The role of triglyceride-glucose index in the differential diagnosis of atherosclerotic stroke and cardiogenic stroke.

OBJECTIVE: This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). METHOD: In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People's Hospital and Lianyungang First People's Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. RESULT: The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11-2.39, OR = 1.72,95%CI = 1.16-2.55, OR = 2.06,95%CI = 1.36-3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566-0.623;P<0.001). CONCLUSION: Summarily, the TyG index has slight significance in the identification of LAA and CE; it is particularly a marker for their preliminary identification.

Association analysis of transcriptome and quasi-targeted metabolomics reveals the regulation mechanism underlying broiler muscle tissue development at different levels of dietary guanidinoacetic acid.

The development and characteristics of muscle fibers in broilers are critical determinants that influence their growth performance, as well as serve as essential prerequisites for the production of high-quality chicken meat. Guanidinoacetic acid (GAA) is a crucial endogenous substance in animal creatine synthesis, and its utilization as a feed additive has been demonstrated the capabilities to enhance animal performance, optimize muscle yield, and augment carcass quality. The objective of this study was to investigate the regulation and molecular mechanism underlying muscle development in broilers at different levels of GAA via multiple omics analysis. The 90 Cobb broilers, aged 1 day, were randomly allocated into three treatments consisting of five replicates of six chickens each. The control group was provided with a basal diet, while the Normal GAA and High GAA groups received a basal diet supplemented with 1.2 g/kg and 3.6 g/kg of GAA, respectively. After a feeding period of 42 days, the pectoralis muscles were collected for histomorphological observation, transcriptome and metabolomic analysis. The results demonstrated that the addition of 1.2 g/kg GAA in the diet led to an augmentation in muscle fiber diameter and up-regulation of IGF1, IHH, ASB2, and ANKRD2 gene expression. However, a high dose of 3.6 g/kg GAA in the diet potentially reversed the beneficial effects on chicken breast development by excessively activating the TGF-ß signaling pathway and reducing nucleotide metabolite content. These findings would provide a theoretical foundation for enhancing the performance and meat quality of broilers by incorporating GAA as a feed additive.

AMPK activation eliminates senescent cells in diabetic wound by inducing NCOA4 mediated ferritinophagy.

BACKGROUND: Diabetic wounds are one of the long-term complications of diabetes, with a disordered microenvironment, diabetic wounds can easily develop into chronic non-healing wounds, which can impose a significant burden on healthcare. In diabetic condition, senescent cells accumulate in the wound area and suppress the wound healing process. AMPK, as a molecule related to metabolism, has a close relationship with aging and diabetes. The purpose of this study was to investigate the effects of AMPK activation on wound healing and explore the underlying mechanisms. METHODS: AMPK activator A769662 was topically applied in wound models of diabetic mice. Alterations in the wound site were observed and analyzed by immunohistochemistry. The markers related to autophagy and ferritinophagy were analyzed by western blotting and immunofluorescence staining. The role of AMPK activation and ferritinophagy were also analyzed by western blotting. RESULTS: Our results show that AMPK activation improved diabetic wound healing and reduced the accumulation of senescent cells. Intriguingly, we found that AMPK activation-induced ferroptosis is autophagy-dependent. We detected that the level of ferritin had deceased and NCOA4 was markedly increased after AMPK activation treatment. We further investigated that NCOA4-mediated ferritinophagy was involved in ferroptosis triggered by AMPK activation. Most importantly, AMPK activation can reverse the ferroptosis-insensitive of senescent fibroblast cells in diabetic mice wound area and promote wound healing. CONCLUSIONS: These results suggest that activating AMPK can promote diabetic wound healing by reversing the ferroptosis-insensitive of senescent fibroblast cells. AMPK may serve as a regulatory factor in senescent cells in the diabetic wound area, therefore AMPK activation can become a promising therapeutic method for diabetic non-healing wounds.

Advancements and trends in exosome research in lung cancer from a bibliometric analysis (2004-2023).

