Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling.

mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling. Mechanistically, SRPK2 promotes SR protein binding to U1-70K to induce splicing of lipogenic pre-mRNAs. Inhibition of this signaling pathway leads to intron retention of lipogenic genes, which triggers nonsense-mediated mRNA decay. Genetic or pharmacological inhibition of SRPK2 blunts de novo lipid synthesis, thereby suppressing cell growth. These results thus reveal a novel role of mTORC1-SRPK2 signaling in post-transcriptional regulation of lipid metabolism and demonstrate that SRPK2 is a potential therapeutic target for mTORC1-driven metabolic disorders.

FAM120A couples SREBP-dependent transcription and splicing of lipogenesis enzymes downstream of mTORC1.

The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that stimulates macromolecule synthesis through transcription, RNA processing, and post-translational modification of metabolic enzymes. However, the mechanisms of how mTORC1 orchestrates multiple steps of gene expression programs remain unclear. Here, we identify family with sequence similarity 120A (FAM120A) as a transcription co-activator that couples transcription and splicing of de novo lipid synthesis enzymes downstream of mTORC1-serine/arginine-rich protein kinase 2 (SRPK2) signaling. The mTORC1-activated SRPK2 phosphorylates splicing factor serine/arginine-rich splicing factor 1 (SRSF1), enhancing its binding to FAM120A. FAM120A directly interacts with a lipogenic transcription factor SREBP1 at active promoters, thereby bridging the newly transcribed lipogenic genes from RNA polymerase II to the SRSF1 and U1-70K-containing RNA-splicing machinery. This mTORC1-regulated, multi-protein complex promotes efficient splicing and stability of lipogenic transcripts, resulting in fatty acid synthesis and cancer cell proliferation. These results elucidate FAM120A as a critical transcription co-factor that connects mTORC1-dependent gene regulation programs for anabolic cell growth.

mTORC1 promotes cell growth via m6A-dependent mRNA degradation.

Dysregulated mTORC1 signaling alters a wide range of cellular processes, contributing to metabolic disorders and cancer. Defining the molecular details of downstream effectors is thus critical for uncovering selective therapeutic targets. We report that mTORC1 and its downstream kinase S6K enhance eIF4A/4B-mediated translation of Wilms' tumor 1-associated protein (WTAP), an adaptor for the N6-methyladenosine (m6A) RNA methyltransferase complex. This regulation is mediated by 5' UTR of WTAP mRNA that is targeted by eIF4A/4B. Single-nucleotide-resolution m6A mapping revealed that MAX dimerization protein 2 (MXD2) mRNA contains m6A, and increased m6A modification enhances its degradation. WTAP induces cMyc-MAX association by suppressing MXD2 expression, which promotes cMyc transcriptional activity and proliferation of mTORC1-activated cancer cells. These results elucidate a mechanism whereby mTORC1 stimulates oncogenic signaling via m6A RNA modification and illuminates the WTAP-MXD2-cMyc axis as a potential therapeutic target for mTORC1-driven cancers.

mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3-Dependent Foxk1 Phosphorylation.

The mammalian Target of Rapamycin Complex 1 (mTORC1)-signaling system plays a critical role in the maintenance of cellular homeostasis by sensing and integrating multiple extracellular and intracellular cues. Therefore, uncovering the effectors of mTORC1 signaling is pivotal to understanding its pathophysiological effects. Here we report that the transcription factor forkhead/winged helix family k1 (Foxk1) is a mediator of mTORC1-regulated gene expression. Surprisingly, Foxk1 phosphorylation is increased upon mTORC1 suppression, which elicits a 14-3-3 interaction, a reduction of DNA binding, and nuclear exclusion. Mechanistically, this occurs by mTORC1-dependent suppression of nuclear signaling by the Foxk1 kinase, Gsk3. This pathway then regulates the expression of multiple genes associated with glycolysis and downstream anabolic pathways directly modulated by Foxk1 and/or by Foxk1-regulated expression of Hif-1α. Thus, Foxk1 mediates mTORC1-driven metabolic rewiring, and it is likely to be critical for metabolic diseases where improper mTORC1 signaling plays an important role.

FUS Contributes to Nerve Injury-Induced Nociceptive Hypersensitivity by Activating NF-κB Pathway in Primary Sensory Neurons.

Dysregulation of pain-associated genes in the dorsal root ganglion (DRG) is considered to be a molecular basis of neuropathic pain genesis. Fused in sarcoma (FUS), a DNA/RNA-binding protein, is a critical regulator of gene expression. However, whether it contributes to neuropathic pain is unknown. This study showed that peripheral nerve injury caused by the fourth lumbar (L4) spinal nerve ligation (SNL) or chronic constriction injury (CCI) of the sciatic nerve produced a marked increase in the expression of FUS protein in injured DRG neurons. Blocking this increase through microinjection of the adeno-associated virus (AAV) 5-expressing Fus shRNA into the ipsilateral L4 DRG mitigated the SNL-induced nociceptive hypersensitivities in both male and female mice. This microinjection also alleviated the SNL-induced increases in the levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and glial fibrillary acidic protein (GFAP) in the ipsilateral L4 dorsal horn. Furthermore, mimicking this increase through microinjection of AAV5 expressing full-length Fus mRNA into unilateral L3/4 DRGs produced the elevations in the levels of p-ERK1/2 and GFAP in the dorsal horn, enhanced responses to mechanical, heat and cold stimuli, and induced the spontaneous pain on the ipsilateral side of both male and female mice in the absence of SNL. Mechanistically, the increased FUS activated the NF-κB signaling pathway by promoting the translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Our results indicate that DRG FUS contributes to neuropathic pain likely through the activation of NF-κB in primary sensory neurons.SIGNIFICANCE STATEMENT In the present study, we reported that fused in sarcoma (FUS), a DNA/RNA-binding protein, is upregulated in injured dorsal root ganglion (DRG) following peripheral nerve injury. This upregulation is responsible for nerve injury-induced translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Because blocking this upregulation alleviates nerve injury-induced nociceptive hypersensitivity, DRG FUS participates in neuropathic pain likely through the activation of NF-κB in primary sensory neurons. FUS may be a potential target for neuropathic pain management.

Sulfone-Functionalized Chichibabin's Hydrocarbons: Stable Diradicaloids with Symmetry Breaking Charge Transfer Contributing to NIR Emission beyond 900 nm.

While monoradical emitters have emerged as a new route toward efficient organic light-emitting diodes, the luminescence property of organic diradicaloids is still scarcely explored. Herein, by devising a novel radical-radical coupling-based synthetic approach, we report a new class of sulfone-functionalized Chichibabin's hydrocarbon derivatives, SD-1-3, featuring varied substituent patterns and moderate to high diradical characters of 0.44-0.70, as highly stable diradicaloids with rarely seen NIR emission beyond 900 nm. Via comprehensive experimental and theoretical investigations, we reveal that the optoelectronic and magnetic properties of these materials are significantly tuned by the variations of substitutions (H/CF3/OMe) on the molecular skeletons. More importantly, quantum chemical computations indicate that the embedding of sulfone groups has contributed to a breaking of their quasi-C2 symmetry of these diradicaloid molecules and results in an excited-state charge transfer character. Therefore, a remarkably deep NIR emissive wavelength of up to 998 nm, together with a large Stokes shift (∼386 nm), is achieved for the CF3-based SD-2 molecule in tetrahydrofuran. To the best of our knowledge, such a luminescent wavelength of SD-2 has represented the longest wavelengths among the currently reported organic fluorescent radicals. Overall, our work not only establishes a new synthetic approach toward stable Chichibabin's hydrocarbons but also paves the way for designing NIR emissive open-shell materials with both fundamental understanding and feasible control of their luminescent properties.

Phosphorylated viral protein evades plant immunity through interfering the function of RNA-binding protein.

Successful pathogen infection in plant depends on a proper interaction between the invading pathogen and its host. Post-translational modification (PTM) plays critical role(s) in plant-pathogen interaction. However, how PTM of viral protein regulates plant immunity remains poorly understood. Here, we found that S162 and S165 of Chinese wheat mosaic virus (CWMV) cysteine-rich protein (CRP) are phosphorylated by SAPK7 and play key roles in CWMV infection. Furthermore, the phosphorylation-mimic mutant of CRP (CRPS162/165D) but not the non-phosphorylatable mutant of CRP (CRPS162/165A) interacts with RNA-binding protein UBP1-associated protein 2C (TaUBA2C). Silencing of TaUBA2C expression in wheat plants enhanced CWMV infection. In contrast, overexpression of TaUBA2C in wheat plants inhibited CWMV infection. TaUBA2C inhibits CWMV infection through recruiting the pre-mRNA of TaNPR1, TaPR1 and TaRBOHD to induce cell death and H2O2 production. This effect can be supressed by CRPS162/165D through changing TaUBA2C chromatin-bound status and attenuating it's the RNA- or DNA-binding activities. Taken together, our findings provide new knowledge on how CRP phosphorylation affects CWMV infection as well as the arms race between virus and wheat plants.

Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.

More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience.

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57 %) and had small esophageal varices (87 %). En bloc, R0, and curative resections were achieved in 22 (96 %), 21 (91 %), and 19 (83 %) of patients, respectively. Severe intraprocedural bleeding (n = 1) and delayed bleeding (n = 1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.

