Transcription factors PuPRE6/PuMYB12 and histone deacetylase PuHDAC9-like regulate sucrose levels in pear.

The improvement of fruit quality, in particular sugar content, has been a major goal of plant breeding programmes for many years. Here, 2 varieties of the Ussurian pear (Pyrus ussuriensis), Nanguo, and its high-sucrose accumulation bud sport, Nanhong, were used to study the molecular mechanisms regulating sucrose transport in fruits. Comparative transcriptome analysis showed that in Nanhong fruit, an MYB transcription factor, PuMYB12, and a sucrose transporter protein, PuSUT4-like, were expressed at higher levels, while a paclobutrazol resistance transcription factor, PuPRE6, and a histone deacetylase (HDAC), PuHDAC9-like, were expressed at lower levels in Nanguo fruit. PuSUT4-like silencing and overexpression experiments in Nanguo pear showed that PuSUT4-like is essential for sucrose transportation. PuPRE6 and PuMYB12 act as antagonistic complexes to regulate PuSUT4-like transcription and sucrose accumulation. The histone deacetylation levels of the PuMYB12 and PuSUT4-like promoters were higher in Nanguo fruit than in Nanhong fruit, and Y1H assays showed that HDAC PuHDAC9-like bound directly to the promoters of PuMYB12 and PuSUT4-like. Our results uncovered transcription regulation and epigenetic mechanisms underlying sucrose accumulation in pears.

Single-Atom Co─O4 Sites Embedded in a Defective-Rich Porous Carbon Layer for Efficient H2O2 Electrosynthesis.

The production of hydrogen peroxide (H2O2) via the two-electron electrochemical oxygen reduction reaction (2e- ORR) is an essential alteration in the current anthraquinone-based method. Herein, a single-atom Co─O4 electrocatalyst is embedded in a defective and porous graphene-like carbon layer (Co─O4@PC). The Co─O4@PC electrocatalyst shows promising potential in H2O2 electrosynthesis via 2e- ORR, providing a high H2O2 selectivity of 98.8% at 0.6 V and a low onset potential of 0.73 V for generating H2O2. In situ surface-sensitive attenuated total reflection Fourier transform infrared spectra and density functional theory calculations reveal that the electronic and geometric modification of Co─O4 induced by defective carbon sites result in decreased d-band center of Co atoms, providing the optimum adsorption energies of OOH* intermediate. The H-cell and flow cell assembled using Co─O4@PC as the cathode present long-term stability and high efficiency for H2O2 production. Particularly, a high H2O2 production rate of 0.25 mol g-1 cat h-1 at 0.6 V can be obtained by the flow cell. The in situ-generated H2O2 can promote the degradation of rhodamine B and sterilize Staphylococcus aureus via the Fenton process. This work can pave the way for the efficient production of H2O2 by using Co─O4 single atom electrocatalyst and unveil the electrocatalytic mechanism.

Absolute Ranging with Time Delay Interferometry for Space-Borne Gravitational Wave Detection.

In future space-borne gravitational wave (GW) detectors, time delay interferometry (TDI) will be utilized to reduce the overwhelming noise, including the laser frequency noise and the clock noise etc., by time shifting and recombining the data streams in post-processing. The successful operation of TDI relies on absolute inter-satellite ranging with meter-level precision. In this work, we numerically and experimentally demonstrate a strategy for inter-satellite distance measurement. The distances can be coarsely determined using the technique of arm-locking ranging with a large non-ambiguity range, and subsequently TDI can be used for precise distance measurement (TDI ranging) by finding the minimum value of the power of the residual noises. The measurement principle is introduced. We carry out the numerical simulations, and the results show millimeter-level precision. Further, we perform the experimental verifications based on the fiber link, and the distances can be measured with better than 0.05 m uncertainty, which can well satisfy the requirement of time delay interferometry.

Time delay interferometry with a transfer oscillator.

In this work, we experimentally perform time delay interferometry by using a transfer oscillator, which is capable of reducing the laser frequency noise and the clock noise simultaneously in the post processing. The iodine frequency reference is coherently downconverted to the microwave frequency using a laser frequency comb. The residual noise of the downconversion network is 5 × 10-6Hz/Hz1/2 at 0.7 mHz, and 4 × 10-6Hz/Hz1/2 at 0.1 Hz, indicating high homology between the optical frequency and the microwave frequency. We carry out time delay interferometry with the aid of the electrical delay module, which can introduce large time delays. The results show that the laser frequency noise and the clock noise can be reduced simultaneously by ten and three orders of magnitude, respectively, in the frequency band from 0.1 mHz to 0.1 Hz. The performance of the noise reduction can reach 6 × 10-8Hz/Hz1/2 at 0.1 mHz, and 7 × 10-7Hz/Hz1/2 at 1 mHz, meeting the requirements of the space-borne gravitational wave detection. Our work will be able to offer an alternative method for the frequency comb-based time delay interferometry in the future space-borne gravitational wave detectors.

NUCLEOCYTOPLASMIC shuttling of ETHYLENE RESPONSE FACTOR 5 mediated by nitric oxide suppresses ethylene biosynthesis in apple fruit.

Nitric oxide (NO) is known to modulate the action of several phytohormones. This includes the gaseous hormone ethylene, but the molecular mechanisms underlying the effect of NO on ethylene biosynthesis are unclear. Here, we observed a decrease in endogenous NO abundance during apple (Malus domestica) fruit development and exogenous treatment of apple fruit with a NO donor suppressed ethylene production, suggesting that NO is a ripening suppressor. Expression of the transcription factor MdERF5 was activated by NO donor treatment. NO induced the nucleocytoplasmic shuttling of MdERF5 by modulating its interaction with the protein phosphatase, MdPP2C57. MdPP2C57-induced dephosphorylation of MdERF5 at Ser260 is sufficient to promote nuclear export of MdERF5. As a consequence of this export, MdERF5 proteins in the cytoplasm interacted with and suppressed the activity of MdACO1, an enzyme that converts 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene. The NO-activated MdERF5 was observed to increase in abundance in the nucleus and bind to the promoter of the ACC synthase gene MdACS1 and directly suppress its transcription. Together, these results suggest that NO-activated nucleocytoplasmic MdERF5 suppresses the action of ethylene biosynthetic genes, thereby suppressing ethylene biosynthesis and limiting fruit ripening.

The mechanism for brassinosteroids suppressing climacteric fruit ripening.

The plant hormone ethylene is important for the ripening of climacteric fruit, such as pear (Pyrus ussuriensis), and the brassinosteroid (BR) class of phytohormones affects ethylene biosynthesis during ripening via an unknown molecular mechanism. Here, we observed that exogenous BR treatment suppressed ethylene production and delayed fruit ripening, whereas treatment with a BR biosynthesis inhibitor promoted ethylene production and accelerated fruit ripening in pear, suggesting BR is a ripening suppressor. The expression of the transcription factor BRASSINAZOLE-RESISTANT 1PuBZR1 was enhanced by BR treatment during pear fruit ripening. PuBZR1 interacted with PuACO1, which converts 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene, and suppressed its activity. BR-activated PuBZR1 bound to the promoters of PuACO1 and of PuACS1a, which encodes ACC synthase, and directly suppressed their transcription. Moreover, PuBZR1 suppressed the expression of transcription factor PuERF2 by binding its promoter, and PuERF2 bound to the promoters of PuACO1 and PuACS1a. We concluded that PuBZR1 indirectly suppresses the transcription of PuACO1 and PuACS1a through its regulation of PuERF2. Ethylene production and expression profiles of corresponding apple (Malus domestica) homologs showed similar changes following epibrassinolide treatment. Together, these results suggest that BR-activated BZR1 suppresses ACO1 activity and the expression of ACO1 and ACS1, thereby reducing ethylene production and suppressing fruit ripening. This likely represents a conserved mechanism by which BR suppresses ethylene biosynthesis during climacteric fruit ripening.

Impedimetric aptasensor based on porphyrin-based covalent-organic framework for determination of diethylstilbestrol.

An impedimetric sensing strategy was developed for sensitively determining diethylstilbestrol (DES) based on a platform of porphyrin-containing covalent-organic framework (p-COF). The p-COF was synthesized using 5,10,15,20-tetra (4-aminophenyl) porphyrin (TAPP) and 1,3,6,8-tetrakis(4-formylphenyl) pyrene (TFPy) as building blocks via condensation reaction, for which p-COF was named as TAPP-TFPy-COF. Considering the large specific surface area (302.9 m2 g-1), high porosity, rich nitrogen functionality, superior electrochemical activity, and strong bioaffinity toward DNA strands, the TAPP-TFPy-COF-based platform exhibited enhanced, non-label, and amplified electrochemical signal, large number of immobilized DES-targeted aptamer strands, and fast-response toward the analyte. Electrochemical results reveal that the TAPP-TFPy-COF-based aptasensor promoted the sensing performance for the detection of DES, resulting in an extremely low limit of detection of 0.42 fg mL-1 within a DES concentration ranging from 1 fg mL-1 to 0.1 pg mL-1, which was substantially lower than those of most reported DES sensors. Furthermore, the TAPP-TFPy-COF-based aptasensor possessed outperformed stability, high selectivity, ascendant reproducibility, and acceptable applicability in diverse environments. The recovery values for DES detection in milk, tap water, and frozen shrimp were in the range 91.80-118.50% with low relative standard deviation of 0.11-4.26%. This work provides a new sensing electrochemical approach based on COF network for DES detection and shows a deep insight into the construction of COF-based biosensors, which can be extended to be used for other target compounds.

Weak-Light Phase-Locking Time Delay Interferometry with Optical Frequency Combs.

In the future space-borne gravitational wave (GW) detector, the optical transponder scheme, i.e., the phase-locking scheme, will be utilized so as to maintain the signal-to-noise ratio (SNR). In this case, the whole constellation will share one common laser equivalently, which enables the considerable simplification of time delay interferometry (TDI) combinations. Recently, and remarkably, the unique combination of TDI and optical frequency comb (OFC) has shown a bright prospect for the future space-borne missions. When the laser frequency noise and the clock noise are synchronized using OFC as the bridge, the data streams will be reasonably simplified. However, in the optical transponder scheme, the weak-light phase-locking (WLPL) loops could bring additional noises. In this work, we analyze the phase-locking scheme with OFC and transfer characteristics of the noises including the WLPL noise. We show that the WLPL noise can be efficiently reduced by using the specific TDI combination, and the cooperation of phase-locking and frequency combs can greatly simplify the post-processing.

Preparation and Characterization of Red Mud/Fly Ash Composite Material (RFCM) for Phosphate Removal.

In this study, a new red mud/fly ash composite material (RFCM) for phosphate removal was prepared by granulation and activation methods, using bauxite residue (red mud, RM) as the main raw material, adding with some fly ash and a few adhesives. The effects of different types of RM and adhesives on RFCM for phosphate removal were discussed. It was found that RFCM prepared from sintering red mud and cement waste performed better on phosphate removal than that prepared from Bayer red mud and common industrial adhesives. After calcination activated at appropriate temperature around 800-900℃, the specific surface area of RFCM increased, and new substances with hydroxyl (-OH) appeared on the surface of RFCM, which were the functional groups for phosphate removal. Mechanism of RFCM for phosphate removal was speculated as a combination of physical adsorption, chemical adsorption and chemical precipitation, which mainly depended on ligand exchange and chemical reaction. This research will provide a potential application of bauxite residue in environmental remediation.

Psychological aspect of patients with inflammatory bowel disease, which may be related to the quality of life, sleep and disease characteristics.

OBJECTIVES: Inflammatory bowel disease (IBD) usually present with systemic and gastrointestinal problems. This may result in both physical and psychological burden. The aim of the study was to investigate the association between psychological burden and Health Related Quality of Life (HRQoL), sleep quality and disease characteristics. METHODS: A total of 106 patients and 165 general populations were enrolled in this study. The demographic information, disease characteristics of participants were investigated. The SCL-90 was self-administered to evaluate psychometric properties. SF-36 and IBDQ were both used to the assessment of HRQoL, and PSQI to quality of sleep. RESULTS: The SCL-90 score of IBD was significantly higher than that of the control (p = .0007), especially in somatization, anxiety, depression, hostility and psychosis dimensions. Similar to IBDQ (p < .0001), the results of SF-36 (p < .0001) showed that the HRQoL of both Ulcerative colitis (UC) and Crohn's disease (CD) were somehow inferior to control. However, undifferentiated results were noted in patients between UC and CD. Good linear relationship between disease activity and SCL-90 (RUC = 0.53, pUC = .001; RCD = 0.36, pCD = .002), SF-36 (RUC = -0.42, pUC = .01; RCD = -0.49, pCD < .0001), IBDQ (RUC = -0.57, pUC = .0005; RCD = -0.52, pCD < .0001), PSQI (RUC = 0.50, pUC = .003; RCD = 0.27, pCD = .02) were observed. With the score of SCL-90 of patients increased, the SF-36 (R = -0.78, p < .0001) and IBDQ decreased (R = -0.74, p < .0001), PSQI increased (R = -0.70, p < .0001). Multiple stepwise regression analysis revealed that disease activity, extraintestinal manifestations, weight loss may contribute to identify the psychological anomalies. CONCLUSIONS: Altered psychological status can be found in IBD, reflecting the necessity of providing psychological care for them. The disease itself results in lower HRQoL. Better HRQoL and sleep quality are in concordance with better psychological health.

A novel esterase LanE from Edaphocola flava HME-24 and the enantioselective degradation mechanism of herbicide lactofen.

Lactofen is a chiral herbicide and widely used against broadleaf weeds in agriculture. As a pesticide, it is directly released to the environment, and easily caused contamination in soil and aquatic ecosystem. The enantioselective degradation of lactofen in the environment has been reported, but the molecular biological mechanism of this phenomenon is still unclear. In this study, strain Edaphocola flava HME-24 could degrade 96.7% of 50 mg L-1 lactofen within 72 h. Lactofen was initially hydrolyzed to desethyl lactofen and subsequently acifluorfen by strain HME-24. A novel gene lanE, involved in lactofen transformation, was obtained from Edaphocola flava HME-24. Gene lanE encoded a protein of 471 amino acids that contained the conserved GXSXG esterase motif and clustered into esterase subfamily V. LanE shared the highest identity with esterase EstD (Q9WYH1) from Thermotoga maritima MSB8 (29.14%). This esterase was also able to transform p-nitrophenyl esters (C4-C8), and the activity decreased when the carbon chain length increased. LanE showed enantioselectivity during the degradation of lactofen, diclofop-methyl, and quizalofop-ethyl, with a higher degradation efficiency of (S)-enantiomers than (R)-enantiomers. The three-dimensional structure of LanE was simulated, and molecular docking revealed that when the (S)-enantiomers of lactofen occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated the formation of the transition state complex. The results in this study enhanced our understanding of the preferential catabolism of the (S)-enantiomers of lactofen on the molecular level and could illustrate the reported enantioselective degradation of lactofen in the environment.

Glial Fibrillary Acidic Protein as a Potential Indicator for Symptomatic Intracranial Hemorrhage in Acute Ischemic Patients Undergoing Endovascular Thrombectomy.

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH. Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification. Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150-0.576] versus 0.065 [0.041-0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150-0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269-1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153-2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070-0.295, p = 0.001). Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.

The allelopathic effects of Heterosigma akashiwo on Skeletonema costatum: Insights from gene expression and metabolomics analysis.

The globally distributed harmful algal blooms (HAB) species, Heterosigma akashiwo, has been found to exhibit ichthyotoxicity. Previous studies have shown that H. akashiwo achieves a competitive edge during bloom occurrences by inhibiting the growth of a coexisting diatom, Skeletonema costatum, through allelopathy. However, the specific allelopathic mechanisms underlying the allelopathic effects of H. akashiwo on S. costatum remain unknown. To bridge this gap, our study utilized a combination of quantitative real-time PCR and metabolomics to examine the allelopathic processes of H. akashiwo on S. costatum. Our results demonstrate that the growth of S. costatum is hindered when co-cultured with H. akashiwo (initial cell concentration, 2 × 104 cell/mL). Gene expression investigation showed a substantial reduction in the mRNA levels of cytochrome b6, ribulose bisphosphate carboxylase large chain, and silicon transporter in S. costatum when grown in co-culture conditions. Furthermore, metabolic pathway analysis suggested that the allelopathic effects of H. akashiwo disrupted several vital metabolic pathways in S. costatum, including a reduction in purine and pyrimidine metabolism and an increase in fatty acid biosynthesis. Our investigation has revealed the intricate and substantial involvement of allelopathy in the formation of H. akashiwo blooms, demonstrating the complexity of the allelopathic interaction between H. akashiwo and S. costatum. These insights also contribute significantly to our understanding of the dynamics within HAB species.

Molecularly imprinted solid-phase extraction combined with non-ionic hydrophobic deep eutectic solvents dispersed liquid-liquid microextraction for efficient enrichment and determination of the estrogens in serum samples.

Hormonal drugs in biological samples are usually in low concentration and highly intrusive. It is of great significance to enhance the sensitivity and specificity of the detection process of hormone drugs in biological samples by utilizing appropriate sample pretreatment methods for the detection of hormone drugs. In this study, a sample pretreatment method was developed to effectively enrich estrogens in serum samples by combining molecularly imprinted solid-phase extraction, which has high specificity, and non-ionic hydrophobic deep eutectic solvent-dispersive liquid-liquid microextraction, which has a high enrichment ability. The theoretical basis for the effective enrichment of estrogens by non-ionic hydrophobic deep eutectic solvent was also computed by simulation. The results showed that the combination of molecularly imprinted solid-phase extraction and deep eutectic solvent-dispersive liquid-liquid microextraction could improve the sensitivity of HPLC by 33∼125 folds, and at the same time effectively reduce the interference. In addition, the non-ionic hydrophobic deep eutectic solvent has a relatively low solvation energy for estrogen and possesses a surface charge similar to that of estrogen, and thus can effectively enrich estrogen. The study provides ideas and methods for the extraction and determination of low-concentration drugs in biological samples and also provides a theoretical basis for the application of non-ionic hydrophobic deep eutectic solvent extraction.

Prediction model of preeclampsia using machine learning based methods: a population based cohort study in China.

Introduction: Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11-13 + 6 weeks' gestation, providing an effective tool for early screening and prediction of preeclampsia. Methods: This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation. Results: We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively). Conclusions: Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes.

Engineering Sb/Zn4(OH)6SO4·5H2O interfacial layer by in situ chemically reacting for stable Zn anode.

Rechargeable aqueous zinc ion batteries with abundant resources and high safety have gained extensive attention in energy storage technology. However, the cycle stability is largely limited by notorious Zn dendrite growth and water-induced interfacial side reactions. Here, a uniform and robust protection layer consisting of metal antimony (Sb) nanoparticles and micrometer-size sheets Zn4(OH)6SO4·5H2O (ZHS) is purposely designed to stabilize Zn anode via an in situ chemical reaction strategy. The two-phase protection layers (Sb/ZHS) induce a reinforcement effect on the Zn anode (Zn@Sb/ZHS). Specifically, Sb nanoparticles play the part of nucleation sites to facilitate uniform Zn plating and homogenize the electric field around the Zn surface. ZHS micrometer-size sheets possess sufficient electrolyte wettability, fast ion transfer kinetics, and anti-corrosion, thus guaranteeing uniform ion flux and inhibiting H2O decomposition. As expected, the symmetric Zn@Sb/ZHS//Zn@Sb/ZHS cells achieve a minimal voltage hysteresis and a reversible cycle of over 2000 h at 1 mA cm-2. By pairing with the MnO2 cathode, the full cell exhibits a significantly improved stability (∼94.17 % initial capacity after 1500 cycles). This study provides a new strategy to design artificial protection layers.

Ether-Water Co-Solvent Electrolytes Enhanced Vanadium Oxide Cathode Cyclic Behaviors for Zinc Batteries.

Vanadium-based compounds are fantastic cathodes for aqueous zinc metal batteries due to the high specific capacity and excellent rate capability. Nevertheless, the practical application has been hampered by the dissolution of vanadium in traditional aqueous electrolytes owing to the strong polarity of water molecules. Herein, we propose a hybrid electrolyte made of Zn(ClO4)2 salt in tetraethylene glycol dimethyl ether (G4) and H2O solvents to upgrade the cycle life of Zn//K0.486V2O5 battery. The G4 jointly solvates with Zn2+ ions and replaces a portion of the H2O molecules in the Zn2+ solvation sheath. It forms a strong bond with H2O, reducing its activity, and significantly inhibiting vanadium dissolution and water-induced parasitic reaction. Consequently, the optimized electrolyte with H2O and G4 volume ratio of 5 : 5 enhances the cycling stability of Zn//K0.486V2O5 battery, enabling it to reach up to 600 cycles. In addition, the battery demonstrates a satisfactory reversible capacity of 475.7 mAh g-1 and excellent rate performance attributed to the moderate ionic conductivity (28.8 mS cm-1) of the hybrid electrolyte. Last but not least, in the optimized electrolyte, the symmetric Zn//Zn cells deliver a long cycling performance of 400 h, while the asymmetric Zn//Cu cells shows a high average coulombic efficiency of 97.4 %.

Full-Length Transcriptome Analysis of the Ichthyotoxic Harmful Alga Heterosigma akashiwo (Raphidophyceae) Using Single-Molecule Real-Time Sequencing.

The raphidophyte Heterosigma akashiwo is a harmful algal species. The bloom of this organism has been associated with the massive mortality of fish in many coastal waters. To investigate the molecular mechanism of H. akashiwo blooms, having a reliable reference transcriptome of this species is essential. Therefore, in this study, a full-length transcriptome of H. akashiwo was obtained by single-molecule real-time sequencing. In total, 45.44 Gb subread bases were generated, and 16,668 unigenes were obtained after the sequencing data processing. A total of 8666 (52.00%) unigenes were successfully annotated using seven public databases. Among them, mostly phosphorus and nitrogen metabolism genes were detected. Moreover, there were 300 putative transcription factors, 4392 putative long non-coding RNAs, and 7851 simple sequence repeats predicted. This study provides a valuable reference transcriptome for understanding how H. akashiwo blooms at a molecular level.

An updated review of gastrointestinal toxicity induced by PD-1 inhibitors: from mechanisms to management.

PD-1 inhibitors, as one of commonly used immune checkpoint inhibitors, enable T-cell activation and prevent immune escape by blocking the PD-1/PD-L1 signaling pathway. They have transformed the treatment landscape for cancer in recent years, due to the advantages of significantly prolonging patients' survival and improving their life quality. However, the ensuing unpredictable immune-related adverse effects (irAEs) plague clinicians, such as colitis and even potentially fatal events like intestinal perforation and obstruction. Therefore, understanding the clinical manifestations and grading criteria, underlying mechanisms, available diverse therapies, accessible biomarkers, and basis for risk stratification is of great importance for the management. Current evidence suggests that irAEs may be a marker of clinical benefit to immunotherapy in patients, so whether to discontinue PD-1 inhibitors after the onset of irAEs and rechallenge after remission of irAEs requires further evaluation of potential risk-reward ratios as well as more data from large-scale prospective studies to fully validate. At the end, the rare gastrointestinal toxicity events caused by PD-1 inhibitors are also sorted out. This review provides a summary of available data on the gastrointestinal toxicity profile caused by PD-1 inhibitors, with the aim of raising clinicians' awareness in daily practice, so that patients can safely benefit from therapy.

Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease.

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45 µg/g. These values were 26.94, 66.77, and 327.22 µg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 µg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 µg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.