TGFA expression is associated with poor prognosis and promotes the development of cervical cancer.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the second most common cancers in women aged 20-39. While HPV screening can help with early detection of cervical cancer, many patients are already in the medium to late stages when they are identified. As a result, searching for novel biomarkers to predict CESC prognosis and propose molecular treatment targets is critical. TGFA is a polypeptide growth factor with a high affinity for the epidermal growth factor receptor. Several studies have shown that TGFA can improve cancer growth and progression, but data on its impact on the occurrence and advancement of CESC is limited. In this study, we used clinical data analysis and bioinformatics techniques to explore the relationship between TGFA and CESC. The results showed that TGFA was highly expressed in cervical cancer tissues and cells. TGFA knockdown can inhibit the proliferation, migration and invasion of cervical cancer cells. In addition, after TGFA knockout, the expression of IL family and MMP family proteins in CESC cell lines was significantly reduced. In conclusion, TGFA plays an important role in the occurrence and development of cervical cancer. Therefore, TGFA may become a new target for cervical cancer treatment.

Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

A Hybrid Model for Fetal Growth Restriction Assessment by Automatic Placental Radiomics on T2-Weighted MRI and Multifeature Fusion.

BACKGROUND: MRI-based placental analyses have been used to improve fetal growth restriction (FGR) assessment by complementing ultrasound-based measurements. However, these are still limited by time-consuming manual annotation in MRI data and the lack of mother-based information. PURPOSE: To develop and validate a hybrid model for accurate FGR assessment by automatic placental radiomics on T2-weighted imaging (T2WI) and multifeature fusion. STUDY TYPE: Retrospective. POPULATION: 274 pregnant women (29.5 ± $$ \pm $$ 4.0 years) from two centers were included and randomly divided into training (N = 119), internal test (N = 40), time-independent validation (N = 43), and external validation (N = 72) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, T2WI half-Fourier acquisition single-shot turbo spin-echo pulse sequence. ASSESSMENT: First, the placentas on T2WI were manually annotated, and a deep learning model was developed to automatically segment the placentas. Then, the radiomic features were extracted from the placentas and selected by three-step feature selection. In addition, fetus-based measurement features and mother-based clinical features were obtained from ultrasound examinations and medical records, respectively. Finally, a hybrid model based on random forest was constructed by fusing these features, and further compared with models based on other machine learning methods and different feature combinations. STATISTICAL TESTS: The performances of placenta segmentation and FGR assessment were evaluated by Dice similarity coefficient (DSC) and the area under the receiver operating characteristic curve (AUROC), respectively. A P-value <0.05 was considered statistically significant. RESULTS: The placentas were automatically segmented with an average DSC of 90.0%. The hybrid model achieved an AUROC of 0.923, 0.931, and 0.880 on the internal test, time-independent validation, and external validation sets, respectively. The mother-based clinical features resulted in significant performance improvements for FGR assessment. DATA CONCLUSION: The proposed hybrid model may be able to assess FGR with high accuracy. Furthermore, information complementation based on placental, fetal, and maternal features could also lead to better FGR assessment performance. TECHNICAL EFFICACY: Stage 2.

Synthesis, antibacterial activity, and 3D-QASR studies of matrine-indole derivatives as potential antibiotics.

Matrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). The obtained results demonstrated promising antibacterial efficacy, particularly for compounds A20 and A18, which exhibited MICs.au values of 0.021 and 0.031 mg/ml, respectively, against S. aureus. Moreover, compounds A20 and A27 displayed remarkable MICc.al values of 2.806 and 4.519 mg/ml, respectively, against C. albicans, surpassing the performance of the clinical antibiotic penicillin G sodium (0.0368 mg/ml) and fluconazole (4.849 mg/ml). These findings underscore the significant bacteriostatic activity of the matrine derivatives. Furthermore, to gain a deeper understanding 3D-QSAR modeling was employed, revealing the critical influence of steric structure, charge distribution, hydrophobic interactions, and hydrogen bonding within the molecular structure on the bacteriostatic activity of the compounds. Additionally, molecular docking simulations shed light on the interaction between compound A20 and bacterial proteins, highlighting the involvement of hydrogen bonding, hydrophobic interactions, and π-π conjugation in the formation of stable complexes that inhibit the normal functioning of the proteins. This comprehensive analysis provided valuable insights into the antibacterial mechanism of the novel matrine derivatives, offering theoretical support for their potential application as antibiotics.

Clip-and-snare method with a pre-looping technique versus conventional method in the treatment of precancerous lesion and early gastric cancer: a retrospective study.

BACKGROUND: Low grade intraepithelial neoplasia (LGIN) and high grade intraepithelial neoplasia (HGIN) are potential precancerous lesion of gastric neoplasms. Endoscopic submucosal dissection (ESD) is the first option for the treatment of precancerous lesion and early gastric cancer (EGC). Traction is an effective method to improve efficiency, and reduce complications during ESD. In this study, we shared a useful traction method using the clip-and-snare method with a pre-looping technique (CSM-PLT) for precancerous lesion and EGC. METHODS: We retrospectively analyzed patients received ESD combined with CSM-PLT or conventional ESD from June 2018 to December 2021 in Shenzhen People's hospital. The primary outcome was resection speed. RESULTS: Forty-two patients were enrolled in ESD combined with CSM-PLT group and sixty-five patients in conventional ESD group respectively. Baseline characteristics were comparable among two groups (P>0.05). There were no significant differences in terms of R0 resection rate, en bloc resection rate (97.6% vs. 98.5%, P = 1.000 and 97.6% vs. 96.9%, P = 1.000, respectively), operation costs (933.7 (644.1-1102.4) dollars vs. 814.7 (614.6-988.3) dollars, P = 0.107), and hospital stays (8.0 ± 3.1 days vs. 7.3 ± 3.2 days, P = 0.236). In addition, no significant difference was observed with respect to complications (P>0.05). However, the resection speed of ESD combined with CSM-PLT was faster than that of conventional ESD (11.3 (9.4-14.9) mm2/min vs. 8.0 (5.8-10.9) mm2/min, P < 0.001), particularly lesions located in anterior wall and lesser curvature. In addition, the association between ESD combined with CSM-PLT and resection speed was still supported after propensity matching scores (PMS). CONCLUSIONS: CSM-PLT can help to improve ESD efficiency without reducing the en bloc resection rate or increasing the incidence of complications.

Novel chiral matrine derivatives as potential antitumor agents: Design, synthesis and biological evaluation.

Since the thalidomide incident, research on chiral drugs has escalated immensely. Differences in drug configuration can lead to significant variations in therapeutic efficacy. Matrine, a natural product esteemed for its low toxicity and high water solubility, has garnered significant attention in research endeavors. Nonetheless, its precise target has proven elusive. In this study, we designed and synthesized a novel chiral matrine derivative. Their cytotoxicity against three types of tumor cells was assessed. Comparing the newly synthesized derivatives to the parent matrine, most compounds exhibited significantly enhanced inhibitory effects on cancer cells. Among them, Q12 exhibited the highest activity, with IC50 values of 8.31 µM against rat glioma cells C6, 6.3 µM against human liver cancer cells HepG2 and 7.14 µM against human gastric cancer cells HGC-27, meanwhile showing low toxicity. Based on IC50 values, we constructed a preliminary structure-activity relationship (SAR). Compound Q12 significantly suppressed the cloning and migration of HepG2 cells. Further mechanistic studies indicated that Q12 inhibited Topo I in HepG2 cells, leading to DNA damage, induction of G0/G1 cell cycle arrest and ultimately causing apoptosis. The molecular docking experiments provided a rational binding mode of Q12 with the Topo I-DNA complex. In vivo, experiments demonstrated that Q12 exhibited a higher tumor growth inhibition rate (TGI) compared to the positive control drug Lenvatinib, while maintaining good safety. In summary, it suggests that Topo I might be a potential target for matrine and Q12 represents a promising candidate for cancer treatment.

cGAS Deficiency Regulates the Phenotypic Polarization and Glycolysis of Microglia Through Lactylation in Hypoxic-Ischemic Encephalopathy Cell Model.

Promoting the M2 phenotype polarization of microglia is of great significance in alleviating hypoxic-ischemic encephalopathy (HIE). The umbilical artery blood sample was collected to evaluate the expression of cGAS, and the aberrant expressed cGAS was verified in the oxygen glucose deprivation (OGD) microglia which was established to mimic HIE in vitro. Then the regulating role of cGAS on the transformation of microglia M2 phenotype polarization and glycolysis was investigated. Moreover, the lactylation of cGAS in OGD treated microglia was evaluated by western blot. cGAS was found to be highly expressed in umbilical artery blood of HIE group, and OGD treated microglia. OGD interference activated microglia into M1 phenotype by enhancing CD86 and suppressing CD206 levels; meanwhile, the microglia in OGD group highly expressed IL-1ß, iNOS and TNF-α, and lowly expressed IL-4, IL-10, and Arg-1. Inhibition of cGAS promotes the transformation of microglia from M1 to M2 phenotype. Meanwhile, OGD increased ECAR and decreased OCR to regulate glycolysis, cGAS deficiency inhibits glycolysis in OGD treated microglia. Moreover, the pan lysine lactylation (Pan-Kla) levels and lactated cGAS levels in microglia were upregulated in the OGD group. Lactate reversed the effects of cGAS knockdown on microglia polarization and glycolysis. The present study reveals that the cGAS-mediated neuron injury is associated with high level of cGAS lactylation. Inhibition of cGAS promotes the M2 phenotype polarization of microglia and suppress glycolysis. Thereby, targeting cGAS provides a new strategy for the development of therapeutic agents against HIE.

Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy.

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

Pseudo-submucosal tumor in the colon: seeing is believing.

A 65-year-old woman was admitted to our hospital with complaints of lower abdominal pain. Her physical examination was unremarkable. The results of routine laboratory testing were within the normal limits. In addition, abdominal CT was normal. Colonoscopy showed a cecum submucosal tumor with a pale yellow surface. Endoscopic ultrasound revealed homogeneous hypoechoic lesions originated from submucosal layer. ESD was subsequently performed to remove the submucosal lesion. During the ESD procedure, fecal outflowed from appendix opening . Yellow fecal-like material was visible after submucosal incision. The trap electrocut surface uplift showed more fecal attachment on the lamina propria surface, and myolayer integrity after clean the fecal (Fig1c), The final pathology of the surface bulge suggested hyperplasia (Fig1d). Patients were discharged with relieved lower abdominal pain. The final diagnosis was submucosal fecalith mimicking a submucosal tumor, eventually leads to chronic appendicitis. Common causes of cecal submucosal tumor include neuroendocrine tumors, lipomas, etc. There was few report about fecalith mimicking a submucosal tumor. ERTA is currently an effective endoscopic method for treating appendicitis combined with fecalith blockage. To our knowledge, this is the first report on a case of cecum submucosal fecalith mimicking a submucosal tumor and was successfully removed using endoscopy.

Endoscopic submucosal dissection for duodenal-type follicular lymphoma.

Duodenal-type follicular lymphoma (D-FL) is a special type of follicular lymphoma, which tends to occur in the descending segment of the duodenum. The lesion is mostly limited to the mucosal layer. The treatment approach for D-FL has not been clearly established and the watch and wait (WW) approach is generally recommended as a major option. Since D-FL may be transformed into a more serious type of lymphoma, it is of clinical significance to explore active treatment methods. We diagnosed and successfully treated a case of D-FL with Endoscopic submucosal dissection (ESD). Because D-FL is limited to mucosa in the descending segment of the duodenum, ESD can completely dissect the lesion to achieve the purpose of complete resection. Compared with the WW, the method of WW after endoscopic therapy is more active, safe and effective.

"Clip coupled with an elastic ring" internal traction for endoscopic submucosal dissection of a rectal neuroendocrine tumor: a junior endoscopist experience.

A 64-year-old female was found a rectal neuroendocrine tumor (NET) for cancer screening examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic lesion (8.3*6.6 mm) originating from the submucosa layer. "Clip coupled with elastic ring" internal traction for endoscopic submucosal dissection (ESD) was used to remove the NET according to the procedure removal of a duodenal tumor1. The procedures are following: 1. Marking around the lesion with a margin of approximately 5 mm. 2. Submucosal injection and circumference incision around the lesion. 3. Applied clip coupled with elastic ring internal traction. 4. Submucosal injection. 5.Precise dissection was performed with the NET being en bloc resection. 5. Closed the mucosal defect. Finally, the Histopathology confirmed a neuroendocrine tumor.

A case of achalasia associated with early esophageal cancer.

A 65-year-old man was admitted to our hospital complaining of reflux for more than 20 years. After endoscopy and barium-swallow examination, he was diagnosed with achalasia as well as a squamous cell carcinoma. Therefore, peroral endoscopic myotomy (POEM) combined with endoscopic submucosal dissection (ESD) was performed simultaneously. During the procedure, a mucosal erosion with a clear boundary was shown in the middle segment of the esophagus. ESD was first performed and the lesion was removed en-bloc. Subsequent POEM therapy was performed after marking the left esophageal wall 10cm above the cardia. After submucosal injection, the submucosal plane was created through a length 2cm longitudinal incision, then the muscle was cut a length of 10 cm into the esophagus and 2 cm below the cardia, and finally the incision was closed by clips. Pathological examination revealed high-grade intraepithelial neoplasia of squamous epithelium (carcinoma in situ) with a negative margin. The patient was recovered without complication four days after the procedure. The endoscopy showed perfect healing of the esophageal lesions during two-months follow-up , and the reflux symptom was resolved.

New options for endoscopic treatment of gastric varices.

BACKGROUND: Gastric venous bleeding is one of the most common adverse events in liver cirrhosis. The therapeutic effect of isolated gastric varices is relatively clear. However, there is no appropriate clinical and endoscopic treatment for extensive variceal bleeding in the gastric fundus and body. METHODS: In this patient with non-isolated gastric varices, we decided to perform endoscopic multi-point ligation of the obvious varices in the gastric fundus and body. RESULTS: In this patient, endoscopic treatment of gastric varices with bleeding after surgery achieved a significant therapeutic effect. Reexamination of gastroscopy at 3 months after operation showed that multiple scars were formed in the gastric fundus and fundus, and no obvious varices were found. CONCLUSIONS: For patients with non-isolated gastric varices, endoscopic multi-point ligation is a safe and effective treatment option for the varices with obvious gastric fundus and body.

Double-balloon enteroscopy for the detection of GIST in a patient with neurofibromatosis type 1.

NF1 is an autosomal dominant hereditary disease, with a prevalence of at least 1 in 4000-5000 population. The diagnosis criteria of NF1 included typical manifestations such as café-au-lait spots, frecking in the axilla or inguinal region, multiple neurofibromas, Lisch nodeules, and distinctive osseous lesions. Genetic testing shows NF1 mutation. It is essential for tumor surveillance in NF1 patients because their life expectancy is about 54 years due to malignancy. A case of NF-1 patient receive laparoscopic small bowel resection and finally diagnosed as adenocarcinoma and ganglioneuroma. About 25% of NF1 patients had GISTs , most of them were asymptomatic and some may manifest with abdominal pain, bowel obstruction, or gastrointestinal bleeding. CT and MRI are commonly used imaging modalities for GIST in NF1, while they may be negative sometimes. As DBE a more practical and non-invasive method now, we consider it is a valuable method for screening and early detecting small intestine disease for NF1 patients.

An unpredictable gastrointestinal bleed.

A 65-year-old male complained of persistent melena for 6 days, and displayed anemia symptoms without hematemesis, vomiting, and abdominal distention. He was diagnosed as ruptured aneurysm of aortic sinus Valsalva, and had received coronary artery occlusion 1 month ago. After the operation, he was continually prescribed clopidogrel 75 mg once daily. The laboratory examination showed blood hemoglobin concentration was 60 g/L without other conspicuous abnormality. Unfortunately, neither esophagogastroduodenoscopy (EGD) nor colonoscopy found no obvious bleeding lesions. And abdominal computed tomography angiography (CTA) and enhanced computed tomography (CT) showed no obvious abnormal findings. Moreover, capsule endoscopy revealed small intestinal with mucosal erosion (Figure 1A). After discontinued clopidogrel, blood transfusion, and support therapy, his symptoms was resolved with negative fecal occult blood, continued clopidogrel 75 mg once daily, and uneventfully discharged 1 week later.

Endoloop pre-ligation assisted resection of a giant Brunner's gland adenoma of the duodenal bulb.

Brunner's gland adenoma (BGA), also known as Brunneroma or polypoid hamartoma, is a rare benign duodenal tumor that proliferates from Brunner's glands of the duodenum. They are usually asymptomatic and discovered by chance during endoscopy. Some giant lesions can sometimes present with chronic abdominal pain, nausea, vomiting, and anemia, including gastrointestinal bleeding and obstructive symptoms, and need to be resected by surgery or endoscopy. Here we report a giant BGA that was easily and safely removed by Endoloop pre-ligation assisted resection.

A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Successful removal of a duodenal lesion in difficult location using "a sandwich method".

A 69-year-old woman was diagnosed with a duodenal adenoma near major duodenal papilla during cancer screening examination (Figure 1A). Therefore, endoscopic mucosal resection (EMR) was proposed to remove the duodenal lesion. Unfortunately, satisfactory visualization of the duodenal lesion was not obtained during gastroscopic operation. Unexpectedly, duodenoscopy provided optimal visualization of the duodenal lesion. Consequently, the "sandwich method" using duodenoscopy-gastroscopy-duodenoscopy was successfully performed to remove the challenging duodenal lesion. Firstly, the duodenoscopy was used to create a submucosal bleb through injecting saline containing 0.3 % indigo carmine. Subsequently, the gastroscopy with a transparent capwas used to remove the duodenal lesion with en bloc resection. Then, the duodenoscopy was reused to close the mucosal defect. Finally, pathologic examination showed a tubule-villous adenoma. The patient was recovered uneventfully, and discharged 2 days later.

MRI-based two-stage deep learning model for automatic detection and segmentation of brain metastases.

OBJECTIVES: To develop and validate a two-stage deep learning model for automatic detection and segmentation of brain metastases (BMs) in MRI images. METHODS: In this retrospective study, T1-weighted (T1) and T1-weighted contrast-enhanced (T1ce) MRI images of 649 patients who underwent radiotherapy from August 2019 to January 2022 were included. A total of 5163 metastases were manually annotated by neuroradiologists. A two-stage deep learning model was developed for automatic detection and segmentation of BMs, which consisted of a lightweight segmentation network for generating metastases proposals and a multi-scale classification network for false-positive suppression. Its performance was evaluated by sensitivity, precision, F1-score, dice, and relative volume difference (RVD). RESULTS: Six hundred forty-nine patients were randomly divided into training (n = 295), validation (n = 99), and testing (n = 255) sets. The proposed two-stage model achieved a sensitivity of 90% (1463/1632) and a precision of 56% (1463/2629) on the testing set, outperforming one-stage methods based on a single-shot detector, 3D U-Net, and nnU-Net, whose sensitivities were 78% (1276/1632), 79% (1290/1632), and 87% (1426/1632), and the precisions were 40% (1276/3222), 51% (1290/2507), and 53% (1426/2688), respectively. Particularly for BMs smaller than 5 mm, the proposed model achieved a sensitivity of 66% (116/177), far superior to one-stage models (21% (37/177), 36% (64/177), and 53% (93/177)). Furthermore, it also achieved high segmentation performance with an average dice of 81% and an average RVD of 20%. CONCLUSION: A two-stage deep learning model can detect and segment BMs with high sensitivity and low volume error. KEY POINTS: • A two-stage deep learning model based on triple-channel MRI images identified brain metastases with 90% sensitivity and 56% precision. • For brain metastases smaller than 5 mm, the proposed two-stage model achieved 66% sensitivity and 22% precision. • For segmentation of brain metastases, the proposed two-stage model achieved a dice of 81% and a relative volume difference (RVD) of 20%.

Successive Promotion of Formal [3+2] Cycloaddition of Aryl Methyl Ketones by I2 and Zn: Access to 2-Hydroxy-4-morpholin-2,5-diarylfuran-3(2H)-ones with a Quaternary Carbon Center.

2-Hydroxy-4-morpholin-2,5-diarylfuran-3(2H)-one derivatives were constructed sequentially using iodine and zinc dust from simple and readily available methyl ketone and morpholine as the starting materials. Under mild conditions, C-C, C-N, and C-O bonds formed in a one-pot synthesis. A quaternary carbon center was successfully constructed, and the active drug fragment morpholine was introduced into the molecule.