upregulated and associated with worse overall survival (OS) in OC. UCHL3 depletion repressed cell proliferation and migration both in vitro and in vivo. Furthermore, 237 genes were differentially expressed between the high and low UCHL3 expression groups. Subsequently, a UCHL3-related prognostic signature was built based on six prognostic genes (PI3, TFAP2B, MUC7, PSMA2, PIK3C2G, and NME1). Independent prognostic analysis suggested that age, tumor mutational burden, and RiskScore can be used as independent prognostic factors. The immune infiltration analysis and GSEA suggested that UCHL3 expression was related to the immune response. In addition, UCHL3 expression was higher in platinum-resistant OC patients than in platinum-sensitive patients. UCHL3 overexpression was associated with poorer OS. CONCLUSION: UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC.

Lattice Strain and Charge Redistribution of Pt Cluster/Ir Metallene Heterostructure for Ethylene Glycol to Glycolic Acid Conversion Coupled with Hydrogen Production.

Upgrading overall water splitting (OWS) system and developing high-performance electrocatalysts is an attractive way to the improve efficiency and reduce the consumption of hydrogen (H2 ) production from electrolyzed water. Here, a Pt cluster/Ir metallene heterojunction structure (Pt/Ir hetero-metallene) with a unique Pt/Ir interface is reported for the conversion of ethylene glycol (EG) to glycolic acid (GA) coupled with H2 production. With the assistance of ethylene glycol oxidation (EGOR), the Pt/Ir||Pt/Ir hetero-metallene two-electrode water electrolysis system exhibits a lower cell voltage of 0.36 V at 10 mA cm-2 . Furthermore, the Faradaic efficiency of EG to GA is as high as 87%. The excellent performance of this new heterostructure arise from the charge redistribution and strain effects induced by Pt-Ir interactions between the heterogeneous interfaces, as well as the larger specific surface area and more active sites due to the metallene structure.

Electronic structure engineering on Co-based metal-organic frameworks for concurrent electrocatalytic hydrogen generation and formate electrosynthesis.

A facile one-step solvothermal method was developed to synthesize Ir-doped Co-based metal-organic framework (CoIr-MOF) nanoarrays as a bifunctional electrocatalyst for water-glucose co-electrolysis. It was demonstrated that in situ incorporation of a low-content of Ir cations could modulate the electronic structure of Co active centers and thus boost the electrocatalytic performance towards both the hydrogen evolution reaction and glucose-to-formate oxidation reaction.