Impact of Warehouse Expansion on Ambient PM2.5 and Elemental Carbon Levels in Southern California's Disadvantaged Communities: A Two-Decade Analysis.

Over the past two decades, the surge in warehouse construction near seaports and in economically lower-cost land areas has intensified product transportation and e-commerce activities, particularly affecting air quality and health in nearby socially disadvantaged communities. This study, spanning from 2000 to 2019 in Southern California, investigated the relationship between ambient concentrations of PM2.5 and elemental carbon (EC) and the proliferation of warehouses. Utilizing satellite-driven estimates of annual mean ambient pollution levels at the ZIP code level and linear mixed effect models, positive associations were found between warehouse characteristics such as rentable building area (RBA), number of loading docks (LD), and parking spaces (PS), and increases in PM2.5 and EC concentrations. After adjusting for demographic covariates, an Interquartile Range increase of the RBA, LD, and PS were associated with a 0.16 µg/m³ (95% CI = [0.13, 0.19], p < 0.001), 0.10 µg/m³ (95% CI = [0.08, 0.12], p < 0.001), and 0.21 µg/m³ (95% CI = [0.18, 0.24], p < 0.001) increase in PM2.5, respectively. For EC concentrations, an IQR increase of RBA, LD, and PS were each associated with a 0.021 µg/m³ (95% CI = [0.019, 0.024], p < 0.001), 0.014 µg/m³ (95% CI = [0.012, 0.015], p < 0.001), and 0.021 µg/m³ (95% CI = [0.019, 0.024], p < 0.001) increase. The study also highlighted that disadvantaged populations, including racial/ethnic minorities, individuals with lower education levels, and lower-income earners, were disproportionately affected by higher pollution levels.

The genetic diversity and evolution analysis of the Hainan melioidosis outbreak strains.

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.

Target of rapamycin coordinates auxin are involved in exogenous melatonin regulated low temperature tolerance in cucumber seedlings.

Low temperature (LT) is an important environmental factor affecting the growth and yield of plants. Melatonin (MT) can effectively enhance the LT tolerance of cucumber. This study found that LT stress induced the expression of Comt1 (caffeic acid O-methyltransferase 1), with the highest expression being about 2-times that of the control. Meanwhile, the content of MT was found to be roughly 63.16% of that in the control samples. Compared with LT treatment alone, exogenous MT pretreatment upregulated the expression levels of TOR (Target of rapamycin), PIN1 (Pin-formed 1), and YUC4 (YUCCA 4), with maximum upregulations reaching approximately 66.67%, 79.32%, and 42.86%, respectively. These results suggest that MT may modulate the tolerance of cucumber seedlings to LT stress by regulating the expression of TOR, PIN1, and YUC4. In addition, co-treatment with AZD-8055 (a TOR inhibitor) or NPA (N-1-naphthylphthalamic acid, an auxin polar transport inhibitor) and MT attenuated MT-induced resistance to LT stress, leading to higher levels of reactive oxygen species (ROS), reduced antioxidant defense capacity, and increased damage to the membrane system in cucumber seedlings. Concurrently, the content of osmoregulatory substances and the photosynthesis decreased. These results demonstrate that both TOR and auxin were required for MT to alleviate LT-induced damage in cucumber. In summary, the present study demonstrates that TOR and auxin signaling synergistically contribute to alleviating LT damage in cucumber seedlings by exogenous MT. These findings help us understand the function of MT and provide insights into the regulatory network of MT that regulates the LT tolerance of plants.

Melatonin-mediated low-temperature tolerance of cucumber seedlings requires Ca2+/CPKs signaling pathway.

Melatonin (Mel) is recognized as a prominent plant growth regulator. This study investigated the alleviating effect of Mel pretreatment on growth inhibition caused by low-temperature (LT) stress (10 °C/6 °C) in cucumber seedlings and explored the role of the Ca2+/Calcium-dependent protein kinases (CPKs) signaling pathway in Mel-regulated LT tolerance. The main results are as follows: compared to LT treatment alone, 100 µM Mel increased both the content of Ca2+ (highest about 42.01%) and the expression levels of Ca2+ transporter and cyclic nucleotide-gated channel (CNGC) genes under LT. Similarly, Mel enhanced the content of CPKs (highest about 27.49%) and the expression levels of CPKs family genes in cucumber leaves under LT. Additionally, pretreatment with 100 µM Mel for three days strengthened the antioxidant defense and photosynthesis of seedlings under LT. Genes in the ICE-CBF-COR pathway and the MAPK cascade were upregulated by Mel, with maximum upregulations reaching approximately 2.5-fold and 1.9-fold, respectively, thus conferring LT tolerance to cucumber seedlings. However, the above beneficial effects of Mel were weakened by co-treatment with calcium signaling blockers (LaCl3 or EGTA) or CPKs inhibitors (TFP or W-7), suggesting that the Ca2+/CPKs pathway is involved in the Mel-mediated regulation of LT tolerance. In conclusion, this study revealed that Mel can alleviate growth inhibition in cucumber seedlings under LT stress and demonstrated that the Ca2+/CPKs signaling pathway is crucial for the Mel-mediated enhancement of LT tolerance. The findings hold promise for providing theoretical insights into the application of Mel in agricultural production and for investigating its underlying mechanisms of action.

XBAT31 regulates reproductive thermotolerance through controlling the accumulation of HSFB2a/B2b under heat stress conditions.

Heat shock transcription factors (HSFs) play a crucial role in heat stress tolerance in vegetative tissues. However, their involvement in reproductive tissues and their post-translational modifications are not well understood. In this study, we identify the E3 ligase XB3 ORTHOLOG 1 IN ARABIDOPSIS THALIANA (XBAT31) as a key player in the ubiquitination and degradation of HSFB2a/B2b. Our results show that the xbat31 mutant exhibits a higher percentage of unfertile siliques and decreased expression of HSPs in flowers under heat stress conditions compared to the wild type. Conversely, the hsfb2a hsfb2b double mutant displays improved reproductive thermotolerance. We find that XBAT31 interacts with HSFB2a/B2b and mediates their ubiquitination. Furthermore, HSFB2a/B2b ubiquitination is reduced in the xbat31-1 mutant, resulting in higher accumulation of HSFB2a/B2b in flowers under heat stress conditions. Overexpression of HSFB2a or HSFB2b leads to an increase in unfertile siliques under heat stress conditions. Thus, our results dissect the important role of the XBAT31-HSFB2a/B2b module in conferring reproductive thermotolerance in plants.

Assessment of the sacroiliac joint in patients with axial spondyloarthritis via three-dimensional ultrashort echo time magnetic resonance imaging.

Background: Bone erosion in the sacroiliac joint (SIJ) is highly specific for the diagnosis of axial spondyloarthritis (axSpA) and may indicate early disease progression. The 3D ultrashort echo time (3D-UTE) technique excels in providing clear contrast between the articular cartilage and the bone cortex interface. Additionally, it is emerging as a promising quantitative tool for detecting early cartilage changes. Therefore, this study aimed to evaluate the diagnostic performance of 3D-UTE sequences in identifying bone erosion in the SIJ of patients with axSpA and to clarify the potential of cartilage T2* values as a quantitative biomarker for axSpA. Methods: This prospective study employed convenience and consecutive sampling methods to recruit patients diagnosed with axSpA in Peking University Third Hospital who met the Assessment of Spondyloarthritis International Society (ASAS) criteria and also an equal number of healthy volunteers. After providing informed consent, all participants underwent 3D-UTE sequences and conventional T2* mapping of the SIJs. Two radiologists separately interpreted the bone erosion of each SIJ on 3D-UTE sequences. Erosion detection of SIJs via computed tomography (CT) served as the standard of reference. The T2* values of the cartilage were measured and compared, and the diagnostic efficacy of the T2* value for axSpA diagnosis was evaluated. Results: A total of 32 patients and 32 healthy volunteers were included. The 3D-UTE sequence, as separately assessed by two reviewers in terms of its ability to detect erosions, exhibited a notable level of accuracy. For the two reviewers, the respective diagnostic sensitivities were 94.7% and 92.9%, the specificities were 97.4% and 96.5%, positive predictive values were 96.7% and 95.4%, the negative predictive values were 95.9% and 94.5%, the accuracies were 96.2% and 94.9%, and the areas under the curve (AUCs) were 96.1% and 94.7%. For the detection of erosions, the interreader κ value was 0.949. The T2* values of the SIJ cartilage were significantly higher in patients with axSpA than in healthy volunteers. The intraobserver intraclass correlation coefficients (ICCs) for T2* measurements ranged between 80.5% and 82.2%. Meanwhile, the interobserver ICCs for UTE-T2* and gradient echo T2* measurements were 81.5% and 80.8%, respectively. The AUCs of the UTE-T2* values for discriminating patients with axSpA from the healthy volunteers of the two readers were 73.3% and 71.6%, respectively. Conclusions: 3D-UTE sequences can be used as a reliable morphological imaging technique for detecting bone erosion in the SIJ. Additionally, UTE-T2* values of the cartilage may offer a quantitative method for identifying patients with axSpA.

