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1.
J Air Waste Manag Assoc ; : 1-7, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38753760

ABSTRACT

Polychlorinated biphenyls (PCBs), including all 209 congeners, are designated as persistent organic pollutants (POPs) due to their high toxicity and bioaccumulation in human bodies and the ecosystem. The need for PCB remediation still remains long after their production ban. In this study, a catalytic hydro-dechlorination (HDC) method was employed to dechlorinate 2,4,4'-trichlorobiphenyl (PCB 28), a congener found ubiquitously in multiple environmental media. The HDC of PCB 28 was experimentally studied at mild temperatures viz. ~20, 50, and ~77°C and atmospheric pressure. Et3N (triethylamine) was added as a co-catalyst. The dechlorination rates increased with temperature as well as Et3N dosage, and the HDC pathway was hypothesized based on the product and intermediates observed. The less chlorinated intermediates suggested that the position of the chlorine strongly impacted HDC rates, and the preference of HDC at para positions can be orders of magnitudes higher than the ortho. The activation energy was estimated in the range of 12.4-13.9 kJ/mole, indicating a diffusion-controlled HDC system.Implications: The remediation need for polychlorinated biphenyls (PCBs) still remains long after their production ban around the world. The development of low-cost methods is highly desirable, especially for developing countries, in response to the Stockholm Convention. In this study, the dechorination of a ubiquitously present PCB congener was studied using a catalytic hydro-dechlorination (HDC) method in low temperatures up to ~77°C and was able to achieve near 100% dechlorination in 6 hr. Results indicated that the HDC process can be performed under mild temperatures and atmospheric conditions and can be a potential solution to real world PCB contamination issues.

2.
Chem Commun (Camb) ; 60(29): 3958-3961, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38501223

ABSTRACT

A novel and interesting controllable spirocyclization of unsaturated barbiturates with enamino esters for the assembly of cyclopentenyl and pyrrolinyl spirobarbiturates has been developed under ball-milling conditions. The present protocol features high chemoselectivity and efficiency, excellent functional group tolerance and mild reaction conditions.

3.
Pediatr Neurol ; 153: 159-165, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38394830

ABSTRACT

BACKGROUND: To explore the risk factors for preoperative massive cerebral infarction (MCI) in pediatric patients with moyamoya disease (MMD). METHODS: Pediatric patients with MMD treated between 2017 and 2022 were enrolled. Logistic regression analysis was performed to identify risk factors for MCI among the patients, and a nomogram was constructed to identify potential predictors of MCI. Receiver operating characteristic (ROC) curves and areas under the curves were calculated to determine the effects of different risk factors. RESULTS: This study included 308 pediatric patients with MMD, including 36 with MCI. The MCI group exhibited an earlier age of onset than the non-MCI group. Significant intergroup differences were observed in familial MMD history, postcirculation involvement, duration from diagnosis to initiation of treatment, Suzuki stage, magnetic resonance angiography (MRA) score, collateral circulation score, and RNF213 p.R4810K variations. Family history, higher MRA score, lower collateral circulation score, and RNF213 p.R4810K variations were substantial risk factors for MCI in pediatric patients with MMD. The nomogram demonstrated excellent discrimination and calibration capabilities. The integrated ROC model, which included all the abovementioned four variables, showed superior diagnostic precision with a sensitivity of 67.86%, specificity of 87.01%, and accuracy of 85.11%. CONCLUSIONS: This study showed that family history, elevated MRA score, reduced collateral circulation score, and RNF213 p.R4810K variations are risk factors for MCI in pediatric patients with MMD. The synthesized model including these variables demonstrated superior predictive efficacy; thus, it can facilitate early identification of at-risk patients and timely initiation of appropriate interventions.


Subject(s)
Moyamoya Disease , Humans , Child , Moyamoya Disease/complications , Moyamoya Disease/diagnostic imaging , Genetic Predisposition to Disease , Adenosine Triphosphatases , Ubiquitin-Protein Ligases/genetics , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/etiology , Risk Factors
4.
Eur Radiol ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38172442

ABSTRACT

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

5.
Eur J Contracept Reprod Health Care ; 29(2): 76-78, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38284985

ABSTRACT

CASE: Intrauterine device (IUD) is used worldwide as an effective contraceptive method, but the migration of IUD is a serious complication. We report the case of IUD migration leading to bladder calculus formation and a minimally invasive transurethral surgical approach was performed for treatment. Holmium laser was used to break up the bladder calculus and cut through the bladder mucosa where the IUD was attached, finally the IUD was removed through the urethra. This minimally invasive procedure is a safe and effective treatment for IUD migration, and similar cases have not been reported in the literature. CONCLUSION: That the secondary bladder calculus were smashed by intense pulse mode of holmium laser, and the bladder tissue around the attached IUD was opened by cutting mode of holmium laser, and finally the IUD was completely removed from urethra, this surgical method is safe and effective, and there is no case report on IUD removal of transurethral cystoscope in the literature.

6.
J Magn Reson Imaging ; 59(4): 1456-1463, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37357525

ABSTRACT

BACKGROUND: Little is known about the association between stroke and imaging and clinical features in conservatively treated patients with moyamoya disease (MMD). PURPOSE: To investigate independent risk factors for stroke in conservatively treated patients with MMD during a long-term follow-up. STUDY TYPE: Prospective study. SUBJECTS: One hundred sixty conservatively managed patients with MMD (median age 46 years, 89 male). FIELD STRENGTH/SEQUENCE: Time of flight, turbo inversion recovery magnitude T1WI, turbo spin echo (TSE) T2WI, echo-planar imaging DWI, T2-fluid attenuated inversion recovery, dynamic susceptibility contrast-magnetic resonance imaging, and pre- and post-contrast 3D TSE T1WI sequences at 3.0 Tesla. ASSESSMENT: Patients were assessed at baseline and followed yearly. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical (modified Rankin score [mRS]), and cerebral imaging (cerebral blood volume [CBV] and concentric enhancement of arterial wall) factors at baseline were considered as potential predictors of stroke during the follow-up period. STATISTICAL TESTS: Univariable and multivariable Cox proportional hazards models to calculate the hazard ratios (HRs) and corresponding 95% confidence interval (CI) for stroke. Cumulative risk of stroke was estimated by the Kaplan-Meier product-limit method. A P value <0.05 was considered statistically significant. RESULTS: The median follow-up duration was 47 months. During the follow-up period, 18 (11.25%) patients experienced stroke events (13 [8.13%] ischemic, 5 [3.12%] hemorrhagic). Univariable analysis showed that 11 factors were significantly associated with stroke. After adjustment for clinical characteristics, multivariable analysis showed that mRS score ≥3 (HR, 1.99; 95% CI, 1.26-3.14), decreased CBV (HR, 5.31; 95% CI, 2.32-12.13), and concentric enhancement of the arterial wall (HR, 4.16; 95% CI, 1.55-11.15) were significantly associated with stroke. DATA CONCLUSION: Decreased CBV, mRS score ≥ 3, and concentric enhancement of the arterial wall were significantly associated with increased incidence of stroke in conservatively treated MMD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.


Subject(s)
Moyamoya Disease , Stroke , Humans , Male , Middle Aged , Follow-Up Studies , Moyamoya Disease/complications , Moyamoya Disease/diagnostic imaging , Prospective Studies , Retrospective Studies , Stroke/diagnostic imaging , Stroke/complications , Magnetic Resonance Imaging/methods
7.
Nucleic Acids Res ; 52(D1): D1315-D1326, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37870452

ABSTRACT

Human endogenous retroviruses (HERVs), as remnants of ancient exogenous retrovirus infected and integrated into germ cells, comprise ∼8% of the human genome. These HERVs have been implicated in numerous diseases, and extensive research has been conducted to uncover their specific roles. Despite these efforts, a comprehensive source of HERV-disease association still needs to be added. To address this gap, we introduce the HervD Atlas (https://ngdc.cncb.ac.cn/hervd/), an integrated knowledgebase of HERV-disease associations manually curated from all related published literature. In the current version, HervD Atlas collects 60 726 HERV-disease associations from 254 publications (out of 4692 screened literature), covering 21 790 HERVs (21 049 HERV-Terms and 741 HERV-Elements) belonging to six types, 149 diseases and 610 related/affected genes. Notably, an interactive knowledge graph that systematically integrates all the HERV-disease associations and corresponding affected genes into a comprehensive network provides a powerful tool to uncover and deduce the complex interplay between HERVs and diseases. The HervD Atlas also features a user-friendly web interface that allows efficient browsing, searching, and downloading of all association information, research metadata, and annotation information. Overall, the HervD Atlas is an essential resource for comprehensive, up-to-date knowledge on HERV-disease research, potentially facilitating the development of novel HERV-associated diagnostic and therapeutic strategies.


Subject(s)
Endogenous Retroviruses , Knowledge Bases , Virus Diseases , Humans , Virus Diseases/genetics , Virus Diseases/virology , Atlases as Topic , Internet Use
8.
Chemosphere ; 349: 140987, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38122941

ABSTRACT

Polychlorinated biphenyls (PCBs) is a group of persistent organic pollutants that still requires remediation and reduction long after the production is discontinued. Aroclor 1232 is a commercial PCB mixture that has been much less studied. To address this void, this paper presented catalytic hydro-dechlorination (HDC) of Aroclor 1232 using palladium on activated carbon (Pd/AC) at atmospheric pressure. Experimental variables studied including three mild temperatures, 22.5 °C, 50 °C, and 80 °C, and four different co-catalyst loadings. This batch of Aroclor 1232 constituted of more than 83% of mono-, di-, and tri-, chlorinated biphenyls (CB), in addition to biphenyl, tetra- and penta CBs. HDC efficiency increased with temperature, and reached 99.9% within 4 h of reaction at 80 °C. HDC efficiency also increased with co-catalyst loading. HDC efficiencies followed the trend of para > meta > ortho positions among isomers. The increase of temperature and Et3N dosage are especially effective in dechlorination at ortho and meta positions. The apparent activation energy of Aroclor 1232 HDC was estimated as 25.57 kJ/mol based on pseudo-first order assumption, indicating that the reaction may be diffusion limited. Given the modest reaction conditions used, the HDC of Aroclor 1232 can potentially be a low-cost process.


Subject(s)
Aroclors , Polychlorinated Biphenyls , Palladium , Catalysis , Temperature , Chlorine
9.
Ann Med ; 55(2): 2274512, 2023.
Article in English | MEDLINE | ID: mdl-37980573

ABSTRACT

BACKGROUND: Forsythin, an active compound from Forsythiae Fructus, has the potential to treat the common cold and influenza through its antipyretic-analgesic, anti-inflammatory and antiviral effects. The safety, tolerability and pharmacokinetic (PK) profile of forsythin were evaluated in healthy Chinese subjects. METHODS: This phase 1a study included three parts: double-blind, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 400, 600 or 800 mg), food effect investigation (100 mg) and multiple-ascending-dose (MAD) (50, 100 or 200 mg TID for 5 days). RESULTS: Forsythin is safe and tolerable in healthy Chinese subjects. The rates of adverse events (AEs) in the forsythin cohort were similar to those in the placebo cohort. Forsythin is well-absorbed after single or multiple doses and is extensively metabolized. The primary metabolites were aglycone M1, M1 sulphate (M2) and M1 glucuronide (M7). Exposure to forsythin (100 mg) was higher after food intake by approximately 1.4-fold, whereas M2 and M7 did not change. The steady state was reached around three days in the MAD study. Forsythin, M2 and M7 accumulation on day 5 was 1, 3 and 2, respectively. CONCLUSIONS: The safety and PK profiles of forsythin support further evaluation of its efficacy in individuals with the common cold or influenza.


Subject(s)
Common Cold , Influenza, Human , Humans , Healthy Volunteers , Common Cold/drug therapy , Area Under Curve , Double-Blind Method , Dose-Response Relationship, Drug
10.
ACS Appl Bio Mater ; 6(12): 5798-5808, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-37988327

ABSTRACT

Shiga toxin (Stx) is associated with foodborne infections of some Shigella spp. and Shiga toxin-producing Escherichia coli (STEC), leading to life-threatening hemolytic uremic syndrome (HUS). Target-specific therapeutics against HUS are currently unavailable in clinical practice. Herein, we reported the construction and in vitro characterization of Gb3-coated bovine milk exosomes (Gb3-mExo) as a multivalent Shiga toxin neutralizer, utilizing the natural advantages of milk exosomes (mExo) in drug delivery and multivalent interactions between Stx and its receptor Gb3. Gb3-mExo constructs were achieved by conjugating mExo with the Gb3 derivatives containing stearic acid-derived lipid tail, which was prepared through an efficient chemoenzymatic approach. The constructs were able to potently neutralize the binding of the B subunit of Stx2 (Stx2B) to receptor Gb3 immobilized on the plate or expressed on model cells. General safety of the constructs was evidenced by the cytotoxicity analysis and hemolysis assay. In addition to the excellent stability under conventional storage and handling conditions, the construct can also retain most of its neutralization potency under gastrointestinal pH extremes, showing the potential for oral administration. Considering the natural availability and excellent biocompatibility of mExo, Gb3-mExo conjugates should prove to be a practical prophylactic and therapeutic for the Shiga toxin-related infections.


Subject(s)
Exosomes , Shiga-Toxigenic Escherichia coli , Animals , Shiga Toxin , Shiga Toxin 2/metabolism , Exosomes/metabolism , Milk/metabolism , Shiga-Toxigenic Escherichia coli/metabolism
11.
J Magn Reson Imaging ; 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37823479

ABSTRACT

BACKGROUND: The features of intracranial arteries in patients with Moyamoya disease (MMD) have been widely investigated. However, the MR characteristics of extracranial internal carotid artery (EICA) and their effect on outcomes of revascularization treatment are not fully understood. PURPOSE: To investigate the characteristics of EICA and their relationship with outcomes of revascularization treatment in adult patients with MMD based on higher-resolution MRI (HRMRI). STUDY TYPE: Prospective interventional outcomes. SUBJECTS: Two hundred eighty-eight consecutive patients with MMD (mean age: 43.7 ± 11.2 years; 140 male). FIELD STRENGTH/SEQUENCE: Turbo inversion recovery magnitude T1-weighted imaging and turbo spin echo (TSE) T2-weighted imaging, three-dimensional time-of-flight MR angiography, T2-fluid attenuated inversion recovery, and 3D T1-SPACE vessel wall imaging at 3.0 T. ASSESSMENT: The HRMRI characteristics of EICA were determined. The relationship between the characteristics of EICA (proximal stenosis, diffuse wall thickening, carotid plaques, and luminal thrombosis) and stroke outcomes of revascularization treatment in patients with MMD was analyzed. The discriminative ability of EICA characteristics in combination with intracranial carotid artery features (involvement of vessel segments, bilateral involvement, and Suzuki stage) to determine stroke outcomes was compared with that of intracranial artery features alone during a mean 8.0 months follow-up period. STATISTICAL TESTS: Cox proportional hazards models and Kaplan-Meier curves to calculate the hazard ratios (HRs) for stroke with 95% confidence intervals (CIs). Area under the receiver operating characteristic curve (AUC) for assessing discriminative performance. A P value <0.05 was considered statistically significant. RESULTS: During a mean 8.0 ± 2.2 months follow-up, of the 288 participants, 137 had proximal stenosis (47.6%), 106 had diffuse wall thickening (36.8%), 60 had carotid plaques (20.8%), and 27 had luminal thrombosis (9.4%) of EICA. Of these features, proximal stenosis (HR = 2.86; 95% CI = 1.13-7.29) and diffuse wall thickening (HR = 2.62; 95% CI = 1.16-5.94) of EICA were significantly associated with stroke after surgery, before and after adjusting for confounding factors. In discriminating the stroke outcomes after surgery, combining characteristics of EICA with features of intracranial arteries resulted in a significant incremental improvement (DeLong test, P < 0.05) in the AUC over that obtained with features of intracranial arteries alone (AUC: 0.73 vs. 0.60-0.64). CONCLUSION: Proximal stenosis and diffuse wall thickening of EICA were significantly associated with stroke outcomes after surgery in patients with MMD. Our findings suggest that understanding the characteristics of EICA has added value for intracranial vessels in predicting future events after surgery in patients with MMD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.

12.
Commun Biol ; 6(1): 899, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37658226

ABSTRACT

Genome-wide association study has identified fruitful variants impacting heritable traits. Nevertheless, identifying critical genes underlying those significant variants has been a great task. Transcriptome-wide association study (TWAS) is an instrumental post-analysis to detect significant gene-trait associations focusing on modeling transcription-level regulations, which has made numerous progresses in recent years. Leveraging from expression quantitative loci (eQTL) regulation information, TWAS has advantages in detecting functioning genes regulated by disease-associated variants, thus providing insight into mechanisms of diseases and other phenotypes. Considering its vast potential, this review article comprehensively summarizes TWAS, including the methodology, applications and available resources.


Subject(s)
Genome-Wide Association Study , Transcriptome , Databases, Factual , Fruit , Phenotype
13.
Eur Radiol ; 33(10): 6918-6926, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37453985

ABSTRACT

OBJECTIVES: To evaluate the diagnostic performance of high-resolution magnetic resonance-vessel wall imaging (HRMR-VWI) in differentiating moyamoya disease (MMD) from atherosclerosis-associated moyamoya vasculopathy (AS-MMV) and investigate an accurate approach for the differential diagnosis. METHODS: Adult patients who were diagnosed as MMD or AS-MMV and underwent HRMR-VWI were retrospectively included. The three vessel wall features (outer diameter (OD), remodeling index (RI), and pattern of vessel wall thickening) of middle cerebral artery (MCA) in identifying MMD from AS-MMV were assessed and compared. Furthermore, subgroup analysis stratified by degree of luminal stenosis was performed and the cutoff values of different vessel wall features in differentiating MMD from AS-MMV were also calculated. RESULTS: A total of 265 patients (160 cases of MMD and 105 AS-MMV) were included. Patients with AS-MMV had greater OD and RI and were more likely to exhibit eccentric thickening of vessel wall compared to those with MMD (all p < 0.001). The ROC analysis showed that the AUC value of OD was greater than that of RI (0.912 vs. 0.889, p = 0.007) in differentiating MMD from AS-MMV, and their corresponding cutoff values were 1.77 mm and 0.27, respectively. And the AUC value of pattern of vessel wall thickening was 0.786 in non-occluded patients. With the increase of lumen stenosis, the discrimination power of the three indicators enhanced correspondingly. CONCLUSIONS: HRMR-VWI is valuable in distinguishing MMD from AS-MMV. The OD of MCA has better diagnostic performance in differentiating AS-MMV from MMD compared to RI and pattern of vessel wall thickening. CLINICAL RELEVANCE STATEMENT: The outer diameter of the involved artery proved to be both accurate and convenient in distinguishing atherosclerosis-associated moyamoya vasculopathy from moyamoya disease and may provide a quantitative reference for clinical diagnosis. KEY POINTS: High-resolution magnetic resonance-vessel wall imaging is valuable in distinguishing atherosclerosis-associated moyamoya vasculopathy from moyamoya disease. Compared to remodeling index and pattern of vessel wall thickening, outer diameter is more accurate in differentiating atherosclerosis-associated moyamoya vasculopathy from moyamoya disease. With the increase of lumen stenosis, the discrimination power of outer diameter, remodeling index, and pattern of vessel wall thickening enhanced correspondingly.


Subject(s)
Atherosclerosis , Moyamoya Disease , Adult , Humans , Moyamoya Disease/complications , Moyamoya Disease/diagnostic imaging , Retrospective Studies , Constriction, Pathologic , Magnetic Resonance Imaging/methods , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Middle Cerebral Artery , Magnetic Resonance Spectroscopy , Magnetic Resonance Angiography/methods
14.
Clin Nutr ; 42(7): 1219-1226, 2023 07.
Article in English | MEDLINE | ID: mdl-37236872

ABSTRACT

IMPORTANCE: Little evidence on the association between adiposity measures and all-cause mortality was observed among centenarians, and no targeted development of optimal weight recommendations for them. OBJECTIVE: To comprehensively assess the association between adiposity indices and all-cause mortality among centenarians. DESIGN SETTING, AND PARTICIPANTS: This prospective population-based cohort study included 1002 centenarians registered in 18 counties and cities in Hainan Province from June 2014 to May 2021. The age of participants at baseline was provided by the civil affairs bureau and verified before enrollment. MAIN OUTCOMES AND MEASURES: All-cause mortality was rigorously confirmed as the primary outcome. BMI was calculated by height and weight. BRI was calculated by height and waist circumference. RESULTS: At baseline, the mean (SD) age was 102.8 ± 2.7 years, and 180 participants (18.0%) were men. The median follow-up time was 5.0 (4.8-5.5) years, with 522 deaths. In BMI categories, compared with the lowest group (mean BMI = 14.2 kg/m2), the highest group (mean BMI = 22.2 kg/m2) had lower mortality (hazard ratio [HR], 0.61; 95%CI, 0.47-0.79) (P for trend = 0.001). In BRI categories, compared with the lowest group (mean BRI = 2.3), the highest group (mean BRI = 5.7) had lower mortality (hazard ratio [HR], 0.66; 95%CI, 0.51-0.85) (P for trend = 0.002), and the risk did not decrease after BRI exceeded 3.9 in women. Higher BRI was associated with lower HRs after adjusting for interaction with comorbidities status. E-values analysis suggested robustness to unmeasured confounding. CONCLUSIONS AND RELEVANCE: BMI and BRI were inverse linear associated with mortality risk in the whole population, while BRI was observed to be J-shaped in women. The interaction of lower multiple complication incidence and BRI had a significant effect on the reduced risk of all-cause mortality.


Subject(s)
Adiposity , Centenarians , Male , Aged, 80 and over , Humans , Female , Prospective Studies , Body Mass Index , Cohort Studies , Obesity/epidemiology , Waist Circumference , Risk Factors
15.
Nat Aging ; 3(6): 705-721, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37118553

ABSTRACT

How N6-methyladenosine (m6A), the most abundant mRNA modification, contributes to primate tissue homeostasis and physiological aging remains elusive. Here, we characterize the m6A epitranscriptome across the liver, heart and skeletal muscle in young and old nonhuman primates. Our data reveal a positive correlation between m6A modifications and gene expression homeostasis across tissues as well as tissue-type-specific aging-associated m6A dynamics. Among these tissues, skeletal muscle is the most susceptible to m6A loss in aging and shows a reduction in the m6A methyltransferase METTL3. We further show that METTL3 deficiency in human pluripotent stem cell-derived myotubes leads to senescence and apoptosis, and identify NPNT as a key element downstream of METTL3 involved in myotube homeostasis, whose expression and m6A levels are both decreased in senescent myotubes. Our study provides a resource for elucidating m6A-mediated mechanisms of tissue aging and reveals a METTL3-m6A-NPNT axis counteracting aging-associated skeletal muscle degeneration.


Subject(s)
Liver , Primates , Animals , Humans , Primates/genetics , Aging/genetics , Homeostasis/genetics , Methyltransferases/genetics
16.
J Neurol Neurosurg Psychiatry ; 94(7): 567-574, 2023 07.
Article in English | MEDLINE | ID: mdl-36868848

ABSTRACT

OBJECTIVES: We aimed to compare the long-term outcomes and surgical benefits between moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) using high-resolution MRI (HRMRI). METHODS: MMV patients were retrospectively included and divided into the MMD and AS-MMV groups according to vessel wall features on HRMRI. Kaplan-Meier survival and Cox regression were performed to compare the incidence of cerebrovascular events and prognosis of encephaloduroarteriosynangiosis (EDAS) treatment between MMD and AS-MMV. RESULTS: Of the 1173 patients (mean age: 42.4±11.0 years; male: 51.0%) included in the study, 881 were classified into the MMD group and 292 into the AS-MMV group. During the average follow-up of 46.0±24.7 months, the incidence of cerebrovascular events in the MMD group was higher compared with that in the AS-MMV group before (13.7% vs 7.2%; HR 1.86; 95% CI 1.17 to 2.96; p=0.008) and after propensity score matching (6.1% vs 7.3%; HR 2.24; 95% CI 1.34 to 3.76; p=0.002). Additionally, patients treated with EDAS had a lower incidence of events than those not treated with EDAS, regardless of whether they were in the MMD (HR 0.65; 95% CI 0.42 to 0.97; p=0.043) or AS-MMV group (HR 0.49; 95% CI 0.51 to 0.98; p=0.048). CONCLUSIONS: Patients with MMD had a higher risk of ischaemic stroke than those with AS-MMV, and patients with both MMD and AS-MMV could benefit from EDAS. Our findings suggest that HRMRI could be used to identify those who are at a higher risk of future cerebrovascular events.


Subject(s)
Atherosclerosis , Brain Ischemia , Moyamoya Disease , Stroke , Humans , Male , Adult , Middle Aged , Moyamoya Disease/complications , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/epidemiology , Retrospective Studies , Brain Ischemia/complications , Stroke/complications , Magnetic Resonance Imaging , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging
17.
Nucleic Acids Res ; 51(D1): D1179-D1187, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36243959

ABSTRACT

Transcriptome-wide association studies (TWASs), as a practical and prevalent approach for detecting the associations between genetically regulated genes and traits, are now leading to a better understanding of the complex mechanisms of genetic variants in regulating various diseases and traits. Despite the ever-increasing TWAS outputs, there is still a lack of databases curating massive public TWAS information and knowledge. To fill this gap, here we present TWAS Atlas (https://ngdc.cncb.ac.cn/twas/), an integrated knowledgebase of TWAS findings manually curated from extensive literature. In the current implementation, TWAS Atlas collects 401,266 high-quality human gene-trait associations from 200 publications, covering 22,247 genes and 257 traits across 135 tissue types. In particular, an interactive knowledge graph of the collected gene-trait associations is constructed together with single nucleotide polymorphism (SNP)-gene associations to build up comprehensive regulatory networks at multi-omics levels. In addition, TWAS Atlas, as a user-friendly web interface, efficiently enables users to browse, search and download all association information, relevant research metadata and annotation information of interest. Taken together, TWAS Atlas is of great value for promoting the utility and availability of TWAS results in explaining the complex genetic basis as well as providing new insights for human health and disease research.


Subject(s)
Quantitative Trait Loci , Transcriptome , Humans , Transcriptome/genetics , Genome-Wide Association Study/methods , Phenotype , Knowledge Bases , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease
18.
Eur Radiol ; 33(4): 2489-2499, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36334103

ABSTRACT

OBJECTIVES: This study aimed to determine the association between vessel wall enhancement and progression of arterial stenosis and clinical outcomes in patients with moyamoya (MMD) using high-resolution magnetic resonance (HRMR) vessel wall imaging. METHODS: Consecutive participants diagnosed with MMD were prospectively recruited and underwent HRMR at baseline and during follow-up, which had an interval period of ≥ 6 months and were clinically followed up for ≤ 24 months to record the occurrence of ischemic stroke. The relationship between vessel wall enhancement and arterial stenosis progression and stroke occurrence was evaluated. RESULTS: HRMR vessel wall imaging was used to identify 309 stenotic lesions at the internal carotid artery (ICA) in 170 participants (mean age: 37.7 ± 11.3 years old, male: 44.1%). The baseline presence (adjusted odds ratio [aOR] = 3.57, 95% CI = 1.97-6.44, p < 0.001) and progression (aOR = 2.96, 95% CI = 1.29-6.80, p = 0.010) of vessel wall enhancement and middle cerebral artery (MCA) involvement (aOR = 4.98, 95% CI = 1.50-16.52, p = 0.009) were significantly associated with rapid progression of arterial stenosis. Furthermore, vessel wall enhancement (adjusted HR = 3.59, 95% CI = 1.33-9.70, p = 0.011) and rapid progression of arterial stenosis (adjusted HR = 4.52, 95% CI = 1.48-13.81, p = 0.008) were correlated with future stroke occurrence. CONCLUSION: The baseline presence of vessel wall enhancement was associated with rapid progression of arterial stenosis and increased risk for stroke in MMD patients. Our findings suggest that vessel wall enhancement may serve as a predictor of disease progression and poor outcomes in MMD. KEY POINTS: • The baseline presence of vessel wall enhancement was significantly associated with the rapid progression of arterial stenosis. • The baseline presence of vessel wall enhancement and rapid progression of arterial stenosis were both correlated with increased risk for future occurrence of stroke. • Our findings suggest that vessel wall enhancement may serve as a predictor of rapid progression of arterial stenosis and poor outcomes in MMD patients.


Subject(s)
Moyamoya Disease , Stroke , Humans , Male , Adult , Middle Aged , Moyamoya Disease/diagnostic imaging , Constriction, Pathologic , Magnetic Resonance Imaging/methods , Stroke/etiology
19.
Appl Opt ; 61(28): 8190-8196, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36256130

ABSTRACT

Ambient temperature is one of the important factors affecting the imaging quality of the optical system. Therefore, it is necessary to analyze the thermal-optical characteristics of the optical system when studying the imaging quality of the optical system. Taking the self-made aerial camera optical system as an example, this paper reports the use of the finite element software ANSYS to analyze the thermal stress of the aerial camera optical system, the use of the homogeneous coordinate transformation method to remove the rigid body displacement caused by the mirror surface, and the performance of a Zernike polynomial simulation on the processed surface data. Together, the Zernike coefficients obtained after the fitting are substituted into the ZEMAX optical software to express the surface shape obtained after deformation to analyze the changes in optical imaging quality under thermal environmental conditions. The results of the experiment show that when the working environmental temperature is 50°C, the (MTF) decreases from 0.371 to 0.315 and, when the working environmental temperature is -40∘C, the MTF decreases from 0.371 to 0.285. The comparison results of the experiment and simulation show that the environmental temperature is heating up or, under the condition of cooling, the imaging quality of the aerial camera will be reduced. The thermal-optical analysis method can be used to simulate the actual use conditions of the aerial camera optical system and predict the imaging quality change trend of the optical system. The method of thermo-optical analysis has important guiding significance for the design of an optical-mechanical system.

20.
Medicine (Baltimore) ; 101(38): e30622, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36197206

ABSTRACT

RATIONALE: Previous clinical reports of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in pregnancy are rare. PATIENT CONCERNS: The present study presents the case of 37-year-old women exhibiting third trimester with progressive painless, abdominal skin nodules. INTERVENTIONS AND OUTCOMES: A 37-year-old pregnant woman with BPDCN and partial placenta previa and racket-shaped placenta. After comprehensive evaluation, the pregnancy status ends at 37 weeks and 6 days by cesarean section of lower uterus and no abnormality in the newborn. LESSONS: Pregnant women diagnosed with BPDCN in the third trimester should terminate the pregnancy promptly for further treatment.


Subject(s)
Hematologic Neoplasms , Myeloproliferative Disorders , Skin Neoplasms , Acute Disease , Adult , Cesarean Section , Dendritic Cells , Female , Hematologic Neoplasms/therapy , Humans , Infant, Newborn , Pregnancy , Skin , Skin Neoplasms/diagnosis
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