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Objective To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients.Methods From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis.Results A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively.Conclusion Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

BackgroundDachaihu decoction (Dachaihu tang) plays a crucial role in treating acute illnesses. Recently, a significant number of clinical studies on Dachaihu decoction for acute cholecystitis (AC) have been published. This study was conducted to assess the efficacy and safety of Dachaihu decoction in patients with this condition.MethodsTo identify relevant randomized controlled trials (RCTs), eight databases and three clinical trial registries were searched from inception to 30 June 2024. Two researchers independently screened and extracted data from eligible studies using EndNote X9 and Microsoft Office Excel 2019. RoB 2.0 was used to assess the risk of bias in the included studies. Stata 17.0 was used for data analysis. Publication bias and its impact on result stability were evaluated using a funnel plot and the “trim-and-fill” method. The quality of evidence was graded using the GRADE assessment system.ResultsThirty-three RCTs involving 2,851 participants were included. The treatment group demonstrated improved clinical efficacy (RR = 1.18; 95% CI = 1.13 to 1.24), significantly reduced length of hospital stay (MD = −1.78 days; 95% CI = –2.02 to −1.53), and the incidence of adverse events (RR = 0.31; 95% CI = 0.20 to 0.48). Additionally, there appeared to be reductions in the time for abdominal pain to resolve (MD = −1.92 days; 95% CI = –2.33 to −1.51), fever to disappear (MD = −1.52 days; 95% CI = –1.90 to −1.14), white blood cell count to return to normal (MD = −2.89 days; 95% CI = –3.32 to −2.46), alanine aminotransferase (ALT) levels (MD = −11.88 U/L; 95% CI = –15.29 to −8.47), aspartate aminotransferase (AST) levels (MD = −8.74 U/L; 95% CI = –9.76 to −7.72), neutrophil percentage (MD = −9.68; 95% CI = –11.33 to −8.03), TNF-α levels (SMD = −2.10 pg/L; 95% CI = –2.43 to −2.78), and certainty of evidence (moderate-to-low certainty).ConclusionDachaihu decoction may be an effective botanical formula for managing AC and a lower incidence of adverse events. However, due to the substantial risk of bias and heterogeneity across the included studies, these findings should be interpreted with caution and require further validation through well-designed, high-quality trials.Systematic Review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=573332.

BackgroundHypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?ObjectiveWe aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults.MethodsData from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.ResultsDuring a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs

Abstract 2,5-Dimethylpyrazine (2,5-DMP) is important pharmaceutical raw material and food flavoring agent. Recently, engineering microbes to produce 2,5-DMP has become an attractive alternative to chemical synthesis approach. In this study, metabolic engineering strategies were used to optimize the modified Escherichia coli BL21 (DE3) strain for efficient synthesis of 2,5-DMP using L-threonine dehydrogenase (EcTDH) from Escherichia coli BL21, NADH oxidase (EhNOX) from Enterococcus hirae, aminoacetone oxidase (ScAAO) from Streptococcus cristatus and L-threonine transporter protein (EcSstT) from Escherichia coli BL21, respectively. We further optimized the reaction conditions for synthesizing 2,5-DMP. In optimized conditions, the modified strain can convert L-threonine to obtain 2,5-DMP with a yield of 2897.30 mg/L. Therefore, the strategies used in this study contribute to the development of high-level cell factories for 2,5-DMP. Graphical Abstract

Background: Acetaldehyde dehydrogenase (ALDH) is a common oxidoreductase and one of the aldehyde dehydrogenases, which can convert toxic acetaldehyde to harmless acetyl CoA. Results: A novel acetaldehyde dehydrogenase (LpALDH) from Lactiplantibacillus plantarum was obtained by gene mining and then was analyzed by a series of bioinformatics software. Phylogenetic tree results showed that LpALDH was highly homologous with acetaldehyde dehydrogenase derived from Pediococcus sp., and their sequence similarity was 62.9%. Moreover, it was successfully expressed in Escherichia coli BL21, its expression level was 195 U/mL, which was about 600 times than that expressed in L. plantarum. After purification by affinity chromatography, the specific activity of reLpALDH was 1709 U/mg. Its temperature optimum was 35°C, and the optimal reaction pH was 8.0. Moreover, the purified LpALDH showed good stability in simulated gastrointestinal fluids, which indicated that it had great potential in functional food additive field. Conclusions: This research also laid a solid foundation for further molecular modification, optimal expression host selection and application of acetaldehyde dehydrogenases.How to cite: Wang Z, He J, Liu X, et al. High-level expression of an acetaldehyde dehydrogenase from Lactiplantibacillus plantarum and preliminary evaluation of its potential as a functional food additive. Electron J Biotechnol 2023;63. https://doi.org/10.1016/j.ejbt.2022.12.005.

