Inhibitory effect of norharmane on Serratia marcescens NJ01 quorum sensing-mediated virulence factors and biofilm formation.

Serratia marcescens NJ01, a Gram-negative bacterium, can infect tomato leaves and cause chlorosis and wilting. The present study evaluated the quorum sensing (QS) and biofilm inhibitory effects of seven carboline compounds against S. marcescens NJ01 at 20 µg ml-1, and subsequently focused the study on norharmane as this had the best inhibitory activity. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed the down-regulation of QS and biofilm related genes bsmA, bsmB, fimA, fimC, flhD, pigA, pigC and shlA on exposure to norharmane. Fourier-Transform Infrared Spectroscopy (FT-IR) analysis showed a reduction in the major components of the exopolysaccharide (EPS) matrix such as nucleic acids, proteins and fatty acids, which are involved in forming the tertiary structure of biofilms. Norharmane exposure also enhanced the susceptibility of the biofilm to ofloxacin. Hence, norharmane has the potential for use as an antibiotic adjuvant to enhance the efficacy of conventional antibiotics to reduce pathogenic bacterial infections.

Growth inhibition and metabolomic analysis of Xanthomonas oryzae pv. oryzae treated with resveratrol.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) can cause destructive bacterial blight in rice. As an antibacterial, resveratrol may inhibit Xoo growth. This study focused on the potential structural-activity relationship of resveratrol and its derivatives against Xoo growth, and 1H-NMR-based metabolomic analysis was applied to investigate the global metabolite changes in Xoo after resveratrol treatment. RESULTS: Resveratrol showed the strongest inhibitory effects on Xoo growth compared with its derivatives, which lacked double bonds (compounds 4-6) or hydroxyls were substituted with methoxyls (compounds 7-9). The IC50 of resveratrol against Xoo growth was 11.67 ± 0.58 µg/mL. Results indicated that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were vital for this inhibition. Interestingly, resveratrol also significantly inhibited Xoo flagellum growth. Based on 1H-NMR global metabolic analysis, a total of 30 Xoo metabolites were identified, the changes in the metabolic profile indicated that resveratrol could cause oxidative stress as well as disturb energy, purine, amino acid, and NAD+ metabolism in Xoo, resulting in the observed inhibitory effects on growth. CONCLUSIONS: This study showed that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were also the important active groups. Resveratrol could cause oxidative stress of Xoo cells, and disturb the metabolism of energy, purine, amino acid and NAD +, thus inhibit Xoo growth.

Tectochrysin increases stress resistance and extends the lifespan of Caenorhabditis elegans via FOXO/DAF-16.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aß1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.

Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives.

Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 µg/mL) and MCA (200 µg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points • DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum. • DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection.

Effective MSTN Gene Knockout by AdV-Delivered CRISPR/Cas9 in Postnatal Chick Leg Muscle.

Muscle growth and development are important aspects of chicken meat production, but the underlying regulatory mechanisms remain unclear and need further exploration. CRISPR has been used for gene editing to study gene function in mice, but less has been done in chick muscles. To verify whether postnatal gene editing could be achieved in chick muscles and determine the transcriptomic changes, we knocked out Myostatin (MSTN), a potential inhibitor of muscle growth and development, in chicks and performed transcriptome analysis on knock-out (KO) muscles and wild-type (WT) muscles at two post-natal days: 3d (3-day-old) and 14d (14-day-old). Large fragment deletions of MSTN (>5 kb) were achieved in all KO muscles, and the MSTN gene expression was significantly downregulated at 14d. The transcriptomic results indicated the presence of 1339 differentially expressed genes (DEGs) between the 3d KO and 3d WT muscles, as well as 597 DEGs between 14d KO and 14d WT muscles. Many DEGs were found to be related to cell differentiation and proliferation, muscle growth and energy metabolism. This method provides a potential means of postnatal gene editing in chicks, and the results presented here could provide a basis for further investigation of the mechanisms involved in muscle growth and development.

[Clinical Characteristics and Risk Factors of ESKAPE Pathogens Bloodstream Infection in Cancer Patients].

OBJECTIVE: To identify the risk factors of ESKAPE pathogens infection and related death in cancer patients, and to supply evidence for clinical precaution and diagnosis. METHODS: A retrospective study of clinical and experimental data of cancer patients with bloodstream infection were carried out in Sichuan Cancer Hospital from 2013 to 2018. The clinical feature, predisposing factors and risk factors of death in ESKAPE group and non-ESKAPE group were analyzed by univariate analysis and multivariate logistic regression. RESULTS: A total of 753 patients were enrolled in the study. Totally 795 pathogenic bacteria strains were isolated from blood culture and there were 278 ESKAPE strains, which took up 34.97% of isolated strains. Univariate analysis and multivariate logistic regression analysis showed that gender of male, multiple pathogens, history of exposure to enzyme inhibitors and agranulocytosis were independent risk factors of ESKAPE pathogens bloodstream infection. Peritoneal infection and combined fungal infection were independent risk factors of ESKAPE bloodstream infection related death. CONCLUSION: The bloodstream infection of ESKAPE pathogens is a problem worthy of clinical attention for cancer patients with neutrophil deficiency, previous antibiotic exposure, and fungal infection and peritoneal infection.

Aspirin Derivative 5-(Bis(3-methylbut-2-enyl)amino)-2-hydroxybenzoic Acid Improves Thermotolerance via Stress Response Proteins in Caenorhabditis elegans.

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity.

Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way.

With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C. elegans). Our results showed that M084 could extend the lifespan of C. elegans, delay age-related decline of phenotypes, and improve stress resistance. M084 could not extend the lifespan of the loss-of-function mutants of daf-16, daf-2, pdk-1, aak-2, clk-1, isp-1, sir-2.1, and skn-1. M084 could decrease the ATP level and increase the gene expression of mitochondrial unfolded protein response factors. Thus, M084 might inhibit the mitochondrial respiration, activate mitochondrial unfolded protein response and AMPK, recruite SIR-2.1 and SKN-1, and finally through the transcription factor DAF-16, delay the aging process of C. elegans. Our findings reveal the new pharmaceutical potential of benzimidazole derivatives and provide clue for developing novel anti-aging agents.

NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation.

Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-α, IL-6, IL-1ß, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-κB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-α, IL-6, IL-1ß, and MCP-1 overproduction, mTOR upregulation, and NF-κB nuclear translocation. The PROMO software analysis indicated NF-κB binding site in the -1643 to -1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-κB promoted the transcription of miR-99a by binding to the -1643 to -1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-κB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-κB signal. NF-κB promoted miR-99a production by binding to the -1643 to -1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis.

Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington's disease.

5-Hydroxymethylcytosine (5-hmC) may represent a new epigenetic modification of cytosine. While the dynamics of 5-hmC during neurodevelopment have recently been reported, little is known about its genomic distribution and function(s) in neurodegenerative diseases such as Huntington's disease (HD). We here observed a marked reduction of the 5-hmC signal in YAC128 (yeast artificial chromosome transgene with 128 CAG repeats) HD mouse brain tissues when compared with age-matched wild-type (WT) mice, suggesting a deficiency of 5-hmC reconstruction in HD brains during postnatal development. Genome-wide distribution analysis of 5-hmC further confirmed the diminishment of the 5-hmC signal in striatum and cortex in YAC128 HD mice. General genomic features of 5-hmC are highly conserved, not being affected by either disease or brain regions. Intriguingly, we have identified disease-specific (YAC128 versus WT) differentially hydroxymethylated regions (DhMRs), and found that acquisition of DhmRs in gene body is a positive epigenetic regulator for gene expression. Ingenuity pathway analysis (IPA) of genotype-specific DhMR-annotated genes revealed that alternation of a number of canonical pathways involving neuronal development/differentiation (Wnt/ß-catenin/Sox pathway, axonal guidance signaling pathway) and neuronal function/survival (glutamate receptor/calcium/CREB, GABA receptor signaling, dopamine-DARPP32 feedback pathway, etc.) could be important for the onset of HD. Our results indicate that loss of the 5-hmC marker is a novel epigenetic feature in HD, and that this aberrant epigenetic regulation may impair the neurogenesis, neuronal function and survival in HD brain. Our study also opens a new avenue for HD treatment; re-establishing the native 5-hmC landscape may have the potential to slow/halt the progression of HD.

Triterpenoids with Promoting Effects on the Differentiation of PC12 Cells from the Steamed Roots of Panax notoginseng.

The roots of Panax notoginseng, an important Chinese medicinal plant, have been used traditionally in both the raw and processed forms, due to the different chemical constituents and bioactivities found. Thirty-eight dammarane-type triterpenoid saponins were isolated from the steam-processed roots of P. notoginseng, including 18 new substances, namely, notoginsenosides SP1-SP18 (1-18). The structures of 1-18 were determined on the basis of spectroscopic analysis and acidic hydrolysis. The absolute configuration of the hydroxy group at C-24 in 1-4, 19, and 20 was determined in each case by Mo2(AcO)4-induced circular dichroism. The new compounds were found to feature a diversity of highly oxygenated side chains, formed by hydrolysis of the C-20 sugar moiety followed by dehydration, dehydrogenation, epoxidation, hydroxylation, or methoxylation of the main saponins in the raw roots. The new saponins 1, 2, 6-8, 14, and 17 and the known compounds 20-27 showed promoting effects on the differentiation of PC12 cells, at a concentration of 10 µM.

Two new dendrocandins with neurite outgrowth-promoting activity from Dendrobium officinale.

Two new bibenzyl derivatives, dendrocandin T (1) and dendrocandin U (2), together with eight known bibenzyls, were isolated from the stems of Dendrobium officinale. Those compounds were sent for the first time for central nervous system-related bioassay and the results indicated that compounds 3, 4, and 5 have a certain degree of neurite outgrowth-promoting activity, and compounds 1, 2, 6, and 7 also have weak activity. The results indicated that D. officinale used as health food and traditional Chinese medicine "Tiepi Shihu" has a health function of neurotrophic effects.

Meta-Analysis of miR-146a Polymorphisms Association with Coronary Artery Diseases and Ischemic Stroke.

Coronary artery disease (CAD) and ischemic stroke (IS) are manifestations of atherosclerosis, with a high death rate. miR-146a is a microRNA that participates in the progress of CAD and IS. A single nucleotide polymorphism (SNP) in the precursor of miR-146a, rs2910164, was found to be associated with the risks of CAD and IS. However, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the relationship of rs2910164 and CAD as well as IS susceptibility. The database Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM) were searched for related studies. Crude odds ratios with 95% confidence intervals were used to investigate the strength of the association by random- or fixed-effect model. A total of eight studies, with 3138 cases and 3097 controls were identified for the meta-analysis. The results shows that rs2910164 is associated with the risk of CAD significantly in allelic model (OR = 0.86), homozygous model (OR = 0.70), heterozygous model (OR = 0.80) and dominant model (OR = 0.76). The subjects carrying the GG genotype, GG + GC genotype or G allele are at lower risks of CAD. For the susceptibility of IS, there are no significant associations between rs2910164 and total studies. However, in subgroup analysis by sample size and ethnicity, the GG, GG + GC and G allele of rs2910164 are found to be associated with higher risks of IS in large sample size group and in Koreans, under homozygous and dominant models. In conclusion, the current meta-analysis suggests lower risks of CAD for GG, GG + GC genotype and G allele of rs2910164, while rs2910164 is not associated with the risk of IS. Thus rs2910164 might be recommended as a predictor for susceptibility of CAD, but not IS.

Chemical constituents from the stems of Excoecaria acertiflia.

Six new compounds, including two diterpenoids excocarinols F and G (1 and 2, resp.), two carotane (daucane) sesquiterpenoids excoecafolinols A and B (3 and 4, resp.), one lignanoid compound, excoecanol A (5), and one simple phenol, excoecanol B (6), together with 17 known compounds, were isolated from the BuOH extract of Excoecaria acerifolia Didr. stems. Their structures were elucidated through the analysis of the spectroscopic data. The AChE-inhibitory activities of 17 compounds were evaluated and revealed that four of them possessed moderate inhibitory activities against AChE.

Efficacy of a full management model in daytime surgery for gastrointestinal polyps based on WeChat: A study protocol for randomized controlled trials.

OBJECTIVE: The objective of this study is to improve the efficiency of daytime surgery for gastrointestinal polyp and ensure the safety of patients. We tried an information management method based on WeChat platform in patients undergoing daytime gastrointestinal polypectomy and to explore the feasibility and effectiveness of a full management model. METHODS: Five hundred and ninety-three patients were randomly divided into two groups: the control group was treated with traditional management methods and the experimental group was treated with the whole-process management mode based on the WeChat platform. The WeChat platform-based full management model included establishing a day surgery management WeChat group, developing multidisciplinary, full-management protocols and processes for day surgery, establishing an information-based surgical scheduling system and adopting diverse forms of day surgery education and continuity of care. This feature included illustrated brochures, vivid verbal presentations, WeChat public numbers and Internet management platforms. The treatment time, hospitalization cost and patient satisfaction of the two groups were counted. RESULTS: In the experimental group, 408 patients were enrolled. The preoperative waiting time and patients' length of stay were 3 days and 1 day, respectively. The medical and nursing intake time was 7 min. The procedure cancellation rate and postoperative complications rate was 0.07% and 0.02%. In the control group, 185 patients were enrolled in the study, The preoperative waiting time and patients' length of stay was 7 days and 3 days. The medical and nursing intake time was 28 min. The procedure cancellation rate and postoperative complications rate were 0.13% and 0.05%, respectively. The hospitalization costs were reduced by an average of $140/person and the satisfaction scores were higher than the control group. In summary, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the observation group were less than those in the control group (p < 0.05). Patient satisfaction scores were significantly higher than those in the control group (p < 0.05). CONCLUSION: Through the full management model based on WeChat, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the experimental group were less than those in the control group. Patient satisfaction scores were significantly higher than those in the control group and the difference was statistically significant.

Clinical efficacy of probiotics in the treatment of alcoholic liver disease: a systematic review and meta-analysis.

Objective: Alcoholic liver disease (ALD) is a liver damage disease caused by long-term heavy drinking. Currently, there is no targeted pharmaceutical intervention available for the treatment of this disease. To address this, this paper evaluates the efficacy and safety of probiotic preparation in treating ALD through conducting a meta-analysis, and provides a valuable insight for clinical decision-making. Methods: A systematic search was conducted across databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM from the inception dates to October 15, 2023, to identify clinical randomized controlled trials on probiotic preparations in the treatment of ALD. After the literature underwent screening, data extraction, and quality assessment, RevMan 5.3 and Stata 14.2 were employed for data analysis and processing. Results: A total of 9 randomized controlled trials fulfilled the inclusion criteria. The results of the meta-analysis showed that probiotic preparation could significantly improve the liver function of patients with alcoholic liver disease compared with the control group. Probiotic intervention led to a significant reduction in the levels of alanine aminotransferase (MD=-13.36,95%CI:-15.80,-10.91;P<0.00001),aspartate aminotransferase (MD=-16.99,95%CI:-20.38,-13.59;P<0.00001),γ-glutamyl transpeptidase (MD=-18.79,95% CI:-28.23,-9.34; P<0.0001). Concurrently, the level of serum albumin (MD=0.19,95% CI:0.02,0.36;P=0.03) was increased. Furthermore, probiotic intervention could also modulate the composition of intestinal flora in patients with alcoholic liver disease, leading to an augmentation in Bifidobacteria and a reduction in Escherichia coli. However, in patients with alcoholic liver disease, probiotic intervention showed no significant effects on total bilirubin (MD=-0.01,95% CI:-0.17,0.15;P=0.91), tumor necrosis factor-α (MD=0.03,95% CI:-0.86,0.92;P=0.94) and interleukin-6 (MD=-5.3,95% CI:-16.04,5.45;P=0.33). Conclusion: The meta-analysis indicates that probiotics can improve liver function in alcoholic liver disease, reduce inflammatory responses, regulate intestinal flora, which have potential value in the treatment of alcoholic liver disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023472527.

A meta-analysis of the value of serum TSH concentration in the diagnosis of differentiated thyroid cancer in patients with thyroid nodules.

Background: In recent years, most studies believe that high TSH level is positively correlated with the incidence of thyroid cancer, but it is still controversial. For this reason, the purpose of this study is to analyze the correlation between preoperative TSH level and thyroid malignant nodules using pathological diagnosis as the gold standard. To evaluate the role of serum TSH in predicting malignancy of thyroid nodules with uncertain cytology.As an important member of the hypothalamus-pituitary-thyroid axis in the endocrine system, TSH plays a crucial role in regulating the growth, differentiation, and function of thyroid cells (Zhang et al., 2023) [1]. Therefore, it has always been considered closely related to TC. Currently, most studies have compared the TSH levels of TC patients and individuals with benign thyroid disease or healthy controls. These findings from various studies indicated that TC patients often demonstrate elevated TSH levels, even when their TSH falls within the normal range. However, it is important to highlight that the current evidence primarily relies on cross-sectional studies, which mainly describe a phenomenon without establishing causal relationships. The involvement of TSH in the early onset or late progression of TC remains unknown, the interaction between TSH and other factors and how it affects TC is not well understood (Gubbi et al., 2020) [2].Symptoms of thyroid cancer are usually insidious, and early thyroid cancer often has no obvious clinical symptoms. Therefore, early detection and early treatment are particularly important, and how to improve the preoperative diagnosis rate of thyroid nodules is also a problem that clinicians pay close attention to. Objective: To evaluate the value of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma in patients with thyroid nodules. Methods: Our study searched databases in both Chinese and English.China Academic Journals FULL-text Database (CNKI), China Online Journals, Chinese Scientific Journals database and Chinese Biomedical Literature Database (CBM) were searched by computer. The English literature was established by PubMed, Embase, Cochrane Library, Web of Science and other databases until June 2022 to search for relevant literatures on the diagnostic test of serum TSH concentration in patients with thyroid nodule. The literatures that met the criteria were screened, the data were extracted, and the literature quality was evaluated. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the method for the diagnosis of differentiated thyroid carcinoma were calculated and summarized. The receiver operating characteristic (SROC) curve was drawn and the area under the curve was obtained. Results: A total of 23 diagnostic tests were included (5348 lesions). Meta-analysis showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma were 0.64, 0.72, 2.511, 0.386 and 7.14, respectively. The area under SROC curve (AUC) was 0.79, and the Q index was 0.7283, indicating no statistically significant difference. Conclusion: Based on current evidence, detection of serum TSH concentration in thyroid nodule patients has high sensitivity and specificity for the diagnosis of differentiated thyroid cancer, which has good clinical application value. However, other auxiliary examinations are still needed to improve the diagnosis rate.

Phloretic acid requires the insulin/IGF-1 pathway and autophagy to enhance stress resistance and extend the lifespan of Caenorhabditis elegans.

Objective: In humans, aging is associated with increased susceptibility to most age-related diseases. Phloretic acid (PA), a naturally occurring compound found in Ginkgo biloba and Asparagus, exhibits has potential as an anti-aging agent and possesses antioxidant, anti-inflammatory, and immunomodulatory properties. This study aimed to investigate the effects of PA on longevity and stress resistance in Caenorhabditis elegans (C.elegans) and the mechanisms that underlie its effects. Methods: First, we examined the effects of PA on lifespan and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, we examined the insulin/insulin-like pathway, mitochondria, autophagy-related proteins, and gene expression to explain the possible mechanism of PA prolonging lifespan. Results: Our findings demonstrated that PA dose-dependently extended the C.elegans lifespan, with 200 µM PA showing the greatest effect and increased the C.elegans lifespan by approximately 16.7%. PA enhanced motility and the pharyngeal pumping rate in senescent C.elegans while reducing the accumulation of aging pigments. Further investigations revealed that daf-16, skn-1, and hsf-1 were required for mediating the lifespan extension effect of PA in C.elegans since its impact was suppressed in mutant strains lacking these genes. This suggests that PA activates these genes, leading to the upregulation of downstream genes involved in stress response and senescence regulation pathways. Furthermore, PA did not extend the lifespan of the RNAi atg-18 and RNAi bec-1 but it attenuated SQST-1 accumulation, augmented autophagosome expression, upregulated autophagy-related gene expression, and downregulated S6K protein levels. These findings suggest that the potential life-extending effect of PA also involves the modulation of the autophagy pathway. Conclusion: These findings results highlight the promising anti-aging effects of PA and warrant further investigation into its pharmacological mechanism and medicinal development prospects.

Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase.

A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BuChE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BuChE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100µM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face π-π stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09Å) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BuChE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BuChE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

Competent mitral valve after annulus ring removal for infective endocarditis.

The mitral annulus plays an essential role in mitral valve (MV) competency. When surgical intervention is needed, the placement of an annular ring is considered a major component of MV repair. However, the use of a foreign material increases the risk of infectious and thromboembolic complications and is problematic in children as it does not allow for annular growth. Herein is reported a case of infective endocarditis affecting a mitral ring that was implanted to treat severe mitral valve regurgitation (MR) some 10 years earlier. Surgery was performed to remove the MV vegetation, and subsequent echocardiography revealed only trace MR. The concept that the ring may be needed for a limited period of time to induce valve remodeling is consistent with new data on biodegradable rings. These rings degrade over months, inducing dense fibrous tissue that replaces the ring and maintains valve competency. The present case is one of the first human examples to support the potential efficacy of a biodegradable ring.