IL-22, a vital cytokine in autoimmune diseases.

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

Association between composite dietary antioxidant index and hypertension: insights from NHANES.

AIM: The association between composite dietary antioxidant index (CDAI) and hypertension remains unknown. Our study was to investigate the association of CDAI with hypertension in general adults. METHODS: A total of 21 526 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The CDAI was calculated from the intake of six dietary antioxidants. Multivariable logistic regressions were performed to explore the associations between CDAI and the prevalence of hypertension. Non-linear correlations were explored using restricted cubic splines. And the inflection point was determined by the two-piecewise linear regression. RESULTS: In the multivariate logistic regression model with full adjustment for confounding variables, the odds ratio (95% confidence interval) of CDAI associating with hypertension was 0.98 (0.97-1.00; P = .016). Besides, compared to the lowest quartile, the highest quartile of CDAI was associated with a lower risk of hypertension (0.81 [0.70-0.94]; P = .006). Furthermore, a linear association was found by restricted cubic spline, with 3.4 being the turning point. CONCLUSION: Our study highlighted a negative linear association between CDAI and hypertension in general adults.

Preparation and properties of cellulosenanofiber (CNF) /polyvinyl alcohol (PVA) /graphene oxide (GO): Application of CO2 absorption capacity and molecular dynamics simulation.

In order to solve the environmental problems caused by greenhouse gas emissions, cellulosenanofiber (CNF)/polyvinyl alcohol (PVA)/graphene oxide (GO) aerogel was obtained by step-by-step heating, tert-butanol replacement, freeze-drying, and high-temperature activation in this paper. The micromorphology, specific surface area, pore size distribution, and thermal stability of the prepared aerogels were analyzed by scanning electron microscopy, automatic surface area and porosity analysis, and thermo-gravimetric analysis. The interaction state and adsorption mechanism of CO2 and aerogel physical adsorption were described by Materials Studio simulation. The results showed that the adsorption process conformed to the Langmuir adsorption isotherm. After carbonization, the thermal stability of the aerogel was good (mass loss rate <1%). With the increase of GO content, its specific surface area increased (392.41 m2/g) and CO2 adsorption capacity increased (432.76 cm3/g at 273 K). The simulation results show that hydrogen bond energy and van der Waals adsorption are the main factors that help in adsorption of CO2 on the surface aerogel, and electrostatic adsorption is the secondary adsorption factor. The application of green material carbon-based aerogels is also in line with the concept of sustainable development.

Empagliflozin protects against atherosclerosis progression by modulating lipid profiles and sympathetic activity.

BACKGROUND: Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown. METHODS: ApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1ß, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA. RESULTS: Empagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P < 0.001]; LDL: [-2.9 mmol/L, P = 0.010]), RAAS (renin [-9.3 ng/L, P = 0.047]; aldosterone [-16.7 ng/L, P < 0.001]) and sympathetic activity (norepinephrine [-8.9 ng/L, P = 0.019]; neuropeptide Y [-8.8 ng/L, P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident. CONCLUSIONS: The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.

Impact of China's zero mark-up drug policy on drug cost of NCDs' outpatients: an interrupted time series analysis.

BACKGROUND: China proposed the Zero Markup Drug Policy (ZMDP), which popularized in tertiary hospitals across the country in 2017, to control drug expenditures' rapid growth further and reduce the public's medical burden. This study aims to evaluate the impact of ZMDP on the drug cost of chronic disease outpatients in the tertiary hospital in Chongqing. METHODS: We collected and described the drug-cost data for outpatients with chronic diseases in a Chongqing's tertiary hospital from 2015 to 2019. The instantaneous and long-term changes of the outpatient volume and average drug cost after the ZMDP were evaluated using interrupted time series (ITS). We also analyzed the policy's impact under the stratification of gender, age, and basic medical insurance types. RESULTS: A total of 350,848 outpatients were collected from January 2015 to February 2019. After the ZMDP, the outpatient volume for diabetes, hypertension, and coronary heart disease (CHD) all showed a downward trend, with a decrease of 53.04 (P = 0.012), 142.19 (P < 0.01) and 12.16 (P < 0.001) per month. Simultaneously, the average drug cost decreased by 4.44 yuan (P = 0.029), 5.87 yuan (P < 0.001) and 10.23 yuan (P = 0.036) per month, respectively. By gender, the average drug cost of diabetes in males had the most considerable instantaneous change, reducing by 51.21 yuan (P = 0.017); the decline of CHD in women is the most obvious, with an average monthly decrease of 12.51 yuan (P < 0.001). By age, the instantaneous change of CHD was the greatest for those older than 65 years old, with a decrease of 102.61 yuan (P = 0.030). CHD in 46-65 years old showed the most significant reduction, with an average monthly decline of 11.70 yuan (P < 0.01). BMIUE's hypertension had the most considerable instantaneous change, which decreased 59.63 yuan (P = 0.010). BMIUE's CHD showed the most apparent downward trend, with an average monthly decrease of 10.02 yuan (P = 0.010). CONCLUSION: The ITS analysis is an effective method of health policy evaluation. The implementation of the ZMDP can reduce the drug cost for chronic disease outpatients in the tertiary hospital and their economic burden. Follow-up policies still require targeted price adjustments in the health service system to adjust the drug cost-effectively.

Evaluate the performance of four artificial intelligence-aided diagnostic systems in identifying and measuring four types of pulmonary nodules.

PURPOSE: This study aims to evaluate the performance of four artificial intelligence-aided diagnostic systems in identifying and measuring four types of pulmonary nodules. METHODS: Four types of nodules were implanted in a commercial lung phantom. The phantom was scanned with multislice spiral computed tomography, after which four systems (A, B, C, D) were used to identify the nodules and measure their volumes. RESULTS: The relative volume error (RVE) of system A was the lowest for all nodules, except for small ground glass nodules (SGGNs). System C had the smallest RVE for SGGNs, -0.13 (-0.56, 0.00). In the Bland-Altman test, only systems A and C passed the consistency test, P = 0.40. In terms of precision, the miss rate (MR) of system C was 0.00% for small solid nodules (SSNs), ground glass nodules (GGNs), and solid nodules (SNs) but 4.17% for SGGNs. The comparable system D MRs for SGGNs, SSNs, and GGNs were 71.30%, 25.93%, and 47.22%, respectively, the highest among all the systems. Receiver operating characteristic curve analysis indicated that system A had the best performance in recognizing SSNs and GGNs, with areas under the curve of 0.91 and 0.68. System C had the best performance for SGGNs (AUC = 0.91). CONCLUSION: Among four types nodules, SGGNs are the most difficult to recognize, indicating the need to improve higher accuracy and precision of artificial systems. System A most accurately measured nodule volume. System C was most precise in recognizing all four types of nodules, especially SGGN.

The effector cells and cellular mediators of immune system involved in cardiac inflammation and fibrosis after myocardial infarction.

The cardiac repair after myocardial infarction (MI) involves two phases, namely, inflammatory response and proliferative response. The former is an inflammatory reaction, evoked by different kinds of pro-inflammatory leukocytes and molecules stimulated by myocardial necrosis, while the latter is a repair process, predominated by a magnitude of anti-inflammatory cells and cytokines, as well as fibroblasts. Cardiac remodeling post-MI is dependent on the balance of individualized intensity of the post-MI inflammation and subsequent cardiac fibrosis. During the past 30 years, enormous studies have focused on investigating immune cells and mediators involved in cardiac inflammation and fibrosis, which are two interacting processes of post-MI cardiac repair. These results contribute to revealing the mechanism of adverse cardiac remodeling after MI and alleviating the impairment of cardiac function. In this study, we will broadly discuss the role of immune cell subpopulation and the involved cytokines and chemokines during cardiac repair post-MI, particular in cardiac inflammation and fibrosis.

Association between Triglyceride and glycose (TyG) index and subclinical myocardial injury.

BACKGROUND AND AIMS: Triglyceride and glycose (TyG) index has been viewed as a reliable surrogate of cardiovascular disease (CVD) risk. We hypothesized that elevated TyG index is associated with increased risk of subclinical myocardial injury (SC-MI). METHODS AND RESULTS: A total of 6093 participants without history of CVD were extracted from the third National Health and Nutrition Examination Survey (NHANES III). SC-MI was defined by cardiac infarction/injury score (CIIS) ≥10. Multivariate logistic regression was performed to examine the association between TyG index (as a qualitative or quantitative variable) and SC-MI. TyG index was positively correlated with CIIS (ß = 0.54; p = 0.004) in the multivariable linear regression analysis. In a multivariable model, TyG index was independently associated with an increased risk of SC-MI (OR = 1.17, 95% CI: 1.05 to 1.30; p = 0.004). Also, TyG>9.00 increased the risk of SC-MI (OR = 1.21, 95% CI: 1.03 to 1.43; p = 0.024) independent of other risk factors. CONCLUSION: Elevated TyG index increases the risk of CIIS and SC-MI, which could be a new biomarker in the clinical practice.

Autophagy and Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor system dysfunction. The etiology of PD has been linked with aging, environmental toxins and genetic mutation, while molecular pathogenesis of PD includes various factors, such as impaired protein homeostasis, oxidative stress, mitochondria dysfunction, synaptic transmission impairment, calcium homeostasis imbalance, prion-like α-synuclein transmission and neuron inflammation. Autophagy is a conserved bulk degradation process to maintain cellular homeostasis. Impairment of autophagy has been reported to be involved in the pathogenesis of PD. Coding proteins of several PD-related genes, such as SNCA, LRRK2, GBA, ATP13A2, VPS35 and FBXO7, are implicated in or affected by autophagy process. Furthermore, various pathogenic events during PD directly or indirectly interfere with the autophagy pathway, and dysregulation of autophagy has been observed in different neurotoxic PD models. Autophagy has been regarded as a potential therapeutic target for PD treatment. Indeed, modulations of autophagy-regulated genes (BECN1 and TFEB) expression exerted neuroprotection against PD models, and various autophagy regulators, such as rapamycin, trehalose, lysosome modulators and other small molecule autophagy inducers, have displayed neuroprotective effects in experimental PD models. Taken together, autophagy dysfunction has been implicated in the pathogenesis of PD, and pharmacological modulation of autophagy may be a new therapeutic strategy for the PD treatment.

Shock on Admission as a Potential Marker for ICU Mortality of Cardiac Arrest Patients.

To investigate the association of shock on admission with predicting intensive care unit (ICU) mortality, hospital mortality, and neurological outcomes of post cardiac arrest patients.This was a retrospective study of cardiac arrest (CA) patients admitted to ICU. Student's t test and Chi-square test were performed to compare the difference of non-shock and shock group. Multivariable regression analysis was performed to investigate shock and its association with ICU mortality, hospital mortality, and neurologic outcomes and linear regression analysis to explore its correlation with length of stay in hospital.A total of 374 CA patients were analyzed, with 200 (53.5%) patients in the presence of shock on admission. Shock was significantly associated with higher ICU mortality (OR 2.42, 95% CI 1.60 to 3.68; P < 0.001), hospital mortality (OR 2.33, 95% CI 1.54 to 3.54; P < 0.001), and more unfavorable neurological outcomes (OR 1.98, 95% CI 1.30 to 3.02; P = 0.001). After adjusting for confounding factors, shock was still an independent predictor of ICU mortality (OR 2.40, 95% CI 1.30 to 4.43; P = 0.005).Shock on admission of CA patients was significantly associated with ICU mortality.

Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic γ-Lactams and Kinetic Resolution of γ-Substituted Allenoates.

A C2-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities. A kinetic resolution process of racemic γ-substituted allenoates was developed for the generation of optically enriched chiral allenoates.

Neuroprotective effects of berberine in animal models of Alzheimer's disease: a systematic review of pre-clinical studies.

BACKGROUND: Berberine is an isoquinoline alkaloid extracted from various Berberis species which is widely used in East Asia for a wide range of symptoms. Recently, neuroprotective effects of berberine in Alzheimer's disease (AD) animal models are being extensively reported. So far, no clinical trial has been carried out on the neuroprotective effects of berberine. However, a review of the experimental data is needed before choosing berberine as a candidate drug for clinical experiments. We conducted a systematic review on AD rodent models to analyze the drug effects with minimal selection bias. METHODS: Five online literature databases were searched to find publications reporting studies of the effect of berberine treatment on animal models of AD. Up to March 2018, 15 papers were identified to describe the efficacy of berberine. RESULTS: The included 15 articles met our inclusion criteria with different quality ranging from 3 to 5. We analyzed data extracted from full texts with regard to pharmacological effects and potential anti-Alzheimer's properties. Our analysis revealed that in multiple memory defects animal models, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects. CONCLUSION: AD is likely to be a complex disease driven by multiple factors. Yet, many therapeutic strategies based on lowering ß-amyloid have failed in clinical trials. This suggest that the threapy should not base on a single cause of Alzheimer's disease but rather a number of different pathways that lead to the disease. Overall we think that berberine can be a promising multipotent agent to combat Alzheimer's disease.

Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis.

BACKGROUND: Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. METHODS: Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. RESULTS: Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%). CONCLUSIONS: Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

MAL62 overexpression and NTH1 deletion enhance the freezing tolerance and fermentation capacity of the baker's yeast in lean dough.

BACKGROUND: Trehalose is related to several types of stress responses, especially freezing response in baker's yeast (Saccharomyces cerevisiae). It is desirable to manipulate trehalose-related genes to create yeast strains that better tolerate freezing-thaw stress with improved fermentation capacity, which are in high demand in the baking industry. RESULTS: The strain overexpressing MAL62 gene showed increased trehalose content and cell viability after prefermention-freezing and long-term frozen. Deletion of NTH1 in combination of MAL62 overexpression further strengthens freezing tolerance and improves the leavening ability after freezing-thaw stress. CONCLUSIONS: The mutants of the industrial baker's yeast with enhanced freezing tolerance and leavening ability in lean dough were developed by genetic engineering. These strains had excellent potential industrial applications.

X-linked microtubule-associated protein, Mid1, regulates axon development.

Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.

Asymmetric Construction of Spirooxindoles by Organocatalytic Multicomponent Reactions Using Diazooxindoles.

The first highly diastereo- and enantioselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes using a newly developed hydrogen-bond catalyst has been successfully developed for the efficient construction of a series of spirooxindole derivatives with excellent functional-group tolerance. Spirooxindoles are formed in excellent yields and stereoselectivities, and the method represents an unprecedented approach for trapping the active intermediate with a nitroalkene to form biologically important compounds having three contiguous stereogenic centers with excellent asymmetric induction.

Quantitative assessment of the influence of CYP1B1 polymorphisms and head and neck squamous cell carcinoma risk.

The associations between CYP1B1 polymorphisms and head and neck squamous cell carcinoma (HNSCC) risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Six published case-control studies were collected; odds ratios (ORs) with 95% confidence interval (CI) were used to assess the association between CYP1B1 Leu432Val, Asn453Ser polymorphisms, and HNSCC risk. The Sensitivity analysis and publication bias also were performed to guarantee the statistical power. Overall, the pooled OR with 95% CIs indicated that CYP1B1 Leu432Val polymorphism was significantly related with HNSCC risk (for Val vs. Leu: OR = 1.13, 95% CI = 1.03-1.25, P = 0.014, P(heterogeneity) = 0.141; for Val/Val vs. Leu/Leu: OR = 1.30, 95% CI = 1.06-1.60, P = 0.013, P heterogeneity = 0.253; for Val/Val vs. Leu/Leu + Leu/Val: OR = 1.23, 95% CI = 1.05-1.46, P = 0.013, P(heterogeneity) = 0.456). The similar results were also been found in succeeding analysis of HWE and stratified analysis of Caucasian population. Furthermore, no significant association between CYP1B1 Asn453Ser polymorphism and HNSCC risk was found in this meta-analysis. In conclusion, our meta-analysis demonstrates that CYP1B1 Leu432Val polymorphism may be a risk factor for developing HNSCC.

Enhanced production of 2,3-butanediol by overexpressing acetolactate synthase and acetoin reductase in Klebsiella pneumoniae.

Mutants with overexpression of α-acetolactate synthase (ALS), α-acetolactate decarboxylase, and acetoin reductase (AR), either individually or in combination, were constructed to improve 2,3-butanediol (2,3-BD) production in Klebsiella pneumoniae. The recombinant strains were characterized in terms of the enzyme activity, 2,3-BD yield, and expression levels. The recombinant K. pneumoniae strain (KG-rs) that overexpressed both ALS and AR showed an improved 2,3-BD yield. When cultured in the media with five different carbon sources (glucose, galactose, fructose, sucrose, and lactose), the mutant exhibited higher 2,3-BD productivity and production than the parental strain in all the tested carbon sources except for lactose. The 2,3-BD production of KG-rs in a batch fermentation with glucose as the carbon source was 12% higher than that of the parental strain.

Highly enantioselective kinetic resolution of axially chiral BINAM derivatives catalyzed by a Brønsted acid.

A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.

Molecular Modulators and Receptors of Selective Autophagy: Disease Implication and Identification Strategies.

Autophagy is a highly conserved physiological process that maintains cellular homeostasis by recycling cellular contents. Selective autophagy is based on the specificity of cargo recognition and has been implicated in various human diseases, including neurodegenerative diseases and cancer. Selective autophagy receptors and modulators play key roles in this process. Identifying these receptors and modulators and their roles is critical for understanding the machinery and physiological function of selective autophagy and providing therapeutic value for diseases. Using modern researching tools and novel screening technologies, an increasing number of selective autophagy receptors and modulators have been identified. A variety of Strategies and approaches, including protein-protein interactions (PPIs)-based identification and genome-wide screening, have been used to identify selective autophagy receptors and modulators. Understanding the strengths and challenges of these approaches not only promotes the discovery of even more such receptors and modulators but also provides a useful reference for the identification of regulatory proteins or genes involved in other cellular mechanisms. In this review, we summarize the functions, disease association, and identification strategies of selective autophagy receptors and modulators.