A comprehensive review on the recent advances for 5-aminolevulinic acid production by the engineered bacteria.

5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid essential for synthesizing tetrapyrrole compounds, including heme, chlorophyll, cytochrome, and vitamin B12. As a plant growth regulator, 5-ALA is extensively used in agriculture to enhance crop yield and quality. The complexity and low yield of chemical synthesis methods have led to significant interest in the microbial synthesis of 5-ALA. Advanced strategies, including the: enhancement of precursor and cofactor supply, compartmentalization of key enzymes, product transporters engineering, by-product formation reduction, and biosensor-based dynamic regulation, have been implemented in bacteria for 5-ALA production, significantly advancing its industrialization. This article offers a comprehensive review of recent developments in 5-ALA production using engineered bacteria and presents new insights to propel the field forward.

The growth and nutrient removal properties of heterotrophic microalgae Chlorella sorokiniana in simulated wastewater containing volatile fatty acids.

To reduce the high cost of organic carbon sources in waste resource utilization in the cultivation of microalgae, volatile fatty acids (VFAs) derived from activated sludge were used as the sole carbon source to culture Chlorella sorokiniana under the heterotrophic cultivation. The addition of VFAs in the heterotrophic condition enhanced the total nitrogen (TN) and phosphorus (TP) removal of C. sorokiniana, which proved the advantageous microalgae in using VFAs in the heterotrophic culture after screening in the previous study. To discover the possible mechanism of nitrogen and phosphorus adsorption in heterotrophic conditions by microalgae, the effect of different ratios of VFAs (acetic acid (AA): propionic acid (PA): butyric acid (BA)) on the nutrient removal and growth properties of C. sorokiniana was studied. In the 8:1:1 group, the highest efficiency (77.19%) of VFAs assimilation, the highest biomass (0.80 g L-1) and lipid content (31.35%) were achieved, with the highest TN and TP removal efficiencies of 97.44 % and 91.02 %, respectively. Moreover, an aerobic denitrifying bacterium, Pseudomonas, was determined to be the dominant genus under this heterotrophic condition. This suggested that besides nitrate uptake and utilization by C. sorokiniana under the heterotrophy, the conduct of the denitrification process was also the main reason for obtaining high nitrogen removal efficiency.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

[Accumulation and biosynthesis mechanism of volatile oils in glandular scale of Agastache rugosa].

The volatile oils are the effective components of Agastache rugosa, which are stored in the glandular scale. The leaves of pulegone-type A. rugosa were used as materials to observe the leaf morphology of A. rugosa at different growth stages, and the components of volatile oils in gland scales were detected by GC-MS. At the same time, qRT-PCR was used to determine the relative expression of key enzyme genes in the biosynthesis pathway of monoterpenes in volatile oils. The results showed that the density of A. rugosa glandular scale decreased first and then tended to be stable. With the growth of leaves, the relative content of pulegone decreased from 79.26% to 3.94%(89.97%-41.44%), while that of isomenthone increased from 2.43% to 77.87%(0.74%-51.01%), and the changes of other components were relatively insignificant. The correlation analysis between the relative content of monoterpenes and the relative expression levels of their key enzyme genes showed that there was a significant correlation between the relative content of menthone and isomenthone and the relative expression levels of pulegone reductase(PR)(r>0.6, P<0.01). To sum up, this study revealed the accumulation rules of the main components of the contents of the glandular scale of A. rugosa and the expression rules of the key enzyme genes for biosynthesis, which provided a scientific basis and data support for determining the appropriate harvesting period and quality control of the medicinal herbs. This study also initially revealed the biosynthesis mechanism of the monoterpenes mainly composed of pulegone and isomenthone in A. rugosa, laying a foundation for further research on the molecular mechanism of synthesis and accumulation of monoterpenes in A. rugosa.

Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration.

Amuc_1100 is a membrane protein from Akkermansia muciniphila, which has been found to play a role in host immunological homeostasis in the gastrointestinal tract by activating TLR2 and TLR4. In this study we investigated the effects and underlying mechanisms of Amuc_1100 on acute pancreatitis (AP) induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). The mice were treated with the protein Amuc_1100 (3 µg, i.g.) for 20 days before caerulein injection. Cecal contents of the mice were collected for 16S rRNA sequencing. We found that pretreatment with Amuc_1100 significantly alleviated AP-associated pancreatic injury, reduced serum amylase and lipase. Amuc_1100 pretreatment significantly inhibited the expression of proinflammatory cytokines (TNF-α, IL-1ß, IFN-γ and IL-6) in spleen and pancreas through inhibiting NF-κB signaling pathway. Moreover, Amuc_1100 pretreatment significantly decreased the inflammatory infiltration, accompanied by the reduction of Ly6C+ macrophages and neutrophils in the spleen of AP mice. Gut microbiome analysis showed that the abundance of Bacteroidetes, Proteobacteria, Desulfobacterota and Campilobacterota was decreased, while the proportion of Firmicutes and Actinobacteriota was increased in AP mice pretreated with Amuc_1100. We further demonstrated that Amuc_1100 pretreatment restored the enrichment of tryptophan metabolism, which was mediated by intestinal flora. These results provide new evidence that Amuc_1100 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophages and neutrophil infiltration, as well as its regulation of the composition of intestinal flora and tryptophan metabolism.

IL-33/ST2L signaling alleviates diabetic nephropathy by regulating endoplasmic reticulum stress and apoptosis.

OBJECTIVE: Diabetic nephropathy (DN) is a serious chronic complication of diabetes mellitus (DM). Endoplasmic reticulum (ER) stress is an important factor in the regulation of pathological processes in DN, and excessive ER stress can lead to apoptosis. Although the IL-33/ST2 axis is known to be involved in diabetic kidney disease or related nephropathy, its role and molecular mechanisms remain poorly understood in terms of DN. The purpose of this study was to investigate the effects of IL-33/ST2 signaling on DN and to characterize the roles that ER stress and apoptosis play in DN. METHODS: To investigate this study, mice were randomly assigned into DN (induced by 0.1% STZ) and Control groups. Biochemical indices (FBG, BUN, UPR, UCE) were measured in serum and urine samples to reflect blood glucose and kidney damage. Quantitative real-time PCR, western blot, and immunofluorescence were used to assess gene and protein expression of the IL-33/ST2 axis and ER stress relative signaling molecule. Apoptosis was analyzed by flow cytometry. RESULTS: IL-33 levels are significantly increased in the kidneys of patients and mice with DN. Double immunofluorescence staining showed that IL-33 colocalized with CD31-positive endothelial cells. Treatment with IL-33 attenuated kidney injury in Streptozotocin (STZ)-treated mice. In vitro, we showed that IL-33 attenuated ER stress and apoptosis in glomerular endothelial cells. However, sST2 treatment significantly reversed these effects of IL-33. CONCLUSION: Together, these data suggest that IL-33/ST2 signaling mitigates STZ-induced renal damage, partly at least, by suppressing ER stress and apoptosis. Therefore, IL-33 may be an effective therapeutic target in DN.

[Identification and analysis of terpene synthase (TPS) gene family in Schizonepeta tenuifolia].

Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.

Highly Efficient Stable Luminescent Radical-Based X-ray Scintillator.

Stable luminescent radicals are open-shell emitters with unique doublet emission characteristics. This feature makes stable luminescent radicals exhibit widespread application prospects in constructing optical, electrical, and magnetic materials. In this work, a stable luminescent radical-based X-ray scintillator of AuPP-1.0 was prepared, which exhibited a high X-ray excited luminescence (XEL) efficiency as well as excellent stability. A mechanism study showed that the heavy atom of Au in AuPP-1.0 endowed it with effective absorption of X-rays, and the doublet emission characteristics of AuPP-1.0 significantly increased its exciton utilization rate in the radioluminescence process. Moreover, AuPP-1.0 has good processability to fabricate a flexible screen for high-quality X-ray imaging, whose resolution can reach 20 LP mm-1. This work demonstrates that the doublet emission is beneficial for improving the exciton utilization rate of radioluminescence, providing a brand-new strategy for the construction of high-performance X-ray scintillators.

Improving Gibberellin GA3 Production with the Construction of a Genome-Scale Metabolic Model of Fusarium fujikuroi.

Liquid fermentation is the primary method for GA3 production usingFusarium fujikuroi. However, production capacity is limited due to unknown metabolic pathways. To address this, we constructed a genome-scale metabolic model (iCY1235) with 1753 reactions, 1979 metabolites, and 1235 genes to understand the GA3 regulation mechanisms. The model was validated by analyzing growth rates under different glucose uptake rates and identifying essential genes. We used the model to optimize fermentation conditions, including carbon sources and dissolved oxygen. Through the OptForce algorithm, we identified 20 reactions as targets. Overexpressing FFUJ_02053 and FFUJ_14337 resulted in a 37.5 and 75% increase in GA3 titers, respectively. These targets enhance carbon flux toward GA3 production. Our model holds promise for guiding the metabolic engineering of F. fujikuroi to achieve targeted overproduction. In summary, our study utilizes the iCY1235 model to understand GA3 regulation, optimize fermentation conditions, and identify specific targets for enhancing GA3 production through metabolic engineering.

The effects of carbon nitrogen ratio and salinity on the treatment of swine digestion effluent simultaneously producing bioenergy by microalgae biofilm.

In order to remove high concentrations of ammonia nitrogen (NH4+-N) and refractory sulfamethazine (SM2) from swine digestion effluent, different carbon/nitrogen (C/N) ratios and salinity were used to determine the effects of pollutants removal in the microalgae biofilm system. Microalgae biofilm treatment under optimal environmental conditions in synthetic swine digestion effluent were C/N ratio of 20 and salinity of 140 mM. In order to make the actual swine digestion effluent discharge up to the standard, three different two-cycle treatments (suspended microalgae, microalgae biofilm, microalgae biofilm under the optimal conditions) were studied. The results showed that after two-cycle treatment with microalgae biofilm under the optimal conditions, the actual swine digestion effluent levels of total nitrogen (TN), NH4+-N, total phosphorus (TP), chemical oxygen demand (COD), SM2 were 22.65, 9.32, 4.11, 367.28, and 0.99 mg L-1, respectively, which could satisfy the discharge standards for livestock and poultry wastewater in China. At the same time, first-order kinetic simulation equations suggested a degradation half-life of 4.85 d for SM2 under optimal conditions in microalgae biofilm, and microbial community analysis indicated that the dominant genus was Halomonas. Furthermore, 35.66% of lipid, 32.56% of protein and 18.44% of polysaccharides were harvested after two-cycle in microalgae biofilm treatment under optimal environmental conditions. These results indicated that the regulation of C/N and salinity in microalgae biofilm for the treatment of swine digestion effluent was a high-efficiency strategy to simultaneously achieve wastewater treatment and bioenergy production.

Comparison of Carotid Blood Flow Measured by Ultrasound and Cardiac Output in Patients Undergoing Cardiac Surgery.

BACKGROUND: In general, cerebral blood flow accounts for 10-15% of cardiac output (CO), of which about 75% is delivered through the carotid arteries. Hence, if carotid blood flow (CBF) is constantly proportional to CO with high reproducibility and reliability, it would be of great value to measure CBF as an alternative to CO. The aim of this study was to investigate the direct correlation between CBF and CO. We hypothesized that measurement of CBF could be a good substitute for CO, even under more extreme hemodynamic conditions, for a wider range of critically ill patients. METHODS: Patients aged 65-80 years, undergoing elective cardiac surgery were included in this study. CBF in different cardiac cycles were measured by ultrasound: systolic carotid blood flow (SCF), diastolic carotid blood flow (DCF), and total (systolic and diastolic) carotid blood flow (TCF). CO simultaneously was measured by transesophageal echocardiography. RESULTS: For all patients, the correlation coefficients between SCF and CO, TCF and CO were 0.45 and 0.30, respectively, which were statistically significant, but not between DCF and CO. There was no significant correlation between either SCF, TCF or DCF and CO, when CO was <3.5 L/min. CONCLUSIONS: Systolic carotid blood flow may be used as a better index to replace CO. However, the method of direct measurement of CO is essential when the patient's heart function is poor.

Realizing Nanolime Aqueous Dispersion via Ionic Liquid Surface Modification to Consolidate Stone Relics.

After decades of research in the conservation of cultural heritage, nanolime (NL) has emerged as a potential alternative inorganic material to the frequently used organic materials. However, its poor kinetic stability in water has been a major challenge that restricted its penetration depth through cultural relics and resulted in unsatisfactory conservation outcomes. Here, for the first time, we realize NL water dispersion by modification of ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) via a sample aqueous solution deposit method. Our findings indicate that the cation of the ionic liquid (IL) binds strongly to the surface of NL particles (IL-NL) by forming hydrogen bonds with Ca(OH)2 facets. The absorption of IL causes an unexpected significant alteration in the morphology of NL particles and results in a drastic reduction in NL's size. More importantly, this absorption endows NL excellent kinetic stability dispersed into water and implements NL water dispersion, which makes a breakthrough in terms of extreme poor kinetic stability of as-synthesized NL and commercial NL in water. The mechanism driving IL-NL water dispersion is explained by Stern theory. In the context of consolidating weathered stone, the presence of IL may delay carbonation of NL but the penetration depth of IL-NL through stone samples is three times deeper than that of as-synthesized and commercial NLs. Additionally, the consolidation strength of IL-NL is similar to that of as-synthesized NL and commercial NL. Moreover, IL-NL has no significant impact on the permeability, pore size, and microstructure of consolidated stone relics. Our research contributes to the field of NL-related materials and will enhance the dissemination and utilization of NL-based materials in the preservation of water-insensitive cultural heritage.

Pelvic floor dysfunction and electrophysiology in postpartum women at 6-8 weeks.

Objective: To investigate the incidence of pelvic floor dysfunction (PFD) and electrophysiological indicators in postpartum women at 6-8 weeks and explore the influence of demographic characteristics and obstetric factors. Methods: A survey questionnaire collected information about the conditions of women during their pregnancy and puerperal period and their demographic characteristics; pelvic organ prolapse quantitation (POP-Q) and pelvic floor muscle electrophysiology (EP) examination were conducted in postpartum women at 6-8 weeks. Results: Vaginal delivery was a risk factor for anterior pelvic organ prolapse (POP) (OR 7.850, 95% confidence interval (CI) 5.804-10.617), posterior POP (OR 5.990, 95% CI 3.953-9.077), anterior and posterior stage II POP (OR 6.636, 95% CI 3.662-15.919), and postpartum urinary incontinence (UI) (OR 6.046, 95% CI 3.894-9.387); parity was a risk factor for anterior POP (OR 1.397,95% CI 0.889-2.198) and anterior and posterior stage II POP (OR 4.162, 95% CI 2.125-8.152); age was a risk factor for anterior POP (OR 1.056, 95% CI 1.007-1.108) and postpartum UI (OR 1.066, 95% CI 1.014-1.120); body mass index (BMI) was a risk factor for postpartum UI (OR 1.117, 95% CI 1.060-1.177); fetal birth weight was a risk factor for posterior POP (OR 1.465, 95% CI 1.041-2.062); and the frequency of pregnancy loss was a risk factor for apical POP (OR 1.853, 95% CI 1.060-3.237). Conclusion: Pelvic floor muscle EP is a sensitive index of early pelvic floor injury. The changes in muscle strength and fatigue degree coexist in different types of postpartum PFD, and each has its own characteristics.

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy.

Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (- 2.82, 11.85) mm3 vs. - 1.12 (- 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160-6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients.Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

Preliminary study of the significance of reverberation by IVUS detection for patients with severe calcified lesions.

To explore the potential significance of the reverberation of calcification by comparing both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) measurement post manual coregistration. The reverberation phenomenon is often detected by IVUS for severe calcified lesions post rotational atherectomy (RA), which is thought to be due to the glassy and smooth inner surfaces of calcifications. Because of the poor penetration of IVUS, it is impossible to measure the thickness of calcifications, and the relationship between multiple reverberations and the thickness of calcification lesions has not been reported before. A total of forty-nine patients with severe calcified coronary lesions that were detected by IVUS and OCT simultaneously were enrolled in our retrospective study. If reverberation phenomena were detected by IVUS, intravascular imaging (IVI) data (including distance between the IVUS catheter center and the inner surface of the reverberation signal, the intervals between all adjacent reverberation signals, the number of layers of reverberation in IVUS, and the thickness of the calcification in OCT) were measured at the same position and same direction (each cross-section had 4 mutually perpendicular directions) at 1-mm intervals. The correlation between each reverberation observational value and OCT data was the primary target in this retrospective study, and the correlation between reverberation and calcium crack post predilatation was analyzed in other 15 patients. Four hundred twenty-eight valid observational points were analyzed simultaneously by IVUS and OCT; among them, 300 points had a single layer of reverberation, 83 had double layers of reverberation and 42 had multiple layers (≥ 3 layers) of reverberation by IVUS detection post-RA. Multivariate logistic regression analysis showed that the number of layers of reverberation by IVUS was significantly related to the thickness of calcifications by OCT at the same point and in the same direction (p < 0.001). Single, double, and multiple layers of reverberation in IVUS correspond to median calcification thicknesses (interquartile ranges (IQRs)) of 0.620 mm (0.520-0.720), 0.950 mm (0.840-1.040) and 1.185 mm (1.068-1.373), respectively, by OCT detection. Another 100 points in other 15 patients with integrated IVUS data pre- and post-predilatation showed that only single layer of reverberation was related to calcium crack (p < 0.001). The number of layers of reverberation signal detected by IVUS is positively correlated with the thickness of calcifications measured by OCT post-RA and single layer of reverberation is correlated to calcium crack post-predilatation.

Selective inhibition of inflammatory cytokine storm in macrophages by α-momorcharin / 中国药理学通报

Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).

[Responses of soil microbial carbon use efficiency to short-term nitrogen addition in Castanopsis fabri forest]. / ç½—æµ®æ ²æž—åœŸå£¤å¾®ç”Ÿç‰©ç¢³åˆ©ç”¨æ•ˆçŽ‡å¯¹çŸ­æœŸæ°®æ·»åŠ çš„å“åº”.

As an important parameter regulating soil carbon mineralization, microbial carbon use efficiency (CUE) is essential for the understanding of carbon (C) cycle in terrestrial ecosystems. Three nitrogen supplemental levels, including control (0 kg N·hm-2·a-1), low nitrogen (40 kg N·hm-2·a-1), and high nitrogen (80 kg N·hm-2·a-1), were set up in a Castanopsis fabri forest in the Daiyun Mountain. The basic physical and chemical properties, organic carbon fractions, microbial biomass, and enzyme activities of the soil surface layer (0-10 cm) were measured. To examine the effects of increasing N deposition on microbial CUE and its influencing factors, soil microbial CUE was measured by the 18O-labelled-water approach. The results showed that short-term N addition significantly reduced microbial respiration rate and the activities of C and N acquisition enzymes, but significantly increased soil microbial CUE. ß-N-acetyl amino acid glucosidase (NAG)/microbial biomass carbon (MBC), microbial respiration rate, ß-glucosidase (BG)/MBC, cellulose hydrolase (CBH)/MBC, and soil organic carbon content were the main factors affecting CUE. Moreover, CUE significantly and negatively correlated with NAG/MBC, microbial respiration rate, BG/MBC, and CBH/MBC, but significantly and positively correlated with soil organic carbon. In summary, short-term N addition reduced the cost of soil microbial acquisition of C and N and microbial respiration, and thus increased soil microbial CUE, which would increase soil carbon sequestration potential of the C. fabri forest.

B-cell receptor associated protein 31 deficiency decreases the expression of adhesion molecule CD11b/CD18 and PSGL-1 in neutrophils to ameliorate acute lung injury.

Acute lung injury (ALI) and its more severe condition acute respiratory distress syndrome (ARDS) are critical life-threatening disorders characterized by an excessive influx of neutrophils into the alveolar space. Neutrophil infiltration is a multi-step process involving the sequential engagement of adhesion molecules. The adhesion molecule CD11b/CD18 acts as an important role in the recruitment of neutrophils to lung tissues in the ALI model. B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum transmembrane protein, has been reported to regulate the cellular anterograde transport of CD11b/CD18 in human neutrophils. To explore how BAP31 regulates CD11b/CD18 in mouse neutrophils, we constructed myeloid-specific BAP31 knockdown mice in this study. Biological investigations indicated that BAP31 deficiency could significantly alleviated lung injury, as evidenced by the improved histopathological morphology, reduced pulmonary wet/dry weight ratio, inhibited myeloperoxidase level and decreased neutrophil counts in the bronchoalveolar lavage fluid. Further studies clarified that BAP31 deficiency obviously down-regulated the expression of CD11b/CD18 and P-selectin glycoprotein ligand-1 (PSGL-1) by deactivating the nuclear factor kappa B (NF-κB) signaling pathway. Collectively, our results revealed that BAP31 depletion exerted a protective effect on ALI, which was possibly dependent on the attenuation of neutrophil adhesion and infiltration by blocking the expression of adhesion molecules CD11b/CD18 and PSGL-1. These findings implied the potential of BAP31 as an appealing protein to mediate the occurrence of ALI.

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up.

BACKGROUND AND AIMS: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. METHODS: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. RESULTS: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). CONCLUSIONS: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.