Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: a meta-analysis of cohort studies.

PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.

Complete androgen insensitivity syndrome coexisting with müllerian duct remnants: a case report and literature review.

This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from androgen receptor (AR) gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of "primary amenorrhea." Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the AR gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.

Dynamics of collagen oxidation and cross linking in regenerating and irreversibly infarcted myocardium.

In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.

Wildfire Impacts on Molecular Changes of Dissolved Organic Matter during Its Passage through Soil.

The frequency and intensity of global wildfires are escalating, leading to an increase in derived pyrogenic dissolved organic matter (pyDOM), which potentially influences the riverine carbon reservoir and poses risks to drinking water safety. However, changes in pyDOM properties as it traverses through soil to water bodies are highly understudied due to the challenges of simulating such processes under laboratory conditions. In this study, we extracted soil DOM along hillslope gradients and soil depths in both burned and unburned catchments post wildfire. Using high-resolution mass spectrometry and a substrate-explicit model, we observed significant increases in the relative abundance of condensed aromatics (ConAC) and tannins in wildfire-affected soil DOM. Wildfire-affected soil DOM also displayed a broader spectrum of molecular and thermodynamic properties, indicative of its diverse composition and reactivity. Furthermore, as the fire-induced weakening of topsoil microbial reprocessing abilities hindered the transformation of plant-derived DOM, the relative abundance of lignin-like compounds increased with soil depth in the fire regions. Meanwhile, the distribution of shared molecular formulas along the hillslope gradient (from shoulder to toeslope) exhibited analogous patterns in both burned and unburned catchments. Although there was an increased prevalence of ConAC and tannin in the burned catchments, the relative abundance of these fractions diminished along the hillslope in all three catchments. Based on the substrate-explicit model, the biodegradability exhibited by wildfire-affected DOM fractions offers the possibility of its conversion along hillslopes. Our findings reveal the spatial distribution of DOM properties after a wildfire, facilitating accurate evaluation of dissolved organic carbon composition involved in the watershed-scale carbon cycle.

Multiscale dilated convolutional neural network for Atrial Fibrillation detection.

Atrial Fibrillation (AF), a type of heart arrhythmia, becomes more common with aging and is associated with an increased risk of stroke and mortality. In light of the urgent need for effective automated AF monitoring, existing methods often fall short in balancing accuracy and computational efficiency. To address this issue, we introduce a framework based on Multi-Scale Dilated Convolution (AF-MSDC), aimed at achieving precise predictions with low cost and high efficiency. By integrating Multi-Scale Dilated Convolution (MSDC) modules, our model is capable of extracting features from electrocardiogram (ECG) datasets across various scales, thus achieving an optimal balance between precision and computational savings. We have developed three MSDC modules to construct the AF-MSDC framework and assessed its performance on renowned datasets, including the MIT-BIH Atrial Fibrillation Database and Physionet Challenge 2017. Empirical results unequivocally demonstrate that our technique surpasses existing state-of-the-art (SOTA) methods in the AF detection domain. Specifically, our model, with only a quarter of the parameters of a Residual Network (ResNet), achieved an impressive sensitivity of 99.45%, specificity of 99.64% (on the MIT-BIH AFDB dataset), and an [Formula: see text] score of 85.63% (on the Physionet Challenge 2017 AFDB dataset). This high efficiency makes our model particularly suitable for integration into wearable ECG devices powered by edge computing frameworks. Moreover, this innovative approach offers new possibilities for the early diagnosis of AF in clinical applications, potentially improving patient quality of life and reducing healthcare costs.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of SARS-CoV-2 uncertain, use of safe and effective COVID-19 vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month-<12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month-<5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5-<12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month-<5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5-<12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable to dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6 month-<12-year-olds. Reactogenicity events were generally mild-to-moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

A novel copper ion enhanced electrochemical DNA biosensor for the determination of epinephrine.

A novel electrochemical biosensor was developed for the detection of epinephrine (EP) by immobilizing double-strand DNA (dsDNA) bound with copper ions on a gold electrode (Cu2+/dsDNA/MCH/AuE). The electrochemical behavior of EP at Cu2+/dsDNA/MCH/AuE was examined, and the results demonstrated a significant enhancement in the electrocatalytic oxidation peak current of EP due to the formation of a stable G-Cu(II)-G sandwich structure between Cu2+ and guanine at the modified electrode. The modification process of the electrode was characterized by scanning electron microscopy, infrared spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. A study on the effect of pH in phosphate buffer solution on the electrochemical oxidation of EP indicated that the catalytic oxidation process was pH-dependent. A plot of catalytic current versus EP concentration exhibited a dual-linear relationship within two ranges: 1.0-12.5 µM and 12.5-1000.0 µM, with correlation coefficients of 0.995 and 0.997, respectively. The limit of detection was determined to be 47 nM (S/N = 3). According to the calculated Hill coefficient (0.99), it can be concluded that the electrocatalytic process followed the Michaelis-Menten kinetic mechanism. The maximum catalytic current Im was 25 µA, while the apparent Michaelis-Menten constant Km was 1.425 mM. These findings indicated excellent electrocatalytic activity of the modified electrode towards oxidation of EP. The developed biosensor successfully detected EP in spiked mouse serum as well as epinephrine hydrochloride injection with high selectivity, sensitivity, stability, and accuracy.

Relationship of long-term exposure to air pollutant mixture with metabolic-associated fatty liver disease and subtypes: A retrospective cohort study of the employed population of Southwest China.

BACKGROUND: While evidence suggests that PM2.5 is associated with overall prevalence of Metabolic (dysfunction)-Associated Fatty Liver Disease (MAFLD), effects of comprehensive air pollutant mixture on MAFLD and its subtypes remain unclear. OBJECTIVE: To investigate individual and joint effects of long-term exposure to comprehensive air pollutant mixture on MAFLD and its subtypes. METHODS: Data of 27,699 participants of the Chinese Cohort of Working Adults were analyzed. MAFLD and subtypes, including overweight/obesity, lean, and diabetes MAFLD, were diagnosed according to clinical guidelines. Concentrations of NO3-, SO42-, NH4+, organic matter (OM), black carbon (BC), PM2.5, SO2, NO2, O3 and CO were estimated as a weighted average over participants' residential and work addresses for the three years preceding outcome assessment. Logistic regression and weighted quantile sum regression were used to estimate individual and joint effects of air pollutant mixture on presence of MAFLD. RESULTS: Overall prevalence of MAFLD was 26.6 % with overweight/obesity, lean, and diabetes MAFLD accounting for 92.0 %, 6.4 %, and 1.6 %, respectively. Exposure to SO42-, NO3-, NH4+, BC, PM2.5, NO2, O3and CO was significantly associated with overall MAFLD, overweight/obesity MAFLD, or lean MAFLD in single pollutant models. Joint effects of air pollutant mixture were observed for overall MAFLD (OR = 1.10 [95 % CI: 1.03, 1.17]), overweight/obesity (1.09 [1.02, 1.15]), and lean MAFLD (1.63 [1.28, 2.07]). Contributions of individual air pollutants to joint effects were dominated by CO in overall and overweight/obesity MAFLD (Weights were 42.31 % and 45.87 %, respectively), while SO42- (36.34 %), SO2 (21.00 %) and BC (12.38 %) were more important in lean MAFLD. Being male, aged above 45 years and smoking increased joint effects of air pollutant mixture on overall MAFLD. CONCLUSIONS: Air pollutant mixture was associated with MAFLD, particularly the lean MAFLD subtype. CO played a pivotal role in both overall and overweight/obesity MAFLD, whereas SO42- were associated with lean MAFLD.

Microcystin-LR (MC-LR) inhibits green algae growth by regulating antioxidant and photosynthetic systems.

Microcystins release from bloom-forming cyanobacteria is considered a way to gain competitive advantage in Microcystis populations, which threaten water resources security and aquatic ecological balance. However, the effects of microcystins on microalgae are still largely unclear. Through simulated culture experiments and the use of UHPLC-MS-based metabolomics, the effects of two microcystin-LR (MC-LR) concentrations (400 and 1,600 µg/L) on the growth and antioxidant properties of three algae species, the toxic Microcystis aeruginosa, a non-toxic Microcystis sp., and Chlorella vulgaris, were studied. The MC-LR caused damage to the photosynthetic system and activated the protective mechanism of the photosynthetic system by decreasing the chlorophyll-a and carotenoid concentrations. Microcystins triggered oxidative stress in C. vulgaris, which was the most sensitive algae species studied, and secreted more glycolipids into the extracellular compartment, thereby destroying its cell structure. However, C. vulgaris eliminated reactive oxygen species (ROS) by secreting terpenoids, thereby resisting oxidative stress. In addition, two metabolic pathways, the vitamin B6 and the sphingolipid pathways, of C. vulgaris were significantly disturbed by microcystins, contributing to cell membrane and mitochondrial damage. Thus, both the low (400 µg/L) and the high (1,600 µg/L) MC-LR concentration inhibited algae growth within 3 to 7 days, and the inhibition rates increased with the increase in the MC-LR concentration. The above results indicate that the toxin-producing Microcystis species have a stronger toxin tolerance under longer-term toxin exposure in natural water environments. Thus, microcystins participates in interspecific interaction and phytoplankton population regulation and creates suitable conditions for the toxin-producing M. aeruginosa to become the dominant species in algae blooms.

Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer.

Neoadjuvant therapy (NAT) is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis allysine residues are formed on collagen proteins by the action of lysyl oxidases (LOX). Here we report the application of an allysine-targeted molecular magnetic resonance imaging (MRI) probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of NAT with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, while no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes.

Clinical study of enhanced recovery after surgery in laparoscopic appendectomy for acute appendicitis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a comprehensive management modality that promotes patient recovery, especially in the patients undergoing digestive tumor surgeries. However, it is less commonly used in the appendectomy. AIM: To study the application value of ERAS in laparoscopic surgery for acute appendicitis. METHODS: A total of 120 patients who underwent laparoscopic appendectomy due to acute appendicitis were divided into experimental group and control group by random number table method, including 63 patients in the experimental group and 57 patients in the control group. Patients in the experimental group were managed with the ERAS protocol, and those in the control group were received the traditional treatment. The exhaust time, the hospitalization duration, the hospitalization expense and the pain score between the two groups were compared. RESULTS: There was no significant difference in age, gender, body mass index and Sunshine Appendicitis Grading System score between the experimental group and the control group (P > 0.05). Compared to the control group, the patients in the experimental group had earlier exhaust time, shorter hospitalization time, less hospitalization cost and lower degree of pain sensation. The differences were statistically significant (P < 0.01). CONCLUSION: ERAS could significantly accelerate the recovery of patients who underwent laparoscopic appendectomy for acute appendicitis, shorten the hospitalization time and reduce hospitalization costs. It is a safe and effective approach.

A strategy to enhance the water solubility of luminescent ß-diketonate-Europium(III) complexes for time-gated luminescence bioassays.

Luminescent ß-diketonate-europium(III) complexes have been found a wide range of applications in time-gated luminescence (TGL) bioassays, but their poor water solubility is a main problem that limits their effective uses. In this work we propose a simple and general strategy to enhance the water solubility of luminescent ß-diketonate-europium(III) complexes that permits facile synthesis and purification. By introducing the fluorinated carboxylic acid group into the structures of ß-diketone ligands, two highly water-soluble and luminescent Eu3+ complexes, PBBHD-Eu3+ and CPBBHD-Eu3+, were designed and synthesized. An excellent solubility exceeding 20 mg/mL for PBBHD-Eu3+ was found in a pure aqueous buffer, while it also displayed strong and long-lived luminescence (quantum yield φ = 26%, lifetime τ = 0.49 ms). After the carboxyl groups of PBBHD-Eu3+ were activated, the PBBHD-Eu3+-labeled streptavidin-bovine serum albumin (SA-BSA) conjugate was prepared, and successfully used for the immunoassay of human α-fetoprotein (AFP) and the imaging of an environmental pathogen Giardia lamblia under TGL mode, which demonstrated the practicability of PBBHD-Eu3+ for highly sensitive TGL bioassays. The carboxyl groups of PBBHD can also be easily derivatized with other reactive chemical groups, which enables PBBHD-Eu3+ to meet diverse requirements of biolabeling technique, to provide new opportunities for developing functional europium(III) complex biolabels serving for TGL bioassays.

Seeing Your Stories: Visualization for Narrative Medicine.

Importance: Narrative medicine (NM), in which patient stories play a crucial role in their diagnosis and treatment, can potentially support a more holistic approach to patient care than traditional scientific ones. However, there are some challenges in the implementation of narrative medicine, for example, differences in understanding illnesses between physicians and patients and physicians' increased workloads and overloaded schedules. This paper first presents a review to explore previous visualization research for narrative medicine to bridge the gap between visualization researchers and narrative medicine experts and explore further visualization opportunities. Highlights: The review is conducted from 2 perspectives: (a) the contexts and domains in which visualization has been explored for narrative medicine and (b) the forms and solutions applied in these studies. Four applied domains are defined, including understanding patients from narrative records, medical communication, medical conversation training in education, and psychotherapy and emotional wellness enhancement. Conclusions: A future work framework illustrates some opportunities for future research, including groups of specific directions and future points for the 4 domains and 3 technological exploration opportunities (combination of narrative and medical data visualization, task-audience-based visual storytelling, and user-centered interactive visualization). Specifically, 3 directions of future work in medical communication (asynchronous online physician-patient communication, synchronous face-to-face medical conversation, and medical knowledge dissemination) were concluded.

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-µg doses were randomized to receive BNT162b2 30 µg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 µg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 µg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.

Photochemical processes transform dissolved organic matter differently depending on its initial composition.

Dissolved organic matter (DOM) is one of the most important fluxes in the global carbon cycle but its response to light exposure remains unclear at a molecular-level. The chemical response of DOM to light should vary with its molecular composition and environmental conditions while some basic hypotheses are still unclear, such as the balance between photobleaching and photo-humification and the question of oxidative properties. Here we exposed aquatic DOM from diverse freshwaters impacted by different levels of anthropogenic activity and algal exudates to environmentally-realistic light conditions. We found that photobleaching occurred in DOM with relatively high initial humic content producing low H/C molecules, whereas DOM with low initial humic content was humified. DOM pools with relatively high initial saturation and low aromaticity were prone to transform towards more unsaturated molecular formulae and high H/C molecules with a distinct decrease of bioavailability. Photo-transformation was mainly influenced by reactive intermediates, with reactive oxygen species (ROS) playing a dominant role in humification when the initial humus content of DOM was high. In contrast, for algal DOM with high protein content, it was likely that the autoxidation of excited state DOM was more important than indirect oxidation involving ROS. Our results reveal how photo-transformation patterns depend on the initial composition of DOM and provide new insights into the role of photochemical processes in biogeochemical cycling of DOM.

Explore on the Mechanism of miRNA-146a/TAB1 in the Regulation of Cellular Apoptosis and Inflammation in Ulcerative Colitis Based on NF-κB Pathway.

OBJECTIVE: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear. MATERIALS AND METHODS: The in vivo and in vitro models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays. RESULTS: MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR- 146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC. CONCLUSION: MiR-146a knockdown inhibited cell apoptosis and inflammation via targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

Mortality risk of people living with HIV under hypothetical intervention scenarios of PM2.5 and HIV severity: a prospective cohort study.

This study estimated and compared mortality risks among people living with HIV (PLWH) under the real-world and hypothetical scenarios of PM2.5 concentrations and HIV severity. An open cohort from all PLWH receiving antiretroviral therapy in Sichuan during 2010-2019 was constructed, resulting in 541,515 person-years. Annual mean concentrations of PM2.5 were estimated and linked to PLWH by their residential address. The parametric g-formula were used to assess 3- and 5-year mortality risks under the real-world and hypothetical scenarios of PM2.5 (10-35, 35-50, 50-75 µg/m3) and CD4 concentrations (0-200, 200-500, 500-800, 800-1100 counts/µl). The estimated 3- and 5-year mortality risks among the PLWH were 14.43 % and 19.38 %, respectively, which would decrease substantially when annual PM2.5 concentration were reduced to between 10 and 35 µg/m3 (risk difference [RD] = -3.23 % and - 4.06 %) and would increase when PM2.5 concentration were elevated to between 50 and 75 µg/m3 (RD = 3.59 % and 5.04 %). The mortality risk would increase when CD4 concentration were reduced to <200 counts/µl (RD = 15.90 % and 20.27 %) and would decrease when CD4 concentration were ≥ 200 counts/µl, especially to between 800 and 1100 counts/µl (RD = -9.01 % and - 11.75 %). The elevated concentration of PM2.5 may disproportionately affect individuals with immune deficiency, especially those with more severity. The findings would serve as justifications for future intervention design and policy making to alleviate air pollution and improve environmental justice and health equity.

Network analysis of illness perception, stigma, and resilience with cognition in old people living with HIV.

OBJECTIVES: Old people living with HIV (PLWH) are highly susceptible to HIV-related psychological and neurocognitive disorders, which are multidimensional and inseparably intertwined. Despite this, few studies have investigated the interrelationship between these disorders. We aimed to estimate the detailed associations and identify potential intervention points between HIV-related psychological factors and cognitive function in old PLWH. METHODS: This cross-sectional study drew on the Older People with HIV Infections Cohort from 65 communities in Sichuan, China. Three HIV-related psychological factors, including illness perception, HIV stigma perception and resilience, were collected using a self-reported questionnaire. Cognitive function was measured using the MoCA-B scale. Network analysis was used to estimate the interrelationships between HIV-related psychological factors and cognitive function dimensions in old PLWH, and to identify factors that act as bridges in connecting these factors in the network. RESULTS: Of the 1587 old PLWH, 47.0% had mild or severe cognitive function impairment. Network analysis revealed that better visual perception was directly connected with poorer negative self-image (edge weight: 0.13), and poorer illness comprehensibility was connected with poor visual perception (-0.09) and executive functioning (-0.13). The cognitive illness perceptions (bridge strength: 0.41), illness comprehensibility (0.36) and negative self-image (0.39) were identified as bridges connecting HIV-related psychological and cognitive function. CONCLUSIONS: The interconnection of HIV-related illness perception, stigma perception, and resilience with cognition may be achieved through the links of negative self-image, illness comprehensibility and cognitive illness perceptions. These factors may serve as potential non-pharmaceutical action points to improve psychological and cognitive health among old PLWH.