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1.
Pharmacol Rep ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954373

ABSTRACT

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury.

2.
Gen Psychiatr ; 37(4): e101479, 2024.
Article in English | MEDLINE | ID: mdl-38962431

ABSTRACT

Background: Major depressive disorders (MDDs) impose substantial burdens on individuals and society; however, further detailed analysis is still needed for its long-term trends. Aims: This study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades. Methods: Employing the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019, this research identified and analysed incidence trends of MDD among Chinese males and females aged 5-94 years from 1990 to 2019 across three dimensions, encompassing age, period and birth cohort. Results: The analysis reveals age-related effects, indicating heightened MDD risk among adolescents and older adults. Specifically, individuals entering the older adulthood at the age of 65-69 significantly increased the risk of MDD by 64.9%. People aged 90-94 years witnessed a 105.4% increase in MDD risk for the overall population, with females and males in this age group experiencing a 75.1% and 103.4% increase, respectively. In terms of period effects, the risk of MDD displayed a decline from 1990 to 1994, followed by a rebound in 2008. Cohort effects demonstrated diverse generational patterns, with generation I and generation III manifesting opposing 'age-as-level' trends. Generation II and generation IV exhibited 'cumulative disadvantage' and 'cumulative advantage' patterns, respectively. Age effects indicated an overall higher risk of MDD incidence in females, while cohort effects showed greater variations of MDD incidence among females. Conclusions: The study underscores the substantial effects of age, period and cohort on MDD across genders in China. Priority interventions targeting vulnerable populations, including children, adolescents, older adults, females and the post-millennium birth cohort, are crucial to mitigate the impact of MDD.

3.
J Cardiothorac Surg ; 19(1): 378, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926754

ABSTRACT

OBJECTIVES: The goal of this research is to pinpoint the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer. METHODS: We identified the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer by searching the Web of Science database. We extracted key information from the selected studies, including the author, journal, impact factor, type of article, year of publication, country, organization, and keyword. RESULTS: To the best of our understanding, this is the inaugural bibliometric study on sublobectomy for non-small cell lung cancer. The publication years of the top 100 most frequently referenced studies span from 1994 to 2022, with citation counts ranging from 51 to 795. The majority of the included studies are original (93/100) and primarily retrospective studies (82/93). The United States leads in terms of published articles and citations, with the Annals of Thoracic Surgery being the most frequently sourced journal (n = 27). High-density keywords primarily originate from limited resection, lobectomy, survival, carcinoma, recurrence, randomized trial, radiotherapy, lung cancer, outcome, 2 cm, as revealed by CiteSpace analysis. CONCLUSIONS: Our research compiles and analyzes the top 100 most frequently referenced studies in the field of sublobectomy for non-small cell lung cancer. The United States has the most published and cited works on this topic. Currently, the hot keywords for sublobectomy research are gradually shifting towards prognosis and obtaining better evidence-based medical evidence to demonstrate its value in the treatment of non-small cell lung cancer.


Subject(s)
Bibliometrics , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Humans , Pneumonectomy/methods , Journal Impact Factor
4.
Anal Bioanal Chem ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864917

ABSTRACT

We present a novel approach for iodide sensing based on the heavy-atom effect to quench the green fluorescent emission of organosilicon nanoparticles (OSiNPs). The fluorescence of OSiNPs was significantly quenched (up to 97.4% quenching efficiency) in the presence of iodide ions (I-) through oxidation by hydrogen peroxide. Therefore, OSiNPs can serve as a fluorescent probe to detect I- with high selectivity and sensitivity. The highly selective response is attributed to the hydrophilic surface enabling good dispersion in aqueous solutions and the lipophilic core allowing the generated liposoluble I2 to approach and quench the fluorescence of OSiNPs. The linear working range for I- was from 0 to 50 µM, with a detection limit of 0.1 µM. We successfully applied this nanosensor to determine iodine content in edible salt. Furthermore, the fluorescent OSiNPs can be utilized for the determination of total antioxidant capacity (TAC). Antioxidants reduce I2 to I-, and the extent of quenching by the remaining I2 on the OSiNPs indicates the TAC level. The responses to ascorbic acid, pyrogallic acid, and glutathione were investigated, and the detection limit for ascorbic acid was as low as 0.03 µM. It was applied to the determination of TAC in ascorbic acid tablets and fruit juices, indicating the potential application of the OSiNP-based I2 sensing technique in the field of food analysis.

6.
Orphanet J Rare Dis ; 19(1): 232, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38863016

ABSTRACT

BACKGROUND: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. METHODS: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. RESULTS: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. CONCLUSIONS: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management.


Subject(s)
Carcinoma, Neuroendocrine , Lung Neoplasms , Nomograms , Humans , Female , Male , Carcinoma, Neuroendocrine/surgery , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/mortality , Middle Aged , Retrospective Studies , Prognosis , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Aged , Adult , Aged, 80 and over
7.
Nat Struct Mol Biol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918638

ABSTRACT

Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in transcription repression, is dynamically regulated by the opposing activities of Polycomb repressive complex 1 (PRC1) and nucleosome deubiquitinases including the primary human USP16 and Polycomb repressive deubiquitinase (PR-DUB) complex. Recently, the catalytic mechanism for the multi-subunit PR-DUB complex has been described, but how the single-subunit USP16 recognizes the H2AK119Ub nucleosome and cleaves the ubiquitin (Ub) remains unknown. Here we report the cryo-EM structure of USP16-H2AK119Ub nucleosome complex, which unveils a fundamentally distinct mode of H2AK119Ub deubiquitination compared to PR-DUB, encompassing the nucleosome recognition pattern independent of the H2A-H2B acidic patch and the conformational heterogeneity in the Ub motif and the histone H2A C-terminal tail. Our work highlights the mechanism diversity of H2AK119Ub deubiquitination and provides a structural framework for understanding the disease-causing mutations of USP16.

8.
eNeuro ; 11(6)2024 Jun.
Article in English | MEDLINE | ID: mdl-38729764

ABSTRACT

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.


Subject(s)
Cognitive Dysfunction , Hippocampus , Neural Stem Cells , Neurogenesis , PTEN Phosphohydrolase , Signal Transduction , Tetrahydrofolates , Animals , Neurogenesis/drug effects , Neurogenesis/physiology , Hippocampus/drug effects , Hippocampus/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , PTEN Phosphohydrolase/metabolism , Male , Signal Transduction/drug effects , Signal Transduction/physiology , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Tetrahydrofolates/pharmacology , Mice , Hemorrhagic Stroke , Mice, Inbred C57BL , Mice, Transgenic , Cell Proliferation/drug effects
9.
Int J Biol Macromol ; 271(Pt 1): 132378, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750853

ABSTRACT

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.


Subject(s)
Bone Regeneration , Osteogenesis , Polyesters , Polyesters/chemistry , Animals , Porosity , Bone Regeneration/drug effects , Osteogenesis/drug effects , Calcification, Physiologic/drug effects , Durapatite/chemistry , Cell Differentiation/drug effects , Serum Albumin, Bovine/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Gelatin/chemistry , Tissue Scaffolds/chemistry , Mice , Rabbits
10.
J Aging Soc Policy ; : 1-21, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38734975

ABSTRACT

Older adults' access to healthcare services may have been affected by the COVID-19 pandemic. This study explored the effect of the first wave pandemic on the medical expenditure of older adults in China. Difference-in-Difference models captured both temporal and geographical variation in COVID-19 exposure to estimate the impacts of the pandemic on medical expenditure through a quasi-natural experiment. Data derived from the China Family Panel Studies. Results indicate that exposure to the pandemic significantly decreased total medical expenditures, hospital expenditures, and non-hospital medical expenditures of Chinese older adults by 15% (95% CI 12%-17%), 5% (95% CI 2%-7%), and 15% (95% CI 13%-16%), respectively, for each standardized severity increment. Females, less well-educated people, and individuals without internet access were most susceptible to experiencing these reductions. This study revealed that COVID-19 exerted a detrimental influence on the medical expenditure of older adults in mainland China. The "hidden epidemic" of non-COVID-19 medical needs of older adults deserves more attention on the part of policymakers.

11.
Cell Death Differ ; 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762597

ABSTRACT

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.

12.
Open Forum Infect Dis ; 11(5): ofae241, 2024 May.
Article in English | MEDLINE | ID: mdl-38756766

ABSTRACT

Background: Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal-infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB. Methods: This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum. Results: The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)-positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0-5.9] vs 8.6 [8.4-8.7] log10 U/mL; P < .01) and pgRNA (median [IQR], 0.0 [0.0-2.5] vs 7.8 [7.6-8.1] log10 copies/mL; P < .01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P < .05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 (P < .05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively (P > .05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg. Conclusions: HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients.

13.
Nat Prod Res ; : 1-7, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726924

ABSTRACT

Two new phenylpropanoids, ainsbons A and B (1 and 2), along with a known analogue coniferyl diisovalerate (3) were isolated from the whole plant of Ainsliaea bonatii. Their structures were elucidated by analysis of NMR spectroscopic data and HRESIMS, and the absolute configuration of 2 was established by the optical rotation calculations. Compounds 1-3 were evaluated for their effects on LPS-induced nitric oxide production, and 1 and 3 showed inhibitory activities with IC50 values of 43.43 and 7.57 µM, respectively.

14.
BMC Surg ; 24(1): 140, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720305

ABSTRACT

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Propensity Score , Humans , Female , Male , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Middle Aged , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/therapy , Adenocarcinoma of Lung/mortality , Chemotherapy, Adjuvant , Risk Factors , Aged , Retrospective Studies , Treatment Outcome , Pneumonectomy/methods , Disease-Free Survival , Prognosis , Kaplan-Meier Estimate
15.
Acta Cardiol ; : 1-9, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771335

ABSTRACT

Atherosclerosis, caused by lipid deposit in the arterial wall for narrowing the arteries, is an increased risk factor of developing heart failure. Presently, clinical first-line drug therapy can be found with side effects, and thus new substitute medication should be developed needfully. Calycosin is one of the most bioactive products refined from natural plant, and it exerts promising cardiovascular protective effect. However, the pharmacological mechanisms of calycosin against atherosclerosis have not been elaborated. In this study, a systematic network pharmacology combined with molecular docking analysis was used to reveal the interaction activity and biological target in calycosin against atherosclerosis. We screened all preparative targets linked to calycosin and atherosclerosis from the available public databases. These results indicated total 409 putative targets in calycosin action, 71 of which were interacted with atherosclerosis. Further biological docking analysis suggested that calycosin displayed the powerful binding affinities with target proteins, including interleukin-6 (IL6) and mitogen-activated protein kinase 3 (MAPK3) MAPK3. Then enrichment findings revealed that calycosin action to treat atherosclerosis might be related to inhibition of inflammatory reaction and oxidative stress through modulating nucleolus transcription factor for improving lipid metabolism. In conclusion, the anti-atherosclerotic targets and molecular mechanisms in calycosin action were revealed systematically through preclinical evaluation. And calycosin may be a potential natural compound for the treatment of atherosclerosis.

16.
Gynecol Endocrinol ; 40(1): 2360085, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38813955

ABSTRACT

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.


Subject(s)
Primary Ovarian Insufficiency , Stress, Psychological , Humans , Primary Ovarian Insufficiency/psychology , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/therapy , Female , Stress, Psychological/complications , Oxidative Stress/physiology , Risk Factors , Depression/etiology
17.
ACS Chem Biol ; 19(6): 1237-1242, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38723147

ABSTRACT

As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.


Subject(s)
Bacillus subtilis , Glucosamine , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) , Protein Engineering , Glucosamine/biosynthesis , Glucosamine/metabolism , Glucosamine/chemistry , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/chemistry , Bacillus subtilis/enzymology , Bacillus subtilis/metabolism , Bacillus subtilis/genetics , Molecular Docking Simulation , Fructose/metabolism , Fructose/chemistry , Fructose/biosynthesis , Molecular Dynamics Simulation , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Catalytic Domain
18.
Environ Sci Technol ; 58(25): 11003-11015, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38807562

ABSTRACT

Labile organic matter (OM) immobilized by secondary iron (Fe) minerals from chemodenitrification may be an effective way to immobilize organic carbon (OC). However, the underlying mechanisms of coupled chemodenitrification and OC sequestration are poorly understood. Here, OM immobilization by secondary Fe minerals from chemodenitrification was investigated at different C/Fe ratios. Kinetics of Fe(II) oxidation and nitrite reduction rates decreased with increasing C/Fe ratios. Despite efficient sequestration, the immobilization efficiency of OM by secondary minerals varied with the C/Fe ratios. Higher C/Fe ratios were conducive to the formation of ferrihydrite and lepidocrocite, with defects and nanopores. Three contributions, including inner-core Fe-O and edge- and corner-shared Fe-Fe interactions, constituted the local coordination environment of mineral-organic composites. Microscopic analysis at the molecular scale uncovered that labile OM was more likely to combine with secondary minerals with poor crystallinity to enhance its stability, and OM distributed within nanopores and defects had a higher oxidation state. After chemodenitrification, high molecular weight substances and substances high in unsaturation or O/C ratios including phenols, polycyclic aromatics, and carboxylic compounds exhibited a stronger affinity to Fe minerals in the treatments with lower C/Fe ratios. Collectively, labile OM immobilization can occur during chemodenitrification. The findings on OM sequestration coupled with chemodenitrification have significant implications for understanding the long-term cycling of Fe, C, and N, providing a potential strategy for OM immobilization in anoxic soils and sediments.


Subject(s)
Iron , Minerals , Minerals/chemistry , Iron/chemistry , Oxidation-Reduction , Carbon/chemistry , Kinetics
19.
Sci Rep ; 14(1): 10578, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38719853

ABSTRACT

Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.


Subject(s)
Evoked Potentials, Auditory, Brain Stem , Neuroma, Acoustic , Humans , Neuroma, Acoustic/surgery , Neuroma, Acoustic/physiopathology , Female , Evoked Potentials, Auditory, Brain Stem/physiology , Male , Middle Aged , Adult , Retrospective Studies , Aged , Hearing , Young Adult
20.
Ren Fail ; 46(1): 2332492, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38584135

ABSTRACT

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.


Subject(s)
Acute Kidney Injury , Reperfusion Injury , Animals , Humans , Rats , Acute Kidney Injury/etiology , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Apoptosis , Hypoxia/metabolism , Hypoxia/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Ischemia , Kidney/pathology , Membrane Proteins/metabolism , Mitochondrial Proteins , Mitophagy , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Signal Transduction
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