Construction of Reverse Type-II InP/ZnxCd1-xS Core/Shell Quantum Dots with Low Interface Strain to Enhance Photocatalytic Hydrogen Evolution.

The InP-based quantum dots (QDs) have attracted much attention in the field of photocatalytic H2 evolution. However, a shell should be used for InP-based photocatalytic systems to passivate the numerous surface defects. Different from the traditional InP-based core/shell QDs with Type-I or Type-II band alignment, herein, the "reverse Type-II" core/shell QDs in which both the conduction and valence bands of shell materials are more negative than those of core materials have been well-designed by regulating the ratio of Cd/Zn of the alloyed ZnxCd1-xS shell. The reverse Type-II band alignment would realize the spatial separation of photogenerated carriers. More importantly, the photogenerated holes tend to rest on the shell in the reverse Type-II QDs, which facilitate hole transfer to the surface, the rate-determining step for solar H2 evolution using QDs. Therefore, the obtained InP/Zn0.25Cd0.75S core/shell QDs exhibit superior photocatalytic activity and stability under visible light irradiation. The rate of solar H2 evolution reaches 376.19 µmol h-1 mg-1 at the initial 46 h, with a turnover number of ∼2,157,000 per QD within 70 h irradiation.

The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Tranexamic Acid Ameliorates Skin Hyperpigmentation by Downregulating Endothelin-1 Expression in Dermal Microvascular Endothelial Cells.

BACKGROUND: Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined. OBJECTIVE: To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells. METHODS: Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants. RESULTS: The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation. CONCLUSION: Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

Oral vitamin D supplementation on the prevention of peritoneal dialysis-related peritonitis: A pilot randomised controlled trial.

OBJECTIVE: Peritoneal dialysis (PD)-related peritonitis is independently associated with low serum 25-hydroxy vitamin D [25(OH)D] levels. Our objective is to examine the feasibility of conducting a large, randomised controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis. DESIGN: Pilot, prospective, open-label randomised controlled trial. SETTING: Peking University First Hospital, China. PARTICIPANTS: Patients receiving PD who had recovered from a recent episode of peritonitis between 30 September 2017 and 28 May 2020. INTERVENTIONS: Oral natural vitamin D supplementation (2000 IU per day) versus no vitamin D supplementation for 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25(OH)D level during follow-up) for a large, randomised controlled trial in the future to determine the effects of vitamin D on PD-related peritonitis. Secondary outcomes were time to peritonitis occurrence and outcome of subsequent peritonitis. RESULTS: Overall, 60 among 151 patients were recruited (recruitment rate was 39.7%, 95% CI 31.9-47.5%, recruitment rate among eligible patients was 61.9%, 95% CI 52.2-71.5%). Retention and adherence rates were 100.0% (95% CI 100.0-100.0%) and 81.5% (95% CI 66.8-96.1%), respectively. During follow-up, serum 25(OH)D levels increased in the vitamin D (VD) group (from 19.25 ± 10.11 nmol/L to 60.27 ± 23.29 nmol/L after 6 months, p < 0.001, n = 31), and remained higher (p < 0.001) than those in the control group (n = 29). No differences were observed between the two groups with respect to time to subsequent peritonitis (hazard ratio 0.85, 95% CI 0.33-2.17) or any of the peritonitis outcomes. Adverse events were uncommon. CONCLUSIONS: A randomised controlled trial of the effect of vitamin D supplementation on peritonitis occurrence in patients receiving PD is feasible, safe and results in adequate serum 25(OH)D levels.

Regulating Lewis Acidic Sites of 1T-2H MoS2 Catalysts for Solar-Driven Photothermal Catalytic H2 Production from Lignocellulosic Biomass.

Solar-driven photothermal catalytic H2 production from lignocellulosic biomass was achieved by using 1T-2H MoS2 with tunable Lewis acidic sites as catalysts in an alkaline aqueous solution, in which the number of Lewis acidic sites derived from the exposed Mo edges of MoS2 was successfully regulated by both the formation of an edge-terminated 1T-2H phase structure and tunable layer number. Owing to the abundant Lewis acidic sites for the oxygenolysis of lignocellulosic biomass, the 1T-2H MoS2 catalyst shows high photothermal catalytic lignocellulosic biomass-to-H2 transformation performance in polar wood chips, bamboo, rice straw corncobs, and rice hull aqueous solutions, and the highest H2 generation rate and solar-to-H2 (STH) efficiency respectively achieves 3661 µmol·h-1·g-1 and 0.18% in the polar wood chip system under 300 W Xe lamp illumination. This study provides a sustainable and cost-effective method for the direct transformation of renewable lignocellulosic biomass to H2 fuel driven by solar energy.

Collaborative governance effects of carbon market on GHG and air pollutants emission reduction in 3E model -- analysis based on System Dynamics.

The carbon market is regarded as one of the important means to achieve China's dual carbon target. It has ancillary effect for reducing air pollution while regulating carbon emissions since climate change and air pollution share the same origin and homology. Research on how to design the carbon market mechanism in order to maximize the synergistic effect of reducing greenhouse gas and air pollution will have a very important practical impact for China. This study conducts a theoretical analysis of the collaborative emission reduction path of China's carbon market, and constructs an Energy-Economy-Environment (3E) model of the collaborative emission reduction effect of carbon trading system based on System Dynamics. After analyzing the feedback path of the core cycle of the model and verifying its performance, three main policy factors in the carbon market are explored, and their effects under the dual objectives of emission control and economic development are comprehensively evaluated. This study suggests that the exploration of the potential of carbon market for collaborative governance should be accelerated, and ensure the orderly expansion of coverage and precise setting of limits, so as to ensure the smooth achievement of carbon reduction targets while guaranteeing the social and economic development.

Study of electronic and optical properties of CdI2 modulated by electric field: a first-principles study.

We found that an out-of-plane vertical electric field of 1.0 V/Ang helps to maintain the thermodynamic and kinetic stability of monolayer CdI2.The results indicated that the electric field modulates monolayer CdI2 to produce the Mexican-hat electronic state and the giant Stark effect of the vertical electric field on monolayer CdI2 originates from electric field lifting its conduction band. The results based on HSE06 + SOC calculations show that electric field induces strong spin polarization, leading to significant energy level splitting and spin flipping in the valence band. Based on GW0 + BSE, the electric field broadens effective optical response range of monolayer CdI2, the new peak in the optical absorption spectrum under electric field indicates that electric field helps to diminish excitonic effect of monolayer CdI2.

Lithium Triethylborohydride (LiHBEt3)-Promoted Hydrosilylation of Allenes to Prepare (E)-Allylsilanes.

A transition-metal-free hydrosilylation of allenes is reported herein by using commercially available lithium triethylborohydride (LiHBEt3) as the catalyst. Both mono- and disubstituted allenes could be hydrosilylated with primary or secondary silanes effectively. This reaction represents an environmental and economic method to prepare (E)-allylsilanes in good yields along with decent selectivities.

Rheumatoid arthritis-associated interstitial lung disease hotspots and future directions: A Web-of-Science based scientometric and visualization study.

OBJECTIVE: To identify new trends and potential hotspots in research on rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS: The Web of Science (WOS) database was used to search for RA-ILD-related literature published between August 31, 2002 and August 31, 2022. CiteSpace 6.1.R3, VOSviewer version 1.6.17, Scimago Graphica, and Pajek V2.0 visualization software were used to conduct a comprehensive analysis and network visualization mapping of the authors, countries, institutions, journals, cited references, and keywords. RESULTS: A total of 2412 articles were retrieved, and the number of articles published has grown annually since 2002. Eric L. Matteson was the most prolific author, and the Mayo Clinic and UNITED STATES have the highest publishing volume and influence. Clinical Rheumatology is the journal with the most papers published. Rheumatology was the most cited journal. The citation clusters and keywords concentrated on the mechanism, treatment, and predictive and prognostic factors. CONCLUSION: Pathogenesis, treatment, and predictive and prognostic factors were among the RA-ILD research directions and hotspots. Antirheumatoid drugs, especially biologics and small molecule inhibitors, were among the most actively researched treatment options. The results of this study provides an in-depth understanding of the development of RA-ILD publications, aids researchers in understanding hotspots and trends and provides a new perspective for future RA-ILD research.

Comparison between different treatment regimens of vascular targeting drug to malignant pleural effusion in patients with lung cancer: A Bayesian network meta-analysis.

BACKGROUND: The presence of malignant pleural effusion in lung cancer patients often suggests a poor prognosis. We plan to investigate which regimen of vascular targeting drug is preferable to control the malignant pleural effusion in such patients. METHODS: Two investigators dependently searched and screened for randomized controlled trials in PubMed, Embase, Web of Science and China National Knowledge Infrastructure from the database inception to August 2022. R software was applied to build a network model in Bayesian method. Objective response rate of malignant pleural effusion is the primary outcome measure. Besides, the incidence of 3 adverse events were compared, including gastrointestinal reaction, leukopenia and hypertension. Due to the disconnection of network, we analysis and discuss the short-term treatment (3-4 weeks) and long-term treatment (6-12 weeks) respectively. RESULTS: 31 studies with 2093 patients were identified. Four targeting drugs contain bevacizumab (Bev), anlotinib, apatinib and Endostar. Two administration routes include intracavity perfusion (icp) and intravenous injection. Based on the current evidence, for short-term treatments, compared with single-agent chemotherapy (CT), Bev_icp + CT, anlotinib + CT, Bev_icp and anlotinib + endorstar_icp present better objective response, and no statistical significance was found in objective response between Bev_icp + CT, anlotinib + CT and Bev_icp. For long-term treatments, compared with doublet or triplet chemotherapy (2CT or 3CT), Bev_icp + 2CT, apatinib + 2CT, Bev_icp + 3CT, and Bev_intravenous injection + 2CT are more effective option, but no statistical significance was found in objective response between the 4 combination regimens with chemotherapy. CONCLUSION: Our findings suggest that no statistical significance between above vascular targeting regimens. Pathological type of lung cancer may affect the effect of bevacizumab intracavity infusion plus chemotherapy. The influence of different administration routes of vascular targeting drugs on efficacy remains to be investigated. There are some concerns with the quality of the studies, and some limitations should be considered when interpreting these results, which includes limited geographical region and sample size of studies. Despite these limitations, this study may inform vascular targeting therapy choice in such a patient population.

MXene@Hydrogel composite nanofibers with the photo-stimulus response and optical monitoring functions for on-demand drug release.

The photo-stimulus response has the advantage of non-invasiveness, which could be used to control the "on" and "off" of drug release achieving on-demand release. Herein, we design a heating electrospray during electrospinning to prepare photo-stimulus response composite nanofibers consisting of MXene@Hydrogel. This heating electrospray enables to spray MXene@Hydrogel during the electrospinning process, and the hydrogel is uniformly distributed which cannot be achieved by the traditional soaking method. In addition, this heating electrospray can also overcome the difficulty that hydrogels are hard to be uniformly distributed in the inner fiber membrane.The "on" and "off" state of drug release could be controlled by light. Not only near infrared (NIR) light but also sunlight could trigger the drug release, which could benefit outdoor use when cannot find NIR light. Evidence by hydrogen bond has been formed between MXene and Hydrogel, the mechanical property of MXene@Hydrogel composite nanofibers is significantly enhanced, which is conducive to the application of human joints and other parts that need to move. These nanofibers also possess fluorescence property, which is further used to real-time monitor the in-vivo drug release. No matter the fast or slow release, this nanofiber can achieve sensitive detection, which is superior to the current absorbance spectrum method.

Nagimycins A and B, Antibacterial Ansamycin-Related Macrolactams from Streptomyces sp. NA07423.

Chemical investigation of Streptomyces sp. NA07423 led to the discovery of two unreported macrolactams, nagimycins A (1) and B (2). Their structures were elucidated by NMR, HRESIMS, X-ray crystallography, and comparison of experimental and theoretical ECD spectra. The nagimycins have a unique butenolide moiety rarely found in ansamycin antibiotics. Genome analysis revealed the putative biosynthetic gene cluster for nagimycins, and a likely biosynthetic pathway was proposed. Notably, compounds 1 and 2 exhibited potent antibacterial activity against two pathogenic Xanthomonas bacteria.

Halomonas dongshanensis sp. nov., isolated from the seawater of Dongshan Island.

A taxonomic study was carried out on strain yzlin-01T, isolated from Dongshan Island seawater. The bacterium was Gram-stain-negative, catalase-positive, oxidase-negative, rod-shaped, and motile by polar flagella. Growth was observed at temperatures of 10-40 °C, at salinities of 0.5-18 %, and at pH of 6-10. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain yzlin-01T belonged to the genus Halomonas, with the highest sequence similarity to Halomonas malpeensis YU-PRIM-29T (96.7 %), followed by Halomonas johnsoniae T68687T (96.4 %) and Halomonas gomseomensis M12T (96.4 %), and other species of the genus Halomonas (93.4-96.3 %). The ANI and digital DNA-DNA hybridization estimate values between strain yzlin-01T and the closest type strain Halomonas malpeensis YU-PRIM-29T were 77.44 and 21.6 %, respectively. The principal fatty acids were summed feature 8 (consisting of C18 : 1 ω7c and/or C18 : 1 ω6c; 55.7 %), C16 : 0 (20.6 %), C12 : 0 3-OH (6.8 %), summed feature 3 (consisting of C16 : 1 ω7c and/or C16 : 1 ω6c; 5.1 %). The G+C content of the chromosomal DNA was 60.0 mol %. The respiratory quinone was identified as Q-9 (100 %). Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid, and three unidentified phospholipids were present. Combined genotypic and phenotypic data suggest that strain yzlin-01T represents a novel species within the genus Halomonas, for which the name Halomonas dongshanensis sp. nov. is proposed, with the type strain yzlin-01T (=GDMCC 1.3202T=KCTC 92467T).

Point-of-care ultrasound diagnosis of skull fracture in Chinese children 0-6 years old with scalp hematoma from minor head trauma: A preliminary prospective observational study.

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0-6 years old. Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0-6 years old with scalp hematoma in China. Methods: We performed a prospective observational study and screened children 0-6 years old with closed scalp hematoma and a Glasgow coma scale of 14-15 at Hospital in China. Enrolled children (N = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan. Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P < 0.0001), with kappa = 0.87 (95% confidence interval, i.e., 95% CI, [0.69, 1.00]) and area under the curve = 0.95 (95% CI [0.86, 1], P < 0.0001). The point-of-care ultrasound examination had the sensitivity of 91.7% (95% CI [62.5%, 100%]), specificity of 98.6% (95% CI [94.6%, 100%]), positive predictive value of 84.6% (95% CI [56.5%, 96.9%]), negative predictive value of 99.2% (95% CI [95.6%, 100%]), and accuracy of 98.0% (95% CI [94.1%, 99.6%]). Conclusions: While our study is preliminary in nature, our findings may guide future larger studies in assessing the utility of point-of-care ultrasound examination in diagnosing skull fractures in children with scalp hematoma from minor head trauma.

Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs.