Unveiling the micronutrient-immunity puzzle in inactivated COVID-19 vaccination: A comprehensive analysis of circulating micronutrient levels and humoral responses in healthy adults.

While micronutrients are crucial for immune function, their impact on humoral responses to inactivated COVID-19 vaccination remains unclear. We investigated the associations between seven key micronutrients and antibody responses in 44 healthy adults with two doses of an inactivated COVID-19 vaccine. Blood samples were collected pre-vaccination and 28 days post-booster. We measured circulating minerals (iron, zinc, copper, and selenium) and vitamins (A, D, and E) concentrations alongside antibody responses and assessed their associations using linear regression analyses. Our analysis revealed inverse associations between blood iron and zinc concentrations and anti-SARS-CoV-2 IgM antibody binding affinity (AUC for iron: ß = -258.21, p < 0.0001; zinc: ß = -17.25, p = 0.0004). Notably, antibody quality presented complex relationships. Blood selenium was positively associated (ß = 18.61, p = 0.0030), while copper/selenium ratio was inversely associated (ß = -1.36, p = 0.0055) with the neutralizing ability against SARS-CoV-2 virus at a 1:10 plasma dilution. There was no significant association between circulating micronutrient concentrations and anti-SARS-CoV-2 IgG binding affinity. These findings suggest that circulating iron, zinc, and selenium concentrations and copper/selenium ratio, may serve as potential biomarkers for both quantity (binding affinity) and quality (neutralization) of humoral responses after inactivated COVID-19 vaccination. Furthermore, they hint at the potential of pre-vaccination dietary interventions, such as selenium supplementation, to improve vaccine efficacy. However, larger, diverse studies are needed to validate these findings. This research advances the understanding of the impact of micronutrients on vaccine response, offering the potential for personalized vaccination strategies.

Phospholipid remodeling and its derivatives are associated with COVID-19 severity.

BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.

Acoustic characteristics of microperforated plate with variable cross-sectional holes.

Broadband sound absorption performance and high mechanical strength are major concerns for designing a microperforated plate (MPP) absorber, which is generally difficult to achieve for a single-layer MPP with straight holes. A MPP was proposed with variable cross-sectional holes, including large dents on one side, grooves on the other side, and intermediate micro-slits. The beneficial effects of the special geometrical features are thoroughly discussed and experimentally validated. Models to calculate the acoustic impedance are established, and acoustic behaviors within holes are simulated. It was found that the micro-slits could provide necessary acoustic resistance for impedance matching and very low reactance to expand sound absorption bandwidth. The large dents or grooves could provide the necessary thickness with negligible acoustic impedance to enhance plate mechanical strength. This research helps to implement a single-layer MPP design with good acoustical and mechanical performance.

Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study.

BACKGROUND: Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV). METHODS: This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP. RESULTS: CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r2 = 0.308-0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804-0.943; P = .001), with r2 = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489-47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709-196.660; P = .001) having the highest risks of CSVD (r2 = 0.413). CONCLUSIONS: Lower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.

Consecutive false-negative rRT-PCR test results for SARS-CoV-2 in patients after clinical recovery from COVID-19.

This study reviewed the serial real-time reverse-transcription polymerase chain reaction (rRT-PCR) results of 37 patients admitted to our hospital in Wuhan, China, who had three or more sequential negative results before discharge. Of these 37 patients, 14 (~38%) had a positive rRT-PCR result after a negative result during convalescence, and 5 (~14%) had a positive rRT-PCR result after two consecutive negative results during convalescence. These results suggest that it may be necessary to require that patients have three consecutive negative results before discharge, to ensure that they do not spread infection among members of their household, or in the community. We believe that our study makes a significant contribution to the literature because it is not currently the standard of care to require patients to have three consecutive negative results before discharge. Our results suggest that a relatively high proportion of patients may continue to shed severe acute respiratory syndrome coronavirus 2 after they have clinically recovered, and thus may transmit the infection to others.

Asymmetrical cortical vein sign predicts early neurological deterioration in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion.

BACKGROUND: Susceptibility weighted imaging (SWI) provides an approximate assessment of tissue perfusion and shows prominent hypointense cortical veins in the ischemic territory because of the increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO). METHODS: One hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as an increase in the National Institutes of Health Stroke Scale score ≧2 points despite standard treatment in the first 72 h after admission. The APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI. RESULTS: Thirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P = 0.001). Patients with APCVS were more likely to have END (40.0%, vs. 12.2%, P = 0.001) than those without END. Multivariate logistic regression indicated that APCVS (OR = 4.349, 95% C.I. = 1.580-11.970, P = 0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume. CONCLUSIONS: In acute ischemic stroke patients with SIASO, the APCVS might be a useful neuroimaging marker for predicting END, which suggests the importance of evaluation of perfusion status.

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations.

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

Overexpression of miR-98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models.

MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR-98 has been reported to be involved in various diseases. However, little is known about the role of miR-98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR-98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR-98 was downregulated in CCI rat models. Overexpression of miR-9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR-98 and the direct correlation was confirmed. Then, miR-98 was overexpressed in CCI rats and it was found that miR-98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) expression was obviously induced in CCI rats, while miR-98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR-98 on neuropathic pain development. Taken these together, we reported that overexpression of miR-98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.

miR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3.

MicroRNAs (miRNA) play important roles in neuroinflammation and neuropathic pain development; however, the underlying mechanism requires further investigation. The expression of miR-21-5p was remarkably upregulated in chronic constrictive injury (CCI) rat model. A significant alleviated neuropathic pain development and reduced the expression of cytokines was observed in CCI rat after exogenous injection of miR-21-5p mimic. The dual-luciferase analysis revealed that tissue inhibitor of metalloproteinase-3 (TIMP3) and chemokines C-C motif ligand 1 (CCL1) was direct downstream target of miR-21-5p. Moreover, silencing of TIMP3 and CCL1 could rescue mechanical allodynia, thermal hyperalgesia and cytokine release in CCI rat, suggesting that TIMP3 and CCL1 exert their function by mediating neuroinflammation in neuropathic pain development. Therefore, we have identified a novel miR-21-5p-CCL1/TIMP3-cytokine axis in regulation of neuropathic pain development in CCI rat model, which is valuable for enhancing our understanding of neuropathic pain and developing miRNAs as potential therapeutic options in the future.

Delirium in the Acute Phase of Ischemic Stroke: Incidence, Risk Factors, and Effects on Functional Outcome.

OBJECTIVE: The aim of this prospective cohort study was to assess the incidence and risk factors of delirium following acute ischemic stroke, as well as its effects on functional outcome. METHODS: Two hundred and sixty-one patients with acute ischemic stroke were screened for delirium during the first week after admission. Delirium was diagnosed according to the Confusion Assessment Method. If delirium was present, delirium rating scale-revised-98 was used to assess its severity. Neurologic deficits were assessed with the National Institutes of Health Stroke Scale (NIHSS). Brain magnetic resonance imaging assessment quantified the infarction, white matter lesions, and medial temporal lobe atrophy. Functional outcome assessment included the modified Rankin Scale and Lawton Instrumental Activities of Daily Living scale at 3 and 6 months after the index stroke. RESULTS: Thirty-eight (14.6%) patients with acute ischemic stroke developed delirium during the first week of admission. Patients with poststroke delirium (PSD) were older, had higher NIHSS scores on admission, and were more likely to have a previous stroke, an infection, and a left cortical infarct. Furthermore, left cortical infarction, older age, severer neurological deficit and having a previous stroke increased the risk of PSD. PSD was associated with a worse functional outcome. CONCLUSION: The incidence of delirium was 14.8% in the first week after admission with acute ischemic stroke. Age, having a previous stroke, stroke severity, and left-cortical infarction were independently predictors of PSD. PSD may result in a significantly worse functional outcome.

siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster.

Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.

Induced multipotency in adult keratinocytes through down-regulation of ΔNp63 or DGCR8.

The roles of microRNAs (miRNAs) and the miRNA processing machinery in the regulation of stem cell biology are not well understood. Here, we show that the p53 family member and p63 isoform, ΔNp63, is a transcriptional activator of a cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a unique miRNA signature resulting in reprogramming cells to multipotency. Strikingly, ΔNp63(-/-) epidermal cells display profound defects in terminal differentiation and express a subset of markers and miRNAs present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors. Moreover, ΔNp63(-/-) epidermal cells transduced with an inducible DGCR8 plasmid can differentiate into multiple cell fates in vitro and in vivo. We found that human primary keratinocytes depleted of ΔNp63 or DGCR8 can be reprogrammed in 6 d and express a unique miRNA and gene expression signature that is similar but not identical to human induced pluripotent stem cells. Our data reveal a role for ΔNp63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells.

Intracranial Atherosclerosis and Poststroke Depression in Chinese Patients with Ischemic Stroke.

BACKGROUND: Intracranial atherosclerosis (ICAS) is a common etiology of ischemic stroke in Chinese patients, probably leading to regional hypoperfusion in the brain. The purpose of this prospective study was to investigate the association between ICAS and poststroke depression in Chinese patients with ischemic stroke. METHODS: During the study period, a total of 569 patients aged between 40 and 80 years with acute ischemic stroke were consecutively admitted and screened. Patients with a National Institutes of Health Stroke Scale (NIHSS) total score of 15 or higher, with severe cognitive impairment, or with a history of depression before stroke were excluded. Two hundred seven patients with ischemic stroke were consecutively recruited in the study. Depressive symptoms were assessed in the acute stage and 3 months after stroke. Poststroke depression was defined as a score of 8 or higher in the 24-item Hamilton Depression Rating Scale. The evaluation of the magnetic resonance imaging scans focused on infarctions, white matter lesions, brain atrophy, and ICAS. RESULTS: In the acute stage of stroke, logistic regression revealed that female sex, NIHSS score at admission, prestroke insomnia, and ICAS were significant predictors of poststroke depression. At 3 months after stroke, prestroke insomnia, the Mini-Mental State Examination score and ICAS were significant predictors of poststroke depression. CONCLUSIONS: ICAS may be a significant independent predictor of poststroke depression in Chinese patients with ischemic stroke.

Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of cesarean section and adverse fetal outcomes. Currently, ICP diagnosis depends largely on serum levels of bile acids and lacks sensitivity and specificity for accurate diagnosis. Tongue diagnosis is an important diagnostic tool in traditional Chinese medicine (TCM) and is used in our clinic as complementary treatment and personalized medicine for ICP. However, the molecular basis of the manifestation of greasy white tongue coatings in ICP remains unknown. In this study, we performed untargeted metabolomic profiling of the serum, tongue coating, and saliva of 66 pregnant women, including 22 with ICP. The metabolomic profiles of the serum and tongue coatings showed marked differences between the two clinical groups. Forty-six differentially abundant metabolites were identified, and their relative concentrations correlated with total bile acid levels. These differential metabolites included bile acids, lipids, microbiota- and diet-related metabolites, and exposomes. Conventional biochemical markers, including serum aminotransferases and bilirubin, were not significantly increased in the ICP group, whereas the total cholesterol and triglyceride levels were significantly increased as early as the first trimester. Our data provide insights into the pathophysiology of ICP and implicate the gut-liver axis and environmental exposure. Tongue coating has the potential to be a non-invasive diagnostic approach. Further studies are required to validate the clinical utility of these findings.

Constructing an efficient electrocatalyst for water oxidation: an Fe-doped CoO/Co catalyst enabled by in situ MOF growth and a solvent-free strategy.

The development of non-precious metal electrocatalysts with high activity for the oxygen evolution reaction (OER) is a crucial and challenging task. In this work, we proposed a solvent-free in situ metal-organic framework (MOF) growth strategy for the fabrication of an Fe-doped CoO/Co electrocatalyst. This approach not only partially granted the MOF's porous structure to the catalyst but also resulted in a tighter combination between the Co metal and CoO, thereby enhancing its electrical conductivity. Furthermore, this method enabled the Fe species to be more uniformly dispersed on CoO/Co, which significantly exposed more active sites for efficient electrocatalysis. The entire synthesis process was solvent-free, except for a small amount of water and ethanol used during catalyst washing. The as-synthesized Fe-CoO/Co electrocatalyst exhibited superior OER activity on a glass carbon electrode, with η = 276 mV at a current density of 10 mA cm-2, even higher than that of the commercial precious IrO2/C catalyst. Additionally, it was also extended to prepare a Ni-doped CoO/Co electrocatalyst by the same procedure with satisfactory OER performance. This work presents a new preparation approach for MOF-derived catalysts with potential applications in energy conversion and beyond.

Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and characterized by emphysema, small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in traditional Chinese medicine for chronic lung disease. Given that citrus peels are known for containing antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang Chenpi (GC), in preventing the development of COPD induced by diesel exhaust particles (DEPs) and its potential mechanism. DEP-induced COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of DEP-induced COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell hyperplasia (PAS positive cells) and fibrosis of the small airways, decreased macrophage infiltration as well as carbon loading in the peripheral lungs, and facilitated the resolution of emphysema and small airway remodeling in DEP-induced COPD rats. An in vitro free radical scavenging assay revealed robust antioxidant potential of GC in scavenging DPPH free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of IL-8 and MUC5AC from DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to DEP exposure. These protective effects further contributed to the resolution of COPD-like pathologies.

General anesthesia in children and long-term neurodevelopmental deficits: A systematic review.

Background: Millions of children experienced surgery procedures requiring general anesthesia (GA). Any potential neurodevelopmental risks of pediatric anesthesia can be a serious public health issue. Various animal studies have provided evidence that commonly used GA induced a variety of morphofunctional alterations in the developing brain of juvenile animals. Methods: We conducted a systematic review to provide a brief overview of preclinical studies and summarize the existing clinical studies. Comprehensive literature searches of PubMed, EMBASE, CINAHL, OVID Medline, Web of Science, and the Cochrane Library were conducted using the relevant search terms "general anesthesia," "neurocognitive outcome," and "children." We included studies investigating children who were exposed to single or multiple GA before 18, with long-term neurodevelopment outcomes evaluated after the exposure(s). Results: Seventy-two clinical studies originating from 18 different countries published from 2000 to 2022 are included in this review, most of which are retrospective studies (n = 58). Two-thirds of studies (n = 48) provide evidence of negative neurocognitive effects after GA exposure in children. Neurodevelopmental outcomes are categorized into six domains: academics/achievement, cognition, development/behavior, diagnosis, brain studies, and others. Most studies focusing on children <7 years detected adverse neurocognitive effects following GA exposure, but not all studies consistently supported the prevailing view that younger children were at greater risk than senior ones. More times and longer duration of exposures to GA, and major surgeries may indicate a higher risk of negative outcomes. Conclusion: Based on current studies, it is necessary to endeavor to limit the duration and numbers of anesthesia and the dose of anesthetic agents. For future studies, we require cohort studies with rich sources of data and appropriate outcome measures, and carefully designed and adequately powered clinical trials testing plausible interventions in relevant patient populations.

Systematic Screening of Trigger Moieties for Designing Formaldehyde Fluorescent Probes and Application in Live Cell Imaging.

Formaldehyde (FA) is involved in multiple physiological regulatory processes and plays a crucial role in memory storage. Meanwhile, FA has a notorious reputation as a toxic compound, and it will cause a variety of diseases if its level is unbalanced in the human body. To date, there have been numerous fluorescent probes for FA imaging reported. Among them, the probes based on the 2-aza-Cope rearrangement have attracted the most attention, and their applications in cell imaging have been greatly expanded. Herein, we screened the various trigger moieties of FA fluorescent probes based on the mechanism of 2-aza-Cope rearrangement. FA-2, in which a fluorophore is connected to a 4-nitrobenzylamine group and an allyl group, demonstrated the highest sensitivity, selectivity, and reaction kinetics. Furthermore, FA-Lyso, derived from FA-2, has been successfully designed and applied to monitor exogenous and endogenous FA fluctuations in lysosomes of living cells.

Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ~25 and ~40 µg/dL, respectively, on PN10 and by PN30 all were ≤ 1 µg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity.

Risk factors of mortality and contribution of treatment in patients infected with COVID-19: a retrospective propensity score matched study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has now brought major challenges to public health and the economy globally since December 2019, which requires effective treatment and prevention strategies to adapt to the impact of the pandemic. We, therefore, explored the prognostic factors for patients with COVID-19 and the contribution of immunomodulatory therapy on COVID-19 outcome. METHODS: From 1 February to 16 March 2020, consecutive cases with COVID-19 were analyzed in the West Campus of Wuhan Union Hospital, a tertiary care center that is designated to care for patients with COVID-19 in Wuhan, China. The observation was based on follow-up until in-hospital death or discharge. Logistic regressions were performed for prognostic factors associated with in-hospital death. Furthermore, a propensity score-matched analysis was done using a multivariable logistic regression model to analyze the contributions of multiple treatments on COVID-19 death. RESULTS: Three hundred and seventeen patients with COVID-19 were enrolled, of whom 269 were discharged and 48 died in hospital. After propensity score matching based on age, gender, symptoms and comorbidities, multivariable logistic regression was performed with the adjustment of other variables that were significant risk factors in the univariate regression. Treatments with glucocorticoids, immunoglobulin, thymosin, and ammonium glycyrrhizinate were significantly associated with a higher rate of COVID-19 death. CONCLUSIONS: For in-hospital patients with COVID-19 of all severity levels, a high risk for fatal outcome was observed in those treated with glucocorticoids, immunoglobulin, thymosin, and ammonium glycyrrhizinate. The results of this study do not support immunomodulatory therapy in patients admitted to the hospital with COVID-19. Further prospective studies are essential to clarify our findings, especially for non-critically ill patients.