B-Glycine as a marker for ß cell imaging and ß cell mass evaluation.

PURPOSE: ß cell mass (BCM) and function are essential to the diagnosis and therapy of diabetes. Diabetic patients serve ß cell loss is, and damage of ß cells leads to severe insulin deficiency. Our understanding of the role of BCM in diabetes progression is extremely limited by lacking efficient methods to evaluate BCM in vivo. In vitro methods of labeling islets, including loading of contrast reagent or integration of exogenous biomarker, require artificial manipulation on islets, of which the clinical application is limited. Imaging methods targeting endogenous biomarkers may solve the above problems. However, traditional reagents targeting GLP-1R and VAMT2 result in a high background of adjacent tissues, complicating the identification of pancreatic signals. Here, we report a non-invasive and quantitative imaging technique by using radiolabeled glycine mimics ([18F]FBG, a boron-trifluoride derivative of glycine) to assay islet function and monitor BCM changes in living animals. METHODS: Glycine derivatives, FBG, FBSa, 2Me-FBG, 3Me-FBG, were successfully synthesized and labeled with 18F. Specificity of glycine derivatives were characterized by in vitro experiment. PET imaging and biodistribution studies were performed in animal models carring GLYT over-expressed cells. In vivo evaluation of BCM with [18F]FBG were performed in STZ (streptozocin) induced T1D (type 1 diabetes) models. RESULTS: GLYT responds to excess blood glycine levels and transports glycine into islet cells to maintain the activity of the glycine receptor (GLYR). Best PET imaging condition was 80 min after given a total of 240 ~ 250 nmol imaging reagent (a mixture of [18F]FBG and natural glycine) intravenously. [18F]FBG can detect both endogenous and exogenous islets clearly in vivo. When applied to STZ induced T1D mouse models, total uptake of [18F]FBG in the pancreas exhibited a linear correlation with survival BCM. CONCLUSION: [18F]FBG targeting the endogenous glycine transporter (GLYT), which is highly expressed on islet cells, avoiding extra modification on islet cells. Meanwhile the highly restricted expression pattern of GLYT excluded the background in adjacent tissues. This [18F]FBG-based imaging technique provides a non-invasive method to quantify BCM in vivo, implying a new evaluation index for diabetic assessment.

Identification of multiple plasma lipids as diagnostic biomarkers of hypercholesterolemia and the underlying mechanisms based on pseudo-targeted lipidomics.

RATIONALE: Hypercholesterolemia is an important risk factor for cardiovascular diseases and death. This study performed pseudo-targeted lipidomics to identify differentially expressed plasma lipids in hypercholesterolemia, to provide a scientific basis for the diagnosis and pathogenesis of hypercholesterolemia. METHODS: Pseudo-targeted lipidomic analyses of plasma lipids from 20 patients with hypercholesterolemia and 20 normal control subjects were performed using liquid chromatography-mass spectrometry. Differentially expressed lipids were identified by principal component analysis and orthogonal partial least squares discriminant analysis. Receiver operating characteristic curves were used to identify differentially expressed lipids with high diagnostic value. The Kyoto Encyclopedia of Genes and Genomes pathway database was used to identify enriched metabolic pathways. RESULTS: We identified 13 differentially expressed lipids in hypercholesterolemia using variable importance of projection > 1 and p < 0.05 as threshold parameters. The levels of eight sphingomyelins and cholesterol sulfate were higher and those of three triacylglycerols and lysophosphatidylcholine were reduced in hypercholesterolemia. Seven differentially expressed plasma lipids showed high diagnostic value for hypercholesterolemia. Functional enrichment analyses showed that pathways related to necroptosis, sphingolipid signaling, sphingolipid metabolism, and steroid hormone biosynthesis were enriched. CONCLUSIONS: This pseudo-targeted lipidomics study demonstrated that multiple sphingomyelins and cholesterol sulfate were differentially expressed in the plasma of patients with hypercholesterolemia. We also identified seven plasma lipids, including six sphingomyelins and cholesterol sulfate, with high diagnostic value.

Impact of diabetes on COVID-19 and glucocorticoids on patients with COVID-19 and diabetes during the Omicron variant epidemic: a multicenter retrospective cohort study in South China.

BACKGROUND: To explore the impact of diabetes on the clinical features and prognosis of COVID-19 and assess the influence of glucocorticoid use on the prognosis of patients with COVID-19 and diabetes. METHODS: This retrospective multicenter cohort study included patients admitted between December 2022 and January 2023. The patients were grouped according to diabetes and glucocorticoid use. The primary outcome was in-hospital mortality. RESULTS: Among 400 patients with glucocorticoid data, 109 (27.3%) had diabetes. The inflammatory cytokines were higher in patients with diabetes, manifested by higher IL-6 (25.33 vs. 11.29 ng/L, p = 0.011), CRP (26.55 vs. 8.62 mg/L, p = 0.003), and PCT (0.07 vs. 0.04 ng/ml, p = 0.010), while CD4+ (319 vs. 506 /mL, p = 0.004) and CD8+ (141 vs. 261 /mL, p < 0.001) T lymphocytes were lower. The overall mortality rate of hospitalized COVID-19 patients with diabetes was 13.46%. The diabetic patients who received glucocorticoids vs. those who did not receive glucocorticoids had a similar mortality (15.00% vs. 11.39%, p = 0.591). CONCLUSIONS: Patients with COVID-19 and diabetes are more likely to experience hyperinflammatory response and T cell reduction, especially those with severe/critical disease. Glucocorticoid use was not associated with the prognosis of COVID-19 in patients with diabetes. Still, glucocorticoids should be used cautiously in diabetic patients with severe/critical COVID-19.

Adaptive orthogonal directional total variation with kernel regression for CT image denoising.

BACKGROUND: Low-dose computed tomography (CT) has been successful in reducing radiation exposure for patients. However, the use of reconstructions from sparse angle sampling in low-dose CT often leads to severe streak artifacts in the reconstructed images. OBJECTIVE: In order to address this issue and preserve image edge details, this study proposes an adaptive orthogonal directional total variation method with kernel regression. METHODS: The CT reconstructed images are initially processed through kernel regression to obtain the N-term Taylor series, which serves as a local representation of the regression function. By expanding the series to the second order, we obtain the desired estimate of the regression function and localized information on the first and second derivatives. To mitigate the noise impact on these derivatives, kernel regression is performed again to update the first and second derivatives. Subsequently, the original reconstructed image, its local approximation, and the updated derivatives are summed using a weighting scheme to derive the image used for calculating orientation information. For further removal of stripe artifacts, the study introduces the adaptive orthogonal directional total variation (AODTV) method, which denoises along both the edge direction and the normal direction, guided by the previously obtained orientation. RESULTS: Both simulation and real experiments have obtained good results. The results of two real experiments show that the proposed method has obtained PSNR values of 34.5408 dB and 29.4634 dB, which are 1.2392-5.9333 dB and 2.828-6.7995 dB higher than the contrast denoising algorithm, respectively, indicating that the proposed method has good denoising performance. CONCLUSIONS: The study demonstrates the effectiveness of the method in eliminating strip artifacts and preserving the fine details of the images.

[A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies].

OBJECTIVE: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment. METHODS: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs. RESULTS: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever (P=0.002) and rapid progressive interstitial lung disease (RP-ILD) (P=0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype (P=0.007), interstitial lung disease (ILD) (P=0.001), eleva-ted AST (P=0.012), elevated serum ferritin (P=0.016) and decreased count of CD4+T cells in peripheral blood (P=0.004) might be the risk factors for IIMs non-complete clinical response. CONCLUSION: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Detection and analysis of potential landslides based on SBAS-InSAR technology in alpine canyon region.

The Lancang River flows through the alpine canyon region of southwest China, an area that has experienced frequent geological disasters over the years. Early monitoring of geological hazards is essential for disaster prevention and mitigation. However, traditional ground monitoring techniques are limited by the complex terrain conditions in high-altitude valley regions. In contrast, interferometric synthetic aperture radar (InSAR) technology can provide a high-precision, wide-range monitoring of slow rock-slope deformation, making it an effective tool for studying geological hazards. Within the study area, multiple synthetic aperture radar (SAR) images from the Sentinel-1A satellite were collected, and surface deformation was obtained using the small baseline subset InSAR (SBAS-InSAR). The results demonstrate that combining ascending and descending orbit images can be successfully applied to landslide monitoring in complex mountainous areas. Over 30 potential landslides were identified by combining InSAR results with optical images. The Line-Of-Sight (LOS) direction deformation features and their relationship with precipitation were analyzed based on two typical landslides, and two-dimensional/three-dimensional (2D/3D) deformation decomposition was carried out to reveal its motion characteristics. It was found that the cumulative deformation fluctuation amplitude was higher during the rainy season, and the main movement direction of the landslide was east-west. In addition, based on the spatial distribution and statistical analysis of deformation points along with meteorological data, geological elements, human activities, and topographic conditions, it is inferred that factors such as low vegetation coverage, tectonic movements, human activities, and high-altitude glacier thawing may contribute to the occurrence of disasters. And it was found that areas with high vegetation cover, high rainfall, and snow cover exhibit lower coherence coefficients. This study offers valuable insights for investigating large-scale geological in alpine canyon regions.

Establishment and assessment of mortality risk prediction model in patients with sepsis based on early-stage peripheral lymphocyte subsets.

This study is aimed to explore the value of lymphocyte subsets in evaluating the severity and prognosis of sepsis. The counts of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and NK cells significantly decreased between day 1 and day 3 in both the survivor and the non-survivor groups. The peripheral lymphocyte subsets (PLS) at day 1 were not significantly different between the survivor and the non-survivor groups. However, at day 3, the counts of lymphocytes, CD3+ T cells, CD4+ T cells, and NK cells were remarkably lower in the non-survivor group. No significant differences in CD8+ T cells, or CD19+ B cells were observed. The PLS index was independently and significantly associated with the 28-day mortality risk in septic patients (OR: 3.08, 95% CI: 1.18-9.67). Based on these clinical parameters and the PLS index, we developed a nomograph for evaluating the individual mortality risk in sepsis. The area under the curve of prediction with the PLS index was significantly higher than that from the model with only clinical parameters (0.912 vs. 0.817). Our study suggests that the decline of PLS occurred in the early stage of sepsis. The new novel PLS index can be an independent predictor of 28-day mortality in septic patients. The prediction model based on clinical parameters and the PLS index has relatively high predicting ability.

Influence of climate extremes on long-term changes in cyanobacterial blooms in a eutrophic and shallow lake.

Climate change and human activities have crucial effects on the variations in phytoplankton blooms in lakes worldwide. A record-breaking heatwave and drought event was reported in the middle and lower reaches of the Yangtze River during the summer of 2022, but only little is known about how cyanobacterial blooms in lakes respond to such climate extremes. Here, we utilized MODIS images to generate the area, occurrence, and initial blooming date (IBD) of cyanobacterial blooms in Lake Chaohu from 2000 to 2022. We found that the area and occurrence of cyanobacterial blooms were largely reduced. At the same time, the IBD was delayed in 2022 compared with the previous 20 years. The annual occurrence and mean area of cyanobacterial blooms in 2022 were 17 % and 23.1 km2, respectively, which were the lowest reported levels since the 21st century. The IBD in 2022 was four months late compared with the IBD in 2020. The high wind speed in spring delayed the spring blooms in 2022. The record-breaking heatwaves and drought from June to August reduced the blooms by influencing the growth of cyanobacteria and reducing the flow of nutrients from the watershed into the lake. This study highlights the compound impact of heatwave and drought climate events on reducing cyanobacterial blooms in a long-term period, enhancing additional understanding of the changes in phytoplankton blooms in lakes.

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer.

Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

[Retracted] Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the certain of the cell proliferation assay data shown in Fig. 4C on p. 1444 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been submitted for publication [Shi N, Shan B, Song Y, Chu H and Qian L: Circular RNA circ­PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR­3680­3p in esophageal squamous cell carcinoma. J Cell Biochem 120: 10021­10030, 2019]. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 1439­1448, 2020; DOI: 10.3892/mmr.2020.10957].

Comparative chloroplast genomes: insights into the identification and phylogeny of rapid radiation genus Rhodiola.

Rhodiola L. is a genus exhibiting rapid radiation and represents a typical case for studying plastid gene adaptation in species that spread from high altitudes to low altitudes. In this study, 23 samples of 18 Rhodiola species were collected from the Qinghai-Tibetan Plateau and five scattered alpine areas, and the plastid genomes (plastomes) of these species were sequenced, annotated, and compared between high-altitude and widely distributed groups. The plastomes of Rhodiola were found to be highly conserved in terms of gene size, content, and order but highly variable in several lineage-specific features, such as codon usage bias, IR boundary shifting, and distinct repeat sequence structures binding to SSRs. Codon usage in the genes of photosystem II exhibited an obvious preference, reflecting significant environmental adaptation pressures. In this study, three repeat regions compounded with trinucleotide and mononucleotide repeats were found for the first time in R. forrestii, R. himalensis, and R. yunnanensis. High-variability regions such as ndhF, ycf1, trnH-psbA, and rpoC1-rpoB were screened, laying the foundation for the precise identification of these species. The phylogenetic analysis revealed the occurrence of cyto-nuclear discordance, likely originating from the frequent interspecific hybridization events observed within Rhodiola species during rapid radiation. Dioecious and hermaphrodite species can be broadly categorized into two subclades, probably they have different environmental adaptation strategies in response to climate change. In addition, the phylogenetic tree supported the monophyly of R. forrestii and R. yunnanensis, which compose R. Sect. Pseudorhodiola. In conclusion, plastome data enrich the genetic information available for the Rhodiola genus and may provide insight into species migration events during climate change.

Clinicopathologic features and new factors affecting constitution of eyelid neoplasms: a 10-year multicentre experience in southern coastal China.

OBJECTIVE: This study aims to delineate the key characteristics of eyelid neoplasms in central and southern coastal China and to explore potential factors affecting tumour development. METHODS: This was a retrospective, multicentre observational study. In total, 1302 cases of eyelid neoplasms diagnosed in 2 tertiary hospitals were reviewed from January 2013 to May 2023. Histogenesis, pathologic diagnosis, and potential risk factors were investigated, and the findings were compared with data from various regions and countries. Age- and sex-specific incidence rates, time trends, distributions across age groups, and the relationship with the Sociodemographic Index, latitude, and altitude were calculated. RESULTS: There were 1162 benign (89.2%) and 140 malignant (10.8%) cases, representing 63 pathologic types. The median age of benign cases (50 years) was significantly lower than that of malignant cases (72 years) (P < 0.05). The most common benign and malignant lesions were intradermal nevus (28.83%) and basal cell carcinoma (BCC) (74.29%). A relatively younger median age (68 years) for sebaceous gland carcinoma (SGC) was observed, with a male preponderance (sex ratio 2:1). Analyses of the proportions of BCC, SGC, and squamous cell carcinoma in eyelid malignancies revealed significant regression equations (P < 0.05). CONCLUSIONS: Most eyelid neoplasms are of epithelial and melanocytic origin, with benign tumours being predominant. The regions with greater Sociodemographic Index exhibit a greater incidence of BCC and a lower incidence of squamous cell carcinoma and SGC. BCC appears to have a greater incidence in regions located at higher latitudes.

Efficacy of the COVID-19 vaccination in patients with asymptomatic or mild illness during the Omicron epidemic in Guangzhou: a multi-centre retrospective cohort study.

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

A novel predictive model for optimizing diabetes screening in older adults.

INTRODUCTION: The fasting blood glucose test is widely used for diabetes screening. However, it may fail to detect early-stage diabetes characterized by elevated postprandial glucose levels. Hence, we developed and internally validated a nomogram to predict the diabetes risk in older adults with normal fasting glucose levels. MATERIALS AND METHODS: This study enrolled 2,235 older adults, dividing them into a Training Set (n = 1,564) and a Validation Set (n = 671) based on a 7:3 ratio. We employed the least absolute shrinkage and selection operator regression to identify predictors for constructing the nomogram. Calibration and discrimination were employed to assess the nomogram's performance, while its clinical utility was evaluated through decision curve analysis. RESULTS: Nine key variables were identified as significant factors: age, gender, body mass index, fasting blood glucose, triglycerides, alanine aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, blood urea nitrogen, and hemoglobin. The nomogram demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.824 in the Training Set and 0.809 in the Validation Set. Calibration curves for both sets confirmed the model's accuracy in estimating the actual diabetes risk. Decision curve analysis highlighted the model's clinical utility. CONCLUSIONS: We provided a dynamic nomogram for identifying older adults at risk of diabetes, potentially enhancing the efficiency of diabetes screening in primary healthcare units.

spread.gl: visualising pathogen dispersal in a high-performance browser application.

Phylogeographic analyses are able to exploit the location data associated with sampled molecular sequences to reconstruct the spatio-temporal dispersal history of a pathogen. Visualisation software is commonly used to facilitate the interpretation of the accompanying estimation results, as these are not always easily interpretable. spread.gl is a powerful, open-source and feature-rich browser application that enables smooth, intuitive and user-friendly visualisation of both discrete and continuous phylogeographic inference results, enabling the animation of pathogen geographic dispersal through time. spread.gl can render and combine the visualisation of several data layers, including a geographic layer (e.g., a world map), multiple layers that contain information extracted from the input phylogeny, and different types of layers that represent environmental data. As such, users can explore which environmental data may have shaped pathogen dispersal patterns, that can subsequently be formally tested through more principled statistical analyses. We showcase the visualisation features of spread.gl on several representative pathogen dispersal examples, including the smooth animation of a phylogeny encompassing over 17,000 genomic sequences resulting from a large-scale SARS-CoV-2 analysis.

Cadmium exposure induces multigenerational inheritance of germ cell apoptosis and fertility suppression in Caenorhabditis elegans.

Cadmium is a significant environmental pollutant that poses a substantial health hazard to humans due to its propensity to accumulate in the body and resist excretion. We have a comprehensive understanding of the damage caused by Cd exposure and the mechanisms of tolerance, however, the intricate mechanisms underlying multigenerational effects resulting from Cd exposure remain poorly understood. In this study, Caenorhabditis elegans were used as a model organism to investigate Cd-induced multigenerational effects and its association with epigenetic modifications. The results showed that Cd exposure leads to an increase in germ cell apoptosis and a decrease in fertility, which can be passed down to subsequent generations. Further analysis revealed that transcription factors DAF-16/FOXO and SKN-1/Nrf2 play essential roles in responding to Cd exposure and in the transgenerational induction of germ cell apoptosis. Additionally, histone H3K4 trimethylation (H3K4me3) marks stress-responsive genes and enhances their transcription, ultimately triggering multigenerational germ cell apoptosis. This study provides compelling evidence that the detrimental effects of Cd on the reproductive system can be inherited across generations. These findings enhance our understanding of the multigenerational effects of environmental pollutants and may inform strategies for the prevention and control of such pollutants.