Association between monocyte to high-density lipoprotein cholesterol ratio and telomere length: based on NHANES 1999-2002.

BACKGROUND: Telomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them. RESULTS: The results of correlation analysis showed that MHR levels were negatively correlated with telomere length (ρ=-0.083, P < 0.001), and this relationship remained statistically significant after controlling for other covariates (P all < 0.001). Weighted linear regression analysis showed that after adjusting for all covariates, MHR remained negatively associated with telomere length (ß = -0.020; 95% CI: -0.039 to -0.002; P = 0.037). Subgroup analysis shows that the negative association between MHR and telomere length appeared more striking among females (𝛽 = -0.024; 95%CI: -0.050 to 0.001; P = 0.058), the Non-Hispanic White (𝛽 = -0.022; 95%CI: -0.045 to 0.002; P = 0.066), and other race (𝛽 = -0.067; 95%CI: -0.134 to -0.000; P = 0.049). Using RCS explored potential nonlinear relationships between MHR and telomere length, revealing no nonlinear relationship between the two (P = 0.102). CONCLUSIONS: This study suggests a negative correlation between MHR levels and telomere length in American adults. More comprehensive research is needed to confirm these findings in the future.

Association between aromatic amines and serum neurofilament light chain as a biomarker of neural damage: a cross-sectional study from NHANES.

Background: Aromatic amines (AAs) are a group of compounds widely found in chemical industry, tobacco smoke, and during food processing, with established carcinogenic properties. To date, there have been no reports on the potential neurotoxic effects of adult exposure to AAs. Serum neurofilament light chain (sNfL) is a protein released into the bloodstream following nerve axon injury and has been validated as a reliable biomarker for various neurological diseases. However, there has been no research to investigate the relationship between AAs exposure and sNfL. Methods: In this study, we selected adults (aged ≥20 years) with data on both AAs and sNfL from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013-2014. We used multivariable linear regression models to explore the correlation between urinary AAs and sNfL. Results: In total, 510 adult participants with an average age of 43.58 ± 14.74 years were included in the study. Our findings indicate that, based on univariate linear regression and between-group comparative analyses, 1-Aminonaphthalene (1-AN), 2-Aminonaphthalene (2-AN), 4-Aminobiphenyl (4-AN) and o-Anisidine (o-ANI) showed a positive correlation with serum neurofilament light chain (P < 0.05). However, multiple linear regression analysis revealed that only 2-AN exhibited a positive correlation with serum neurofilament light chain (P < 0.05), while the correlations of other compounds with serum neurofilament light chain became non-significant. Conclusion: Although our cross-sectional study fails to establish causal relationships or determine clinical significance, the findings indicate a potential association between adult exposure to AAs, notably 2-AN, and nerve damage. Consequently, further research is needed to explore the connection between AAs exposure, sNfL, and neurological conditions in adults.

Combined inhibition of MET and VEGF enhances therapeutic efficacy of EGFR TKIs in EGFR-mutant non-small cell lung cancer with concomitant aberrant MET activation.

BACKGROUND: Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined. METHODS: The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo. RESULTS: We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case. CONCLUSIONS: Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.

Association between asthma and visceral adipose tissue in adults, a cross-sectional study from NHANES 2011-2018.

Asthma is a chronic inflammatory disease that affects millions of people worldwide. Obesity, particularly visceral adipose tissue (VAT), is known to secrete adipokines and pro-inflammatory factors, which are closely associated with various metabolic and cardiovascular diseases. Research indicates that these metabolic disturbances can exacerbate inflammatory conditions, contributing to both cardiovascular and respiratory diseases, including asthma. Despite these associations, studies on the specific relationship between VAT and asthma remain limited and warrant further investigation. Utilizing the NHANES database from 2011 to 2018, we included a total of 11,137 participants. Multivariable regression analysis was performed, stratifying subjects based on VAT levels and adjusting for various confounders. Subgroup interaction analysis and nonlinear analysis were conducted to explore potential effect modifiers and nonlinear associations. In this study, 11,137 participants were included, with 49.74% being female. Among the 509 asthma patients, 69.35% were female. The number of asthma patients among Non-Hispanic Whites was 212, representing 41.65% of the total, the highest proportion among the studied groups. The VAT for asthma patients was 529 g, significantly higher than the 455 g in the non-asthma group (P < 0.001). Multivariable regression analysis showed that for every 200 g increase in VAT, the risk of asthma increased by 10.4% (P = 0.032), 20.8% (P < 0.001), and 20.3% (P = 0.004) across three models (unadjusted, adjusted for demographic factors, and fully adjusted). Subgroup analysis indicated a stronger association between VAT and asthma risk in females and individuals over 40 years old. Nonlinear analysis uncovers a J-shaped relationship between VAT and asthma, with the lowest risk observed at 464.57 g (P < 0.001). The study findings suggest that increased VAT is associated with elevated asthma risk, particularly among females and older individuals. These results underscore the importance of considering VAT in asthma risk assessment and highlight potential targeted interventions to reduce asthma risk associated with excess visceral adiposity.

Development of predictive model for post-stroke depression at discharge based on decision tree algorithm: A multi-center hospital-based cohort study.

OBJECTIVE: Post-stroke depression (PSD) is one of the most common and severe neuropsychological sequelae after stroke. Using a prediction model composed of multiple predictors may be more beneficial than verifying the predictive performance of any single predictor. The primary objective of this study was to construct practical prediction tools for PSD at discharge utilizing a decision tree (DT) algorithm. METHODS: A multi-center prospective cohort study was conducted from May 2018 to October 2019 and stroke patients within seven days of onset were consecutively recruited. The independent predictors of PSD at discharge were identified through multivariate logistic regression with backward elimination. Classification and regression tree (CART) algorithm was employed as the DT model's splitting method. RESULTS: A total of 876 stroke patients who were discharged from the neurology departments of three large general Class A tertiary hospitals in Wuhan were eligible for analysis. Firstly, we divided these 876 patients into PSD and non-PSD groups, history of coronary heart disease (OR = 1.835; 95 % CI, 1.106-3.046; P = 0.019), length of hospital stay (OR = 1.040; 95 % CI, 1.013-1.069; P = 0.001), NIHSS score (OR = 1.124; 95 % CI, 1.052-1.201; P = 0.001), and Mini mental state examination (MMSE) score (OR = 0.935; 95 % CI, 0.893-0.978; P = 0.004) were significant predictors. The subgroup analysis results have shown that hemorrhagic stroke, history of hypertension and higher modified Rankin Scale score (mRS) score were associated with PSD at discharge in the young adult stroke patients. CONCLUSIONS: Several predictors of PSD at discharge were identified and convenient DT models were constructed to facilitate clinical decision-making.

Targeting ferroptosis in the neurovascular unit: A promising approach for treating diabetic cognitive impairment.

The cognitive decline associated with chronic metabolic disease diabetes has garnered extensive scrutiny, yet its pathogenesis remains incompletely understood, and the advancement of targeted therapeutics has posed a persistent challenge. Ferroptosis, a novel form of cell death characterized by intracellular lipid peroxidation and iron overload, has recently emerged as a significant factor. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetes-induced cognitive impairment. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetic cognitive impairment (DCI). This article initially conducts a profound analysis of the mechanism of ferroptosis, followed by a detailed elucidation of the specific manifestations of neurovascular unit ferroptosis in the context of diabetic cognitive function impairment. Furthermore, an exhaustive review of pertinent literature from April 2020 to March 2024 has been undertaken, resulting in the selection of 31 documents of significant reference value. These documents encompass studies on 11 distinct drugs, all of which are centered around investigating methods to inhibit the ferroptosis pathway as a potential treatment for DCI. Simultaneously, we conducted a review of 12 supplementary literary sources that presented 10 pharmacological agents with anti-ferroptosis properties in other neurodegenerative disorders. This article critically examines the potential influence of neurovascular unit ferroptosis on the progression of cognitive impairment in diabetes, from the three aforementioned perspectives, and organizes the existing and potential therapeutic drugs. It is our aspiration that this article will serve as a theoretical foundation for scholars in related disciplines when conceptualizing, investigating, and developing novel clinical drugs for DCI.

Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis.

Background: A previous network meta-analysis (NMA) compared the efficacy of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC). The phase III INSPIRE study of iruplinalkib was published recently. The present study aimed to add the results related to iruplinalkib to the NMA. Methods: A systematic literature search was performed in PubMed, Embase, Cochrane Library, Google, and Baidu. Randomized controlled trials (RCTs) reporting the independent review committee-assessed progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR) results of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC were eligible for inclusion in the NMA. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Bayesian fixed-effect models were used for the direct and indirect pairwise comparisons. This study was registered with PROSPERO (CRD42024555299). Results: Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. In terms of the overall risks of bias, all of the studies had "some concerns". All the next-generation ALK inhibitors were statistically superior to crizotinib in terms of PFS. Iruplinalkib had the best surface under the cumulative ranking curve (74.0%), followed by brigatinib (69.1%) and ensartinib (63.7%). Most of the pairwise comparisons did not reveal significant differences in the ORR and DCR. In terms of both the ORR and DCR, alectinib ranked first, followed by lorlatinib. Conclusions: Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.

Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer.

BACKGROUND: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. METHODS: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. RESULTS: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. CONCLUSIONS: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Geriatric nutritional risk index has a prognostic value for recovery outcomes in elderly patients with brain abscess.

Background: The Geriatric Nutritional Risk Index (GNRI) is a straightforward and objective tool for nutritional screening in older patients and has been demonstrated to possess prognostic predictive value in several diseases. Nonetheless, there is a lack of research on the nutritional risk associated with brain abscess in the older. This study aimed to evaluate the prevalence of nutritional risk among these patients by GNRI and to investigate its potential prognostic value for clinical outcomes. Materials and methods: From August 2019 to April 2023, 100 older patients diagnosed with brain abscess were enrolled in this single-center prospective cohort study, which evaluated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in elderly brain abscess patients. Data collected included demographic, and clinical characteristics at admission and calculated the GNRI, and the Glasgow Outcome Scale (GOS) score 6 months post-discharge. A GOS score of 5 was considered indicative of a good recovery, whereas scores ranging from 1 to 4 were classified as poor recovery. Results: The results revealed that 48% of older brain abscess patients were at risk of malnutrition according to the GNRI. These patients had significantly higher post-admission C-reactive protein (CRP) levels (p = 0.017), more comorbidities (p < 0.001), and higher age-adjusted Charlson Comorbidity Index (aCCI) scores (p < 0.001) compared to those without nutritional risk. Spearman correlation analysis showed that GNRI scores were negatively correlated with CRP levels, comorbidities, and aCCI scores, and positively correlated with Glasgow Outcome Scale (GOS) scores (Spearman's ρ = 0.624, p < 0.001). Multivariate logistic regression revealed that lower GNRI values were linked to reduced GOS levels (OR = 0.826, 95% CI: 0.775-0.880). ROC analysis determined a GNRI threshold of 97.50 for predicting poor recovery, with 90.57% sensitivity and 87.23% specificity. Conclusion: The older brain abscess patients exhibited a high malnutrition risk. GNRI showed an important predictive value for recovery in older patients, which could be helpful in clinical intervention and rehabilitation.

Nobiletin Regulates Polyinosinic-polycytidylic Acid-induced Inflammation in Macrophages Partially via the PPAR-γ Signaling Pathway.

INTRODUCTION: Macrophage dysregulation is a common pathogenic feature of viruses that provides extensive targets for antiviral therapy. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has a multitude of effects. METHODS: We investigated the effect of nobiletin on polyinosinic-polycytidylic acid (poly(I:C))-induced inflammation in RAW264.7 cells. RESULTS: Nobiletin inhibited the production of poly(I:C)-induced inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and CXCL10. High-throughput sequencing revealed that nobiletin inhibited the expression of TNF-α, IL-6, and CXCL10 and promoted the expression of CD206, Chil3, and Vcam1. In the Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the upregulated differential genes were significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The PPAR-γ inhibitor T0070907 significantly reversed the inhibitory effects of nobiletin on IL-6 and CXCL10 but had no significant effect on TNF-α secretion. CONCLUSION: Thus, nobiletin regulated poly(I:C)-induced inflammatory responses in RAW264.7 cells partially via the PPAR-γ signaling pathway.

Circadian rhythms and breast cancer: unraveling the biological clock's role in tumor microenvironment and ageing.

Breast cancer (BC) is one of the most common and fatal malignancies among women worldwide. Circadian rhythms have emerged in recent studies as being involved in the pathogenesis of breast cancer. In this paper, we reviewed the molecular mechanisms by which the dysregulation of the circadian genes impacts the development of BC, focusing on the critical clock genes, brain and muscle ARNT-like protein 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK). We discussed how the circadian rhythm disruption (CRD) changes the tumor microenvironment (TME), immune responses, inflammation, and angiogenesis. The CRD compromises immune surveillance and features and activities of immune effectors, including CD8+ T cells and tumor-associated macrophages, that are important in an effective anti-tumor response. Meanwhile, in this review, we discuss bidirectional interactions: age and circadian rhythms, aging further increases the risk of breast cancer through reduced vasoactive intestinal polypeptide (VIP), affecting suprachiasmatic nucleus (SCN) synchronization, reduced ability to repair damaged DNA, and weakened immunity. These complex interplays open new avenues toward targeted therapies by the combination of clock drugs with chronotherapy to potentiate the immune response while reducing tumor progression for better breast cancer outcomes. This review tries to cover the broad area of emerging knowledge on the tumor-immune nexus affected by the circadian rhythm in breast cancer.

Radical alkylation and protonation induced anti-Markovnikov hydroalkylation of unactivated olefins via cobalt catalysis.

Although strategies of olefin hydroalkylation continue to emerge rapidly, the precise control of the regio- or chemoselectivity and the expansion of the reaction range are still challenges. Herein, a straightforward route for cobalt-catalyzed anti-Markovnikov hydroalkylation of unactivated olefins with alkyl iodides has been achieved. The developed reaction is compatible with oxa-, aza-, cyclo- and a series of other functional groups as well as the frameworks of some bioactive compounds. Mechanism studies confirm that an alkyl radical is involved and cobalt-alkyl insertion followed by protonation with water are possible pathways in this reaction.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Ocular surface in patients with different degrees of myopia.

AIM: To investigate the clinical features of the ocular surface in patients with different degrees of myopia. METHODS: A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. RESULTS: Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). CONCLUSION: AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

Towards high-performance polarimeters with large-area uniform chiral shells: a comparative study on the polarization detection precision enabled by the Mueller matrix and deep learning algorithm.

Polarization detection and imaging technologies have attracted significant attention for their extensive applications in remote sensing, biological diagnosis, and beyond. However, previously reported polarimeters heavily relied on polarization-sensitive materials and pre- established mapping relationships between the Stokes parameters and detected light intensities. This dependence, along with fabrication and detection errors, severely constrain the working waveband and detection precision. In this work, we demonstrated a highly precise, stable, and broadband full-Stokes polarimeter based on large-area uniform chiral shells and a post-established mapping relationship. By precisely controlling the geometry through the deposition of Ag on a large-area microsphere monolayer with a uniform lattice, the optical chirality and anisotropy of chiral shells can reach about 0.15 (circular dichroism, CD) and 1.7, respectively. The post-established mapping relationship between the Stokes parameters and detected light intensities is established through training a deep learning algorithm (DLA) or fitting the derived mapping-relationship formula based on the Mueller matrix theory with a large dataset collected from our home-built polarization system. For the detection precision with DLA, the mean squared errors (MSEs) at 710 nm can reach 0.10% (S1), 0.41% (S2), and 0.24% (S3), while for the Mueller matrix theory, the corresponding values are 0.14% (S1), 0.46% (S2), and 0.48% (S3). The in-depth comparative studies indicate that the DLA outperforms the Mueller matrix theory in terms of detection precision and robustness, especially for weak illumination, small optical anisotropy and chirality. The averaged MSEs over a broad waveband ranging from 500 nm to 750 nm are 0.16% (S1), 0.46% (S2), and 0.61% (S3), which are significantly smaller than those derived from the Mueller matrix theory (0.45% (S1), 1% (S2), and 39.8% (S3)). The optical properties of chiral shells, the theory and DLA enabled mapping-relationships, the combination modes of chiral shells, and the MSE spectra have been systematically investigated.

Coarse particulate air pollution and mortality in a multidrug-resistant tuberculosis cohort.

RATIONALE: The association between ambient coarse particulate matter (PM2.5-10) and mortality in multi-drug resistant tuberculosis (MDR-TB) patients has not yet been studied. The modifying effects of temperature and humidity on this association are completely unknown. OBJECTIVES: To evaluate the effects of long-term PM2.5-10 exposures, and their modifications by temperature and humidity on mortality among MDR-TB patients. METHODS: A Chinese cohort of 3469 MDR-TB patients was followed up from diagnosis until death, loss to follow-up, or the study's end, averaging 2567 days per patient. PM2.5-10 concentrations were derived from the difference between PM10 and PM2.5. Cox proportional hazard models estimated hazard ratios (HRs) per 3.74 µg/m3 (interquartile range, IQR) exposure to PM2.5-10 and all-cause mortality for the full cohort and individuals at distinct long-term and short-term temperature and humidity levels, adjusting for other air pollutants and potential covariates. Exposure-response relationships were quantified using smoothed splines. RESULTS: Hazard ratios of 1.733 (95% CI, 1.407, 2.135) and 1.427 (1.114, 1.827) were observed for mortality in association with PM2.5-10 exposures for the full cohort under both long-term and short-term exposures to temperature and humidity. Modifying effects by temperature and humidity were heterogenous across sexes, age, treatment history, and surrounding environment measured by greenness and nighttime light levels. Nonlinear exposure-response curves suggestes a cumulative risk of PM2.5-10-related mortality starting from a low exposure concentration around 15 µg/m3. CONCLUSION: Long-term exposure to PM2.5-10 poses significant harm among MDR-TB patients, with effects modified by temperature and humidity. Immediate surveillance of PM2.5-10 is crucial to mitigate the progression of MDR-TB severity, particularly due to co-exposures to air pollution and adverse weather conditions.

Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis.

Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.