Neu5Gc regulates decidual macrophages leading to abnormal embryo implantation.

Repeated implantation failure (RIF) is one of the most prominent problems in the field of assisted reproduction. Neu5Gc on the surface of decidual macrophages (dMΦ) leads to different activation patterns of dMΦ, which affects embryo implantation and development. Cmah-/- (Neu5Gc-deficient) mice induced to produce anti-Neu5Gc antibodies in vivo were given a special diet rich in Neu5Gc and their fertility was monitored. The long-term diet rich in Neu5Gc induced the decrease of endometrial receptivity of female mice. The pregnancy rate of female mice fed the normal diet was 63.6% (n = 11) and the average number of embryos was 9.571 ± 1.272, while the pregnancy rate of female mice fed the diet rich in Neu5Gc was 36.4% (n = 11) and the average number of embryos in pregnant mice was 5.750 ± 3.304. The intake of Neu5Gc and the production of anti-Neu5Gc antibody led to M1 polarization of endometrial dMΦ and abnormal embryo implantation.

A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Epidemiological trends and mid-term to long-term outcomes of acetabular fractures in the elderly in China.

PURPOSE: To explore the epidemiological trends in acetabular fracture and report the mid-term to long-term clinical outcomes of the elderly treated with operation. METHODS: Retrospective study. Patients aged ≥ 14 years with operative treatment of the Acetabular fracture from Jan 2010 to Dec 2019 at a level-1 trauma centre were identified to analyze the epidemiological trends, and the difference in fracture patterns between young and elderly patients (≥ 60 years old) were compared. The elderly patients were followed up to evaluate their clinical outcomes and satisfaction degree (worst to best: 0 to10). The patients were divided into the 2010-2014 group and the 2015-2019 group according to the year of admission, and the clinical outcomes of the two groups were compared to verify the stability from mid-term to long-term after surgery for acetabular fracture. RESULTS: A total of 1024 patients (mean age 43.35 years, range 14-86 years) with acetabular fractures received operative treatment in this decade. The mean age of the acetabular fracture patients increased from 41.1 years to 47.7 years, and the proportion of elderly patients increased from 5.7% to 24.0%, with some volatility. The ratio of male to female decreased year by year, and the proportion of female patients increased with age. And the anterior fracture patterns were more common in the elderly patients compared to the young patients (P < 0.001). 118 elderly patients (82 males, 36 females; mean age 66.91 years, range 60-86 years) were followed-up (mean 77.4 months, range 35-152 months). The overall mortality rate of the elderly patients was 7.69% (9/118). The Harris hip score of those alive patients was 90.41 ± 12.91 points (excellent and good rate 84.4%). 87 patients completed the SF-12 with a normal HRQoL (PCS 50.49 ± 8.88 points; MCS 55.66 ± 8.86 points). 90.8% of the patients achieved a satisfaction score of 9 or higher. And there was no significant difference in clinical outcomes between the 2010-2014 group and the 2015-2019 group (P > 0.05). CONCLUSIONS: In conclusion, acetabular fractures presented an obvious ageing trend in China, and the fracture patterns of the elderly patients differed from those in the young patients. Operative treatment for elderly acetabular fractures yielded satisfactory and persistent clinical outcomes from mid-term to long-term clinical.

Determination of components in Radix paeoniae rubra based on QAMS.

The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.

Optical fiber surface waveguide with Fabry-Perot cavity for sensing.

A parallel structured optical fiber Fabry-Perot interferometer sensor is proposed and demonstrated for refractive index and strain sensing with low temperature cross sensitivity. The device consists of two Fabry-Perot cavities fabricated by a femtosecond laser: one is inscribed in the fiber surface waveguide and used for sensing, and the other one is located in the fiber core for referencing. Part of the light propagating in the fiber core can be directed to the fiber surface waveguide via an X coupler. Because of the evanescent field, the light traveling along the fiber surface waveguide interacts with the surrounding medium and enables external refractive index sensing. The measurement sensitivity of the device is enhanced due to the Vernier effect associated with the parallel structured two Fabry-Perot interferometers. The sensitivities of ∼843.3nm/RIU and ∼101.8pm/µÎµ have been obtained for refractive index and strain, respectively, and the corresponding temperature cross sensitivities are ∼9.6×10-6RIU/∘C and ∼7.956×10-2µÎµ/∘C, respectively. The device is featured with high robustness, compact size, and large sensitivity.

Nine glycolysis-related gene signature predicting the survival of patients with endometrial adenocarcinoma.

BACKGROUND: Endometrial cancer is the fourth most common cancer in women. The death rate for endometrial cancer has increased. Glycolysis of cellular respiration is a complex reaction and is the first step in most carbohydrate catabolism, which was proved to participate in tumors. METHODS: We analyzed the sample data of over 500 patients from TCGA database. The bioinformatic analysis included GSEA, cox and lasso regression analysis to select prognostic genes, as well as construction of a prognostic model and a nomogram for OS evaluation. The immunohistochemistry staining, survival analysis and expression level validation were also performed. Maftools package was for mutation analysis. GSEA identified Glycolysis was the most related pathway to EC. qRT-PCR verified the expression level of hub gene in clinical samples. RESULTS: According to the prognostic model using the train set, 9 glycolysis-related genes including B3GALT6, PAM, LCT, GMPPB, GLCE, DCN, CAPN5, GYS2 and FBP2 were identified as prognosis-related genes. Based on nine gene signature, the EC patients could be classified into high and low risk subgroups, and patients with high risk score showed shorter survival time. Time-dependent ROC analysis and Cox regression suggested that the risk score predicted EC prognosis accurately and independently. Analysis of test and train sets yielded consistent results A nomogram which incorporated the 9-mRNA signature and clinical features was also built for prognostic prediction. Immunohistochemistry staining and TCGA validation showed that expression levels of these genes do differ between EC and normal tissue samples. GSEA revealed that the samples of the low-risk group were mainly concentrated on Bile Acid Metabolism. Patients in the low-risk group displayed obvious mutation signatures compared with those in the high-risk group. The expression levels of B3GALT6, DCN, FBP2 and GYS2 are lower in tumor samples and higher in normal tissue samples. The expression of CAPN5 and LCT in clinical sample tissues is just the opposite. CONCLUSION: This study found that the Glycolysis pathway is associated with EC and screened for hub genes on the Glycolysis pathway, which may serve as new target for the treatment of EC.

Mesenchymal stem cells alleviate atherosclerosis by elevating number and function of CD4(+)CD25 (+)FOXP3 (+) regulatory T-cells and inhibiting macrophage foam cell formation.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaques inside arteries, leading to narrowing and blockage. Potential therapeutic strategies include expanding the population of regulatory T-cells (Tregs) to enhance atheroprotective immunity, and inhibiting the formation of macrophage foam cells. Here, we studied the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on atherosclerotic plaque formation in Apolipoprotein E(-/-) (ApoE-KO) mice, and elucidated the underlying mechanism. BM-MSCs isolated from 4 week-old ApoE-KO mice were evaluated by flow cytometry for expression of MSC-specific markers. Thirty eight week-old ApoE-KO mice were randomly divided into three experimental groups (n = 10 per group): 1. MSC group-received BM-MSCs intravenously; 2. Vehicle group-received DMEM; 3. Control group-did not receive any treatment. Administration of MSCs resulted in a marked decrease in the size of atherosclerotic plaques 3 months after treatment. In addition, the number and function of CD4(+)CD25(+)FOXP3(+) regulatory T-cells (Tregs) in cultured splenocytes, and the expression of FOXP3 at both mRNA and protein levels, was significantly increased in the MSC group. In vitro experiments further indicated that the formation of macrophage foam cells was inhibited by treatment with MSCs, accompanied by a significant downregulation in CD36 and scavenger receptor A (SRA). Our findings suggest that MSCs play an atheroprotective role by enhancing the number and function of Tregs and inhibiting the formation of macrophage foam cells. Hence, administration of MSCs to atherosclerotic patients might have significant clinical benefits.

Changes of naturally occurring CD4(+)CD25(+) FOXP3(+) regulatory T cells in patients with acute coronary syndrome and the beneficial effects of atorvastatin treatment.

To determine the number and function of naturally occurring CD4(+)CD25(+)FOXP3(+) regulatory T cells (nTregs) in patients with acute coronary syndrome (ACS) and to determine the effects of a low dose of atorvastatin treatment (20 mg/day) on nTregs.Patients with ACS were randomly divided into a group receiving conventional therapy (n = 60) or conventional therapy supplemented with atorvastatin (20 mg/day) (n = 60). A group of healthy volunteers that did not suffer from ACS was used as controls (n = 60). T lymphocytes were isolated from ACS patients, both before and 4 weeks after treatment, or control patients and the percentage of nTregs was determined by flow cytometry. Serum levels of cytokines were determined by enzyme-linked immunosorbent assays. A mixed lymphocyte reaction was used to determine the ability of nTregs to inhibit proliferation of effector T cells. Quantitative PCR and Western blot were used to analyze (forkhead box P3) FOXP3 mRNA transcript levels and the expression of FOXP3 protein.In ACS patients, the percentage and inhibitory properties of nTregs were reduced, IFN-γ and hsCRP levels were increased, and IL-10 and TGF-ß1 levels were lowered. Atorvastatin treatment increased the percentage and inhibitory ability of nTregs, decreased serum IFN-γ and hsCRP levels, and decreased IL-10 and TGF-ß1 levels, as compared with the non-atorvastatin group.Our findings suggest that nTregs play an atheroprotective role in atherosclerosis. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on nTregs and restoration of immune homeostasis.

Molecular cloning and characterization of NPR1 gene from Arachis hypogaea.

The NPR1 gene was an important regulator for a plant disease resistance. The cDNA of NPR1 gene was cloned from peanut cultivar Ri Hua 1 by rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The full length cDNA of Arachis hypogaea NPR1 consisted of 2,078 base pairs with a 1,446 bp open-reading frame encoding 481 amino acids. The predicted NPR1 contained the highly conserved functional domains (BTB/POZ domain from M1 to D116), protein-protein interaction domains (three ankyrin repeats from K158 to L186; N187 to L217 and R221 to D250) and one NPR1-like domain (C262 to S469). The DNA sequence of the NPR1 gene was 2,332 or 2,223 bp. Both two sequences contained three introns and four exons. The NPR1 transcripts were expressed mainly in roots and leaves, while fewer signals were detected in the stems. Amount of the NPR1 transcript was significantly increased 1 h after salicylic acid challenge and was eventually 5.3 times greater than that in the control group. Both the DNA sequence and the coding sequence were obtained from eight cultivars and nine wild species of Arachis. Maximum likelihood analyses of d N/d S ratios for 25 sequences from different species showed that different selection pressures may have acted on different branches.

Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

Global incidence trends of autoimmune diseases from 1990 to 2021 and projections to 2050: A systemic analysis of the global burden of disease study 2021.

BACKGROUND: The analysis of the incidence trends of four autoimmune diseases (ADs) globally from 1990 to 2021, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), and psoriasis, reveals significant patterns of change, which further projects the incidence of these diseases at the global, regional, and national levels up to the year 2050. METHODS: The estimates for the number of incident cases and age-standardized incidence rates (ASIR), along with the 95 % uncertainty intervals (UI) for RA, IBD, MS and psoriasis, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global incidence trends of these four ADs from 1990 to 2021. Additionally, a Bayesian age-period-cohort model was employed to project the number of new cases and incidence rates of these four ADs up to 2050. RESULTS: From 1990 to 2021, the global ASIR of MS showed a declining trend (EAPC = -0.02 %, 95 % UI: -0.07 to 0.03), while the global ASIRs of IBD (EAPC = 0.29 %, 95 % UI: 0.20 to 0.38), RA (EAPC = 0.49 %, 95 % UI: 0.46 to 0.52), and psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.26) demonstrated increasing trends. From 2022 to 2050, the global ASIRs of these four ADs are projected to rise, with the number of cases for all these conditions expected to continue increasing. CONCLUSIONS: The global incidence trends and projected changes in ADs reveal that the burden of ADs is expected to continue growing in the future, underscoring the necessity for developing targeted policies to address this emerging challenge.

Novel Retractor-Camera System Facilitates Less Traumatic Minimally Invasive Procedures and Declutters the Operation Field.

OBJECTIVE: To develop a novel endoscopic system that reduces trauma to the patient and declutters the surgical field for the surgeon in minimally invasive heart valve surgery. METHODS: We designed and developed a retractor-camera combination for minimally invasive heart surgery; the cable and camera were connected to the underbelly of the left atrial retractor blade to provide an illuminated, wide-angle view of the mitral valve. We conducted ex vivo, in vivo, and, ultimately, a first-in-man randomized, nonanonymized clinical trial on 20 patients who required minimally invasive mitral valve surgery. Data from the preoperative period and the immediate postoperative period were gathered, and patients were followed for 3 months. RESULTS: Our camera-retractor combo demonstrated safe and efficient exposure and vision in all detailed studies. The total operation time for the intervention group (316.5 ± 65.1 min) was slightly shorter than for the control group (317.5 ± 50.8 min). There was no significant difference in the ability to provide exposure of the mitral valve and surrounding left atrial tissue for both control and test articles. The novel camera-retractor reduced clutter in the operation field substantially and eliminated chest penetration for the camera. We also observed that the camera did not fog, did not stain with blood, and did not require frequent corrections to its position. CONCLUSIONS: We launch a novel atrial retraction-imaging platform that is less invasive for the patient and eliminates clutter and redundant movements for the surgeon.

[Effects of soothing liver and invigorating spleen recipes on the mRNA and protein expression of TLR4 in hepatic tissues of rats with NASH].

OBJECTIVE: To research the effects of soothing liver and invigorating spleen recipes on expression of TLR4 mRNA and protein expression in hepatic tissue of rats with non-alcoholic steatohepatitis and its mechanism. METHODS: 72 male SD rats were randomly divided into 8 groups: normal group, model group, high-dose soothing liver group (receiving gavage of Chaihu Shugan Powder 9. 6 g/kg), low-dose soothing liver group (receiving gavage of Chaihu Shugan Powder 3.2 g/kg), high-dose invigorating spleen group (receiving gavage of Shen Ling Baizhu Powder 30 g/kg), low-dose invigorating spleen group (receiving gavage of Shen Ling Baizhu Powder 10 g/kg), high-dose integrated Group (receiving gavage of Chaihu Shugan Powder and Shen Ling Baizhu Powder combination recipes 39.6 g/kg), low-dose integrated Group (receiving gavage of Chaihu Shugan Powder and Shen Ling Baizhu Powder combination recipes 13.2 g/kg), 9 rats were in each group. Used high fat diet (10 mL/kg) to establish experiment model of NASH rat. At the end of the sixteenth weeks, the levels of serum lipids, liver lipids and serum aminotransferase were measured by automatic biochemical analyzer; Liver pathology was analyzed by HE and Oil red O staining; TLR4 mRNA was assayed by real-time fluorescent quantitative polymerase chain reaction (RT Q-PCR); TLR4 protein was detected by Western blot. RESULTS: Compared with normal group, the levels of TC, LDL-C in the serum, TC,TG as well as the expression of TLR4 mRNA and protein in the hepatic tissue were dramatically increased in model group (P < 0.01). Compared with the model group, the levels of serum lipids, liver lipids, the expression of TLR4 mRNA and protein in the hepatic tissue were decreased in each treatment group (P < 0.05 or P < 0.01). CONCLUSION: Soothing liver and invigorating spleen recipes can inhibit hepatic TLR4 expression, that may be one of their therapeutic mechanisms. There is much difference between high-does and low-does treatment groups in various testing items, which shows that there is does-effect relationship in intervention NASH.

[Effects of soothing liver and invigorating spleen recipes on NF-kappaB signal pathway related genes and proteins in primary hepatocytes of rats with NASH].

OBJECTIVE: To observe the effects of soothing liver and invigorating spleen recipes on NF-kappaB signal pathway related genes and proteins in primary hepatocytes of rats with NASH. METHODS: SD male rats were randomly divided into 8 groups: normal, model, high/low-dose soothing liver group, high/low-dose invigorating spleen group, high/low-dose integrated group. 15 rats in each group. The NASH model rats were induced by feeding high-fat diet (HFD). The treatment lasted for 16 weeks. Then TC, TG in the liver tissue and serum were determined with automatic biochemical analyzer. HE staining and oil red O staining were operated to observe the pathological changes. Another 6 rats of each group were taken respectively and collagenase (Type IV) was perfused to digest liver tissue with the circulation in vitro to separate hepatocytes. The expression levels of IKK(beta), NF-kappaB mRNA, proteins and phosphorylated IKK(beta) protein in hepatocytes of rats from each group were detected by Real-time Q-PCR and Western Blotting, respectively. RESULTS: Compared with normal group, liver histopathology was changed and levels of TC and TG were elevated in model group indicating hepatocytes had lipid accumulation and lipid metabolic disturbance obviously; The levels of serum TC, and hepatic homogenate TC, TG as well as the expression of IKK(beta) NF-kappa-B mRNA, proteins and phosphorylated IKK(beta) protein in hepatocytes were dramatically increased in model group (P < 0.01). Compared with the model group, the levels of IKK(beta), NF-kappaB mRNA expression were decreased most significanly in the invigorating spleen (with high dose) group and the integrated group (with high dose) (P < 0.01 or P < 0.05). The expression levels of the IKK(beta), NF-kappaB proteins and the phosphorylated IKK(beta) protein in hepatocytes were decreased significaniy in the treatment groups (P < 0.01 or P < 0.05), especially for the invigorating spleen (with high dose) group and the integrated (with high dose). CONCLUSION: Soothing liver and invigorating spleen recipes have effect on NASH rats induced by HFD and its mechanism may be related to the suppression of IKK(beta)/NF-kappaB signal pathway related genes and proteins. And the effect probably has a dose response relationship.

Multidimensional performance assessment, government competition and ecological welfare performance.

Improving the efficiency of converting natural resources into social benefits is an important issue for sustainable development in today's world. Based on this background this paper applies the super-efficient SBM model with non-expected output to measure the ecological welfare performance (EWP) of Chinese provinces from 2005-2019, and explores the relationship between government competition and EWP under different assessment systems. The research results show that government competition under economic performance assessment is self-interested and short-sighted, which can negatively affect ecological welfare performance in the current period as well as in the next four years. In contrast, government competition under the environmental assessment system promotes EWP in both the current and long term, balancing short-term and long-term benefits. The results of the spatial GMM found that government competition under economic performance appraisal can deteriorate EWP in local as well as surrounding areas, but government competition under the environmental assessment system can achieve an increase in local ecological welfare performance and the spillover effect is not significant. To alleviate the limitations of a single appraisal system, this paper incorporates both economic and ecological appraisals into the multidimensional appraisal system. When the weights of both are between 1:9 and 3:7, the government competition under multidimensional performance appraisal can promote both current and longer-term EWP, and achieve its own ecological welfare performance without affecting the surrounding areas.

Neurosyphilis with positive anti-N-methyl-D-aspartate receptor antibody: a case report.

A case of neurosyphilis with a positive anti-N-methyl-D-aspartate receptor (NMDAR) antibody was reported. A 54-year-old man who presented with acute memory deficits was admitted to our hospital. Acute ischemic stroke (AIS) was initially considered, and he was prescribed intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). However, the intermittent onset of episodic memory and orientation disorder still occurred. No diffusion restriction was indicated by magnetic resonance imaging (MRI), and subclinical seizures were frequently found by electroencephalogram (EEG). Rapid plasma reagin (RPR) test of serum showed positive results for syphilis. Analysis of cerebrospinal fluid (CSF) revealed elevated leukocyte count and protein level. RPR test, Treponema pallidum particle agglutination (TPPA) assay, and Treponema pallidum antibody (TP-Ab) in CSF showed positive results, and the anti-NMDAR antibodies were positive in CSF and serum. Finally, the patient was diagnosed with neurosyphilis with a positive anti-NMDAR antibody. The clinical symptoms were improved, and the leukocyte count in CSF was reduced after treatment with intravenous penicillin G and levetiracetam. This case suggests that in cases with positive results for neurosyphilis and NMDAR antibodies, the proper treatment has to be decided based on all of the available clinical and diagnostic testing data.

Unveiling the Therapeutic Potentials of Mushroom Bioactive Compounds in Alzheimer's Disease.

Alzheimer's disease (AD) stands as a prevailing neurodegenerative condition (NDs), leading to the gradual deterioration of brain cells and subsequent declines in memory, thinking, behavior, and emotion. Despite the intensive research efforts and advances, an effective curative treatment for the disease has not yet been found. Mushrooms, esteemed globally for their exquisite flavors and abundant nutritional benefits, also hold a wealth of health-promoting compounds that contribute to improving AD health. These compounds encompass polysaccharides, proteins, lipids, terpenoids, phenols, and various other bioactive substances. Particularly noteworthy are the potent neuroprotective small molecules found in mushrooms, such as ergothioneine, erinacine, flavonoids, alkaloids, ergosterol, and melanin, which warrant dedicated scrutiny for their therapeutic potential in combating AD. This review summarizes such positive effects of mushroom bioactive compounds on AD, with a hope to contribute to the development of functional foods as an early dietary intervention for this neurodegenerative disease.

Neurosarcomatous amelanotic transformation of malignant melanoma presenting as malignant periopheral nerve sheath tumor: Rare case report.

RATIONALE: Malignant melanoma (MM) is notorious for its remarkable morphological variation and aberrant histopathological patterns. In addition, Malignant Periopheral Nerve Sheath Tumor (MPNST) is an uncommon but aggressive soft tissue sarcoma. Because of the common embryological origin of melanocytes and Schwann cells in the neural crest, discriminating between a particular type of MM and MPNST can be difficult, particularly when they are amelanotic. Our goal is to increase awareness among clinicians of the rare variations of MM and the importance of medical history in improving the accuracy of the final clinical diagnosis. PATIENT CONCERNS: A 68-year-old man was admitted to the hospital due to pain in his right ankle, which had persisted for 8 months, along with swelling for 4 months. Medical history revealed delayed healing of right plantar for 5 years after a traumatic injury. DIAGNOSES: The ankle mass was initially diagnosed as MPNST through biopsy. After reviewing the patient's medical history and receiving the final pathological report following amputation, we have revised the diagnosis to metastatic amelanotic desmoplastic melanoma in the ankle part and lentigo maligna melanoma in the plantar part. This is due to both lesions displaying positive markers or mutated genes in immunohistology and Gene Mutation Detection, indicating homology between the 2 tumors. INTERVENTIONS: Due to the malignant characteristics of the tumor and the patient's wishes, amputation of the right lower leg was carried out. OUTCOMES: Subsequently, the patient was treated with interferon-γ and immunosuppressant PD-1 inhibitor, and survived for 1 year after amputation. LESSONS: Clinical data, immunohistochemisty biomarkers and genes detection results can serve as valuable evidence for pathologists and clinicians in identifying the disease process. Collaborative efforts between clinicians and scientists are crucial in order to identify specific markers that can effectively differentiate between the 2 tumors, thereby enhancing the conclusiveness of the diagnosis.

TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study.

Objective: To explore the difference in gut microbiota between different traditional Chinese Medicine (TCM) syndromes in patients with colorectal cancer (CRC) and its internal relationship. Methods: From June 2020 to August 2021, 109 colorectal cancer patients with a clear pathological diagnosis who had not yet undergone surgery or chemotherapy were classified according to the TCM syndrome classification, and the feces samples of 109 patients with preoperative colorectal cancer were collected. 16s rRNA gene sequencing was used to determine gut microbiota diversity and abundance in CRC patients with different TCM syndrome, and LEfSe analysis was made to screen different TCM syndrome for differential representative microbiota. Results: 109 patients were divided into 5 syndromes by TCM syndrome classification, which were Liver and Kidney Yin Deficiency Syndrome (LKYDS, n = 19), Spleen Deficient Qi Stagnation Syndrome (SDQSS, n = 30), Stasis and Poison Obstruction Syndrome (SPOS, n = 17), Damp-Heat Syndrome (DHS, n = 30), Qi and Blood Deficiency Syndrome (QBDS, n = 13). Alpha diversity index showed significant differences among the five groups of TCM syndromes, with Shannon index being highest in the SDQSS group and lowest in the LKYDS (p = 0.003). ACE index being highest in the SDQSS group and lowest in the SPOS (p = 0.010). PD whole tree index being highest in the SDQSS group and lowest in the SPOS (p = 0.017). Similarly, beta diversity showed significant differences among the five groups of TCM syndromes, with principal coordinate analysis (PCo1 = 31.86 %, PCo2 = 5.62 %) showing separation and coincidence between the groups, and Adonis group differences showing coincidence between the QBDS-LKYDS (p = 0.702), QBDS-DHS (p = 0.133), and SDQSS-DHS (p = 0.260) groups. LEfSe analysis revealed that the representative microbiota of DHS patients was Dialister sp Marseille P5638 (LDA = 3.05, p＜0.001), the representative microbiota of SPOS patients was Oscillospirales (LDA = 4.78, p = 0.029), the representative microbiota of SDQSS patients was Selenomonadaceae (LDA = 3.94, p = 0.003), the representative microbiota of LKYDS patients was Dialister (LDA = 4.19, p = 0.001), and the representative microbiota of QBDS patients was Akkermansia muciniphila (LDA = 4.23, p = 0.006). Conclusions: There are significant differences in gut microbiota between different TCM syndromes in CRC patients. The five microbiota, Dialister sp Marseille P5638, Oscillospirales, Selenomonadaceae, Dialister, and Akkermansia muciniphila, may be differential markers of TCM syndrome in CRC and are expected to be one of the bases for accurate TCM syndrome differentiation of CRC.

BRD4770 inhibits vascular smooth muscle cell proliferation via SUV39H2, but not EHMT2 to protect against neointima formation.

The behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers. However, whether and how BRD4770 regulates the behavior of VSMCs remain unknown. In this study, we evaluate the cellular effect of BRD4770 on VSMCs by series of experiments in vivo and ex vivo. We demonstrated that BRD4770 inhibited VSMCs' growth by blockage in G2/M phase in VSMCs. Moreover, our results demonstrated that the inhibition of proliferation was independent on autophagy or EHMT2 suppression which we previous reported. Mechanistically, BRD4770 exhibited an off-target effect from EHMT2 and our further study reveal that the proliferation inhibitory effect by BRD4770 was associated with suppressing on SUV39H2/KTM1B. In vivo, BRD4770 was also verified to rescue VIH. Thus, BRD4770 function as a crucial negative regulator of VSMC proliferation via SUV39H2 and G2/M cell cycle arrest and BRD4770 could be a molecule for the therapy of vascular restenosis.