Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer's disease.

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD-associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD-associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD.

Aculeaxanthones A-E, new xanthones from the marine-derived fungus Aspergillus aculeatinus WHUF0198.

Introduction: Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A-E (4-8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4-4'-secalonic acid D (9), from different fermentation batches of the title fungus. Methods: A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1-9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay. Results and Discussion: The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4-8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1-9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 µg/mL, respectively.

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism.

Introduction: Forebrain neural networks are vital for cognitive functioning, and their excitatory-inhibitory (E-I) balance is governed by neural homeostasis. However, the homeostatic control strategies and transcriptomic mechanisms that maintain forebrain E-I balance and optimal cognition remain unclear. Methods: We used patch-clamp and RNA sequencing to investigate the patterns of neural network homeostasis with suppressing forebrain excitatory neural activity and spatial training. Results: We found that inhibitory transmission and receptor transcription were reduced in tamoxifen-inducible Kir2.1 conditional knock-in mice. In contrast, spatial training increased inhibitory synaptic connections and the transcription of inhibitory receptors. Discussion: Our study provides significant evidence that inhibitory systems play a critical role in the homeostatic control of the E-I balance in the forebrain during cognitive training and E-I rebalance, and we have provided insights into multiple gene candidates for cognition-related homeostasis in the forebrain.

Multiomics analysis of the mechanisms behind flavonoid differences between purple and green tender shoots of Camellia sinensis var. assamica.

Flavonoids are rich in tea plants (Camellia sinensis), and responsible for the flavor and healthful benefits of tea beverage. The anthocyanin levels in the purple tender shoots are higher than in the general green leaves of tea plant, which provide special materials to search metabolic mechanisms of flavonoid enrichment in plant. In this work, flavonoid differences between purple and green shoots from tea cultivars "Zijuan" (ZJ) and "Yunkang10" (YK-10) were investigated through metabolomic analysis, and mechanisms for their difference were surveyed by comparative transcriptomic and proteomic analysis. Levels of 34 flavonoids were different between ZJ and YK-10 shoots. Among them, 8 and 6 were marker metabolites in ZJ and YK-10, respectively. The differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and different-level metabolites (DLMs) between ZJ and YK-10 were researched, respectively; and interactions including DEG-DLM, DEP-DLM, DEG-DEP, and DEG-DEP-DLM were analyzed; the contents of 18 characteristic flavonoids in tea leaves and expressions of 34 flavonoid metabolic genes were measured to verify the omics results. Integrated above analyses, a proposed model of flavonoids biosynthesis in tea shoots were established. The differential expression of the leucoanthocyanidin reductase (LAR), anthocyanidin synthase (ANS), anthocyanidin reductase (ANR), UDPG-flavonoid glucosyltransferase (UGT) 75L12 and 94P1 at gene level, and the ANS, ANR, and UGT78A15 at protein level, were closely associated with differences in flavonoids between ZJ and YK-10 shoot. Together, this study provides new information on the flavonoid accumulation mechanism in tea plant.

Pre-expanded muscle-sparing Latissimus Dorsi free flap: An ideal option for the reconstruction of extensive anterior knee contractures.

BACKGROUND: Extensive and complex contractures in the anterior knee area can pose a significant challenge for reconstruction due to insufficient skin and soft tissue coverage and poor cosmetic and functional outcomes using traditional methods. We presented our experience with pre-expanded muscle-sparing latissimus dorsi (LD) free flap as an alternative option for large-scale anterior knee reconstruction. METHODS: From January 2016 to December 2020, we applied this surgical technique in six patients with large postburn or post-traumatic contractures of the anterior knee. After tissue expansion of several months, the expanded muscle-sparing LD free flap was harvested and transferred to resurface the lesions. Operative procedures, postoperative complications, and long-term outcomes were evaluated. RESULTS: A total of six patients aged 7 to 32 years (mean: 20 years) were reconstructed successfully without any major complication. The flap ranged from 20 × 8 cm to 40 × 16 cm. All donor sites were primarily closed. Follow-up (range: 12 to 24 months) evaluation showed satisfactory results in both cosmetic and functional aspects. CONCLUSIONS: Pre-expanded muscle-sparing LD free flap is a reliable and effective choice for extensive anterior knee contracture reconstruction with satisfactory esthetic and functional outcome. It can provide substantial amount of soft tissue coverage with minimal complications and donor-site morbidity. Furthermore, it offers a good basis for next-step orthopedic surgery, such as total knee arthroplasty (TKA).