Abstract Introduction This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. Methods Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. Results TEAS ameliorated sleep quality at D1 and D3 (PSQI P

Abstract Background Lactiplantibacillus plantarum has various healthcare functions including the regulation of immunity and inflammation, reduction of serum cholesterol levels, anti-tumor activity, and maintenance of the balance of intestinal flora. However, the underlying metabolic and regulatory mechanisms of these processes remain unclear. Our previous studies have shown that the LysR type transcriptional regulator of L. plantarum (LpLttR) regulates the biotransformation of conjugated linoleic acids (CLAs) through the transcriptional activation of cla-dh (coding gene for CLA short-chain dehydrogenase) and cla-dc (coding gene for CLA acetoacetate decarboxylase). However, the regulatory network and function of LpLttR have not yet been characterized in L. plantarum. Results In this study, the regulatory role of LpLttR in various cellular processes was assessed using transcriptome analysis. The deletion of LpLttR had no evident influence on the bacterial growth. The transcriptome data showed that the expression of nine genes were positively regulated by LpLttR, and the expression of only two genes were negatively regulated. Through binding motif analysis and molecular interaction, we demonstrated that the regulatory region of the directly regulated genes contained a highly conserved sequence, consisting of a 15-base long box and rich in AT. Conclusion This study revealed that LpLttR of L. plantarum did not play a global regulatory role similar to that of the other transcriptional regulators in this family. This study broadens our knowledge of LpLttR and provides a theoretical basis for the utilization of L. plantarum.

Nicotinamide riboside kinase (NRK) plays an important role in the synthesis of β -nicotinamide nucleotide (NMN). NMN is a key intermediate of NAD+ synthesis, and it actually contribute to the well-being of our health. In this study, gene mining technology was used to clone nicotinamide nucleoside kinase gene fragments from S. cerevisiae, and the ScNRK1 was achieved a high level of soluble expression in E. coli BL21. Then, the reScNRK1 was immobilized by metal affinity label to optimize the enzyme performance. The results showed that the enzyme activity in the fermentation broth was 14.75 IU/mL, and the specific enzyme activity after purification was 2252.59 IU/mg. After immobilization, the optimum temperature of the immobilized enzyme was increased by 10°C compared with the free enzyme, and the temperature stability was improved with little change in pH. Moreover, the activity of the immobilized enzyme remained above 80% after four cycles of immobilized reScNRK1, which makes the enzyme more advantageous in the enzymatic synthesis of NMN.

Abstract Many policies and studies globally have highlighted the pivotal role of wetland ecosystems regarding wetland biota and their ecological status. With the strengthening of wetland ecosystem management legislation and policy, wetland restoration should also consider increasing habitat diversity to improve biota. We explore whether the construction of artificial ecological islands can increase the diversity of and macroinvertebrates before assessing the effects of actively constructing islands via human intervention on wetland protection. We discuss changes in macroinvertebrate diversity (i) with and without islands, (ii) at different water‐level gradients surrounding the islands, (ⅲ) on different island substrates, and (ⅳ) at different time scales. We used ANOVA, ANOSIM, and cluster analysis to test the differences. The macroinvertebrate communities had spatially heterogeneous distributions which changes over time due to both natural and anthropogenic stresses. The establishment of islands significantly increased the community composition and biodiversity of the macroinvertebrate. Water depth and substrate affect community composition of macrozoobenthos. The abundance and diversity of macroinvertebrates can influence the biodiversity of their predators (fish and waterbirds). Potentially, the construction of islands could provide some cobenefits for the conservation of wetland fauna. Synthesis and applications. Establishing artificial ecological islands in broad open‐water areas and increasing water‐level gradient and substrate diversity can increase microhabitat availability and habitat heterogeneity. These changes can adapt to different ecological niches of aquatic organisms, increase biodiversity, and have a positive effect on the ecological restoration of inland freshwater marshes and wetlands.

ABSTRACT CLA (conjugated linoleic acid) has attracted substantial attention due to its physiological functions, including regulating immunity, reducing obesity, and contributing to cancer suppression. In Lactiplantibacillus plantarum, CLA oleate hydratase (CLA-HY), CLA short-chain dehydrogenase (CLA-DH), and CLA acetoacetate decarboxylase (CLA-DC) catalyze the biotransformation of linoleic acid (LA) to CLA. However, the underlying transcriptional regulation mechanism of this pathway remains largely unknown. In this study, the potential transcriptional regulators that might bind to the cla promoter of L. plantarum AR195 were investigated by DNA pulldown. Interestingly, ArgR2, the transcriptional regulator of arginine metabolism, was identified as a potential regulator involved in the regulation of CLA biotransformation. Electrophoretic mobility shift assay (EMSA) and molecular interaction results demonstrated the specific binding of ArgR2 to the regulatory region of the cla operon. The knockout of argR2 led to the downregulation of cla-dh and cla-dc by 91% and 34%, respectively, resulting in a decline in the CLA yield by 14%. A segmental EMSA revealed that ArgR2 bound to three distinct sites in the cla regulatory region, and these binding sites were highly conserved and rich in AT. The regulatory mechanism of ArgR2 on CLA biosynthesis further expanded our knowledge of the regulatory mechanism of CLA biosynthesis in L. plantarum and laid the theoretical foundation for the production and application of CLA. IMPORTANCE CLA (conjugated linoleic acid) has received extensive attention owing to its important physiological functions. CLA from natural sources is far from meeting people’s demands. Lactic acid bacteria can efficiently synthesize cis-9,trans-11-CLA and trans-10,cis-12-CLA, which possess physiological activities. However, little is known about the regulatory mechanism. In this study, we identified that the biosynthesis of CLA in L. plantarum AR195 was transcriptionally regulated by the arginine biosynthesis regulatory protein ArgR2. The regulation mechanism of ArgR2 on CLA biosynthesis lays a theoretical foundation for the regulation of CLA synthesis and industrial production.

Abstract Background Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β (IL-1β)-induced chondrocytes. Results No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1β significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1β-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways. Conclusion Our results provide the evidence that UA could attenuate IL-1β-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.

Purpose: Graft- versus -host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. Methods: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0–2.0) × 10 6 /kg once a week. Results: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 10 6 cells/kg (range, 0.8–1.8 × 10 6 ) cells/kg, and the median numbers of infusion were 2 (range, 1–7) and 3 (range, 2–12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16–118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression ( n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function ( n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22–84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression ( n = 2), severe fungal pneumonia ( n = 1), and relapse ( n = 1). Conclusion: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future.

Introduction: Results from recent trials assessing the effect of oral vitamin C supplementation on serum uric acid (SUA) have been inconsistent. Objectives: The purpose of this study was to explore the association between oral vitamin C supplementation and serum uric acid. Methods: PUBMED, EMBASE, CNKI, Web of Science, and CENTRAL of Cochrane library databases were searched to identify relevant articles published up to February 2020. Heterogeneity was evaluated using I-square (I2) statistics. Random-effects model was used to pool weighted mean differences (WMD) and 95 % confidence interval (CI) as summary effect sizes. Results: The total sixteen eligible randomized controlled trials (RCTs) containing 1,013 participants were included in this meta-analysis. The pooled findings showed that vitamin C supplementation had a significant effect of lowering SUA. The subgroup analyses showed that the effect of vitamin C supplementation on SUA has positive association with mean age of participants

5-Hydroxytryptophan (5-HTP) plays an important role in the regulation of emotion, behavior, sleep, pain, body temperature, and other physiological functions. It is used in the treatment of depression, insomnia, migraine, and other diseases. Due to a lack of effective biosynthesis methods, 5-HTP is mainly obtained by natural extraction, which has been unable to meet the needs of the market. Through the directed evolution of enzymes and the introduction of substrate supply pathways, 5-HTP biosynthesis and yield increase have been realized. This review provides examples that illustrate the production mode of 5-HTP and the latest progress in microbial synthesis.

As a type of flexible impermeable material, a PVC geomembrane must be cooperatively used with cushion materials. The contact interface between a PVC geomembrane and cushion easily loses stability. In this present paper, we analyzed the shear models and parameters of the interface to study the stability. Two different cushion materials were used: the common extrusion sidewall and non-fines concrete. To simulate real working conditions, flexible silicone cushions were added under the loading plates to simulate hydraulic pressure loading, and the loading effect of flexible silicone cushions was demonstrated by measuring the actual contact areas under different normal pressures between the geomembrane and cushion using the thin-film pressure sensor. According to elastomer shear stress, there are two main types of shear stress between the PVC geomembrane and the cushion: viscous shear stress and hysteresis shear stress. The viscous shear stress between the geomembrane and the cement grout was measured using a dry, smooth concrete sample, then the precise formula parameters of the viscous shear stress and viscous friction coefficient were obtained. The hysteresis shear stress between the geomembrane and the cushion was calculated by subtracting the viscous shear stress from the total shear stress. The formula parameters of the hysteresis shear stress and hysteresis friction coefficient were calculated. The three-dimensional box-counting dimensions of the cushion surface were calculated, and the formula parameters of the hysteresis friction were positively correlated with the three-dimensional box dimensions.

AIM: To compare the optic nerve head (ONH) perfusion in both eyes of unilateral idiopathic macular hole (IMH) with normal control group by using optical coherence tomography angiography (OCTA) and investigate its correlationship with the macular blood perfusion. METHODS: We performed a prospective and cross-sectional study that included 19 patients with full-thickness unilateral IMH and 24 age- and sex-matched controls. All participants received OCTA test. The ONH perfusion was evaluated by the regions of peripapillary and whole en face (the sum of peripapillary and optic disc). The potential correlationship between ONH and parafovea were implied. All the data were performed using the nonparametric test. RESULTS: The mean values of ONH presented that normal control >IMH >unaffected eyes. A statistical variation was found between three groups in the region of temporal (P=0.007). Vessel density notablely decreased on the layers of superficial, deep and choroid of parafovea region in IMH group. The correlative coefficients showed that respectively whole en face and deep retina: r=0.528, peripapillary and deep retina: r=0.525, whole en face and choriocapillaries: r=0.569, peripapillary and choriocapillaries: r=0.504. CONCLUSION: Our study demonstrate a reduced ONH vessel density in both eyes of IMH patients and the vessel density of ONH in IMH eyes are positively correlated with both the retina capillary and choriocapillary in parafoveal. The reduction of vessel densities may indicate the hypoperfusion in IMH eyes.

Phenanthrene (PHE) is a common pollutant of acidic and non-acidic environments that is recalcitrant to biodegradation. Herein, Burkholderia fungorum FM-2 (GenBank accession no. KM263605) was isolated from oil-contaminated soil in Xinjiang and characterized morphologically, physiologically, and phylogenetically. Environmental parameters including PHE concentration, pH, temperature, and salinity were optimized, and heavy metal tolerance was investigated. The MIC of strain FM-2 tolerant to Pb(II) and Cd(II) was 50 and 400 mg L−1, respectively, while the MIC of Zn(II) was >1,200 mg L−1. Atypically for a B. fungorum strain, FM-2 utilized PHE (300 mg L−1) as a sole carbon source over a wide pH range (between pH 3 and 9). PHE and heavy metal metabolism were assessed using gas chromatography (GC), inductively coupled plasma optical emission spectroscopy (ICP-OES), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), Fourier-transform infrared (FTIR) spectroscopy and ultraviolet (UV) absorption spectrometry. The effects of heavy metals on the bioremediation of PHE in soil were investigated, and the findings suggest that FM-2 has potential for combined bioremediation of soils co-contaminated with PHE and heavy metals.

Background: Enhanced recovery after surgery (ERAS) protocols or fast-track (FT) programs enable a shorter hospital stay and lower complication rate. Minimally invasive surgery (MIS) is associated with a lesser trauma and a quicker recovery in many elective abdominal surgeries. However, little is known of the safety and effectiveness made by ERAS protocols combined with MIS for gastric cancer. The purpose of this study was to evaluate the safety and effectiveness made by FT programs and MIS in combination or alone. Methods: We summarized an 11-year experience on gastric cancer patients undergoing elective laparotomy or minimally invasive gastric resection in standard cares (SC) or FT programs during January 2004 to December 2014. A total of 984 patients were enrolled and assigned into four groups: open gastrectomies (OG) with SC (OG + SC group, n = 167); OG with FT programs (OG + FT group, n = 277); laparoscopic gastrectomies (LG) with FT programs (LG + FT group, n = 248); and robot-assisted gastrectomies (RG) with FT programs (RG + FT group, n = 292). Patients' data were collected to evaluate the clinical outcome. The primary end point was the length of postoperative hospital stay. Results: The OG + SC group showed the longest postoperative hospital stay (mean: 12.3 days, median: 11 days, interquartile range [IQR]: 6–16 days), while OG + FT, LG + FT, and RG + FT groups recovered faster (mean: 7.4, 6.4, and 6.6 days, median: 6, 6, and 6 days, IQR: 3–9, 4–8, and 3–9 days, respectively, all P< 0.001). The postoperative rehabilitation parameters such as flatus time after surgery (4.7 ± 0.9, 3.1 ± 0.8, 3.0 ± 0.9, and 3.1 ± 0.9 days) followed the same manner. After 30 postoperative days' follow-up, the total incidence of complications was 9.6% in OG + SC group, 10.1% in OG + FT group, 8.1% in LG + FT group, and 10.3% in RG + FT group. The complications showed no significant differences between the four groups (all P > 0.05). Conclusions: ERAS protocols alone could significantly bring fast recovery after surgery regardless of the surgical technique. MIS further reduces postoperative hospital stay. It is safe and effective to apply ERAS protocols combined with MIS for gastric cancer.

Assimilation of short-chain fatty acids (SCFAs) plays an important role in the survival and lipid biosynthesis of Mycobacteria. However, regulation of this process has not been thoroughly described. In the present work, we demonstrate that GlnR as a well-known nitrogen-sensing regulator transcriptionally modulates the AMP-forming propionyl-CoA synthetase (MsPrpE), and acetyl-CoA synthetases (MsAcs) is associated with SCFAs assimilation in Mycobacterium smegmatis, a model Mycobacterium. GlnR can directly activate the expression of MsprpE and Msacs by binding to their promoter regions based upon sensed nitrogen starvation in the host. Moreover, GlnR can activate the expression of lysine acetyltransferase encoding Mspat, which significantly decreases the activity of MsPrpE and MsAcs through increased acylation. Next, growth curves and resazurin assay show that GlnR can further regulate the growth of M. smegmatis on different SCFAs to control the viability. These results demonstrate that GlnR-mediated regulation of SCFA assimilation in response to the change of nitrogen signal serves to control the survival of M. smegmatis. These findings provide insights into the survival and nutrient utilization mechanisms of Mycobacteria in their host, which may enable new strategies in drug discovery for the control of tuberculosis.

Objective: Sitagliptin, a dipeptidyl peptidase IV (DPP-Ⅳ) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats. Materials and methods: The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis. Cardiac inflammation, fibrosis, cardiomyocyte density, lipid accumulation, and receptor-interacting protein kinase 3 (RIP3) level, related to apoptosis, were detected by histopathologic analysis, RT-PCR and western blot analysis to evaluate the effects of sitagliptin on myocardial remodeling of the left ventricle. Results: Diabetic rats showed myocardial hypertrophy or apoptosis, inflammation, lipid accumulation, myocardial fibrosis, elevated collagen content, RIP3 overexpression, and left-ventricular dysfunction. Sitagliptin could reverse the overexpression of RIP3 and alleviate cellular apoptosis in myocardial tissues. It could significantly improve left-ventricular systolic pressure and +dp/dt max, reduce the E/E′ ratio, left ventricular end diastolic pressure, −dp/dt max and Tau in diabetic rats. Conclusions: Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes.