Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

The first homosporous lycophyte genome revealed the association between the recent dynamic accumulation of LTR-RTs and genome size variation.

The contrasting genome size between homosporous and heterosporous plants is fascinating. Different from the heterosporous seed plants and mainly homosporous ferns, the lycophytes are either heterosporous (Isoetales and Selaginellales) or homosporous (Lycopodiales). Many lycophytes are the resource plants of Huperzine A (HupA) which is invaluable for treating Alzheimer's disease. For the seed-free vascular plants, several high-quality genomes of heterosporous Selaginella, homosporous ferns (maidenhair fern, monkey spider tree fern), and heterosporous ferns (Azolla) have been published and provided important insights into the origin and evolution of early land plants. However, the homosporous lycophyte genome has not been decoded. Here, we assembled the first homosporous lycophyte genome and conducted comparative genomic analyses by applying a reformed pipeline for filtering out non-plant sequences. The obtained genome size of Lycopodium clavatum is 2.30 Gb, distinguished in more than 85% repetitive elements of which 62% is long terminal repeat (LTR). This study disclosed a high birth rate and a low death rate of the LTR-RTs in homosporous lycophytes, but the opposite occurs in heterosporous lycophytes. we propose that the recent activity of LTR-RT is responsible for the immense genome size variation between homosporous and heterosporous lycophytes. By combing Ks analysis with a phylogenetic approach, we discovered two whole genome duplications (WGD). Morover, we identified all the five recognized key enzymes for the HupA biosynthetic pathway in the L. clavatum genome, but found this pathway incomplete in other major lineages of land plants. Overall, this study is of great importance for the medicinal utilization of lycophytes and the decoded genome data will be a key cornerstone to elucidate the evolution and biology of early vascular land plants.

MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort.

BACKGROUND: Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms. METHODS: A case-control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining. RESULTS: The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000-1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017-1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018-1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele. CONCLUSION: The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3'UTR of IKBA and activating NF-κB inflammatory pathways.

Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region.

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.

Development and validation of a radiomics-based prediction pipeline for the response to stereotactic radiosurgery therapy in brain metastases.

OBJECTIVES: The first treatment strategy for brain metastases (BM) plays a pivotal role in the prognosis of patients. Among all strategies, stereotactic radiosurgery (SRS) is considered a promising therapy method. Therefore, we developed and validated a radiomics-based prediction pipeline to prospectively identify BM patients who are insensitive to SRS therapy, especially those who are at potential risk of progressive disease. METHODS: A total of 337 BM patients (277, 30, and 30 in the training set, internal validation set, and external validation set, respectively) were enrolled in the study. 19,377 radiomics features (3 masks × 3 MRI sequences × 2153 features) extracted from 9 ROIs were filtered through LASSO and Max-Relevance and Min-Redundancy (mRMR) algorithms. The selected radiomics features were combined with 4 clinical features to construct a two-stage cascaded model for the prediction of BM patients' response to SRS therapy using SVM and an ensemble learning classifier. The performance of the model was evaluated by its accuracy, specificity, sensitivity, and AUC curve. RESULTS: Radiomics features were integrated with the clinical features of patients in our optimal model, which showed excellent discriminative performance in the training set (AUC: 0.95, 95% CI: 0.88-0.98). The model was also verified in the internal validation set and external validation set (AUC 0.93, 95% CI: 0.76-0.95 and AUC 0.90, 95% CI: 0.73-0.93, respectively). CONCLUSIONS: The proposed prediction pipeline could non-invasively predict the response to SRS therapy in patients with brain metastases thus assisting doctors to precisely designate individualized first treatment decisions. CLINICAL RELEVANCE STATEMENT: The proposed prediction pipeline combines the radiomics features of multi-modal MRI with clinical features to construct machine learning models that noninvasively predict the response of patients with brain metastases to stereotactic radiosurgery therapy, assisting neuro-oncologists to develop personalized first treatment plans. KEY POINTS: • The proposed prediction pipeline can non-invasively predict the response to SRS therapy. • The combination of multi-modality and multi-mask contributes significantly to the prediction. • The edema index also shows a certain predictive value.

Anthracite Releases Aromatic Carbons and Reacts with Chlorine to Form Disinfection Byproducts in Drinking Water Production.

Anthracite is globally used as a filter material for water purification. Herein, it was found that up to 15 disinfection byproducts (DBPs) were formed in the chlorination of anthracite-filtered pure water, while the levels of DBPs were below the detection limit in the chlorination of zeolite-, quartz sand-, and porcelain sandstone-filtered pure water. In new-anthracite-filtered water, the levels of dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and ammonia nitrogen (NH3-N) ranged from 266.3 to 305.4 µg/L, 37 to 61 µg/L, and 8.6 to 17.1 µg/L, respectively. In aged anthracite (collected from a filter at a DWTP after one year of operation) filtered water, the levels of the above substances ranged from 475.1 to 597.5 µg/L, 62.1 to 125.6 µg/L, and 14 to 28.9 µg/L, respectively. Anthracite would release dissolved substances into filtered water, and aged anthracite releases more substances than new anthracite. The released organics were partly (around 5%) composed by the µg/L level of toxic and carcinogenic aromatic carbons including pyridine, paraxylene, benzene, naphthalene, and phenanthrene, while over 95% of the released organics could not be identified. Organic carbon may be torn off from the carbon skeleton structure of anthracite due to hydrodynamic force in the water filtration process.

Uric acid and evaluate the coronary vascular stenosis gensini score correlation research and in gender differences.

BACKGROUND AND AIMS: Recent studies have shown that the negative effect of uric acid (UA) on coronary arteries determines the severity of atherosclerotic disease. This study aims to explore the relationship between serum UA level and Gensini score, which reflects the severity of coronary artery disease. METHODS: A total of 860 patients with suspected coronary heart disease who were admitted to hospital due to angina pectoris or myocardial ischemia related symptoms and received coronary angiography were selected. Based on the findings of the angiography, they were categorized into two groups: the coronary heart disease (CHD) group (n = 625) and the control group (n = 235). The uric acid levels and other clinical data were compared between these groups. Additionally, the prevalence of coronary heart disease and Gensini score were compared between the groups, considering gender-specific quartiles of uric acid levels. The clinical baseline data were analyzed using appropriate statistical methods, and multivariate logistic regression analysis was conducted to identify independent risk factors for coronary heart disease. RESULTS: Of 860 patients (mean age, 63.97 ± 11.87 years), 528 were men (mean age, 62.06 ± 11.5 years) and 332 were women (mean age, 66.99 ± 10.11 years). The proportion of smoking, diabetes, hypertension, and hyperlipidemia in the coronary heart disease group was higher than that in the control group (P < 0.05). HbA1C, Gensini score, BMI, TG and hsCRP in the coronary heart disease group were higher than those in the control group (P < 0.05), and HDL-C was lower than that in the control group (P < 0.05). There were no significant differences in age, heart rate, Cr, TC and LDL-C between the two groups (P > 0.05).Multivariate logistic regression analysis showed that age, hypertension, hsCRP and SUA levels increased the risk of coronary heart disease, and the difference was statistically significant(OR = 1.034,95%CI 1.016-1.052, P = 0.001; OR = 1.469,95%CI 1.007-2.142, P = 0.046;OR = 1.064,95%CI 1.026-1.105, P = 0.001; OR = 1.011,95%CI 1.008-1.014, P < 0.001). CONCLUSION: Serum uric acid is positively correlated with Gensini score in patients with coronary heart disease, which is an independent factor for evaluating the degree of coronary artery stenosis and has a predictive effect.

Mendelian randomization studies of depression: evidence, opportunities, and challenges.

BACKGROUND: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. METHODS: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. RESULTS: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. CONCLUSIONS: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

[Oral absorption and effect of macromolecules in traditional Chinese medicine: a new perspective and research mode of phase structure].

Protein polypeptides and polysaccharides, the indispensable macromolecular active components in traditional Chinese medicine, are widely found in Chinese medicine decoction after the decoction of traditional Chinese medicine. However, through oral administration, these macromolecules are digested by the stomach and intestine and thus fail to be absorbed in prototype. This is inconsistent with the actual clinical efficacy of Chinese medicine decoction. According to modern research, new phase structures and effects of the macromolecules emerge during the decoction of traditional Chinese medicine, but the phase change law caused by the interaction among the components of traditional Chinese medicine and the relationship between phase structure and effect are still unclear. Thus, this study reviewed the oral absorption of macromolecular components of traditional Chinese medicine, analyzed the internal relationship of the form of macromolecules in traditional Chinese medicine with the absorption and effect based on phase structure, and summarized the research mode of oral absorption and effect of macromolecules in traditional Chinese medicine with phase structures as the core, providing new ideas and methods for future research.

VSMC-Specific Deletion of FAM3A Attenuated Ang II-Promoted Hypertension and Cardiovascular Hypertrophy.

RATIONALE: Dysregulated purinergic signaling transduction plays important roles in the pathogenesis of cardiovascular diseases. However, the role and mechanism of vascular smooth muscle cell (VSMC)-released ATP in the regulation of blood pressure, and the pathogenesis of hypertension remain unknown. FAM3A (family with sequence similarity 3 member A) is a new mitochondrial protein that enhances ATP production and release. High expression of FAM3A in VSMC suggests it may play a role in regulating vascular constriction and blood pressure. OBJECTIVE: To determine the role and mechanism of FAM3A-ATP signaling pathway in VSMCs in the regulation of blood pressure and the pathogenesis of hypertension. METHODS AND RESULTS: In the media layer of hypertensive rat and mouse arteries, and the internal mammary artery of hypertensive patients, FAM3A expression was increased. VSMC-specific deletion of FAM3A reduced vessel contractility and blood pressure levels in mice. Moreover, deletion of FAM3A in VSMC attenuated Ang II (angiotensin II)-induced vascular constriction and remodeling, hypertension, and cardiac hypertrophy in mice. In cultured VSMCs, Ang II activated HSF1 (heat shock factor 1) to stimulate FAM3A expression, activating ATP-P2 receptor pathway to promote the change of VSMCs from contractile phenotype to proliferative phenotype. In the VSMC layer of spontaneously hypertensive rat arteries, Ang II-induced hypertensive mouse arteries and the internal mammary artery of hypertensive patients, HSF1 expression was increased. Treatment with HSF1 inhibitor reduced artery contractility and ameliorated hypertension of spontaneously hypertensive rats. CONCLUSIONS: FAM3A is an important regulator of vascular constriction and blood pressure. Overactivation of HSF1-FAM3A-ATP signaling cascade in VSMCs plays important roles in Ang II-induced hypertension and cardiovascular diseases. Inhibitors of HSF1 could be potentially used to treat hypertension.

Chloramphenicol-activated electro-chemiluminescent behavior of BNQDs-Ru(phen)32+ system for ultra-sensitive sensing of chloramphenicol in pharmaceutical and milk samples.

To improve the sensitivity for electro-chemiluminescent (ECL) detection of chloramphenicol (CAP), a common broad-spectrum antibiotic, boron nitride quantum dots (BNQDs) were prepared with excellent photoelectric property and low toxicity. After its structure and electrochemical property were investigated in detail, it was noted that the ECL signal of Ru(Phen)32+could be strengthened by the proposed BNQDs, which was further activated by ten's times in the presence of CAP. Under the optimized conditions, there was an excellent linear relationship between ΔECL and lgcCAPin a wide linear range from 1.0 × 10-10to 1.0 × 10-6mol l-1CAP. The detection limit was super-low to be 3.3 × 10-11mol l-1(S/N = 3). When applied for CAP detection in real pharmaceutical and food samples, the recoveries were between 97.8% and 105.7% with R.S.D. less than 3.3%. A possible CAP-activated ECL mechanism of BNQDs-Ru(phen)32+was also proposed. This work will offer a great potential for efficient monitoring of CAP pollution and clinical diagnosing of CAP-related diseases in future.

Chloramphenicol-activated electro-chemiluminescent behavior of BNQDs-Ru(phen)32+ system for ultra-sensitive sensing of chloramphenicol in pharmaceutical and milk samples.

To improve the sensitivity for electro-chemiluminescent (ECL) detection of chloramphenicol (CAP), a common broad-spectrum antibiotic, boron nitride quantum dots (BNQDs) were prepared with excellent photoelectric property and low toxicity. After its structure and electrochemical property were investigated in detail, it was noted that the ECL signal of Ru(Phen)32+ could be strengthened by the proposed BNQDs, which was further activated by ten's times in the presence of CAP. Under the optimized conditions, there was an excellent linear relationship between △ECL and lgcCAP in a wide linear range from 1.0×10-10 to 1.0×10-6 mol/L CAP. The detection limit was super-low to be 3.3×10-11 mol/L (S/N=3). When applied for CAP detection in real pharmaceutical and food samples, the recoveries were between 97.8 and 105.7 % with R.S.D. less than 3.3%. A possible CAP-activated ECL mechanism of BNQDs-Ru(phen)32+ was also proposed. This work will offer a great potential for efficient monitoring of CAP pollution and clinical diagnosing of CAP-related diseases in future.

Efficacy and safety of a bridging strategy that uses intravenous platelet glycoprotein receptor inhibitors for patients undergoing surgery after coronary stent implantation: a meta-analysis.

BACKGROUND: Current guidelines indicate we can consider a bridging strategy that uses intravenous, reversible glycoprotein inhibitors for patients that required surgery following recent stent implantation. However, no strong clinical evidence exists that demonstrates the efficacy and safety of this treatment. Therefore, in this study, the efficacy and safety of a bridging strategy that uses intravenous platelet glycoprotein receptor inhibitors will be evaluated. METHODS: A meta-analysis was performed on preoperative bridging studies in patients undergoing coronary stent surgery. The primary outcome was the success rate of no major adverse cardiovascular events (MACE). The secondary outcomes were the success rate of no reoperations to stop bleeding. RESULTS: A total of 10 studies that included 382 patients were used in this meta-analysis. For the primary endpoint, the success rate was 97.7% (95% CI 94.4-98.0%) for glycoprotein IIb/IIIa inhibitors, 98.8% (95% CI 96.0-100%) for tirofiban (6 studies) and 95.8% (95% CI 90.4-99.4%) for eptifibatide (4 studies). For secondary endpoints, the success rate was 98.0% (95% CI 94.8-99.9%) for glycoprotein IIb/IIIa inhibitors, 99.7% (95% CI 97.1-100%) for tirofiban (5 studies), and 95.3% (95% CI 88.5-99.4%) for eptifibatide (4 studies). CONCLUSION: The results of this study showed that the use of intravenous platelet glycoprotein IIb/IIIa inhibitors as a bridging strategy might be safe and effective for patients undergoing coronary stent implantation that require surgery soon after.

FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication characterized by learning and memory deficits. In diabetic patients, hyperactivated hypothalamic-pituitary-adrenal (HPA) axis leads to abnormal increase of glucocorticoids (GCs), which causes the damage of hippocampal neurons and cognitive impairment. In this study we investigated the cognition-improving effects of a non-steroidal glucocorticoid receptor (GR) antagonist 5-chloro-N-[4-chloro-3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (FX5) in diabetic mice. Four weeks after T1DM or T2DM was induced, the mice were administered FX5 (20, 40 mg·kg-1·d-1, i.g.) for 8 weeks. Cognitive impairment was assessed in open field test, novel object recognition test, Y-maze test, and Morris water maze test. We showed that FX5 administration significantly ameliorated the cognitive impairments in both type 1 and 2 diabetic mice. Similar cognitive improvement was observed in diabetic mice following brain GR-specific knockdown by injecting AAV-si-GR. Moreover, AAV-si-GR injection occluded the cognition-improving effects of FX5, suggesting that FX5 functioning as a non-steroidal GR antagonist. In PA-treated primary neurons (as DCI model in vitro), we demonstrated that FX5 (2, 5, 10 µM) dose-dependently ameliorated synaptic impairment via upregulating GR/BDNF/TrkB/CREB pathway, protected against neuronal apoptosis through repressing GR/PI3K/AKT/GSK3ß-mediated tauopathy and subsequent endoplasmic reticulum stress. In LPS-treated primary microglia, FX5 dose-dependently inhibited inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway. These beneficial effects were also observed in the hippocampus of diabetic mice following FX5 administration. Collectively, we have elucidated the mechanisms underlying the beneficial effects of non-steroidal GR antagonist FX5 on DCI and highlighted the potential of FX5 in the treatment of the disease.

The prognostic effect of hemoglobin on patients with cancer cachexia: a multicenter retrospective cohort study.

OBJECTIVES: To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS: This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS: Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION: Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

Long Noncoding RNAs in the Pathogenesis of Insulin Resistance.

Insulin resistance (IR), designated as the blunted response of insulin target tissues to physiological level of insulin, plays crucial roles in the development and progression of diabetes, nonalcoholic fatty liver disease (NAFLD) and other diseases. So far, the distinct mechanism(s) of IR still needs further exploration. Long non-coding RNA (lncRNA) is a class of non-protein coding RNA molecules with a length greater than 200 nucleotides. LncRNAs are widely involved in many biological processes including cell differentiation, proliferation, apoptosis and metabolism. More recently, there has been increasing evidence that lncRNAs participated in the pathogenesis of IR, and the dysregulated lncRNA profile played important roles in the pathogenesis of metabolic diseases including obesity, diabetes and NAFLD. For example, the lncRNAs MEG3, H19, MALAT1, GAS5, lncSHGL and several other lncRNAs have been shown to regulate insulin signaling and glucose/lipid metabolism in various tissues. In this review, we briefly introduced the general features of lncRNA and the methods for lncRNA research, and then summarized and discussed the recent advances on the roles and mechanisms of lncRNAs in IR, particularly focused on liver, skeletal muscle and adipose tissues.

CXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma.

The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT-associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up-regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann-like cell through Twist/S100A4 axis in SACC.

Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus.

Akkermansia muciniphila is a kind of beneficial microorganism colonized in the human gut. A. muciniphila is closely related to human intestinal health and has a good effect on diseases related to intestinal metabolism. The proteins encoded by the Amuc_1098-Amuc_1102 gene cluster, which are related to the formation and assembly of the pilus, are highly expressed in the membrane protein components of A. muciniphila. In this paper, we report the crystal structure of Amuc_1102 at a resolution of 1.75 Å, which adopts an immunoglobulin (Ig)-like fold. Amuc_1102 shares a similar fold to three archaeal proteins related to type IV pilus (T4P)-like structure, Pilin, FlaF, and FlaG, indicating a similar function. Amuc_1102 exists as a trimer both in the crystal structure and in solution, which differs from the assemblies of Pilin, FlaF, and FlaG. This study provides a structural basis for the elucidation of the T4P formation of A. muciniphila.

Angle-resolved polarized Raman spectra of the basal and edge plane of MoS2.

Angle-resolved polarized (ARP) Raman spectroscopy can be utilized to characterize the Raman modes of two-dimensional layered materials based on crystal symmetry or crystal orientation. In this paper, the polarization properties of E 1 2g and A1g modes on the basal plane and edge plane of high purity 2H-MoS2 bulk crystal grown by chemical vapor transport (CVT) method were investigated by ARP Raman spectroscopy. The I and II type ARP Raman spectroscopy with four kinds of polarization configurations: αY, αX, ßY, and ßX were used to explore the intensity dependence of E 1 2g and A1g modes at different planes on the polarization direction of incident/scattered light. The results show that the E 1 2g and A1g modes exhibit different polarization properties dependent on the polarization of the incident laser and the in-plane rotation of the sample at different planes. The experimental results were confirmed and analyzed through theoretical calculation. Our work sheds light on the intriguing effect of the subtle atomic structure in stacked MoS2 layers on the resulting ARP Raman properties. This provides a reference for the study of other two-dimensional layered crystalline materials by ARP Raman spectroscopy.