RNF213 modulates γ-herpesvirus infection and reactivation via targeting the viral Replication and Transcription Activator.

Interferons (IFNs) and the products of interferon-stimulated genes (ISGs) play crucial roles in host defense against virus infections. Although many ISGs have been characterized with respect to their antiviral activity, their target specificities and mechanisms of action remain largely unknown. Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is linked to several human malignancies. Here, we used the genetically and biologically related virus, murine gammaherpesvirus 68 (MHV-68) and screened for ISGs with anti-gammaherpesvirus activities. We found that overexpression of RNF213 dramatically inhibited MHV-68 infection, whereas knockdown of endogenous RNF213 significantly promoted MHV-68 proliferation. Importantly, RNF213 also inhibited KSHV de novo infection, and depletion of RNF213 in the latently KSHV-infected iSLK-219 cell line significantly enhanced lytic reactivation. Mechanistically, we demonstrated that RNF213 targeted the Replication and Transcription Activator (RTA) of both KSHV and MHV-68, and promoted the degradation of RTA protein through the proteasome-dependent pathway. RNF213 directly interacted with RTA and functioned as an E3 ligase to ubiquitinate RTA via K48 linkage. Taken together, we conclude that RNF213 serves as an E3 ligase and inhibits the de novo infection and lytic reactivation of gammaherpesviruses by degrading RTA through the ubiquitin-proteasome pathway.

Selenium(II)-Nitrogen Exchange (SeNEx) Chemistry: A Good Chemistry Suitable for Nanomole-Scale Parallel Synthesis, DNA-encoded Library Synthesis, and Bioconjugation.

The continuous development of click reactions with new connecting linkage is crucial for advancing the frontiers of click chemistry. Selenium-nitrogen exchange (SeNEx) chemistry, a versatile chemistry in click chemistry, represents an all-encompassing term for nucleophilic substitution events that replace nitrogen at an electrophilic selenium(II) center, enabling the flexible and efficient assembly of linkages around a Se(II) core. Several SeNEx chemistries have been developed inspired by the biochemical reaction between Ebselen and cysteine residue, and demonstrated significant potential in on-plate nanomole-scale parallel synthesis, selenium-containing DNA-encoded library (SeDEL) synthesis, as well as peptide and protein bioconjugation. This concept aims to present the origins, advancements, and applications of selenium(II)-nitrogen exchange (SeNEx) chemistry while also outlining the potential directions for future research in this field.

The efficacy and safety of pH-responsive and photothermal-sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer.

A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.

The prognostic role of palliative gastrectomy in advanced gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of palliative gastrectomy for advanced GC remains a topic of debate. This study sought to establish whether palliative gastrectomy has an impact on prolonging survival. METHODS: We carried out systematic searches in PubMed, Cochrane Library, Web of Science, and the EMBASE databases from database inception to July 2023 to gather studies that examined the connection between palliative gastrectomy and the prognosis of advanced GC. The study employed overall survival as the primary outcome, with the hazard ratio serving as the selected parameter to gauge the association. Subgroup analyses were performed to delve into potential differences within the included studies, categorizing them by study region and sample size in order to examine possible sources of heterogeneity. The stability of individual studies was assessed through sensitivity analysis. The analysis included 20 articles, encompassing a total of 23,061 patients. RESULTS: According to the meta-analysis results, patients who underwent palliative gastrectomy exhibited a noteworthy enhancement in overall survival (HR: 1.49; 95% CI: 1.12-1.99; P = 0.006) in comparison to those who did not receive this procedure. There was no association between the type of surgery and the length of hospital stay, as revealed by the analysis (HR = -0.02; 95% CI: -0.84-0.81; P = 0.970). CONCLUSIONS: Based on this meta-analysis, patients with advanced gastric cancer who underwent palliative gastrectomy may experience an extended survival duration without a significant prolongation of their hospitalization.

NEK2 affects the ferroptosis sensitivity of gastric cancer cells by regulating the expression of HMOX1 through Keap1/Nrf2.

NEK2 is a serine/threonine protein kinase that is involved in regulating the progression of various tumors. Our previous studies have found that NEK2 is highly expressed in gastric cancer and suggests that patients have a worse prognosis. However, its role and mechanism in gastric cancer are only poorly studied. In this study, we established a model of ferroptosis induced by RSL3 or Erastin in AGS cells in vitro, and konckdown NEK2, HOMX1, Nrf2 by siRNA. The assay kit was used to analyzed cell viability, MDA levels, GSH and GSSG content, and FeRhoNox™-1 fluorescent probe, BODIPY™ 581/591 C11 lipid oxidation probe, CM-H2DCFDA fluorescent probe were used to detected intracellular Fe2+, lipid peroxidation, and ROS levels, respectively. Calcein-AM/PI staining was used to detect the ratio of live and dead cells, qRT-PCR and Western blot were used to identify the mRNA and protein levels of genes in cells, immunofluorescence staining was used to analyze the localization of Nrf2 in cells, RNA-seq was used to analyze changes in mRNA expression profile, and combined with the FerrDb database, ferroptosis-related molecules were screened to elucidate the impact of NEK2 on the sensitivity of gastric cancer cells to ferroptosis. We found that inhibition of NEK2 could enhance the sensitivity of gastric cancer cells to RSL3 and Erastin-induced ferroptosis, which was reflected in the combination of inhibition of NEK2 and ferroptosis induction compared with ferroptosis induction alone: cell viability and GSH level were further decreased, while the proportion of dead cells, Fe2+ level, ROS level, lipid oxidation level, MDA level, GSSG level and GSSG/GSH ratio were further increased. Mechanism studies have found that inhibiting NEK2 could promote the expression of HMOX1, a gene related to ferroptosis, and enhance the sensitivity of gastric cancer cells to ferroptosis by increasing HMOX1. Further mechanism studies have found that inhibiting NEK2 could promote the ubiquitination and proteasome degradation of Keap1, increase the level of Nrf2 in the nucleus, and thus promote the expression of HMOX1. This study confirmed that NEK2 can regulate HMOX1 expression through Keap1/Nrf2 signal, and then affect the sensitivity of gastric cancer cells to ferroptosis, enriching the role and mechanism of NEK2 in gastric cancer.

Utilizing nanotechnology and advanced machine learning for early detection of gastric cancer surgery.

Nanotechnology has emerged as a promising frontier in revolutionizing the early diagnosis and surgical management of gastric cancers. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high surgical and pharmacological therapy recurrence rates. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for detecting and treating cancer. Considering the limitations of GIC MRI and endoscopy and the complexity of gastric surgery, the early diagnosis and prompt treatment of gastric illnesses by nanotechnology has been a promising development. Nanoparticles directly target tumor cells, allowing their detection and removal. It also can be engineered to carry specific payloads, such as drugs or contrast agents, and enhance the efficacy and precision of cancer treatment. In this research, the boosting technique of machine learning was utilized to capture nonlinear interactions between a large number of input variables and outputs by using XGBoost and RNN-CNN as a classification method. The research sample included 350 patients, comprising 200 males and 150 females. The patients' mean ± SD was 50.34 ± 13.04 with a mean age of 50.34 ± 13.04. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.034), distant metastasis (P = 0.004), and tumor stage (P = 0.014) were shown to have a statistically significant link with GC patient survival. AUC was 93.54%, Accuracy 93.54%, F1-score 93.57%, Precision 93.65%, and Recall 93.87% when analyzing stomach pictures. Integrating nanotechnology with advanced machine learning techniques holds promise for improving the diagnosis and treatment of gastric cancer, providing new avenues for precision medicine and better patient outcomes.

Modulating mitochondrial dynamics ameliorates left ventricular dysfunction by suppressing diverse cell death pathways after diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) triggers a detrimental shift in mitochondrial dynamics, characterized by increased fission and decreased fusion, contributing to cardiomyocyte apoptosis and cardiac dysfunction. This study investigated the impact of modulating mitochondrial dynamics on DCM outcomes and underlying mechanisms in a mouse model. DCM induction led to upregulation of fission genes (Drp1, Mff, Fis1) and downregulation of fusion genes (Mfn1, Mfn2, Opa1). Inhibiting fission with Mdivi-1 or promoting fusion with Ginsenoside Rg1 preserved cardiac function, as evidenced by improved left ventricular ejection fraction (LVEF), fractional shortening (FS), and E/A ratio. Both treatments also reduced infarct size and attenuated cardiomyocyte apoptosis, indicated by decreased caspase-3 activity. Mechanistically, Mdivi-1 enhanced mitochondrial function by improving mitochondrial membrane potential, reducing reactive oxygen species (ROS) production, and increasing ATP generation. Ginsenoside Rg1 also preserved mitochondrial integrity and function under hypoxic conditions in HL-1 cardiomyocytes. These findings suggest that restoring the balance of mitochondrial dynamics through pharmacological interventions targeting either fission or fusion may offer a promising therapeutic strategy for mitigating MI-induced cardiac injury and improving patient outcomes.

Isolation and Identification of Monoterpenoids from Callicarpa Nudiflora.

A phytochemical and directional investigation was carried out on the leaves of Callicarpa nudiflora. Various separation methods including silica gel, sephadex LH-20, medium pressure liquid chromatography (MPLC), preparative thin-layer chromatography (p-TLC) and preparative high performance liquid chromatography (p-HPLC) were used to isolate 10 compounds. The comprehensive structural elucidation of five novel monoterpenoids (1-5) was achieved through multi-spectroscopic analyses, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of the identified compounds was assessed.

Three New Steroids from the Roots of Marsdenia tenacissima.

Three undescribed pregnane steroids, 12ß-O-4-hydroxybenzoyl tenacigenin D (1), 12ß-O-4-hydroxybenzoyl tenacigenin A (2), and 11α-nicotinoyl-17ß-marsdenin (3), along with two known analogues (4 and 5), were isolated from the roots of Marsdenia tenacissima. Their structures were elucidated using one- and two-dimensional NMR, high-resolution electron ionization-mass spectrometry, single-crystal X-ray diffraction data, and experimental and density-functional-theory-calculated electronic circular dichroism measurements. All isolated compounds were evaluated for their cytotoxic activities against human lung cancer cells (A549), ovarian carcinoma cells (SKOV-3), gastric cancer cells (MGC 803) and breast cancer cells (MCF-7). Notably, 3 exhibited significant cytotoxic activity against both A549 (median inhibitory concentration (IC50)=16.79 µM) and SKOV-3 (IC50=12.30 µM) cells while exhibiting moderate cytotoxicity on MGC803 and MCF-7 cells.

Fall Detection System Based on Point Cloud Enhancement Model for 24 GHz FMCW Radar.

Automatic fall detection plays a significant role in monitoring the health of senior citizens. In particular, millimeter-wave radar sensors are relevant for human pose recognition in an indoor environment due to their advantages of privacy protection, low hardware cost, and wide range of working conditions. However, low-quality point clouds from 4D radar diminish the reliability of fall detection. To improve the detection accuracy, conventional methods utilize more costly hardware. In this study, we propose a model that can provide high-quality three-dimensional point cloud images of the human body at a low cost. To improve the accuracy and effectiveness of fall detection, a system that extracts distribution features through small radar antenna arrays is developed. The proposed system achieved 99.1% and 98.9% accuracy on test datasets pertaining to new subjects and new environments, respectively.

Bioinspired Selenium-Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole-Scale Medicinal Chemistry and Bioconjugation.

Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage is of great importance for expanding the click chemistry toolbox. We report the first selenium-nitrogen exchange (SeNEx) click reaction between benzoselenazolones and terminal alkynes (Se-N to Se-C), which is inspired by the biochemical SeNEx between Ebselen and cysteine (Cys) residue (Se-N to Se-S). The formed selenoalkyne connection is readily elaborated, thus endowing this chemistry with multidimensional molecular diversity. Besides, this reaction is modular, predictable, and high-yielding, features fast kinetics (k2≥14.43 M-1 s-1), excellent functional group compatibility, and works well at miniaturization (nanomole-scale), opening up many interesting opportunities for organo-Se synthesis and bioconjugation, as exemplified by sequential click chemistry (coupled with ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) and sulfur-fluoride exchange (SuFEx)), selenomacrocycle synthesis, nanomole-scale synthesis of Se-containing natural product library and DNA-encoded library (DEL), late-stage peptide modification and ligation, and multiple functionalization of proteins. These results indicated that SeNEx is a useful strategy for new click chemistry developments, and the established SeNEx chemistry will serve as a transformative platform in multidisciplinary fields such as synthetic chemistry, material science, chemical biology, medical chemistry, and drug discovery.

Metabolic engineering of the acid-tolerant yeast Pichia kudriavzevii for efficient L-malic acid production at low pH.

Currently, the biological production of L-malic acid (L-MA) is mainly based on the fermentation of filamentous fungi at near-neutral pH, but this process requires large amounts of neutralizing agents, resulting in the generation of waste salts when free acid is obtained in the downstream process, and the environmental hazards associated with the waste salts limit the practical application of this process. To produce L-MA in a more environmentally friendly way, we metabolically engineered the acid-tolerant yeast Pichia kudriavzevii and achieved efficient production of L-MA through low pH fermentation. First, an initial L-MA-producing strain that relies on the reductive tricarboxylic acid (rTCA) pathway was constructed. Subsequently, the L-MA titer and yield were further increased by fine-tuning the flux between the pyruvate and oxaloacetate nodes. In addition, we found that the insufficient supply of NADH for cytoplasmic malate dehydrogenase (MDH) hindered the L-MA production at low pH, which was resolved by overexpressing the soluble pyridine nucleotide transhydrogenase SthA from E. coli. Transcriptomic and metabolomic data showed that overexpression of EcSthA contributed to the activation of the pentose phosphate pathway and provided additional reducing power for MDH by converting NADPH to NADH. Furthermore, overexpression of EcSthA was found to help reduce the accumulation of the by-product pyruvate but had no effect on the accumulation of succinate. In microaerobic batch fermentation in a 5-L fermenter, the best strain, MA009-10-URA3 produced 199.4 g/L L-MA with a yield of 0.94 g/g glucose (1.27 mol/mol), with a productivity of 1.86 g/L/h. The final pH of the fermentation broth was approximately 3.10, meaning that the amount of neutralizer used was reduced by more than 50% compared to the common fermentation processes using filamentous fungi. To our knowledge, this is the first report of the efficient bioproduction of L-MA at low pH and represents the highest yield of L-MA in yeasts reported to date.

Enolate-Azide [3 + 2]-Cycloaddition Reaction Suitable for DNA-Encoded Library Synthesis.

The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate-azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles. Thus, it will not only further enrich the DEL chemistry toolbox but also will have great potential in practical DEL synthesis.

Dual-band complementary metamaterial perfect absorber for multispectral molecular sensing.

Metamaterial perfect absorbers (MPAs) show great potential in achieving exceptional sensing performance, particularly in the realm of surface-enhanced infrared absorption (SEIRA) spectroscopy. To this aim, it is highly desirable for the localized hotspots to be readily exposed and accessible to analyte with strong mode confinement to enhance absorption. Here, we propose a quasi-three-dimensional MPA based on cross-shaped coupled complementary plasmonic arrays for highly sensitive refractive index sensing and molecular vibrational sensing. Dual-band perfect absorption can be approached with the two plasmonic resonances corresponding to the electric dipole-like mode of cross antenna array and the magnetic dipole-like mode of cross hole array, respectively. Large portions of the electric field of the hotspots are exposed and concentrated in the gap between the elevated cross antenna and its complementary structure on the substrate, leading to improved sensing sensitivities. An ultrathin polymethyl methacrylate (PMMA) film induces a significant redshift of the magnetic dipole-like mode with an 11.8 nm resonance shift per each nanometer polymer thickness. The value is comparable to the reported sensitivity of single molecule layer sensors. Additionally, the simultaneous detection of the C = O and C-H vibrations of PMMA molecules is enabled with the two plasmonic resonances adjusted by changing the lengths of the two cross branches. Remarkably, the observed mode splitting and anti-crossing behavior imply the strong interaction between plasmonic resonance and molecular vibration. Our dual-band MPA based on coupled complementary plasmonic arrays opens a new avenue for developing highly sensitive sensors for the detection of refractive index and multispectral molecular vibrations.

Dual color infrared photodetector with superconducting metamaterials.

Superconducting photodetection offers a wide spectral coverage ranging from the microwave to X-ray, and in the short wavelength range, single photon sensitivity can be achieved. However, in the longer wavelength infrared region, the system detection efficiency is low due to the lower internal quantum efficiency and weak optical absorption. Here, we utilized the superconducting metamatieral to enhance the light coupling efficiency and reach nearly perfect absorption at dual color infrared wavelengths. Dual color resonances arise from hybridization of local surface plasmon mode of the metamaterial structure and the Fabry-Perot-like cavity mode of metal (Nb)-dielectric (Si)-metamatieral (NbN) tri-layer structure. We demonstrated that, at the working temperature of 8 K slightly below TC ∼8.8 K, this infrared detector exhibits the peak responsivity of 1.2 × 106V/W and 3.2 × 106V/W at two resonant frequencies 36.6 THz and 104 THz, respectively. The peak responsivity is enhanced about ∼8 and ∼22 times, respectively, compared to that of non-resonant frequency (67 THz). Our work provides a way to harvest infrared light efficiently and hence improve the sensitivity of superconducting photodetectors in multispectral infrared range, which may find promising applications in thermal image and gas sensing etc.

Phenylethanoid Glycosides from Caryopteris aureoglandulosa and Their Biological Activities.

This study describes the isolation and identification of two novel phenylethanoid glycosides, aureoglanduloside A (1) and aureoglanduloside B (2), as well as a newly discovered diterpene glycoside, aureoglanduloside C (29). Additionally, 31 known compounds were isolated from the n-butyl alcohol (BuOH) soluble fraction of Caryopteris aureoglandulosa whole dried plants. Their structures were characterized using various spectroscopic techniques and high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, the neuroprotective effects of all phenylethanoid glycosides were evaluated. Specifically, compounds 2 and 10-12 exhibited the ability to promote the phagocytosis of myelin by microglia, and compounds 2, 10-11, and 24 showed the ability to promote the phagocytosis of myelin by astrocytes.

Risk factor analysis for diabetic foot ulcer-related amputation including Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio.

Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer-related amputation including the Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high-risk factors and Kaplan-Meier analysis to correlate high-risk factors with amputation-free survival. Overall, 389 patients underwent 247 amputations over the follow-up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer-related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil-to-lymphocyte ratio and nutritional status. Amputation-free survival was lower for the moderate-to-severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil-to-lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil-to-lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.

Nano-Carbon-Based Application of Parecoxib Sodium Combined with Hydromorphone in Preventing Anesthesia Hyperalgesia Caused by Remifentanil after Thyroidectomy.

Nano-carbon is often used as a tracer in thyroidectomy, to improve the accuracy of the operation. Remifentanil is the most commonly used anesthetic during thyroidectomy, but the use of remifentanil can sometimes cause patients with anesthesia hyperalgesia. Therefore, auxiliary anesthetics are often used in surgery to prevent remifentanil from causing anesthesia hyperalgesia. The purpose of this article is to explore the specific application effect of the fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon in the prevention of remifentanil-induced anesthesia hyperalgesia. Taking 60 patients who underwent thyroidectomy based on carbon nanotechnology in our hospital as the research object, the patients were divided into the parecoxib sodium group, hydromorphone control group and hydromorphone and parecoxib sodium fusion agent group. All patients were injected with remifentanil before surgery for general paralysis. Ten minutes before the end of the operation, the parecoxib sodium group was injected with quantitative parecoxib sodium, and the hydromorphone control group was injected with quantitative hydromorphone, hydromorphone and the parecoxib sodium fusion medicament group was injected with a quantitative combination of parecoxib sodium and hydromorphone. The patient's comfort, calmness, pain, adverse reactions and recovery time of consciousness were counted. The results of the study showed that the sedation score of the hydromorphone and parecoxib sodium fusion drug group was (15.8±1.5), the pain degree score was (1.9±0.5), lower than the other two groups, and the postoperative recovery time was (38±5.0) )min, lower than the other two groups. It can be seen that the use of a fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon is effective in preventing and reducing remifentanil-induced anesthesia hyperalgesia.

Metabolic engineering of microorganisms for L-alanine production.

L-alanine is extensively used in chemical, food, and medicine industries. Industrial production of L-alanine has been mainly based on the enzymatic process using petroleum-based L-aspartic acid as the substrate. L-alanine production from renewable biomass using microbial fermentation process is an alternative route. Many microorganisms can naturally produce L-alanine using aminotransferase or L-alanine dehydrogenase. However, production of L-alanine using the native strains has been limited due to their low yields and productivities. In this review, metabolic engineering of microorganisms for L-alanine production was summarized. Among them, the Escherichia coli strains developed by Dr. Lonnie Ingram's group which can produce L-alanine with anaerobic fermentation process had several advantages, especially having high L-alanine yield, and it was the first one that realized commercialization. L-alanine is also the first amino acid that could be industrially produced by anaerobic fermentation.

Characterization of inflammatory profiles and endothelial dysfunction in diabetic limb arterial occlusion.

Our study aims to detect the changes of adiponectin (APN), endothelin 1 (ET)-1, nitric oxide (NO), cystatin C (cysC) in diabetic limb arterial occlusion (DLAO) patients and unravel their associations with endothelial function. Total 240 type 2 diabetes mellitus (T2DM) patients were divided into a DM group (n = 80, ankle brachial index (ABI) ≥ 0.9) and a DLAO group (n = 160, ABI < 0.9). ABI, flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), serum APN, ET-1, NO, and cysC were compared. There were significant increases in cysC and ET-1, and significant decreases in APN, NO, FMD and NMD of DLAO patients compared to T2DM patients. Serum APN and NO were positively correlated with ABI, while serum cysC and ET-1 were negatively correlated with ABI. cysC, ET-1 and diastolic blood pressure (DBP) were independent predictors of the severity of DLAO. Serum APN was positively correlated with FMD, NMD and NO, but was negatively correlated with ET-1 and cysC. FMD and NMD were positively correlated with APN and NO, and negatively correlated with ET-1 and cysC. Our study deciphers opposite roles of APN, NO, cysC and ET-1 in the development of DLAO and maintaining endothelial function.