Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy.

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

ExtraTrees-hidden Markov model based equalizer for mode division multiplexing ring-core fiber communication with non-orthogonal MultiCAP modulation.

This paper presents an orbital angular momentum mode division multiplexing (OAM-MDM) ring-core fiber transmission method based on non-orthogonal multiband carrierless amplitude and phase (NMCAP) modulation with an extremely randomized trees-hidden Markov model (ExtraTrees-HMM)-based equalizer. The ExtraTrees-HMM equalizer uses the statistical characteristics of the received distorted signals to model the nonlinear channel of the system to classify these distorted signals into corresponding constellation classes. Experiments were conducted using a 216 Gbit/s OAM-MDM NMCAP modulation optical fiber communication system with 2 km ring-core fiber transmission and the results show that compared with a conventional Volterra nonlinear equalizer (VNE), the proposed ExtraTrees-HMM equalizer could improve the receiver sensitivity by 1 dB for OAM mode l = + 2, and 0.6 dB for OAM mode l = + 3. In addition, the computational complexity of the proposed equalizer was reduced by 43.94% compared with the VNE. In brief, the ExtraTrees-HMM is a promising equalization candidate for ultra-high-capacity inter-data-center interconnections.

End-to-end learning strategy based on a frequency domain feature decoupling network emulator with joint probabilistic shaping and equalization for a 300-Gbit/s OAM mode division multiplexing transmission.

Mode coupling and device nonlinear impairment appear to be a long-standing challenge in the orbital angular momentum (OAM) mode division multiplexing (MDM) of intensity modulation direct detection (IM/DD) transmission systems. In this paper, we propose an end-to-end (E2E) learning strategy based on a frequency domain feature decoupling network (FDFDnet) emulator with joint probabilistic shaping (PS) and equalization for an OAM-MDM IM/DD transmission with three modes. Our FDFDnet emulator can accurately build a complex nonlinear model of an OAM-MDM system by separating the signal into features from different frequency domains. Furthermore, a FDFDnet-based E2E strategy for joint PS and equalization is presented with the aim of compensating the signal impairment for the OAM-MDM IM/DD system. An experiment is carried out on a 300 Gbit/s carrierless amplitude phase-32 (CAP-32) signal with three OAM modes over a 10 km ring-core fiber transmission, and the results show that the proposed FDFDnet emulator outperforms the traditional CGAN emulator, with improvements in the modelling accuracy of 30.8%, 26.3% and 31% for the three OAM modes. Moreover, the receiver sensitivity of the proposed E2E learning strategy is higher than for the CGAN emulator by 3, 2.5, 2.2 dBm and the real channel by 5.5, 5.1, and 5.3 dBm for the three OAM modes, respectively. Our experimental results demonstrate that the proposed FDFDnet emulator-based E2E learning strategy is a promising contender for achieving ultra-high-capacity interconnectivity between data centers.

Dual vector millimeter-wave signal generation based on optical carrier suppression modulation and direct detection with one photodetector.

We propose a novel, to the best of our knowledge, scheme for dual vector millimeter-wave (mm-wave) signal generation and transmission, based on optical carrier suppression (OCS) modulation, precoding, and direct detection by a single-ended photodiode (PD). At the transmitter side, two independent vector radio frequency (RF) signals with precoding, generated via digital signal processing (DSP), are used to drive an in-phase/quadrature (I/Q) modulator operating at the optical OCS modulation mode to simultaneously generate two independent frequency-doubling optical vector mm-wave signals, which can reduce the bandwidth requirement of transmitter's components and enhance spectral efficiency. With the aid of the single-ended PD and subsequent DSP at the receiver side, two independent frequency-doubling vector mm-wave signals can be separated and demodulated without data error. Based on our proposed scheme, we experimentally demonstrate the generation, transmission, and detection of 2-Gbaud 30-GHz quadrature-phase-shift-keying (QPSK) and 2-Gbaud 46-GHz QPSK signals over 10-km single-mode fiber-28 (SMF-28) and 1-m wireless transmission. The results indicate that the bit-error ratio (BER) of the dual vector mm-wave signals can each reach the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.

