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2.
Ecotoxicol Environ Saf ; 278: 116411, 2024 May 06.
Article En | MEDLINE | ID: mdl-38714085

Cadmium (Cd), a toxic element, often makes a serious threat to plant growth and development. Previous studies found that melatonin (Mel) reduced Cd accumulation and reestablished the redox balance to alleviate Cd stress in Medicago sativa L., however, the complex molecular mechanisms are still elusive. Here, comparative transcriptome analysis and biochemical experiments were conducted to explore the molecular mechanisms of Mel in enhancing Cd tolerance. Results showed that 7237 differentially expressed genes (DEGs) were regulated by Mel pretreatment to Cd stress compared to the control condition in roots of Medicago sativa L. Besides, in comparison with Cd stress alone, Mel upregulated 1081 DEGs, and downregulated 1085 DEGs. These DEGs were mainly involved in the transcription and translation of genes and folding, sorting and degradation of proteins, carbohydrate metabolism, and hormone signal network. Application of Mel regulated the expression of several genes encoding ribosomal protein and E3 ubiquitin-protein ligase involved in folding, sorting and degradation of proteins. Moreover, transcriptomic analyse suggested that Mel might regulate the expression of genes encoding pectin lyase, UDP-glucose dehydrogenase, sucrose-phosphate synthase, hexokinase-1, and protein phosphorylation in the sugar metabolism. Therefore, these could promote sucrose accumulation and subsequently alleviate the Cd damage. In conclusion, above findings provided the mining of important genes and molecular basis of Mel in mitigating Cd tolerance and genetic cultivation of Medicago sativa L.

3.
J Org Chem ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38717970

This study reports selective dual amino acylation and C-H bromination of aniline compounds enabled by Cu/O2 catalyst systems. This method involves crucial oxidation-induced C-CN bond cleavage of α-methylene nitriles to generate an acylcyanide intermediate that is facilely intercepted by anilines. After amino acylation, the Cu(II) precatalyst in combination with NBS generates Cu(III)-Br in situ that engages in selective electrophilic para- or ortho-C-H bromination. The substrate scope, mechanistic aspects, and late-stage functionalization of biologically active anilines are studied. This study shows the synthetic potential of oxidative C-CN bond activation of nitriles for the development of valuable reactions.

4.
Mol Neurobiol ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38713438

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

5.
Adv Colloid Interface Sci ; 328: 103175, 2024 May 03.
Article En | MEDLINE | ID: mdl-38723295

Gallium oxide (Ga2O3), as a new kind of ultra-wide band gap semiconductor material, is widely studied in many fields, such as power electronics, UV - blind photodetectors, solar cells and so on. Owing to the advantages of its excellent performance and broad application prospects in semiconductor technology, Ga2O3 materials have attracted extensive academic and technological attention. This review mainly focuses on introducing the main liquid-phase synthesis methods of Ga2O3 nanoparticles, such as direct-precipitation, chemical bath deposition, hydrothermal, solvothermal, and sol-gel method, including the characteristics in process and advantages and disadvantages of these methods. Then, the effects of reaction conditions, such as pH, capping agent, aging and calcination conditions, on the morphologies and sizes of the precursor and the final products were elucidated. Moreover, the applications of Ga2O3 particles in the fields of catalysis, gas sensors, and other devices in current research on Ga2O3 nanomaterials are discussed with the description of the basic working principle and influence factors.

6.
J Investig Med ; : 10815589241249991, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715217

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of eGFR in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants mean age was 59 years, median eGFR 60 ml/min/1.73m2, 45 participants died, 33 received VAD, and 25 received OHT. Higher baseline serum standardized suPAR [ß coefficient =-0.36 √(ml/min/1.73m2), 95% CI (-0.48, -0.24), P<0.001], standardized galectin-3 [-0.14 √(ml/min/1.73m2) (-0.27, -0.02), P=0.02], and log NT-proBNP [-0.23 √(ml/min/1.73m2) (-0.31, -0.15), P<0.001], were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

7.
Front Neurol ; 15: 1354311, 2024.
Article En | MEDLINE | ID: mdl-38694779

Background: Currently, the incidence of cerebral palsy is high in newborns. However, the current methods for diagnosing and treating patients with cerebral palsy are complex and poorly targeted. Moreover, these studies lack the support of bibliometric analysis results. Objective: Our study focused on a bibliometric analysis of published papers on the diagnosis and treatment of patients with cerebral palsy. This study identified the primary authors, institutions, and countries involved in analyzing the status and trends of research on the diagnosis and treatment of patients with cerebral palsy. Additionally, the study also involved screening pathways related to cerebral palsy. Methods: The PubMed database was searched for publications on the diagnosis and treatment of patients with cerebral palsy between 1990 and 2023. R v4.2.2 and VOSviewer v1.6.18 software tools were utilized to perform bibliometric analysis and visualization. Results: There were 1,965 publications on cerebral palsy diagnosis and 5,418 articles on the qualified treatment strategies, and the annual number of publications also increased. The United States dominated in this field of research. Gregory Y.H. Lip and Patrizio Lancellotti published the most number of papers. The Cleveland Clinic published the most number of papers in the field. According to the analysis of the co-occurrence of keywords, we found that the main research directions were age, sex, disease diagnosis, and treatment. Newly emerging research has focused mainly on heart failure, which is related to valvular heart disease. Conclusion: The findings presented in this study offer valuable insights into ongoing research and potential future directions pertaining to cerebral palsy. These insights can assist researchers in identifying suitable collaborators and enhancing their investigations aimed at identifying the underlying molecular mechanisms associated with cerebral palsy, encompassing its etiology, preventive measures, and therapeutic interventions.

8.
DNA Cell Biol ; 2024 May 03.
Article En | MEDLINE | ID: mdl-38700464

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

9.
Nat Nanotechnol ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38740936

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

10.
Sci Adv ; 10(16): eadl4336, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38630829

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting NLRP3 to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.


CRISPR-Cas Systems , Gene Editing , Animals , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Gene Transfer Techniques , Genetic Therapy , Polymers/chemistry , Ribonucleoproteins/genetics
11.
N Engl J Med ; 390(13): 1196-1206, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38598574

BACKGROUND: Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking. METHODS: In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death. RESULTS: We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P = 0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%). CONCLUSIONS: In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.).


Diabetes Mellitus, Type 2 , Hospitalization , Hypertension , Renal Insufficiency, Chronic , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Hospitalization/statistics & numerical data , Hypertension/epidemiology , Hypertension/therapy , Renal Dialysis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Precision Medicine , Electronic Health Records , Algorithms , Primary Health Care/statistics & numerical data
12.
Polymers (Basel) ; 16(7)2024 Apr 05.
Article En | MEDLINE | ID: mdl-38611253

Chitin and chitosan are important structural macromolecules for most fungi and marine crustaceans. The functions and application areas of the two molecules are also adjacent beyond their similar molecular structure, such as tissue engineering and food safety where solution systems are involved. However, the elasticities of chitin and chitosan in solution lack comparison at the molecular level. In this study, the single-molecule elasticities of chitin and chitosan in different solutions are investigated via atomic force microscope (AFM) based single-molecule spectroscopy (SMFS). The results manifest that the two macromolecules share the similar inherent elasticity in DOSM due to their same chain backbone. However, obvious elastic deviations can be observed in aqueous conditions. Especially, a lower pH value (acid environment) is helpful to increase the elasticity of both chitin and chitosan. On the contrary, the tendency of elastic variation of chitin and chitosan in a larger pH value (alkaline environment) shows obvious diversity, which is mainly determined by the side groups. This basic study may produce enlightenment for the design of intelligent chitin and chitosan food packaging and biomedical materials.

13.
Kidney360 ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38664867

BACKGROUND: CKD is often underdiagnosed during early stages when GFR is preserved due to underutilization of testing for quantitative urine albumin-to-creatinine ratio (UACR) or protein-to-creatinine ratio (UPCR). Semi-quantitative dipstick proteinuria (DSP) on urinalysis is widely obtained but not accurate for identifying clinically significant proteinuria. METHODS: We identified all patients with a urinalysis and UACR or UPCR obtained on the same day at a tertiary referral center. The accuracy of DSP alone or in combination with specific gravity against a gold-standard of UACR ≥30 mg/g or UPCR ≥0.15 g/g, characterizing clinically significant proteinuria, was evaluated using logistic regression. Models were internally validated using 10-fold cross validation. The specific gravity for each DSP above which significant proteinuria is unlikely was determined. RESULTS: Of 11,229 patients, clinically significant proteinuria was present in 4,073 (36%). The area under the receiver operating characteristic curve (95% confidence interval) was 0.77 (0.76, 0.77) using DSP alone and 0.82 (0.82, 0.83) in combination with specific gravity (P<0.001), yielding a specificity of 0.93 (standard error, SE=0.02) and positive likelihood ratio of 9.52 (SE=0.85). The optimal specific gravity cut-offs to identify significant proteinuria were ≤1.0012, 1.0238, and 1.0442, for DSP of trace, 30, and 100 mg/dL. At any specific gravity, a DSP ≥300 mg/dL was extremely likely to represent significant proteinuria. CONCLUSION: Adding specific gravity to DSP improves recognition of clinically significant proteinuria and can be easily used to identify patients with early-stage CKD who may not have otherwise received a quantified proteinuria measurement for both clinical and research purposes.

14.
Sci Rep ; 14(1): 9015, 2024 04 19.
Article En | MEDLINE | ID: mdl-38641633

A recent study investigated the impact of culture of Asian groups on leadership attainment in the U.S. It revealed that East Asians (EAs) are less likely than South Asians (SAs) and white people (WP) to attain leadership positions, and SAs may even surpass WP in leadership attainment. The study explained that the underrepresentation of EAs in leadership positions in the U.S. (the so called bamboo ceiling) is partly because EAs communicate less assertively. Specifically, EA cultures value collectivism (e.g., humility and harmony), which are at odds with western cultures that value individualism (e.g., extraversion and assertiveness), whereas SA cultures are congruent with western cultures. However, the study did not distinguish the different impact of home culture (i.e., EA cultures) and host culture (i.e., western cultures) on US-born EAs versus foreign-born EAs. We argue that for US-born EAs (i.e., second generation EAs), host culture plays a more important role than home culture in their growth and they may not be underrepresented in leadership attainment compared to WP. The bamboo ceiling effect is mostly demonstrated among foreign-born EAs (i.e., first generation EAs) who are shaped mainly under the home culture. We support the argument by conducting analysis on one of the datasets in the original study and a new dataset from Fortune's 40-under-40 list. Our study suggests that when studying the underrepresentation of leadership attainment for EAs, US-born EAs and foreign-born EAs should not be aggregated in one category. Considering the ethnic EA group, the bamboo ceiling phenomenon may exist mainly among foreign-born EAs because US-born EAs, with a median age of 21.3, are much younger than the general American population, who may not be experienced enough to be considered for leadership positions in established large companies.


Ethnicity , Leadership , Humans , United States , Asian People , Asian , White
15.
Heliyon ; 10(8): e29483, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38644842

Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.

17.
Nat Commun ; 15(1): 3514, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664401

Amino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.


Eating , Enteroendocrine Cells , Glutamic Acid , Neuropeptides , Peptide YY , Animals , Enteroendocrine Cells/metabolism , Female , Neuropeptides/metabolism , Neuropeptides/genetics , Eating/physiology , Peptide YY/metabolism , Glutamic Acid/metabolism , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Drosophila melanogaster/metabolism , Feeding Behavior/physiology , Receptors, Metabotropic Glutamate/metabolism , Dopaminergic Neurons/metabolism , Diet
18.
Nanomicro Lett ; 16(1): 170, 2024 Apr 09.
Article En | MEDLINE | ID: mdl-38592515

Rapid advancements in flexible electronics technology propel soft tactile sensing devices toward high-level biointegration, even attaining tactile perception capabilities surpassing human skin. However, the inherent mechanical mismatch resulting from deficient biomimetic mechanical properties of sensing materials poses a challenge to the application of wearable tactile sensing devices in human-machine interaction. Inspired by the innate biphasic structure of human subcutaneous tissue, this study discloses a skin-compliant wearable iontronic triboelectric gel via phase separation induced by competitive hydrogen bonding. Solvent-nonsolvent interactions are used to construct competitive hydrogen bonding systems to trigger phase separation, and the resulting soft-hard alternating phase-locked structure confers the iontronic triboelectric gel with Young's modulus (6.8-281.9 kPa) and high tensile properties (880%) compatible with human skin. The abundance of reactive hydroxyl groups gives the gel excellent tribopositive and self-adhesive properties (peel strength > 70 N m-1). The self-powered tactile sensing skin based on this gel maintains favorable interface and mechanical stability with the working object, which greatly ensures the high fidelity and reliability of soft tactile sensing signals. This strategy, enabling skin-compliant design and broad dynamic tunability of the mechanical properties of sensing materials, presents a universal platform for broad applications from soft robots to wearable electronics.

19.
JAMA Netw Open ; 7(4): e246589, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38635271

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.


Colorectal Neoplasms , Emergence Delirium , Frailty , Laparoscopy , Transcranial Direct Current Stimulation , Female , Humans , Male , Middle Aged , Anxiety , Fatigue , Pain , Aged
20.
Food Microbiol ; 121: 104499, 2024 Aug.
Article En | MEDLINE | ID: mdl-38637070

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.


Monascus , Fermentation , Monascus/genetics , Monascus/metabolism , Pigments, Biological/metabolism , Microbial Consortia , Glycolysis
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