Preclinical testing of CT1113, a novel USP28 inhibitor, for the treatment of T-cell acute lymphoblastic leukaemia.

T-cell acute lymphoblastic leukaemia (T-ALL) is a highly aggressive and heterogeneous lymphoid malignancy with poor prognosis in adult patients. Aberrant activation of the NOTCH1 signalling pathway is involved in the pathogenesis of over 60% of T-ALL cases. Ubiquitin-specific protease 28 (USP28) is a deubiquitinase known to regulate the stability of NOTCH1. Here, we report that genetic depletion of USP28 or using CT1113, a potent small molecule targeting USP28, can strongly destabilize NOTCH1 and inhibit the growth of T-ALL cells. Moreover, we show that USP28 also regulates the stability of sterol regulatory element binding protein 1 (SREBP1), which has been reported to mediate increased lipogenesis in tumour cells. As the most critical transcription factor involved in regulating lipogenesis, SREBP1 plays an important role in the metabolism of T-ALL. Therefore, USP28 may be a potential therapeutic target, and CT1113 may be a promising novel drug for T-ALL with or without mutant NOTCH1.

Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI). METHODS: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes. RESULTS: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression. CONCLUSION: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.

Travel Burden and Timely Linkage to Care Among People Newly Diagnosed with HIV Infection in South Carolina from 2005 to 2020.

This retrospective study explored the association between travel burden and timely linkage to care (LTC) among people with HIV (PWH) in South Carolina. HIV care data were derived from statewide all-payer electronic health records, and timely LTC was defined as having at least one viral load or CD4 count record within 90 days after HIV diagnosis before the year 2015 and 30 days after 2015. Travel burden was measured by average driving time (in minutes) to any healthcare facility visited within six months before and one month after the initial HIV diagnosis. Multivariable logistic regression models with the least absolute shrinkage and selection operator were employed. From 2005 to 2020, 81.2% (3,547 out of 4,366) of PWH had timely LTC. Persons who had longer driving time (adjusted Odds Ratio (aOR): 0.37, 95% CI: 0.14-0.99), were male versus female (aOR: 0.73, 95% CI: 0.58-0.91), had more comorbidities (aOR: 0.73, 95% CI: 0.57-0.94), and lived in counties with a higher percentage of unemployed labor force (aOR: 0.21, 95% CI: 0.06-0.71) were less likely to have timely LTC. However, compared to those aged between 18 and 24 years old, those aged between 45 and 59 (aOR:1.47, 95% CI: 1.14-1.90) or older than 60 (aOR:1.71, 95% CI: 1.14-2.56) were more likely to have timely LTC. Concentrated and sustained interventions targeting underserved communities and the associated travel burden among newly diagnosed PWH who are younger, male, and have more comorbidities are needed to improve LTC and reduce health disparities.

Multi-level Factors Associated with HIV Late Presentation with Advanced Disease and Delay Time of Diagnosis in South Carolina, 2005-2019.

This study explored individual- and county-level risk factors of late presentation with advanced disease (LPAD) among people with HIV (PWH) and their longer delay time from infection to diagnosis in South Carolina (SC), using SC statewide Enhanced HIV/AIDS Reporting System (eHARS). LPAD was defined as having an AIDS diagnosis within three months of initial HIV diagnosis, and delay time from HIV infection to diagnosis was estimated using CD4 depletion model. 3,733 (41.88%) out of 8,913 adult PWH diagnosed from 2005 to 2019 in SC were LPAD, and the median delay time was 13.04 years. Based on the generalized estimating equations models, PWH who were male (adjusted prevalence ratio [aPR]: 1.22, 95% CI: 1.12 ∼ 1.33), aged 55+ (aPR: 1.76, 95% CI: 1.62 ∼ 1.92), were Black (aPR: 1.09, 95% CI: 1.03 ∼ 1.15) or Hispanic (aPR: 1.42, 95% CI: 1.26 ∼ 1.61), and living in counties with a larger proportion of unemployment individuals (aPR: 1.02, 95% CI: 1.01 ∼ 1.03) were more likely to be LPAD. Among PWH who were LPAD, Hispanic (adjusted beta: 1.17, 95% CI: 0.49 ∼ 1.85) instead of Black (adjusted beta: 0.11, 95% CI: -0.30 ∼ 0.52) individuals had significant longer delay time compared to White individuals. Targeted and sustained interventions are needed for older, male, Hispanic or Black individuals and those living in counties with a higher percentage of unemployment because of their higher risk of LPAD. Additionally, specific attention should be paid to Hispanic individuals due to their longer delay time to diagnosis.

Use of machine learning approaches to predict transition of retention in care among people living with HIV in South Carolina: a real-world data study.

Maintaining retention in care (RIC) for people living with HIV (PLWH) helps achieve viral suppression and reduce onward transmission. This study aims to identify the best machine learning model that predicts the RIC transition over time. Extracting from the enhanced HIV/AIDS reporting system, this study included 9765 PLWH from 2005 to 2020 in South Carolina. Transition of RIC was defined as the change of RIC status in each two-year time window. We applied seven classifiers, such as Random Forest, Support Vector Machine, eXtreme Gradient Boosting and Long-short-term memory, for each lagged response to predict the subsequent year's RIC transition. Classification performance was assessed using balanced prediction accuracy, the area under the curve (AUC), recall, precision and F1 scores. The proportion of the four categories of RIC transition was 13.59%, 29.78%, 9.06% and 47.57%, respectively. Support Vector Machine was the best approach for every lag model based on both the F1 score (0.713, 0.717 and 0.719) and AUC (0.920, 0.925 and 0.928). The findings could facilitate the risk augment of PLWH who are prone to follow-up so that clinicians and policymakers could come up with more specific strategies and relocate resources for intervention to keep them sustained in HIV care.

The dynamic risk factors of cardiovascular disease among people living with HIV: a real-world data study.

BACKGROUND: This study aims to investigate the incidence and dynamic risk factors for cardiovascular diseases (CVD) among people living with HIV (PLWH). METHODS: In this population-based statewide cohort study, we utilized integrated electronic health records data to identify adult (age ≥ 18) who were diagnosed with HIV between 2006 and 2019 and were CVD event-free at the HIV diagnosis in South Carolina. The associations of HIV-related factors and traditional risk factors with the CVD incidence were investigated during the overall study period, and by different follow-up periods (i.e., 0-5yrs, 6-10yrs 11-15yrs) using multivariable logistic regression models. RESULTS: Among 9,082 eligible participants, the incidence of CVD was 18.64 cases per 1000 person-years. Overall, conventional risk factors, such as tobacco use, hypertension, obesity, chronic kidney disease (CKD), were persistently associated with the outcome across all three groups. While HIV-related factors, such as recent CD4 count (e.g., > 350 vs. <200 cells/mm3: adjusted odds ratio [aOR] range: 0.18-0.25), and percent of years in retention (e.g., 31-75% vs. 0-30%: aOR range: 0.24-0.57) were associated with lower odds of CVD incidence regardless of different follow up periods. The impact of the percent of days with viral suppression gradually diminished as the follow-up period increased. CONCLUSIONS: Maintaining an optimal viral suppression might prevent CVD incidence in the short term, whereas restoring immune recovery may be beneficial for reducing CVD risk regardless of the duration of HIV diagnosis. Our findings suggest the necessity of conducting more targeted interventions during different periods of HIV infection.

Generation and characterization of PDGFRα-GFP knock-in mice for visualization of PDGFRα+ fibroblasts in vivo.

The platelet-derived growth factor (PDGF) and its receptor, PDGFRα, are critical for tissue development and injury repair. To track PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expresses green fluorescent protein (GFP) under the control of the PDGFRα promoter. This genetic tool enabled us to detect PDGFRα expression in various organs during both neonatal and adult stages. Additionally, we confirmed the correlation between endogenous PDGFRα and transgenic PDGFRα expression using mouse injury models, showing the potential of this genetic reporter for studying PDGFRα-mediated signaling pathways and developing therapeutic strategies. Overall, the PDGFRα-GFP knock-in mouse line serves as a valuable tool for investigating the biology of PDGFRα and its role in normal development and disease.

Incidence of Chronic Kidney Disease Following Acute Coronavirus Disease 2019 Based on South Carolina Statewide Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was associated with severe acute illness including multiple organ failure. Acute kidney injury (AKI) was a common finding, often requiring dialysis support. OBJECTIVE: Define the incidence of new clinically identified chronic kidney disease (CKD) among patients with COVID-19 and no pre-existing kidney disease. DESIGN PARTICIPANTS: The South Carolina (SC) Department of Health and Environmental Control (DHEC) COVID-19 mandatory reporting registry of SC residents testing for COVID-19 between March 2020 and October 2021 was included. DESIGN MAIN MEASURES: The primary outcome was a new incidence of a CKD diagnosis (N18.x) in those without a pre-existing diagnosis of CKD during the follow-up period of March 2020 to January 14, 2022. Patients were stratified by severity of illness (hospitalized or not, intensive care unit needed or not). The new incidence of CKD diagnosis was examined using logistic regression and cox proportional hazards analyses. KEY RESULTS: Among patients with COVID-19 (N = 683,958) without a pre-existing CKD diagnosis, 8322 (1.2 %) were found to have a new diagnosis of CKD. The strongest predictors for subsequent CKD diagnosis were age ≥ 60 years hazard ratio (HR) 31.5 (95% confidence interval [95%CI] 25.5-38.8), and intervening (between COVID-19 and CKD diagnoses) AKI diagnosis HR 20.7 (95%CI 19.7-21.7). The presence of AKI was associated with an HR of 23.6, 95% CI 22.3-25.0, among those not hospitalized, and HR of 6.2, 95% CI 5.7-6.8 among those hospitalized, for subsequent CKD. COVID-19 was not significantly associated with subsequent CKD after accounting for the severity of illness and comorbidities. CONCLUSION: Among SC residents, COVID-19 was not associated with CKD independent from indicators of the severity of illness, especially AKI diagnosis. Kidney-specific follow-up testing may be reserved for those high-risk for CKD development. Further prospective registries should examine the long-term kidney consequences to confirm these findings.

Associations Between Internalized and Anticipated HIV Stigma and Depression Symptoms Among People Living with HIV in China: A four-wave Longitudinal Model.

Previous research has documented that HIV-related stigma (e.g., internalized and anticipated stigma) is detrimental to the mental health of people living with HIV (PLWH). However, longitudinal data on the bidirectional relationship between HIV-related stigma and depression symptoms are limited. The purpose of this study was to examine the bidirectional association among internalized and anticipated HIV stigma and depression symptoms among Chinese PLWH. A four-wave longitudinal design (6 months intervals) was employed among 1,111 Chinese PLWH (Mage = 38.58, SD = 9.16, age range: 18-60 years; 64.1% men). The bidirectional model was examined using a random-intercept cross-lagged panel model (RI-CLPM), which evaluated the within- and between-person effects of study variables. At the within-person level, results indicated that depression symptoms at T2 mediated the linkage between internalized HIV stigma at T1 and anticipated HIV stigma at T3, and that anticipated HIV stigma at both T2 and T3 mediated the relationship between depression symptoms at the previous time point and internalized HIV stigma at the subsequent time point. Furthermore, a bidirectional association was found between anticipated HIV stigma and depression symptoms across four waves. At the between-person level, internalized and anticipated HIV stigma were significantly associated with depression symptoms. This study highlights the complex interplay between different forms of HIV-related stigma and mental health problems among PLWH and underscores the importance of considering the bidirectional relationship between the development of psychopathology and stigmatization process in clinical practice.

Impact of HIV on COVID-19 Outcomes: A Propensity Score Matching Analysis with Varying Age Differences.

To exploratorily test (1) the impact of HIV and aging process among PLWH on COVID-19 outcomes; and (2) whether the effects of HIV on COVID-19 outcomes differed by immunity level. The data used in this study was retrieved from the COVID-19 positive cohort in National COVID Cohort Collaborative (N3C). Multivariable logistic regression models were conducted on populations that were matched using either exact matching or propensity score matching (PSM) with varying age difference between PLWH and non-PLWH to examine the impact of HIV and aging process on all-cause mortality and hospitalization among COVID-19 patients. Subgroup analyses by CD4 counts and viral load (VL) levels were conducted using similar approaches. Among the 2,422,864 adults with a COVID-19 diagnosis, 15,188 were PLWH. PLWH had a significantly higher odds of death compared to non-PLWH until age difference reached 6 years or more, while PLWH were still at an elevated risk of hospitalization across all matched cohorts. The odds of both severe outcomes were persistently higher among PLWH with CD4 < 200 cells/mm3. VL ≥ 200 copies/ml was only associated with higher hospitalization, regardless of the predefined age differences. Age advancement in HIV might significantly contribute to the higher risk of COVID-19 mortality and HIV infection may still impact COVID-19 hospitalization independent of the age advancement in HIV.

COVID-19 Testing Among People with HIV: A Population Level Analysis Based on Statewide Data in South Carolina.

People with HIV (PWH) are at an elevated risk of developing severe COVID-19 outcomes because of compromised immunity and more comorbidities. However, existing literature suggests a lower rate of COVID-testing among PWH. This study aimed to explore the temporal trend of county-level COVID-19 testing rate and multi-level predictors of COVID-19 ever-testing among PWH in South Carolina (SC). Leveraging linked statewide HIV and COVID-19 datasets, we defined the study population as all adult (18 + years) PWH who were alive on March 2020 and living in SC. PWH with a COVID-19 testing record between March 2020 and October 2021 were defined as COVID-19 ever-testers. Logistic regression and generalized mixed models were used to investigate the association of PWH's demographic profile, HIV clinical characteristics (e.g., CD4 count, viral load), comorbidities, and social factors with COVID-19 testing among PWH. Among 15,660 adult PWH, 8,005 (51.12%) had ever tested for COVID-19 during the study period (March 2020-October 2021). PWH with older age, being male, and Hispanics were less likely to take COVID-19 testing, while men who have sex with men or injection drug users were more likely to take COVID-19 testing. PWH with higher recent viral load (10,000-100,000 copies/ml vs. <200 copies/ml: adjusted odds ratio [AOR]: 0.64, 95%CI: 0.55-0.75) and lower CD4 counts (> 350 cells/mm3 vs. <200 cells/mm3: AOR: 1.25, 95%CI: 1.09-1.45) had lower odds for COVID-19 testing. Additionally, PWH with lower comorbidity burden and those living in rural areas were less likely to be tested for COVID-19. Differences in COVID-19 test-seeking behaviors were observed among PWH in the current study, which could help provide empirical evidence to inform the prioritization of further disease monitoring and targeted intervention. More efforts on building effective surveillance and screening systems are needed to allow early case detection and curbing disease transmission among older, male, Hispanic, and immune-suppressed PWH, especially in rural areas.

Associations between HIV disclosure and HIV care continuum outcomes among men who have sex with men living with HIV: systematic review and meta-analysis.

ABSTRACTThe objective of this study is to synthesize the existing empirical literature and perform a systematic review and meta-analysis on the relationship between HIV disclosure and engagement in the HIV care continuum among men who have sex with men living with HIV. Twenty-three studies were included, with thirteen quantitative studies and ten qualitative studies. Meta-analytic techniques were used to compute and aggregate effect sizes (odds ratio [OR] and their confidence intervals [95%CI]) for the quantitative studies and a thematic analysis was employed for qualitative studies. Given the small number of eligible studies, meta-analysis was only conducted for the linkage to care outcome, where a positive association was observed from the pooled estimation (OR = 1.51, 95%CI [1.15, 1.99]). Regarding ART initiation, retention in care, and viral suppression outcomes, most of the individual studies revealed a positive association between HIV disclosure and these outcomes. Thematic analysis from qualitative studies complemented the quantitative findings by incorporating the approaching and avoidance motivations underlying the relationship between non-HIV disclosure and the participation in HIV care continuum. The small number of available studies limits the definitive conclusions, and more research is needed to ascertain the magnitude of effect sizes.

Toward a molecular understanding of the conductivity of lithium-ion conducting polyanion polymer electrolytes by molecular dynamics simulation.

With the improved lithium-ion transference number near unity, the low conductivity of single lithium-ion conducting solid polymer electrolytes (SLIC-SPEs) still hinders their application in high-rate batteries. Though some empirical conclusions on the conducting mechanism of SLIC-SPEs have been obtained, a more comprehensive study on the quantitative relationship between the molecular structure factors and ionic conduction performance is expected. In this study, a model structure that contains adjustable main chain and anion groups in the polyethylene oxide (PEO) matrix was used to clarify the influence of molecular structural factors on ionic conductivity and electrochemical stability of SLIC-SPEs. The anionic group was further disassembled into the intermediate group and end group while the main chain structure was distinguished into different degrees of polymerization and various lengths of the spacers between anions. Therefore, a well-defined molecular structure was employed to describe its relationship with ionic conductivity. In addition, the dissociation degree of salts and mobility of ions changing with the molecular structure were also discussed to explore the fundamental causes of conductivity. It can be concluded that the anion group affects the conductivity mainly via the dissociation degree, while the main chain structure impacts the conductivity by both dissociation degree and mobility.

The association between the maternal pre-pregnancy platelet count and fecundability in mainland China: a population-based cohort study.

BACKGROUND: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability. METHODS: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis. RESULTS: The median of pre-pregnancy PC among women was 221.00×109/L. The first (<177.00 ×109/L) and second quintile (177.00-207.99 ×109/L) of PC showed slightly increased fecundability (Q1: adjusted FR 1.05, 95% CI 1.04-1.06; Q2: adjusted FR 1.04, 95% CI 1.03-1.05), while higher quintals (Q4: 236.00-271.99 ×109/L; Q5: ≥272.00 ×109/L) were related to reduction of fecundability, when compared with the third quintile of PC (208.00-235.99 ×109/L) (Q4: adjusted FR 0.96, 95% CI 0.95-0.97; Q5: adjusted FR 0.88, 95% CI 0.87-0.89). In the first quintiles (<177.00×109/L), only 20.93% women had PC below 129.94×109/L. An inverse-U shape association was consistently observed among women such that the lower PC of normal range (<118.03×109/L) and higher PC (>223.06×109/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01). CONCLUSION: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

Understanding social risk factors of county-level disparities in COVID-19 tests per confirmed case in South Carolina using statewide electronic health records data.

BACKGROUND: COVID-19 testing is essential for pandemic control, and insufficient testing in areas with high disease burdens could magnify the risk of poor health outcomes. However, few area-based studies on COVID-19 testing disparities have considered the disease burden (e.g., confirmed cases). The current study aims to investigate socioeconomic drivers of geospatial disparities in COVID-19 testing relative to disease burden across 46 counties in South Carolina (SC) in the early (from April 1, 2020, to June 30, 2020) and later (from July 1, 2020, to September 30, 2021) phases of the pandemic. METHODS: Using SC statewide COVID-19 testing data, the COVID-19 testing coverage was measured by monthly COVID-19 tests per confirmed case (hereafter CTPC) in each county. We used modified Lorenz curves to describe the unequal geographic distribution of CTPC and generalized linear mixed-effects regression models to assess the association of county-level social risk factors with CTPC in two phases of the pandemic in SC. RESULTS: As of September 30, 2021, a total of 641,201 out of 2,941,227 tests were positive in SC. The Lorenz curve showed that county-level disparities in CTPC were less apparent in the later phase of the pandemic. Counties with a larger percentage of Black had lower CTPC during the early phase (ß = -0.94, 95%CI: -1.80, -0.08), while such associations reversed in the later phase (ß = 0.28, 95%CI: 0.01, 0.55). The association of some other social risk factors diminished as the pandemic evolved, such as food insecurity (ß: -1.19 and -0.42; p-value is < 0.05 for both). CONCLUSIONS: County-level disparities in CTPC and their predictors are dynamic across the pandemic. These results highlight the systematic inequalities in COVID-19 testing resources and accessibility, especially in the early stage of the pandemic. Counties with greater social vulnerability and those with fewer health care resources should be paid extra attention in the early and later phases, respectively. The current study provided empirical evidence for public health agencies to conduct more targeted community-based testing campaigns to enhance access to testing in future public health crises.

Electrochemical aptasensor based on gold nanoparticle decorated Ti3C2Tx nanocomposites for chloramphenicol detection.

Using gold (Au) nanoparticle decorated Ti3C2Tx (Ti3C2Tx-Au) nanocomposites, a highly sensitive electrochemical aptasensor for the effective detection of chloramphenicol has been developed. As a two-dimensional layered material, the prepared composite not only provides high surface area, good conductivity, and thermal stability but also substantial binding sites for aptamers with high sensitivity and selectivity for the accurate determination of chloramphenicol. Interestingly, the conductivity and active sites were enhanced by freeze-drying Ti3C2Tx and in situ formation of Ti3C2Tx-Au nanocomposite. The fabricated aptasensor exhibited a very low detection limit (S/N ≥ 3) of 13.18 fg mL-1 with a linear range of 1 ~ 700 pg mL-1 and correlation coefficient of 0.9992. The fabricated aptasensor demonstrated an excellent reproducibility, repeatability, long-term stability, and high selectivity toward chloramphenicol. Further, the aptasensor was applied to real milk samples, and the recoveries were ranged from 98.93 to 101.93%.

Application of transcriptome in time analysis and donor characterization in blood samples.

As an effective supplement to the current forensic DNA typing and one of the research hotpots in forensic science, the in-depth mining and characterization of biological evidence can provide rich and reliable clues for case investigation. In this study, the time-dependent variations of transcriptome were confirmed in in vitro blood samples within 0-168 days and a random forest model was established to realize the classification of blood samples with different TSD (time since deposition). Meanwhile, significant differences were observed in the transcripts of blood samples with different smoking habits and genders within a certain time period. HLA-DRB1, HLA-DQB1 and HLA-DQA2 were identified as markers for smoking habit identification, while the transcripts for RPS4Y1 and EIF1AY from the non-recombining region of the Y chromosome (NRY) were identified as markers for male sex identification. Thus, this study provides a theoretical foundation and experimental strategy for establishing a transcriptome-based method for characterizing blood sample retention time and donor characteristics in the field of forensic investigation.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy.

OBJECTIVES: To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy. METHODS: The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types. RESULTS: According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy. CONCLUSIONS: Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Liver tumor-initiating cells initiate the formation of a stiff cancer stem cell microenvironment niche by secreting LOX.

Accumulating evidence has shown that the traits of tumor-initiating cells (TICs) are controlled by the microenvironment niches (MENs), but the composition and remodeling mechanisms of the MENs of TICs are poorly defined. Here, we report that the voltage-gated calcium channel α2δ1 subunit-positive TICs of hepatocellular carcinoma (HCC) specifically secret lysyl oxidase (LOX), which leads to the cross-linking of collagen, forming a stiff extracellular matrix (ECM) that is sufficient to drive the formation of TICs with a stiff mechanical trait and is subsequently required for the maintenance the properties of HCC TICs. Furthermore, the cross-linked collagen results in the upregulation of integrin α7 (ITGA7), increased phosphorylation of FAK and extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ITGA7 abolishes all the effects of cross-linked collagen mediated by LOX. Hence, the α2δ1+ HCC TICs initiate ECM remodeling by secreting LOX to create a stiff MEN of TIC with cross-linked collagen, which drives the acquisition and subsequent maintenance of the properties of HCC TICs through ITGA7-FAK-ERK1/2 signaling pathway.

Population Mobility and Aging Accelerate the Transmission of Coronavirus Disease 2019 in the Deep South: A County-Level Longitudinal Analysis.

Population mobility and aging at local areas contributed to the geospatial disparities in the coronavirus disease 2019 (COVID-19) transmission among 418 counties in the Deep South. In predicting the incidence of COVID-19, a significant interaction was found between mobility and the proportion of older adults. Effective disease control measures should be tailored to vulnerable communities.