Machine learning models for abstract screening task - A systematic literature review application for health economics and outcome research.

OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Retrieval of Trophoblast Cells from The Robertsonian Translocations for Prenatal Diagnosis.

Objective: To provide genetic information about the fetuses from carriers of Robertsonian (Rob) translocation and to explore the application value of extravillous trophoblasts (EVTs) cells collected from the cervical canal for prenatal diagnosis. Method: Trophoblast retrieval and isolation from the cervix (TRIC) is an approach that non-invasively isolates homogeneous trophoblast cells. In this study, the EVT cells were collected from the cervix of 20 pregnant women between 5-7 weeks gestation. Thereafter, STR analysis and fluorescence in situ hybridization (FISH) were performed on these trophoblast cells. Results: In 1 case (P5), we failed to collect the trophoblast cells, STR analysis showed maternal cell contamination in 4 cases, 6 cases were normal/balanced chromosome, and 9 cases were associated with unbalanced chromosome. The results of these 15 cases were consistent with those of villi FISH examination or cytogenetic analysis of cultured amniocytes. Conclusion: The collection of fetal trophoblast cells from the cervix provides a feasible approach for prenatal diagnosis. Rob translocation homozygosity could be seen as a potential means of speciation in humans with 44 chromosomes.

Clinical Characteristics of Multiple Sclerosis Patients Complicated by Disabilities and Analysis of Risk Factors Related to Disease Progression.

Objective: To analyze the clinical characteristics of multiple sclerosis (MS) patients complicated by disabilities in China, and to discuss the related factors of disease progression. Methods: Ninety-three MS patients presented to our hospital between March 2017 and December 2019 were selected as the research participants to conduct a retrospective analysis. Demographic information, onset time, onset age, clinical symptoms, MS types, and Expanded Disability Status Scale (EDSS) score were collected from all patients, and preliminary observation was made on MS cases in China. Subsequently, patients were grouped according to their sex, onset age and MS types to observe the differences in clinical characteristics of MS under different conditions. Finally, Logistic analysis was conducted to analyze the related factors affecting disease progression in MS patients. Results: MS was likely to occur in all age groups, among which the 30-40 age group had a slightly higher predilection. Women were more predisposed to MS, with motor symptoms as the major clinical presentations. The number of patients with sensory symptoms and the frequency of episodes in the past year were higher in female patients than in male patients (P < .05). Clinical isolated syndrome (CIS) patients had lower baseline ESDD than relapsing remitting MS (RRMS) patients (P < .05). According to Logistic regression analysis, baseline ESDD score and the frequency of episodes in the past year were independent risk factors affecting MS progression (P < .05). Conclusions: The clinical characteristics of MS in the Chinese population are basically similar to those in foreign countries, but RRMS accounts for a relatively low proportion. The ESDD score and the frequency of episodes in the past year are independent risk factors for MS progression.

Estimating Rotational Acceleration in Shoulder and Elbow Joints Using a Transformer Algorithm and a Fusion of Biosignals.

In the present study, we used a transformer model and a fusion of biosignals to estimate rotational acceleration in elbow and shoulder joints. To achieve our study objectives, we proposed a mechanomyography (MMG) signal isolation technique based on a variational mode decomposition (VMD) algorithm. Our results show that the VMD algorithm delivered excellent performance in MMG signal extraction compared to the commonly used technique of empirical mode decomposition (EMD). In addition, we found that transformer models delivered estimates of joint acceleration that were more precise than those produced by mainstream time series forecasting models. The average R2 values of transformer are 0.967, 0.968, and 0.935, respectively. Finally, we found that using a fusion of signals resulted in more precise estimation performance compared to using MMG signals alone. The differences between the average R2 values are 0.041, 0.053, and 0.043, respectively. Taken together, the VMD isolation method, the transformer algorithm and the signal fusion technique described in this paper can be seen as supplying a robust framework for estimating rotational acceleration in upper-limb joints. Further study is warranted to examine the effectiveness of this framework in other musculoskeletal contexts.

A Co-Localization Algorithm for Underwater Moving Targets with an Unknown Constant Signal Propagation Speed and Platform Errors.