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4+ T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

Late contralateral recurrence of retinal detachment in incontinentia pigmenti: A case report.

BACKGROUND: Incontinentia pigmenti (IP) is a rare X-linked genetic disease. It mainly manifests as skin lesions and causes problems in the eyes, teeth, bones, and central nervous system. Of the various ocular manifestations, the most severe with difficult recovery is retinal detachment (RD). Here, we report an unusual case of bilateral asymmetrical RD. CASE SUMMARY: We present the case of an 11-year-old Chinese girl with IP who complained of sudden blurring of vision in the left eye. At that time, she had been blind in her right eye for 4 years. RD with traction was observed in both eyes. A massive retinal proliferative membrane, exudation, and hemorrhage were seen in the left eye. We performed vitrectomy in her left eye. Her visual acuity recovered to 20/50, and her retina had flattened within 2 d after surgery. During the 3-mo follow-up, we performed retinal laser treatment of the non-perfused retinal area in her left eye. Eventually, her visual acuity returned to 20/32, and no new retinal abnormalities developed. CONCLUSION: In patients with IP with fundal abnormalities in one eye, it is important to focus on the rate of fundal change in the other eye. RD in its early stages can be effectively treated with timely vitrectomy and laser photocoagulation.

Identification of 2,2',4,5,5'-Pentachlorobiphenyl (PCB101) metabolites and their transmission characteristics in silver crucian carp (Carassius auratus gibelio).

Polychlorinated biphenyls (PCBs) have been attracting global concern due to their persistence and toxicity. However, the study on the metabolites of PCBs in freshwater fish is limited. In this study, the metabolites of 2,2',4,5,5'-Pentachlorobiphenyl (PCB101) in silver crucian carp (Carassius auratus gibelio) were identified for the first time. After intraperitoneal injection of PCB101 (2 mg/kg), the results showed that it could be metabolized to at least three types of metabolites, including hydroxylated (OH-), methoxylated (MeO-) and methyl sulfonated (MeSO2-) PCB101. The OH- metabolites identified in most tissues were 3-OH-PCB101and 4-OH-PCB101, such as liver, gallbladder, blood and muscle. MeSO2- metabolites identified in gallbladder, blood and brain were 3-MeSO2-PCB101 and 4-MeSO2-PCB101. Meanwhile, the MeO- metabolite identified in liver, gallbladder, blood and spleen of silver crucian carp was 4-MeO-PCB101. The investigation of the types and structures of PCB101 and its metabolites, as well as the tissue distribution and accumulation characteristics in silver crucian carp are beneficial to understand the transformation and metabolic mechanisms of PCBs in aquatic organisms. It is of great significance to identify potential pollution hazards of precursor compounds and their metabolites on aquatic products and ensure the quality and safety of aquatic products.

Bacterial lipopolysaccharide induces settlement and metamorphosis in a marine larva.

How larvae of the many phyla of marine invertebrates find places appropriate for settlement, metamorphosis, growth, and reproduction is an enduring question in marine science. Biofilm-induced metamorphosis has been observed in marine invertebrate larvae from nearly every major marine phylum. Despite the widespread nature of this phenomenon, the mechanism of induction remains poorly understood. The serpulid polychaete Hydroides elegans is a well established model for investigating bacteria-induced larval development. A broad range of biofilm bacterial species elicit larval metamorphosis in H. elegans via at least two mechanisms, including outer membrane vesicles (OMVs) and complexes of phage-tail bacteriocins. We investigated the interaction between larvae of H. elegans and the inductive bacterium Cellulophaga lytica, which produces an abundance of OMVs but not phage-tail bacteriocins. We asked whether the OMVs of C. lytica induce larval settlement due to cell membrane components or through delivery of specific cargo. Employing a biochemical structure­function approach with a strong ecological focus, the cells and OMVs produced by C. lytica were interrogated to determine the class of the inductive compounds. Here, we report that larvae of H. elegans are induced to metamorphose by lipopolysaccharide produced by C. lytica. The widespread prevalence of lipopolysaccharide and its associated taxonomic and structural variability suggest it may be a broadly employed cue for bacterially induced larval settlement of marine invertebrates.

Injection of Leukocyte-Poor Platelet-Rich Plasma for Moderate-to-Large Rotator Cuff Tears Does Not Improve Clinical Outcomes but Reduces Retear Rates and Fatty Infiltration: A Prospective, Single-Blinded Randomized Study.

OBJECTIVES: To determine whether leukocyte-poor platelet-rich plasma (Lp-PRP) reduced retear rates, reduced fatty infiltration, and improved functional outcomes in patients with degenerative moderate-to-large rotator cuff tears. METHODS: This was a randomized controlled study at a single center. A consecutive series of 104 patients with moderate-to-large rotator cuff tears was enrolled and randomly allocated to a control group (double-row suture-bridge arthroscopic rotator cuff repair alone, n = 52) and a study group (double-row suture-bridge repair followed by 3 Lp-PRP injections at the tendon repair site during surgery, at days 7 and 14 after surgery, n = 52). All patients were followed up for 27.2 months (range 24-36 months), with University of California at Los Angeles (UCLA) shoulder rating scale, the Constant score, and a visual analog scale (VAS) evaluated respectively. The integrity and fatty infiltration of repaired tissue were assessed by magnetic resonance imaging using the Sugaya classification and Goutallier grade classification at 24 months after surgery. Statistical analysis was performed based on the t test, χ2 test, and the Kendall tau-b correlation coefficient. RESULTS: Four patients refused follow-up, and 11 patients had incomplete data. Eventually, a total of 89 patients were available for 24 months follow-up. The mean UCLA score increased from 14.80 ± 2.53 to 29.37 ± 2.06 in control group and from 13.74 ± 3.30 to 30.14 ± 2.32 in study group (P = .103). The mean Constant score increased from 46.56 ± 5.90 to 86.83 ± 4.94 in control group and from 44.37 ± 7.92 to 88.80 ± 4.92 in study group (P = .063). The VAS score decreased from 3.22 ± 1.24 to 0.97 ± 1.12 in control group and in 3.49 ± 1.52 to 1.16 ± 0.99 in study group (P = .41). All differences in UCLA score, Constant score, and VAS between pre- and postoperation achieved minimal clinically important differences proposed for arthroscopic rotator cuff repair. Of the 89 patients, 76 had magnetic resonance imaging performed at 24 months after surgery. The retear rate was 17.6% in study group, which was lower than that in control group (38.1%, P = .049). In addition, the Goutallier grade was found to be significant difference between groups postoperatively (Kendall tau-b -0.24, P = .03) but no significant difference preoperatively (Kendall tau-b -0.18, P = .11). There were no complications in the patients. CONCLUSIONS: Our procedures involving repeated injections of Lp-PRP during surgery and at days 7 and 14, as described in this study, have positive effects on reducing retear rate and promoting Goutallier grade in patients following arthroscopic rotator cuff repair and could also provide substantial clinical outcomes that reach the minimal clinically important difference for surgical treatment. However, given the numbers available for analysis, it did not promote better clinical results when compared with the control group. LEVEL OF EVIDENCE: II, randomized controlled study.

Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour.

Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC50 values of 2.61, 1.19, and 1.74 µM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 µg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC50 of 20.06 µM) and α-glycosidase inhibitor (IC50 of 17.18 µM), while tabernamine, ervahanine B, and ervadivaricatine B only showed α-glycosidase inhibitory activities with IC50 values in the range of 0.95-4.61 µM.

Aculeaquamide A, cytotoxic paraherquamide from the marine fungus Aspergillus aculeatinus WHUF0198.

A new paraherquamide named aculeaquamide A (1) was isolated from an EtOAc extract of Aspergillus aculeatinus WHF0198 culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compound 1 was confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines, Bel-7402, A549, and HCT-116. Compounds 1 and 2 showed cytotoxicity against Bel-7402 with IC50 values of 3.3 and 1.9 µM, respectively.

Phylogenetic analysis and character evolution of tribe Arethuseae (Orchidaceae) reveal a new genus Mengzia.

Delimitation of the tribe Arethuseae has varied considerably since it was first defined. The relationships within Arethuseae, particularly within the subtribe Arethusinae, remain poorly elucidated. In this study, we reconstructed the phylogeny of Arethuseae, using six plastid markers (matK, ycf1, rbcL rpoc1, rpl32-trnL and trnL-F) from 83 taxa. The ancestral state reconstruction of 11 selected morphological characters was also conducted to identify synapomorphies and assess potential evolutionary transitions. Morphological character comparision between the distinct species Bletilla foliosa and other species are conducted. Our results unequivocally supported the monophyly of Arethuseae, which included highly supported clades and a clear synapomorphy of non-trichome-like lamellae. Furthermore, B. foliosa formed a separate clade in the subtribe Arethusinae, instead of clustering with the other Bletilla species in the subtribe Coelogyninae. The morphological characters comparision further showed that the B. foliosa clade could be distinguished from other genera in Arethuseae by multiple characters, including presence of lateral inflorescence, three lamellae with trichome-like apex and four pollinia. In light of these molecular and morphological evidences, we propose Mengzia as a new genus to accommodate B. foliosa and accordingly provide descriptions of this new genus and combination.

Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb.

Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and α-glucosidase.

Simulation experiment on OH-PCB being ingested through daily diet: Accumulation, transformation and distribution of hydroxylated-2, 2', 4, 5, 5'-pentachlorobiphenyl (OH-PCB101) in mice.

Animals exposure to polychlorinated biphenyls (PCBs) may result in retention of hydroxylated PCBs (OH-PCBs). OH-PCBs can be accumulated in animals, including humans, through the transmission of food chain. However, there are few studies on the accumulation and metabolism of OH-PCBs exposed to the body through daily diet. Therefore, this study was conducted to investigate the fate of OH-PCBs after being ingested through dietary intake. By adding 3-OH-PCB101 and 4-OH-PCB101 to the edible tissue of crucian carp, which were used as raw materials to prepare mouse feed, with an exposure concentration of 2.5 µg/kg ww. The exposure experiment lasted for a total of 80 days. The blood, feces and 11 tissues of mice at different times were analyzed qualitatively and quantitatively. It was found that major OH-PCB101 were accumulated in intestine or excreted with feces. A small part was accumulated in heart, lung and spleen. For the first time that the conversion from OH-PCB101 to PCB101 in mice was discovered, which shows from another perspective that persistent organic pollutants are difficult to be completely degraded in the environment. 4-MeO-PCB101, 3-MeSO2-PCB101, and 4-MeSO2-PCB101 were also found in various tissues. The results of this study show that after OH-PCBs accumulated in animals re-enter the organism through the food chain, they can be metabolized again and may be reversely transformed into the parent compounds. The present research shed new light on simulating the metabolic transformation process of OH-PCBs exposed to mammals through ingestion of fish. Available data show that second-generation persistent organic pollutants in the environment still need to be continuously concerned.

Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice.

Necroptosis, a form of programmed cell death, accounts for many inflammations in a wide range of diseases. Diet-induced obesity is manifested by low-grade inflammation in the mediobasal hypothalamus (MBH), and microglia are implicated as critical responsive components for this process. Here, we demonstrate that microglial necroptosis plays a pivotal role in obesity-related hypothalamic inflammation, facilitating proinflammatory cytokine production, such as TNF-α and IL-1ß. Treatment with the anti-diabetic drug metformin effectively reduces the obese phenotypes in the high-fat diet (HFD)-fed mice, attributing to remission of hypothalamic inflammation partly through repressing microglial necroptosis. Importantly, using the receptor-interacting protein kinase 1 inhibitor, necrostatin-1s, could not suppress the microglial inflammation nor prevent body weight gain in the obese mice, indicating that the microglial necroptosis is RIPK1-independent. Altogether, these findings offer new insights into hypothalamic inflammation in diet-induced obesity and provide a novel mechanism of action for metformin in obesity treatment.

Effectiveness of Various Dosages and Administration Methods of Tanezumab for the Treatment of Pain in Knee and Hip Osteoarthritis: a Network Meta-Analysis.

BACKGROUND: Previous meta-analyses have reported the superiority of tanezumab versus placebo in the treatment of osteoarthritis (OA). However, they did not compare different injection methods (intravenous or subcutaneous), doses of injection. OBJECTIVE: The goal of this network meta-analysis (NMA) was to evaluate the therapeutic effects of different dosages and methods of injection of tanezumab on relieving pain in patients with OA. METHODS: An online systematic search was performed by using the PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov databases from inception to November 9, 2019. The goal was to identify randomized controlled trials (RCTs) that concentrated on the therapeutic effects of different dosages and methods of injection of tanezumab in patients with OA. The pairwise meta-analyses with the fixed effects model were undertaken with the "meta" package using R 3.6.0 programming language. In addition, an NMA with fixed effects was assessed using a gemtc software. The surface under the cumulative ranking curve value of each intervention was calculated to obtain a hierarchy of treatments. RESULTS: Of the 328 RCTs identified through the literature search, 12 RCTs were included in the current NMA. In terms of the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, the most effective treatment was intravenous injection of tanezumab (10 mg; surface under the cumulative ranking curve values of 90% and 88%, respectively), and the least effective therapy was subcutaneous injection of tanezumab (2.5 mg; 20% and 19%). CONCLUSIONS: To achieve high therapeutic efficacy and avoid treatment failure, an intravenous injection of tanezumab (10 mg) is recommended as an efficacious therapy, facilitating pain relief in patients with OA. However, this conclusion may also be affected by the limitations of this study owing to the small sample size and data heterogeneity, and further research should therefore be conducted to eliminate these limitations and to confirm the findings.

Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system.

Angustmycin A has anti-mycobacterial and cytokinin activities, and contains an intriguing structure in which an unusual sugar with C5'-C6' dehydration is linked to adenine via an N-glycosidic bond. However, the logic underlying the biosynthesis of this molecule has long remained obscure. Here, we address angustmycin A biosynthesis by the full deciphering of its pathway. We demonstrate that AgmD, C, A, E, and B function as D-allulose 6-phosphate 3-epimerase, D-allulose 6-phosphate pyrophosphokinase, adenine phosphoallulosyltransferase, phosphoribohydrolase, and phosphatase, respectively, and that these collaboratively catalyze the relay reactions to biosynthesize angustmycin C. Additionally, we provide evidence that AgmF is a noncanonical dehydratase for the final step to angustmycin A via a self-sufficient strategy for cofactor recycling. Finally, we have reconstituted the entire six-enzyme pathway in vitro and in E. coli leading to angustmycin A production. These results expand the enzymatic repertoire regarding natural product biosynthesis, and also open the way for rational and rapid discovery of other angustmycin related antibiotics.

Decline of three farmland pest species in rapidly urbanizing landscapes.

Urbanization is a pressing challenge for earth's humans because it is changing not only natural environments but also agricultural lands. Yet, the consequences of cropland loss on pest insect populations that largely depend on these habitats remain largely unclear. We used a 17-year data set to investigate the dynamics of three moth pest species (i.e., striped stem borer, yellow stem borer, and pink stem borer) and their driving forces across the largest mega-urban region of China. Total abundance of three pest species is declined by about 80%, which was strongly associated with cropland loss during rapid urbanization. Our findings indicate that not only the increasing conversion of natural areas to human-dominated landscapes but also that of agricultural lands to urban landscapes can be critical to insect populations. It is therefore essential to monitor and understand the insect dynamics in rapidly urbanizing regions, which are currently found in many developing countries worldwide.

A New Fusicoccane-Type Norditerpene and a New Indone from the Marine-Derived Fungus Aspergillus aculeatinus WHUF0198.

A new norditerpene named aculeaterpene A (1) and a new indone named aculeaindone A (2), along with eight known compounds 3-10 were isolated from the culture extract of Aspergillus aculeatinus WHUF0198. The structural characterization of compounds 1 and 2 were performed by spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments, whereas the absolute configurations were determined by comparing their experimental or calculated ECD spectra. Compound 1 was the first report of fusicoccane-based norditerpene, in which the C-20 was degraded and tured into a hydroxy group.