Long-term source apportionment of PM2.5 across the contiguous United States (2000-2019) using a multilinear engine model.

Identifying PM2.5 sources is crucial for effective air quality management and public health. This research used the Multilinear Engine (ME-2) model to analyze PM2.5 from 515 EPA Chemical Speciation Network (CSN) and Interagency Monitoring of Protected Visual Environments (IMPROVE) sites across the U.S. from 2000 to 2019. The U.S. was divided into nine regions for detailed analysis. A total of seven source types (tracers) were resolved across the country: (1) Soil/Dust (Si, Al, Ca and Fe); (2) Vehicle emissions (EC, OC, Cu and Zn); (3) Biomass/wood burning (K); (4) Heavy oil/coal combustion (Ni, V, Cl and As); (5) Secondary sulfate (SO42-); (6) Secondary nitrate (NO3-) and (7) Sea salt (Mg, Na, Cl and SO42-). Furthermore, we extracted and calculated secondary organic aerosols (SOA) based on the secondary sulfate and nitrate factors. Notably, significant reductions in secondary sulfate, nitrate, and heavy oil/coal combustion emissions reflect recent cuts in fossil-fueled power sector emissions. A decline in SOA suggests effective mitigation of their formation conditions or precursors. Despite these improvements, vehicle emissions and biomass burning show no significant decrease, highlighting the need for focused control on these persistent pollution sources for future air quality management.

HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis.

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Association of anemia with all-cause mortality in Chinese centenarians: a prospective cohort study.

OBJECTIVES: This study aimed to examine the relationship between anemia and all-cause mortality in Chinese centenarians. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We included 1002 Chinese centenarians from the China Hainan Centenarian Cohort Study (CHCCS) MEASUREMENTS: Standard procedures were followed to perform blood analysis, home interviews, and physical examinations. Anemia was defined as a hemoglobin level of less than 130 g/L for men and less than 120 g/L for women. RESULTS: During the 9-year follow-up period, a total of 929 (92.7%) deaths were identified. Cox proportional hazards regression models revealed that anemia (hazard ratio [HR] 1.289, 95% confidence interval [CI]: 1.117-1.489) was significantly associated with all-cause mortality. There was an apparent dose-response relationship between anemia and all-cause mortality. Centenarians with severe anemia had approximately 1.6 times higher likelihood of all-cause mortality than those without anemia (HR 1.662; 95% CI: 1.154-2.394). CONCLUSION: Anemia is associated with an increased risk of all-cause mortality in Chinese centenarians. Further research will be needed to collect more comprehensive data on the etiology of anemia and causes of death in centenarians.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

Regulation of metal homoeostasis by two F-group bZIP transcription factors bZIP48 and bZIP50 in rice.

Zinc (Zn) deficiency not only impairs plant growth and development but also has negative effects on human health. Rice (Oryza Sativa L.) is a staple food for over half of the global population, yet the regulation of Zn deficiency response in rice remains largely unknown. In this study, we provide evidence that two F-group bZIP transcription factors, OsbZIP48/50, play a crucial role in Zn deficiency response. Mutations in OsbZIP48/50 result in impaired growth and reduced Zn/Fe/Cu content under Zn deficiency conditions. The N-terminus of OsbZIP48/OsbZIP50 contains two Zn sensor motifs (ZSMs), deletion or mutation of these ZSMs leads to increased nuclear localization. Both OsbZIP48 and OsbZIP50 exhibit transcriptional activation activity, and the upregulation of 1117 genes involved in metal uptake and other processes by Zn deficiency is diminished in the OsbZIP48/50 double mutant. Both OsbZIP48 and OsbZIP50 bind to the promoter of OsZIP10 and activate the ZDRE cis-element. Amino acid substitution mutation of the ZSM domain of OsbZIP48 in OsbZIP50 mutant background increases the content of Zn/Fe/Cu in brown rice seeds and leaves. Therefore, this study demonstrates that OsbZIP48/50 play a crucial role in regulating metal homoeostasis and identifies their downstream genes involved in the Zn deficiency response in rice.

Clinical Characteristics and Molecular Genetic Analysis of a Pedigree with Glanzmann's Thrombasthenia.

Objective: The objective of this study was to investigate the clinical phenotype and genetic etiology of Glanzmann's thrombasthenia in a consanguineous pedigree. Methods: Clinical data and ancillary test results were collected from pedigrees with Glanzmann's thrombasthenia. High-throughput sequencing was used to detect variants in the proband. Candidate variants were verified by Sanger sequencing. Results: Two patients in the pedigree were homozygous for the c.2248C>T (p. Arg750Ter) variant of the ITGB3 gene. The parents and maternal grandmother, who didn't have any recurrent haemorrhage, were found to carry a heterozygous c.2248C>T variant of the ITGB3 gene, which was absent in the aunt and paternal grandmother. Conclusion: The homozygous variant c.2248C>T (p. Arg750Ter) in the ITGB3 gene underlies the disease in this pedigree. This diagnosis will facilitate genetic counselling in this pedigree for better patient management and life guidance.

Artificial intelligence for segmentation and classification of lobar, lobular, and interstitial pneumonia using case-specific CT information.

Background: Pneumonia can be anatomically classified into lobar, lobular, and interstitial types, with each type associated with different pathogens. Utilizing artificial intelligence (AI) to determine the anatomical classifications of pneumonia and assist in refining the differential diagnosis may offer a more viable and clinically relevant solution. This study aimed to develop a multi-classification model capable of identifying the occurrence of pneumonia in patients by utilizing case-specific computed tomography (CT) information, categorizing the pneumonia type (lobar, lobular, and interstitial pneumonia), and performing segmentation of the associated lesions. Methods: A total of 61 lobar pneumonia patients, 60 lobular pneumonia patients, and 60 interstitial pneumonia patients were consecutively enrolled at our local hospital from June 2020 and May 2022. All selected cases were divided into a training cohort (n=135) and an independent testing cohort (n=46). To generate the ground truth labels for the training process, manual segmentation and labeling were performed by three junior radiologists. Subsequently, the segmentations were manually reviewed and edited by a senior radiologist. AI models were developed to automatically segment the infected lung regions and classify the pneumonia. The accuracy of pneumonia lesion segmentation was analyzed and evaluated using the Dice coefficient. Receiver operating characteristic curves were plotted, and the area under the curve (AUC), accuracy, precision, sensitivity, and specificity were calculated to assess the efficacy of pneumonia classification. Results: Our AI model achieved a Dice coefficient of 0.743 [95% confidence interval (CI): 0.657-0.826] for lesion segmentation in the training set and 0.723 (95% CI: 0.602-0.845) in the test set. In the test set, our model achieved an accuracy of 0.927 (95% CI: 0.876-0.978), precision of 0.889 (95% CI: 0.827-0.951), sensitivity of 0.889 (95% CI: 0.827-0.951), specificity of 0.946 (95% CI: 0.902-0.990), and AUC of 0.989 (95% CI: 0.969-1.000) for pneumonia classification. We trained the model using labels annotated by senior physicians and compared it to a model trained using labels annotated by junior physicians. The Dice coefficient of the model's segmentation improved by 0.014, increasing from 0.709 (95% CI: 0.589-0.830) to 0.723 (95% CI: 0.602-0.845), and the AUC improved by 0.042, rising from 0.947 to 0.989. Conclusions: Our study presents a robust multi-task learning model with substantial promise in enhancing the segmentation and classification of pneumonia in medical imaging.

NFXL1 functions as a transcriptional activator required for thermotolerance at reproductive stage in Arabidopsis.

Plants are highly susceptible to abiotic stresses, particularly heat stress during the reproductive stage. However, the specific molecular mechanisms underlying this sensitivity remain largely unknown. In the current study, we demonstrate that the Nuclear Transcription Factor, X-box Binding Protein 1-Like 1 (NFXL1), directly regulates the expression of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A (DREB2A), which is crucial for reproductive thermotolerance in Arabidopsis. NFXL1 is upregulated by heat stress, and its mutation leads to a reduction in silique length (seed number) under heat stress conditions. RNA-Seq analysis reveals that NFXL1 has a global impact on the expression of heat stress responsive genes, including DREB2A, Heat Shock Factor A3 (HSFA3) and Heat Shock Protein 17.6 (HSP17.6) in flower buds. Interestingly, NFXL1 is enriched in the promoter region of DREB2A, but not of either HSFA3 or HSP17.6. Further experiments using electrophoretic mobility shift assay have confirmed that NFXL1 directly binds to the DNA fragment derived from the DREB2A promoter. Moreover, effector-reporter assays have shown that NFXL1 activates the DREB2A promoter. The DREB2A mutants are also heat stress sensitive at the reproductive stage, and DEREB2A is epistatic to NFXL1 in regulating thermotolerance in flower buds. It is known that HSFA3, a direct target of DREB2A, regulates the expression of heat shock proteins genes under heat stress conditions. Thus, our findings establish NFXL1 as a critical upstream regulator of DREB2A in the transcriptional cassette responsible for heat stress responses required for reproductive thermotolerance in Arabidopsis.

Multiple cardiometabolic diseases enhance the adverse effects of hypoalbuminemia on mortality among centenarians in China: a cohort study.

BACKGROUND: Although hypoalbuminemia was associated with high risk of mortality in community-dwelling older adults, as well as in the hospitalized older adults, little is known among centenarians. And there are limited data on whether having cardiometabolic diseases (CMDs) is associated with additive effects. METHODS: Baseline examinations including a determination of albumin levels were performed in 1002 Chinese centenarians from January 2014 through to December 2016, and the survival status was subsequently ascertained until 31 May 2021. Cox proportional risk model was performed to assess the risk of all-cause mortality associated with albumin levels and hypoalbuminemia combined with CMDs. RESULTS: Of 1002 participants included in the analysis, the mean level of albumin was 38.5 g/L (± standard deviation, 4.0 g/L), and 174 (17.4%) had hypoalbuminemia (albumin < 35 g/L). The multivariable analyses showed that albumin level was negatively associated with all-cause mortality (Ptrend < 0.05). Compared to normoalbuminemia, hypoalbuminemia was associated with an increased mortality risk in the overall participants (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.22-1.97). Furthermore, the HR (95% CI) of hypoalbuminemia combined with multiple CMDs was 2.15 (1.14-4.07). There was evidence of an additive deleterious dose effect of an increasing number of CMDs (Ptrend = 0.001). CONCLUSIONS: Hypoalbuminemia is associated with an increased risk of all-cause mortality in Chinese centenarians, and this risk is more pronounced among centenarians with multiple cardiometabolic diseases. Our findings suggest that older adults with hypoalbuminemia, especially comorbid multiple CMDs warrant early identification and management.

C-Reactive Protein, Neutrophil-to-Lymphocyte Ratio, and Long-Term Mortality in Chinese Centenarians.

This cohort study explores whether biomarkers of inflammation-related aging, including C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, are associated with long-term mortality in Chinese centenarians.

Long-term association of air pollution and incidence of lung cancer among older Americans: A national study in the Medicare cohort.

BACKGROUND: Despite strong evidence of the association of fine particulate matter (PM2.5) exposure with an increased risk of lung cancer mortality, few studies had investigated associations of multiple pollutants simultaneously, or with incidence, or using causal methods. Disparities were also understudied. OBJECTIVES: We investigated long-term effects of PM2.5, nitrogen dioxide (NO2), warm-season ozone, and particle radioactivity (PR) exposures on lung cancer incidence in a nationwide cohort. METHODS: We conducted a cohort study with Medicare beneficiaries (aged ≥ 65 years) continuously enrolled in the fee-for-service program in the contiguous US from 2001 to 2016. Air pollution exposure was averaged across three years and assigned based on ZIP code of residence. We fitted Cox proportional hazards models to estimate the hazard ratio (HR) for lung cancer incidence, adjusted for individual- and neighborhood-level confounders. As a sensitivity analysis, we evaluated the causal relationships using inverse probability weights. We further assessed effect modifications by individual- and neighborhood-level covariates. RESULTS: We identified 166,860 lung cancer cases of 12,429,951 studied beneficiaries. In the multi-pollutant model, PM2.5 and NO2 exposures were statistically significantly associated with increased lung cancer incidence, while PR was marginally significantly associated. Specifically, the HR was 1.008 (95% confidence interval [CI]: 1.005, 1.011) per 1-µg/m3 increase in PM2.5, 1.013 (95% CI: 1.012, 1.013) per 1-ppb increase in NO2, and 1.005 (0.999, 1.012) per 1-mBq/m3 increase in PR. At low exposure levels, all pollutants were associated with increased lung cancer incidence. Men, older individuals, Blacks, and residents of low-income neighborhoods experienced larger effects of PM2.5 and PR. DISCUSSION: Long-term PM2.5, NO2, and PR exposures were independently associated with increased lung cancer incidence among the national elderly population. Low-exposure analysis indicated that current national standards for PM2.5 and NO2 were not restrictive enough to protect public health, underscoring the need for more stringent air quality regulations.

Climate Penalty on Air Pollution Abated by Anthropogenic Emission Reductions in the United States.

Climate change poses direct and indirect threats to public health, including exacerbating air pollution. However, how a warmer temperature deteriorates air quality, known as the "climate penalty" effect, remains highly uncertain in the United States, particularly under rapid reduction in anthropogenic emissions. Here we examined the sensitivity of surface-level fine particulate matter (PM2.5) and ozone (O3) to summer temperature anomalies in the contiguous US and their decadal changes using high-resolution datasets generated by machine learning models. Our findings demonstrate that, in the eastern US, efficient emission control strategies have significantly reduced the climate penalty effects on PM2.5 and O3, lowering the associated population exposure. In contrast, summer and annual PM2.5 in the western US became more sensitive to temperature, highlighting the urgent need for the management and mitigation of worsening wildfires. Our results have important implications for air quality management and risk assessments of future climate change.

A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer.

BACKGROUND: Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations. METHODS: Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort. RESULTS: A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively). CONCLUSION: This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.

Increasing the Compressive Strength of Helicoidal Laminates after Low-Velocity Impact upon Mixing with 0° Orientation Plies and Its Analysis.

The helicoidal laminate is a kind of nature inspired fiber reinforced polymer, and the ply orientation affects their mechanical properties for engineering structural applications. A variety of helicoidal laminates with uniform and non-linear pitch angles mixed with additional 0° plies are fabricated to investigate the impact resistance through low-velocity impact and after-impact compression tests. Additionally, helicoidal laminates with constant pitch angles, quasi-isotropic laminate, and cross-ply laminates are also fabricated for a comparative study. The impact characteristics and the compressive strength are analyzed in view of the impact model, shear stress distribution, and fracture toughness. The results suggest that 10° or 20° are the better basic pitch angles before mixing 0° orientation plies. The 0° orientation plies may affect the contact stiffness, bending stiffness, damage extent, and compressive modulus. The compressive strength reaches the highest in tests on two samples with different percentages of 0° orientation plies and ply setups. Bending stiffness also dominates the impact response. The analysis on the laminate parameters provides ideas to improve the residual strength of helicoidal laminate.