Underwater mobile acoustic source target localization encounters several challenges, including the unknown propagation speed of the source signal, uncertainty in the observation platform's position and velocity (i.e., platform systematic errors), and economic costs. This paper proposes a new two-step closed-form localization algorithm that jointly estimates the angle of arrival (AOA), time difference of arrival (TDOA), and frequency difference of arrival (FDOA) to address these challenges. The algorithm initially introduces auxiliary variables to construct pseudo-linear equations to obtain the initial solution. It then exploits the relationship between the unknown and auxiliary variables to derive the exact solution comprising solely the unknown variables. Both theoretical analyses and simulation experiments demonstrate that the proposed method accurately estimates the position, velocity, and speed of the sound source even with an unknown sound speed and platform systematic errors. It achieves asymptotic optimality within a reasonable error range to approach the Cramér-Rao lower bound (CRLB). Furthermore, the algorithm exhibits low complexity, reduces the number of required localization platforms, and decreases the economic costs. Additionally, the simulation experiments validate the effectiveness of the proposed localization method across various scenarios, outperforming other comparative algorithms.

Genome-Wide Analysis of Serine Carboxypeptidase-like Genes in Soybean and Their Roles in Stress Resistance.

The serine carboxypeptidase-like (SCPL) gene family plays a crucial role in the regulation of plant growth, development, and stress response through activities such as acyltransferases in plant secondary metabolism pathways. Although SCPL genes have been identified in various plant species, their specific functions and characteristics in soybean (Glycine max) have not yet been studied. We identified and characterized 73 SCPL genes, grouped into three subgroups based on gene structure and phylogenetic relationships. These genes are distributed unevenly across 20 soybean chromosomes and show varied codon usage patterns influenced by both mutation and selection pressures. Gene ontology (GO) enrichment suggests these genes are involved in plant cell wall regulation and stress responses. Expression analysis in various tissues and under stress conditions, including the presence of numerous stress-related cis-acting elements, indicated that these genes have varied expression patterns. This suggests that they play specialized roles such as modulating plant defense mechanisms against nematode infections, enhancing tolerance to drought and high salinity, and responding to cold stress, thereby helping soybean adapt to environmental stresses. Moreover, the expression of specific GmSCPLs was significantly affected following exposure to nematode infection, drought, high salt (NaCl), and cold stresses. Our findings underscore the potential of SCPL genes in enhancing stress resistance in soybean, providing a valuable resource for future genetic improvement and breeding strategies.

A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China.

PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

Dihydropyridopyrazine Functionalized Xanthene: Generating Stable NIR Dyes with Small-Molecular Weight by Enhanced Charge Separation.

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.

Using high-diffraction-efficiency holographic optical elements in a full-color augmented reality display system.

Holographic optical elements (HOEs) play an important role in augmented reality (AR) systems. However, the fabrication of full-color HOEs is difficult and the diffraction efficiency is low. In this paper, we use the time-scheduled iterative exposure method to fabricate full-color HOEs with high diffraction efficiency. Through this method, a full-color HOE with an average diffraction efficiency of 73.4% was implemented in a single photopolymer, the highest rate yet reported. In addition, the AR system is simulated by the geometric optics method combining k-vector circle and ray tracing and structured by combining laser micro-drop and high diffraction efficiency HOEs. A good color blending effect was achieved in a full-color AR system by using the reconstruction wavelength consistent with the recording light. It can present clear holographic images in a full-color AR display system.

Field recovery via simplified carrier-assisted differential detection with interleaved subcarrier loading scheme at low CSPR condition.

In this Letter, we propose a simplified carrier-assisted differential detection (CADD) receiver with interleaved subcarrier loading scheme to further reduce the system hardware complexity while preserving the capability of field recovery of double sideband (DSB) complex-valued signals at the low carrier to signal power ratio (CSPR) condition. The numerical results show that the simplified CADD receiver requires less gap subcarriers to achieve a bit-error-rate (BER) below the 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3 as compared with a conventional CADD receiver. Despite the robustness to the time delay fluctuation decreases, which can be avoided using time-independent components in place of time delay line, more than a 3.2-dB optical signal-to-noise ratio (OSNR) gain can be obtained regardless of CSPR.

Gram-scale synthesis of alstoscholarinoid B via a bio-inspired strategy.

Alstoscholarinoid A is a novel rearranged triterpene with an unprecedented 6/6/5/6/6/6 framework and an additional unique C28 → C11-olide F-ring, and displays antihyperuricemic bioactivity. Herein, we report a bio-inspired synthesis of alstoscholarinoid B in a stepwise manner, which is amenable to gram-scale synthesis. The synthesis involved the Chugaev elimination as a key step to realize the migration of the Δ11,12-double bond of oleanolic acid, and also featured a sequential LiHMDS-mediated intramolecular aldol condensation/lactonization to establish the polycyclic ring system. Additionally, a tandem deprotection/aldol condensation/lactonization process under the influence of LiI/2,4,6-collidine for forging the polycyclic scaffold was also serendipitously discovered. Mechanistic studies indicated that lithium carboxylate might function as an inner base for the chemoselective α-deprotonation of the C12-aldehyde.