Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography.

AIMS: To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). METHODS: 40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry. RESULTS: Macular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power. CONCLUSION: SLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.

Structural insights into type III polyketide synthase CylI from cylindrocyclophane biosynthesis.

Type III polyketide synthases (PKSs) catalyze the formation of a variety of polyketide natural products with remarkable structural diversity and biological activities. Despite significant progress in structural and mechanistic studies of type III PKSs in bacteria, fungi, and plants, research on type III PKSs in cyanobacteria is lacking. Here, we report structural and mechanistic insights into CylI, a type III PKS that catalyzes the formation of the alkylresorcinol intermediate in cylindrocyclophane biosynthesis. The crystal structure of apo-CylI reveals a distinct arrangement of structural elements that are proximal to the active site. We further solved the crystal structures of CylI in complexes with two substrate analogues at resolutions of 1.9 Å. The complex structures indicate that N259 is the key residue that determines the substrate preference of CylI. We also solved the crystal structure of CylI complexed with the alkylresorcinol product at a resolution of 2.0 Å. Structural analysis and mutagenesis experiments suggested that S170 functions as a key residue that determines cyclization specificity. On the basis of this result, a double mutant was engineered to completely switch the cyclization of CylI from aldol condensation to lactonization. This work elucidates the molecular basis of type III PKS in cyanobacteria and lays the foundation for engineering CylI-like enzymes to generate new products.

The Analgesic Mechanism and Recent Clinical Application of Erector Spinae Plane Block: A Narrative Review.

Now, the erector spinae plane block (ESPB) is widely used in various thoracolumbar surgeries. It has unique advantages: simple and convenient operation, low safety risks, and reduced opioid use. The ESPB is used in thoracic surgery, abdominal surgery, and spinal surgery. There are also relevant research reports on postoperative analgesia during general anesthesia surgery. This article searches the PubMed and Web of Science databases to find and screen relevant studies on ESPB since 2019 and retrospectively summarizes the current indications of ESPB. The methodological quality of the included studies was assessed using the Cochrane bias risk tool. The results showed that the current research on ESPB generally provides low-level clinical evidence. The complex anatomy of the erector spinae muscles is both responsible for its unique advantages and restricts its development. Few anatomical studies have clearly and completely demonstrated the diffusion relationship of local anesthetics among the anatomical structures of the erector spinal muscles. The uncontrollability of the diffusion plane prevents ESPB from being applied on a wider scale with a high level of evidence. To further clarify the scope of application of ESPB and achieve the best analgesic effect, in the future, we should focus on the unique anatomical course and distribution of the erector spinal muscles and their fascia and nerves. It is necessary to combine anatomical, imaging, and histological methods to obtain high-quality evidence to guide clinical application.

Utilizing artificial intelligence for precision exploration of N protein targeting phenanthridine sars-cov-2 inhibitors: A novel approach.

The persistent mutation of the novel coronavirus presents a continual threat of infections and associated illnesses. While considerable research efforts have concentrated on the functional proteins of SARS-CoV-2 in the development of anti-COVID-19 therapeutics, the structural proteins, particularly the N protein, have received comparatively less attention. This study focuses on the N protein, a critical structural component of the virus, and employs advanced deep learning models, including EMPIRE and DeepFrag, to optimize the structures of phenanthridine-based compounds. More than 10,000 small molecules, derived through deep learning, underwent high-throughput virtual screening, resulting in the synthesis of 44 compounds. Compound 38 showed a binding potential energy of -8.2 kcal/mol in molecular docking. Surface Plasmon Resonance (SPR) and Microscale Thermophoresis (MST) validation yielded dissociation constants of 353 nM and 726 nM, confirming strong binding to the N protein. Compound 38 demonstrated antiviral activity in vitro and exhibited anti-COVID-19 effects by interfering with the binding of N proteins to RNA. This research underscores the potential of targeting the SARS-CoV-2 N protein for therapeutic intervention and illustrates the efficacy of deep learning model in the design of lead compounds. The application of these deep learning models represents a promising approach for accelerating the discovery and development of antiviral agents.

Subchronic toxic effects of bisphenol A on the gut-liver-hormone axis in rats via intestinal flora and metabolism.

Background: Bisphenol A (BPA), a characteristic endocrine disruptor, is a substance that seriously interferes with the human endocrine system and causes reproductive disorders and developmental abnormalities. However, its toxic effects on the gut-liver-hormone axis are still unclear. Method: Male and female rats were exposed to BPA (300 mg/kg) by oral gavage for 60 consecutive days. H&E staining was used for histopathological evaluation, and the serum biochemical indexes were determined using an automatic analyzer. The 16S rRNA gene sequencing was used to detect the intestinal microbial diversity, and the GC-MS was used to analyze the contents of short-chain fatty acids (SCFAs) in colon contents. UPLC-QTOF MS was used to analyze the related metabolites. The ELISA method was used to assess the levels of serum inflammatory factors. Results: Histopathological analysis indicated that the liver, heart, and testis were affected by BPA. There was a significant effect on alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the male-BPA group (P < 0.05), and globulin (GLB), indirect bilirubin (IBIL), alkaline phosphatase (ALP), ALT, TG, TC, high-density lipoprotein (HDL), and creatinine (Cr) in the female-BPA group (P < 0.05). Metagenomics (16S rRNA gene sequencing) analysis indicated that BPA reduced the diversity and changed the composition of gut microbiota in rats significantly. Compared with the control and blank groups, the contents of caproic acid, isobutyric acid, isovaleric acid, and propanoic acid in the colon contents decreased in the male-BPA group (P < 0.05), and caproic acid, isobutyric acid, isovaleric acid, and valeric acid in the colon contents decreased in the female-BPA group (P < 0.05). Metabolomic analysis of the serum indicated that BPA could regulate bile acid levels, especially ursodeoxycholic acid (UDCA) and its conjugated forms. The contents of amino acids, hormones, and lipids were also significantly affected after exposure to BPA. The increase in interleukin-6 (IL-6), interleukin-23 (IL-23), and transforming growth factor-ß (TGF-ß) in the serum of the male-BPA group suggests that BPA exposure affects the immune system. Conclusion: BPA exposure will cause toxicity to rats via disrupting the gut-liver-hormone axis.

Sonodynamic inactivation of gram-negative and gram-positive bacteria in the presence of phenothiazine compounds toluidine blue and azurin A.

BACKGROUND: Sonodynamic antimicrobial chemotherapy (SACT) is an effective antimicrobial treatment that can avoid the production of drug-resistant bacteria. Design and development of new high-efficiency sonosensitizers play a key role in the practical application of SACT. METHODS: The bacteriostatic effects of two phenothiazine compounds, toluidine blue (TB) and azure A (AA) combined with ultrasonic (US) on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were studied, and the sonodynamic antibacterial activities of TB and AA were compared. The reactive oxygen species (ROS) and the types of ROS produced in the sonodynamic system were detected and the sonodynamic mechanisms of TB and AA were proposed. RESULTS: The sonodynamic bacteriostasis mediated by TB and AA increased with the increasing concentration of sonosensitizer, the extension of sonication time and the increase of reaction temperature. The production of ROS was the main reason that TB and AA had excellent sonodynamic antibacterial performance. Singlet oxygen (1O2) and hydroxyl radical (•OH) were the main ROS types in the sonodynamic antibacterial system. The ROS produced by the combined action of AA and US was higher than that of TB. CONCLUSION: Both TB and AA displayed excellent sonodynamic antibacterial activities. Moreover, AA had a higher sonodynamic activity than TB. The electron donation effect and steric hindrance effect of the methyl group of phenothiazine parent nucleus of TB might be the cause of the decrease of its sonodynamic activity. These results would provide a valuable reference for the further study of phenothiazines sonosensitizers and their clinical application in SACT.

FGL2 improves experimental colitis related to gut microbiota structure and bile acid metabolism by regulating macrophage autophagy and apoptosis.

Inflammatory bowel disease (IBD) is a refractory disease with immune abnormalities and pathological changes. Intestinal macrophages are considered to be the main factor in establishing and maintaining intestinal homeostasis. The immunoregulatory and anti-inflammatory activity of fibrinogen-like protein 2 (FGL2) can regulate macrophage polarization. However, its function in IBD is unclear. In this study, we explored the effect of FGL2 on macrophage polarization, autophagy, and apoptosis in bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS) and further investigated changes in the intestinal barrier, flora, and bile acid in dextran sodium sulfate (DSS)-treated mice. Our results demonstrated that FGL2-/- weakened ERK signaling to promote M1 polarization and upregulate inflammation, autophagy, and apoptosis in LPS-stimulated BMDMs. rFGL2 treatment reversed these effects. FGL2-/- mice exhibited higher sensitivity to DSS exposure, with faster body weight loss, shorter colon lengths, and higher disease activity index (DAI) values. rFGL2 treatment protected against experimental ulcerative colitis (UC), restrained excessive autophagy, apoptosis, and improved gut barrier impairment. Gut microbiota structure and bile acid homeostasis were more unbalanced in FGL2-/- DSS mice than in wild-type (WT) DSS mice. rFGL2 treatment improved gut microbiota structure and bile acid homeostasis. Altogether, our results established that FGL2 is a potential therapeutic target for IBD.

Diterpenoids target SARS-CoV-2 RdRp from the roots of Euphorbia fischeriana Steud.

Introduction: Currently, the development of new antiviral drugs against COVID-19 remains of significant importance. In traditional Chinese medicine, the herb Euphorbia fischeriana Steud is often used for antiviral treatment, yet its therapeutic effect against the COVID-19 has been scarcely studied. Therefore, this study focuses on the roots of E. fischeriana Steud, exploring its chemical composition, antiviral activity against COVID-19, and the underlying basis of its antiviral activity. Methods: Isolation and purification of phytochemicals from E. fischeriana Steud. The elucidation of their configurations was achieved through a comprehensive suite of 1D and 2D NMR spectroscopic analyses as well as X-ray diffraction. Performed cytopathic effect assays of SARS-CoV-2 using Vero E6 cells. Used molecular docking to screen for small molecule ligands with binding to SARS-CoV-2 RdRp. Microscale thermophoresis (MST) was used to determine the dissociation constant Kd. Results: Ultimately, nine new ent-atisane-type diterpenoid compounds were isolated from E. fischeriana Steud, named Eupfisenoids A-I (compounds 1-9). The compound of 1 was established as a C-19-degraded ent-atisane-type diterpenoid. During the evaluation of these compounds for their antiviral activity against COVID-19, compound 1 exhibited significant antiviral activity. Furthermore, with the aid of computer virtual screening and microscale thermophoresis (MST) technology, it was found that this compound could directly bind to the RNA-dependent RNA polymerase (RdRp, NSP12) of the COVID-19, a key enzyme in virus replication. This suggests that the compound inhibits virus replication by targeting RdRp. Discussion: Through this research, not only has our understanding of the antiviral components and material basis of E. fischeriana Steud been enriched, but also the potential of atisane-type diterpenoid compounds as antiviral agents against COVID-19 has been discovered. The findings mentioned above will provide valuable insights for the development of drugs against COVID-19.

A Miniaturized and Highly Stable Frequency-Selective Rasorber Incorporating an Embedded Transmission Window.

In this article, a miniaturized and highly stable frequency-selective rasorber (FSR) incorporating an embedded transmission window is designed. This FSR consists of a lossy layer loaded with resistors, an air layer, and a bandpass layer. The lossy layer is provided with a rectangular, square ring structure loaded with four 180 Ω resistors and four quadrilateral metal plates. The four metal plates are connected to the four corners of the inner ring around the square ring and are radially distributed along the diagonal. The bandpass layer is a square metal patch that a cross-ring slot structure is loaded inside of, and the cross points lie in the direction along the diagonal of the unit. The inner boundary of the cross-ring is composed of two mutually perpendicular and long rectangular elements. This FSR shows an embedded transmission window from 3.63 GHz to 3.80 GHz and has a transmission rate of 93% at 3.72 GHz. Moreover, both sides of the transmission band, namely, 1.86-3.35 GHz and 3.99-8.28 GHz, have an absorption rate of more than 80% and bilateral relative bandwidth of more than 50%. In addition, this structure exhibits excellent miniaturization performance, polarization insensitivity, and angular stability. Finally, a prototype of the designed FSR is processed and measured. The measured results are basically consistent with the simulation results.

Design and Evolution of an Artificial Friedel-Crafts Alkylation Enzyme Featuring an Organoboronic Acid Residue.

Creating artificial enzymes by the genetic incorporation of noncanonical amino acids with catalytic side chains would expand the enzyme chemistries that have not been discovered in nature. Here, we report the design of an artificial enzyme that uses p-boronophenylalanine as the catalytic residue. The artificial enzyme catalyzes Michael-type Friedel-Crafts alkylation through covalent activation. The designer enzyme was further engineered to afford high yields with excellent enantioselectivities. We next developed a practical method for preparative-scale reactions by whole-cell catalysis. This enzymatic C-C bond formation reaction was combined with palladium-catalyzed dearomative arylation to achieve the efficient synthesis of spiroindolenine compounds.

Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs.

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

Potential SARS-CoV-2 Mpro steroid inhibitors from Aphanamixis polystachya (Wall.) R. N. Parker.

Herein, six previously undescribed steroids (1-6), were isolated from leaves and twigs of Aphanamixis polystachya (Wall.) R. N. Parker (Meliaceae). Their structures were elucidated by comprehensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, UV, and IR. Antiviral activity of these compounds were evaluated. Compounds 1-6 showed varying degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 200 µM.

Promising roles of combined therapy based on immune response and iron metabolism in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an intricate autoimmune disease with diverse manifestations. Immunometabolism reprogramming contributes to the progression of SLE by regulating the phenotype and function of immune cells. Dysregulated iron metabolism is implicated in SLE pathogenesis, affecting both systemic and immune cell-specific iron homeostasis. This review explores the systemic and cellular iron handling and regulation. Additionally, the advancements regarding iron metabolism in SLE with a focus on the distinct subsets of immune cells are highlighted. By gaining insight into the interplay between iron dysregulation and immune dysfunction, the potential therapeutic avenues may be unveiled. However, challenges remain in elucidating cell-specific iron metabolic reprogramming and its contribution to SLE pathogenesis needs further research for personalized therapeutic interventions and biomarker discovery. This review provides an in-depth understanding of immune cell-specific regulatory mechanisms of iron metabolism and new insights in current challenges as well as possible clinical applications.

A Dual-Passband Frequency Selective Surface with High Angular Stability and Polarization Insensitivity.

In this paper, a dual-passband frequency selective surface (FSS) with high angular stability and polarization insensitivity is proposed. The unit structure consists of a circular aperture, two annular apertures and four cross apertures. The designed FSS can achieve a double-passband at the interested frequencies of 8.45 GHz and 12.76 GHz with an insertion loss of less than 1 dB, and it can retain a stable transmission characteristic with the incident angle ranging from 0° to 86° for TE mode and from 0° to 83° for TM mode. Good agreement between the experimental results and the simulated response verifies the feasibility of the proposed FSS.

Analysis of risk factors for the sigmoid stoma complications in patients after abdominoperineal resection surgery: An observational study.

To analyze the risk factors for intraperitoneal sigmoid stoma complications after abdominoperineal resection (APR) surgery to guide clinical practice. Patients who were diagnosed with rectal cancer and underwent APR surgery from June 2013 to June 2021 were retrospectively enrolled. The characteristics of the stoma complication group and the no stoma complication group were compared, and univariate and multivariate logistic analyses were employed to identify risk factors for sigmoid stoma-related complications. A total of 379 patients who were diagnosed with rectal cancer and underwent APR surgery were enrolled in this study. The average age of the patients was 61.7 ±â€…12.1 years, and 226 (59.6%) patients were males. Patients in the short-term stoma complication group were younger (55.7 vs 62.0, P < .05) and had a more advanced tumor stage (P < .05). However, there was no significant difference between the long-term stoma complication group and the no stoma complication group. Multivariate logistic regression analysis revealed that operation time was an independent risk factor (P < .05, OR = 1.005, 95% CI = 1.000-1.010) for short-term stoma complications. Both the short-term and long-term stoma complication rates in our institution were low. A longer operation time was an independent risk factor for short-term stoma complications after APR surgery.

Preparation of fluorescent polyurethane microspheres and their applications as reusable sensor for 4-nitrophenol detection and as microplastics model for visualizing polyurethane in cells and zebrafish.

Fluorescent microspheres are of significant interests due to their wide applications in biotechnology fields. However, their preparation presents several challenges, such as the need for dye labeling, the complexity of materials and often sophisticated preparation conditions. Here a simple process for hydrophilic and crosslinked polyurethane (CPU) microspheres, with carboxyl groups on the surface via one-step precipitation polymerization in 40 min, is presented. The microsphere size is easily adjusted by varying experimental conditions. CPU microspheres exhibit high thermal and pH stability with good redispersibility in water, and emit fluorescence without any modification or dye labeling. The emission mechanism is discussed. CPU microspheres are used as fluorescent probe to detect 4-nitrophenol (4-NP) based on their emission in UV light region, with excellent selectivity and sensitivity. In addition, they are reusable with detection limit unchanged after 7 cycles of reuses, a significant feature of this work. The mechanism of fluorescence detection is thoroughly explored and ascribed to the internal filtration effect. Based on the emission in visible light region, CPU microspheres are used as a model of PU microplastics (MPs) to visualize their biodistribution in HeLa and macrophage cells, as well as in zebrafish larvae, providing a reliable tracer for the visualization and tracking of PU MPs in organisms.

Acetyl-CoA Synthetase Mutations S868G and V949I Do Not Confer Resistance to Antimalarial Drugs in vitro in Plasmodium falciparum.

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

Patrinia villosa (Thunb.) Juss alleviates CCL4-induced acute liver injury by restoring bile acid levels and inhibiting apoptosis/autophagy.

Background: Patrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine "Bai jiang cao (herba patriniae)," and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown. Method: UPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague-Dawley rats were categorized into five groups, and PV groups (125 and 375 mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serum level of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4. Results: A total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4. Conclusion: The results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent.

Predictors of complications after prophylactic ileostomy reversal for rectal cancer: A retrospective study.

BACKGROUND: Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer (RC), but there were significant differences in the reported risk factors for complications after stoma reversal. No studies have analyzed the risk factors for stoma-related complications and overall postoperative complications separately. AIM: To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with RC. METHODS: This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September 2022. Continuous variables are expressed as the mean ± SD and were analyzed with independent-sample t tests, while frequency variables are expressed as n (%), and the χ2 test or Fisher's exact test was used. Univariate and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related complications. RESULTS: The overall complication rate after ileostomy reversal was 11.4%. Patients with lower preoperative albumin concentration (P < 0.01), greater blood loss (P = 0.017), and longer operative times (P < 0.01) were more likely to experience postoperative complications. The incidence of stoma-related complications was 6.4%. Analysis of the study showed that a higher body mass index (BMI) (P < 0.01), preoperative comorbid hypertension (P = 0.049), time from primary surgery to ileostomy reversal (P < 0.01) and longer operation time (P = 0.010) were more likely to result in stoma-related complications postoperatively. Multivariate logistic regression analysis revealed that a lower preoperative albumin level (P < 0.01, OR = 0.888, 95%CI: 0.828-0.958) was an independent risk factor for overall complications. Moreover, multivariate analysis revealed that BMI (P < 0.01, OR = 1.176, 95%CI: 1.041-1.330) and time from primary surgery to ileostomy reversal (P < 0.01, OR = 1.140, 95%CI: 1.038-1.252) were independent risk factors for stoma-related complications after stoma reversal. CONCLUSION: The preoperative albumin level was a predictor of overall complications. Preoperative BMI and the time from primary surgery to ileostomy reversal were predictors of stoma-related complications.

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes-Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.