Effects and mechanisms of salidroside on the behavior of SPS-induced PTSD rats.

Post-traumatic stress disorder (PTSD) is a complex mental disorder, closely associated with stress and traumatic events. Salidroside (Sal) has been reported to possess neuroprotective effects. However, the behavioral effects and mechanisms of Sal on PTSD remain unknown. In this study, we utilized a rat model of PTSD induced by single prolonged stress (SPS) and administered Sal intraperitoneally (25, 50, 75 mg/kg/d) for 14 days. We then examined the behavioral effects and underlying mechanisms of Sal on SPS-induced PTSD rats. Our findings demonstrated that Sal alleviated anxiety-like behavior and spatial learning and memory impairment in SPS-induced PTSD rats. Furthermore, Sal treatment preserved the histomorphology of the hippocampal region. It was observed that Sal protected against hippocampal neuronal apoptosis in PTSD rats by reducing the number of TUNEL-positive cells and modulating apoptosis-related proteins (Bcl-2 and Bax). Additionally, Sal inhibited the activation of the NF-κB/iNOS/COX-2 signaling pathway in the hippocampus of PTSD rats, thereby suppressing the release of inflammatory factors (TNF-α and IL-1ß) and the activation of microglia. Notably, Sal increased the expression of synapse-associated proteins PSD95 and Synapsin I in the hippocampus, while also enhancing dendritic density in the region. In conclusion, our results demonstrated that Sal could attenuate SPS-induced PTSD-like behaviors by inhibiting hippocampal neuronal apoptosis, enhancing hippocampal synaptic plasticity, and reducing neuroinflammatory responses. These findings may provide a foundation for the potential clinical application of Sal in the treatment of PTSD.

Proinflammatory phenotype in major depressive disorder with adulthood adversity: In line with social signal transduction theory of depression.

BACKGROUND: The social signal transduction theory of depression proposes that life stress can be transformed into inflammatory signals, and ultimately lead to the development of major depressive disorder (MDD). The hypotheses of this study were: (1) The pro-inflammatory effect of life stress was only seen in patients with MDD, but not in healthy controls (HCs); (2) Inflammation can mediate the relationship between life stress and depressive symptoms. METHODS: This study included 170 MDD patients and 196 HCs, and 13 immune-inflammatory biomarkers closely related to MDD were measured, principal component analysis (PCA) was adopted to extract the inflammatory index. Life stress was assessed by Life Event Scale (LES), a total score of >32 points on the LES was considered as adulthood adversity (AA). Path analyses were used to explore the relationship among adulthood stress, inflammatory index, and severity of depression. RESULTS: Among MDD patients, α2M, CXCL-1, IL-1ß, and TLR-1 levels were higher in patients with AA than non-AA group (all FDR-adjusted P values <0.05), meanwhile, the levels of CCL-2 and IL-18 were lower. Path analyses suggested that pro- and anti-inflammatory index could mediate the association between AA and severity of depression in MDD patients. CONCLUSION: This study found that inflammatory signals can mediate the relationship between adulthood adversity and depression, however, the causal relationship need to be further confirmed. These findings shed light on further understanding the theory of social signal transduction in MDD and provide clues for stress management and controlling inflammation strategies in depression. CLINICAL TRIALS: NCT02023567.

Unprecedented Neoverrucosane and Cyathane Diterpenoids with Anti-Neuroinflammatory Activity from Cultures of the Culinary-Medicinal Mushroom Hericium erinaceus.

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10-12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2-5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC50 values as low as 5.82 ± 0.18 µM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.

Black carbon, soil organic matter molecular signatures under different land uses in Shenyang, China and relationship with PAHs.

