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1.
Lung ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38743087

BACKGROUND: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

2.
Nutrients ; 16(9)2024 Apr 27.
Article En | MEDLINE | ID: mdl-38732561

Background: Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10-18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the "Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)". According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into <9 h and ≥9 h, high school students into <8 h and ≥8 h, divided the workdays into weekend PA time < 1 h and ≥1 h, and divided the workdays into weekend ST < 2 h and ≥2 h. The multinomial logistic regression model was used to examine the association. Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students.


Exercise , Health Literacy , Screen Time , Sleep , Humans , Adolescent , Cross-Sectional Studies , Male , Female , China , Sleep/physiology , Child , Health Literacy/statistics & numerical data , Time Factors , Students/statistics & numerical data
3.
Bioorg Med Chem Lett ; : 129793, 2024 May 10.
Article En | MEDLINE | ID: mdl-38735343

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

4.
Sci Total Environ ; 930: 172861, 2024 Jun 20.
Article En | MEDLINE | ID: mdl-38685417

The mechanism of carboxymethylammonium chloride (CC) regulating cadmium (Cd) accumulation in rice was studied in field and hydroponic experiments. Field experiments showed that 0.2-1.2 mmol L-1 CC spraying effectively reduced Cd accumulation by 44 %-77 % in early rice grains and 39 %-78 % in late rice grains, significantly increased calcium (Ca) content and amino acids content in grains, as well as alleviated Cd-induced oxidative damage in leaves. Hydroponic experiments further verified the inhibition effect of CC on Cd accumulation. 1.2 mmol L-1 CC made the highest decrease of Cd content in shoots and roots of hydroponic seedlings by 45 % and 53 %, respectively. Exogenous CC significantly increased glutamate (Glu), glycine (Gly) and glutathione (GSH) content, and improved the activities of catalase (CAT) and superoxide dismutase (SOD) by 41-131 % and 11-121 % in shoots of hydroponic seedlings, respectively. Exogenous CC also increased the relative expression of OsGLR3.1-3.5 in the shoots and roots of hydroponic seedlings. The quantum computational chemistry was used to clarify that the Gly radical provided by CC could form various complexes with Cd through carboxyl oxygen atoms. These results showed that exogenous application of CC improved the tolerance to Cd by enhancing the antioxidant capacity; inhibited the absorption, transport and accumulation of Cd in rice by (1) promoting chelation, (2) increasing the GLRs activity through upregulating the content of Glu, Gly, as well as the expression of OsGLR3.1-3.5.


Cadmium , Oryza , Oryza/metabolism , Oryza/genetics , Cadmium/metabolism , Soil Pollutants/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Gene Expression Regulation, Plant
5.
Neuroreport ; 35(7): 439-446, 2024 May 08.
Article En | MEDLINE | ID: mdl-38597327

We aimed to clarify the correlation between dynamic change of blood HSP70 and the prognosis of thrombolysis in human and rats, so as to explain the neuroprotection and early warning role of HSP70 in cerebral ischemia-reperfusion. Forty-two patients with acute ischemic stroke were divided into two groups according to the time from onset to thrombolytic therapy: 0 h-3 h (27 patients) and 3-4.5 h group (15 patients). The level of HSP70 in serum before and after thrombolysis was detected by ELISA. Furthermore, a rat model was also used to mimic the ischemic stroke and reperfusion. Peripheral blood of rat samples was collected to detect the level of HSP70 using Elisa. Several signal proteins from MAPK signaling pathway including JNK, p38, ERK (p42/44) were detected at different time points by Western blot of brain tissue. Patients who underwent thrombolytic therapy within 0-3 h had the highest HSP70 level at 1 h after thrombolysis. The higher HSP70 after thrombolysis, the better the patient prognosis. NIHSS scores showed HSP70 was positively correlated with cerebral ischemia. The levels of ERK family (p42/44 MAPK) and p-JNK were decreased gradually along with the time suffering cerebral ischemia. P-ERK, JNK, p-p38 had dynamic changes with increased ischemic time in the middle cerebral artery occlusion model. Dynamic change of HSP70 level in blood may be a biological index that reflects the functional condition of cell survival for cerebral ischemia and estimating the prognostic conditions. Importantly, HSP70 levels in blood were positively correlated with the p38 MAPK pathway in brain tissue.


Brain Ischemia , Ischemic Stroke , Reperfusion Injury , Animals , Humans , Rats , Infarction, Middle Cerebral Artery , p38 Mitogen-Activated Protein Kinases/metabolism , Reperfusion
6.
Adv Mater ; : e2401724, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575151

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

7.
Stem Cell Res Ther ; 15(1): 96, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38570892

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.


Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice , Animals , Female , Ovary/metabolism , Tissue Distribution , Cell Proliferation , Mesenchymal Stem Cells/metabolism , Disease Models, Animal , Umbilical Cord
8.
Carcinogenesis ; 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38558058

Lung cancer is the most common and lethal malignancy, with lung adenocarcinoma accounting for approximately 40% of all cases. Despite some progress in understanding the pathogenesis of this disease and developing new therapeutic approaches, the current treatments for lung adenocarcinoma remain ineffective due to factors such as high tumour heterogeneity and drug resistance. Therefore, there is an urgent need to identify novel therapeutic targets. CacyBP can regulate a variety of physiological processes by binding to different proteins, but its function in lung adenocarcinoma is unknown. Here, we show that CacyBP is highly expressed in lung adenocarcinoma tissues, and high CacyBP expression correlates with poorer patient survival. Moreover, overexpression of CacyBP promoted the proliferation, migration and invasion of lung adenocarcinoma cell lines. Further mechanistic studies revealed that CacyBP interacts with the tumour suppressor OTUD5, enhances the ubiquitination and proteasomal degradation of OTUD5, and regulates tumorigenesis via OTUD5. In conclusion, our study reveals a novel mechanism by which CacyBP promotes tumorigenesis by increasing the ubiquitination level and proteasome-dependent degradation of OTUD5, providing a potential target for the treatment of lung adenocarcinoma.

9.
Nutrients ; 16(6)2024 Mar 17.
Article En | MEDLINE | ID: mdl-38542780

Objective This study aimed to investigate the current status and influencing factors of healthy diet knowledge, attitude, and practice (KAP) among middle-aged and older adults aged 45-75 in Southwest China. Methods A questionnaire survey was conducted among 1822 middle-aged and older adults in Southwest China (including Guizhou, Sichuan, Yunnan, and Chongqing) from February to May 2021. Results The average score of healthy diet knowledge was (4.82 ± 2.98), with a passing rate of 7.6%. The mean score of healthy diet attitude was (21.26 ± 4.18), with a passing rate of 69.5%. The average score of healthy diet practice was (13.76 ± 2.84), with a passing rate of 55.5%. The score for healthy diet KAP was (39.85 ± 7.21), with a passing rate of 41.2%. Univariate analysis showed that the scores of healthy diet KAP were significantly different among participants of different ages, genders, ethnicities, residences, education levels, monthly household incomes, and regions, as well as varying according to whether several generations have lived in the same area (p < 0.05). The results of multiple linear regression showed that the healthy diet KAP of participants was influenced by age, gender, residence, education level, monthly household income, and region (p < 0.05). Conclusion The healthy diet KAP of middle-aged and older adults aged 45-75 in Southwest China shows room for improvement. The knowledge regarding healthy diet was relatively low, and certain specific healthy diet practices were not up to the standard. However, there was a positive trend in the attitude towards a healthy diet. Healthy diet education should be promoted for middle-aged and older adults.


Diet, Healthy , Health Knowledge, Attitudes, Practice , Middle Aged , Humans , Male , Female , Aged , Cross-Sectional Studies , China , Surveys and Questionnaires , Health Status
10.
J Cell Biol ; 223(6)2024 Jun 03.
Article En | MEDLINE | ID: mdl-38551495

Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.


Alcohol Oxidoreductases , Caenorhabditis elegans Proteins , Lipid Droplets , Homeostasis , Lipase/genetics , Lipid Droplet Associated Proteins/metabolism , Lipid Droplets/metabolism , Lipid Metabolism/genetics , Lipids , Lipolysis/physiology , Proteins/metabolism , Caenorhabditis elegans , Animals , Alcohol Oxidoreductases/metabolism , Caenorhabditis elegans Proteins/metabolism
11.
Chem Sci ; 15(12): 4538-4546, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38516083

Oceans and salt lakes contain vast amounts of uranium. Uranium recovery from natural water not only copes with radioactive pollution in water but also can sustain the fuel supply for nuclear power. The adsorption-assisted electrochemical processes offer a promising route for efficient uranium extraction. However, competitive hydrogen evolution greatly reduces the extraction capacity and the stability of electrode materials with electrocatalytic activity. In this study, we got inspiration from the biomineralisation of marine bacteria under high salinity and biomimetically regulated the electrochemical process to avoid the undesired deposition of metal hydroxides. The uranium uptake capacity can be increased by more than 20% without extra energy input. In natural seawater, the designed membrane electrode exhibits an impressive extraction capacity of 48.04 mg-U per g-COF within 21 days (2.29 mg-U per g-COF per day). Furthermore, in salt lake brine with much higher salinity, the membrane can extract as much uranium as 75.72 mg-U per g-COF after 32 days (2.37 mg-U per g-COF per day). This study provides a general basis for the performance optimisation of uranium capture electrodes, which is beneficial for sustainable access to nuclear energy sources from natural water systems.

12.
J Ovarian Res ; 17(1): 69, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38539230

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.


Gastrointestinal Microbiome , Hyperandrogenism , Insulin Resistance , Polycystic Ovary Syndrome , Female , Humans , Polycystic Ovary Syndrome/complications , Gastrointestinal Microbiome/physiology , Polyphenols/pharmacology , Polyphenols/therapeutic use , Dysbiosis/complications , Insulin Resistance/physiology , Inflammation/drug therapy , Inflammation/metabolism
13.
Heliyon ; 10(5): e27205, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38449594

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.

14.
ACS Cent Sci ; 10(2): 469-476, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38435527

With the rapid development of the lithium ion battery industry, emerging lithium (Li) enrichment in nature has attracted ever-growing attention due to the biotoxicity of high Li levels. To date, fast lithium ion (Li+) detection remains urgent but is limited by the selectivity, sensitivity, and stability of conventional technologies based on passive response processes. In nature, archaeal plasma membrane ion exchangers (NCLX_Mj) exhibit Li+-gated multi/monovalent ion transport behavior, activated by different stimuli. Inspired by NCLX_Mj, we design a pH-controlled biomimetic Li+-responsive solid-state nanochannel system for on-demand Li+ detection using 2-(2-hydroxyphenyl)benzoxazole (HPBO) units as Li+ recognition groups. Pristine HPBO is not reactive to Li+, whereas negatively charged HPBO enables specific Li+ coordination under alkaline conditions to decrease the ion exchange capacity of nanochannels. On-demand Li+ detection is achieved by monitoring the decline in currents, thereby ensuring precise and stable Li+ recognition (>0.1 mM) in the toxic range of Li+ concentration (>1.5 mM) for human beings. This work provides a new approach to constructing Li+ detection nanodevices and has potential for applications of Li-related industries and medical services.

16.
J Trace Elem Med Biol ; 83: 127415, 2024 May.
Article En | MEDLINE | ID: mdl-38377659

BACKGROUND: Environmental arsenic (As) exposure is strongly related to the progression of chronic obstructive pulmonary disease (COPD). Pulmonary epithelial cells apoptosis is implicated in the pathophysiological mechanisms of COPD. However, the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one biomarker of apoptosis, remains unclear in As-mediated pulmonary function alternations in COPD patients. METHODS: This study included 239 COPD patients. The serum level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was measured by enzyme-linked immunosorbent assay (ELISA). The blood As level was determined through inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Blood As levels exhibited a negative and dose-dependent correlation with pulmonary function. Per unit elevation of blood arsenic concentrations was related to reductions of 0.339 L in FEV1, 0.311 L in FVC, 1.171% in FEV1/FVC%, and 7.999% in FEV1% in COPD subjects. Additionally, a positive dose-response correlation of blood As with serum TRAIL was found in COPD subjects. Additionally, the level of serum TRAIL was negatively linked to lung function. Elevated TRAIL significantly mediated As-induced decreases of 11.05%, 13.35%, and 31.78% in FVC, FEV1, and FEV1%, respectively among the COPD patients. CONCLUSION: Blood As level is positively correlated with pulmonary function decline and serum TRAIL increase in individuals with COPD. Our findings suggest that elevated TRAIL levels may serve as a mediating mechanism through which As contributes to declining lung function in COPD patients.


Arsenic , Pulmonary Disease, Chronic Obstructive , Humans , Ligands , Lung/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Tumor Necrosis Factor-alpha , Apoptosis
17.
J Hazard Mater ; 468: 133704, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38364577

Our previous study revealed that 1-nitropyrene (1-NP) exposure evoked pulmonary fibrosis in mice. However, the exact mechanism remained elusive. We found that 1-NP induced telomere damage and cellular senescence in mice lungs, and two alveolar epithelial cells lines. 1-NP downregulated telomere repeat binding factor 2 (TRF2), and upregulated FBXW7. Mechanistically, 1-NP-caused TRF2 ubiquitination and proteasomal degradation depended on E3 ubiquitin ligase activity of FBXW7. Moreover, 1-NP upregulated FBXW7 m6A modification via an ALKBH5-YTHDF1-dependent manner. Further analysis suggested 1-NP promoted ALKBH5 SUMOylation and subsequent proteasomal degradation. Additionally, 1-NP evoked mitochondrial reactive oxygen species (mtROS) overproduction. Mito-TEMPO, a mitochondrial-targeted antioxidant, mitigated 1-NP-caused mtROS overproduction, ALKBH5 SUMOylation, FBXW7 m6A modification, TRF2 degradation, cellular senescence, and pulmonary fibrosis. Taken together, mtROS-initiated ALKBH5 SUMOylation and subsequent FBXW7 m6A modification is indispensable for TRF2 degradation and cellular senescence in alveolar epithelial cells during 1-NP-induced pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis.


Adenine/analogs & derivatives , Pulmonary Fibrosis , Pyrenes , Sumoylation , Animals , Mice , F-Box-WD Repeat-Containing Protein 7/genetics , F-Box-WD Repeat-Containing Protein 7/metabolism , Alveolar Epithelial Cells/metabolism , Pulmonary Fibrosis/chemically induced
18.
Front Endocrinol (Lausanne) ; 15: 1322395, 2024.
Article En | MEDLINE | ID: mdl-38370350

Primary vesicoureteral reflux (VUR) is the prevailing congenital anomaly of the kidneys and urinary tract, posing a significant risk for pyelonephritis scarring and chronic renal insufficiency in pediatric patients. Nevertheless, the precise genetic etiology of VUR remains enigmatic. In this current investigation, we conducted whole-exome sequencing on a child exhibiting single kidney, devoid of any familial VUR background, along with both biological parents. Two missense variants (NM_019105.8: exon11: c.4111G>A and NM_019105.8: exon2: c.31A>T) in the TNXB gene were identified through whole-exome sequencing of the child. These variants were found to be inherited from the child's parents, with each parent carrying one of the variants. Molecular dynamics simulations were conducted to assess the impact of these variants on the tenascin XB proteins encoded by them, revealing varying degrees of impairment. Based on our findings, it is suggested that the TNXB compound heterozygous variant, consisting of c.4111G>A and c.31A>T, may be the underlying cause of right renal agenesis and left hydronephrosis in afflicted child. This discovery broadens the genetic range of the TNXB gene and establishes a genetic foundation for disease-specific preimplantation genetic diagnosis (PGD) in prospective pregnancies involving the parents of this afflicted child.


Kidney/abnormalities , Solitary Kidney , Urogenital Abnormalities , Vesico-Ureteral Reflux , Humans , Child , Vesico-Ureteral Reflux/complications , Vesico-Ureteral Reflux/genetics , Vesico-Ureteral Reflux/diagnosis , Prospective Studies
19.
iScience ; 27(2): 108887, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38318376

UB-612 pan-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine targets the monomeric Spike S1-receptor binding domain (RBD) subunit protein along with five sequence-conserved T cell epitopes found on Spike S2 and non-Spike M and N proteins. UB-612 vaccination safely induces potent, broad, and long-lasting immunity against SARS-CoV-2. A phase-2 trial-extended observational study during the Omicron BA.2-/BA.5-dominated outbreak was conducted to investigate UB-612's protective effect against COVID-19 hospitalization and intensive care unit (ICU) admission (H-ICU). Additionally, memory viral-neutralizing titer and T cell immunity behind disease protection were explored. No cases of H-ICU were reported beyond 14 months post-second dose or beyond 10 months post-booster (third dose). The positive outcome correlates with strong cytotoxic CD8 T cell immunity, in line with the results of an ongoing phase-3 heterologous booster trial showing that UB-612 can enhance anti-BA.5 seroconversion rate and viral-neutralizing titer for mRNA, adeno-vectored, and virus-inactivated vaccine platforms. The UB-612 multitope vaccine may serve as an effective primer and booster for those at risk of SARS-CoV-2 infection.

20.
Respir Res ; 25(1): 91, 2024 Feb 17.
Article En | MEDLINE | ID: mdl-38368333

BACKGROUND: Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. METHODS: Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. RESULTS: Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. CONCLUSION: Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.


Cadmium , Pulmonary Disease, Chronic Obstructive , Humans , Prospective Studies , Disease Progression , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/complications , Hospitalization
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