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1.
Cell ; 186(9): 1912-1929.e18, 2023 04 27.
Article in English | MEDLINE | ID: mdl-37044097

ABSTRACT

The spectrin-based membrane skeleton is a ubiquitous membrane-associated two-dimensional cytoskeleton underneath the lipid membrane of metazoan cells. Mutations of skeleton proteins impair the mechanical strength and functions of the membrane, leading to several different types of human diseases. Here, we report the cryo-EM structures of the native spectrin-actin junctional complex (from porcine erythrocytes), which is a specialized short F-actin acting as the central organizational unit of the membrane skeleton. While an α-/ß-adducin hetero-tetramer binds to the barbed end of F-actin as a flexible cap, tropomodulin and SH3BGRL2 together create an absolute cap at the pointed end. The junctional complex is strengthened by ring-like structures of dematin in the middle actin layers and by patterned periodic interactions with tropomyosin over its entire length. This work serves as a structural framework for understanding the assembly and dynamics of membrane skeleton and offers insights into mechanisms of various ubiquitous F-actin-binding factors in other F-actin systems.


Subject(s)
Cytoskeleton , Erythrocytes , Animals , Humans , Actin Cytoskeleton/metabolism , Actins/metabolism , Cytoskeleton/metabolism , Erythrocytes/cytology , Erythrocytes/metabolism , Spectrin/analysis , Spectrin/metabolism , Swine
2.
Nat Mater ; 23(1): 95-100, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38036625

ABSTRACT

Inherent symmetry breaking at the interface has been fundamental to a myriad of physical effects and functionalities, such as efficient spin-charge interconversion, exotic magnetic structures and an emergent bulk photovoltaic effect. It has recently been demonstrated that interface asymmetry can induce sizable piezoelectric effects in heterostructures, even those consisting of centrosymmetric semiconductors, which provides flexibility to develop and optimize electromechanical coupling phenomena. Here, by targeted engineering of the interface symmetry, we achieve piezoelectric phenomena behaving as the electrical analogue of the negative Poisson's ratio. This effect, termed the auxetic piezoelectric effect, exhibits the same sign for the longitudinal (d33) and transverse (d31, d32) piezoelectric coefficients, enabling a simultaneous contraction or expansion in all directions under an external electrical stimulus. The signs of the transverse coefficients can be further tuned via in-plane symmetry anisotropy. The effects exist in a wide range of material systems and exhibit substantial coefficients, indicating potential implications for all-semiconductor actuator, sensor and filter applications.

3.
FASEB J ; 38(3): e23458, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38315453

ABSTRACT

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is characterized by its complex pathogenesis, high risk of chronic renal failure, and lack of effective diagnosis and treatment methods. GSK3ß (glycogen synthase kinase 3ß), a highly conserved threonine/serine kinase, was found to activate glycogen synthase. As a key molecule of the glucose metabolism pathway, GSK3ß participates in a variety of cellular activities and plays a pivotal role in multiple diseases. However, these effects are not only mediated by affecting glucose metabolism. This review elaborates on the role of GSK3ß in DKD and its damage mechanism in different intrinsic renal cells. GSK3ß is also a biomarker indicating the progression of DKD. Finally, the protective effects of GSK3ß inhibitors on DKD are also discussed.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Glycogen Synthase Kinase 3 beta , Humans , Diabetic Nephropathies/drug therapy , Glucose/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Kidney/metabolism
4.
Exp Cell Res ; 439(1): 114094, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38750718

ABSTRACT

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolization (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.


