Multidimensional visualization of the dynamic evolution of Li metal via in situ/operando methods.

The growing demands for high-energy density electrical energy storage devices stimulate the coupling of conversion-type cathodes and lithium (Li) metal anodes. While promising, the use of these "Li-free" cathodes brings new challenges to the Li anode interface, as Li needs to be dissolved first during cell operation. In this study, we have achieved a direct visualization and comprehensive analysis of the dynamic evolution of the Li interface. The critical metrics of the interfacial resistance, Li growth, and solid electrolyte interface (SEI) distribution during the initial dissolution/deposition processes were systematically investigated by employing multidimensional analysis methods. They include three-electrode impedance tests, in situ atomic force microscopy, scanning electrochemical microscopy, and cryogenic scanning transmission electron microscopy. The high-resolution imaging and real-time observations show that a loose, diffuse, and unevenly distributed SEI is formed during the initial dissolution process. This leads to the dramatically fast growth of Li during the subsequent deposition, deviating from Fick's law, which exacerbates the interfacial impedance. The compactness of the interfacial structure and enrichment of electrolyte species at the surface during the initial deposition play critical roles in the long-term stability of Li anodes, as revealed by operando confocal Raman spectroscopic mapping. Our observations relate to ion transfer, morphological and structural evolution, and Li (de)solvation at Li interfaces, revealing the underlying pathways influenced by the initial dissolution process, which promotes a reconsideration of anode investigations and effective protection strategies.

Endocytosis triggers V-ATPase-SYK-mediated priming of cGAS activation and innate immune response.

The current view of nucleic acid-mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)-mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK-mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

Amorphous AlOCl Compounds Enabling Nanocrystalline LiCl with Abnormally High Ionic Conductivity.

LiCl is a promising solid electrolyte, providing it possesses high ionic conductivity. Numerous efforts have been made to enhance its ionic conductivity through aliovalent doping. However, aliovalent substitution changes the intrinsic structure of LiCl, compromising its cost-effectiveness and electrochemical stability. Here, we report nanocrystalline LiCl embedded in amorphous AlOCl compounds with a heterogeneous structure to enhance its ionic conductivity. Nanocrystallization enlarges the LiCl unit cell, while amorphization facilitates interfacial ion transport. As a result, the amorphous AlOCl-modified LiCl nanocrystal (AlOCl-nanoLiCl) demonstrates a high ionic conductivity of 1.02 mS cm-1, which is 5 orders of magnitude higher than that of LiCl. Additionally, it exhibits high oxidative stability, low cost ($19.87 US kg-1), and low Young's modulus (2-3 GPa). When AlOCl-nanoLiCl is coupled with Li-rich cathodes (Li1.17Mn0.55Ni0.24Co0.05O2, 4.8 V vs Li+/Li), all-solid-state batteries exhibit remarkable long-term cycling stability (>1000 cycles). This work presents a novel strategy to enhance the ionic conductivity of alkaline chlorides without compromising their intrinsic advantages.

Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury.

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

Photosynthesis regulates tillering bud elongation and nitrogen-use efficiency via sugar-induced NGR5 in rice.

Rice tillering is one of the most important agronomical traits largely determining grain yield. Photosynthesis and nitrogen availability are two important factors affecting rice tiller bud elongation; however, underlying mechanism and their cross-talk is poorly understood. Here, we used map-based cloning, transcriptome profiling, phenotypic analysis, and molecular genetics to understand the roles of the Decreased Tiller Number 1 (DTN1) gene that encodes the fructose-1,6-bisphosphate aldolase and involves in photosynthesis required for light-induced axillary bud elongation in rice. Deficiency of DTN1 results in the reduced photosynthetic rate and decreased contents of sucrose and other sugars in both leaves and axillary buds, and the reduced tiller number in dtn1 mutant could be partially rescued by exogenous sucrose treatment. Furthermore, we found that the expression of nitrogen-mediated tiller growth response 5 (NGR5) was remarkably decreased in shoot base of dtn1-2, which can be activated by sucrose treatment. Overexpression of NGR5 in the dtn1-2 could partially rescue the reduced tiller number, and the tiller number of dtn1-2 was insensitive to nitrogen supply. This work demonstrated that the sugar level regulated by photosynthesis and DTN1 could positively regulate NGR5 expression, which coordinates the cross-talk between carbon and nitrate to control tiller bud outgrowth in rice.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Suitability of reduced dose glucocorticoids therapy regimen for antibody-associated vasculitis patients with TB: a retrospective study.

INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.

Hierarchical Hollow TiO2@Bi2WO6 with Light-Driven Excited Bi(3-x)+ Sites for Efficient Photothermal Catalytic CO2 Reduction.

Converting CO2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3-x)+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 µmol h-1 g-1, which is 15 and 4.7 times higher than that of pure Bi2WO6 and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2 into CO over our TiO2@Bi2WO6 proceeds via two important intermediates, including COO- and COOH-. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2 conversion.

The clinical value of serum creatinine to bilirubin ratio in predicting the severity and prognosis of acute pancreatitis.

BACKGROUND: Bilirubin (BIL) and creatinine (Cr) have been used as potential early predictors of the severity of many diseases. A recent study found that the Cr to BIL ratio (CTR) was more sensitive and specific than either serum Cr or BIL alone. Our research focused on the clinical significance of CTR in evaluating the severity and prognosticating outcomes of acute pancreatitis (AP) in patients. METHODS: Patients diagnosed with AP at the First Affiliated Hospital of Guangdong Pharmaceutical University between July 1, 2016, and December 31, 2020 were included. The analysis then focused on examining the relationship between CTR levels and the severity of the illness, the occurrence of complications, and the prognosticating outcomes for individuals diagnosed with AP. A total of 286 AP patients were enrolled. RESULTS: Multivariate regression analyses showed that patients with AP with increased CTR levels had a poorer disease (easier to develop severe AP); higher Ranson, and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores; higher incidence of organ failure (acute heart failure, acute kidney injury and acute myocardial infarction ); and leading to a worse prognosis characterized more by frequent use of vasoactive and diuretic agents. When CTR >14.05, AP patients had increased occurrence of AHF and AKI, higher 30-day all-cause mortality rates, more frequently using vasoactive agent and diuretic agent. Besides, the disease severity scores and hospital stays were markedly increased. CONCLUSION: Patients with AP who exhibit higher CTR levels tend to experience escalating disease severity, more complications, and a poorer outcome compared with those with lower CTR levels.

Enhancing Ozone Decomposition in Humid Environments through Carbon Doping to Disrupt the Hydrogen Bond Network in Mullite YMn2O5.

The strong adsorption of water molecules at the active site of the catalyst presents significant challenges in ozone decomposition, particularly at room temperature and in humid environments. To address this issue, we doped carbon atoms into the Mn-mullite YMn2O5 catalyst to replace oxygen, resulting in efficient and stable ozone decomposition under highly humid conditions. Utilizing DFT calculations, our study demonstrated that carbon doping disrupts hydrogen bond networks on the catalyst surface, thereby reducing water adsorption. Furthermore, carbon doping regulated the electronic structure of active sites, fundamentally reversing the adsorption strength of water and ozone molecules, which avoids the decline in catalytic activity caused by competitive water adsorption. Experimentally, under room temperature and relative humidity (RH) 50%, the carbon-doped YMn2O5 catalyst maintained 100% conversion in decomposing 100 ppm of ozone for at least 24 h, surpassing the most reported catalysts against water poisoning. Furthermore, the utilization of a carbon-doped mullite-loaded air cleaner demonstrated promising application in degrading ozone. The approach of enhancing catalyst water resistance through carbon doping, which disrupts hydrogen bonds, provided valuable insights into the design of stable and efficient room-temperature ozonolysis catalysts.

Discovery of non-sulfonamide carbonic anhydrase IX inhibitors through structure-based virtual screening.

Carbonic anhydrase IX (CA IX) is a subtype of the human carbonic anhydrase (hCA) family and exhibits high expression in various solid tumors, rendering it a promising target for tumor therapy. Currently, marketed carbonic anhydrase inhibitors (CAIs) are primarily composed of sulfonamides derivatives, which may have impeded their potential for further expansion. Therefore, we have developed a structure-based virtual screening approach to explore novel CAIs exhibiting distinctive structures and anti-tumor potential in the FDA database. In vitro experiments demonstrated that 3-pyridinemethanol (0.42 µM), procodazole (8.35 µM) and pamidronic acid (8.51 µM) exhibited inhibitory effects on CA IX activity. The binding stability and interaction mode between the CA IX and the hit compounds are further investigated through molecular dynamics simulations and binding free energy calculations. Furthermore, the ADME/Tox prediction results indicated that these compounds exhibited favorable pharmacological properties and minimal toxic side effects. Our study successfully applied computational strategies to discover three non-sulfonamide inhibitors of carbonic anhydrase IX (CA IX) that demonstrate inhibitory activity in vitro. These findings have significant implications for the development of CA IX inhibitors and anti-tumor drugs, contributing to their progress in the field.

Cyanotic Nephropathy in an Adult Patient with Eisenmenger Syndrome: A Case Report and Literature Review.

INTRODUCTION: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. CASE PRESENTATION: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. CONCLUSION: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

Effect of blockage of Trem1 on the M1 polarization of macrophages in the regulation dental pulp inflammation.

Dental pulp inflammation is a common and significant factor related to poor dental prognosis. Current treatment strategies primarily concentrate on managing the inflammatory response, with specific targets for intervention still under investigation. Triggering receptors expressed on myeloid cells (TREMs) are a group of receptor molecules extensively present on myeloid cell surfaces, crucial in the regulation of inflammatory process. Our analysis of transcriptomic sequencing data from clinical pulp samples of dataset GSE77459 and animal models revealed up-regulation of Trem1 during pulpitis. Administration of the Trem1-blocking peptide LP17 led to lower (more than 1-fold) levels of several pro-inflammatory factors and inhibition of M1 macrophage polarization both in vivo and in vitro. This study of the expression patterns and functions of Trem1 in the development of dental pulp inflammation provides novel insights into the therapeutic strategies for clinical pulpitis.

A novel compound heterozygous PCDH15 variants is associated with arRP in a Chinese pedigree.

BACKGROUND: Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 variants and RP. METHODS: In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing (WES). The variants were validated in the family members by Sanger sequencing and co-segregation analysis. RESULTS: Novel compound heterozygous, Frame shift variants of the PCDH15 gene, NM_001384140.1:c.4368 - 2147_4368-2131del and NM_001384140.1:c exon19:c.2505del: p. T836Lfs*6 were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species. CONCLUSION: This is the first study to identify novel compound heterozygous variants c.4368 - 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing variants, and extending the variant spectra. All above findings may be contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.

Prenatal diagnosis of interrupted aortic arch using high-definition flow render mode and spatiotemporal image correlation.

OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.

Prenatal Diagnosis of Persistent Left Superior Vena Cava Using High-Definition Flow Render Mode and Spatiotemporal Image Correlation.

OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.

Urinary heavy metals and overall survival of advanced high-grade serous ovarian cancer: A nested case-control study in China.

BACKGROUND: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis. OBJECTIVE: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC). METHODS: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models. RESULTS: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures. CONCLUSIONS: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings.