Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure.

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.

The determinants of mental health inequalities between Chinese migrants and non-migrants during the Shanghai 2022 lockdown: a Blinder-Oaxaca decomposition.

BACKGROUND: The mental health inequality between migrants and non-migrants was exacerbated by the COVID-19 pandemic. Identifying key determinants of this inequality is essential in promoting health equity. METHODS: This cross-sectional study recruited Shanghai residents by purposive sampling during the city-wide lockdown (from April 29 to June 1, 2022) using an online questionnaire. Migration statuses (non-migrants, permanent migrants, and temporary migrants) were identified by migration experience and by household registration in Shanghai. Mental health symptoms (depression, anxiety, loneliness, and problematic anger) were assessed by self-report scales. The nonlinear Blinder-Oaxaca decomposition was used to quantify mental health inequality (i.e., differences in predicted probabilities between migration groups) and the contribution of expected correlates (i.e., change in predicted probability associated with variation in the correlate divided by the group difference). RESULTS: The study included 2738 participants (771 [28.2%] non-migrants; 389 [14.2%] permanent migrants; 1578 [57.6%] temporary migrants). We found inequalities in depression (7.1%) and problematic anger (7.8%) between permanent migrants and non-migrants, and inequalities in anxiety (7.3%) and loneliness (11.3%) between temporary migrants and non-migrants. When comparing permanent migrants and non-migrants, age and social capital explained 12.7% and 17.1% of the inequality in depression, and 13.3% and 21.4% of the inequality in problematic anger. Between temporary migrants and non-migrants, age and social capital also significantly contributed to anxiety inequality (23.0% and 18.2%) and loneliness inequality (26.5% and 16.3%), while monthly household income (20.4%) and loss of monthly household income (34.0%) contributed the most to anxiety inequality. CONCLUSIONS: Significant inequalities in depression and problematic anger among permanent migrants and inequalities in anxiety and loneliness among temporary migrants were observed. Strengthening social capital and economic security can aid in public health emergency preparedness and promote mental health equity among migrant populations.

Individualized small bowel preparation for computed tomography enterography: A prospective randomized controlled trial.

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2, 1500 mL for patients with 18.5 kg/m2 ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2, 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2, 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

Superconductivity in Ca-intercalated bilayer graphene: C2CaC2.

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

Arabic version of the SF-Qualiveen: cross-cultural adaptation, translation, and validation of urinary disorder-specific instruments in patients with multiple sclerosis.

BACKGROUND: The Short Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic-speaking patients with multiple sclerosis (MS). METHODS: The English version of the SF-Qualiveen was translated into Arabic using an algorithm for linguistic and cultural adaptation. MS patients completed the SF-Qualiveen, and the Neurogenic Bladder Symptom Score(NBSS) questionnaire. Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the NBSS questionnaire. Internal consistency was measured using Cronbach's alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability. RESULTS: One hundred and two patients with MS were included in this study. The internal consistency of the total SF-Qualiveen, and the domains "Bother with limitations," "Fear," "Feeling," and "Frequency of limitations" showed good internal consistency (Cronbach's alpha of > 0.7). ICC was 0.91 for the total score 0.85 for the Bother with limitations, 0.81 for Fears, 0.86 for Feeling, and 0.81 for Frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.473, p = 0.027), fears (r = 0.611, p = 0.031), feelings (r = 0.572, p = 0.04), and frequency of limitations (r = 0.514, p = 0.013). CONCLUSIONS: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with MS in both research and clinical practice.

Oxygen-Bridged Long-Range Dual Sites Boost Ethanol Electrooxidation by Facilitating C-C Bond Cleavage.

Optimizing the interatomic distance of dual sites to realize C-C bond breaking of ethanol is critical for the commercialization of direct ethanol fuel cells. Herein, the concept of holding long-range dual sites is proposed to weaken the reaction barrier of C-C cleavage during the ethanol oxidation reaction (EOR). The obtained long-range Rh-O-Pt dual sites achieve a high current density of 7.43 mA/cm2 toward EOR, which is 13.3 times that of Pt/C, as well as remarkable stability. Electrochemical in situ Fourier transform infrared spectroscopy indicates that long-range Rh-O-Pt dual sites can increase the selectivity of C1 products and suppress the generation of a CO intermediate. Theoretical calculations further disclose that redistribution of the surface-localized electron around Rh-O-Pt can promote direct oxidation of -OH, accelerating C-C bond cleavage. This work provides a promising strategy for designing oxygen-bridged long-range dual sites to tune the activity and selectivity of complicated catalytic reactions.

Modulation of fried spring roll wrapper quality upon treatment of batter with maltogenic amylase, transglutaminase and bromelain.

BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.

Feedback Inhibition of Bacterial Nucleotidyltransferases by Rare Nucleotide l-Sugars Restricts Substrate Promiscuity.

Bacterial glycomes are rich in prokaryote-specific or "rare" sugars that are absent in mammals. Like common sugars found across organisms, rare sugars are typically activated as nucleoside diphosphate sugars (NDP-sugars) by nucleotidyltransferases. In bacteria, the nucleotidyltransferase RmlA initiates the production of several rare NDP-sugars, which in turn regulate downstream glycan assembly through feedback inhibition of RmlA via binding to an allosteric site. In vitro, RmlA activates a range of common sugar-1-phosphates to produce NDP-sugars for biochemical and synthetic applications. However, our ability to probe bacterial glycan biosynthesis is hindered by limited chemoenzymatic access to rare NDP-sugars. We postulate that natural feedback mechanisms impact nucleotidyltransferase utility. Here, we use synthetic rare NDP-sugars to identify structural features required for regulation of RmlA from diverse bacterial species. We find that mutation of RmlA to eliminate allosteric binding of an abundant rare NDP-sugar facilitates the activation of noncanonical rare sugar-1-phosphate substrates, as products no longer affect turnover. In addition to promoting an understanding of nucleotidyltransferase regulation by metabolites, this work provides new routes to access rare sugar substrates for the study of important bacteria-specific glycan pathways.

Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer.

ß-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods are mainly achieved by amino(hetero)arylation reaction with the aid of transition metals and preactivated substrates. Herein, we report a metal-free and photoinduced intermolecular amino(hetero)arylation reaction for the single-step installation of both (hetero)aryl and iminyl groups across alkenes in an efficient and regioselective manner. This method shows broad scope (up to 124 examples) and excellent tolerance of various olefins─from the simplest ethylene to complex multisubstituted alkenes can all participate in the reaction. Furthermore, aminosulfonylation of alkenes can be also conducted in the presence of sodium bisulfite as the SO2 source.

Preference of Bacterial Rhamnosyltransferases for 6-Deoxysugars Reveals a Strategy To Deplete O-Antigens.

Bacteria synthesize hundreds of bacteria-specific or "rare" sugars that are absent in mammalian cells and enriched in 6-deoxy monosaccharides such as l-rhamnose (l-Rha). Across bacteria, l-Rha is incorporated into glycans by rhamnosyltransferases (RTs) that couple nucleotide sugar substrates (donors) to target biomolecules (acceptors). Since l-Rha is required for the biosynthesis of bacterial glycans involved in survival or host infection, RTs represent potential antibiotic or antivirulence targets. However, purified RTs and their unique bacterial sugar substrates have been difficult to obtain. Here, we use synthetic nucleotide rare sugar and glycolipid analogs to examine substrate recognition by three RTs that produce cell envelope components in diverse species, including a known pathogen. We find that bacterial RTs prefer pyrimidine nucleotide-linked 6-deoxysugars, not those containing a C6-hydroxyl, as donors. While glycolipid acceptors must contain a lipid, isoprenoid chain length, and stereochemistry can vary. Based on these observations, we demonstrate that a 6-deoxysugar transition state analog inhibits an RT in vitro and reduces levels of RT-dependent O-antigen polysaccharides in Gram-negative cells. As O-antigens are virulence factors, bacteria-specific sugar transferase inhibition represents a novel strategy to prevent bacterial infections.

Defect-Mediated Synergistic Effect of POM/UiO-66(Zr) Host-Guest Catalysts for Robust Deep Desulfurization at Ambient Temperature.

Stable platforms of host-guest catalysts are indispensable in the field of heterogeneous catalysis, however, clarifying the specific effect of host remains challenging. Herein, polyoxometalate (POM) is encapsulated in three types of UiO-66(Zr) with different controlled densities of defects by the aperture opening and closing strategy at ambient-temperature. It is found that catalytic activity of POM for oxidative desulfurization (ODS) at room temperature is turned on when encapsulated in the defective UiO-66(Zr), and the sulfur oxidation efficiency shows an obvious increasing trend (from 0.34 to 10.43 mmol g-1 h-1 ) with the increased concentration of defects in UiO-66(Zr) host. The as-prepared catalyst with the most defective host displays ultrahigh performance which removed 1000 ppm sulfur with exceptionally diluted oxidant at room-temperature within 25 min. The turnover frequency can reach 620.0 h-1 at 30 °C, which surpassed all the reported MOFs based ODS catalysts. A substantial guest/host synergistic effect mediated by the defective sites in UiO-66(Zr) is responsible for the enhancement. Density functional theory calculations reveal that OH/OH2 capped on the open Zr sites of host UiO-66(Zr) can decompose H2 O2 to OOH group and enables the formation of WVI -peroxo intermediates that determine the ODS activity.

Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.

Intranasal Monophosphoryl Lipid a Administration Ameliorates depression-like Behavior in Chronically Stressed Mice Through Stimulation of Microglia.

We and others have reported that systematic stimulation of the central innate immune system by a low dose of lipopolysaccharide (LPS) can improve depression-like behavior in chronically stressed animals. However, it is unclear whether similar stimulation by intranasal administration could improve depression-like behavior in animals. We investigated this question using monophosphoryl lipid A (MPL), a derivative of LPS that lacks the adverse effects of LPS but is still immuno-stimulatory. We found that a single intranasal administration of MPL at a dose of 10 or 20 µg/mouse, but not at a dose of 5 µg/mouse, ameliorated chronic unpredictable stress (CUS)-induced depression-like behavior in mice, as evidenced by the decrease in immobility time in tail suspension test and forced swimming test and the increase in sucrose intake in sucrose preference test. In the time-dependent analysis, the antidepressant-like effect of a single intranasal MPL administration (20 µg/mouse) was observed 5 and 8 h but not 3 h after drug administration and persisted for at least 7 days. Fourteen days after the first intranasal MPL administration, a second intranasal MPL administration (20 µg/mouse) still showed an antidepressant-like effect. The innate immune response mediated by microglia might mediate the antidepressant-like effect of intranasal MPL administration, because both inhibition of microglial activation by pretreatment with minocycline and depletion of microglia by pretreatment with PLX3397 prevented the antidepressant-like effect of intranasal MPL administration. These results suggest that intranasal administration of MPL can produce significant antidepressant-like effects in animals under chronic stress conditions via stimulation of microglia.

Zymosan A produces a rapid and sustained antidepressant effect in chronically stressed mice by stimulating hippocampal microglia.

Recent studies had reported that compounds that stimulate microglia could be developed as potential drugs for the treatment of depression due to their reversal effect on depression-like behaviors in chronically stressed mice. Zymosan A is a cell wall preparation of Saccharomyces cerevisiae composed of ß-glucans. Based on its immuno-stimulatory activities, we hypothesized that zymosan A might have a therapeutic effect on depression. Our results showed that a single injection of zymosan A 5 h before behavioral tests at a dose of 1 or 2 mg/kg, but not at a dose of 0.5 mg/kg, reversed chronic unpredictable stress (CUS)-induced depression-like behaviors in mice in the tail suspension test, forced swimming test, and sucrose preference test. Time-dependent analysis showed that the antidepressant effect of zymosan A (2 mg/kg) in CUS mice became statistically significant at 5 and 8 h, but not at 3 h, and persisted for at least 7 days. Fourteen days after a single injection of zymosan A, no antidepressant effect was observed anymore. However, the disappeared antidepressant effect of zymosan A was restored by a second zymosan A injection (2 mg/kg, 5 h) 14 days after the first zymosan A injection. Stimulation of microglia was essential for the antidepressant effect of zymosan A because pre-inhibition of microglia by minocycline or pre-depletion of microglia by PLX3397 prevented the antidepressant effect of zymosan A. Based on these effects of zymosan A, zymosan A administration could be developed as a new strategy for the treatment of depression.

Superconductivity of monolayer functionalized biphenylene with Dirac cones.

Monolayer biphenylene is a new two-dimensional (2D) carbon allotrope, which has been experimentally synthesized and theoretically predicted to show superconductivity. In this work, we investigate functionalized biphenylene with the adsorption of Li. The superconducting critical temperature (Tc) can be pushed from 0.59 K up to 3.91 K after Li adsorption. Our calculations confirm that the adsorption pushes the peak showing a high electronic density of states closer to the Fermi level, which usually leads to a larger Tc. Furthermore, the application of biaxial tensile strain can soften phonons and further enhance the Tc up to 15.86 K in Li-deposited biphenylene. Interestingly, a pair of type-II Dirac cones below the Fermi level has been observed, expanding the range of Dirac materials. It suggests that monolayer biphenylene deposited with Li may be a material with potential applications and improves the understanding of Dirac-type superconductors.

Evaluation of guidelines for the diagnosis and treatment of achalasia.

Due to the unclear quality of the current guidelines, users may be confused about how to diagnose and treat achalasia. The objective of this work is to systematically evaluate the methodological quality of the current guidelines for diagnosing and treating achalasia and to determine the heterogeneity among recommendations. We systematically searched literature databases to retrieve relevant guidelines for the diagnosis and treatment of achalasia. The Appraisal of Guidelines for Research and Evaluation II tool was used to evaluate the quality of the included guidelines. Key recommendations in the guidelines were extracted, and the reasons for the heterogeneity of the key recommendations between different guidelines were further analyzed. Seven guidelines on the diagnosis and treatment of achalasia are included in this study. The overall score of three guidelines exceeded 60%. The average score in domain 5 was the lowest, at 41.8%. The average scores in domain 2, domain 3, and domain 6 were also low, at 45.4%, 57.1% and 56.9%, respectively. The main recommendations and quality of evidence for different guidelines vary greatly, mainly due to the different emphases among different guidelines, the lack of systematic retrieval, or the unfairness of evidence use in some guidelines. There are considerable differences in the methodological quality of diagnosis and treatment guidelines for achalasia. Additionally, the differences in the main recommendations and evidence support among guidelines are also obvious. Guideline developers should improve the above related factors to decrease the heterogeneity, and they should further formulate or update the guidelines for the diagnosis and treatment of achalasia.