Development and validation of a nomogram predictive model for cognitive impairment in cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes. Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD. Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA). Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set. Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition.

Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Well-defined survival outcome disparity across age cutoffs at 45 and 60 for medullary thyroid carcinoma: a long-term retrospective cohort study of 3601 patients.

Background: Medullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages. Methods: 3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied. Results: A linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45-50, 50-55, and 55-60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly "5%" increase in MTC-specific death risks and an approximately "3 times" increase in non-MTC-specific death risks. Conclusions: The survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.

1,25-Dihydroxyvitamin D3 reduces early mortality post severe burn injury via alleviating endotoxemia, oxidative stress and inflammation.

Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.

Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.

Mitotic catastrophe (MC), which occurs under dysregulated mitosis, represents a fascinating tactic to specifically eradicate tumor cells. Whether pyroptosis can be a death form of MC remains unknown. Proteasome-mediated protein degradation is crucial for M-phase. Bortezomib (BTZ), which inhibits the 20S catalytic particle of proteasome, is approved to treat multiple myeloma and mantle cell lymphoma, but not solid tumors due to primary resistance. To date, whether and how proteasome inhibitor affected the fates of cells in M-phase remains unexplored. Here, we show that BTZ treatment, or silencing of PSMC5, a subunit of 19S regulatory particle of proteasome, causes G2- and M-phase arrest, multi-polar spindle formation, and consequent caspase-3/GSDME-mediated pyroptosis in M-phase (designated as mitotic pyroptosis). Further investigations reveal that inhibitor of WEE1/PKMYT1 (PD0166285), but not inhibitor of ATR, CHK1 or CHK2, abrogates the BTZ-induced G2-phase arrest, thus exacerbates the BTZ-induced mitotic arrest and pyroptosis. Combined BTZ and PD0166285 treatment (named BP-Combo) selectively kills various types of solid tumor cells, and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 monotreatment. Studies using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment, and no obvious toxicity is observed in BP-Combo-treated mice. These findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase, characterize pyroptosis as a new death form of mitotic catastrophe, and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

Arteriovenous malformation-related headache and seizures in pregnancy masquerading as eclampsia: A case report.

OBJECTIVE: Cerebral arteriovenous malformation during pregnancy is rare but lethal disease that usually present with new-onset seizures and headaches mimicking eclampsia. We report a rare case of cerebral arteriovenous malformation with abrupt seizures in the third trimester. CASE REPORT: A 28-year-old primipara was brought to our emergency department at 32 6/7 weeks of gestation with new-onset acute seizures and hypertension. Owing to neurological deterioration, the patient underwent emergency cesarean delivery. However, 24 h after cesarean delivery and eclampsia treatment, the seizures worsened. Computed tomography and magnetic resonance imaging showed unruptured arteriovenous malformation of the right frontal lobe. Subsequently, intraarterial embolization was performed. The patient was discharged 5 days after surgery without neurological sequelae or obstetric complications. CONCLUSION: This case report highlights the differential diagnoses of sudden new-onset seizures in late pregnancy for obstetricians and emergency medicine physicians. Lethal cerebral diseases, apart from eclampsia, should be considered during pregnancy.

Development of a long-term care service integration self-assessment tool.

The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.

Phylogeny and taxonomy of two new species in Dictyosporiaceae (Pleosporales, Dothideomycetes) from Guizhou, China.

Two novel species within the family Dictyosporiaceae are described and illustrated from terrestrial habitats on dead culms of bamboo and an unidentified plant, respectively. Through morphological comparisons and the multi-locus phylogenetic analyses of combined LSU, ITS, SSU, and tef1-α sequence dataset, two species, Gregaritheciumbambusicola, Pseudocoleophomaparaphysoidea are identified. Phylogenetically, both species clustered into a monophyletic clade with strong bootstrap support. Gregaritheciumbambusicola sp. nov. can be distinguished from other species within the genus based on its almost straight ascospores. Pseudocoleophomaparaphysoidea sp. nov. differs from other species in its conidiogenous cells intermixed with paraphyses, longer conidiogenous cells and larger conidia. The identification of this lineage contributes to our understanding of the classification of Dictyosporiaceae.

Two new species of Paraphlomis (Lamiales, Lamiaceae) from limestone karsts in Guangdong Province, China.

Paraphlomisqingyuanensis and P.baiwanensis (Lamiaceae), two new species from the limestone area in Guangdong Province, China, are described. Morphologically, both species belong to P.ser.Subcoriaceae C.Y. Wu & H.W. Li. A close relationship between the two new and P.subcoriacea was revealed by molecular phylogenetic analyses based on ETS and ITS. Further morphological and population genetic evidence indicated that they are distinct species in Paraphlomis. According to the IUCN Red List Categories and Criteria, P.qingyuanensis and P.baiwanensis were assessed as Endangered (EN) and Deficient (DD), respectively.

Developing and validating a predictive model of delivering large-for-gestational-age infants among women with gestational diabetes mellitus.

BACKGROUND: The birth of large-for-gestational-age (LGA) infants is associated with many short-term adverse pregnancy outcomes. It has been observed that the proportion of LGA infants born to pregnant women with gestational diabetes mellitus (GDM) is significantly higher than that born to healthy pregnant women. However, traditional methods for the diagnosis of LGA have limitations. Therefore, this study aims to establish a predictive model that can effectively identify women with GDM who are at risk of delivering LGA infants. AIM: To develop and validate a nomogram prediction model of delivering LGA infants among pregnant women with GDM, and provide strategies for the effective prevention and timely intervention of LGA. METHODS: The multivariable prediction model was developed by carrying out the following steps. First, the variables that were associated with LGA risk in pregnant women with GDM were screened by univariate analyses, for which the P value was < 0.10. Subsequently, Least Absolute Shrinkage and Selection Operator regression was fit using ten cross-validations, and the optimal combination factors were selected by choosing lambda 1se as the criterion. The final predictors were determined by multiple backward stepwise logistic regression analysis, in which only the independent variables were associated with LGA risk, with a P value < 0.05. Finally, a risk prediction model was established and subsequently evaluated by using area under the receiver operating characteristic curve, calibration curve and decision curve analyses. RESULTS: After using a multistep screening method, we establish a predictive model. Several risk factors for delivering an LGA infant were identified (P < 0.01), including weight gain during pregnancy, parity, triglyceride-glucose index, free tetraiodothyronine level, abdominal circumference, alanine transaminase-aspartate aminotransferase ratio and weight at 24 gestational weeks. The nomogram's prediction ability was supported by the area under the curve (0.703, 0.709, and 0.699 for the training cohort, validation cohort, and test cohort, respectively). The calibration curves of the three cohorts displayed good agreement. The decision curve showed that the use of the 10%-60% threshold for identifying pregnant women with GDM who are at risk of delivering an LGA infant would result in a positive net benefit. CONCLUSION: Our nomogram incorporated easily accessible risk factors, facilitating individualized prediction of pregnant women with GDM who are likely to deliver an LGA infant.

Chemical space exploration with Molpher: Generating and assessing a glucocorticoid receptor ligand library.

Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery of new biologically active compounds. In this study, we present a detailed analysis of the chemical library of potential glucocorticoid receptor (GR) ligands generated by the molecular generator, Molpher. To generate the targeted GR library and construct the classification models, structures from the ChEMBL database as well as from the internal IMG library, which was experimentally screened for biological activity in the primary luciferase reporter cell assay, were utilized. The composition of the targeted GR ligand library was compared with a reference library that randomly samples chemical space. A random forest model was used to determine the biological activity of ligands, incorporating its applicability domain using conformal prediction. It was demonstrated that the GR library is significantly enriched with GR ligands compared to the random library. Furthermore, a prospective analysis demonstrated that Molpher successfully designed compounds, which were subsequently experimentally confirmed to be active on the GR. A collection of 34 potential new GR ligands was also identified. Moreover, an important contribution of this study is the establishment of a comprehensive workflow for evaluating computationally generated ligands, particularly those with potential activity against targets that are challenging to dock.

Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis (P=0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P=0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis (P=0.007, log-rank test) and higher IPI score (63% vs. 30%, P=0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD (MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH, SLC1A1, CD96, INPP4B, and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN. Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.

Racial difference in receiving computed tomography for head injury patients in emergency departments.

STUDY OBJECTIVE: Prior studies have suggested potential racial differences in receiving imaging tests in emergency departments (EDs), but the results remain inconclusive. In addition, most prior studies may only have limited racial groups for minority patients. This study aimed to investigate racial differences in head computed tomography (CT) administration rates in EDs among patients with head injuries. METHODS: Patients with head injuries who visited EDs were examined. The primary outcome was patients receiving head CT during ED visits, and the primary exposure was patient race/ethnicity, including Asian, Hispanic, Non-Hispanic Black (Black), and Non-Hispanic White (White). Multivariable logistic regression analyses were performed using the National Hospital Ambulatory Medical Care Survey database, adjusting for patients and hospital characteristics. RESULTS: Among 6130 patients, 51.9% received a head CT scan. Asian head injury patients were more likely to receive head CT than White patients (59.1% versus 54.0%, difference 5.1%, p < 0.001). This difference persisted in adjusted results (odds ratio, 1.52; 95% CI, 1.06-2.16, p = 0.022). In contrast, Black and Hispanic patients have no significant difference in receiving head CT than White patients after the adjustment. CONCLUSIONS: Asian head injury patients were more likely to receive head CT than White patients. This difference may be attributed to the limited English proficiency among Asian individuals and the fact that there is a wide variety of different languages spoken by Asian patients. Future studies should examine rates of receiving other diagnostic imaging modalities among different racial groups and possible interventions to address this difference.

Immunotoxicity and oxidative damage in Litopenaeus vannamei induced by polyethylene microplastics and copper co-exposure.

This study examines the combined effects of polyethylene microplastics (PE-MP) and copper (Cu2+) on the immune and oxidative response of Litopenaeus vannamei. PE-MP adsorbed with Cu2+ at 2.3, 6.8, and 16.8 ng (g shrimp)-1) were injected into L. vannamei. Over 14 days, survival rates were monitored, and immune and oxidative stress parameters were assessed. The results showed that combined exposure to PE-MP and Cu2+ significantly reduced the survival rate and decreased total haemocyte count. Immune-related parameters (phagocytic rate, phenoloxidase and superoxide dismutase (SOD)) and antioxidant-related parameters (SOD, catalase and glutathione peroxidase mRNA and enzyme) also decreased, while respiratory burst activity significantly increased, indicating immune and antioxidant system disruption. Additionally, there was a significant increase in oxidative stress, as measured by malondialdehyde levels. Histopathological analysis revealed severe muscle, hepatopancreas, and gill damage. These results suggest that simultaneous exposure to PE-MP and Cu2+ poses greater health risks to white shrimp.

Self-Organization of Sinusoidal Vessels in Pluripotent Stem Cell-derived Human Liver Bud Organoids.

The induction of tissue-specific vessels in in vitro living tissue systems remains challenging. Here, we directly differentiated human pluripotent stem cells into CD32b + putative liver sinusoidal progenitors (iLSEP) by dictating developmental pathways. By devising an inverted multilayered air-liquid interface (IMALI) culture, hepatic endoderm, septum mesenchyme, arterial and sinusoidal quadruple progenitors self-organized to generate and sustain hepatocyte-like cells neighbored by divergent endothelial subsets composed of CD32b low CD31 high , LYVE1 + STAB1 + CD32b high CD31 low THBD - vWF - , and LYVE1 - THBD + vWF + cells. Wnt2 mediated sinusoidal-to-hepatic intercellular crosstalk potentiates hepatocyte differentiation and branched endothelial network formation. Intravital imaging revealed iLSEP developed fully patent human vessels with functional sinusoid-like features. Organoid-derived hepatocyte- and sinusoid-derived coagulation factors enabled correction of in vitro clotting time with Factor V, VIII, IX, and XI deficient patients' plasma and rescued the severe bleeding phenotype in hemophilia A mice upon transplantation. Advanced organoid vascularization technology allows for interrogating key insights governing organ-specific vessel development, paving the way for coagulation disorder therapeutics.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Selective Solid-Liquid Extraction of Lithium Cation Using Tripodal Sulfate-Binding Receptors Driven by Electrostatic Interactions.

Owing to the important role of and increasing demand for lithium resources, lithium extraction is crucial. The use of molecular extractants is a promising strategy for selective lithium recovery, in which the interaction between lithium and the designed extractant can be manipulated at the molecular level. Herein, we demonstrate that anion receptors of tripodal hexaureas can selectively extract Li2SO4 solids into water containing DMSO (0.8% water) compared to other alkali metal sulfates. The hexaurea receptor with terminal hexyl chains displays the best Li+ extraction selectivity at 2-fold over Na+ and 12.5-fold over K+. The driving force underpinning selective lithium extraction is due to the combined interactions of Li+-SO42- electrostatics and the ion-dipole interaction of the lithium-receptor (carbonyl groups and N atoms); the latter was found to be cation size dependent, as supported by computational calculations. This work indicates that anion binding receptors could drive selective cation extraction, thus providing new insights into the design of receptors for ion recognition and separation.

Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China.

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

Cordycepin Ameliorates Psoriasis-Like Skin Lesion by Regulating p53/MDM2 Feedback Loop.

Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.