Multiplication-free and hardware-efficient baud-rate timing error detector for Nyquist and faster than Nyquist optical IM/DD systems.

Clock recovery (CR) algorithms that support higher baud rates and advanced modulation formats are crucial for short-distance optical interconnections, and it is desirable to push CR to operate at baud rate with minimal computing resources and power. In this Letter, we proposed a hardware-efficient and multiplication operation-free baud-rate timing error detector (TED) as a solution to meet these demands. Our approach involves employing both the absolute value of samples and the nonlinear sign operation to emphasize the clock tone, which is deteriorated by severe bandwidth limitation in Nyquist and faster than Nyquist (FTN) systems. Through experimental investigations based on a transceiver system with a 3 dB bandwidth of 30 GHz, the proposed baud-rate TED exhibits excellent performance. The proposed scheme successfully achieves clock synchronization of the received signals with the transmitted signals, including 50 GBaud PAM4/8, 80 GBaud PAM4, and up to 120 GBaud PAM4 FTN signals. To the best of our knowledge, the CR based on the proposed baud-rate TED is the most optimal solution for ultrahigh-speed short-reach IM/DD transmission, comprehensively considering the timing jitter, bit error rate (BER), and implementation complexity.

Influence of Organic Impurities on Fractional Crystallization of NaCl and Na2SO4 from High-Salinity Coal Chemical Wastewater: Thermodynamics and Nucleation Kinetics Analysis.

It is a valid path to realize the zero discharge of coal chemical wastewater by using the fractional crystallization method to recycle the miscellaneous salt in high-salinity wastewater. In this study, the thermodynamics and nucleation kinetics of sodium chloride (NaCl) and sodium sulfate (Na2SO4) crystallization in coal chemical wastewater were systematically studied. Through analyses of solubility, metastable zone width, and induction period, it was found that the impurity dimethoxymethane would increase the solid-liquid interface energy and critical crystal size during the nucleation of Na2SO4. Ternary phase diagrams of the pseudo-ternary Na2SO4-NaCl-H2O systems in simulated wastewater were plotted in the temperature range of 303.15 to 333.15 K, indicating that a co-ionization effect existed between NaCl and Na2SO4, and NaCl had a strong salting out effect on Na2SO4. Finally, the nucleation rate and growth rate of Na2SO4 crystals under simulated wastewater conditions were determined by the intermittent dynamic method, and the crystallization kinetic models of Na2SO4 were established. The crystallization nucleation of Na2SO4 crystals was found to be secondary nucleation controlled by surface reactions. The basic theoretical research of crystallization in this study is expected to fundamentally promote the application of fractional crystallization to realize the resource utilization of high-salinity wastewater in the coal chemical industry.

Discovery of P450-Modified Sesquiterpenoids Levinoids A-D through Global Genome Mining.

Cytochrome P450-modified bacterial terpenoids remain in a vast chemical space to be explored. In the present study, we conducted global genome mining of 223,829 bacterial genomes and identified 2892 bacterial terpenoid biosynthetic gene clusters (BGCs) with cytochrome P450 genes. Among these, we selected 562 with multiple P450 enzymes, which were further clustered as 355 gene cluster families by sequence similarity analysis. We then chose lev, a BGC from Streptomyces levis MCCC1A01616, for heterologous expression and discovered four new α-amorphene-type sesquiterpenoids, levinoids A-D (1-4). The structures and absolute configurations of these four new compounds were determined by employing extensive NMR analysis, NMR chemical shift calculations with DP4+, and ECD calculations. Furthermore, levinoid C (3) exhibited a moderate level of neuroprotective activity (EC50 = 21 µM) in the glutamate-induced excitotoxicity cell model. Our findings highlight the untapped chemical diversity of P450-modified bacterial terpenoids, opening new avenues for further exploration and discovery.

Ubiquitous occurrence of p-Phenylenediamine (PPD) antioxidants and PPD-quinones in fresh atmospheric snow and their amplification effects on associated aqueous contamination.

p-Phenylenediamine (PPD) antioxidants are heavily used for protection of commercial rubber products (e.g., vehicle tire), resulting in their widespread contamination in ecosystem. PPD-quinones (PPDQs), the toxic quinone derivatives of PPDs, are also discovered as novel environmental pollutants. However, the contamination characteristics of PPDs/PPDQs in fresh atmospheric snow (without deposition on the Earth surface) have seldom been studied. This work first reports the broad distributions of PPDs and PPDQs in fresh atmospheric snow collected from seven Chinese urban areas. Individual median values of detected concentrations were in the ranges of 0.4 to 260 pg g-1 (PPDs) and 0.7 to 104 pg g-1 (PPDQs). The concentration deviation by long-term deposition on the ground was eliminated. In most sampling regions, wearing of vehicle rubber tires was possibly responsible for spatial-dependent PPDs' pollution level variations, and high concentrations of PPDs promoted PPDQs' formation in snow from atmosphere. Yet, excessive O3 may further oxidize and reduce PPDQs in atmospheric fresh snow from Zhengzhou, which is different from previous research. Furthermore, snowfall was noticed might amplify concentrations of three PPDs and PPDQs in an inland lake, which possibly worsen corresponding pollution in water system. Current study elucidates the potential impacts of snow-bound PPDs/PPDQs on ecosystems should not be underestimated.

Bright Nonblinking Photoluminescence with Blinking Lifetime from a Nanocavity-Coupled Quantum Dot.

Colloidal quantum dots (QDs) are excellent luminescent nanomaterials for many optoelectronic applications. However, photoluminescence blinking has limited their practical use. Coupling QDs to plasmonic nanostructures shows potential in suppressing blinking. However, the underlying mechanism remains unclear and debated, hampering the development of bright nonblinking dots. Here, by deterministically coupling a QD to a plasmonic nanocavity, we clarify the mechanism and demonstrate unprecedented single-QD brightness. In particular, we report for the first time that a blinking QD could obtain nonblinking photoluminescence with a blinking lifetime through coupling to the nanocavity. We show that the plasmon-enhanced radiative decay outcompetes the nonradiative Auger process, enabling similar quantum yields for charged and neutral excitons in the same dot. Meanwhile, we demonstrate a record photon detection rate of 17 MHz from a colloidal QD, indicating an experimental photon generation rate of more than 500 MHz. These findings pave the way for ultrabright nonblinking QDs, benefiting diverse QD-based applications.

Intercropped Flemingia macrophylla successfully traps tea aphid (Toxoptera aurantia) and alters associated networks to enhance tea quality.

BACKGROUND: The tea aphid, Toxoptera aurantia is a destructive pest causing severe damage to the quality and yield of tea, Camellia sinensis. Relying on chemical insecticides to control this pest causes adverse ecological and economic consequences. Trap plants are an eco-friendly alternative strategy to mitigate pest damage on focal plants by attracting target insects and natural enemies. Yet, the utilization of trap plants in tea plantations remains limited. Besides, the effects of the trap plant on the tea aphid-ant-predator community and tea quality and yield are unknown. RESULTS: Intercropped Flemingia macrophylla successfully trapped tea aphids and enhanced the complexity of aphid-ant-predator networks over three consecutive years compared to monoculture management. Moreover, F. macrophylla significantly increased the abundance of natural predators by 3100% and species richness by 57%. The increasing predators suppressed the aphid population and hampered its spillover to neighbouring tea plants. Consequently, F. macrophylla improved tea quality by an 8% increase in soluble sugar and a 26% reduction in polyphenols to amino acids ratio. CONCLUSION: The study illustrated that F. macrophylla is a suitable trap crop for tea aphid control in tea plantations. This legume increases species nodes and strengthens multiple connections in aphid-associated communities through its cascade effects, improving tea quality. These findings shed light on the potential application of trap plants in tea plantations as an efficient integrated pest management (IPM) strategy. © 2023 Society of Chemical Industry.

Mutagenesis-Derived Resistance to Black Point in Wheat.

Black point, a severe global wheat disease, necessitates deploying resistant cultivars for effective control. However, susceptibility remains prevalent among most wheat cultivars. Identifying new sources of resistance and understanding their mechanisms are crucial for breeding resistant cultivars. This study pinpointed black point resistance in an ethyl methane sulfonate (EMS)-mutagenized wheat population of Wanyuanbai 1 (WYB) and analyzed resistant mutants using RNA-Seq. The findings revealed the following: (i) wyb-18, among 10,008 EMS-mutagenized lines, exhibited robust resistance with significantly lower black point incidence under artificial Bipolaris sorokiniana inoculation in 2020 and 2021 (average incidence of 5.2% over 2 years), markedly reduced compared with WYB (50.9%). (ii) wyb-18 kernels displayed black point symptoms at 12 days after inoculation (dai), 3 days later than WYB. At 15 dai, wyb-18 kernels had isolated black spots, unlike WYB kernels, where the entire embryo turned black. (iii) wyb-18 showed heightened antioxidant enzyme activity, including peroxidase, catalase, and superoxide dismutase. (iv) Analysis of 543 differentially expressed genes between wyb-18 and WYB at 9 dai identified enrichment in the MAPK signaling pathway through KEGG analysis. Ten genes in this pathway exhibited upregulated expression, while one was downregulated in wyb-18. Among these genes, PR1, WRKY11, SAPK5, and TraesCS1A02G326800 (chitin recognition protein) consistently showed upregulation in wyb-18, making them potential candidates for black point resistance. These results offer valuable germplasm resources for breeding and novel insights into the mechanisms of black point resistance.

Discovery of Natural Potent HMG-CoA Reductase Degraders for Lowering Cholesterol.

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.

Photocatalytic degradation of perfluorooctanoic acid (PFOA) from water: A mini review.

Perfluorooctanoic acid (PFOA) has drawn increasing attention as a highly persistent organic pollutant. The inherent stability, rigidity and potential toxicities characteristics make it a challenge to develop efficient technologies to eliminate it from water. Photocatalytic technology, as one advanced method, has been widely used in the degradation of PFOA in water. In this review, recent progress in the design of photocatalysts including doping, defects engineering, heterojunction and surface modification to boost the photocatalytic performance toward PFOA is summarized. The relevant degradation mechanisms were also discussed in detail. Finally, future prospect and challenges are proposed. This review may provide new guidelines for researchers to design much more efficient photocatalysts applied in the elimination of PFOA.

Land use change alters carbon and nitrogen dynamics mediated by fungal functional guilds within soil aggregates.

Land use change is one of the greatest threats to soil biodiversity and ecological functions; however, how such a transition affects soil carbon (C) and nitrogen (N) dynamics driven by fungal communities at the aggregate level remains unclear. Here, we explored the variation in soil C and N pools, specific enzyme activities and fungal communities and functional guilds within three aggregate sizes (megaaggregates, > 2 mm; macroaggregates, 0.25-2 mm; microaggregates, < 0.25 mm) in a natural forest, 12- and 24-year-old rubber monocultures and corresponding agroforestry systems in tropical China. Tropical forest conversion to rubber monocultures generally reduced C and N pools in all aggregates, while agroforestry systems decreased microbial biomass C and N. Carbon- and N-degrading enzyme activities responded differently to forest conversion and were enhanced in agroforestry systems. The levels of C and N pools and their related enzyme activities increased as the aggregate size decreased. Moreover, fungal compositional shifts in dominance from copiotrophic Ascomycota and Basidiomycota (r-strategists) into oligotrophic Zygomycota (K-strategists) were noted following forest conversion, resulting in more pathogenic fungi at the expense of saprotrophic and arbuscular mycorrhizal fungi. Pathogenic fungi were greatly inhibited due to abundant Mortierella after the establishment of 12-year-old agroforestry systems. The diversity of saprotrophic fungi was the highest in microaggregates. Regardless of land use type, aggregate-associated C and N pools, especially DOC, MBC, NO3--N and DON in microaggregates, were interactively mediated by functional guilds of fungi, which was primarily driven by soil pH. These results highlight the importance of fungal functional guilds in determining C and N dynamics at the aggregate level and provide insights into the sustainable management of cash tree plantations.

Low complexity joint clock recovery and adaptive equalization based on a baud-rate timing phase error detector for short-reach digital coherent transmission.

Digital coherent receivers adopting joint clock recovery and adaptive equalization (JCA) can avoid failures of the adaptive equalizer (AEQ) or clock recovery algorithm (CRA) due to clock asynchrony and chromatic dispersion (CD). But in the previous JCA scheme, the AEQ has a heavy computational load as it has to generate two samples per symbol (SPS) for the subsequent timing phase error detector (TPED) which is the core of the CRA. Furthermore, the previous JCA scheme cannot compensate for receiver skew or accommodate Nyquist signals with small roll-off factors (ROFs). These shortcomings hinder its practical applications in ultrahigh-speed short-reach coherent transmission requiring low power consumption, high spectral efficiency, whilst being sensitive to receiver skew. To solve this problem, we propose a new JCA scheme by integrating a two-section real-valued (RV) AEQ with an all-digital feedback CRA based on a baud-rate TPED versatile for different ROFs. Experiments for 61-GBaud dual-polarization (DP) Nyquist 16QAM signals with an ROF of 0.01 show that, compared with the previous JCA scheme, the proposed scheme can reduce the AEQ computational load by about 70% for 10-km transmission, whilst improving the receiver sensitivity by more than 1.7 dB for a receiver skew of 1.5 ps. As far as we know, the proposed JCA scheme is the most comprehensive and efficient solution for ultrahigh-speed short-reach coherent transmission where CD, receiver skew, clock asynchrony, and Nyquist signals with small ROFs have to be dealt with.

[Risk Factors and Sampling Range Evaluation of Lymph node Metastasis for 
Non-small Cell Lung Cancer with Diameter ≤2 cm].

BACKGROUND: More early-stage non-small cell lung cancer (NSCLC) are diagnosed in time and treated surgically, but systematic lymph node dissection can not bring enough survival benefits for them, and even increase the probability of postoperative complications. This study aims to analyze the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes for NSCLC with diameter ≤2 cm, so as to provide reference for surgery. METHODS: We collected 1051 patients with pulmonary nodule diameter ≤2 cm who were treated by pulmonary lobectomy with lymph node sampling/dissection in Department of Thoracic Surgery of the First Affiliated Hospital with Nanjing Medical University from December 2009 to December 2019. SPSS 26.0 statistical software was used for statistical analysis, to explore the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes. RESULTS: 95 of 1051 (9.04%) patients presented lymph node metastasis. Male, pathological non-adenocarcinoma, 1 cm0.05). Lymph nodes in group N1 were significantly correlated with lymph node metastasis in groups #2R, #4R, #5, #6, #7 and #9 (P<0.01). CONCLUSIONS: Lobe-specific lymph node dissection (LSND) can be performed for early-stage NSCLC. Male, pathological non-adenocarcinoma, 1 cm

Quantitative trait loci for resistance to black point caused by Bipolaris sorokiniana in bread wheat.

Black point disease is a serious concern in wheat production worldwide. In this study, we aimed to identify the major quantitative trait loci (QTL) for resistance to black point caused by Bipolaris sorokiniana and develop molecular markers for marker-assisted selection (MAS). A recombinant inbred line (RIL) population derived from a cross between PZSCL6 (highly susceptible) and Yuyou1 (moderately resistant) was evaluated for black point resistance at four locations under artificial inoculation with B. sorokiniana. Thirty resistant and 30 susceptible RILs were selected to form resistant and susceptible bulks, respectively, which were genotyped by the wheat 660 K SNP array. Two hundred and four single-nucleotide polymorphisms (SNPs) were identified, among which 41(20.7%), 34 (17.2%), 22 (11.1%), and 22 (11.1%) were located on chromosomes 5A, 5B, 4B, and 5D, respectively. The genetic linkage map for the RIL population was constructed using 150 polymorphic SSR and dCAPS markers. Finally, five QTL were detected on chromosomes 5A, 5B, and 5D, designated QBB.hau-5A, QBB.hau-5B.1, QBB.hau-5B.2, QBB.hau-5D.1, and QBB.hau-5D.2, respectively. All resistance alleles were contributed by the resistant parent Yuyou1. QBB.hau-5D.1 is likely to be a new locus for black point resistance. The markers Xwmc654 and Xgwm174 linked to QBB.hau-5A and QBB.hau-5D.1, respectively, have potential utility in MAS-based breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01356-6.

Mechanistic Insight into the Inhibitory Activity of Elasnin-Based Coating against Early Marine Biofilms.

Marine biofilms are multispecies microbial communities on surfaces that are crucial to the marine environment. They cause marine corrosion, biofouling, and transmission of marine pathogens and thus pose a great threat to public health and the maritime industry. To control marine biofilms, effective and environmentally friendly antibiofilm compounds are highly needed. Elasnin is a potent antibiofilm compound that exhibits high efficiency in inhibiting marine biofilms and biofouling, but its mode of action remains unclear. In the present study, multiomic analysis combined with quorum-sensing assays and in silico study revealed that elasnin acted as a signaling molecule in the microbial community. Elasnin promoted the growth of dominant species in the biofilm but deprived their ability of sensing and responding to environmental changes by disturbing their regulations of the two-component system, i.e., the ATP-binding cassette transport system and the bacterial secretion system. Consequently, biofilm maturation and subsequent biofouler settlement were inhibited. Elasnin also exhibited higher antibiofilm efficiency than dichlorooctylisothiazolinone and had low toxicity potential on the embryos and adults of marine medaka fish. Overall, this study provided molecular and ecological insights into elasnin's mode of action, highlighting its application potential in controlling marine biofilms and the feasibility and advantages of using signal molecules to develop eco-friendly technologies.

High receiver skew-tolerant and hardware-efficient clock recovery for short-reach coherent transmission.

The performance of the high-baud-rate and high-order-modulation-format short-reach coherent transmission systems is sensitive to the in-phase and quadrature (IQ) skew. The conventional receiver IQ skew compensation schemes based on adaptive equalizers (AEQs) suffer from the IQ skew enhanced timing jitter incurred by the clock recovery algorithm (CRA), resulting in a serious sensitivity degradation. In this paper, we first propose a novel multiplication-free timing phase error detector (TPED) with the gain insensitive to the receiver IQ skew and the capability to deal with the complex-valued Nyquist signal with an arbitrary roll-off factor and its real-valued IQ tributaries. Based on the TPED, we then propose a new all-digital feedback CRA able to compensate for the receiver IQ skew. With the novel CRA, the IQ skew enhanced timing jitter is eliminated and the receiver sensitivity can be improved by more than 1 dB for the 61 GBaud dual-polarization Nyquist 16QAM system for an IQ skew of 5 ps. Furthermore, the proposed CRA can reduce the computation complexity of the AEQ by more than 25% compared with the existing schemes by relieving the AEQ from IQ skew compensation. Both numerical simulations and experiments are carried out to validate the advantages of the proposed algorithms. The high-skew-tolerant and low-complexity CRA is a strong candidate for the power-sensitive high-speed short-reach coherent transmission systems.

Multiplication-free timing phase error detector for Nyquist and non-Nyquist optical signals.

A versatile digital coherent receiver capable of handling optical signals with different kinds of pulse shaping schemes (PSSs) is indispensable for future flexible and heterogeneous coherent optical communication networks. Therefore, a low-complexity timing phase error detector (TPED) versatile for all PSSs is of particular interest. In this paper, we propose a TPED suitable for both Nyquist signals with different roll-off factors and non-Nyquist signals. It requires two samples per symbol and involves no multiplications. As far as we know, it has the lowest computation complexity compared with the existing TPEDs used in coherent systems, while incurring no receiver sensitivity penalty. Numerical simulations and experiments are carried out to demonstrate the superior timing performance and PSS versatility of the proposed TPED in both open-loop and closed-loop working conditions. We also implement the novel TPED in a field programmable gate array (FPGA) and verify its real-time clock recovery performance using the 10 Gbaud very low roll-off Nyquist and non-Nyquist quadrature phase shift keying (QPSK) signals.

Exosomal lncRNA PCAT1 Promotes Tumor Circulating Cell-Mediated Colorectal Cancer Liver Metastasis by Regulating the Activity of the miR-329-3p/Netrin-1-CD146 Complex.

Objective: This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1- (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis. Methods: Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer. Results: PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. Conclusions: LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.

Photonic-circuited resonance fluorescence of single molecules with an ultrastable lifetime-limited transition.

Resonance fluorescence as the emission of a resonantly-excited two-level quantum system promises indistinguishable single photons and coherent high-fidelity quantum-state manipulation of the matter qubit, which underpin many quantum information processing protocols. Real applications of the protocols demand high degrees of scalability and stability of the experimental platform, and thus favor quantum systems integrated on one chip. However, the on-chip solution confronts several formidable challenges compromising the scalability prospect, such as the randomness, spectral wandering and scattering background of the integrated quantum systems near heterogeneous and nanofabricated material interfaces. Here we report an organic-inorganic hybrid integrated quantum photonic platform that circuits background-free resonance fluorescence of single molecules with an ultrastable lifetime-limited transition. Our platform allows a collective alignment of the dipole orientations of many isolated molecules with the photonic waveguide. We demonstrate on-chip generation, beam splitting and routing of resonance-fluorescence single photons with a signal-to-background ratio over 3000 in the waveguide at the weak excitation limit. Crucially, we show the photonic-circuited single molecules possess a lifetime-limited-linewidth transition and exhibit inhomogeneous spectral broadenings of only about 5% over hours' measurements. These findings and the versatility of our platform pave the way for scalable quantum photonic networks.

Aspcandine: A Pyrrolobenzazepine Alkaloid Synthesized by a Fungal Nonribosomal Peptide Synthetase-Polyketide Synthase Hybrid.

Characterization of an orphan biosynthetic gene cluster found in the fungus Aspergillus candidus CBS 102.13 resulted in the discovery of a pyrrolobenzazepine alkaloid, aspcandine (1). The unique molecular scaffold of 1 is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which unusually incorporates 3-hydroxy-l-kynurenine as a building block. AcdB subsequently performs one round of chain elongation using malonyl-CoA, which is followed by the chain release to furnish the tricyclic system of 1.

Bathiapeptides: Polythiazole-Containing Peptides from a Marine Biofilm-Derived Bacillus sp.

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 µM. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.