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1.
Angew Chem Int Ed Engl ; : e202408894, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830120

ABSTRACT

Developing a desirable ethanol dehydrogenation process necessitates a highly efficient and selective catalyst with low cost. Herein, we show that the "complex active site" consisting of atomically dispersed Au atoms with the neighboring oxygen vacancies (Vo) and undercoordinated cation on oxide supports can be prepared and display unique catalytic properties for ethanol dehydrogenation. The "complex active site" Au-Vo-Zr3+ on Au1/ZrO2 exhibits the highest H2 production rate, with above 37,964 mol H2 per mol Au per hour (385 g H2 g-1 Au h-1) at 350 oC, which is 3.32, 2.94 and 15 times higher than Au1/CeO2, Au1/TiO2, and Au1/Al2O3, respectively. Combining experimental and theoretical studies, we demonstrate the structural sensitivity of these complex sites by assessing their selectivity and activity in ethanol dehydrogenation. Our study sheds new light on the design and development of cost-effective and highly efficient catalysts for ethanol dehydrogenation. Fundamentally, atomic-level catalyst design by colocalizing catalytically active metal atoms forming a structure-sensitive "complex site", is a crucial way to advance from heterogeneous catalysis to molecular catalysis. Our study advanced the understanding of the structure sensitivity of the active site in atomically dispersed catalysts.

2.
Nat Med ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830992

ABSTRACT

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 108, six with 3.75 × 108 and three with 5.0 × 108 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

3.
World J Gastroenterol ; 30(16): 2272-2280, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38690021

ABSTRACT

BACKGROUND: The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula (TEF), but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control. We designed a T-shaped magnet system to overcome these problems and verified its effectiveness via animal experiments. AIM: To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs. METHODS: Twelve beagles were randomly assigned to groups in which magnets of the T-shaped scheme (study group, n = 6) or normal magnets (control group, n = 6) were implanted into the trachea and esophagus separately under gastroscopy. Operation time, operation success rate, and accidental injury were recorded. After operation, the presence and timing of cough and the time of magnet shedding were observed. Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing, and gross specimens of TEFs were obtained. Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery, and gross specimens were obtained. Fistula size was measured in all animals, and then harvested fistula specimens were examined by hematoxylin and eosin (HE) and Masson trichrome staining. RESULTS: The operation success rate was 100% for both groups. Operation time did not differ between the study group (5.25 min ± 1.29 min) and the control group (4.75 min ± 1.70 min; P = 0.331). No bleeding, perforation, or unplanned magnet attraction occurred in any animal during the operation. In the early postoperative period, all dogs ate freely and were generally in good condition. Dogs in the control group had severe cough after drinking water at 6-9 d after surgery. X-ray indicated that the magnets had entered the stomach, and gastroscopy showed TEF formation. Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm ± 1.29 mm (range, 3.52-6.56 mm). HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas. Dogs in the study group did not exhibit obvious coughing after surgery. X-ray examination 2 wk after surgery indicated fixed magnet positioning, and gastroscopy showed no change in magnet positioning. The magnets were removed using a snare under endoscopy, and TEF was observed. Gross specimens showed well-formed fistulas with a diameter of 6.11 mm ± 0.16 mm (range, 5.92-6.36 mm), which exceeded that in the control group (P < 0.001). Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining, and the structure was more regular than that in the control group. CONCLUSION: Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets. Most importantly, this model offers better controllability, which improves the flexibility of follow-up studies.


Subject(s)
Disease Models, Animal , Magnets , Trachea , Tracheoesophageal Fistula , Animals , Dogs , Tracheoesophageal Fistula/surgery , Tracheoesophageal Fistula/pathology , Tracheoesophageal Fistula/etiology , Trachea/surgery , Trachea/pathology , Esophagus/surgery , Esophagus/pathology , Esophagus/diagnostic imaging , Gastroscopy/instrumentation , Gastroscopy/methods , Operative Time , Male , Magnetics/instrumentation , Equipment Design , Humans
4.
Ann Hematol ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691144

ABSTRACT

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

5.
Acta Diabetol ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691241

ABSTRACT

AIMS: Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. METHODS: Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. RESULTS: There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. CONCLUSION: Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

6.
Psychiatry Investig ; 21(4): 329-339, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38695040

ABSTRACT

OBJECTIVE: Narrative exposure therapy (NET) has been used in various contexts for the treatment of the effects of trauma, with promising results in clinical trials. However, its effects on anxiety and depression are still unclear. The present study is a systematic review and meta-analysis of the effects of NET on depression and anxiety. METHODS: The Embase, Cumulative Index of Nursing and Allied Health Literature, PubMed, Web of Science core collection, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and Wangfang databases were searched from the earliest records to March 2023. Two researchers independently screened the literature, extracted data, evaluated the risk of bias, and cross-checked the data. Meta-analysis was performed using the program RevMan 5.3. RESULTS: Eleven randomized controlled trials with a total of 754 participants were included in the study. The results showed that NET reduced both the depression (standard mean difference [SMD]=-0.51, 95% confidence interval [CI] -0.73--0.29, p<0.00001) and anxiety (SMD=-0.65, 95% CI -1.13--0.18, p=0.007) scores of the patients. Furthermore, NET was found to alleviate negative emotions associated with guilt (mean difference [MD]=-3.60, 95% CI -5.52--1.68, p=0.0005) and negative change (MD=-5.80, 95% CI -9.76--1.83, p=0.004). CONCLUSION: This analysis showed that NET can alleviate depression and anxiety. It may thus be used in clinical settings to alleviate patients' negative feelings and aid their overall recovery.

8.
Parasit Vectors ; 17(1): 218, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735919

ABSTRACT

BACKGROUND: Epigenetic modifications of histones play important roles in the response of eukaryotic organisms to environmental stress. However, many histone acetyltransferases (HATs), which are responsible for histone acetylation, and their roles in mediating the tick response to cold stress have yet to be identified. In the present study, HATs were molecularly characterized and their associations with the cold response of the tick Haemaphysalis longicornis explored. METHODS: HATs were characterized by using polymerase chain reaction (PCR) based on published genome sequences, followed by multiple bioinformatic analyses. The differential expression of genes in H. longicornis under different cold treatment conditions was evaluated using reverse transcription quantitative PCR (RT-qPCR). RNA interference was used to explore the association of HATs with the cold response of H. longicornis. RESULTS: Two HAT genes were identified in H. longicornis (Hl), a GCN5-related N-acetyltransferase (henceforth HlGNAT) and a type B histone acetyltransferase (henceforth HlHAT-B), which are respectively 960 base pairs (bp) and 1239 bp in length. Bioinformatics analysis revealed that HlGNAT and HlHAT-B are unstable hydrophilic proteins characterized by the presence of the acetyltransferase 16 domain and Hat1_N domain, respectively. RT-qPCR revealed that the expression of HlGNAT and HlHAT-B decreased after 3 days of cold treatment, but gradually increased with a longer period of cold treatment. The mortality rate following knockdown of HlGNAT or HlHAT-B by RNA interference, which was confirmed by RT-qPCR, significantly increased (P < 0.05) when H. longicornis was treated at the lowest lethal temperature (- 14 °C) for 2 h. CONCLUSIONS: The findings demonstrate that HATs may play a crucial role in the cold response of H. longicornis. Thus further research is warranted to explore the mechanisms underlying the epigenetic regulation of the cold response in ticks.


Subject(s)
Cold Temperature , Histone Acetyltransferases , Ixodidae , Animals , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Ixodidae/genetics , Ixodidae/enzymology , Ixodidae/physiology , Cold-Shock Response/genetics , RNA Interference , Epigenesis, Genetic , Computational Biology , Phylogeny , Haemaphysalis longicornis
9.
10.
Adv Sci (Weinh) ; : e2404143, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38785180

ABSTRACT

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

11.
J Clin Oncol ; : JCO2302314, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788174

ABSTRACT

PURPOSE: CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). PATIENTS AND METHODS: These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. RESULTS: The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. CONCLUSION: In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

12.
Zhen Ci Yan Jiu ; 49(5): 506-511, 2024 May 25.
Article in English, Chinese | MEDLINE | ID: mdl-38764122

ABSTRACT

OBJECTIVES: To observe the effect of scalp-abdominal acupuncture combined with donepezil hydrochloride on cognition and life ability of patients with Alzheimer's disease (AD), so as to evaluate its clinical efficacy. METHODS: Sixty AD patients were collected and randomly divided into control group (30 cases) and observation group (30 cases). Patients in the control group were treated with oral donepezil hydrochloride (5 mg, once daily). Patients in the observation group were treated with scalp-abdominal acupuncture at Baihui (GV20), Yintang (GV24+), Sishencong (EX-HN1), "emotional area", Shenting (GV24), "abdominal area 1""abdominal area 8", and bilateral Fengchi (GB20), Taixi (KI3), Xuanzhong (GB39), Zusanli (ST36) on the basis of control group, and electroacupuncture (10 Hz/50 Hz, 0.5 to 5.0 mA) was applied to EX-HN1, "emotional area""abdominal area 1" and "abdominal area 8", once daily, 30 min each time. Four weeks as a course of treatment, both the two groups were treated for two consecutive courses. Before and after treatment, the mini-mental state examination (MMSE), AD assessmennt scale-cognitive subscale (ADAS-Cog) and activity of daily living scale (ADL) were evaluated. The clinical efficacy index was calculated and safety was evaluated. RESULTS: After treatment, the MMSE and ADL scores were higher (P<0.05) and the ADAS-Cog score was lower (P<0.05) than those before treatment in both groups. Compared with the control group, the MMSE and ADL scores were increased (P<0.05) and ADAS-Cog score was decreased (P<0.05) in the observation group. The total effective rate of the observation group (26/30, 86.67%) was higher (P<0.05) than that of the control group (23/30, 76.67%). No adverse reactions occurred in both groups during the treatment. CONCLUSIONS: Scalp-abdominal acupuncture combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of AD patients, and the efficacy is better than that of oral donepezil hydrochloride alone.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Alzheimer Disease , Donepezil , Scalp , Humans , Donepezil/therapeutic use , Alzheimer Disease/therapy , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Female , Male , Aged , Abdomen , Middle Aged , Cognition/drug effects , Treatment Outcome , Piperidines/therapeutic use , Combined Modality Therapy , Aged, 80 and over , Indans/therapeutic use
13.
Sci Rep ; 14(1): 11528, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773317

ABSTRACT

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types. In addition, PBC increases the risk of autoimmune thyroid diseases such as autoimmune hyperthyroidism and Graves' disease, as well as multiple sclerosis and psoriasis. Additionally, PBC is identified as a risk factor for Crohn's disease and Celiac disease. Based on genetic evidence, there may be connections between PBC and specific EHAIDs: not all coexisting EHAIDs induce PBC, and vice versa. This underscores the significance of prioritizing PBC in clinical practice. Additionally, if any liver function abnormalities are observed during treatment or with EHAIDs, it is crucial to consider the possibility of comorbid PBC.


Subject(s)
Autoimmune Diseases , Genome-Wide Association Study , Liver Cirrhosis, Biliary , Mendelian Randomization Analysis , Humans , Liver Cirrhosis, Biliary/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/complications , Colitis, Ulcerative/genetics , Colitis, Ulcerative/complications , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/complications , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/complications , Sjogren's Syndrome/genetics , Sjogren's Syndrome/complications , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/complications , Genetic Predisposition to Disease , Celiac Disease/genetics , Celiac Disease/complications , Graves Disease/genetics , Risk Factors , Crohn Disease/genetics , Crohn Disease/complications , Scleroderma, Systemic/genetics , Multiple Sclerosis/genetics , Polymorphism, Single Nucleotide , Psoriasis/genetics , Psoriasis/complications
14.
Sci Rep ; 14(1): 10728, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38730027

ABSTRACT

The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.


Subject(s)
Alzheimer Disease , Ubiquitination , Alzheimer Disease/genetics , Alzheimer Disease/diagnosis , Alzheimer Disease/metabolism , Humans , Gene Expression Profiling , Transcriptome , Gene Regulatory Networks , Databases, Genetic
15.
Article in English | MEDLINE | ID: mdl-38808395

ABSTRACT

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

16.
J Exp Bot ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820225

ABSTRACT

Citrus bacterial canker (CBC) is a disease that poses a major threat to global citrus production and is caused by infection with Xanthomonas citri subsp. citri (Xcc). Wall-associated receptor-like kinase (WAKL) proteins play an important role in shaping plant resistance to various bacterial and fungal pathogens. In a prior report, CsWAKL01 was identified as a candidate Xcc-inducible gene found to be upregulated in CBC-resistant citrus plants. However, the functional role of CsWAKL01 and the mechanisms whereby it may influence resistance to CBC have yet to be clarified. Here, CsWAKL01 was found to localize to the plasma membrane, and the overexpression of the corresponding gene in transgenic sweet oranges resulted in the pronounced enhancement of CBC resistance, whereas its knockdown had the opposite effect. Mechanistically, the ability of CsWAKL01 was linked to its ability to reprogram jasmonic acid, salicylic acid, and abscisic acid signaling activity. CsWRKY53 was further identified as a transcription factor capable of directly binding the CsWAKL01 promoter and inducing its transcriptional upregulation. CsWRKY53 silencing conferred greater CBC susceptibility to infected plants. Overall, these data support a model wherein CsWRKY53 functions as a positive regulator of CsWAKL01 to enhance resistance to CBC via the reprogramming of phytohormone signaling. Together these results offer new insight into the mechanisms whereby WAKLs shape phytopathogen resistance while underscoring the potential value of targeting the CsWRKY53-CsWAKL01 axis when seeking to breed CBC-resistant citrus plant varieties.

17.
Adv Mater ; : e2402679, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821488

ABSTRACT

Graphene is a promising candidate for the thermal management of downscaled microelectronic devices owing to its exceptional electrical and thermal properties. Nevertheless, a comprehensive understanding of the intricate electrical and thermal interconversions at a nanoscale, particularly in field-effect transistors with prevalent gate operations, remains elusive. In this study, nanothermometric imaging is employed to examine a current-carrying monolayer graphene channel sandwiched between hexagonal boron nitride dielectrics. We reveal for the first time that beyond the expected Joule heating, the thermoelectric Peltier effect actively plays a significant role in generating hotspots beneath the gated region. With gate-controlled charge redistribution and a shift in the Dirac point position, we demonstrate an unprecedented systematic evolution of thermoelectric hotspots, underscoring their remarkable tunability. Our study reveals the field-effect Peltier contribution in a single graphene-material channel of transistors, offering valuable insights into field-effect thermoelectrics and future on-chip energy management. This article is protected by copyright. All rights reserved.

18.
World J Gastrointest Surg ; 16(5): 1336-1343, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38817276

ABSTRACT

BACKGROUND: Magnetic anchor technique (MAT) has been applied in laparoscopic cholecystectomy and laparoscopic appendectomy, but has not been reported in laparoscopic partial hepatectomy. AIM: To evaluate the feasibility of the MAT in laparoscopic left lateral segment liver resection. METHODS: Retrospective analysis was conducted on the clinical data of eight patients who underwent laparoscopic left lateral segment liver resection assisted by MAT in our department from July 2020 to November 2021. The Y-Z magnetic anchor devices (Y-Z MADs) was independently designed and developed by the author of this paper, which consists of the anchor magnet and magnetic grasping apparatus. Surgical time, intraoperative blood loss, intraoperative accidents, operator experience, postoperative incision pain score, postoperative complications, and other indicators were evaluated and analyzed. RESULTS: All eight patients underwent a MAT-assisted laparoscopic left lateral segment liver resection, including three patients undertaking conventional 5-port and five patients having a transumbilical single-port operation. The mean operation time was 138 ± 34.32 min (range 95-185 min) and the mean intraoperative blood loss was 123 ± 88.60 mL (range 20-300 mL). No adverse events occurred during the operation. The Y-Z MADs showed good workability and maneuverability in both tissue and organ exposure. In particular, the operators did not experience either a "chopstick" or "sword-fight" effect in the single-port laparoscopic operation. CONCLUSION: The results show that the MAT is safe and feasible for laparoscopic left lateral segment liver resection, especially, exhibits its unique abettance for transumbilical single-port laparoscopic left lateral segment liver resection.

19.
World J Gastrointest Surg ; 16(5): 1443-1448, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38817285

ABSTRACT

BACKGROUND: The treatment of postoperative anastomotic stenosis (AS) after resection of colorectal cancer is challenging. Endoscopic balloon dilation is used to treat stenosis in such cases, but some patients do not show improvement even after multiple balloon dilations. Magnetic compression technique (MCT) has been used for gastrointestinal anastomosis, but its use for the treatment of postoperative AS after colorectal cancer surgery has rarely been reported. CASE SUMMARY: We report a 72-year-old man who underwent radical resection of colorectal cancer and ileostomy one year ago. An ileostomy closure was prepared six months ago, but colonoscopy revealed a narrowing of the rectal anastomosis. Endoscopic balloon dilation was performed three times, but colonoscopy showed no significant improvement in stenosis. The AS was successfully treated using MCT. CONCLUSION: MCT is a minimally invasive method that can be used for the treatment of postoperative AS after colorectal cancer surgery.

20.
Int J Biol Macromol ; 271(Pt 2): 132672, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38810855

ABSTRACT

Wound infection not only hinders the time sequence of tissue repair, but also may lead to serious complications. Multifunctional wound dressings with biocompatibility, excellent mechanical properties and antibacterial properties can promote wound healing during skin infection and reduce the use of antibiotics. In this study, a multifunctional dual-network antibacterial hydrogel was constructed based on the electrostatic interaction of two polyelectrolytes, hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and sodium alginate (SA). Attributing to the suitable physical crosslinking between HACC and SA, the hydrogel not only has good biocompatibility, mechanical property, but also has broad-spectrum antibacterial properties. In vivo results showed that the hydrogel could regulate M2 polarization, promote early vascular regeneration, and create a good microenvironment for wound healing. Therefore, this hydrogel is an effective multifunctional wound dressing. Consequently, we propose a novel hydrogel with combined elements to expedite the intricate repair of wound infection.

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