OAM mode-division multiplexing IM/DD transmission at 4.32†Tbit/s with a low-complexity adaptive-network-based fuzzy inference system nonlinear equalizer.

Stochastic nonlinear impairment is the primary factor that limits the transmission performance of high-speed orbital angular momentum (OAM) mode-division multiplexing (MDM) optical fiber communication systems. This Letter presents a low-complexity adaptive-network-based fuzzy inference system (LANFIS) nonlinear equalizer for OAM-MDM intensity-modulation direct-detection (IM/DD) transmission with three OAM modes and 15 wavelength division multiplex (WDM) channels. The LANFIS equalizer could adjust the probability distribution functions (PDFs) of the distorted pulse amplitude modulation (PAM) symbols to fit the statistical characteristics of the WDM-OAM-MDM transmission channel. Therefore, although the transmission symbols in the WDM-OAM-MDM system are subjected to a stochastic nonlinear impairment, the proposed LANFIS equalizer can effectively compensate the distorted signals. The proposed equalizer outperforms the Volterra equalizer with improvements in receiver sensitivity of 2, 1.5, and 1.3 dB for three OAM modes at a wavelength of 1550.12 nm, respectively. It also outperforms a CNN equalizer, with improvements in receiver sensitivity of 1, 0.5, and 0.3 dB, respectively. Moreover, complexity reductions of 67%, 74%, and 99.9% are achieved for the LANFIS equalizer compared with the Volterra, CNN, and ANFIS equalizers, respectively. The proposed equalizer has high performance and low complexity, making it a promising candidate for a high-speed WDM-OAM-MDM system.

Efficient Initialization of Fluxonium Qubits based on Auxiliary Energy Levels.

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

Native Approach to Controlled-Z Gates in Inductively Coupled Fluxonium Qubits.

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation.

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Association of ultra-processed food consumption with muscle mass among young and middle-aged US adults.

INTRODUCTION: Muscle mass is vital for physical activity and fundamental physiological processes supporting long-term health. While aging is inevitable, certain modifiable factors positively influence muscle preservation and overall well-being. However, the relationship between the consumption of ultra-processed foods (UPF) and muscle mass is not yet clear. METHODS: This study included 7,173 men and nonpregnant women aged 20-59 years with valid 24-hour dietary recalls and accessible whole-body dual-energy x-ray absorptiometry (DXA) scans from NHANES 2011-2018. UPFs were identified through the NOVA classification system, and the percentage of energy derived from UPF consumption was evaluated in quintiles. Muscle mass measures were derived from DXA scans and quantified by the total and regional muscle mass index (MMI, kg/m²) and appendicular muscle mass index (AMMI, kg/m²). Multivariable-adjusted generalized linear regression models were applied to investigate the association between consumption of UPFs and muscle mass measures overall and by sociodemographic subgroups. RESULTS: The multivariable-adjusted differences of total MMI from the lowest to highest quintile of UPF consumption were 0 (reference), -0.03 (95% CI, -0.13, 0.07), -0.13 (95%CI, -0.24, -0.04), -0.12 (95% CI, -0.23, -0.01), and - 0.17 (95% CI, -0.27, -0.08) (P for trend < 0.001). Subtotal MMI followed a similar magnitude of associational pattern as total MMI. For trunk MMI, corresponding values from the lowest to highest quintiles of UPF consumption were 0 (reference), -0.02 (95% CI, -0.07, 0.02), -0.05 (95%CI, -0.11, 0.00), -0.07 (95% CI, -0.13, -0.01), and - 0.07 (95% CI, -0.12, -0.01). For AMMI, corresponding values from the lowest to highest quintiles of UPF consumption were 0 (reference), -0.004 (95% CI, -0.07, 0.06), -0.08 (95%CI, -0.14, -0.02), -0.05 (95% CI, -0.11, 0.02), and - 0.10 (95% CI, -0.16, -0.04) (All P for trend < 0.001). While most subgroups maintained similar overall patterns, heterogeneous findings were also observed. For example, the multivariable-adjusted differences in total MMI between the lowest and highest quantile of UPF consumption were - 0.19 (95% CI, -0.32, -0.06) for non-Hispanic Whites, 0.18 (95% CI, 0.01, 0.36) for non-Hispanic Blacks, -0.25 (95%CI, -0.45, -0.04) for Hispanics, -0.25 (95% CI, -0.51, 0.05) for non-Hispanic Asians and - 0.32 (95% CI, -0.75, 0.12) for others (P for interaction < 0.001). CONCLUSION: Higher consumption of UPFs was significantly associated with lower values of total and regional muscle mass. Specifically, comparing the highest quantile of UPF consumption to the lowest, total MMI decreased by 0.93%, trunk MMI decreased by 0.76%, and AMMI decreased by 1.25%. The differences in associational patterns between UPF consumption and muscle mass across sociodemographic subgroups require further investigation.

Role of diet in the risks of esophageal adenocarcinoma and squamous cell carcinoma: an updated umbrella review.

PURPOSE: This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. RESULTS: We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. CONCLUSIONS: This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.

DACNN-aided nonlinear equalizer for a probabilistic shaping coherent optical communication system.

The probabilistic shaping (PS) technique is a key technology for fiber optic communication systems to further approach the Shannon limit. To solve the problem that nonlinear equalizers are ineffective for probabilistic shaping optical communication systems with non-uniform distribution, a distribution alignment convolutional neural network (DACNN)-aided nonlinear equalizer is proposed. The approach calibrates the equalizer using the probabilistic shaping prior distribution, which reduces the training complexity and improves the performance of the equalizer simultaneously. Experimental results show nonlinear equalization of 120 Gb/s PS 64QAM signals in a 375 km transmission scenario. The proposed DACNN equalizer improves the receiver sensitivity by 2.6 dB and 1.1 dB over the Volterra equalizer and convolutional neural network (CNN) equalizer, respectively. Meanwhile, DACNN converges with fewer training epochs than CNN, which provides great potential for mitigating the nonlinear distortion of PS signals in fiber optic communication systems.

16QAM optical signal generation scheme based on weighted optimal Euclidean distance.

A two-dimensional signal constellation scheme for binary uniform memoryless source transmission in optical fiber channels is studied in this paper. In geometric shaping (GS), optimization algorithms are usually used to change the overall position of constellation points while maintaining the probability of constellation points unchanged. Different optimization functions are used to allocate the position of constellation symbols, thereby improving constellation performance. A 16 quadrature amplitude modulation (QAM) optical signal generation scheme based on weighted optimal Euclidean distance is proposed in this paper. In order to obtain the best constellation diagram and increase the shaping gain, the weighted optimal Euclidean distance that can minimize the bit error rate (BER) over multiple iterative optimizations is used as the objective function. On the one hand, the proposed 16QAM optical signal generation scheme based on weighted optimal Euclidean distance always outperforms the uniform square 16QAM and the uniform circle 16QAM schemes in the back to back (BTB) transmission. On the other hand, after analyzing the simulation demonstration in a 50GBaud coherent optical communication system over 3000 km, results demonstrate that the optical signal to noise ratio (OSNR) performance of this system is better than that of the uniform square 16QAM and the uniform circle 16QAM, which is improved by 0.52 dB and 0.85 dB, respectively. In addition, the proposed 16QAM system increases the transmission distance by 989 km and 741 km, respectively, compared to the other two systems. The performance confirms that the proposed novel 16QAM scheme, to the best of our knowledge, can effectively improve the reliability and transmission distance. Therefore, the proposed scheme has a certain development prospect in the future long-distance transmission of high-speed optical fiber communication.

Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric-Aß mediates pathology maturation.

INTRODUCTION: The "prion-like" features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid-ß (Aß) have never been experimentally studied in primates phylogenetically close to humans. METHODS: We injected 17 macaques in the entorhinal cortex with nanograms of seeding-competent tau aggregates purified from AD brains or control extracts from aged-matched healthy brains, with or without intracerebroventricular co-injections of oligomeric-Aß. RESULTS: Pathological tau injection increased cerebrospinal fluid (CSF) p-tau181 concentration after 18 months. Tau pathology spreads from the entorhinal cortex to the hippocampal trisynaptic loop and the cingulate cortex, resuming the experimental progression of Braak stage I to IV. Many AD-related molecular networks were impacted by tau seeds injections regardless of Aß injections in proteomic analyses. However, we found mature neurofibrillary tangles, increased CSF total-tau concentration, and pre- and postsynaptic degeneration only in Aß co-injected macaques. DISCUSSION: Oligomeric-Aß mediates the maturation of tau pathology and its neuronal toxicity in macaques but not its initial spreading. HIGHLIGHTS: This study supports the "prion-like" properties of misfolded tau extracted from AD brains. This study empirically validates the Braak staging in an anthropomorphic brain. This study highlights the role of oligomeric Aß in driving the maturation and toxicity of tau pathology. This work establishes a novel animal model of early sporadic AD that is closer to the human pathology.

Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line.

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer's disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

Iron-mediated DAMO-anammox process: Revealing the mechanism of electron transfer.

The nitrate denitrifying anaerobic methane oxidation-anaerobic ammonia oxidation (DAMO-anammox) can accomplish nitrogen removal and methane (CH4) reduction. This process greatly contributes to carbon emission mitigation and carbon neutrality. In this study, we investigated the electron transfer process of functional microorganisms in the iron-mediated DAMO-anammox system. Fe3+ could be bound to several functional groups (-CH3, COO-, -CH) in extracellular polymeric substance (EPS), and the functional groups bound were different at different iron concentration. Fe3+ underwent reduction reactions to produce Fe2+. Most Fe3+ and Fe2+ react with microorganisms and formed chelates with EPS. Three-dimensional fluorescence spectra showed that Fe3+ affected the secretion of tyrosine and tryptophan, which were essential for cytochrome synthesis. The presence of Fe3+ accelerated c-type cytochrome-mediated extracellular electron transfer (EET), and when more Fe3+ existed, the more cytochrome C expressed. DAMO archaea (M. nitroreducens) in the system exhibited a high positive correlation with the functional genes (resa and ccda) for cytochrome c synthesis. Some denitrifying microorganisms showed positive correlations with the abundance of riboflavin. This finding showed that riboflavin secreted by functional microorganisms acted as an electron shuttle. In addition, DAMO archaea were positively correlated with the hair synthesis gene pily1, which indicated that direct interspecies electron transfer (DIET) may exist in the iron-mediated DAMO-anammox system.

Structural insights into the Oryza sativa cation transporters HKTs in salt tolerance.

The high-affinity potassium transporters (HKTs), selectively permeable to either Na+ alone or Na+/K+, play pivotal roles in maintaining plant Na+/K+ homeostasis. Although their involvement in salt tolerance is widely reported, the molecular underpinnings of Oryza sativa HKTs remain elusive. In this study, we elucidate the structures of OsHKT1;1 and OsHKT2;1, representing two distinct classes of rice HKTs. The dimeric assembled OsHKTs can be structurally divided into four domains. At the dimer interface, a half-helix or a loop in the third domain is coordinated by the C-terminal region of the opposite subunit. Additionally, we present the structures of OsHKT1;5 salt-tolerant and salt-sensitive variants, a key quantitative trait locus associated with salt tolerance. The salt-tolerant variant of OsHKT1;5 exhibits enhanced Na+ transport capability and displays a more flexible conformation. These findings shed light on the molecular basis of rice HKTs and provide insights into their role in salt tolerance.

[Simultaneous determination of seven artemisinin-related compounds in Artemisia annua by UPLC-QQQ-MS/MS].

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

Mendelian randomization study on the causal effect of chickenpox on dementia.

Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome-wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two-sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse-variance weighted analysis (ß = 0.070, 95% confidence interval [CI] for ß: 0.014-0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015-1.134; p = 0.014) and weighted median (ß = 0.071, 95% CI for ß: 0.002-0.141; OR = 1.074, 95% CI for OR: 1.002-1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia.