Association between long-term exposure to fine particulate matter and its chemical constituents and premature death in individuals living with HIV/AIDS.

Long-term exposure to fine particulate matter (PM2.5) is associated with an increased total mortality. However, the association of PM2.5 with mortality in people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS, PLWHA) and the relationship between its constituents and adverse outcomes remain unknown. In this cohort study, 28,140 PLWHA were recruited from the HIV/AIDS Comprehensive Response Information Management System of the Hubei Provincial Centre for Disease Control and Prevention in China between 2001 and 2020. The annual PM2.5 chemical composition data, including sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC), and organic matter (OM), was extracted from the Tracking Air Pollution (TAP) dataset in China. A Cox proportional hazard model with time-varying exposure and time-to-event quantile-based generalized (g) computation was used to assess the associations between PM2.5 chemical constituents, and mortality in PLWHA. A multivariate Cox proportional hazard model estimated an excess hazard ratio (eHR) of 0.32% [95% confidence interval (CI): (0.01%, 0.64%)] for AIDS-related death (ARD), associated with 1 µg/m3 rise in PM2.5 exposure. An increase of 1 µg/m3 in NH4+ was associated with 5.13% [95% CI: (2.89%, 7.43%)] and 2.97% [95% CI: (1.52%, 4.44%)] increase in the risk of ARD and all-cause deaths (ACD), respectively. When estimated using survival-based quantile g-computation, the eHR for ARD with a joint change in a decile increase in all five components was 6.10% [95% CI: 3.77%, 8.48%)]. Long-term exposure to PM2.5 chemical composition, particularly NH4+ increased the risk of death in PLWHA. This study provides epidemiological evidence that SO42- and NH4+ increased the risk of ARD and that NH4+ increased the risk of ACD in PLWHA. Multi-constituent analyses further suggested that NH4+ may be a key component in increasing the risk of premature death in patients with HIV/AIDS. Individuals aged ≥65 with HIV/AIDS are more vulnerable to SO42-, and consequent ACD.

Utilizing daily excessive concentration hours to estimate small for gestational age infants attributable to fine particulate matter in Wuhan, China.

Limited studies in China have explored the association between gravidae exposure to PM2.5 and small for gestational age infants (SGA), yielding inconsistent results. This study in Wuhan utilized daily excessive concentration hours (DECH) as a novel measure to assess PM2.5's impact on SGA. Data on air pollutants and pregnant women were collected from the Wuhan Municipal Ecology and Environmental Bureau and Wuhan Children's Hospital, respectively. Logistic regression models were employed to evaluate the contribution of PM2.5-DECH and PM2.5-mean to SGA. Significant correlations were observed between PM2.5-mean and SGA during the second trimester [OR = 1.23 (95% CI: 1.14-1.32)] and the entire pregnancy [OR = 1.15 (95% CI: 1.07-1.24)]. Similar correlations were found between PM2.5-DECH and SGA. These findings suggest that increased PM2.5 exposure is associated with a higher risk of SGA, and DECH may be used as a prospective substitute indicator for daily average concentration in similar studies.

Global burden of non-optimal temperature attributable stroke: The long-term trends, population growth and aging effects.

Since the 20th century, the world has undergone climate change, population growth and population aging, which may result in alterations in the epidemiology of non-optimal temperature-associated strokes. We employed multiple methodologies and data from the global burden of disease 2019 to unveil the long-term curvilinear trends in strokes attributed to non-optimal temperature and the impact of aging and population growth on its changing epidemiology. From 1990 to 2019, the age-standardized DALYs rate (ASDR) of strokes attributable to low temperature had been decreasing, but from 2016, the continued downward trend in ASDR disappeared and began to remain stable. On the contrary, the ASDR of strokes attributable to high temperature continued to increase. The high socio-demographic index (SDI) region experienced the fastest decreased trend. The disease burden of stroke attributable to low temperature is increased by aging in 178 countries (87.25%), compared with 130 (63.73%) for high temperature. After excluding aging and population growth, the DALY rate for strokes attributed to high temperature was increasing in 87 countries and territories (42.64%). The disease burden of strokes attributed to low temperature is far greater than that of high temperature in absolute figures. However, globally, there is a significant trend toward an increase in strokes attributed to high temperature. Social development has largely offset the burden of strokes attributed to low temperature, but most regions of the world are equally affected by strokes attributed to high temperature. Simultaneously, in the framework of climate change, aging is also largely hindering stroke prevention efforts.

Association between traffic-related air pollution and osteoporotic fracture hospitalizations in inland and coastal areas: evidences from the central areas of two cities in Shandong Province, China.

Our result showed that short-term exposure to traffic-related air pollutants (TRAPs) might increase the risk of hospitalizations for osteoporotic fractures. It was suggested that government should formulate emission reduction policies to protect the health of citizens. INTRODUCTION: As the main source of urban air pollution in China, exhaust emissions of motor vehicles have been linked to adverse health outcomes, but evidence of the relationship between short-term exposure to TRAPs and osteoporotic fractures is still relatively rare. METHODS: In this study, a total of 5044 inpatients from an inland city (Jinan) and a coastal city (Qingdao), two cities with developed transportation in Shandong Province, were included. A generalized additive model (GAM) was used to investigate the association between TRAPs and hospitalizations for osteoporotic fractures. The stratified analyses were performed by gender and age. RESULTS: Positive associations between TRAPs and osteoporotic fracture hospitalizations were observed. We found that short-term exposure to TRAPs was associated with increased numbers of hospitalizations for osteoporotic fractures. PM2.5 and PM10 were statistically significant associated with hospitalizations for osteoporotic fractures at both single-day and multiday lag structures only in Qingdao, with the strongest associations at lag06 and lag07 [RR=1.0446(95%CI: 1.0018,1.0891) for PM2.5, RR=1.0328(95%CI: 1.0084,1.0578) for PM10]. For NO2 and CO, we found significant associations at lag4 in the single lag structure in Jinan [RR=1.0354 (95%CI: 1.0071, 1.0646) for NO2, RR=1.0014 (95%CI: 1.0002, 1.0025) for CO], while only CO at lag4 was significantly associated with hospitalizations for osteoporotic fractures in Qingdao [1.0038 (1.0012, 1.0063)]. Stratified analyses indicated that the associations were stronger in females and older individuals (65 + years). CONCLUSION: This study implied that short-term exposure to TRAPs pollution was associated with an increased risk of hospitalizations for osteoporotic fractures. Female patients and patients aged 65 + years appeared to be more vulnerable to TRAPs, suggesting that poor air quality is a modifiable risk factor for osteoporotic fractures.

Independent and interactive effects of ozone and thermal inversion exposure on the risk of gestational diabetes mellitus in Wuhan, China.

The adverse effects of exposure to thermal inversion (TI) and ozone (O3) on human health have been reported; however, there are few studies have explored the independent and potential interactive effects of them on gestational diabetes mellitus (GDM). A total of 31,262 pregnant women from the Wuhan Children's Hospital covering the period from 2017 to 2021 were included in this study. The logistic regression adjusted for the covariates was applied to explore the independent effect of exposure to O3 and TI on GDM. The relative excess risk due to the interaction (RERI) analysis was applied to assess the possible interactive effect. Per 10 µg/m3 increased in O3 (OR = 1.069, 95% CI: 1.049, 1.089) during the first trimester and per 10 days increased in TI (OR = 1.041, 95% CI: 1.005, 1.080) in the second trimester were significantly associated with the risk of GDM. The synergistic effect of exposure to TI and O3 was larger than their sum effect (RERI = 0.330, 95% CI: 0.170, 0.476). This study added further support for public health-related policy to improve maternal health by curbing TI and O3.

Based on cuproptosis-related lncRNAs, a novel prognostic signature for colon adenocarcinoma prognosis, immunotherapy, and chemotherapy response.

Introduction: Colon adenocarcinoma (COAD) is a special pathological subtype of colorectal cancer (CRC) with highly heterogeneous solid tumors with poor prognosis, and novel biomarkers are urgently required to guide its prognosis. Material and methods: RNA-Seq data of COAD were downloaded through The Cancer Genome Atlas (TCGA) database to determine cuproptosis-related lncRNAs (CRLs) using weighted gene co-expression network analysis (WGCNA). The scores of the pathways were calculated by single-sample gene set enrichment analysis (ssGSEA). CRLs that affected prognoses were determined via the univariate COX regression analysis to develop a prognostic model using multivariate COX regression analysis and LASSO regression analysis. The model was assessed by applying Kaplan-Meier (K-M) survival analysis and receiver operating characteristic curves and validated in GSE39582 and GSE17538. The tumor microenvironment (TME), single nucleotide variants (SNV), and immunotherapy response/chemotherapy sensitivity were assessed in high- and low-score subgroups. Finally, the construction of a nomogram was adopted to predict survival rates of COAD patients during years 1, 3, and 5. Results: We found that a high cuproptosis score reduced the survival rates of COAD significantly. A total of five CRLs affecting prognosis were identified, containing AC008494.3, EIF3J-DT, AC016027.1, AL731533.2, and ZEB1-AS1. The ROC curve showed that RiskScore could perform well in predicting the prognosis of COAD. Meanwhile, we found that RiskScore showed good ability in assessing immunotherapy and chemotherapy sensitivity. Finally, the nomogram and decision curves showed that RiskScore would be a powerful predictor for COAD. Conclusion: A novel prognostic model was constructed using CRLs in COAD, and the CRLs in the model were probably a potential therapeutic target. Based on this study, RiskScore was an independent predictor factor, immunotherapy response, and chemotherapy sensitivity for COAD, providing a new scientific basis for COAD prognosis management.

The effects of fine particulate matter, solid fuel use and greenness on the risks of diabetes in middle-aged and older Chinese.

BACKGROUND: Previous studies provided clues that environmental factors were closely related to diabetes incidence. However, the evidence from high-quality and large cohort studies about the effects of PM2.5, solid fuel use and greenness on the development of diabetes among middle-aged and older adults in China was scarce. OBJECTIVE: To separately investigate the independent effects of PM2.5, solid fuel use and greenness on the development of diabetes among middle-aged and older adults. METHODS: A total of 9242 participants were involved in this study extracted from the China Health and Retirement Longitudinal Study. Time-varying Cox regression was applied to detect the association of diabetes with PM2.5, solid fuel use and greenness, separately. The potential interactive effect of air pollution and greenness were explored using the relative excess risk due to interaction (RERI). RESULTS: Per 10 µg/m3 increases in PM2.5 were associated with 6.0% (95% CI: 1.9, 10.2) increasing risks of diabetes incidence. Females seemed to be more susceptible to PM2.5. However, the effects of solid fuel use only existed in older and lower BMI populations, with hazard ratios (HRs) of 1.404 (1.116, 1.766) and 1.346 (1.057, 1.715), respectively. In addition, exposure to high-level greenness might reduce the risks of developing diabetes [HR = 0.801 (0.687, 0.934)]. Weak evidence of the interaction effect of PM2.5/solid fuel use and greenness on diabetes was found. SIGNIFICANCE: Both PM2.5 and solid fuel use were associated with the increasing incidence of diabetes. In addition, high-level greenness might be a beneficial environmental factor for reducing the risks of developing diabetes. All in all, our findings might provide valuable references for public health apartments to formulate very fruitful policies to reduce the burden of diabetes. IMPACT STATEMENT: Both PM2.5 and solid fuel use were associated with the increasing incidence of diabetes while high-level greenness was not, which might provide valuable references for public health apartments to make policies.

Synergic effects of PM1 and thermal inversion on the incidence of small for gestational age infants: a weekly-based assessment.

BACKGROUND: The synergic effects of thermal inversion (TI) and particulate matter with an aerodynamic diameter ≤1 µm (PM1) exposure and incidence of small for gestational age (SGA) was not clear. OBJECTIVE: We aimed to explore the independent effects of prenatal TI and PM1 exposure on incidence of SGA and their potential interactive effects. METHODS: A total of 27,990 pregnant women who delivered in Wuhan Children's Hospital from 2017 to 2020 were included. The daily mean concentration of PM1 was obtained from ChinaHighAirPollutants (CHAP) and matched with the residential address of each woman. Data on TI was derived from National Aeronautics and Space Administration (NASA). The independent effects of PM1 and TI exposures on SGA in each gestational week were estimated by the distributed lag model (DLM) nested in Cox regression model, and the potential interactive effects of PM1 and TI on SGA were investigated by adapting the relative excess risk due to interaction (RERI) index. RESULTS: Per 10 µg/m3 increase in PM1 was associated with an increase in the risk of SGA at 1-3 and 17-23 gestational weeks, with the strongest effect at the first gestational week (HR = 1.043, 95%CI: 1.008, 1.078). Significant links between one day increase of TI and SGA were found at the 1-4 and 13-23 gestational weeks and the largest effects were observed at the 17th gestational week (HR = 1.018, 95%CI: 1.009, 1.027). Synergistic effects of PM1 and TI on SGA were detected in the 20th gestational week, with RERI of 0.208 (95%CI: 0.033,0.383). IMPACT STATEMENT: Both prebirth PM1 and TI exposure were significantly associated with SGA. Simultaneous exposure to PM1 and TI might have synergistic effect on SGA. The second trimester seems to be a sensitive window of environmental and air pollution exposure.

Short-term exposure to ambient particulate matter and mortality among HIV/AIDS patients: Case-crossover evidence from all counties of Hubei province, China.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been a worrisome public health problem in the world. However, evidence for associations between short-term exposure to particulate matter (PM) and mortality among HIV/AIDS patients is scarce. METHODS: We collected daily death records in people with HIV/AIDS from all counties (N = 103) of Hubei province, China from 2018 to 2019. The county-level daily concentrations of PM1, PM2.5 and PM10 in the same period were extracted from ChinaHighAirPollutants dataset. A time-stratified case-crossover design with conditional logistic regression analysis was performed to assess the associations between PM and mortality. RESULTS: Each 1 µg/m3 increased in PM1 corresponded with 0.89 % elevated in all-cause deaths (ACD) at lag 0-4 days. The largest effects of PM1, PM2.5 and PM10 on AIDS-related deaths (ARD) were detected at lag 0-4 days, and PM1 [percent changes in odds ratio: 2.51 % (95 % CIs: 0.82, 4.22)] appeared greater health hazards than PM2.5 [1.24 % (95 % CIs: 0.33, 2.15)] as well as PM10 [0.65 % (95 % CIs: 0.01, 1.30)]. In subgroup analyses, the significant associations of PM1/PM2.5 and ACD were only found in male and the cold season. We also observed the effects of PM1 and PM10 on ARD were significantly stronger (P for interaction <0.05) in males than females. In addition, we caught sight of HIV/AIDS patients aged over 60 years old were more susceptible to ARD caused by PM than younger population. CONCLUSIONS: Our study suggested PM1 was positively linked with the risk of ACD and ARD. Male patients with HIV/AIDS were more significantly susceptible to PM1, PM2.5 and PM10. PM1/PM2.5 appeared stronger associations with ARD in HIV/AIDS patients aged over 60 years old and in the cold season.