Subject(s)
Apoptosis , Autophagy-Related Proteins , Autophagy , Berberine , Carcinoma, Hepatocellular , Doxorubicin , Liver Neoplasms , Mice, Nude , Berberine/pharmacology , Berberine/analogs & derivatives , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Autophagy/drug effects , Animals , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Autophagy-Related Proteins/metabolism , Autophagy-Related Proteins/genetics , Mice , Apoptosis/drug effects , Doxorubicin/pharmacology , Doxorubicin/analogs & derivatives , Xenograft Model Antitumor Assays , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Mice, Inbred BALB C , Antineoplastic Agents/pharmacology , Signal Transduction/drug effects , Cysteine Endopeptidases
5.
J Am Chem Soc ; 146(5): 3545-3552, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38277257

ABSTRACT

Atom-precise metal nanoclusters (NCs) with large bulk (nuclearity >60) are important species for insight into the embryonic phase of metal nanoparticles and their top-down etching synthesis. Herein, we report a metastable rod-shaped 70-nuclei copper-hydride NC, [Cl@Cu70H22(PhC≡C)29(CF3COO)16]2+ (Cu70), with Cl- as the template, in which the Cl@Cu59 kernel adopts a distinctive metal packing mode along the bipolar direction, and the protective ligand shell exhibits corresponding site differentiation. In terms of metal nuclearity, Cu70 is the largest alkynyl-stabilized Cu-hydride cluster to date. As a typical highly active intermediate, Cu70 could undergo a transformation into a series of robust modularly assembled Cu clusters (B-type Cu8, A-A-type Cu22, A-B-type Cu23, and A-B-A-type Cu38) upon etching by p-tert-butylthiacalix[4]arene (H4TC4A), which could not be achieved by "one-pot" synthetic methods. Notably, the patterns of A and B blocks in the Cu NCs could be effectively modulated by employing appropriate counterions and blockers, and the modular assembly mechanism was illustrated through comprehensive solution chemistry analysis using HR-ESI-MS. Furthermore, catalytic investigations reveal that Cu38 could serve as a highly efficient catalyst for the cycloaddition of propargylic amines with CO2 under mild conditions. This work not only enriched the family of high-nuclear copper-hydride NCs but also provided new insights into the growth mechanism of metal NCs.

6.
J Am Chem Soc ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365881

ABSTRACT

The functionalization of metal-organic frameworks (MOFs) to enhance the adsorption of benzene at trace levels remains a significant challenge. Here, we report the exceptional adsorption of trace benzene in a series of zirconium-based MOFs functionalized with chloro groups. Notably, MFM-68-Cl2, constructed from an anthracene linker incorporating chloro groups, exhibits a remarkable benzene uptake of 4.62 mmol g-1 at 298 K and 0.12 mbar, superior to benchmark materials. In situ synchrotron X-ray diffraction, Fourier transform infrared microspectroscopy, and inelastic neutron scattering, coupled with density functional theory modeling, reveal the mechanism of binding of benzene in these materials. Overall, the excellent adsorption performance is promoted by an unprecedented cooperation between chloro-groups, the optimized pore size, aromatic functionality, and the flexibility of the linkers in response to benzene uptake in MFM-68-Cl2. This study represents the first example of enhanced adsorption of trace benzene promoted by -CH···Cl and Cl···π interactions in porous materials.

7.
BMC Plant Biol ; 24(1): 8, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38163903

ABSTRACT

Patchoulol, a valuable compound belonging to the sesquiterpenoid family, is the primary component of patchouli oil produced by Pogostemon cablin (P. cablin). It has a variety of pharmacological and biological activities and is widely used in the medical and cosmetic industries. However, despite its significance, there is a lack of research on the transcriptional modulation of patchoulol biosynthesis.Salicylic acid (SA), is a vital plant hormone that serves as a critical signal molecule and plays an essential role in plant growth and defense. However, to date, no studies have explored the modulation of patchoulol biosynthesis by SA. In our study, we discovered that the application of SA can enhance the production of patchoulol. Utilizing transcriptome analysis of SA-treated P. cablin, we identified a crucial downstream transcription factor, PatWRKY71. The transcription level of PatWRKY71 was significantly increased with the use of SA. Furthermore, our research has revealed that PatWRKY71 was capable of binding to the promoter of PatPTS, ultimately leading to an increase in its expression. When PatWRKY71 was silenced by a virus, the expression of both PatWRKY71 and PatPTS was reduced, resulting in the down-regulation of patchoulol production. Through our studies, we discovered that heterologous expression of PatWRKY71 leads to an increase in the sensitivity of Arabidopsis to salt and Cd, as well as an outbreak of reactive oxygen species (ROS). Additionally, we uncovered the regulatory role of PatWRKY71 in both patchoulol biosynthesis and plant defense response. This discovery provided a theoretical basis for the improvement of the content of patchoulol and the resistance of P. cablin through genetic engineering.


Subject(s)
Arabidopsis , Pogostemon , Sesquiterpenes , Transcription Factors/genetics , Transcription Factors/metabolism , Plants/metabolism , Pogostemon/genetics , Sesquiterpenes/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism
8.
Small ; : e2403313, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377344

ABSTRACT

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

9.
J Virol ; 97(3): e0180122, 2023 03 30.
Article in English | MEDLINE | ID: mdl-36840584

ABSTRACT

The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.


Subject(s)
Zika Virus Infection , Zika Virus , Animals , Mice , Phylogeny , Virus Replication , Cell Line
10.
J Transl Med ; 22(1): 172, 2024 02 18.
Article in English | MEDLINE | ID: mdl-38369469

ABSTRACT

The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.


Subject(s)
Gastrointestinal Microbiome , Renal Insufficiency, Chronic , Humans , Gastrointestinal Microbiome/physiology , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/therapeutic use , Biomarkers , Signal Transduction , Renal Insufficiency, Chronic/drug therapy
11.
Opt Lett ; 49(19): 5499-5502, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352991

ABSTRACT

We propose and numerically investigate a fractional-soliton mode-locked fiber laser by utilizing an intracavity spectral pulse shaper (SPS). The fiber laser can generate stable fractional-soliton pulses for three different Lévy index α (1 < α < 2), whose profiles are all close to the sech shape. We find that the positions of Kelly sidebands, pulse energy, and peak power of the emitted fractional pulses conform to three theoretical expressions, respectively. The numerical results are in good agreement with the theoretical analyses. In addition, the intracavity dynamics of the fractional pulses have been discussed. Our findings not only deepen the fundamental understanding of temporal fractional soliton but also provide a novel, to the best of our knowledge, approach to generating stable ultrashort fractional pulses.

12.
Chemistry ; 30(20): e202303934, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38102961

ABSTRACT

The selective capture of methane (CH4) at low concentrations and its separation from N2 are extremely challenging owing to the weak host-guest interactions between CH4 molecules and any sorbent material. Here, we report the exceptional adsorption of CH4 at low pressure and the efficient separation of CH4/N2 by MFM-300(Fe). MFM-300(Fe) shows a very high uptake for CH4 of 0.85 mmol g-1 at 1 mbar and 298 K and a record CH4/N2 selectivity of 45 for porous solids, representing a new benchmark for CH4 capture and CH4/N2 separation. The excellent separation of CH4/N2 by MFM-300(Fe) has been confirmed by dynamic breakthrough experiments. In situ neutron powder diffraction, and solid-state nuclear magnetic resonance and diffuse reflectance infrared Fourier transform spectroscopies, coupled with modelling, reveal a unique and strong binding of CH4 molecules involving Fe-OH⋯CH4 and C⋯phenyl ring interactions within the pores of MFM-300(Fe), thus promoting the exceptional adsorption of CH4 at low pressure.

13.
Chemistry ; 30(7): e202303289, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37899311

ABSTRACT

Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO2 in the presence of H2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π⋅⋅⋅π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO2 utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals.

14.
Anal Bioanal Chem ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739158

ABSTRACT

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of being easy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308 mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000 µM, and the limit of detection is 17.5 µM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

15.
Sleep Breath ; 28(3): 1355-1363, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38489146

ABSTRACT

PURPOSE: Obstructive sleep apnea (OSA) is often associated with glycemic abnormalities. This study is conducted to investigate the effects of hypoglycemic therapy on OSA-related indicators. METHOD: We systematically searched Web of Science, PubMed, Embase, and the Cochrane Library for articles on OSA patients receiving any hypoglycemic drugs, published until December 25, 2022. Seven original studies were finally included. The proposal was registered with PROSPERO (CRD42022351206). RESULTS: In summary, in addition to reduced glycosylated hemoglobin A1c (HbA1c), we found that hypoglycemic treatment can lower the apnea-hypopnea index (AHI) by 7.07/h (p = 0.0001). Although long-term treatment (> 12 weeks) achieved a more significant reduction in HbA1c (- 1.57% vs. - 0.30%) compared to short-term treatment (≤ 12 weeks), there was no significant difference between the two in terms of AHI (intergroup p-value = 0.27). We also found that patients using sodium glucose cotransporter 2 inhibitors (SGLT2i) experienced a greater reduction in AHI (- 11.00/h, p < 0.00001). Additionally, hypoglycemic treatment also showed certain improvements in related indicators like Epworth Sleepiness Scale, body mass index, and blood pressure. CONCLUSIONS: Our results affirm the benefits of hypoglycemic treatment for OSA patients and highlight the notable effect of SGLT2i. Further researches are needed to help doctors gain a comprehensive understanding of the interaction between OSA and glycemic abnormalities.


Subject(s)
Hypoglycemic Agents , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/drug therapy , Hypoglycemic Agents/therapeutic use , Glycated Hemoglobin/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood
16.
J Nerv Ment Dis ; 212(8): 412-418, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38950421

ABSTRACT

ABSTRACT: The purpose of this study was to determine the influence of knowledge and beliefs on beneficial behaviors and dementia risk scores. A online survey was conducted among Chinese community residents over 18 years old. Multivariate logistic regression was used to identify the impact of knowledge and beliefs on dementia risk scores and beneficial behaviors. The respondents were 760 adults (mean age = 47.6 years, 60.8% female). Knowledge and beliefs were associated with cognitive activities (knowledge, odds ratio [OR] = 1.04; beliefs, OR = 1.17) and dementia risk scores (knowledge, OR = 0.95; beliefs, OR = 0.82). Additionally, lower perceived susceptibility (OR = 1.68; 95% CI, 1.04 to 2.72) and higher perceived benefits (OR = 0.68; 95% CI, 0.57 to 0.80) were associated with lower dementia risk scores. Knowledge and beliefs can promote beneficial behaviors and reduce dementia risk. In particular, perceptions of dementia susceptibility and benefits should be enhanced, which will greatly reduce dementia risk in the general public.


Subject(s)
Dementia , Health Knowledge, Attitudes, Practice , Humans , Dementia/prevention & control , Dementia/psychology , Female , Male , Middle Aged , Cross-Sectional Studies , Risk Factors , Adult , Aged , China , Surveys and Questionnaires , Young Adult
17.
Sleep Breath ; 28(5): 2045-2053, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39031245

ABSTRACT

PURPOSE: Clinical studies suggested associations between obstructive sleep apnea (OSA) and gastrointestinal tract disorders. This study aims to investigate the genetic causal relationship between OSA and gastrointestinal tract disorders, specifically gastroesophageal reflux disease (GERD) and inflammatory bowel disease (IBD). METHODS: In this study, we employed two-sample Mendelian Randomization (MR) analysis to investigate the potential relationships between OSA and GERD, and between OSA and IBD. More specifically, the primary analysis utilized inverse variance weighting (IVW). Weighted median, MR Egger, and MR PRESSO were applied to complicate potential violations of MR assumptions. Also, sensitivity analysis was evaluated and similar analysis was performed again after outliers were removed. Additionally, multivariable MR (MVMR) was conducted for associated pairs to adjust for obesity. RESULTS: Genetically predicted risk of GERD increased OSA risk by approximately 60% (ORIVW = 1.62, 95%CI = [1.43,1.84]) which was also stable by other complicated approaches, and even with BMI adjusted by MVMR (ORadjBMI[95%CI] = 1.26 [1.15,1.37]). Besides, OSA showed a mild causal effect on increased GERD risk after adjusting for obesity (ORadjBMI[95%CI] = 1.05 [1.02,1.08]). Additionally, OSA increased the risks for IBD (ORIVW[95%CI] = 1.36 [1.12,1.65]), including a higher risk of CD (ORIVW[95%CI] = 1.41 [1.08,1.83]), and a trend for increasing UC risk (ORIVW[95%CI] = 1.29 [0.99,1.67]). CONCLUSION: GERD exerts a substantial causality on increasing the risk of OSA. Conversely, the potential for a causal relationship that OSA contributes to the development of GERD or IBD remains probable. These findings support the crosstalk between gastrointestinal tract disorders and OSA.


Subject(s)
Gastroesophageal Reflux , Mendelian Randomization Analysis , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/genetics , Sleep Apnea, Obstructive/epidemiology , Gastroesophageal Reflux/genetics , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/complications , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/epidemiology , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/diagnosis , Obesity/genetics , Obesity/epidemiology
18.
BMC Pulm Med ; 24(1): 72, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326796

ABSTRACT

BACKGROUND: While several traditional observational studies have suggested associations between gut microbiota and asthma, these studies are limited by factors such as participant selection bias, confounders, and reverse causality. Therefore, the causal relationship between gut microbiota and asthma remains uncertain. METHODS: We performed two-sample bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota and asthma as well as its phenotypes. We also conducted MR analysis to evaluate the causal effect of gut metabolites on asthma. Genetic variants for gut microbiota were obtained from the MiBioGen consortium, GWAS summary statistics for metabolites from the TwinsUK study and KORA study, and GWAS summary statistics for asthma from the FinnGen consortium. The causal associations between gut microbiota, gut metabolites and asthma were examined using inverse variance weighted, maximum likelihood, MR-Egger, weighted median, and weighted model and further validated by MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis. RESULTS: We identified nine gut microbes whose genetically predicted relative abundance causally impacted asthma risk. After FDR correction, significant causal relationships were observed for two of these microbes, namely the class Bacilli (OR = 0.84, 95%CI = 0.76-0.94, p = 1.98 × 10-3) and the order Lactobacillales (OR = 0.83, 95%CI = 0.74-0.94, p = 1.92 × 10-3). Additionally, in a reverse MR analysis, we observed a causal effect of genetically predicted asthma risk on the abundance of nine gut microbes, but these associations were no longer significant after FDR correction. No significant causal effect of gut metabolites was found on asthma. CONCLUSIONS: Our study provides insights into the development mechanism of microbiota-mediated asthma, as well as into the prevention and treatment of asthma through targeting specific gut microbiota.


Subject(s)
Asthma , Gastrointestinal Microbiome , Microbiota , Humans , Gastrointestinal Microbiome/genetics , Mendelian Randomization Analysis , Asthma/genetics , Nonoxynol , Genome-Wide Association Study
19.
BMC Pediatr ; 24(1): 385, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849790

ABSTRACT

Inguinal hernia repair is one of the most common surgical procedures in the pediatric population. While a rare complication, bladder injury can impose a significant burden on patients. This study outlined a case of bladder injury following selective inguinal hernia repair and summarized methods to prevent this complication, aiming to emphasize the importance of not underestimating interventions labeled as "routine surgery" in order to avoid avoidable harm to patients.


Subject(s)
Hematuria , Hernia, Inguinal , Herniorrhaphy , Postoperative Complications , Urinary Bladder , Child , Humans , Hematuria/etiology , Hernia, Inguinal/surgery , Herniorrhaphy/adverse effects , Postoperative Complications/etiology , Urinary Bladder/injuries , Urinary Bladder/surgery
20.
Biochem Genet ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642175

ABSTRACT

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.

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