TERT activation targets DNA methylation and multiple aging hallmarks.

Insufficient telomerase activity, stemming from low telomerase reverse transcriptase (TERT) gene transcription, contributes to telomere dysfunction and aging pathologies. Besides its traditional function in telomere synthesis, TERT acts as a transcriptional co-regulator of genes pivotal in aging and age-associated diseases. Here, we report the identification of a TERT activator compound (TAC) that upregulates TERT transcription via the MEK/ERK/AP-1 cascade. In primary human cells and naturally aged mice, TAC-induced elevation of TERT levels promotes telomere synthesis, blunts tissue aging hallmarks with reduced cellular senescence and inflammatory cytokines, and silences p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, TAC alleviates neuroinflammation, increases neurotrophic factors, stimulates adult neurogenesis, and preserves cognitive function without evident toxicity, including cancer risk. Together, these findings underscore TERT's critical role in aging processes and provide preclinical proof of concept for physiological TERT activation as a strategy to mitigate multiple aging hallmarks and associated pathologies.

Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth.

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

Hydrolytic transformation mechanism of tetracycline antibiotics: Reaction kinetics, products identification and determination in WWTPs.

Antibiotic residues and antibiotic resistance have been widely reported in aquatic environments. Hydrolysis of antibiotics is one of the important environmental processes. Here we investigated the hydrolytic transformation of four tetracycline antibiotics i.e. tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DC) under different environmental conditions, and determined their parents and transformation products in the wastewater treatment plants (WWTPs). The results showed that the hydrolysis of the four tetracyclines followed first-order reaction kinetics, and the acid-catalyzed hydrolysis rates were significantly lower than the base-catalyzed and neutral pH hydrolysis rates. The effect of temperature on tetracycline hydrolysis was quantified by Arrhenius equation, with Ea values ranged from 42.0 kJ mol-1 to 77.0 kJ mol-1 at pH 7.0. In total, nine, six, eight and nine transformation products at three different pH conditions were identified for TC, CTC, OTC and DC, respectively. The main hydrolysis pathways involved the epimerization/isomerization, and dehydration. According to the mass balance analysis, 4-epi-tetracycline and iso-chlortetracycline were the main hydrolytic products for TC and CTC, respectively. The 2 tetracyclines and 4 hydrolysis products were found in the sludge samples in two WWTPs, with concentrations from 15.8 ng/g to 1418 ng/g. Preliminary toxicity evaluation for the tetracyclines and their hydrolysis products showed that some hydrolysis products had higher predicted toxicity than their parent compounds. These results suggest that the hydrolysis products of tetracycline antibiotics should also be included in environmental monitoring and risk assessment.

Endoscopic decompression of the optic canal for traumatic optic neuropathy.

PURPOSE: Traumatic optic neuropathy (TON) is a serious complication of head trauma with the incidence rate of 0.5%-5%. The aim of this study was to investigate the therapeutic efficacy of endoscopic decompression of the optic canal for optic nerve injuries. METHODS: In this study, 11 patients treated in our hospital from January 2009 to January 2015 with the visual loss resulting from TON were retrospectively reviewed for preoperative vision, visual evoked potential (VEP) scan, surgical approach, postoperative visual acuity, complications, and follow-up results. RESULTS: All these patients received endoscopic decompression of the optic canal. At the 3-month follow- up, the visual acuity improvement rate of the 11 patients was 45.5%. The vision acuity of 2 cases improved from hand movement to 0.08 and 0.3 after operation. Another patient's vision acuity returned to 0.05 compared to light sensation preoperatively. Two cases had finger counting before surgery but they had a vision acuity of 0.4 and light sensation respectively after surgery. However, the other 6 cases' vision did not improve after surgery. CONCLUSION: Endoscopic decompression of the optic canal is an effective way to cure TON. VEP could be used as an important reference for preoperative and prognosis evaluation. Operative time after trauma is only a relative condition that may affect the therapeutic effect of optic canal decompression. Poor results of this procedure may be related to the severity of the optic nerve injury.

Insights into structure, codon usage, repeats, and RNA editing of the complete mitochondrial genome of Perilla frutescens (Lamiaceae).

Perilla frutescens (L.) Britton, a member of the Lamiaceae family, stands out as a versatile plant highly valued for its unique aroma and medicinal properties. Additionally, P. frutescens seeds are rich in Îs-linolenic acid, holding substantial economic importance. While the nuclear and chloroplast genomes of P. frutescens have already been documented, the complete mitochondrial genome sequence remains unreported. To this end, the sequencing, annotation, and assembly of the entire Mitochondrial genome of P. frutescens were hereby conducted using a combination of Illumina and PacBio data. The assembled P. frutescens mitochondrial genome spanned 299,551 bp and exhibited a typical circular structure, involving a GC content of 45.23%. Within the genome, a total of 59 unique genes were identified, encompassing 37 protein-coding genes, 20 tRNA genes, and 2 rRNA genes. Additionally, 18 introns were observed in 8 protein-coding genes. Notably, the codons of the P. frutescens mitochondrial genome displayed a notable A/T bias. The analysis also revealed 293 dispersed repeat sequences, 77 simple sequence repeats (SSRs), and 6 tandem repeat sequences. Moreover, RNA editing sites preferentially produced leucine at amino acid editing sites. Furthermore, 70 sequence fragments (12,680 bp) having been transferred from the chloroplast to the mitochondrial genome were identified, accounting for 4.23% of the entire mitochondrial genome. Phylogenetic analysis indicated that among Lamiaceae plants, P. frutescens is most closely related to Salvia miltiorrhiza and Platostoma chinense. Meanwhile, inter-species Ka/Ks results suggested that Ka/Ks < 1 for 28 PCGs, indicating that these genes were evolving under purifying selection. Overall, this study enriches the mitochondrial genome data for P. frutescens and forges a theoretical foundation for future molecular breeding research.

The complete Chloroplast genome of Stachys geobombycis and comparative analysis with related Stachys species.

Herb genomics, at the forefront of traditional Chinese medicine research, combines genomics with traditional practices, facilitating the scientific validation of ancient remedies. This integration enhances public understanding of traditional Chinese medicine's efficacy and broadens its scope in modern healthcare. Stachys species encompass annual or perennial herbs or small shrubs, exhibiting simple petiolate or sessile leaves. Despite their wide-ranging applications across various fields, molecular data have been lacking, hindering the precise identification and taxonomic elucidation of Stachys species. To address this gap, we assembled the complete chloroplast (CP) genome of Stachys geobombycis and conducted reannotation and comparative analysis of seven additional species within the Stachys genus. The findings demonstrate that the CP genomes of these species exhibit quadripartite structures, with lengths ranging from 14,523 to 150,599 bp. Overall, the genome structure remains relatively conserved, hosting 131 annotated genes, including 87 protein coding genes, 36 tRNA genes, and 8 rRNA genes. Additionally, 78 to 98 SSRs and long repeat sequences were detected , and notably, 6 highly variable regions were identified as potential molecular markers in the CP genome through sequence alignment. Phylogenetic analysis based on Bayesian inference and maximum likelihood methods strongly supported the phylogenetic position of the genus Stachys as a member of Stachydeae tribe. Overall, this comprehensive bioinformatics study of Stachys CP genomes lays the groundwork for phylogenetic classification, plant identification, genetic engineering, evolutionary studies, and breeding research concerning medicinal plants within the Stachys genus.

The treatment of high concentration wastewater in the natural gas processing industry.

The operation of the Cansolv tail gas treatment device in natural gas plants generates acidic and alkaline wastewater from the venturi unit and amine purification unit (APU), respectively. The APU wastewater is complex in composition and contains hard-to-degrade organic matter, which can adversely impact the normal functioning of the water treatment system. This study assesses the efficacy of three ozone-based advanced oxidation processes (ozone (O3), ozone/hydrogen peroxide (O3/H2O2), and ozone/Fenton (O3/Fenton)) for treating Cansolv wastewater, with chemical oxygen demand (COD) and total organic carbon (TOC) serving as indicators of organic degradation. The findings demonstrate that all three processes effectively eliminate coloration and reducible sulfur, with O3/Fenton exhibiting superior performance in removing organic substances. The treated wastewater has a clarified light-yellow appearance with residual COD levels at 43 mg L-1. Under the optimum Fenton oxidation conditions (initial pH 5, H2O2 dosage 97.8 mmol L-1, FeSO4·7H2O dosage 550 mg L-1), average TOC and COD removal rates reached 50% and 97%, respectively. After a treatment duration of 60 minutes, the wastewater demonstrated an enhanced membrane-specific flux, confirming the effectiveness of the O3/Fenton oxidation process in mitigating membrane fouling while ensuring the stable operation of the wastewater treatment system.

A missense mutation in PKD1 attenuates the severity of renal disease.

Mutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype-phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD.

[Effect of occupational combined exposure of chromium and iron on erythrocyte metabolism].

OBJECTIVE: To investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism. METHODS: A total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B12 in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted. RESULTS: The median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B12 ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B12 were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B12 and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01). CONCLUSION: Combined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B12 metabolism, while iron may via copper metabolism.

Variability in transmission risk of SARS-CoV-2 in close contact settings: A contact tracing study in Shandong Province, China.

BACKGROUND: Understanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing. METHODS: The case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases. RESULTS: We estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20-64%) in households, 30% (95% CrI: 11-67%) in healthcare facilities, 23% (95% CrI: 7-51%) at workplaces, and 4% (95% CrI: 1-17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55-72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15-26%) cases explained 80% of secondary transmissions. CONCLUSIONS: Household, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic.

Exogenous pancreatic kininogenase protects against tacrolimus-induced renal injury by inhibiting PI3K/AKT signaling: The role of bradykinin receptors.

BACKGROUND: Tissue kallikrein offers a wide spectrum of biological activity in the protection against various types of injury. However, information on its role in tacrolimus (TAC)-induced renal injury is limited. OBJECTIVES: This study aimed to assess the beneficial effects of pancreatic kininogenase (PK) in a rat model of chronic TAC nephrotoxicity and in vitro. METHODS: Sprague Dawley rats were treated daily with either TAC or PK or a combination of the two for four weeks. The influence of PK on renal injury was examined in terms of renal function, histopathology, cytokine expression, oxidative stress, intracellular organelles, programmed cell death, and PI3K/AKT signaling. Human kidney proximal tubular (HK-2) cells and mouse mesangial (SV40 MES13) cells treated with TAC and PK were also studied. RESULTS: PK treatment improved renal function and histopathology. This effect was paralleled by downregulation of proinflammatory and profibrotic cytokine expression. TAC-induced oxidative stress was closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, resulting in excessive programmed cell death (apoptosis and autophagy) that was significantly abrogated by concurrent PK interference with PI3K/AKT signaling. PK also stimulated bradykinin receptor 1 (B1R) and B2R mRNA synthesis and increased bioactive nitric oxide (NO) and cAMP concentrations in TAC-treated kidneys. Blockade of either B1R or B2R eliminated the renoprotective effects of PK. In HK-2 and SV40 MES13 cells, PK decreased TAC-induced overproduction of intracellular reactive oxygen species and inhibited apoptotic cells, whereas cell viability was improved. Moreover, activated PI3K/AKT signaling in HK-2 cells was inhibited by PK and the PI3K inhibitor, LY294002. CONCLUSIONS: These findings indicate that PK treatment protects against chronic TAC nephrotoxicity via inhibition of PI3K/AKT signaling.

First Detection of Mukawa Virus in Ixodes persulcatus and Haemaphysalis concinna in China.

Mukawa virus (MKWV), a novel tick-borne virus (TBV) of the genus Phlebovirus of family Phenuiviridae, has been firstly reported in Ixodes persulcatus in Japan. In this study, we made an epidemiological investigation in China to obtain the geographic distribution and genetic features of this virus outside Japan. We screened 1,815 adult ticks (665 I. persulcatus, 336 Dermacentor silvarum, 599 Haemaphysalis longicornis, 170 Rhipicephalus microplus, 45 Haemaphysalis concinna) and 805 wild small mammals collected from eight provinces. The positive rate of 6.77% (45/665, including 18 female and 27 male I. persulcatus) and 2.22% (1/45, 1 male H. concinna) were obtained from I. persulcatus and H. concinna in Heilongjiang province, respectively. No evidence of MKWV infection was found in other three tick species or any of the mammalian species. The virus can infect the Vero cells successfully, indicating the ability of MKWV to replicate in mammalian cells. A phylogenetic tree based on the nucleotide sequences of L, M, and S segments demonstrated that the Japanese MKWV variant, our two MKWV variants, and KURV were clustered with the members of the mosquito/sandfly-borne phleboviruses and distant from other tick-borne phenuiviruses. A phylogenetic analysis based on 895 bp partial L gene sequences (n = 46) showed that all MKWV sequences were separated into three lineages. Our results showed the presence of MKWV in I. persulcatus and H. concinna in northeast of China, highlighting the necessity of epidemiological study in wider regions. Due to the ability of MKWV to replicate in mammalian cells, the potential for zoonosis, and wide distribution of I. persulcatus and H. concinna in China, the important vectors of MKWV, further screening to more tick species, wild animals, domestic animals, and humans raises up practical significance.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate.

OBJECTIVES: Chronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not been fully investigated. This study was designed to examine vitamin B12, folate and homocysteine metabolic changes in workers chronically exposed to chromate. The potential association between metabolic alteration and renal impairment induced by chromate exposure was also assessed. METHODS: The level of chromium exposure was evaluated by measuring chromium concentrations in red blood cells (RBC-Cr) and urine (U-Cr). Renal impairment was assessed with serum cystatin C (Cys-C) and urinary ß2-microglobulin (ß2M). Serum vitamin B(12), folate and plasma total homocysteine (tHcy) were measured and correlations analysed. RESULTS: Significant increases in RBC-Cr, U-Cr, serum Cys-C, plasma tHcy and urinary ß2M concentrations were observed in workers chronically exposed to chromate compared to controls. In the exposed workers, serum vitamin B12 and folate levels were decreased and significantly inversely correlated with RBC-Cr concentrations, and increased plasma tHcy concentrations were mirrored by decreased serum vitamin B12 and folate levels. Elevated plasma tHcy concentrations were positively related to serum Cys-C concentrations. CONCLUSIONS: Hyperhomocysteinemia in chronically exposed workers was primarily induced by vitamin B12 and folate deficiency. This metabolic change might be associated with renal dysfunction in chromate processing workers after long term exposure.

Lycium barbarum polysaccharides ameliorate LPS-induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice.

In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNF-α, IL-1ß, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential anti-inflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. PRACTICAL APPLICATIONS: In recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)-induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity. In addition, by intraperitoneal injection of LPS to establish peritonitis mice models, LBP pretreatment was found to have significantly modified the behavioral score of mice, while decreasing the secretion of inflammatory factors and the damage to several organs. The present study provides a basis for further understanding the effects of LBP in acute inflammation.

Telomerase Reverse Transcriptase Preserves Neuron Survival and Cognition in Alzheimer's Disease Models.

Amyloid-induced neurodegeneration plays a central role in Alzheimer's disease (AD) pathogenesis. Here, we show that telomerase reverse transcriptase (TERT) haploinsufficiency decreases BDNF and increases amyloid-ß (Aß) precursor in murine brain. Moreover, prior to disease onset, the TERT locus sustains accumulation of repressive epigenetic marks in murine and human AD neurons, implicating TERT repression in amyloid-induced neurodegeneration. To test the impact of sustained TERT expression on AD pathobiology, AD mouse models were engineered to maintain physiological levels of TERT in adult neurons, resulting in reduced Aß accumulation, improved spine morphology, and preserved cognitive function. Mechanistically, integrated profiling revealed that TERT interacts with ß-catenin and RNA polymerase II at gene promoters and upregulates gene networks governing synaptic signaling and learning processes. These TERT-directed transcriptional activities do not require its catalytic activity nor telomerase RNA. These findings provide genetic proof-of-concept for somatic TERT gene activation therapy in attenuating AD progression including cognitive decline.

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities. Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011-2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way. Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00-1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75-8.84) vs. 5.30 (3.54-7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40-2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16-4.46) in ≤60 years, to 2.06 (1.34-3.18) in 60-70 years and further to 1.55 (0.97-2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female. Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

[The effects of occupational soluble chromate exposure on immunological function of T-cell].

