Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook.

Dyslipidemia refers to unhealthy changes in blood lipid composition and is a risk factor for atherosclerotic cardiovascular diseases (ASCVD). Usually, low-density lipoprotein-cholesterol (LDL-C) is the primary goal for dyslipidemia management. However, non-high-density lipoprotein cholesterol (non-HDL-C) has gained attention as an alternative, reliable goal. It encompasses all plasma lipoproteins like LDL, triglyceride-rich lipoproteins (TRL), TRL-remnants, and lipoprotein a [Lp(a)] except high-density lipoproteins (HDL). In addition to LDL-C, several other constituents of non-HDL-C have been reported to be atherogenic, aiding the pathophysiology of atherosclerosis. They are acknowledged as contributors to residual ASCVD risk that exists in patients on statin therapy with controlled LDL-C levels. Therefore, non-HDL-C is now considered an independent risk factor or predictor for CVD. The popularity of non-HDL-C is attributed to its ease of estimation and non-dependency on fasting status. It is also better at predicting ASCVD risk in patients on statin therapy, and/or in those with obesity, diabetes, and metabolic disorders. In addition, large follow-up studies have reported that individuals with higher baseline non-HDL-C at a younger age (<45 years) were more prone to adverse CVD events at an older age, suggesting a predictive ability of non-HDL-C over the long term. Consequently, non-HDL-C is recommended as a secondary goal for dyslipidemia management by most international guidelines. Intriguingly, geographical patterns in recent epidemiological studies showed remarkably high non-HDL-C attributable mortality in high-risk countries. This review highlights the independent role of non-HDL-C in ASCVD pathogenesis and prognosis. In addition, the need for a country-specific approach to dyslipidemia management at the community/population level is discussed. Overall, non-HDL-C can become a co-primary or primary goal in dyslipidemia management.

Routine Prophylactic Percutaneous Endoscopic Gastrostomy in Head and Neck Cancers with Bilateral Neck Irradiation: A Regional Cancer Experience in New Zealand.

INTRODUCTION: Patients with head and neck cancer (HNC) are particularly susceptible to dysphagia and malnutrition. Prophylactic percutaneous endoscopic gastrostomy (PEG) placement is a method used to manage these issues, but practices vary among institutions. At Midcentral District Health Board, patients receiving radiotherapy to the primary and bilateral neck regions routinely undergo prophylactic PEG placement. This study aimed to review the nutritional and PEG-related outcomes of these patients. METHODS: Records of 49 patients were retrospectively reviewed. Their demographics, tumour and treatment characteristics were recorded. We evaluated patient weight loss, non-elective hospitalisation, treatment interruption rates, PEG-related complications, usage, dependency rates and late dysphagia rates. RESULTS: Oropharyngeal cancers were the most common primary site (61.2%), and 83.7% of patients received primary chemoradiotherapy. Mean weight loss at treatment completion was 5.6% ± 4.3 (4.6 kg ± 3.9). The rate of non-elective hospitalisations was 26.5%, and only 2% of patients had treatment interruptions. Peristomal infection was the most frequent PEG complication (20.4%). No PEG-related mortality was reported. Median duration of PEG dependency was 97 days (14-388 days). Two patients remained permanently dependent at 3 years due to grade 3 dysphagia, and six patients experienced grade ≥2 late dysphagia. CONCLUSION: Our study showed that prophylactic PEG tube placement was relatively safe, with a high utilisation rate and low long-term dependence on PEG tubes after treatment completion. However, complications related to their use should be addressed through a multidisciplinary approach, with careful assessment by clinicians. The weight loss and hospitalisation rates observed were consistent with earlier studies that utilised prophylactic PEG tubes.

Venous thromboembolism in metastatic pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC). METHODS: A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan-Meier survival plots and Cox proportional hazards regressions. RESULTS: 400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0-1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non-VTE group. Only advanced stage (OR 3.7, p = .001) correlated with increased VTE risk. CONCLUSIONS: The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis.

An incidental finding of Rapunzel syndrome in a case of perforated appendix in a young girl.

A bezoar is a mass of indigestible foreign material found in the gastrointestinal tract, usually in the stomach. Trichobezoars are the second most common bezoars which are usually found in young psychiatric patients. A 15-year-old female patient presented with signs of intestinal obstruction and acute abdomen. The preoperative investigations revealed a perforated appendix, and an exploratory laparotomy was performed. Intraoperative findings showed presence of a mass of hair in the stomach along with a long tail extending into the small intestine. Postoperatively, the patient's condition worsened and she died because of complications of perforation peritonitis on day 3. Early diagnosis of Rapunzel syndrome can help in making early interventions. The prognosis of incidental detection of this condition depends on the accompanying cause.

Functional Characterization of a Regiospecific Sugar-O-Methyltransferase from Nocardia.

Methyltransferases transfer a methyl group to a diverse group of natural products, thus providing structural diversity, stability, and altered pharmacological properties to the molecules. A limited number of regiospecific sugar-O-methyltransferases are functionally characterized. Thus, discovery of such an enzyme could solve the difficulties of biological production of methoxy derivatives of glycosylated molecules. In the current study, a regiospecific sugar-O-methyltransferase, ThnM1, belonging to the biosynthetic gene cluster (BGC) of 1-(α-L-(2-O-methyl)-6-deoxymannopyranosyloxy)-3,6,8-trimethoxynaphthalene produced by Nocardia sp. strain CS682, was analyzed and functionally characterized. ThnM1 demonstrated promiscuity to diverse chemical structures such as rhamnose-containing anthraquinones and flavonoids with regiospecific methylation at the 2'-hydroxyl group of the sugar moiety. Compared with other compounds, anthraquinone rhamnosides were found to be the preferred substrates for methylation. Thus, the enzyme was further employed for whole-cell biotransformation using engineered Escherichia coli to produce a methoxy-rhamnosyl derivative of quinizarin, an anthraquinone derivative. The structure of the newly generated derivative from Escherichia coli fermentation was elucidated by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopic analyses and identified as quinizarin-4-O-α-l-2-O-methylrhamnoside (QRM). Further, the biological impact of methylation was studied by comparing the cytotoxicity of QRM with that of quinizarin against the U87MG, SNU-1, and A375SM cancer cell lines. IMPORTANCE ThnM1 is a putative sugar-O-methyltransferase produced by the Nocardia sp. strain CS682 and is encoded by a gene belonging to the biosynthetic gene cluster (BGC) of 1-(α-l-(2-O-methyl)-6-deoxymannopyranosyloxy)-3,6,8-trimethoxynaphthalene. We demonstrated that ThnM1 is a promiscuous enzyme with regiospecific activity at the 2'-OH of rhamnose. As regiospecific methylation of sugars by chemical synthesis is a challenging step, ThnM1 may fill the gap in the potential diversification of natural products by methylating the rhamnose moiety attached to them.

Te/CdTe and Al/CdTe Interfacial Energy Band Alignment by Atomistic Modeling.

A synergistic approach that incorporates first-principles atomistic modeling with numerical device simulations is used to systematically evaluate the role of heterointerfaces within metal-chalcogenide-based photovoltaic technologies. Two interfaces involving either a tellurium back contact or aluminum back electrode combined with a cadmium telluride absorber layer within cadmium-telluride-based thin-film solar cells are investigated on an atomic scale to determine the mechanisms contributing to variations in device performance. Electronic structures and predicted charge transport behavior with respect to cadmium and tellurium termination of the absorber layer are studied along the polar oriented CdTe{111} facets. The computational methodology reveals a noticeable contrast between the Schottky barrier forming Al/CdTe interface versus the Type I Te/CdTe heterojunction. Greater band bending features are exhibited by the cadmium termination as opposed to the tellurium termination for each interface case. Subsequent device modeling suggests that 3.6% higher photovoltaic conversion efficiency is achievable for the cadmium termination relative to the tellurium termination of the Te/CdTe interface. Based strictly on an idealistic representation, both interface models show the importance of atomic-scale interfacial properties for cadmium telluride solar cell device performance with their bulk properties being validated in comparison to published experimental data. The synergistic approach offers a suitable method to analyze solar cell interfaces through a predictive computational framework for the engineering and optimization of metal-chalcogenide-based thin-film photovoltaic technologies.

Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism.

PURPOSE: Apart from the global disease burden of acute COVID-19 disease, the health complications arising after recovery have been recognized as a long-COVID or post-COVID-19 syndrome. Evidences of long-COVID symptoms involving various organ systems are rapidly growing in literature. The objective was to perform a rapid review and evidence mapping of systemic complications and symptoms of long-COVID and underlying pathophysiological mechanisms. METHODS: Publications reporting clinical trials, observational cohort studies, case-control studies, case-series, meta-analysis, and systematic reviews, focusing on the squeal of the disease, consequences of COVID-19 treatment/hospitalization, long-COVID, chronic COVID syndrome, and post acute COVID-19 were reviewed in detail for the narrative synthesis of frequency, duration, risk factors, and pathophysiology. RESULTS: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies. However, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood. Analysis of the clinical trial landscape suggests that more than 50% of the industry-sponsored trials are focused on pulmonary symptoms. In contrast to the epidemiological trends and academic trials, cardiovascular complications are not a focus of industry-sponsored trials, suggestive of the gaps in the research efforts. CONCLUSION: The gap in epidemiological trends and academic trials, particularly concerning cardiovascular complications not being a focus of industry-sponsored trials is suggestive of the gaps in research efforts and longer follow-up durations would help identify other long-COVID-related health issues such as reproductive health and fertility.

UPLC-PDA coupled HR-TOF ESI/MS2 -based identification of derivatives produced by whole-cell biotransformation of epothilone A using Nocardia sp. CS692 and a cytochrome P450 overexpressing strain.

Epothilone A, a microtubule-stabilizing agent used as therapeutics for the treatment of cancers, was biotransformed into three metabolites using Nocardia sp. CS692 and recombinant Nocardia overexpressing a cytochrome P450 from Streptomyces venezuelae (PikC). Among three metabolites produced in the biotransformation reaction mixtures, ESI/MS2 analysis predicted two metabolites (M1 and M2) as novel hydroxylated derivatives (M1 is hydroxylated at the C-8 position and M2 is hydroxylated at C-10 position), each with an opened-epoxide ring in their structure. Interestingly, metabolite M3 lacks an epoxide ring and is known as deoxyepothilone A, which is also called epothilone C. Metabolite M1 was produced only in PikC overexpressing strain. The endogenous enzymes of Nocardia sp. catalyzed hydroxylation of epothilone A to produce metabolite M2 and removed epoxide ring to produce metabolite M3. All the metabolites were identified based on UV-vis analysis and rigorous ESI/MS2 fragmentation based on epothilone A standard. The newly produced metabolites are anticipated to display novel cytotoxic effects and could be subjects of further pharmacological studies.

Treatment of glioblastoma with re-purposed renin-angiotensin system modulators: Results of a phase I clinical trial.

Glioblastoma is the most common and most aggressive primary brain cancer in adults. Standard treatment of glioblastoma consisting of maximal safe resection, adjuvant radiotherapy and chemotherapy with temozolomide, results in an overall median survival of 14.6 months. The aggressive nature of glioblastoma has been attributed to the presence of glioblastoma stem cells which express components of the renin-angiotensin system (RAS). This phase I clinical trial investigated the tolerability and efficacy of a treatment targeting the RAS and its converging pathways in patients with glioblastoma. Patients who had relapsed following standard treatment of glioblastoma who met the trial criteria were commenced on dose-escalated oral RAS modulators (propranolol, aliskiren, cilazapril, celecoxib, curcumin with piperine, aspirin, and metformin). Of the 17 patients who were enrolled, ten completed full dose-escalation of the treatment. The overall median survival was 19.9 (95% CI:14.1-25.7) months. Serial FET-PET/CTs showed a reduction in both tumor volume and uptake in one patient, an increase in tumor uptake in nine patients with decreased (n = 1), unchanged (n = 1) and increased (n = 7) tumor volume, in the ten patients who had completed full dose-escalation of the treatment. Two patients experienced mild side effects and all patients had preservation of quality of life and performance status during the treatment. There is a trend towards increased survival by 5.3 months although it was not statistically significant. These encouraging results warrant further clinical trials on this potential novel, well-tolerated and cost-effective therapeutic option for patients with glioblastoma.

Four-Step Pathway from Phenylpyruvate to Benzylamine, an Intermediate to the High-Energy Propellant CL-20.

Benzylamine is a commodity chemical used in the synthesis of motion-sickness treatments and anticonvulsants, in dyeing textiles, and as a precursor to the high-energy propellant CL-20. Because chemical production generates toxic waste streams, biosynthetic alternatives have been explored, recently resulting in a functional nine-step pathway from central metabolism (phenylalanine) in E. coli. We report a novel four-step pathway for benzylamine production, which generates the product from cellular phenylpyruvate using enzymes from different sources: a mandelate synthase (Amycolatopsis orientalis), a mandelate oxidase (Streptomyces coelicolor), a benzoylformate decarboxylase (Pseudomonas putida), and an aminotransferase (Salicibacter pomeroyi). This pathway produces benzylamine at 24 mg/L in 15 h (4.5% yield) in cultures of unoptimized cells supplemented with phenylpyruvate. Because the yield is low, supplementation with pathway intermediates is used to troubleshoot the design. This identifies conversion inefficiencies in the mandelate synthase-mediated synthesis of (S)-mandelic acid, and subsequent genome mining identifies a new mandelate synthase (Streptomyces sp. 1114.5) with improved yield. Supplementation experiments also reveal native redirection of ambient phenylpyruvate away from the pathway to phenylalanine. Overall, this work illustrates how retrosynthetic design can dramatically reduce the number of enzymes in a pathway, potentially reducing its draw on cellular resources. However, it also shows that such benefits can be abrogated by inefficiencies of individual conversions. Addressing these barriers can provide an alternative approach to green production of benzylamine, eliminating upstream dependence on chlorination chemistry.

Understanding the Copassivation Effect of Cl and Se for CdTe Grain Boundaries.

Chlorine passivation treatment of cadmium telluride (CdTe) solar cells improves device performance by assisting electron-hole carrier separation at CdTe grain boundaries. Further improvement in device efficiency is observed after alloying the CdTe absorber layer with selenium. High-resolution secondary ion mass spectroscopy (NanoSIMS) imaging has been used to determine the distribution of selenium and chlorine at the CdTe grain boundaries in a selenium-graded CdTe device. Atomistic modeling based on density functional theory (DFT-1/2) further reveals that the presence of selenium and chlorine at an exemplar (110)/(100) CdTe grain boundary passivates critical acceptor defects and leads to n-type inversion at the grain boundary. The defect state analysis provides an explanation for the band-bending effects observed in the energy band alignment results, thereby elucidating mechanisms for high efficiencies observed in Se-alloyed and Cl-passivated CdTe solar cells.

Trilobatin ameliorates bone loss via suppression of osteoclast cell differentiation and bone resorptive function in vitro and in vivo.

AIM: Due to on-going safety concerns or lack of efficacy of currently used medications for the treatment of osteoporosis (OP), identifying new therapeutic agents is an important part of research. In the present study, potential anti-osteoporotic activity of a natural flavonoid glycoside, trilobatin (phloretin 4-O-glucoside, Tri) was evaluated. MATERIAL AND METHODS: Osteoclastic cells were established by treating the RAW264.7 macrophage cells with RANKL and ovariectomized (OVX) C57BL/6 female mice were used as an animal model of postmenopausal OP. Actin ring formation, expression levels of osteoclastogenic marker genes and bone resorptive proteins were measured by RT-PCR, western blot, or fluorometric assays. Bone mineral density (BMD) was determined by pDEXA densitometric measurement and serum osteoprotegerin (OPG) and RANKL were measured by ELISA. KEY FINDING: Tri (5-20 µM) significantly inhibited osteoclast formation and actin ring formation in RANKL-induced osteoclasts. Tri attenuated expression of osteoclastogenic genes (MMP-9 and cathepsin K), bone resorptive proteins (CA II and integrin ß3), and osteoclastogenic signalling proteins (TRAF6, p-Pyk2, c-Cbl, and c-Src). Oral administration of Tri to OVX mice augmented BMD and serum OPG/RANKL ratio. Interestingly, while Tri and phloretin aglycone (Phl) showed similar levels of in vitro anti-osteoclastogenic activity, Tri more potently ameliorated bone loss than Phl in OVX mice. SIGNIFICANCE: This study demonstrated that Tri inhibits osteoclastic cell differentiation and bone resorption by down-regulating the expression of osteoclastogenic marker genes and signalling proteins, bone resorptive proteins, and by augmenting serum OPG/RANKL ratio, suggesting that Tri can be a novel anti-osteoporotic compound for treating senile and postmenopausal OP.

Chryseobacterium antibioticum sp. nov. with antimicrobial activity against Gram-negative bacteria, isolated from Arctic soil.

A yellow-pigmented, non-motile, Gram-stain-negative, pleomorphic bacterium, designated RP-3-3T was obtained from soil sampled at the Arctic region in Cambridge Bay, NU, Canada. The strain is strictly aerobic, psychrotolerant, grow optimally at 15-20 °C and produces flexirubin type pigments. The strain is able to hydrolyse CM-cellulose, casein, starch and DNA. Strain RP-3-3T showed antimicrobial activity against Gram-negative pathogens. A phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain RP-3-3T formed a lineage within the family Weeksellaceae and clustered as members of the genus Chryseobacterium. The closest members were Chryseobacterium shigense DSM 17126T (98.7% sequence similarity), Chryseobacterium carnipullorum DSM 25581T (98.7%) and Chryseobacterium oncorhychi 701B-08T (98%). The genome is 4,910,468 bp long with 73 scaffolds and 4300 protein-coding genes. The anti-SMASH analysis of whole genome showed ten putative biosynthetic gene clusters responsible for various secondary metabolites. The sole respiratory quinone is MK-6. The major cellular fatty acids are iso-C15:0, iso-C17:1 ω9c, iso-C17:0 3-OH, summed feature 3 (iso-C15 :0 2-OH/C16 :1ω7c) and anteiso-C15:0. The major polar lipid is phosphatidylethanolamine. The DNA G + C content of the type strain is 36.9 mol%. In addition, the average nucleotide identity and in silico DNA-DNA hybridization  relatedness values between strain RP-3-3T and phylogenetically closest members are below the threshold value for species delineation. Based on genomic, chemotaxonomic, phenotypic and phylogenetic analyses, strain RP-3-3T represents novel species in the genus Chryseobacterium, for which the name Chryseobacterium antibioticum sp. nov. is proposed. The type strain is RP-3-3T (=KACC 21620T = NBRC 114360T).

Genome-enabled discovery of anthraquinone biosynthesis in Senna tora.

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.

The genome insights of Streptomyces lannensis T1317-0309 reveals actinomycin D production.

The members of Streptomyces have been identified as a major source of antimicrobial agents with broad spectrum. This study is mainly focused on bioactivity-guided isolation and characterization of bioactive molecule from strain Streptomyces sp. T1317-0309 and its whole-genome sequence analysis for possible isolation of novel natural products. Strain Streptomyces sp. T1317-0309 showed 100% sequence similarity with strain Streptomyces lannensis TA4-8T consisting 10, 453,255 bp of genome with 5 scaffolds and 69.9 mol% G + C content. The genome analyses revealed a total of 17 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites including actinomycin, bacteriocin, ectoine, melanin, terpene, siderophore, betalactone, NRPS, T2PKS, and T3PKS. The BGC and bioactivity-guided purification of ethyl acetate extract of strain T1317-0309 showed the great potency of antimicrobial activities against various gram-positive multi-drug resistant human pathogens including MRSA. The BGC-predicted bioactive secondary metabolite was identified by various NMR analyses and confirmed as actinomycin D. In addition, this study reveals the first genome study of Streptomyces lannensis as a novel source for actinomycin D.

Regio-specific biotransformation of alizarin to alizarin methoxide with enhanced cytotoxicity against proliferative cells.

Alizarin has been reported to have an antigenotoxic activity along with an inhibitory effect on the tumor cell growth of human colon carcinoma cells. Alizarin was biotransformed into an O-methoxide derivative using O-methyltransferase from Streptomyces avermitilis MA4680 (SaOMT2) to enhance its bioefficacy. The biotransformed product was extracted, purified, and characterized using various chromatographic and spectroscopic analyses, and confirmed to be an alizarin 2-O-methoxide. The antiproliferative activity of the compound against gastric cancer cells (AGS), uterine cervical cancer (Hela), liver cancer (HepG2), and normal cell lines was investigated. Alizarin 2-O-methoxide showed an inhibitory effect on all three cancer-cell lines at very low concentrations, from 0.078 µM, with no cytotoxicity against 267B1 (human prostate epithelial) and MRC-5 (normal human fetal lung fibroblast).

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence.

Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.

Exploring the Nucleophilic N- and S-Glycosylation Capacity of Bacillus licheniformis YjiC Enzyme.

YjiC, a glycosyltransferase from Bacillus licheniformis, is a well-known versatile enzyme for glycosylation of diverse substrates. Although a number of O-glycosylated products have been produced using YjiC, no report has been updated for nucleophilic N-, S-, and C- glycosylation. Here, we report the additional functional capacity of YjiC for nucleophilic N- and S- glycosylation using a broad substrate spectrum including UDP-α-D-glucose, UDP-N-acetyl glucosamine, UDP-N-acetylgalactosamine, UDP-α-D-glucuronic acid, TDP-α-L-rhamnose, TDP-α-D-viosamine, and GDP-α-Lfucose as donor and various amine and thiol groups containing natural products as acceptor substrates. The results revealed YjiC as a promiscuous enzyme for conjugating diverse sugars at amine and thiol functional groups of small molecules applicable for generating glycofunctionalized chemical diversity libraries. The glycosylated products were analyzed using HPLC and LC/MS and compared with previous reports.