Ventilator-Associated Pneumonia Prediction Models Based on AI: Scoping Review.

Background: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation therapy that affects patients' treatments and prognoses. Owing to its excellent data mining capabilities, artificial intelligence (AI) has been increasingly used to predict VAP. Objective: This paper reviews VAP prediction models that are based on AI, providing a reference for the early identification of high-risk groups in future clinical practice. Methods: A scoping review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The Wanfang database, the Chinese Biomedical Literature Database, Cochrane Library, Web of Science, PubMed, MEDLINE, and Embase were searched to identify relevant articles. Study selection and data extraction were independently conducted by 2 reviewers. The data extracted from the included studies were synthesized narratively. Results: Of the 137 publications retrieved, 11 were included in this scoping review. The included studies reported the use of AI for predicting VAP. All 11 studies predicted VAP occurrence, and studies on VAP prognosis were excluded. Further, these studies used text data, and none of them involved imaging data. Public databases were the primary sources of data for model building (studies: 6/11, 55%), and 5 studies had sample sizes of <1000. Machine learning was the primary algorithm for studying the VAP prediction models. However, deep learning and large language models were not used to construct VAP prediction models. The random forest model was the most commonly used model (studies: 5/11, 45%). All studies only performed internal validations, and none of them addressed how to implement and apply the final model in real-life clinical settings. Conclusions: This review presents an overview of studies that used AI to predict and diagnose VAP. AI models have better predictive performance than traditional methods and are expected to provide indispensable tools for VAP risk prediction in the future. However, the current research is in the model construction and validation stage, and the implementation of and guidance for clinical VAP prediction require further research.

Dependence of evolution of Cyanobacteria superiority on temperature and nutrient use efficiency in a meso-eutrophic plateau lake.

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.

Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer.

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.

Interpreting and modelling the daily extreme sediment events in karst mountain watersheds.

Increasingly frequent extreme rainfall as a result of climate change is strongly damaging the global soil and water environment. However, few studies have focused on daily extreme sediment events (DESE) in heterogeneous karst watersheds based on long-term in-situ observations. This study quantitatively assessed the time effect of DESE on rainfall response, decoupled the impact of environmental factors on DESE by using structural equation modelling, and finally explored the modelling scheme of DESE based on the hybrid model. The results showed that DESE had the highest frequency of occurrence in May-July, with dispersed distribution in the value domain. Rainfall with a time lag of 1 day and a time accumulation of 2 or 3 days was an important contribution to DESE (P < 0.01, R = 0.47-0.68). Combined effects of environmental factors explained 53.6 %-64.1 % of the variation in DESE. Runoff and vegetation exerted the strongest direct and indirect effects on DESE, respectively (ß = 0.66/-0.727). Vegetation was the dominant driver of DESE in Dabanghe and Yejihe (ß = -0.725/-0.758), while the dominant driver in Tongzhihe was climate (ß = 0.743). In the future, the risk of extreme sediments should be prevented and resolved through the comprehensive regulation of multiple paths, such as runoff and vegetation. Hybrid models significantly improved the modelling performance of machine learning models. Generalized additive model-Extreme gradient boost had the best performance, while Partial least squares regression-Extreme gradient boost was the most valuable when considering performance and input data cost. Two methods can be used as recommended solutions for DESE modelling. This study provides new and in-depth insights into DESE in karst watersheds and helps the region develop forward-looking soil and water management models to cope with future extreme erosion hazards.

The role of NLRP3 inflammasome in aging and age-related diseases.

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Tailoring the density of states of Ni(OH)2 with Ni0 towards solar urea wastewater splitting.

Solar urea wastewater splitting is capable of producing hydrogen and degrading the urea pollutant simultaneously. Nickel hydroxide (Ni(OH)2) has been recognized as an effective cocatalyst for the urea oxidation reaction (UOR). But the lack of an efficient preparation method and a suitable Ni(OH)2 based cocatalyst limits the performances of solar urea wastewater splitting. Herein, a potential-cycling method is developed with a high-purity nickel plate serving as the counter electrode and nickel source in a three-electrode configuration. Spherical Ni0-doped Ni(OH)2 nanoparticles are successfully synthesized on the surface of TiO2 nanorod arrays. The photocurrent density of TiO2/Ni0:Ni(OH)2 can reach 0.56 mA cm-2 at 1.23 VRHE in 1 M NaOH and 0.33 M CO(NH2)2 mixed electrolyte under AM1.5G illumination, which is 1.75 and 1.93 times those of TiO2/Ni(OH)2 deposited using a normal potentiostatic method with nickel salt solution and pristine TiO2, respectively. Ni0 doping can significantly decrease the charge transfer resistance and provide a more favorable distribution of density of states of Ni(OH)2 for the UOR. Furthermore, Ni0:Ni(OH)2 decorated TiO2 photoanodes exhibit good photocurrent retention during 12 h continuous testing. This work expands the preparation technique of urea catalysts and the strategy for developing highly efficient nickel-based catalysts.

Food-derived peptides as novel therapeutic strategies for NLRP3 inflammasome-related diseases: a systematic review.

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both in vivo and in vitro models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP.

Ideal serum non-ceruloplasmin bound copper prediction for long-term treated patients with Wilson disease: a nomogram model.

Purpose: This study aimed to explore the factors associated with the optimal serum non-ceruloplasmin bound copper (NCBC) level and develop a flexible predictive model to guide lifelong therapy in Wilson disease (WD) and delay disease progression. Methods: We retrospectively collected clinical data from 144 patients hospitalized in the Encephalopathy Center of the first affiliated hospital of Anhui University of Chinese Medicine between May 2012 and April 2023. Independent variables were selected using variate COX and LASSO regressions, followed by multivariate COX regression analysis. A predictive nomogram was constructed and validated using the concordance index (C-index), calibration curves, and clinical decision curve analysis, of which nomogram pictures were utilized for model visualization. Results: A total of 61 (42.36%) patients were included, with an average treatment duration of 55.0 (range, 28.0, 97.0) months. Multivariate regression analysis identified several independent risk factors for serum NCBC level, including age of diagnosis, clinical classification, laminin liver stiffness measurement, and copper to zinc ratio in 24-h urinary excretion. The C-index indicated moderate discriminative ability (48 months: 0.829, 60 months: 0.811, and 72 months: 0.819). The calibration curves showed good consistency and calibration; clinical decision curve analysis demonstrated clinically beneficial threshold probabilities at different time intervals. Conclusion: The predictive nomogram model can predict serum NCBC level; consequently, we recommend its use in clinical practice to delay disease progression and improve the clinical prognosis of WD.

Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

Multi-modal transformer for fake news detection.

Fake news has already become a severe problem on social media, with substantially more detrimental impacts on society than previously thought. Research on multi-modal fake news detection has substantial practical significance since online fake news that includes multimedia elements are more likely to mislead users and propagate widely than text-only fake news. However, the existing multi-modal fake news detection methods have the following problems: 1) Existing methods usually use traditional CNN models and their variants to extract image features, which cannot fully extract high-quality visual features. 2) Existing approaches usually adopt a simple concatenate approach to fuse inter-modal features, leading to unsatisfactory detection results. 3) Most fake news has large disparity in feature similarity between images and texts, yet existing models do not fully utilize this aspect. Thus, we propose a novel model (TGA) based on transformers and multi-modal fusion to address the above problems. Specifically, we extract text and image features by different transformers and fuse features by attention mechanisms. In addition, we utilize the degree of feature similarity between texts and images in the classifier to improve the performance of TGA. Experimental results on the public datasets show the effectiveness of TGA*. * Our code is available at https://github.com/PPEXCEPED/TGA.

Reverse transcription recombinase-aided amplification assay combined with a lateral flow dipstick for detection of duck Tembusu virus.

Duck Tembusu virus disease, caused by duck Tembusu virus (DTMUV), brings great harm to duck industry. Early diagnosis is of great significance for the prevention and control of this disease. In order to develop a specific and sensitive method for rapid diagnosis of DTMUV, reverse-transcriptase recombinase aided amplification combined with lateral flow dipstick (RT-RAA-LFD) method for detection of DTMUV was established. Firstly, downstream primer was labeled with biotin and probe was labeled with FAM, and primer concentration, reaction time, and reaction temperature were optimized. Then, the specificity and sensitivity of this method was investigated. The results of specificity test showed that it had no cross reaction with other common pathogens such as low pathogenic avian influenza virus (AIV), Newcastle disease virus (NDV), duck hepatitis A virus (DHV), and duck Reovirus. The results of sensitivity test showed that the minimum detection limit of this method was 10 copies/µL, which was 1000 times than conventional RT-PCR (104 copies/µL), and equivalent to that of fluorescent quantitative PCR. Furthermore, this RT-RAA-LFD method demonstrated excellent intragroup and intergroup consistency. Finally, the RT-RAA-LFD assay and real-time PCR were both utilized to examine 58 clinical samples concurrently. The results showed that the RT-RAA-LFD method (5/58) was more sensitive than the fluorescence quantitative PCR method (4/58). In summary, RT-RAA-LFD method established in this study had a strong specificity and high sensitivity, which provided technical support for clinical detection of DTMUV.

Porous pillararene-based polymer as adsorbent and solid disinfectant for water treatment.

Pillararene polymers have been widely used as excellent adsorbents for water treatment, but pillararene polymers with ultra-high specific surface area and versatility are still rarely reported. Herein, a quaternary ammonium salt modified pillar [5] arene polymer, QPBP [5], with specific surface area of 1844 m2 g-1 was successfully synthesized. Since QPBP [5] has abundant different adsorption sites, it exhibits excellent performance for the simultaneously removal of organic pollutants with different charges from water. The selected three model pollutants, Rhodamine B (RhB, positively charged), Sulfamethazine (SMT, electrically neutral) and Fulvic acid (FA, negatively charged), could be rapidly and efficiently removed from water by QPBP [5] within 10 min, which are much faster than them by most of the reported adsorbents. RhB and SMT are mainly adsorbed through hydrophobic interactions with the QPBP [5] surface, while FA is mainly removed through ion exchange. In addition, QPBP [5] also showed excellent reusability and adsorption performance for the environmentally relevant concentration of pollutants. Furthermore, the quaternary ammonium groups on QPBP [5] makes it a solid disinfectant with excellent antibacterial properties. In conclusion, QPBP [5] is a promising multifunctional adsorbent for the treatment of complex pollutants in water.

Expression and immunogenicity of recombinant porcine epidemic diarrhea virus Nsp9.

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, which leads to significant economic losses. Coronavirus nonstructural protein 9 (Nsp9) is an essential RNA binding protein for coronavirus replication, which renders it a promising candidate for developing antiviral drugs and diagnosis targeting PEDV. In this study, PEDV Nsp9 protein fused with MBP protein and His-tag were expressed and purified in Escherichia coli. Furthermore, immunization of MBP-Nsp9 enhances both humoral and cellular immunity responses as compared with that of His-Nsp9 protein. Finally, the swine immunization showed that Nsp9 protein could stimulate the swine immunity system to carry out humoral immunity, and the generated antibody could inhibit the proliferation of PEDV in Vero cells. Altogether, our data provide direct evidence for the immunogenicity of PEDV Nsp9, which sheds light on the future developments of anti-PEDV drugs and vaccines for PED prevention.

Unequal crossing over between CYP11B2 and CYP11B1 causes 11 ß -hydroxylase deficiency in a consanguineous family.

Cytochrome P450 (CYP) family CYP11B2/CYP11B1 chimeric genes have been shown to arise from unequal crossing over of the genes encoding aldosterone synthase (CYP11B2) and 11ß-hydroxylase (CYP11B1) during meiosis. The activity deficiency or impaired activity of aldosterone synthase and 11ß-hydroxylase resulting from these chimeric genes are important reasons for 11ß-hydroxylase deficiency (11ß-OHD). Here，two patients with pseudoprecocious puberty and hypokalemia hypertension and three carriers in a consanguineous marriage family were studied. A single CYP11B2/CYP11B1 chimera consisting of the promoter and exons 1 through 5 of CYP11B2, exons 8 and 9 of CYP11B1, and a breakpoint consisting of part of exon 6 of CYP11B2 and part of exon 6, intron 6, and exon 7 of CYP11B1 were detected in the patients and carriers. At the breakpoint of the chimera, a c 0.1086 G > C ( p.Leu.362 =) synonymous mutation in exon 6 of CYP11B2, a c 0.1157 C＞G(p. A386V) missense mutation in exon 7 of CYP11B1, and an intronic mutation in intron 6 were detected. The allele model of the CYP11B2/CYP11B1 chimera demonstrated homozygosity and heterozygosity in the patients and the carriers, respectively. Molecular docking and enzymatic activity analyses indicated that the CYP11B2/CYP11B1 chimeric protein interacted with the catalytic substrate of aldosterone synthase and had similar enzymatic activity to aldosterone synthase. Our study indicated that deletion of CYP11B1 and CYP11B2 abolished the enzymatic activity of 11 ß-hydroxylase and aldosterone synthase; however, the compensation of the enzymatic activity of aldosterone synthase by the CYP11B2/CYP11B1 chimeric protein maintained normal aldosterone levels in vitro. All of the above findings explained the 11ß-OHD phenotypes of the proband and patients in the family.

Clinical features analysis of Kawasaki disease with abdominal symptoms as the first manifestation.

To investigate the clinical characteristics of Kawasaki disease (KD) presenting with abdominal manifestation as the first manifestation. Our findings may help improve the cognition of KD with abdominal complications, and avoid misdiagnosis and missed diagnosis. A retrospective analysis was conducted of 1490 KD patients admitted to Shengjing Hospital between January 2019 and March 2022. Clinical characteristics, related factors, and prognosis of KD with abdominal manifestation as first manifestation were analyzed. Based on the presenting symptoms, patients were divided into gastrointestinal symptom group (n = 141), liver dysfunction group (n = 55), and control group (n = 1294). In the gastrointestinal group, diarrhea [100 cases (70.9%)], vomiting [55 cases (39.0%)], and abdominal pain [34 cases (24.1%)] were the most common symptoms at onset. 8 cases (5.7%) were complicated with pseudo-intestinal obstruction, 6 cases (4.3%) with ischemic colitis, 5 cases (3.5%) with pancreatitis, 2 cases (1.4%) with appendicitis, and 1 case (0.7%) with cholecystitis. Comparied to ordinary gastroenteritis caused by infection, gastroenteritis with KD has longer fever duration before treatment, higher WBC, PLT, CRP, AST levels and lower albumin levels. All patients in the liver dysfunction group had elevated transaminases, and 19 patients (34.5%) presented with jaundice. In the gastrointestinal group, the average hospital stay was 10.3 days, and the incidence of IVIG unresponsiveness and coronary artery lesion were 18.4% and 19.9%, respectively, which were significantly higher than that in the control group. In the liver dysfunction group, the average hospital stay (11.18 days), incidence of IVIG unresponsiveness (25.5%), and incidence of coronary artery lesion (29.1%) were significantly higher than that in the control group. On multivariate logistic regression analysis, gastrointestinal involvement, fever duration, ALT, PLT, and CRP were identified as risk factors for CAL, younger age, gastrointestinal involvement and fever duration were risk factors for IVIG unresponsiveness.  Conclusion: KD with gastrointestinal involvement is associated with a higher risk of IVIG unresponsiveness and coronary artery lesion. KD should be considered in the differential diagnosis of children with acute fever, especially those with gastrointestinal involvement and liver dysfunction. What is Known: • Fever duration, PLT, and CRP were identified as risk factors for CAL. Timely diagnosis and application of IVIG treatment can avoid exploratory laparotomy for ileus, appendectomy for misdiagnosed appendicitis, colonoscopy for misdiagnosed inflammatory bowel disease, and reduce the complications of CAL and IVIG unresponsiveness. What is New: • Abdominal symptoms as the first manifestation can be an independent risk factor for CAL and IVIG unresponsiveness. KD should be considered in the differential diagnosis of children with acute fever, especially those with gastrointestinal symptoms or liver dysfunction. • Gastroenteritis in KD group had longer fever duration before treatment, accompanied with higher WBC, PLT, CRP, AST levels and lower albumin levels than those gastroenteritis caused by infection. Therefore, high attention should be paid to the possibility of KD when gastroenteritis accompanied by along fever duration, high WBC, PLT, CRP, AST level or lowalbumin level.

Copper homeostasis and cuproptosis in cardiovascular disease therapeutics.

Copper (Cu) homeostasis is gaining increasing attention in human health as both Cu overload and deficiency evokes pathological changes including cardiovascular diseases (CVDs). Cu supplementation, nanocarriers, and chelators have all exhibited therapeutic promise in some human diseases, although how Cu dyshomeostasis and cuproptosis, a novel form of regulated cell death, contribute to CVD pathology remains elusive. Here, we discuss Cu dyshomeostasis and the potential role of cuproptosis in various CVDs. We evaluate underlying cellular mechanisms, aiming to provide some insights regarding the utility of targeting Cu dyshomeostasis and cuproptosis as a novel strategy in the management of CVDs.

Electrochemical Behavior of ß-Cyclodextrin-Ni-MOF-74/Reduced Graphene Oxide Sensors for the Ultrasensitive Detection of Rutin.

Rutin, as a biological flavonoid glycoside, has very important medicinal value. The accurate and rapid detection of rutin is of great significance. Herein, an ultrasensitive electrochemical rutin sensor based on ß-cyclodextrin metal-organic framework/reduced graphene oxide (ß-CD-Ni-MOF-74/rGO) was constructed. The obtained ß-CD-Ni-MOF-74 was characterized by X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and nitrogen adsorption and desorption. The ß-CD-Ni-MOF-74/rGO presented good electrochemical properties benefiting from the large specific surface area and good adsorption enrichment effect of ß-CD-Ni-MOF-74 and the good conductivity of rGO. Under optimal conditions for the detection of rutin, the ß-CD-Ni-MOF-74/rGO/GCE showed a wider linear range (0.06-1.0 µM) and lower detection limit (LOD, 0.68 nM, (S/N = 3)). Furthermore, the sensor shows good accuracy and stability for the detection of rutin in actual samples.

Retyping and molecular pathology diagnosis of dyschromatosis universalis hereditaria.

Dyschromatosis universalis hereditaria (DUH) is characterized by diffuse symmetrically distributed hypopigmented macules mixed with hyperpigmentation. DUH is divided into three types by Online Mendelian inheritance in man (OMIM) that is, DUH1 (OMIM 127500), DUH2 (OMIM 612715) and DUH3 (OMIM 615402) according to the different linkage regions. Although each condition possesses corresponding phenotypic characteristics and the prognosis for each is somewhat different, these disorders are highly overlapped and difficult to differentiate in the clinical setting. Our latest study reveals a novel DUH subtype that presents a mild phenotype of pigmentation anomalies and is named PER3rs772027021 SNP related DUH or DUH4 by us, which make the DUH subtype can be further retyped. Heterozygous distribution or mosaic-like distribution of melanin is a newly discovered pathological features that is uniquely demonstrated in the affected layers of DUH1 and DUH4 patients. In this review, DUH is further divided into four subtypes according the causative genes and their mutational sites, and the mutation regions described in the previous reports. To make an accurate diagnosis, we suggest that Sanger sequencing or the target region sequencing (TRS) to the candidate causative genes related melanogenesis may be the most effective and convenient method of clinical diagnosis or/and prenatal diagnosis for DUH and DUH-like patients. More importantly, heterozygous distribution or mosaic-like distribution of melanin can be utilized for differential diagnosis of DUH. We also investigate the underlying molecular mechanism to form mosaic-like melanin in the affected layers of hyper- and/or hypo-pigmented macules from DUH1 and DUH4 patients. This review provides a molecular and pathological delineation of four types of DUH and aims to establish a concise diagnostic strategy to allow clinical dermatologists to make an accurate diagnosis.