OBJECTIVE: To investigate the early changes of some immunological function of T-cell in chromate workers. METHODS: A total of 115 workers exposed to different levels of soluble chromate were enrolled in exposed group; while 90 non-exposure workers who lived far away from the chromate plant were enrolled as control. The air concentration of soluble chromate was determined by atomic absorption spectrometry. CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+) of T-cell were determined by flow cytometry analysis. RESULTS: The individual air chromate concentration in the exposed group was (27.51 +/- 33.25) microg/m(3), and the control group was (0.16 +/- 0.15) microg/m(3). The significant difference between the two groups was observed (z = 8.045, P < 0.01). The levels of the lymphocyte subsets (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+)) in exposed group were (30.08 +/- 17.75)%, (1.04 +/- 1.73)%, (11.94 +/- 9.78)%, 0.10 +/- 0.14. While, those of control group were (63.00 +/- 13.57)%, (30.51 +/- 5.16)%, (14.82 +/- 4.59)%, 2.17 +/- 0.53, higher than that of the exposed group (z values were 4.484, 5.227, 1.976, -5.218, respectively, P < 0.05). CONCLUSION: On the basis of individual air monitoring, the cellular immune function affected by soluble chromate is mainly based on T lymphocyte inhibition. The indicators CD3(+)CD4(+) mentioned above may be considered as efficient biomarkers in further research.

[The effect of inhalable titanium dioxide on the oxidative stress among occupational population].

OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make an assessment of its oxidative effect on occupational exposed population. METHODS: A total of 7 workers occupationally exposing to inhalable titanium dioxide were recruited into the study. The basic information and occupational history were collected by interview, while their blood sample (10 ml for each subject) were collected before and after the investigation, respectively. Pre- and post-work shift urine samples (60 ml for each subject) were collected for 29 days consecutively. The daily personal titanium dioxide exposure level, temperature and relative humidity were detected too. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were detected by ELISA and latex immunoturbidimetric assay, respectively. RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 ± 1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13 ± 1.08), (1.33 ± 1.01) mg/L, respectively. No statistical significance was observed between hs-CRP level before and after the investigation (t = -0.848, P = 0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 ± 1.39), (3.65 ± 1.06) µmol/mol Cr, respectively. A positive correlation was found between the concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r = 0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift, years of employment, age, body mass index, smoking status, temperature and relative humidity, showed no significant exposure-respond trend between the inhalable titanium dioxide concentration and 8-OHdG level (ß = 0.288, t = 1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link between occupationally exposure to inhalable titanium dioxide and high induction of DNA oxidative stress.

Reconstruction of optical absorption coefficient distribution in intravascular photoacoustic imaging.

Intravascular photoacoustic (IVPA) imaging can discriminate between normal arterial tissues and atheromatous plaques in images, particularly images of lipid-rich plaques with high spatial resolution and optical contrast. However, conventional IVPA only recovers the deposited optical energy that is the product of the tissue optical absorption coefficient and local optical fluence. Herein, a one-step model-based method for single-wavelength IVPA imaging system is proposed. The proposed method directly reconstructs the optical absorption coefficient from the boundary measurement of acoustic pressure. To obtain the theoretical optical deposition, light illumination and transport in multilayered vessel-wall tissues are numerically modelled with the diffusion approximation to radiative transfer equation. Then, the generation and propagation of photoacoustic (PA) waves in acoustically homogeneous vessel-wall tissues are modelled by using the PA wave equation. The theoretical acoustic pressure series is thus obtained. Finally, the optical absorption coefficient is iteratively updated from an initial guess by minimising a nonlinear least-square error function to quantify the difference between the measured and theoretical acoustic pressure with split Bregman optimisation based on total-variation regularisation. The numerical simulation experiments demonstrated that optical absorption coefficient maps can be directly recovered on the basis of the acoustic boundary measurement of vascular cross-sections. Compared with the optical deposition map, the optical absorption coefficient map can provide more reliable qualitative and quantitative information on the morphology and optical properties of the imaged arteries. The proposed method enables the accurate and reliable evaluation of atheromatous lesions and the early identification of vulnerable plaques.