Background: Lung cancer, characterized by its high morbidity and lethality, necessitates thorough research to enhance our understanding of its pathogenesis and discover novel therapeutic approaches. Recent studies increasingly demonstrate that lung cancer cells can modulate the tumor microenvironment, promoting tumor growth, and metastasis through the release of exosomes. Exosomes are small vesicles secreted by cells and contain a variety of bioactive molecules such as proteins, nucleic acids, and metabolites. This paper presents a comprehensive review of exosome research in lung cancer and its progress through bibliometric analysis. Methods: Publications related to exosomes in lung cancer patients were systematically searched on the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviwers, CiteSpace, and the R package "Bibliometrics". Publications were quantitatively analyzed using Microsoft Office Excel 2019. The language of publication was restricted to "English" and the search strategy employed TS=(exosomes or exosomes or exosomes) and TS=(lung cancer). The search period commenced on January 1, 2004, and concluded on November 12, 2023, at noon. The selected literature types included Articles and Reviews. Results: The study encompassed 1699 papers from 521 journals across 71 countries and 2105 institutions. Analysis revealed a consistent upward trend in lung cancer exosome research over the years, with a notable surge in recent times. This surge indicates a growing interest and depth of inquiry into lung cancer exosomes. Major research institutions in China and the United States, including Nanjing Medical University, Shanghai Jiao Tong University, Chinese Academy Of Sciences, and Utmd Anderson Cancer Center, emerged as crucial research hubs. The annual publication count in this field witnessed a continuous rise, particularly in recent years. Key terms such as lung cancer, non-small cell lung cancer (NSCLC), microvesicles, intercellular communication, exosomal miRNAs, and oncology dominated the research landscape. Fields like cell biology, biochemistry, biotechnology, and oncology exhibited close relation with this research. Clotilde Théry emerged as the most cited author in the field, underlining her significant contributions. These results demonstrate the broad impact of exosome research in lung cancer, with key terms covering not only disease-specific aspects such as lung cancer and NSCLC but also basic biological concepts like microvesicles and intercellular communication. Explorations into exosomal microRNAs and oncology have opened new avenues for lung cancer exosome research. In summary, lung cancer exosome research is poised to continue receiving attention, potentially leading to breakthroughs in treatment and prevention. Conclusion: Publications on lung cancer exosomes show a rising trend year by year, with China and the United States ranking first and second in terms of the number of publications. However, there is insufficient academic learning cooperation and exchanges between the two sides, and Chinese universities account for a large proportion of research institutions in this field. Jing Li is the most productive author, Clotilde Théry is the most co-cited author, and Cancers is the journal with the highest number of publications. The current focus in the field of lung cancer exosomes is on biomarkers, liquid biopsies, immunotherapy, and tumor microenvironment.

Multiomics Analysis Unravels Alteration in Molecule and Pathways Involved in Nondiabetic Chronic Wounds.

The prevalence of chronic wounds (CW) continues to grow. A thorough knowledge of the mechanism of CW formation remains elusive due to a lack of relevant studies. Furthermore, most previous studies concentrated on diabetic ulcers with relatively few investigations on other types. We performed this multiomics study to investigate the proteomic and metabolomic changes in wound and surrounding tissue from a cohort containing 13 patients with nondiabetic CW. Differentially expressed proteins (DEPs) and metabolites (DEMs) were filtered out and analyzed through multiomic profiling. The DEPs were further confirmed with the use of parallel reaction monitoring. Compared with the surrounding tissue, there were 82 proteins and 214 metabolites altered significantly in wound tissue. The DEPs were mainly enriched in focal adhesion (FA), extracellular matrix-receptor interaction (ERI), and the PI3K-Akt (PA) signaling pathway. Moreover, the DEMs were significantly enriched in amino sugar and nucleotide sugar metabolism and biosynthesis of nucleotide sugar pathways. In correlation analysis, we discovered that the PA signaling pathway, as well as its upstream and downstream pathways, coenriched some DEPs and DEMs. Additionally, we found that FBLN1, FBLN5, and EFEMP1 (FBLN3) proteins dramatically elevated in wound tissue and connected with the above signaling pathways. This multiomics study found that changes in FA, ERI, and PA signaling pathways had an impact on the cellular activities and functions of wound tissue cells. Additionally, increased expression of those proteins in wound tissue may inhibit vascular and skin cell proliferation and degrade the extracellular matrix, which may be one of the causes of CW formation.

Analysis of microRNA Expression Profiles in Broiler Muscle Tissues by Feeding Different Levels of Guanidinoacetic Acid.

The aim of this study was to explore the molecular mechanisms through which different levels of GAA affect chicken muscle development by influencing miRNA expression, to lay a theoretical foundation for the identification of key functional small RNAs related to poultry muscle development, and to provide new insights into the regulatory mechanisms of GAA on muscle development and meat quality in broilers. It provides a new theoretical basis for using GAA as a feed additive to improve feed performance. Small RNA sequencing technology was utilized to obtain the expression profiles of miRNA in the broiler pectoral muscle fed with different levels of GAA (0 g/kg, 1.2 g/kg and 3.6 g/kg). An analysis of differentially expressed miRNAs revealed 90 such miRNAs in the three combination comparisons, with gga-miR-130b-5p exhibiting significant differences across all three combinations. Furthermore, three of the differentially expressed miRNAs were performed by RT-qPCR verification, yielding results consistent with those obtained from small RNA sequencing. Target gene prediction, as well as the GO and KEGG enrichment analysis of differentially expressed miRNAs, indicated their involvement in muscle cell differentiation and other processes, particularly those associated with the MAPK signaling pathway. This study has, thus, provided valuable insights and resources for the further exploration of the miRNA molecular mechanism underlying the influence of guanidine acetic acid on broiler muscle development. Combined with previous studies and small RNA sequencing, adding 1.2 g/kg GAA to the diet can better promote the muscle development of broilers.

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

BACKGROUND: Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. METHODS: Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. RESULTS: The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. CONCLUSION: This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

Comparing the effectiveness of extracorporeal shockwave therapy and myofascial release therapy in chronic pelvic pain syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome is a highly prevalent syndrome. Previous studies showed that extracorporeal shockwave therapy and myofascial release therapy could improve the quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Theoretically, combined therapy with extracorporeal shockwave therapy and myofascial release therapy will likely have significant advantages in treating CP/CPPS. We, therefore, present a protocol for conducting a well-designed randomized controlled trial to compare the efficacy and safety of each therapy. METHODS: The proposed study will be a three-group randomized control trial (RCT) design that includes 150 participants from Zhongda Hospital Affiliated to Southeast University, with equal allocation of participants to the three intervention groups. The study duration will be 8 weeks, which includes a 4-week treatment period and a 4-week follow-up period. The primary outcome will be the changes in surface electromyography (sEMG) assessment and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). The secondary outcomes will include the changes in three-dimensional quantification, shear wave elastography (SWE), and sympathetic skin response (SSR) testing. Assessments will be conducted before the intervention (T0), before the 5th intervention (T1), immediately after the 8th intervention (T2), and the 4th week after the end of the 8th intervention (T3). DISCUSSION: This trial will compare the differences in efficacy between single extracorporeal shockwave therapy, single myofascial release therapy, and combined therapy to select the most appropriate treatment option for patients with CP/CPPS. The possible pathogenesis of CP/CPPS would also be analyzed by comparing the intercorrelation between each objective and subjective measurement (NIH-CPSI score, sEMG, SWE, SSR). TRIAL REGISTRATION: The name of the registry: Extracorporeal Shockwave and Myofascial Release Therapy in Chronic Pelvic Pain Syndrome. REGISTRATION NUMBER: NCT05659199. Date of registration: December 2022.

Enzyme-responsive nanospheres target senescent cells for diabetic wound healing by employing chemodynamic therapy.

Evidence indicates that prolonged low-level inflammation and elevated-glucose-induced oxidative stress in diabetic wounds can accelerate senescence. The accumulation of senescent cells, in turn, inhibits cellular proliferation and migration, aggravating the inflammatory response and oxidative stress, ultimately impeding wound healing. In this study, we exploited the heightened lysosomal ß-galactosidase activity detected in senescent cells to develop an innovative drug delivery system by encapsulating Fe3O4 with galactose-modified poly (lactic-co-glycolic acid) (PLGA) (F@GP). We found that F@GP can selectively release Fe3O4 into senescent cells, inducing ferroptosis via the Fenton reaction in the presence of elevated intracellular H2O2 levels. This showed that F@GP administration can serve as a chemodynamic therapy to eliminate senescent cells and promote cell proliferation. Furthermore, the F@GP drug delivery system gradually released iron ions into the diabetic wound tissues, enhancing the attenuation of cellular senescence, stimulating cell proliferation, promoting re-epithelialization, and accelerating the healing of diabetic wounds in mice. Our groundbreaking approach unveiled the specific targeting of senescence by F@GP, demonstrating its profound effect on promoting the healing of diabetic wounds. This discovery underscores the therapeutic potential of F@GP in effectively addressing challenging cases of wound repair. STATEMENT OF SIGNIFICANCE: The development of galactose-modified PLGA nanoparticles loaded with Fe3O4 (F@GP) represents a significant therapeutic approach for the treatment of diabetic wounds. These nanoparticles exhibit remarkable potential in selectively targeting senescent cells, which accumulate in diabetic wound tissue, through an enzyme-responsive mechanism. By employing chemodynamic therapy, F@GP nanoparticles effectively eliminate senescent cells by releasing iron ions that mediate the Fenton reaction. This targeted approach holds great promise for promoting diabetic wound healing by selectively eliminating senescent cells, which play a crucial role in impairing the wound healing process. The innovative utilization of F@GP nanoparticles as a therapeutic intervention offers a novel and potentially transformative strategy for addressing the challenges associated with diabetic wound healing.

Safe-Harbor-Targeted CRISPR/Cas9 System and Cmhyd1 Overexpression Enhances Disease Resistance in Cordyceps militaris.

Fungal disease of mushroomCordyceps militaris (CM) caused byCalcarisporium cordycipiticola (CC) is destructive to fruiting body cultivation, resulting in significant economic loss and potential food safety risks. CRISPR/Cas9 genome editing has proven to be a powerful tool for crop improvement but seldom succeeded in mushrooms. Here, the first genomic safe-harbor site, CmSH1 locus, was identified in the CM genome. A safe-harbor-targeted CRISPR/Cas9 system based on an autonomously replicating plasmid was designed to facilitate alien gene integration at the CmSH1 locus. Cmhyd1, one of the hydrophobin genes, was confirmed as a defensive factor against CC infection, and Cmhyd1 overexpression by this system showed enhancement of disease resistance with negligible effect on the agronomic traits of CM. No off-target events and residues of plasmid sequence were tested by PCR and genome resequencing. This study provided the first safe harbor site for genetic manipulations, a safe harbor-targeted CRISPR/Cas9 system, and the first disease-resistant gene-editing breeding system in mushrooms.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

Biogas slurry recirculation regulates food waste fermentation: Effects and mechanisms.

Regularly adding biogas slurry into fermentation reactors is an effective way to enhance hydrogen or methane production. However, how this method affects the production of valuable organic acids and alcohols is still being determined. This study investigated the effects of different addition ratios on semi-continuous fermentation reactors using food waste as a substrate. The results showed that an addition ratio of 0.2 increased lactic acid production by 30% with a yield of 0.38 ± 0.01 g/g VS, while a ratio of 0.4 resulted in mixed acid fermentation dominated by n-butyric acid (0.07 ± 0.01 g/g VS) and n-caproic acid (0.06 ± 0.00 g/g VS). The introduction of Bifidobacteriaceae by biogas slurry played a crucial role in increasing lactic acid production. In contrast, exclusive medium-chain fatty acid producers enhanced the synthesis of caproic acid and heptanoic acid via the reverse ß-oxidation pathway. Mechanism analyses suggested that microbial community structure and activity, substrate hydrolysis, and cell membrane transport system and structure changed to varying degrees after adding biogas slurry.

Effects of different water quality regulators on growth performance, immunologic function, and domestic water quality of GIFT tilapia.

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1ß) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia.

Mitochondrial dynamics-related genes DRP1 and OPA1 contributes to early diagnosis of cognitive impairment in diabetes.

BACKGROUND AND AIM: DRP1 and OPA1 play important roles in mitochondrial fusion and fission. However, the role of DRP1 and OPA1 amplification in mitochondrial cognitive impairment has not been reported. This study aimed to investigate the relationship between DRP1 and OPA1 and the risk of cognitive impairment. METHODS: In this study, 45 elderly patients with diabetes admitted to the Lianyungang Second People's Hospital from September 2020 to January 2021 were included. The patients were divided into normal group, mild cognitive impairment group and dementia group by using MMSE score, and the clinical characteristics of the three groups were compared. The amplification multiples of the two genes' DNA were calculated by ΔΔCT and defined as 2- K. Spearman rank correlation was used to analyze the correlation between the DNA amplification multiples of patients' DRP1 and OPA1 and AD8 and MoCA scores. The sensitivity and specificity of DNA amplification multiples of DRP1 and OPA1 to predict clinical outcomes of diabetic cognitive impairment were evaluated using Receiver operator characteristic (ROC) curves. Multiple logistic regression was used to evaluate the relationship between DNA amplification factor of DRP1 and OPA1 and cognitive function. RESULTS: DRP1(2- K) and OPA1(2- K) significantly increased and decreased in dementia and MCI groups compared with the normal group (P ≤ 0.001). The DNA amplification factor of DRP1 was positively correlated with AD8 score and negatively correlated with MoCA score (P < 0.001). The DNA amplification factor of OPA1 was positively correlated with the MoCA score (P = 0.0002). Analysis of ROCs showed that the DNA amplification factor of OPA1 had a higher predictive value for dementia (P < 0.0001), and that it had a higher predictive value when used in combination with DRP1. Multiple logistic regression results showed that increased DNA amplification in DRP1 was associated with increased risk of dementia (OR 1.149;95%CI,1.035-1.275), and increased DNA amplification in OPA1 was associated with decreased risk of MCI (OR 0.004;95%CI,0.000-0.251) and dementia (OR 0.000;95%CI,0.000-0.134). CONCLUSION: DNA amplification multiples of DRP1 and OPA1 are associated with the risk of dementia in elderly patients and may serve as potential biomarkers.

Establishment of a dynamic nomogram including thyroid function for predicting the prognosis of acute ischemic stroke with standardized treatment.

Purpose: Many patients with acute ischemic stroke (AIS) cannot undergo thrombolysis or thrombectomy because they have missed the time window or do not meet the treatment criteria. In addition, there is a lack of an available tool to predict the prognosis of patients with standardized treatment. This study aimed to develop a dynamic nomogram to predict the 3-month poor outcomes in patients with AIS. Methods: This was a retrospective multicenter study. We collected the clinical data of patients with AIS who underwent standardized treatment at the First People's Hospital of Lianyungang from 1 October 2019 to 31 December 2021 and at the Second People's Hospital of Lianyungang from 1 January 2022 to 17 July 2022. Baseline demographic, clinical, and laboratory information of patients were recorded. The outcome was the 3-month modified Rankin Scale (mRS) score. The least absolute shrinkage and selection operator regression were used to select the optimal predictive factors. Multiple logistic regression was performed to establish the nomogram. A decision curve analysis (DCA) was applied to assess the clinical benefit of the nomogram. The calibration and discrimination properties of the nomogram were validated by calibration plots and the concordance index. Results: A total of 823 eligible patients were enrolled. The final model included gender (male; OR 0.555; 95% CI, 0.378-0.813), systolic blood pressure (SBP; OR 1.006; 95% CI, 0.996-1.016), free triiodothyronine (FT3; OR 0.841; 95% CI, 0.629-1.124), National Institutes of Health stroke scale (NIHSS; OR 18.074; 95% CI, 12.264-27.054), Trial of Org 10172 in Acute Stroke Treatment (TOAST; cardioembolic (OR 0.736; 95% CI, 0.396-1.36); and other subtypes (OR 0.398; 95% CI, 0.257-0.609). The nomogram showed good calibration and discrimination (C-index, 0.858; 95% CI, 0.830-0.886). DCA confirmed the clinical usefulness of the model. The dynamic nomogram can be obtained at the website: predict model (90-day prognosis of AIS patients). Conclusion: We established a dynamic nomogram based on gender, SBP, FT3, NIHSS, and TOAST, which calculated the probability of 90-day poor prognosis in AIS patients with standardized treatment.

Aggregation-caused dual-signal response of gold nanoclusters for ratiometric optical detection of cysteine.

Designing ratiometric sensors for cysteine (Cys) monitoring with high accuracy is of great significance for disease diagnosis and biomedical studies. The current ratiometric methods mainly rely on multiplex probes, which not only complicates the operation but also increases the cost, making it difficult for quantitative Cys detection in resource-limited areas. Herein, one-pot prepared gold nanoclusters (Au NCs) that glow red fluorescent were synthesized by employing glutathione as the stabilizer and reducing agent. When Fe3+ is present with Au NCs, the fluorescence is quenched and the scattering is strong because of the aggregation of Au NCs. With introduction of Cys, Cys can efficiently compete with glutathione-modified Au NCs for Fe3+, which leads to increase of fluorescence and decrease of scattering. The ratiometric determination of Cys can be thereby realized by collecting the fluorescence and SRS spectrum simultaneously. The linear range for Cys was 5-30 µM with a detection limit of 1.5 µM. In addition, the sensing system exhibits good selectivity for Cys and shows potential application in biological samples.

Thyroid hormone levels paradox in acute ischemic stroke.

Objective: Accumulating evidence has suggested that thyroid hormone levels affect the prognosis of acute ischemic stroke (AIS), but the results have been inconsistent. Methods: Basic data, neural scale scores, thyroid hormone levels, and other laboratory examination data of AIS patients were collected. The patients were divided into excellent and poor prognosis group at discharge and 90 days after discharge. Logistic regression models were applied to evaluate the relationship between thyroid hormone levels and prognosis. A subgroup analysis was performed based on stroke severity. Results: A number of 441 AIS patients were included in this study. Those in the poor prognosis group were older, with higher blood sugar levels, higher free thyroxine (FT4) levels, and severe stroke (all p < 0.05) at baseline. Free thyroxine (FT4) showed a predictive value (all p < 0.05) for prognosis in the model adjusted for age, gender, systolic pressure, and glucose level. However, after adjustment for types and severity of stroke, FT4 showed insignificant associations. In the severe subgroup at discharge, the change in FT4 was statistically significant (p = 0.015), odds ratio (95% confidence interval) = 1.394 (1.068-1.820) but not in the other subgroups. Conclusions: High-normal FT4 serum levels in patients with severe stroke receiving conservative medical treatment at admission may indicate a worse short-term prognosis.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

Background and purpose: The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD. Methods: We recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People's Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD. Results: (1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057-67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290-28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2. Conclusion: The promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.

Transcriptome Profile Analysis Identifies Candidate Genes for the Melanin Pigmentation of Skin in Tengchong Snow Chickens.

Tengchong Snow chickens are one of the most precious, black-boned chickens in Yunnan province and usually produce black meat. However, we found a small number of white meat traits in the chicken population during feeding. In order to determine the pattern of melanin deposition and the molecular mechanism of formation in the Tengchong Snow chicken, we measured the luminance value (L value) and melanin content in the skin of black meat chickens (Bc) and white meat chickens (Wc) using a color colorimeter, ELISA kit, and enzyme marker. The results showed that the L value of skin tissues in black meat chickens was significantly lower than that of white meat chickens, and the L value of skin tissues gradually increased with an increase in age. The melanin content of skin tissues in black meat chickens was higher than that of white meat chickens, and melanin content in the skin tissues gradually decreased with an increase in age, but this difference was not significant (p > 0.05); the L value of skin tissues in black meat chickens was negatively correlated with melanin content, and the correlation coefficient was mostly above -0.6. In addition, based on the phenotypic results, we chose to perform the comparative transcriptome profiling of skin tissues at 90 days of age. We screened a total of 44 differential genes, of which 32 were upregulated and 12 were downregulated. These DEGs were mainly involved in melanogenesis, tyrosine metabolism and RNA transport. We identified TYR, DCT, and EDNRB2 as possible master effector genes for skin pigmentation in Tengchong Snow black meat chickens through DEGs analysis. Finally, we measured the mRNA of TYR, DCT, MC1R, EDNRB2, GPR143, MITF, and TYRP1 genes through a quantitative real-time polymerase chain reaction (qPCR) and found that the mRNA of all the above seven genes decreased with increasing age. In conclusion, our study initially constructed an evaluation system for the black-boned traits of Tengchong Snow chickens and found key candidate genes regulating melanin deposition, which could provide an important theoretical basis for the selection and breeding of black-boned chickens.

Ratiometric optical detection of pyrophosphate based on aggregation-caused dual-signal response of gold nanoclusters.

Sensing of pyrophosphate ion (PPi) has received much attention due to the strong demand for clinical diagnostics. Here, based on gold nanoclusters (Au NCs), a ratiometric optical detection method for PPi is developed by simultaneously detecting the dual signals of fluorescence (FL) and second-order scattering (SOS). The PPi is detected by inhibiting the formation of aggregates of Fe3+ with Au NCs. Binding of Fe3+ to Au NCs causes aggregation of Au NCs, which leads to fluorescence quenching and scattering increasing. The presence of PPi can competitively bind Fe3+ to re-disperse the Au NCs and finally recover the fluorescence and reduce the scattering signal. The designed PPi sensor shows a high sensitivity with a linear range 5-50 µM and a detection limit of 1.2 µM. In addition, the assay has excellent selectivity for PPi, which makes its application in real biological samples extremely valuable.