Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients.

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544.

The causal effect of oxidative stress on the risk of glaucoma.

Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848-0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248-0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119-4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927-0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890-0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810-0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978-0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Effect of the gut microbiome in glaucoma risk from the causal perspective.

OBJECTIVE: Evidence from observational studies has reported possible associations between the gut microbiome (GM) and glaucoma. However, the causal effect of GM on glaucoma risk remains to be determined. METHODS AND ANALYSIS: We conducted two-sample bidirectional Mendelian randomisation (MR) analyses to explore the causal association between GM and glaucoma. Genome-wide association study summary statistics of 196 GM taxa (n=18 340) and glaucoma (18 902 cases and 358 375 controls) were obtained from MiBioGen and FinnGen Consortium. Inverse variance weighted, MR-Egger, weighted median, weighted mode, Mendelian Randomisation Pleiotropy Residual Sum and Outlier, MR-Egger intercept and Cochran's Q statistical analyses were used to supplement MR results and sensitivity analysis. An independent cohort from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium (1715 cases and 359 479 controls) was used to validate causal effects. RESULTS: Results of the MR analysis suggested that the family Oxalobacteraceae (OR 0.900, 95% CI 0.843 to 0.961, p=0.002) and the genus Eggerthella (OR 0.881, 95% CI 0.811 to 0.957, p=0.003) had a negative effect on glaucoma, whereas the genus Bilophila (OR 1.202, 95% CI 1.074 to 1.346, p=0.001), LachnospiraceaeUCG010 (OR 1.256, 95% CI 1.109 to 1.423, p=0.0003) and Ruminiclostridium 9 (OR 1.258, 95% CI 1.083 to 1.461, p=0.003) had a positive effect on glaucoma. Among these, the positive causal effect of LachnospiraceaeUCG010 (OR 1.002, 95% CI 1.000 to 1.004, p=0.033) on glaucoma was replicated in an independent cohort. CONCLUSION: This MR analysis from large population studies demonstrated the causal effect of GM on glaucoma risk and supported the role of GM in influencing glaucoma susceptibility.

A hypotensive protocol of inspiratory muscle strength training: Systematic review and meta-analysis with trial sequential analysis.

The aim of this study was to evaluate the hypotensive effect and optimal protocol of inspiratory muscle resistance training (IMST). Randomized controlled trials using IMST to lower blood pressure (BP) were retrieved from 12 databases as of July 2022. A meta-analysis of BP and heart rate variability (HRV) was performed and a trial sequence analysis was performed using trial sequential analysis (TSA) software. Twelve articles (n = 386 participants) from five countries were included, with a mean quality score of 5.83. IMST achieved significant results in reducing systolic, diastolic, and mean arterial pressure (-7.93 [-12.08, -3.78]; -3.80 [-6.08, -1.53]; -4.90 [-13.76, 3.96]). Furthermore, TSA has shown that the findings for systolic and diastolic BP are conclusive. Finally, considerable variation remained between studies when analyzing HRV. The overall hypotensive effect of IMST was demonstrated by the TSA and was well tolerated in different populations. Of these, two interventions, high resistance or low resistance combined with slow breathing, showed the best efficacy under an 8-week exercise intervention. In addition, the process of lowering BP by modulating sympathetic vagal activity has not been further confirmed in this study. Future long-term interventions, especially those over 3 months, are needed to observe the prolonged antihypertensive effects and modulatory mechanisms; controlling for variables such as respiratory rate and executing more rigorous studies to further explore antihypertensive options.

Patient-reported outcome measures in functional dyspepsia: a systematic review and COSMIN analysis.

BACKGROUND: Functional dyspepsia (FD) as a type of disorders of brain-gut interaction (DBGI), patient self-reporting of its symptoms becomes an important component of clinical outcome assessment. We performed a systematic review using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines to identify the best available patient-reported outcome measure (PROM) of FD. METHODS: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched four databases with no date limit, looking for previously confirmed PROMs for evaluating FD symptoms. An overall rating was then assigned based upon COSMIN guidelines, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the level of evidence for psychometric properties of included PROMs. RESULTS: Thirty articles covering outcome indicators of 24 patient reports were included. The Leuven Postprandial Distress Scale (LPDS) showed adequate content validity and moderate quality evidence of adequate internal consistency to generate an A recommendation. CONCLUSION: LPDS is currently the most recommended PROM for patient self-reported FD symptoms. However, it fails to assess two important areas of cross-cultural validity/ measurement invariance and measurement error. Future research can be continuously improved on this basis.

Origin and regulation of triaxial magnetic anisotropy in the ferromagnetic semiconductor CrSBr monolayer.

Magnetic anisotropy plays a vital role in stabilizing the long-range magnetic order of two-dimensional ferromagnetic systems. In this work, using the first-principles method, we systematically explored the triaxial magnetic anisotropic properties of a ferromagnetic semiconductor CrSBr monolayer, which is recently exfoliated from its bulk. Further analysis shows that the triaxial magnetic anisotropic properties originate from the coexistence of the magnetic dipole-dipole interaction (shape anisotropy) and the spin-orbit coupling interaction (magnetocrystalline anisotropy). Interestingly, the shape anisotropy, which has been neglected in most previous works, dominates over the magnetocrystalline anisotropy. Besides, the experimental Curie temperature of the CrSBr monolayer is well reproduced using Monte Carlo simulations. What is more, the easy magnetic axes and ferromagnetism in the CrSBr monolayer can be manipulated by strains and are relatively more susceptible to the uniaxial strain in the x direction. Our study not only explains the mechanism of triaxial magnetic anisotropy of the CrSBr monolayer, but also sheds light on how to tune the magnetic anisotropy and Curie temperature in ferromagnetic monolayers.

Interventions for reducing blood pressure in prehypertension: A meta-analysis.

Background: We aimed to address which interventions best control blood pressure (BP) and delay disease progression in prehypertension and to give recommendations for the best option following a quality rating. Methods: A Bayesian network meta-analysis was used to assess the effect of the intervention on BP reduction, delaying hypertension progression and final outcome, with subgroup analyses for time and ethnicity. Recommendations for interventions were finally based on cumulative ranking probabilities and CINeMA. Results: From 22,559 relevant articles, 101 eligible randomized controlled trial articles (20,176 prehypertensive subjects) were included and 30 pharmacological and non-pharmacological interventions were evaluated. Moderate-quality evidence demonstrated that angiotensin II receptor blockers, aerobic exercise (AE), and dietary approaches to stop hypertension (DASH) lowered systolic blood pressure (SBP). For lowering diastolic blood pressure (DBP), AE combined with resistance exercise (RE) or AE alone provided high quality evidence, with calcium channel blockers, lifestyle modification (LSM) combined with drug providing moderate quality evidence. LSM produced the best BP lowering effect at 12 months and beyond of intervention. In Asians, TCD bubble was moderate quality evidence for lowering SBP and RE may have had a BP lowering effect in Caucasians. No recommendation can be given for delaying the progression of hypertension and reducing mortality outcomes because of low to very low quality of evidence. Conclusion: AE combined RE are preferentially recommended for BP control in prehypertension, followed by DASH. Long-term BP control is preferred to LSM. Asians and Caucasians add TCD bubble and RE to this list as potentially effective interventions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022356302, identifier: CRD42022356302.

High temperature ferromagnetic metal: a Janus CrSSe monolayer.

Two-dimensional (2D) ferromagnets are popular in fields such as spintronic devices, but their low Curie temperature (TC) limits their practical application. In this work, by using a global optimization evolutionary algorithm and density functional theory method, a Janus CrSSe ferromagnetic monolayer was predicted systematically. Monte Carlo simulations show that the Curie temperature of the Janus CrSSe monolayer is about 272 K and can be adjusted to 496 K under a small tensile biaxial strain. Besides, this monolayer possesses large magnetic anisotropy energy (1.4 meV Cr-1). The magnetic order can be changed from ferromagnetic to antiferromagnetic order under compressive strain. What's more, this monolayer possesses the lowest energy in the 2D search space and excellent thermal, dynamic, and mechanical stabilities. Considering its excellent properties and current experimental techniques, it is possible to synthesize CrSSe monolayer experimentally.

[Volume dynamics and volume management in intensive care unit patients].

Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.

Cr2XTe4(X = Si, Ge) monolayers: a new type of two-dimensional high-TCIsing ferromagnetic semiconductors with a large magnetic anisotropy.

Two-dimensional (2D) ferromagnetic semiconductor (FMS) provides the ideal platform for the development of quantum information technology in nanoscale devices. However, most of them suffer from low Curie temperature and small magnetic anisotropic energy (MAE), severely limiting their practical application. In this work, by using first-principles calculations, we predicted two stable 2D materials, namely, Cr2SiTe4and Cr2GeTe4monolayers. Interestingly, both of them are intrinsic direct band gap FMSs (∼1 eV) with a large magnetization (8µBf.u.-1) and sizable MAE (∼500µeV Cr-1). Monte Carlo simulations based on Heisenberg model suggest markedly high Curie temperatures of these monolayers (∼200 K). Besides, their high mechanical, dynamical, and thermal stabilities are further verified by elastic constants, phonon dispersion calculations, andab initiomolecular dynamics simulations. The outstanding attributes render Cr2XTe4(X = Si, Ge) monolayers broadening the candidates of 2D FMS for a wide range of applications.

Ni(NCS)2 monolayer: a robust bipolar magnetic semiconductor.

Searching for experimentally feasible intrinsic two-dimensional ferromagnetic semiconductors is of great significance for applications of nanoscale spintronic devices. Here, based on the first-principles calculations, an Ni(NCS)2 monolayer was systematically investigated. The results showed that the Ni(NCS)2 monolayer was a robust bipolar ferromagnetic semiconductor with a moderate bandgap of ∼1.5 eV. Based on the Monte Carlo simulation, its Curie temperature was about 37 K. Interestingly, the Ni(NCS)2 monolayer remains ferromagnetic ordering when strain and electron doping were applied. However, ferromagnetic-to-antiferromagnetic phase transition occurred when high concentrations of holes were doped. Besides, the Ni(NCS)2 monolayer is confirmed to be potentially exfoliated from its bulk forms due to its small exfoliated energy. Finally, the Ni(NCS)2 monolayer's thermodynamic, dynamic, and mechanical stabilities were confirmed by the phonon spectrum calculation, ab initio molecular dynamics simulation and elastic constants calculation, respectively. The results showed that the Ni(NCS)2 monolayer, as a novel 2D ferromagnetic candidate material of new magnetic molecular framework materials, may have a promising potential for magnetic nanoelectronic devices.

An inertial piezoelectric actuator with small structure but large loading capacity.

For inertial piezoelectric actuators, there generally exists a contradiction between the structure size and loading capacity, i.e., large loading capacity requiring a large structure size. To address this issue, a novel inertial piezoelectric rotary actuator with the size of 30 × 30 × 30 mm3 was proposed. Its structure and working principle were discussed in detail, followed by characterizing its output performances under various driving voltages, frequencies, and vertical loads. The results indicated that this actuator achieved good forward and reverse motion consistency. Under 100 V, it obtained the maximum angular speed of 302 007 µrad/s at about 600 Hz; especially, at 10 Hz, its vertical loading capacity was over 6700 g, being significantly higher than many previous inertial actuators with the similar size.

B2S3monolayer: a two-dimensional direct-gap semiconductor with tunable band-gap and high carrier mobility.

Atomically two-dimensional materials with direct band-gap and high carrier mobility are highly desirable due to their promising applications in electronic devices. Here, on the basis ofab initiocalculations and global particle-swarm optimization method, we predict the B2S3monolayer as a new semiconductor with favorable functional properties. The B2S3monolayer possesses a high electron mobility of 553 cm2V-1s-1and a direct band-gap of 1.85 eV. The direct band-gap can be manipulated under biaxial strain. Furthermore, B2S3monolayer can absorb sunlight efficiently in the entire range of the visible light spectrum. Besides, this monolayer holds good dynamical, thermal, and mechanical stabilities. All the desired properties render B2S3monolayer a promising candidate for future applications in high-speed (opto)electronic devices.

Biocidal effects of volatile organic compounds produced by the myxobacterium Corrallococcus sp. EGB against fungal phytopathogens.

Myxobacteria have excellent biocontrol activity against various phytopathogens due to their rich spectrum of secondary metabolites and active predatory characteristics. In this study, the mycelial growth of Fusarium oxysporum f. sp. cucumerinum (FOC) was found to be significantly inhibited by volatile compounds (VOCs) produced by Corallococcus sp. EGB. A total of 32 compounds were identified among the VOCs produced by strain EGB, of which isooctanol exhibited the highest antifungal activity, with dosages of 3.75 and 4.0 µL/plate being sufficient to suppress FOC and Penicillum digitatum, respectively. Isooctanol was found to damage the cell wall and cell membranes of FOC and P. digitatum. Apoptosis-like cell death of FOC and P. digitatum induced by isooctanol was observed subsequently due to the accumulation of reactive oxygen species (ROS). The transcription level of genes related to cell wall integrity (CWI) pathway and redox reactions were significantly upregulated by 15- to 40-fold, indicating the stress caused by isooctanol. Postharvest storage experiments showed that the disease severity of post-harvest oranges infected with P. digitatum could be significantly reduced by isooctanol at 114.2 µL/L.