The content, composition and molecular signatures of soil organic matter (SOM) have important influences on the cycle of soil organic carbon (SOC) and the partitioning of polycyclic aromatic hydrocarbons (PAHs) in soil. Seventy-nine soil samples from farmland, forest and urban areas were collected in Shenyang, China to investigate black carbon (BC) content, SOM molecular signatures varied with land use patterns, as well as the relationship with PAHs. The content of BC in urban soils was significantly higher than that of farmland and forest. BC was a key contributor of urban SOM which accounted for 0.35 ± 0.31 of SOC in urban soil. Based on BC/SOC ratio, the main sources of BC were identified as fossil fuel combustion for urban soils, while for farmland and forest soils, it is the mixed results of fossil fuel combustion and biomass burning. All categories of PAHs in urban soils showed the highest level compared to farmland and forest soils. Pearson's correlation analysis results showed there were significant positive correlations between BC and PAHs categories in urban soils, indicating the important role of BC in the accumulation of PAHs in soil. SOM from each of the two different land use patterns can be distinguished by molecular signatures. Urban SOM had abundant molecular markers derived from condensed organic carbon inputs, which was consistent with the BC/SOC value. Farmland SOM had abundant carbon from vegetation and microorganisms, and forest SOM was rich in organic carbon from fresh plant materials. The markers enriched in urban SOM showed significant correlations with most PAHs categories, highlighting the affinity of urban SOM for PAHs at the molecular level. This study contributed to understanding the impact of land management methods on SOM molecular composition signatures and its influence on PAHs occurrence in soil, providing a theoretical basis for regional soil pollution management.

Neuroprotective effects of an engineered Escherichia coli Nissle 1917 on Parkinson's disease in mice by delivering GLP-1 and modulating gut microbiota.

Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon-like peptide-1 (GLP-1). However, the extremely short half-life of GLP-1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN-GLP-1 that effectively delivers the heterologous GLP-1 molecule. Subsequently, we assessed its neuroprotective effects on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. We demonstrated that EcN-GLP-1 treatment could improve motor deficits, increase tyrosine hydroxylase-positive neurons, suppress microglia and astrocyte activation, reduce brain and colon inflammation, and ameliorate colonic barrier function damaged by MPTP induction. Meanwhile, we confirmed that the oral administration of EcN-GLP-1 could restore the disturbance of gut microbiota in the MPTP-induced PD mice, by reducing the relative abundances of Akkermansia and Oscillospira, and increasing the level of Prevotella in the gut. These results support further development of an engineered probiotic platform in which production of GLP-1 for gut-brain disorders, such as PD.

Association of systemic immune inflammation index and system inflammation response index with clinical risk of acute myocardial infarction.

Background: Systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are combinations of non-specific inflammatory and adaptive immune response impairments associated with cardiovascular disease. Yet little analysis has been done on SII, SIRI and acute myocardial infarction (AMI) prognosis. The purpose of this study was to investigate the correlation of SII and SIRI with clinical risk factors such as GRACE, Gensini, and QTc after acute myocardial infarction. Methods: This study enrolled 310 patients with AMI from February 1, 2018, to December 31, 2022, at our institution. Routine blood items calculated SII and SIRI. Two groups were divided according to whether MACE occurred: the MACE group (81 cases) and the NMACE group (229 cases); each group was divided into three groups according to the SII and SIRI tertiles. The relationship between SII, SIRI and MACE was analyzed using multifactorial logistic regression analysis after adjusting for confounders; ROC curves were plotted to examine the predictive value of SII and SIRI for MACE. The correlation between SII and SIRI and potential risk factors such as Gensini, QTc and GRACE was further analyzed. Results: The study enrolled 310 patients, comprising 248 men (80%, mean age 60.73 ± 13.695 years) and 62 women (20%, mean age 69.79 ± 11.555 years). In the regression model completely adjusted for confounders, the risk of MACE was higher in AMI patients with SII > 11.00 [OR = 1.061,95% CI (1.018,1.105)] than in SII < 5.98; the risk of MACE was 115.3% higher in AMI patients with SIRI (1.72-3.68) [OR = 2.153, 95% CI (1.251, 3.705)] was 115.3% higher in AMI patients with SIRI < 1.72 and the risk of MACE was 25.1% higher in AMI patients with SIRI > 3.68 [OR = 1.251, 95% CI (1.123, 1.394)] than in AMI patients with SIRI < 1.72. In addition, SII, SIRI, and potential post-infarction risk factors (Gensini, QTc, and GRACE) were also associated. Conclusion: SII and SIRI have been significantly associated with post-myocardial infarction MACE and the predictive potential clinically integrated risk factors in AMI patients, for which more attention should be paid to targeted anti-inflammatory therapy in AMI patients to further reduce the incidence of prognostic MACE in AMI patients.

Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice.

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.

Case Report: Semaglutide-associated depression: a report of two cases.

Semaglutide, as a glucagon-like peptide-1 receptor agonist (GLP-1 RA), was approved for glucose control in type 2 diabetes mellitus in 2017 and approved for weight loss in 2021 by the U.S. Food and Drug Administration (FDA). No psychiatric adverse effect associated with semaglutide has been reported so far. Here we report two cases of semaglutide-associated depression. One is a middle-aged man with no previous history of depression who developed depressive symptoms about 1 month after taking semaglutide. The other one is a middle-aged woman with recurrent depressive disorder whose symptoms also recurred about 1 month after semaglutide treatment. Depression was improved or relieved after discontinuation of semaglutide in both cases. Possible psychiatric adverse effects of depression should be taken into consideration when semaglutide is administered to patients.

Extreme temperature events and dementia mortality in Chinese adults: a population-based, case-crossover study.

BACKGROUND: The effect of exposure to extreme temperature events (ETEs) on dementia mortality remains largely unknown. We aimed to quantify the association of ETE exposure with dementia mortality. METHODS: We conducted a population-based, case-crossover study among 57 791 dementia deaths in Jiangsu province, China, during 2015-20. Daily mean temperatures were extracted from a validated grid dataset at each subject's residential address, and grid-specific exposures to heat wave and cold spell were assessed with a combination of their intensity and duration. We applied conditional logistic regression models to investigate cumulative and lag effects for ETE exposures. RESULTS: Exposure to ETE with each of all 24 definitions was associated with an increased odds of dementia mortality, which was higher when exposed to heat wave. Exposure to heat wave (daily mean temperature ≥95th percentile, duration ≥3 days (d); P95_3d) and cold spell (≤5th percentile, duration ≥3 d; P5_3d) was associated with a 75% (95% CI: 61%, 90%) and 30% (19%, 43%) increase in odds of dementia mortality, respectively. Definitions with higher intensity were generally associated with a higher odds of dementia mortality. We estimated that 6.14% of dementia deaths were attributable to exposure to heat wave (P90_2d) and cold spell (P10_2d). No effect modifications were observed by sex or age, except that the association for heat wave was stronger among women. CONCLUSIONS: Exposure to both heat wave and cold spell was associated with an increased odds of dementia mortality. Our findings highlight that reducing individual ETE exposures may be helpful in preventing deaths from dementia, especially among women in summer.

Perspectives for immunotherapy of EBV-associated GLELC: A relatively "hot" tumor microenvironment.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric lymphoepithelioma-like carcinoma (EBVaGLELC) represents a small number of gastric cancer (GC), and research on tumor microenvironment (TME) and treatment strategy are still lacking. AIMS: Here, we aim to elucidate the immune features of this rare disease and further help to develop more effective treatment options. MATERIALS & METHODS: A retrospective analysis was conducted between 2019 to 2022 in West China Hospital to reveal the immunological characteristics of EBV-positive GLELC. The difference of immune cell subset and tumor vascular structure between gastric denocarcinoma (GAC) and EBVaGLELC will be pointed out. DISCUSSION: 13 patients with GELEC and 8 patients with GAC were retrospectively studied. The heterogeneity of the immune cell profile was then confirmed through multiplexed immunofluorescence staining (mIF), which revealed a higher proportion of CD3+ T cells, CD8+ T cells, and Treg cells in the EBV-associated GLELC group. Such a distinct TME may provide therapeutic advantages, and patients with this rare subtype of GC could be good candidates for immune checkpoint inhibitors (ICIs). Angiogenesis in EBV-positive GLELC may be less intense than that in gastric adenocarcinoma (GAC), a feature that might decrease their susceptibility to antiangiogenic therapy. Furthermore, we reported a 52-year-old male with advanced EBV-positive GLELC who showed a favorable response to the combined therapy with . A repeat evaluation showed sustained partial response (PR), and the progression-free survival (PFS) was more than 34 months until now. CONCLUSION: Compared with GAC, EBVaGLELC revealed higher T cell infiltration and less intense of angiogenesis. It displays relatively "hot" TME that may provide the rationality to treat with immunotherapy in EBV-related GLELC.

Effect of low molecular weight organic acids on the lead and chromium release from widely-used lead chromate pigments under sunlight irradiation.

Lead chromate pigments are commonly used yellow inorganic pigments. They can pose environmental risks as they contain toxic heavy metals lead and chromium. Low molecular weight organic acids (LMWOAs), as widespread dissolved organic matter (DOM), affect the lead and chromium release from the pigment in water. In this work, the role of LMWOAs in the photodissolution of commercial lead chromate pigment was investigated. The pigment underwent significant photodissolution under simulated sunlight exposure with LMWOAs, and subsequently released Cr(III) and Pb(II). The photodissolution process is caused by the reduction of Cr(VI) by photogenerated electrons of the lead chromate pigment. The LMWOAs promoted photodissolution of the pigment by improving the electron-hole separation. The formation of Cr(III)-contained compounds leads to a slower release of chromium than lead. The photodissolution kinetics increase with decreasing pH and increasing LMWOAs concentration. The photodissolution of lead chromate pigment was basically positively related to the total number of hydroxyl and carboxyl groups in LMWOAs. The LMWOAs with stronger affinity to lead chromate pigment, lower adiabatic ionization potential (AIP) and higher energy of the highest occupied molecular orbital (EHOMO) are favorable to Cr(VI) reduction by photogenerated electrons and pigment photodissolution. 2.39% of chromium and 10.34% of lead released from the lead chromate pigment in natural conditions during a 6-h sunlight exposure. This study revealed the photodissolution mechanism of lead chromate pigment mediated by LMWOAs with different molecular structures, which helps understand the environmental photochemical behavior of the pigment. The present results emphasize the important role of DOM in the heavy metals release from commercial inorganic pigments.

Value of the neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease complicated with pulmonary hypertension.

OBJECTIVE: To investigate the relationship between the neutrophil-to-lymphocyte ratio and chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD + PH). METHODS: We retrospectively analyzed clinical data from 242 COPD patients at our hospital from July 2018 to July 2019. Patients underwent examinations including blood analysis, C-reactive protein, N-terminal brain natriuretic peptide (BNP), pulmonary function, and cardiac color ultrasound. RESULTS: Patients were divided into the COPD and COPD + PH groups using pulmonary arterial pressure (<50 and ≥50 mmHg, respectively). Compared with the COPD group, the COPD + PH group had greater pulmonary arterial pressure, smoking history, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, BNP, Chronic Obstructive Pulmonary Disease Assessment Test score, and right atrium and ventricular diameters, but smaller body mass index, forced vital capacity, lymphocyte count, and left ventricular diameter. BNP and NLR had positive effects on PH; forced vital capacity had a negative impact. Moreover, BNP (area under the curve [AUC] = 0.748, sensitivity = 0.692, specificity = 0.701) and NLR (AUC = 0.679, sensitivity = 0.831, specificity = 0.452) had predictive value for PH, and both were positively correlated with PH. CONCLUSIONS: NLR is associated with COPD + PH, and may be useful for its diagnosis.

The Complete Genomic Sequence of Microbial Transglutaminase Producer, Streptomyces mobaraensis DSM40587.

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites.

Antipsychotics reduces mortality in patients with neuropsychiatric systemic lupus erythematosus: a retrospective study of psychiatric consultation cases.

Objective: This study aimed to identify the presence of psychiatric comorbidities as well as investigate the relationship between psychiatric interventions for mental symptoms and mortality in patients with systemic lupus erythematosus (SLE). Method: We retrospectively evaluated the records of 160 inpatients with SLE who required psychiatric consultation for further therapeutic intervention from 2013 to 2020 in a tertiary general hospital. We collected clinical data, including diagnoses, medications, and mortality rate. We compared clinical characteristics among the diagnosis groups and correlations between variables. Results: A total of 138 (86.3%) patients met the diagnostic criteria for at least one mental disorder, with the most common being delirium (54.4%). The average Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score significantly differed among the diagnosis groups (p = 0.003). The mortality rate among patients with delirium was significantly higher than that in the other patient groups (x2 = 12.967, p = 0.024). SLEDAI-2K score was not significantly correlated with mortality (r = 0.123, p = 0.087). Antipsychotics use was associated with mortality (odds ratio 0.053, p = 0.021). Conclusion: Antipsychotic use may decrease death risk for patients with NPSLE. Early psychiatric consultation is necessary for patients with SLE who have developed or have suspected psychiatric symptoms in order to establish a comprehensive intervention plan.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

Next-generation nanomaterials: advancing ocular anti-inflammatory drug therapy.

Ophthalmic inflammatory diseases, including conjunctivitis, keratitis, uveitis, scleritis, and related conditions, pose considerable challenges to effective management and treatment. This review article investigates the potential of advanced nanomaterials in revolutionizing ocular anti-inflammatory drug interventions. By conducting an exhaustive analysis of recent advancements and assessing the potential benefits and limitations, this review aims to identify promising avenues for future research and clinical applications. The review commences with a detailed exploration of various nanomaterial categories, such as liposomes, dendrimers, nanoparticles (NPs), and hydrogels, emphasizing their unique properties and capabilities for accurate drug delivery. Subsequently, we explore the etiology and pathophysiology of ophthalmic inflammatory disorders, highlighting the urgent necessity for innovative therapeutic strategies and examining recent preclinical and clinical investigations employing nanomaterial-based drug delivery systems. We discuss the advantages of these cutting-edge systems, such as biocompatibility, bioavailability, controlled release, and targeted delivery, alongside potential challenges, which encompass immunogenicity, toxicity, and regulatory hurdles. Furthermore, we emphasize the significance of interdisciplinary collaborations among material scientists, pharmacologists, and clinicians in expediting the translation of these breakthroughs from laboratory environments to clinical practice. In summary, this review accentuates the remarkable potential of advanced nanomaterials in redefining ocular anti-inflammatory drug therapy. We fervently support continued research and development in this rapidly evolving field to overcome existing barriers and improve patient outcomes for ophthalmic inflammatory disorders.

Diagnostic techniques for critical respiratory infections: Update on current methods.

Respiratory infections, whether chronic or acute, are frequent in both children and adults and result in an economic burden in health care systems. In particular, for an immunocompromised patient, respiratory infection leads to acute hypoxemic respiratory failure, a leading cause of intensive care unit (ICU) admission. Most respiratory infections are caused by bacteria, viruses, parasites, smoking, or air pollution. Over the last two decades, considerable improvements have been made in understanding and identifying respiratory infections. Various biosensing techniques have been developed with a range of targets to identify the infection at earlier stages. Recently, nanomaterials have been effectively applied to improve biosensors and their analytical performances. This review discusses recent biosensor developments for identifying respiratory infections caused by viruses and bacteria assisted by different types of nanomaterials and target molecules.

Exposure to Fine Particulate Matter Constituents and Human Semen Quality Decline: A Multicenter Study.

Exposure to fine particulate matter (PM < 2.5 µm in diameter [PM2.5]) may accelerate human sperm quality decline, although research on this association is limited. Our objective was to investigate the relationship between exposure to the chemical constituents of PM2.5 air pollution and decreased sperm quality and to further explore the exposure-response relationship. We conducted a multicenter population-based cohort study including 78,952 semen samples from 33,234 donors at 6 provincial human sperm banks (covering central, northern, southern, eastern, and southwestern parts of China) between 2014 and 2020. Daily exposure to PM2.5 chemical composition was estimated using a deep learning model integrating a density ground-based measure network at a 1 km resolution. Linear mixed models with subject- and center-specific intercepts were used to quantify the harmful impacts of PM2.5 constituents on semen quality and explore their exposure-response relationships. Per interquartile range (IQR) increase in PM2.5 exposure levels during spermatogenesis was significantly associated with decreased sperm concentration, progressive motility, and total motility. For PM2.5 constituents, per IQR increment in Cl- (ß: -0.02, 95% CI: [-0.03, -0.00]) and NO3- (ß: -0.05, 95% CI: [-0.08, -0.02]) exposure was negatively associated with sperm count, while NH4+ (ß: -0.03, 95% CI: [-0.06, -0.00]) was significantly linked to decreased progressive motility. These results suggest that exposure to PM2.5 chemical constituents may adversely affect human sperm quality, highlighting the urgent need to reduce PM2.5 exposure.

Association between sensitivity to thyroid hormone indices and osteoporosis in euthyroid patients with type 2 diabetes mellitus.

Background: Thyroid hormones are known to regulate bone metabolism and may influence bone mineral density (BMD), as well as the risk of osteoporosis (OP) and fractures in patients with type 2 diabetes mellitus (T2DM). Recently, sensitivity to thyroid hormone indices has been linked with T2DM and OP independently. However, the relationship between thyroid hormone sensitivity and OP in euthyroid T2DM patients has yet to be investigated. Objectives: The aim of this study was to determine the association between sensitivity to thyroid hormone indices and the risk of OP in euthyroid patients with T2DM. Design: This study employed a retrospective, cross-sectional design and utilized data acquired from the Cangzhou Central Hospital in China between 2019 and 2020. Methods: We retrospectively analyzed the data of 433 patients with T2DM for anthropometric measurements, clinical laboratory test results, and BMD. The thyroid-stimulating hormone index, thyrotroph thyroxine resistance index, and thyroid feedback quantile-based index (TFQI) were calculated to determine thyroid hormone sensitivity. Finally, multivariable logistic regression, generalized additive models, and subgroup analysis were performed to detect the association between sensitivity to thyroid hormone indices and the risk of OP in these patients. Results: We did not observe a statistically significant linear relationship between sensitivity to thyroid hormones indices and OP after covariate adjustment. However, a nonlinear relationship existed between TFQI and the prevalence of OP. The inflection point of the TFQI was at -0.29. The effect sizes (odds ratio) on the left and right of the inflection point were 0.07 [95% confidence interval (CI): 0.01-0.71; p = 0.024] and 2.78 (95% CI: 1.02-7.58; p = 0.046), respectively. This trend was consistent in older female patients with higher body mass index (BMI; 25-30 kg/m2). Conclusion: An approximate U-shaped relationship was observed between sensitivity to thyroid hormone indices and OP risk in euthyroid patients with T2DM with variations in sex, age, and BMI. These findings provide a new perspective to elucidate the role of thyroid hormones in OP, specifically in patients with T2DM.

Short-term exposure to reduced specific-size ambient particulate matter increase the risk of cause-specific cardiovascular disease: A national-wide evidence from hospital admissions.

Evidence for the health effects of ambient PM1 (particulate matter with an aerodynamic diameter ≤ 1 µm) pollution is limited, and it remains unclear whether a smaller particulate matter has a greater impact on human health. We conducted a time-series study in 184 major cities by extracting daily hospital data on admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and stroke between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. City-specific associations were estimated with over-dispersed generalized additive models. A random-effects meta-analysis was used to estimate regional and national average associations. We conducted stratified and meta-regression analyses to explore potential effect modifiers of the association. We recorded 8.83 million cardiovascular admissions during the study period. At the national-average level, a 10-µg/m3 increase in same-day PM1, PM2.5(particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10(particulate matter with an aerodynamic diameter ≤ 10 µm) concentrations corresponded to a 1.14% (95% confidence interval 0.88-1.41%), 0.55% (0.40-0.70%), and 0.45% (0.36-0.55%) increase in cardiovascular admissions, respectively. PM1 exposure was also positively associated with all cardiovascular disease subtypes, including ischemic heart disease (1.28% change; 0.99-1.56%), heart failure (1.30% change; 0.70-1.91%), heart rhythm disturbances (1.11% change; 0.65-1.58%), and ischemic stroke (1.29% change; 0.88-1.71%). The associations between PM1 and cardiovascular admissions were stronger in cities with lower PM1 levels, higher air temperatures and relative humidity, as well as in subgroups with elder age (all P < 0.05). This study provides robust evidence of short-term associations between PM1 concentrations and increased hospital admissions for all major cardiovascular diseases in China. Our findings suggest a greater short-term impact on cardiovascular risk from PM1 in comparison to PM2.5 and PM10.