Large-Scale Chromosomal Changes Lead to Genome-Level Expression Alterations, Environmental Adaptation, and Speciation in the Gayal (Bos frontalis).

Determining the functional consequences of karyotypic changes is invariably challenging because evolution tends to obscure many of its own footprints, such as accumulated mutations, recombination events, and demographic perturbations. Here, we describe the assembly of a chromosome-level reference genome of the gayal (Bos frontalis) thereby revealing the structure, at base-pair-level resolution, of a telo/acrocentric-to-telo/acrocentric Robertsonian translocation (2;28) (T/A-to-T/A rob[2;28]). The absence of any reduction in the recombination rate or genetic introgression within the fusion region of gayal served to challenge the long-standing view of a role for fusion-induced meiotic dysfunction in speciation. The disproportionate increase noted in the distant interactions across pro-chr2 and pro-chr28, and the change in open-chromatin accessibility following rob(2;28), may, however, have led to the various gene expression irregularities observed in the gayal. Indeed, we found that many muscle-related genes, located synthetically on pro-chr2 and pro-chr28, exhibited significant changes in expression. This, combined with genome-scale structural variants and expression alterations in genes involved in myofibril composition, may have driven the rapid sarcomere adaptation of gayal to its rugged mountain habitat. Our findings not only suggest that large-scale chromosomal changes can lead to alterations in genome-level expression, thereby promoting both adaptation and speciation, but also illuminate novel avenues for studying the relationship between karyotype evolution and speciation.

Ether Naphthotube Host-Guest Complexes and [2]Rotaxanes with Dications.

The interactions between ether naphthotube and a series of dication guests in organic solution were investigated. It was found that ether naphthotube formed stable host-guest complexes selectively with these guests in a 1 : 1 stoichiometric ratio with association constants ranging from 102 to 106 M-1, which were confirmed by 1H-NMR spectra and ITC experiments. The host-guest interactions are driven by enthalpy change as the entropic factors are unfavorable. Positive correlations between ΔH and ΔS have been observed in the host-guest complexes. Furthermore, the para-substitution of the guests can significantly affect the binding affinities through a combination of field/inductive and resonance effects by following a linear free energy relationship. Based on the host-guest complexes composed of ether naphthotube and organic cations, two interlocked [2]rotaxanes were prepared by cationization reaction and Huisgen cycloaddition between the cations and the stopper components. The ether naphthotube-based host-guest complexes are useful for creating sophisticated interlocked molecules.

LincRNA-ROR/miR-145/ZEB2 regulates liver fibrosis by modulating HERC5-mediated p53 ISGylation.

The tumor suppressor p53 has been implicated in the pathogenesis of liver fibrosis. HERC5-mediated posttranslational ISG modification of the p53 protein is critical for controlling its activity. Here, we demonstrated that the expression of HERC5 and ISG15 is highly elevated, whereas p53 is downregulated, in fibrotic liver tissues of mice and transforming growth factor-ß1 (TGF-ß1)-induced LX2 cells. HERC5 siRNA clearly increased the protein expression of p53, but the mRNA expression of p53 was not obviously changed. The inhibition of lincRNA-ROR (ROR) downregulated HERC5 expression and elevated p53 expression in TGF-ß1-stimulated LX-2 cells. Furthermore, the expression of p53 was almost unchanged after TGF-ß1-stimulated LX-2 cells were co-transfected with a ROR-expressing plasmid and HERC5 siRNA. We further confirmed that miR-145 is a target gene of ROR. In addition, we also showed that ROR regulates the HERC5-mediated ISGylation of p53 through mir-145/ZEB2. Together, we propose that ROR/miR-145/ZEB2 might be involved in the course of liver fibrosis by regulating ISGylation of the p53 protein.

Kupffer cell pyroptosis mediated by METTL3 contributes to the progression of alcoholic steatohepatitis.

Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1ß (IL-1ß). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH.

The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study.

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.

Dapagliflozin Suppresses Isoprenaline-Induced Cardiac Hypertrophy Through Inhibition of Mitochondrial Fission.

ABSTRACT: Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice. On day 14 after surgery, echocardiography showed that left ventricle mass (LV mass), interventricular septum, left ventricle posterior wall diastole, and left ventricular posterior wall systole were significantly increased, and ejection fraction was decreased compared with control mice. Masson and Wheat Germ Agglutinin staining indicated enhanced myocardial fibrosis and cell morphology compared with control mice. Importantly, these effects were inhibited by DAPA treatment in ISO-induced mice. In H9c2 cells and neonatal rat cardiomyocytes, we found that mitochondrial fragmentation and mitochondrial oxidative stress were significantly augmented in the ISO-induced group. However, DAPA rescued the cardiac hypertrophy in ISO-induced H9c2 cells and neonatal rat cardiomyocytes. Mechanistically, we found that DAPA restored the PIM1 activity in ISO-induced H9c2 cells and subsequent increase in dynamin-associated protein 1 (Drp1) phosphorylation at S616 and decrease in Drp1 phosphorylation at S637 in ISO-induced cells. We found that DAPA mitigated ISO-induced cardiac hypertrophy by suppressing Drp1-mediated mitochondrial fission in a PIM1-dependent fashion.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Biopsy-free AI-aided precision MRI assessment in prediction of prostate cancer biochemical recurrence.

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Study on an Animal Model of Seawater Immersion Injury Following Hemorrhagic Shock.

INTRODUCTION: To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). METHODS: Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. RESULTS: After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. CONCLUSIONS: The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock.

mTORC2 acts as a gatekeeper for mTORC1 deficiency-mediated impairments in ILC3 development.

Group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function. Recent studies have investigated the role of the mammalian target of rapamycin complex (mTOR) in ILC3s, whereas the mTORC1-related mechanisms and crosstalk between mTORC1 and mTORC2 involved in regulating ILC3 homeostasis remain unknown. In this study, we found that mTORC1 but not mTORC2 was critical in ILC3 development, IL-22 production, and ILC3-mediated intestinal homeostasis. Single-cell RNA sequencing revealed that mTORC1 deficiency led to disruption of ILC3 heterogeneity, showing an increase in differentiation into ILC1-like phenotypes. Mechanistically, mTORC1 deficiency decreased the expression of NFIL3, which is a critical transcription factor responsible for ILC3 development. The activities of both mTORC1 and mTORC2 were increased in wild-type ILC3s after activation by IL-23, whereas inhibition of mTORC1 by Raptor deletion or rapamycin treatment resulted in increased mTORC2 activity. Previous studies have demonstrated that S6K, the main downstream target of mTORC1, can directly phosphorylate Rictor to dampen mTORC2 activity. Our data found that inhibition of mTORC1 activity by rapamycin reduced Rictor phosphorylation in ILC3s. Reversing the increased mTORC2 activity via heterozygous or homozygous knockout of Rictor in Raptor-deleted ILC3s resulted in severe ILC3 loss and complete susceptibility to intestinal infection in mice with mTORC1 deficiency (100% mortality). Thus, mTORC1 acts as a rheostat of ILC3 heterogeneity, and mTORC2 protects ILC3s from severe loss of cells and immune activity against intestinal infection when mTORC1 activity is diminished.

A Theoretical Study on the Underlying Factors of the Difference in Performance of Organic Solar Cells Based on ITIC and Its Isomers.

Recently, non-fullerene-based organic solar cells (OSCs) have made great breakthroughs, and small structural differences can have dramatic impacts on the power conversion efficiency (PCE). We take ITIC and its isomers as examples to study their effects on the performance of OSCs. ITIC and NFBDT only differed in the side chain position, and they were used as models with the same donor molecule, PBDB-T, to investigate the main reasons for the difference in their performance in terms of theoretical methods. In this work, a detailed comparative analysis of the electronic structure, absorption spectra, open circuit voltage and interfacial parameters of the ITIC and NFBDT systems was performed mainly by combining the density functional theory/time-dependent density functional theory and molecular dynamics simulations. The results showed that the lowest excited state of the ITIC molecule possessed a larger ∆q and more hybrid FE/CT states, and PBDB-T/ITIC had more charge separation paths as well as a larger kCS and smaller kCR. The reason for the performance difference between PBDB-T/ITIC and PBDB-T/NFBDT was elucidated, suggesting that ITIC is a superior acceptor based on a slight modulation of the side chain and providing a guiding direction for the design of superior-performing small molecule acceptor materials.

Precise Recognition in Water by an Endo-Functionalized Cavity: Tuning the Complementarity of Binding Sites.

Precise binding towards structurally similar substrates is a common feature of biomolecular recognition. However, achieving such selectivity-especially in distinguishing subtle differences in substrates-with synthetic hosts can be quite challenging. Herein, we report a novel design strategy involving the combination of different rigid skeletons to adjust the distance between recognition sites within the cavity, which allows for the highly selective recognition of hydrogen-bonding complementary substrates, such as 4-chromanone. X-ray single-crystal structures and density functional theory calculations confirmed that the distance of endo-functionalized groups within the rigid cavity is crucial for achieving high binding selectivity through hydrogen bonding. The thermodynamic data and molecular dynamics simulations revealed a significant influence of the hydrophobic cavity on the binding affinity. The new receptor possesses both high selectivity and high affinity, which provide valuable insights for the design of customized receptors.

Soluble Klotho-integrin ß1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Association of lactate to albumin ratio and bicarbonate with short-term mortality risk in patients with acute myocardial infarction.

BACKGROUND: Previous studies have indicated that the ratio of lactate/albumin (L/A) has predictive value for the prognosis of critically ill patients with heart failure. Some studies have also indicated that a low serum bicarbonate concentration is inversely related to the mortality risk of patients with cardiogenic shock. However, the value of bicarbonate and the L/A ratio for predicting the mortality risk of patients with acute myocardial infarction (AMI) is still unclear. We therefore conducted a retrospective study to research this problem. METHODS: The subjects of this study were patients with AMI, and the data source was the Medical Information Mart for Intensive Care III database. The primary endpoint was 30-day all-cause mortality after admission. The Receiver operating characteristic (ROC) curve was used to compare the predictive value of L/A ratio, lactate and albumin for end-point events. The effects of different L/A ratio levels and different bicarbonate concentrations on 7-day and 30-day all-cause mortality were compared using Kaplan-Meier (K-M) curves. Hazard ratios for different L/A ratio and different bicarbonate concentrations were investigated using COX proportional hazards models. RESULTS: The Area Under Curve (AUC) of L/A ratio, lactate, and albumin were 0.736, 0.718, and 0.620, respectively. (1) L/A ratio: The patients were divided into three groups according to their L/A ratio: tertile T1 (L/A ratio ≤ 0.47), tertile T2 (L/A ratio ≤ 0.97), and tertile T3 (L/A ratio > 0.97). The T2 and T3 groups had higher 30-day all-cause mortality risks than the T1 group. The restricted cubic spline (RCS) model indicated that there was a nonlinear relationship between L/A ratio and 30-day mortality (P < 0.05). (2) Bicarbonate concentration: The patients were also divided into three groups based on their bicarbonate concentration: G1 (22-27 mmol/L), G2 (< 22 mmol/L), and G3 (> 27 mmol/L). The G2 and G3 groups had higher 30-day all-cause mortality risks than the G1 group. The RCS model indicated that there was a nonlinear relationship between bicarbonate concentration and 30-day mortality (P < 0.05). The RCS model indicated that there was a nonlinear relationship between hemoglobin level and 30-day all-cause mortality (P < 0.05). CONCLUSION: L/A ratio and bicarbonate concentration and hemoglobin level have predictive value for predicting 30-day mortality in patients with acute myocardial infarction.

Effects of dance therapy on non-motor symptoms in patients with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Parkinson's disease (PD) represents the second most common neurodegenerative disease. OBJECTIVE: To evaluate the effects of dance therapy (DT) aimed at improving non-motor symptoms in PD. METHODS: Studies were performed through PubMed, Web of Science, The Cochrane Library, Embase, and Science Direct from inception to October 27, 2021. The data were screened independently by two reviewers, and the quality of the papers was assessed using the Cochrane manual. The included studies were randomized controlled trials and quasi-randomized controlled trials, reporting random-effects standardized mean differences, and 95% confidence intervals as the effect size. I2 statistics were used to assess heterogeneity. The main outcomes included the Montreal Cognitive Assessment Scale (MOCA), Baker Depression Scale (BDI), Parkinson's Fatigue Scale (FPS-16), and Apathy Scale (AS). RevMan 5.3 software was integrated for meta-analysis. RESULTS: Nine literatures were analyzed for the meta-analysis with a total of 307 patients. Random effects showed that DT significantly improved cognitive of PD (MD = 1.50, 95% CI [0.52, 2.48], P = 0.0003; I2 = 51%). However, this meta-analysis demonstrated that dance therapy had no significance for improving depression (MD = - 1.33, 95% CI [- 4.11, 1.45], P = 0.35; I2 = 79%), fatigue (MD = 0.26, 95% CI [- 0.31, 0.83], P = 0.37; I2 = 0%), and apathy (MD = 0.07, 95% CI [- 2.55, 2.69], P = 0.96; I2 = 50%). CONCLUSION: The meta-analysis suggests that dance can improve cognitive function in PD.

Analysis of In Vivo Existence Forms of Nardosinone in Mice by UHPLC-Q-TOF-MS Technique.

Nardosinone, a sesquiterpene peroxide, is one of the main active constituents of the ethnomedicine Nardostachyos Radix et Rhizoma, and it has many bioactivities, such as antiarrhythmia and cardioprotection. To elucidate its in vivo existence forms, its metabolism is first studied using mice. All urine and feces are collected during the six days of oral dosing of nardosinone, and blood is collected at one hour after the last dose. Besides, to validate some metabolites, a fast experiment is performed, in which nardosinone was orally administered and the subsequent one-hour urine is collected and immediately analyzed by UHPLC-Q-TOF-MS. In total, 76 new metabolites are identified in this study, including 39, 51, and 12 metabolites in urine, plasma, and feces, respectively. Nardosinone can be converted into nardosinone acid or its isomers. The metabolic reactions of nardosinone included hydroxylation, hydrogenation, dehydration, glucuronidation, sulfation, demethylation, and carboxylation. There are 56 and 20 metabolites with the structural skeleton of nardosinone and nardosinone acid, respectively. In total, 77 in vivo existence forms of nardosinone are found in mice. Nardosinone is mainly excreted in urine and is not detected in the feces. These findings will lay the foundation for further research of the in vivo effective forms of nardosinone and Nardostachyos Radix et Rhizoma.

Trimethylamine N-oxide is associated with coronary atherosclerotic burden in non-ST-segment myocardial infarction patients: SZ-NSTEMI prospective cohort study.

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

Iron-Catalyzed Radical Annulation of Unsaturated Carboxylic Acids with Disulfides for the Synthesis of γ-Lactones.

An efficient aerobic iron-catalyzed annulation of unsaturated carboxylic acids with disulfides has been developed. This procedure proceeds using FeCl3 as the catalyst and KI as an iodine source under an air atmosphere, which provides practical access to a wide range of substituted γ-lactone derivatives. The disclosed method is quite simple, highly atom-economic, environmentally friendly, and tolerates a broad substrate scope.

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents.

Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.

Potential Biomarkers in Early Pregnancy for Predicting Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) is typically diagnosed based on a 75-g oral glucose tolerance test conducted at 24 - 28 weeks of pregnancy. A method for earlier diagnosis is needed. The present study aimed to identify one or more blood biomarkers detected within the first trimester that can predict the occurrence of GDM and pregnancy outcome. METHODS: This retrospective study included 2,116 pregnant women who underwent examination and delivery in our hospital between January 2018 and December 2019. The predictive value of various clinical measurements in early pregnancy for predicting GDM and pregnancy outcome was analyzed. RESULTS: The fasting plasma glucose (FPG), vitamin A, vitamin E, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), uric acid, free thyroxine (FT3), anti-peroxidase antibody (TPOAb), and ferritin levels differed significantly between the GDM and non-GDM groups (all p < 0.05). The area under the receiver operating characteristic curve for FPG in GDM diagnosis was 0.766 (95% confidence interval [CI] 0.717 - 0.814, p < 0.001). The odds ratios (ORs) for FPG and TG for GDM prediction were 1.318 (95% CI 1.228 - 1.416) and 2.050 (95% CI 1.203 - 3.493), respectively. The ORs for FPG, vitamin A, and vitamin E for pregnancy outcome prediction were 1.214 (95% CI 1.123 - 1.268), 0.717 (95% CI 0.601 - 0.886), and 0.852 (95% CI 0.761 - 0.954), respectively. CONCLUSIONS: Screening of blood biomarkers in early pregnancy may be useful for predicting, and thus preventing, GDM and adverse pregnancy outcomes. Immediate intervention is recommended if an elevated FPG (> 4.7 mmol/L) or TG (> 1.83 mmol/L) level is detected in early pregnancy, and vitamin A, vitamin E, and FT3 levels need to be maintained within normal ranges throughout pregnancy.