Global Burden of osteoarthritis associated with high body mass index in 204 countries and territories, 1990-2019: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To quantify the burden of osteoarthritis (OA) associated with high body mass index (BMI) across 204 countries and territories from 1990 to 2019. METHODS: This study extracted global, regional, and national data on years lived with disability (YLD) of OA associated with high BMI from GBD 2019. The YLD burden of OA associated with high BMI was systematically analyzed by age, SDI, sex, and EAPC. RESULTS: At the global level, ~2.67 million (95% UI: 1.04, 5.75) YLD were attributable to OA associated with high BMI, with an age-standardized rate of 31.9 (95% UI: 12.4, 68.75) YLD per 100,000 population in 2019. There was a 0.5 increase (95% UI: 0.35, 0.79) over the 30 years with an EAPC of 1.45. In 2019, Australasia {57.49 (95% UI: 23.62, 125.38)}, high-income North America {56.2 (95% UI: 23.32, 121.97)}, and Andean Latin America {49.77 (95% UI: 19.73, 111.73)} had the highest age-standardized YLD rates. The population aged at 60-74 group had a higher YLD rate for both males and females. Females tended to be more sensitive to the OA associated with high BMI than male in any region. CONCLUSIONS: In summary, the YLD rate of OA associated with high BMI presented a continuous upward trend in most countries. Women and older people are more sensitive to OA due to physiological and psychological factors. Controlling modifiable risk factors such as maintaining an appropriate BMI is needed for disease prevention.

The associations between short-term exposure to ambient particulate matter and hospitalizations for osteoporotic fracture in Hangzhou: a time-stratified case-crossover study.

Our results suggested that short-term exposure to particulate matter (PM) might increase the risks of hospitalizations for osteoporotic fractures. Government should protect its citizens by putting in place policies to reduce unhealthy emissions and air pollution. INTRODUCTION: Osteoporotic fractures are accompanied by high rates of disability and mortality. PM has been linked with many health outcomes. However, few studies focus on the association of short-term exposure to ambient PM and osteoporotic fractures. METHODS: Data on daily mean air pollution, meteorological factors, and hospitalizations for osteoporotic fractures were collected from Hangzhou, China, 2020-2021. A time-stratified case-crossover design with extended Cox proportional hazards regression was applied to assess the associations between PM and osteoporotic fractures. RESULTS: Short-term exposure to PM significantly increased the risks of hospitalizations for osteoporotic fractures at cumulative lag days. Per 10 µg/m3 increased in PM2.5 (PM with an aerodynamic diameter ≤ 2.5 µm), PMC (PM with an aerodynamic diameter between 2.5 µm and 10 µm), and PM10 (PM with an aerodynamic diameter ≤ 10 µm) were associated with 5.65% (95% confidence intervals (CIs): 1.29, 10.19), 3.19% (0.11, 6.36), and 2.45% (0.57, 4.37) increase in hospitalizations for osteoporotic fractures, respectively. Significant PM-osteoporotic fracture associations were only observed in females and people aged over 65 years old. For the season, the estimates of PM on hospitalizations for osteoporotic fractures were 6.30% (95% CIs: 1.62, 11.20) in the cold season vs. 2.16% (95% CIs: - 4.62, 9.42) in the warm season for per 10 µg/m3 increase of PM2.5, and 0.99 (95% CIs: - 2.69, 4.80) vs. 6.72% (95% CIs: 0.68, 13.13) for PMC. CONCLUSIONS: Our study showed PM was positively linked with the risk of osteoporotic fractures. Females and people aged over 65 years old were more susceptible to PM. The adverse impacts of PM2.5 in the cold season and PMC in the warm season were worthy of special attention.

Trends in the global burden of oral cancer joint with attributable risk factors: Results from the global burden of disease study 2019.

OBJECTIVES: To investigate the characteristics of risk factors for oral cancer and the disease burden they caused. MATERIALS AND METHODS: Data from GBD2019, where the EAPC was calculated to understand mortality trends and the APC model was used for the analysis of age characteristics. RESULTS: Overall oral cancer mortality showed a promising downward trend [EAPC = -0.05 (-0.08 to -0.02)]. Oral cancer mortality attributable to tobacco chewing alone showed a significant upward trend [EAPC = 0.44 (0.36-0.52)]. Males are the majority of oral cancer deaths, while the disease burden of oral cancer in females could be largely attributable to chewing tobacco. The age of death attributable to each risk factor for oral cancer is concentrated between 45 and 74 years. Mortality for oral cancer caused by alcohol and smokeless tobacco was increasing in younger age groups (age < 45), and this trend was more pronounced in middle and middle-high SDI areas. The disease burden of oral cancer in high SDI regions was mainly attributed to alcohol consumption, while in middle and lower SDI regions it was mainly attributed to tobacco. CONCLUSION: Smokeless tobacco proved a critical factor in the significant regional distribution of oral cancer. Oral cancer is on the increase in younger age groups. According to the characteristics of the distribution of risk factors, in traditionally high-incidence regions, such as India and Pakistan, oral cancer kept the highest ASDR, but was not experiencing the fastest growth rate. Additionally, it was oral cancer in middle SDI regions that needs more attention.

Long-term exposure to air pollution might decrease bone mineral density T-score and increase the prevalence of osteoporosis in Hubei province: evidence from China Osteoporosis Prevalence Study.

We hypothesized that air pollution could cause oxidative damage and inflammation in the human body, which was linked to bone loss. Our result showed that long-term exposure to air pollution might decrease bone mineral density (BMD) T-score and increase the prevalence of osteoporosis in Hubei province. INTRODUCTION: Osteoporosis is becoming an increasingly serious public health problem with the advent of global aging. Long-term exposure to air pollution has been linked to multitudinous adverse health outcomes, but evidence is still relatively limited and inconsistent for BMD T-score and osteoporosis. This study aimed at exploring the associations between long-term exposure to air pollution and BMD T-score and osteoporosis. METHODS: The Hubei part of the China Osteoporosis Prevalence Study was extracted. Data on air pollutants were collected by the national air quality real-time release platform of China Environmental Monitoring Station. Linear mixed models and multilevel logistic regression analyses were performed to assess the associations between air pollution and BMD T-score and osteoporosis, respectively. Subgroup analyses were conducted to identify vulnerable populations. RESULTS: A total of 1845 participants were included in this cross-section study. Per 10 ug/m3 increase in PM2.5 and SO2 were associated with 0.20 (95% CI: 0.04, 0.36) and 0.31 (95% CI: 0.11, 0.51) decrease in BMD T-score of the neck of femur, respectively. Per 10 ug/m3 increase in CO was linked with 0.03 (95% CI: 0.02, 0.05) decrease in BMD T-score of the total hip. Per 1 ug/m3 increase in PM2.5 was associated with 5% increase in the prevalence of osteoporosis in all participants. In general, the higher concentrations of PM2.5 with the more adverse effect on osteoporosis (P for trend = 0.01). The impact of PM2.5 on osteoporosis in males was higher than that in females [1.29, 95% CI (1.11, 1.50) vs 1.01, 95% CI (0.95, 1.07)]. Per 1 ug/m3 increase in PM10 corresponded with 4% elevation in the risks of osteoporosis in rural population. The ORs (95% CI) for the association of osteoporosis and NO2 in ever/current smoking and drinking population were 1.07 (1.01, 1.13) and 1.05 (1.00, 1.09), respectively. SO2 had a statistically significant positive effect on people with comorbidity [OR = 1.10, (95% CI: 1.00 to 1.21)], while none in people without comorbidity [OR = 0.96, (95% CI: 0.88 to 1.05)]. CONCLUSION: Our study provided evidence that long-term exposure to PM2.5 was linked with the decreased BMD T-score and increased risk of osteoporosis among all participants. The adverse impacts of PM2.5, PM10, and NO2 were larger in males than in females. People having comorbidity, living in rural areas, and current/ever smoking or drinking were more vulnerable to air pollution. Public health departments should consider air pollution to formulate better preventive measures for osteoporosis.

Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer by remodeling the tumor microenvironment via regulation of GAB2/AKT/mTOR signaling pathway.

BACKGROUND: Non-coding RNAs (ncRNAs), including small nucleolar RNAs (snoRNAs), are widely involved in the physiological and pathological processes of human beings. While up to date, although considerable progress has been achieved in ncRNA-related pathogenesis of non-small cell lung cancer (NSCLC), the underlying mechanisms and biological significance of snoRNAs in NSCLC still need to be further clarified. METHODS: Quantitative real-time polymerase chain reaction or RNAscope was performed to verify the expression of Small Nucleolar RNA, H/ACA Box 38B (SNORA38B) in NSCLC cell lines or clinical samples. BALB/c nude mice xenograft model or C57BL/6J mice syngeneic tumor model were estimated to detect the effects of SNORA38B in tumor growth or tumor immune microenvironment in vivo. Cytometry by time of flight, enzyme-linked immunosorbent assay and flow cytometry assay were conducted to clarify the effects and mechanisms of SNORA38B-mediated tumor immunosuppressive microenvironment. The binding activity between SNORA38B and E2F transcription factor 1(E2F1) was detected by RNA immunoprecipitation and RNA pull-down assays. Then, bioinformatics analysis and chromatin immunoprecipitation were utilized to demonstrate the regulation of GRB2-associated-binding protein 2 (GAB2) by E2F1. Moreover, the combinatorial treatment of SNORA38B locked nucleic acid (LNA) and immune checkpoint blockade (ICB) was used to treat murine Lewis lung carcinoma-derived tumor burden C57BL/6J mice to clarify the effectiveness of targeting SNORA38B in NSCLC immunotherapy. RESULTS: SNORA38B was found highly expressed in NSCLC tissues and cell lines, and associated with worse prognosis. Further results showed that SNORA38B functioned as an oncogene via facilitating cell proliferation, migration, invasion, and inhibiting cell apoptosis in vitro and promoting tumorigenesis of NSCLC cells in vivo. SNORA38B could also recruit the CD4+FOXP3+ regulatory T cells by triggering tumor cells to secrete interleukin 10, which in turn reduced the infiltration of CD3+CD8+ T cells in NSCLC tumor microenvironment (TME), favoring tumor progression and poorer immune efficacy. Mechanistically, SNORA38B mainly distributed in the nucleus, and promoted NSCLC progression by regulating GAB2 transcription to activate protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through directly binding with E2F1. Moreover, we found that SNORA38B LNAs were able to ameliorate CD3+CD8+ T cell infiltration in TME, which sensitized NSCLC to the treatment of ICB. CONCLUSIONS: In conclusion, our data demonstrated that SNORA38B functioned as an oncogene in NSCLC both in vitro and in vivo at least in part by regulating the GAB2/AKT/mTOR pathway via directly binding to E2F1. SNORA38B could also sensitize NSCLC to immunotherapy, which may be a critical therapeutic target for NSCLC.

Vitamin D Affects the Warburg Effect and Stemness Maintenance of Non- Small-Cell Lung Cancer Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: Non-Small-Cell Lung Cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all lung cancer cases and resulting in high morbidity and mortality. Previous studies have demonstrated that 1,25-dihydroxy-vitamin-D3 (vitamin D) exhibited anti-cancer activity against breast and prostate cancer. OBJECTIVES: The aim of the current study is to investigate the effect of vitamin D on NSCLC and its underlying mechanism. METHODS: The effects of vitamin D on stemness maintenance and the Warburg effect in NSCLC cells were investigated both in vitro and in vivo. RESULTS AND DISCUSSION: In vitro experiments revealed that vitamin D inhibited glycolysis and stemness maintenance in A549 and NCI-H1975 cells. Both in vitro and in vivo experiments indicated that vitamin D attenuated the expression of metabolism-related enzymes associated with the Warburg effect (GLUT1, LDHA, HK2, and PKM2). In addition, vitamin D down-regulated the expression of stemness-related genes (Oct-4, SOX-2, and Nanog) and the expression of PI3K, AKT, and mTOR. CONCLUSION: Overall, these findings suggest that vitamin D suppresses the Warburg effect and stemness maintenance in NSCLC cells via the inactivation of PI3K/AKT/mTOR signaling, thereby inhibiting the progression of NSCLC. The current study indicates that vitamin D is a potential candidate in therapeutic strategies against NSCLC.